Systemic and Other System Disorders

(1)

Treatment

Purpose of the Study

1028

ALLERGY

AND IMMUNOLOGY

THYMOPENTIN THERAPY REDUCES THE CLINICAL SEVERITY OF ATOPIC DERMATITIS

Leung BYM, Hirsch RU, Schneider U, Moody C, Takaoka R, Li SH, Myerson LA, Mariam SG, Goldstein

G,

Hanifin JM. J Allergy Clln Immunol. 1 990;85:927-933.

The purpose of the study was to compare the safety and efficacy of thymopentin with placebo in the treat-ment of atopic dermatitis.

Study Population

One hundred patients with moderate to severe atopic dermatitis (AD) aged 2 to 66 years with a mean duration of symptoms of 26 years were included in this study. The extent of involvement was at least 20% of the body surface area.

Methods

Patients were assigned randomly to receive either thy-mopentin or placebo in double-blind trial. Study medi-cation was administered subcutaneously once daily for 6 weeks. No systemic steroids were given. Analysis was performed on total severity scores, individual symptom scores, extent of body involvement, and serum immuno-globulins as well as adverse reactions and infections.

Findings

Reduction of total severity scores was significant in the treated group (P = .4). Individual symptom scores of pruritus and erythema also were decreased significantly in the treated group. Both groups demonstrated a pro-gressive and statistically significant decline in overall severity of the disease, but the reduction was greater in the thymopentin group with a decrease in extent of body involvement. No adverse reactions were observed.

Reviewer’s Comments

Thymopentin appears to have a promising use in the patient with severe atopic dermatitis who does not re-spond to conventional therapy. At present time the man-agement of these patients continues to be difficult with a lack of curative therapy. Further investigation of this drug is indicated to evaluate its effect on the immune function in these individuals which may reflect its actual mechanism of action in the disease.

ALMA M. HERRERA, MD

Mobile, AL

COLIC AND THE EFFECT OF CHANGING FORMULAS: A DOUBLE-BLIND, MULTIPLE-CROSSOVER STUDY Forsyth BWC. J Pediatr. 1 989;1 15:521-526.

Colic is a condition of young infants which consists of excessive crying and apparent abdominal pain. One pos-sible cause is intolerance of cow’s milk. This study ex-amines the effect of cow’s milk vs casein hydrolysate formulas in colicky infants, using a double-blind, cross-over design with a 2-day washout period for each formula change.

Included in the study were 17 infants, 8 weeks old or less, who had greater than 3 hours of crying per day and apparent gastrointestinal distress.

Methods

Infants were fed either Nutramigen or a formula of one third cow’s milk, two thirds Nutramigen in alterna-ting 4-day periods for four study periods. Data were collected by parent diary; data from the second 2 days of each study period were analyzed; hence, the 2-day wash-out period. Data were evaluated for clinically significant changes in crying behavior (defined as a one-third de-crease) with each formula change.

Findings

The authors found a “marked day-to-day variability” in crying behavior independent of the type of formula. There were statistically significant changes in crying and colicky behavior with the first change from cow’s milk to Nutramigen; these differences lessened, however, by the third formula change.

Conclusions

The authors concluded that a short-term change to a casein hydrolysate formula may be warranted in the treatment of colic.

Reviewer’s Comments

This study highlights the difficulties involved in study-ing a common but rather ill-defined, short-lived disorder. One wonders if the 4-day study periods might have been too short.

MARY ELLEN FRIEDMAN, MD

Downey, CA

Systemic

and

Other

System

Disorders

Pathophysiology

TOXIC SHOCK SYNDROME ASSOCIATED WITH

STAPHYLOCOCCUS AUREUS SINUSITIS

Ferguson MA, Todd JK. J Infect Dis. 1 990;1

61:953-955.

at Viet Nam:AAP Sponsored on September 2, 2020

www.aappublications.org/news

(2)

Purpose of the Study Purpose of the Study

This study was performed to highlight, through case reviews, the potential for toxic shock syndrome to occur in pediatric patients as a result of Staphylococcus aureus

sinusitis.

The case studies involved 3 patients between 8 and 14 years of age.

Methods

The study was carried out by case review of medical

records.

Findings

Three cases of toxic shock syndrome with sinusitis as their sole focal site of infection were reviewed. Two of the cases had culture documentation of S aureus with a positive nasal culture and good response to antistaphy-lococcal therapy. Blood and other cultures were negative. All three cases manifested fever, rash, desquamation, and hypotention or orthostatic dizziness, as well as three or more minor criteria demonstrating involvement of other organ systems. The third case, without sinus culture, represented recurrent sinusitis associated with recurrent toxic shock syndrome. All three cases responded to usual therapy for toxic shock syndrome including fluid volume, support, and antistaphylococcal antibiotics.

Conclusions

The authors concluded that sinusitis can be a nonmen-strual site of S aureus infection underlying toxic shock syndrome in pediatric patients. They noted other similar situations such as nasal surgery or nasal packing which had been associated with toxic shock syndrome perhaps due to similar focal growth conditions promoting optimal toxin production. The authors recommended aspiration of sinuses in such cases, not only for diagnosis but as an important therapeutic procedure.

Because sinusitis frequently complicates upper respi-ratory illnesses, these cases heighten the clinical aware-ness of those of us who treat numbers of patients with

these common infections.

NANCY K. OSTROM, MD

San Diego, CA

RESPIRATORY SYNCYTIAL VIRUS INFECTION IN HUMAN IMMUNODEFICIENCY VIRUS-INFECTED CHILDREN

Chandwani 5, Borkowsky W, Krasinski K. J Pediatr. 1990;1 17:251.

The purpose of this study was to describe the experi-ence of respiratory syncytial virus (RSV) infection in 10 patients infected with human immunodeficiency virus

(HIV).

Study Population

Ten HIV-infected patients with RSV infection were studied in the winter of 1986 to 1987. Six patients were less than 1 year of age, 4 were between 2 and 4 years of age. Seven patients were Hispanic, 2 were black, 1 was white, and 4 were female.

Methods

Hospital records and infectious disease records were reviewed to determine clinical and radiologic outcomes and outcomes of RSV infection. Detection of RSV infec-tion was done by use of enzyme-linked immunosorbent assay (ELISA) technique on nasopharyngeal washings. A control population of 18 children admitted with RSV infection, 12 of whom were less than 12 months of age, was used to contrast the course of the patients with HIV. Seven HIV-infected patients and one control patient were treated with ribavirin aerosol. Ribavirin was provided only to patients requiring mechanical ventilation or with significant hypoxemia (arterial oxygen pressure < 60) or persistent fever with a pulmonary infiltrate. IgE antibody to RSV was determined using an ELISA assay on naso-pharyngeal washings. Last, duration of antigen excretion was determined by ELISA for RSV.

Findings

Of 10 HIV-infected patients, 6 had tachypnea with rhonchi and sighs of upper respiratory illness. Only one patient had wheezing. In the control population, in con-trast, 7% (12 patients) had tachypnea, 44% (8 patients) had wheezing, 22% rales, and 44% rhonchi (8). The chest roentgenograms in HIV-infected patients demonstrated infiltrates in 4 of 10 patients with only 2 showing hyper-inflation. In the control group, 5 patients had hyperinfla-tion with diffuse or segmental infiltrates in 10.

The clinical course was remarkably different with 2 of 7 patients treated with ribavirin showing no improve-ment. Both patients were positive for HIV and were co-infected; one with Pseudomorias aeruginosa and the other with Pneumocystis carinii. Only one control patient had cyanosis and hypoxia requiring mechanical ventilation for 2 to 3 days and ribavirin for 5 days. Duration of shedding was also remarkably different with 3 HIV-infected patients with shedding noted for more than 30 days (30, 45, and 90 days) despite ribavirin in 2 of these patients, whereas none of the 6 hospitalized children with nosocomial RSV had any antigen shedding after 20 days

(mean 13.5 days). Six of seven HI V-infected patients had

undetectable IgE titers during the acute and convalescent

phases. Only one patient had high IgE titers, and IgA

(3)

Reviewer’s Comments

1030

ALLERGY

AND

IMMUNOLOGY

This clinical series demonstrates that the RSV infec-tion in HIV-infected children is associated with more frequent pneumonia with relative absence of wheezing and a prolonged viral carriage with a mortality rate of 20% comparable with other rates reported with immu-nocompromised individuals. Deaths were also related to super infection.

Diagnosis

CHRISTOPHER RANDOLPH, MD

Waterbury, CT

ANALYSIS OF PLASMA HISTAMINE LEVELS IN PATIENTS WITH MAST CELL DISORDERS

Friedman BS, Steinberg SC, Meggs WJ, Kaliner MA. Am J Med. 1 989;87:649-654.

Purpose of the Study

The purpose of this study was to determine whether plasma histamine measurements might be a useful screening tool to distinguish patients with recurrent unexplained anaphylaxis, flushing, or both from those with mastocytosis.

Using a radioenzymatic assay, plasma histamine levels were measured in 41 patients with mastocytosis (M), 26 patients with unexplained anaphylaxis (UEA), and 76 normal subjects (N).

Methods

Patients with UEA underwent an extensive evaluation to exclude other causes of anaphylaxis or flushing. Pa-tients with M were subdivided into smaller groups on the basis of clinical and histopathologic findings: (1) isolated urticaria pigmentosa, (2) indolent systemic M, (3) M with dysmelopoesis, and (4) lymphadenopathic M with eosin-ophilia. Plasma histamine levels were obtained on pa-tients with UEA during an asymptomatic period, al-though obtained in those with M “routinely, regardless ofsymptoms.” Multiple samples often were obtained from a given patient. The results were reviewed retrospectively after a 5-year collection period and analyzed to determine the diagnostic usefulness and accuracy of the plasma histamine measurements.

Findings

Patients with UEA had mean plasma histamine values which were not significantly different from those found in N subjects or in patients with urticaria pigmentosa. However, values for the other 3 groups of patients with M were significantly greater than N or UEA. Only 1 of 26 patients with UEA had a plasma histamine value greater than the 95% confidence limit. Analysis of the 27 sets of histamine values collected on patients with

indo-lent systemic M revealed that the earliest value observed fell into the normal range in 8 patients (30%). Data in 4 patients with M demonstrated a diurnal variation in histamine levels with the highest values observed in the early morning (approximately 2 AM) and the lowest value in the afternoon (approximately 2 PM).

Histamine determinations alone are not a useful screening procedure in the evaluation of patients with M. An elevated plasma histamine level, particularly if pres-ent on several occasions, is suggestive, but not diagnostic, for M. A normal histamine level, particularly if measured on several occasions, is suggestive evidence that the pa-tient does not have M. Patients with M exhibit a diurnal variation in plasma histamine levels.

The major flaw in this paper is that plasma histamine levels in patients with UEA were obtained while they were asymptomatic, whereas those in patients with M may have been obtained when they were having symp-toms. Additionally, assays for histamine are very tricky to do and I’m not sure how many commercial laboratories can perform this test accurately. Last, the authors never did analyze the histamine values for diagnostic accuracy. Nevertheless, in a given patient with UEA, repeated histamine values in the normal or abnormal range appear to have some diagnostic relevance. Other diseases such as chronic myelogenous leukemia and histamine-secret-ing carcinoid may also produce elevated plasma histamine levels. Tryptase levels are a very specific marker for mast cell disorders although they lack sensitivity. Commercial kits for tryptase determinations may soon become avail-able. The diagnostic usefulness of using both histamine and tryptase levels in these disorders should be assessed. Others have noted the diurnal variability in plasma his-tamine levels and suggested it as an explanation for the nocturnal worsening of asthma.

ALLEN D. ADINOFF, MD

Aurora, CO

A COMPARATIVE STUDY OF VIRUS ISOLATION, POLYMERASE CHAIN REACTION AND ANTIGEN DETECTION IN CHILDREN OF MOTHERS INFECTED WITH HUMAN IMMUNODEFICIENCY VIRUS

Krivine A, Yakudima A, et al. J Pediatr. 1 990;1

16:372-376.

Purpose of the Study

The purpose of this study was to compare polymerase chain reaction (PCR) with culture and PC-4 measure-ments for the diagnosis of human immunodeficiency in-fection in infants and children.

This study included 45 children born of mothers with antibodies to human immunodeficiency virus (HIV) Type

at Viet Nam:AAP Sponsored on September 2, 2020

(4)

Findings 3 of 4 of the others had AIDS; 12 of 13 were symptom-The results of the study established that the PCR test

was 100% sensitive (10 of 10), 93% specific in relation to cultures, and the concordance between the two tests was 96%. In relation to culture, the p24 assays were only 50% sensitive (6 of 12) and 100% specific. In a larger group of samples tested by both PCR and p24, sensitivity of p24 compared with PCR was 44% (8/18) and specificity was 100%. Culture and sensitivity were incident-specific in children older than 15 months of age with 100% concord-ance between PCR results and clinical findings in sero-logic status. p24 was sensitive to the other two, but very specific. However, in children younger than 15 months

the single test was 100% sensitive to culture, antibody,

or antigen. All children without antibodies had negative PCR results, and cultures agreed with PCR results in 23 of 24 simultaneous tests (25 of 26 children).

Conclusions

The PCR allows amplification of minute quantities of

viral or proviral DNA. It is increasingly emerging as a

tool for early diagnosis of HIV infection in infants and

children. Caution should be exercised in itsinterpretation

and performance as it is an extremely sensitive test,

unlike the p24 antigen assay.

free.

CHRISTOPHER RANDOLPH, MD

Waterbury, CT

INTERPRETATION OF WESTERN BLOTS OF

SPECIMENS FROM CHILDREN INFECTED WITH HUMAN IMMUNODEFICIENCY VIRUS TYPE 1: IMPLICATIONS FOR PROGNOSIS AND DIAGNOSIS

Walter EB, McKinney RE, Lane GA. J Pediatr. 1990;1 17:255.

This study was conducted to determine the significance of negative or indeterminant Western blots in children with suspected human immunodeficiency virus (HIV) infection.

Included in the study were 36 HIV-infected children,

9 of whom had indeterminate Western blot results and 2 of whom had negative results. The mean age of children was 3.2 years with a range of 1 month to 10 years.

Reviewer’s Comments Methods

The findings of this study are in contrast to those of Rogers et al which reported that only 50% (6 of 12) in whom other clinical and laboratory indexes of acquired immunodeficiency syndrome (AIDS) subsequently devel-oped had direct positive PCR results. They also noted discordant results in 7 of 20 samples or 35% of older children using peripheral blood mononuclear cells in com-parison with HIV culture. Furthermore, Laure et al re-ported that 5 children whose serologic test results became negative and were older than 15 months of age had positive PCR test results. Borwosky et al also noted inconsistencies between p24 antigen which could be dem-onstrated in 4 of 14 children before 9 months of age who eventually developed positive HIV cultures and serologic results. PCR is an extremely sensitive system for testing viral or proviral nucleic acids and was able to detect 3 to 10 copies of proviral DNA in iO cells. The danger of carrying DNA from one tube to another is ever present so that positives are defined only as samples that yielded duplicate positive tubes in two separate experiments. While p24, in contrast to PCR, is not a sensitive index, it is simple, rapid, and quantitative. Further disagreement in results between this report and others relates to the fact that patient groups differed, 40 of 45 of the patients included in the Krivine et a! study were outpatients consisting of two groups: one group of 32 children younger than 15 months of age, 25 of whom had HIV detected by enzyme-linked immunosorbent assay and/or Western blot. There were also 13 of these children who were less than 6 months of age, none of whom was a symptom-free neonate and 4 of whom were 1 month of age or younger;

The study was carried out by a retrospective review of Western blot immunoassays for anti-HIV 1 antibody. A Western blot positive result was defined by the presence of the following bands: p24 or p31 and gp4l or gp 120/

160. A negative result was defined as absence of any of these bands. An indeterminate result was defined as the presence of any band or bands without a pattern equiv-alent to a positive finding. p24 antigen and enzyme-linked immunosorbent assays (ELISAs) were done simultane-ously for 34 of 36 patients. Detection of HIV 1 in culture was also accomplished by p24 antigen ELISA. The Mann-Whitney rank-sum test was used for analysis of p24 data and Fisher Exact Test for analysis of death.

Findings

(5)

1032 ALLERGY AND IMMUNOLOGY Reviewer’s Comments

HIV-infected children with indeterminate Western blot results appear to have more antigenemia prognoses than those with positive Western blot results. Therefore, patients with a positive ELISA result and negative or indeterminate Western blot results require additional testing. A p24 antigen determination should be made, or culture for HIV should be grown, or PCR or HIV-specific antibody production and cultured patient lymphocytes.

CHRISTOPHER RANDOLPH, MD

Waterbury, CT

ABNORMAL PULMONARY FUNCTION SPECIFICALLY

HEART

FAILURE:

COMPARISON OF PATIENTS BEFORE AND AFTER CARDIAC TRANSPLANTATION

Hosenpud JD, Stibolt TA, Atwal K, Shelley D. Am J Med. 1990;88:493-496.

Purpose of the Study

A variety of abnormalities in pulmonary function have been attributed to or are believed to be exacerbated by congestive heart failure (CHF). To investigate the impact of cardiac disease on pulmonary function, spirometric measurements were performed on patients before and after cardiac transplantation.

Seventeen patients ( 13 men, 4 women) with a mean age of 44 years (20 to 62 years of age) were studied before and 15 ± 10 (mean ± SD) months after cardiac trans-plantation. Eleven patients had a significant smoking history. No patient had significant pulmonary hyperten-sion or obstructive lung disease.

Findings

In comparing the pretransplant and posttransplant spirometric results, forced vital capacity (FVC) and forced expiratory volume at i second (FEV,) increased substantially after transplant (P = .005 and P = .04, respectively). FEV1/FEV was not significantly different between study states in the entire group, nor was it different in those patients with and without a smoking

history. Normal FVCs were obtained after transplant in

those patients with no smoking history in contrast to

those with a smoking history. The increase in FVC after

cardiac transplantation directly correlated with the de-crease in cardiac volume (r = .83, P = .0001). Almost 70% of the change in FVC could be accounted for by the

change in cardiac volume.

Conclusions

The authors concluded that in patients selected as cardiac transplant patients, restrictive,but not obstruc-tive, pulmonary physiology could be attributed in part to

CHF. A major part of the reduction in FVC was felt

secondary to the space occupied by a large heart. The abnormal pulmonary function due to CHF in the popu-lation was completely reversible with normalization of cardiovascular physiology and anatomy.

It’s a shame these patients were not put in body box and had lung volumes measured directly (especially func-tional residual capacity and residual volume). The changes found in this study might be totally due to patient effort, given the fact that they probably felt better after transplantation and were out of CHF. It’s also too bad that respiratory symptoms and physical findings (wheezes, rales, gallops, etc) were not correlated with changes in pulmonary function. Did any of these patients have cardiac asthma or wheezing? Nevertheless, these findings do suggest that these patients with CHF did not have significant obstructive airways disease. Other fac-tors such as accompanying pleural effusions and intersti-tial and bronchial edema also likely contribute to changes in pulmonary functions seen in patients with CHF.

ALLEN D. ADINOFF, MD

Aurora, CO

Treatment

CROMOLYN SODIUM IN THE MANAGEMENT OF SYSTEMIC MASTOCYTOSIS

Horan RF, Sheffer AL, Austen KF. J Allergy C/in Immunol. I 990;85:853-855.

Purpose of the Study

The purpose of the study was to assess the effectiveness of oral cromolyn sodium in the treatment of patients with systemic mastocytosis.

Included in the study population were 1 1 patients with systemic mastocytosis.

Methods

Patients were studied in a multicenter, double-blind controlled trial of oral cromolyn sodium, 200 mg orally four times a day. Efficacy was measured by physician assessment of overall severity and average daily symptom scores. A baseline 4-week period during which all patients received open labeled cromolyn sodium was compared with 4-week intervals of a 16-week period of randomly assigned cromolyn sodium or placebo. Symptom diary

scores were analyzed for gastrointestinal symptoms and

nongastrointestinal symptoms.

Findings

The average symptom diary scores of patients in the

placebo-treated group increased during the

randomiza-tion phase, and the change from baseline in average

symptom scores in this group was significantly different

at Viet Nam:AAP Sponsored on September 2, 2020

(6)

from the patients in the cromolyn sodium-treated group, reflecting the exacerbation of symptoms in the placebo group when not taking cromolyn sodium. The average gastrointestinal symptoms scores demonstrated a signif-icant increase from baseline during the randomization phase in the placebo group. Benefit for the nongastroin-testinal manifestations did not reach statistical signifi-cance.

Reviewer’s Comments

Although the nongastrointestinal symptoms were not relieved significantly by the use of oral cromolyn sodium, the effects of cromolyn sodium in the individual gastroin-testinal symptoms seem to be of significant benefit. Ke-totifen also has been proposed as being beneficial in the treatment of patients with this disorder.

ALMA H. HERRERA, MD

Mobile, AL

SAFETY AND TOLERANCE OF INTERMITTENT

INTRAVENOUS AND ORAL ZIDOVUDINE THERAPY IN HUMAN IMMUNODEFICIENCY VIRUS INFECTED PEDIATRIC PATIENTS

McKinney RE, et al. J Pediatr. 1 990;1 16:640-647. Purpose of the Study

This study was conducted to evaluate three escalating dose schedules of Zidovudine (ZDV), every 6 hours for 1 to 2 months in a 12-week, three-center phase I study of intravenous (IV) and oral Zidovudine therapy in children with symptomatic human immunodeficiency virus (HIV) infection.

Study Population

Thirty-five children with symptomatic HIV were en-rolled in a 12-week, three-center phase I study. The children ranged in age from 5 months to 13 years with a median age of 3#{189}years. Sixty percent (21 children) had acquired immunodeficiency syndrome, and 40% (14) had related complex. Twenty children had <0.5 X i0 CD4 lymphocytes per liter (<500 cells/mm) at entry. Zido-vudine was infused at 80, i20, or 160 mg/m2 per dose for 1 or 2 months IV every 6 hours followed by orally admin-istered doses on the same schedule. The orally adminis-tered dose was 1#{189}times the intravenous dose.

Methods

Children were assigned to one of three treatment reg-imens. The first 10 children were scheduled to receive ZDV IV for 8 weeks, the next 25 for 4 weeks, although problems with venous access decreased the period to 3 weeks in 3 patients and 2 weeks in one. The other children were affected similarly. Following the intravenous phase all patients received ZDV orally at 1#{189}times the intra-venous dose. All children younger than 12 months re-ceived 80 mg/m2 per dose. Otherwise doses were given in an escalating scale. First, the lower dosage was

estab-lished to be safe, then the higher dose was given. Children had their dose adjusted on a case-by-case basis when toxic drug effects were present with reduction of 30% in dose with resumption of the normal dose as soon as possible. None of the 35 children given ZDV required permanent discontinuation of the drug.

Findings

Neutropenia was noted in 9 patients (defined as a count of 750 cells/mm) with anemia requiring transfu-sion in 7 patients and with dosage adjustments made in 15, in 12 because of anemia or neutropenia. Lowering of total IgG and 1gM concentration toward normal levels with decreased hepatosplenomegaly and rapid weight gain were also positive effects.

Zidovudine appears to be safe with tolerable side ef-fects in children using escalating doses. The most corn-mon significant side effects were hematologic, particu-larly neutropenia and anemia. Last, phlebitis associated with Staphylococcus aureus was a common complication during the intravenous portion of the study.

Waterbury, CT

INTRAVENOUS IMMUNOGLOBULIN IN HIV INFECTION: EVIDENCE FOR THE EFFICACY OF TREATMENT Hague RA, Yap PU, Mok JYQ, Eden OB, Coutts HA, Watson JG, Hargreaves FD, Whitelaw JM. Arch Dis Child. 1 989;64:1 146.

Purpose of the Study

This study investigated the effect of intravenous y-globulin (IVIG) on the course of human immunodefi-ciency virus (HIV) infection in children.

Eight children, aged 9 to 48 months, with clinical and laboratory findings consistent with HIV infection were studied.

Methods

All children had been observed for at least 9 months. Initiation of IVIG was based on a history of two or more episodes of bacterial pneumonia, 3 months of upper res-piratory tract infection, diarrhea, or symptomatic throm-bocytopenia. Dosage of IVIG was 200 mg/kg every 3 weeks, and children were followed up for at least 12 months on this therapy.

Findings

(7)

1034 ALLERGY AND IMMUNOLOGY

the number of hospitalizations. While on IVIG, children also had less difficulty with diarrhea. The administration of IVIG did not alter the decline in T4 lymphocytes, however, three of four children lost detectable HIV core antigen during therapy and this was sustained in three of these children. Investigators calculated that despite the high cost of IVIG the total cost of medical manage-ment in these children was ultimately reduced because of their improved clinical course.

Reviewer’s Comments

This study concurs with previous information (Eur J Paediatr. 1988;i47:300-303) which suggests that IVIG may be helpful in the management of patients with HIV infection. Such a result is not surprising because although these children may have hypergammaglobulinemia, they lack the ability to make specific antibody. Unfortunately, IVIG would not be specific against HIV because all do-nors lack anti-HIV antibody. Therefore, the clinical course may be improved while the underlying immuno-logic defect remains unaltered.

JOHN A. ZORA, MD

Atlanta, GA

THE USE OF

INTRAVENOUS

ADMINISTERED

IMMUNE

GLOBULIN TO PREVENT NOSOCOMIAL SEPSIS IN LOW BIRTH WEIGHT INFANTS: PART OF A PILOT STUDY

Clapp DW, Kliegman RM, et al. J Pediatr.

1 985;1 15:973.

This study was conducted to evaluate the use of intra-venously administered immunoglobulin for prevention of sepsis in preterm infants.

Eligible for this study were all newborns admitted to Rainbow Babies and Children’s Hospital between No-vember 1, 1986 and August 31, 1987 weighing 600 to 2000 g with no major organ malformation or congenital infec-tion.

Methods

One hundred and fifteen patients were assigned ran-domly in a double-blind, controlled trial and received either treatment with intravenous -y-globulin (IVIG) de-signed to maintain a therapeutic serum level of 700 mg/ dL or were placed in the placebo group. Eighty-five infants were not assigned randomly because of parental request and were followed up and analyzed separately.

Findings

There were 7 episodes of acquired sepsis in the placebo group, 9 episodes in the nonassigned group, and no epi-sodes in infants who received IVIG (P < .01). Four of the episodes of sepsis that were documented by positive blood

cultures, cerebral spinal fluid, or both in placebo-treated infants and nonassigned infants were fungal. Thirteen of 16 positive cultures were obtained from infants with a birth weight ofless than 1500 g, and all episodes occurred between 8 and 131 days of life with serum levels of IgG less than 400 mg/dL. There were 3 deaths in the IVIG group secondary to respiratory distress with respiratory syncytial virus infection implicated in one case. An equal number of deaths occurred in the placebo-treated group from respiratory distress and one from disseminated in-travascular coagulation. There were 7 deaths in the non-assigned group secondary to respiratory distress, intra-ventricular hemorrhage (grade 4) and one from entero-colitis stage 3B. Other interesting findings were side effects of noted tachycardia and transient decrease in blood pressure in one patient which resolved with discon-tinuation of infusion. This was the only acute reaction to IVIG in 206 infusions.

Reviewer’s Comments

The size of the patient sample precludes a conclusion that IVIG decreases incidence of nosocomial sepsis in premature infants and should require a sample size of more than 500. Other measurements of morbidity such as duration of protection, duration of intensive care and hospitalization, mechanical ventilation, general nutri-tion, and antibiotic therapy need to be assessed, because IVIG does not decrease mortality rates. Last, a critical IgG serum concentration that lowers the risk of infection should be defined, although it appears that dosing regi-mens should be individualized. In the present study, the investigators were unable to maintain the target level of 700 mg/dL in all cases. There are 3 trials in progress or recently completed. We should avoid routine use of IVIG to prevent nosocomial infection in premature infants until the results of these trials are available. (See the accompanying editorial by Drs Noya and Carol Baker of Baylor College of Medicine.)

Waterbury, CT

REDUCTION OF INFLAMMATION, TISSUE DAMAGE, AND MORTALITY IN BACTERIAL MENINGITIS IN RABBITS TREATED WITH MONOCLONAL ANTIBODIES AGAINST ADHESION PROMOTING RECEPTORS OF LEUKOCYTES

Tuomanen El, Saukkonen K, Sande 5, Cioffe C, Wright SD. J Exp Med. 1 989;1 70:959-968.

Purpose of the Study

Despite more powerful antibiotics, bacterial meningitis remains a significant cause of morbidity and mortality in infants and children. The purpose of this study was to determine if mAb 1B4, a monoclonal antibody directed against CD18 (adhesion) receptors on leukocytes could improve outcome in bacterial meningitis by reducing adhesion of the leukocytes to vascular endothelium, thus blocking their influx into the cerebrospinal fluid (CSF).

at Viet Nam:AAP Sponsored on September 2, 2020

(8)

Study Population

The study population was female New Zealand rabbits.

Methods

The rabbits were inoculated with Streptococcus pneu-moniae, Haemophilus influenzae, Neisseria menirigitidis,

pneumococcal cell wall, lipopolysaccharide, or heat-killed pneumococci. Monoclonal antibody mAb IB4 was given intravenously 40 minutes before inoculation, or at time of inoculation and 24 hours later. Blood-brain barrier permeability was studied using ‘25I-labeled human serum albumin (HSA). CSF was sampled from the cisterna rnagna.

Findings

Pretreatment with intravenous mAb 1B4 effectively blocked accumulation of leukocytes in the CSF in re-sponse to all inoculae. mAb 1B4 given after inoculation had no effect. Intracisternal mAb had no effect. mAb 1B4 treatment decreased the permeability of the blood-brain barrier and eliminated cerebral edema. All pretreated animals survived a normally lethal dose of bacteria. Spread of bacteria from the CSF into the blood was delayed in the treated rabbits.

Conclusions

Blocking influx of leukocytes into infected CSF pre-vented inflammation, cerebral edema, and death.

This is a fascinating study, which initiates many other questions regarding mediators of inflammation and pos-sible therapeutic modalities.

MARY ELLEN FRIEDMAN, MD

Downey, CA

TOXICITY AND SERUM LEVELS OF METHOTREXATE IN CHILDREN WITH JUVENILE RHEUMATOID ARTHRITIS

Wallace CA, Bleyer WA, Sherry DD, Salmonson KU, Wedgewood RJ. Arthritis Rheum. 1 989;32:677-681.

Purpose of the Study

The purpose of this study was to evaluate prospectively the use of methotrexate (MTX) in the treatment of juvenile rheumatoid arthritis (JRA) and to assess

whether serum MTX levels are useful in predicting effi-cacy and/or toxicity to the drug.

Included were 23 children with polyarticular JRA (aged 4 to 18 years) whose disease had been controlled poorly on conventional therapy.

Methods

Patients were treated for 0.5 to 4.3 years (median = 1.6 years) with weekly doses of MTX (0.11 to 0.60 mg/

kg per week). All other previous medications being used by the patient except gold were continued. Improvement in symptoms and reduction in use of arthritis medication (eg, prednisone) were used to determine response. Serum levels of MTX at 1 hour and 24 hours after drug admin-istration were obtained at each dosage level. Laboratory monitoring (complete blood cell count, liver function tests) was performed every 2 weeks initially, and then monthly.

Findings

No significant drug toxicity was noted in any of the patients. Ten patients had transiently elevated serum transaminase levels, but MTX treatment did not need to be discontinued permanently. Arthritis symptoms im-proved in 21 of these 23 JRA patients; 6 of the 9 patients on oral steroids had a significant decrease in their dose. The clinical improvement was associated significantly with a mean 1-hour serum MTX level of 5.8 x i0? mol/ L and a dosage of 0.3 mg/kg per week. Fourteen of 21 patients required one or more increases in the dosage of MTX. The mean 1-hour serum level of MTX at the time response to treatment was evident and was significantly different from the mean i-hour level noted with a MTX dosage to which no response was seen.

MTX therapy now is being investigated for the treat-ment ofchronic, severe asthma in adults. A small number of children with severe asthma have been started on MTX therapy, but results are very preliminary. It is likely with the trend of increasing use in adults that MTX treatment may become more commonplace as a therapeu-tic option for severe, difficult-to-manage pediatric pa-tients. The experience of MTX use in juvenile rheuma-toid arthritis (which has a “head start” on asthma) may turn out to be helpful in giving us guidelines on how to treat children with asthma. This article provides us with the information that MTX was well tolerated, resulted in only transient mild elevation in serum transaminase levels, and appeared to be highly effective in improving the symptoms of JRA. An important finding was that serum MTX levels done at 1-hour postdose were helpful in guiding the treating physician as to what dose of MTX needed to be given to generate a beneficial response. Hopefully, monitoring blood levels of MTX will also be useful when managing children with severe asthma on MTX.

MICHAEL J. WELCH, MD

San Diego, CA

HIGH DOSE EPINEPHRINE IN REFRACTORY PEDIATRIC CARDIAC ARREST

Goetting MG, Paradis HA. Crit Care Med. 1989;17:1258-1 261.

Purpose of the Study

(9)

1036

ALLERGY

AND

IMMUNOLOGY

during cardiac arrest that will result in return of spon-taneous circulation (ROSC).

Study Population

Included in the study were 38 resuscitations in 30 patients done by the senior author. Eighteen were ex-cluded (8 due to unknown time for institution of cardio-pulmonary resuscitation after arrest and 10 due to prompt response to treatment).

Methods

Standard protocols included 0.01 mg/kg epinephrine and 1 mEcijkg sodium bicarbonate initially given intra-venously (IV) with epinephrine repeated every 5 minutes and sodium bicarbonate repeated every 10 minutes. Asys-tole and bradycardia were treated with 0.02 mg/kg atro-pine initially and every 5 minutes as needed. Ventricular tachyarrhythmias were treated with electrical cardiover-sion and IV lidocaine. None of the patients had ROSC if a third dose of epinephrine was needed.

Findings

Seven subsequent cases were described. Four older children (aged 14 months, ii years, 4 years, and 16 years) were used for the analysis. Three neonatal patients were presented as supportive data, but not included in the analysis. None of the 20 previous patients with cardiac arrest had ROSC when three doses of epinephrine were required. Three of four of the patients who were treated initially with the authors’ standard protocol had ROSC after a single dose of 0.2 mg/kg of epinephrine given IV after failure of two “standard doses.”

Previous animal models and the current study suggest that much higher doses of epinephrine (0.2 mg/kg) may be needed in cardiac arrest refractory to standard doses (0.01 mg/kg). The optimal application of this observation to cardiopulmonary resuscitation has yet to be defined.

BRADLEY E. CHIPPS, MD

Sacramento, CA

Immunology

Pathophysiology

EVIDENCE FOR COMPARTMENTALIZATION OF FUNCTIONAL SUBSETS OF CD4 T LYMPHOCYTES IN ATOPIC PATIENTS

Wierenga EA, Snoek H, et al. J lmmunol. 1 990;1 33:4651-4656.

Purpose of the Study

The purpose of the study was to study the lymphocyte secretion profiles of human allergen-specific CD4

lym-phocyte clones and to attempt to define further the nature of lymphokine profiles of these T lymphocyte clones in atopic patients.

There were two atopic patients. The first was a 24-year-old with chronic atopic dermatitis, an IgE level of 24 000 IU/mL, and a history of asthma with a possible allergic component. The second atopic patient was a 21-year-old patient with asthma with a total IgE level of 470 IU/mL. Both patients demonstrated specific IgE to

Der-matophagoides pteronyssinus (Dp) when evaluated by radioallergosorbent test (RAST). Another patient was a nonatopic 37-year-old who had a serum IgE level of 120 IU/mL and a negative Dp-specific RAST with a history not suggestive of any allergic manifestation and therefore considered a nonatopic individual.

Methods

Secretion of interleukin-2 (IL-2), interleukin-4 (IL-4), and interferon-’y (IFN-y) were determined after specific simulation of T lymphocyte clones from the three above subjects using autologous monocytes as antigen-present-ing cells. Atopic individual one, listed as AD1, also had T-cell lymphocyte clones harvested specifically for teta-nus toxoid or Candida albicans.

Findings

1. IL-4 was produced by Dp-specific T lymphocyte clone levels from both atopic donors. IL-4 was not produced from the Dp-specific T lymphocyte clone of nonatopic individuals, and it was produced from the T lympho-cyte clones from patient AD i clones from the tetanus toxoid and C albicans-specific cells.

2. The nonatopic individual and cell lines for AD1 for tetanus and C albicans did produce IFN-y, but the two atopic individuals with Dp-specific T lymphocyte clones did not produce IFN--y.

3. Most T-cell lymphocyte clones from all panels pro-duced IL-2. Based on these data the authors concluded that CD4-positive T lymphocytes that produce IL-4 but not IFN-y occur in high frequency in the allergen-specific T-cell repertoires of atopic donors.

Reviewer’s Comments

The authors suggested, knowing that antigen-specific immunoglobulin production is regulated by CD4 T cells with the same specificity and that murine IgE synthesis in vivo was also regulated by IL-4, that their two patients with atopic disease, namely atopic dermatitis and asthma, resulted from the predominant occurrence of allergen-specific T cells whose lymphokine secretion profile re-semble murine TH2 cells. These data further elucidate the possible type and function of CD4 T cells in the pathogenesis of atopy. This study has two limiting fac-tors: (1) only three patients were studied, two atopic and one nonatopic individual. It would be of interest to see a much larger population studied. (2) The presence of specific IgE to D pteronyssinus does not automatically translate into allergen-induced clinical manifestations of

at Viet Nam:AAP Sponsored on September 2, 2020

(10)

disease. It is not only difficult to characterize the immu-nological profile of atopic patients, it is difficult to just define the process of atopy.

MARTIN I. SACHS, PHD, DO

Rochester, MN

INFECTION WITH HIV IS ASSOCIATED WITH ELEVATED IL-6 LEVELS AND PRODUCTION

Breen EC, Rezai AR, Nakajima

X, Seall GN, Mitsuyasu

RT, Hirano T, Kishimoti T, Martinez-Maza 0. J Immunol. 1 990;44:480-484.

Purpose of the Study

This study was conducted to compare the levels of circulating plasma interleukin-6 (IL-6), spontaneously produced IL-6, and IL-6 mRNA in HIV-infected donors with the levels in healthy control donors and, therefore, to examine the potential mechanism for the polyclonal B cell activation which characteristically is seen in human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS).

Twenty-eight HIV-infected individuals and 1 1 healthy adult control donors were studied. The HIV-infected subjects tested included 17 HIV-seropositive donors, 6 asymptomatic, ii with disease not characterized as AIDS or AIDS-related complex (ARC), 7 patients with AIDS either with Kaposi’s sarcoma or opportunistic infections, and 4 people with ARC.

Methods

Peripheral blood mononuclear cells were isolated. IL-6 assay was measured by using the IL-6 responsive mu-rine hybridoma cell line MH6O.BSF-2. IL-6 mRNA iso-lation and analysis was performed by obtaining total RNA from unstimulated freshly isolated peripheral blood mononuclear cells (PBMCs). The RNA was then blotted onto a nylon membrane, and RNA fractions were ana-lyzed by densitometry.

Findings

Elevated levels of plasma IL-6 and IL-6 mRNA were detected in HIV-infected donors. Unstimulated PBMCs from HIV-infected donors produced markedly elevated amounts of IL-6 when compared with cells isolated from healthy donors. The authors concluded that these results demonstrated that elevated levels of IL-6 were associated with HIV infection and suggested that IL-6 overpro-duction may contribute to the polyclonal B cell activation seen in AIDS and HIV infection.

Other interesting findings included the fact that, al-though previously reported, IL-6 levels in patients had been elevated with concomitant bacterial infections and, after lipopolysaccharide injection in this study, the IL-6

levels in HIV-infected donors were the same regardless of whether they had co-infections such as tuberculosis, candidiasis, syphilis, and Pneumocystis. The fact that HIV donors spontaneously produce larger amounts of IL-6 than healthy controls may suggest that once IL-6 production has been initiated, it is resistant to immuno-suppression. Finally, the authors pointed out that HIV-infected individuals have a higher level of subacute bac-terial and viral infections than healthy individuals and that might contribute to elevated plasma IL-6 levels.

MARTIN I.SACHS, PHD, DO

Rochester, MN

Diagnosis

SUBNORMAL SERUM CONCENTRATIONS OF IgG2 IN CHILDREN WITH FREQUENT INFECTIONS

ASSOCIATED WITH VARIED PATTERNS OF IMMUNOLOGIC DYSFUNCTION

Shackelford PG, Granoff DM, Polmar SH, Scott MG,

Goskowica

NC, Madassery

JV, Nahm MH.

J Pediatr.

1990;1 16:529-538.

Purpose of the Study

This study was performed to look for associated im-munologic abnormalities in symptomatic patients with IgG2 deficiency.

Included in the study were 8 patients with frequent infections and IgG2 deficiency, 1 to 12 years of age.

Methods

All study patients had levels of immunoglobulins and IgG subclasses measured. They all received vaccination with Haemophilus influenzae type B (Hib) (unconju-gated), pneumococcal (type 3 polysaccharide), and teta-nus toxoid vaccines. Antibody responses to the vaccines were measured. Classification of lymphocytes and in vitro stimulation of lymphocytes with pokeweed mitogen and

Staphylococcus protein A was also done.

Findings

All 8 children had normal IgG2 and IgG1 levels. Three of the eight children had subnormal IgG2 alone, but 3 others had low IgA levels, and 2 of these 3 also had low IgG and 1gM levels. Three children had low IgG4 levels and one had a low IgG3 level. During a period of 0.8 to 3.2 years, the IgG2 levels of 2 subjects normalized, 3 subjects had levels increase to low normal, and IgG2 levels of the remaining 3 children declined further.

There was normal antibody response to the Hib and pneumococcal vaccines in the 2 children with normali-zation of IgG2 levels, but the 6 other subjects had weak IgG1 and IgG2 response to the Hib vaccine, and 4 of 6 showed weak response to the pneumococcal vaccine as well. Three of the six had weak responses to tetanus

toxoid. Only 1 of 4 children immunized with an H

(11)

1038 ALLERGY AND IMMUNOLOGY

There were normal T-cell subpopulations in all pa-tients, and normal B-cell populations in all but one patient. Lymphocytes proliferated normally in response to in vitro mitogen stimulation. There was marked de-crease in IgG2 secretion in vitro in five of the children with low IgG2; four of these patients secreted low levels of IgG1 and IgG3 as well.

Conclusions

The authors concluded that impaired antibody re-sponses of children cannot be attributed solely to an inability to secrete IgG2, because the children in the study had impaired response of both IgG1 and IgG2 to the vaccines used in the study and healthy children with low IgG2 levels did not have the impaired antibody responses to vaccines seen in symptomatic children.

This study involves too few patients to characterize definitively the nature of IgG2 deficiency. There is also a discrepancy between the weak response to tetanus toxoid seen in half of the patients in this study compared with the normal response to tetanus toxoid seen in ii children with IgG2 deficiency in the study by Umetsu et al. How-ever, much of the literature supports the authors’ hypoth-esis that poor antibody responses of recurrent infections cannot be explained by the deficiency of IgG2 alone and points to the value of measuring antibody response in defining deficiency rather than measuring -y-globulin lev-els alone.

LAURA E. METZGER, MD

Los Angeles, CA

ABNORMAL FcRIII EXPRESSION BY NEUTROPHIUS FROM VERY PREMATURE NEONATES

Carr R, Davies JM. B/ood. 1 990;76:607-61 1.

The purpose of this study was to determine if the receptors for IgG, FcRII and FcRIII, are decreased on the neutrophils of premature infants.

A total of 27 premature infants (median age 27 weeks, range 24 to 32 weeks) were assessed to determine if they were “well” (no major complications) or “stressed” (res-piratory distress syndrome or sepsis) and were studied at different time intervals (day 1 up to 2 months). A group of healthy term newborns born by elective cesarean sec-tion and healthy adults were studied for comparison.

Methods

Fc receptor expression was measured by fluorescence-activated cell sorter analysis of cells stained with mono-clonal Leu lib for FcRIII and IV.3 for FcRII.

Findings

The well premature infants displayed reduced FcRIII (5i.1 ± 2.0 mean fluorescence channel) as compared with term neonates (69.2 ± 5.5) or adults (71.8 ± 3.0). Stressed premature infantss with respiratory distress syndrome or sepsis had decreased FcRIII (32.7 ± 2.0 and 35.9 ± 1.8, respectively). Expression of FcRIII in well premature infants reached adult levels by 2 weeks of age. FcRII levels in well and stressed premature infants did not differ from those of adults.

Reduced neutrophil FcRIII expression in premature infants may contribute to the abnormalities in phagocy-tosis and bacterial killing in premature neonates. This study may have implications for the use of intravenous -y-globulin for premature infants and also for the devel-opment of monoclonal antibodies that bind specifically to either the FcRII or FcRIII receptors on neutrophils.

ROBERT L. ROBERTS, MD, PHD

Los Angeles, CA

CEREBROSPINAU FLUID CACHECTIN/TUMOR NECROSIS FACTOR AND PLATELET ACTIVATING FACTOR CONCENTRATIONS AND SEVERITY OF BACTERIAL MENINGITIS IN CHILDREN

Arditi M, Manogue KR, Chaplin M, Yogev R. J Infect Dis. 1 990;1 62:139-147.

Purpose of the Study

This study was conducted to determine if the concen-tration of tumor necrosis factor (TNF) and platelet-activating factor (PAF) in the cerebrospinal fluid (CSF) of children with meningitis correlated with the severity of the disease.

CSF samples were obtained from 38 children (aged 6 weeks to i4 years, median 9 months) with confirmed bacterial meningitis (BM). Isolates included Haemophi-lus influenzae (22), Streptococcus pneumoniae (9), Neis-seria meningitidis (3), and Escherichia coli (2). Control CSF samples were obtained from surgical patients (yen-triculoperitoneal shunts) and febrile patients with aseptic (presumed or viral) meningitis.

Methods

TNF was measured by an ELISA assay and PAF by thin layer chromatography.

Findings

TNF was detected in 33 of 38 children with BM, but in none of the 15 children with viral meningitis (P <

.001). CSF TNF levels correlated with CSF bacterial density, CSF protein, and seizure activity. Higher CSF

at Viet Nam:AAP Sponsored on September 2, 2020

(12)

TNF levels were also found in a higher proportion of children who died (P < .Oi) and correlated with bacterial density, CSF TNF levels, and the Herson-Todd severity score.

Reviewer’s Comments

Detectable TNF appears to distinguish BM from viral meningitis, and higher levels of TNF and PAF correlate with the severity of BM. This study indicates that specific cytokines, now being identified, may be responsible for a major portion of the morbidity associated with some infectious diseases. The identification of these cytokines may lead to more specific therapies to prevent the inflam-matory processes that are detrimental to the host.

ROBERT L. ROBERTS, MD, PHD Los Angeles, CA

X-LINKED SEVERE COMBINED IMMUNODEFICIENCY DIAGNOSIS IN MALES WITH SPORADIC SEVERE COMBINED IMMUNODEFICIENCY

Conley ME, Buckley RH, Hong R, Guerra Hanson C, Roifman CM, Brochstein JA, Pahwa 5, Puck JM. J C/in /nvest.1 990;85:1 548-1554.

Purpose of the Study

Severe combined immunodeficiency (SCID) is a term used to describe a heterogeneous group of genetic disor-ders with defects in both cellular and humoral immunity. More than 80% of infants with SCID of unknown genetic etiology (ie, not inherited as an autosomal recessive dis-order) are males, with less than one third having a family history of X-linked disease. This study attempted to identify new mutations of the X-linked SCID gene and to provide genetic counseling.

Sixteen mothers of boys with sporadic SCID and their affected sons all had normal adenosine deaminase and purine nucleoside phosphorylase activity.

Methods

X chromosome inactivation patterns in T cells were examined. Human/hamster hybrids that selectively re-tamed the active human X chromosome were produced from the T cells of each woman and analyzed with an X-linked restriction fragment length polymorphism for which the woman was heterozygous.

Findings

The X chromosome inactivation pattern established the nature of the genetic defect in 7 of the 16 families (ie, carriers). The distinguishing immunologic abnormalities in these patients with X-linked SCID was an elevated proportion of B cells.

This study has demonstrated the high incidence of spontaneous mutation for the X-linked SCID gene and helps clarify the characteristic manifestations of this disorder. The techniques used in this study will permit carrier detection, prenatal diagnosis, and help clarify

future risks for members of the family with the X-linked disorders and will also help with gene therapy when such procedures become available.

Treatment

GARY S. RACHELEFSKY, MD Los Angeles, CA

RECOMBINANT HUMAN IL-4 INDUCES IgE AND lgG

SYNTHESIS

BY NORMAL

AND ATOPIC

DONOR

MONONUCLEAR CELLS

Classen

JL, Levine

AD, Buckley

RH.

J Immunol.

1 990;1 55:2123-2139.

Purpose

of the Study

Previous studies have shown that human interleukin-4 (IL-interleukin-4) induces proliferation of activated T and B cells and stimulates in vitro synthesis of IgE by blood mono-nuclear cells. Other studies suggest that spontaneous IgE synthesis by mononuclear cells from atopic individuals is greater than that of nonatopic donors. This study char-acterizes the response for mononuclear, T, and B cells of atopic and nonatopic individuals to recombinant human IL-4 (rhIL-4).

Study Population

An adult population of 34 individuals was studied, 19 of whom were atopic and 15 who were nonatopic.

Methods

Mononuclear, T-cell, and B-cell subsets from atopic and nonatopic donors were isolated. Mononuclear cells were cultured in medium alone or in the presence of a concentration of purified rhIL-4, and the magnitude and kinetics of the IgE and IgG response was measured. The effect of T cells and T-cell clone supernatants was also evaluated.

Findings

(13)

1040 ALLERGY AND IMMUNOLOGY Reviewers’ Comments

B cells from both atopic and nonatopic donors respond similarly with respect to IgE synthesis via IL-4 stimula-tion. In addition, T cells from both atopic and nonatopic donors have similar effects on B-cell IgE synthesis in the presence of IL-4. It may be that atopy and other disease states characterized by excessive IgE production could be explained by abnormal regulation of IL-4. Treatment would therefore be directed at down-regulation of IL-4 production.

CYNTHIA M. SZELC, MD Los Angeles, CA

ROBERT L. ROBERTS, MD, PHD Los Angeles, CA

GUUCOCORTICOID REGULATION OF THE HUMORAL IMMUNE SYSTEM

Wira CR,

Sandoe

CF, Steele NC. J Immunol. 1990;1 00:102-106.

Purpose of the Study

This study was performed to determine whether glu-cocorticoids influence the level of immunoglobulins in serum, saliva, and vaginal secretions.

Adult female Sprague-Dawley rats were studied.

Methods

Studies were performed in intact and adrenalecto-mized-ovariectomized rats. Studies were also performed after rats were immunized, and immunizations were boosted with sheep red blood cells (SRBC) at two mucosal sites.

Findings

IgA levels in serum were elevated when increasing doses of dexamethasone were administered to intact and adrenalectomized-ovariectomized rats. In contrast, IgA levels decreased in the saliva and vaginal secretions in those rats. Similarly, after immunization with SRBC, dexamethasone increased the anti-SR9C IgA antibody levels in the serum and reduced their presence in vaginal secretions. In contrast, anti-SRBC IgG antibody levels in serum and vaginal secretions were reduced with hor-mone treatment.

Reviewer’s

Comments

The authors hypothesized that glucocorticoid-con-trolled IgA increase in the serum and decreases in the vaginal and salivary secretions may be due in part to the redistribution of polymeric IgA from mucosal services to serum. A further hypothesis is that this redistribution allows for an enhancement of systemic immune protec-tion.

MARTIN I. SACHS, PHD, DO

Rochester, MN

VIRUSES AS THERAPEUTIC AGENTS. I. TREATMENT OF NONOBESE INSULIN-INDEPENDENT DIABETIC MICE WITH VIRUS PREVENTS INSULIN-DEPENDENT DIABETES MEULITUS WHILE MAINTAINING GENERAL IMMUNE COMPETENCE

Oldstone, MBA. J Exp Med. 1 990;1 71:2077-2089.

Purpose of the Study

Viruses, in addition to causing disease, can have effects on immune function. Lymphocytic choriomeningitis vi-rus (LCMV) has been shown to cause selective immuno-suppression of autoimmune diabetes in mice. The pur-pose of this study is to characterize further the effects of LCMV infection.

Nonobese insulin-dependent diabetes (NOD) mice are an inbred strain which develop autoimmune diabetes mellitus by 9 to 12 months of age. The disease is char-acterized by hyperglycemia and hypoinsulinemia, with lymphocytic infiltration of the islets of Langerhans.

Methods

Donor NOD mice were infected with LCMV at birth. For cell transfer experiments, purified splenic lympho-cytes and/or bone marrow cells from 7- to 9-month-old infected or control mice were injected into noninfected 8- to 9-week-old recipients. For some experiments, CD4-, CD8-, or TH-1.2 lymphocyte-depleted specimens were used; depletion was achieved using monoclonal an-tibodies plus complement. To test other CD4-dependent immune responses, control and infected NOD mice were injected with bovine serum albumin, keyhole limpet he-mocyanin, human IgG, or sheep red blood cells. Antibody titers were measured using an enzyme-linked immuno-sorbent assay technique, 7 and 28 days after the first inoculation, and 7 days after a second inoculation of antigen.

Findings

Infection of NOD mice at birth with LCMV prevented the development of diabetes mellitus. Infected mice were both biochemically and histologically normal. Cell trans-fer experiments showed that the protective effect of LCMV involved the infected CD4 splenic lymphocytes. This effect appeared to be specific to autoimmune dia-betes mellitus, because LCMV-infected mice showed nor-mal responses to the other CD4’-dependent antigens.

Astounding! See also: Goldstone, Ahmed, and Salvato. Viruses as therapeutic agents. II. Viral reassortants map prevention of insulin-dependent diabetes mellitus to the small RNA of lymphocytic choriomeningitis virus. J Exp Med. 1990;171:2091-2100.

MARY ELLEN FRIEDMAN, MD Downey, CA

at Viet Nam:AAP Sponsored on September 2, 2020

(14)

1991;87;1028

Pediatrics

NANCY K. OSTROM

Systemic and Other System Disorders

Services

Updated Information &

http://pediatrics.aappublications.org/content/87/6/1028

including high resolution figures, can be found at:

Permissions & Licensing

http://www.aappublications.org/site/misc/Permissions.xhtml

entirety can be found online at:

Information about reproducing this article in parts (figures, tables) or in its

Reprints

http://www.aappublications.org/site/misc/reprints.xhtml

(15)

1991;87;1028

Pediatrics

NANCY K. OSTROM

Systemic and Other System Disorders

the World Wide Web at:

The online version of this article, along with updated information and services, is located on

been published continuously since 1948. Pediatrics is owned, published, and trademarked by the

Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it has

at Viet Nam:AAP Sponsored on September 2, 2020

http://www.aappublications.org/site/misc/Permissions.xhtml

http://www.aappublications.org/site/misc/reprints.xhtml