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Biomedical subjects

A Litwin

Publications and source records attributed to A Litwin.

At least 19 recordsLinked to original sources

Oral immunotherapy with short ragweed extract in a novel encapsulated preparation: a double-blind study.

BACKGROUND: In the past, oral immunotherapy with allergens has had limited clinical effectiveness, presumably because of gastrointestinal destruction of allergens. OBJECTIVE: We have developed a new technique for microencapsulating protein antigens that permits them, when given orally, to bypass the stomach and be delivered to the small intestine in a highly immunogenic form. This study's purpose was to confirm the immunologic potency of orally administered short ragweed pollen extracts (SRW) microencapsulated (mSRW) by this new technique and to study the effectiveness of mSRW in controlling the symptoms of ragweed-induced hay fever. METHODS: Twenty-one SRW-sensitive patients were treated with mSRW in a double-blind placebo-controlled study. Serum SRW IgG and IgE antibodies and nasal secretory IgA antibodies were determined. During the ragweed season, symptoms were quantified by symptom-medication scoring. RESULTS: The treated patients had high titers of serum SRW IgG antibodies (1.15 microg/ml at baseline, increasing to 21.21 microg/ml), experienced regulation of the seasonal increase in serum SRW IgE antibodies (+9% vs +59% in placebo-treated patients), and produced a small amount of nasal SRW IgA antibodies. Despite an insubstantial pollen count, the symptom-medication scores in the treated group were lower than those in the placebo group (4.28 vs 6.18, p = 0.059), but the differences were statistically significant only in the subgroup that tolerated high doses (>20 microg of Amb a 1 in 19 of 21 patients, p = 0.04). These effects were accomplished without inducing any systemic reactions with a dose of mSRW (mean, 23.8 microg of Amb a 1) only slightly higher than that used in high-dose subcutaneous immunotherapy. CONCLUSION: Oral mSRW seems a safe, easily administered, and immunologically potent treatment for ragweed-induced hay fever, but its ultimate utility requires further study.

Administration, Oral↗

Immunologic effects of encapsulated short ragweed extract: a potent new agent for oral immunotherapy.

BACKGROUND: Oral allergen immunotherapy with conventional allergens has not been a useful mode of treatment because of the lack of potency of allergens when administered by this route. OBJECTIVE: To study the immunologic potency of short ragweed pollen extracts microencapsulated by a new technique administered orally to short ragweed pollen-sensitive humans and to establish the dose of oral microencapsulated short ragweed pollen extract required for these effects. METHODS: Nine short ragweed pollen-sensitive patients were treated with a new oral agent for immunotherapy, microencapsulated short ragweed pollen extract, in an open study. The effectiveness of this treatment was determined by comparison to a group of nine matched short ragweed pollen-sensitive patients who received no treatment. Treated patients developed high titers of short ragweed-specific IgG and IgE antibodies and their expected seasonal increase in IgE antibodies was regulated. The dose of microencapsulated short ragweed pollen extract required to achieve these effects was only slightly higher than the dose of short ragweed pollen extract used in high dose subcutaneous immunotherapy. Furthermore, this dose was achieved in 7 weeks. There were no side effects other than mild gastrointestinal ones. The nine treated patients fared clinically better during the ragweed season than the untreated patients in this open study. CONCLUSION: This study suggests that allergens microencapsulated by this new technique may make oral immunotherapy a practical mode of treatment.

Adult↗

Phototherapy for neonatal nonhemolytic hyperbilirubinemia. Analysis of rebound and indications for discontinuing therapy.

Phototherapy, an effective treatment for neonatal indirect hyperbilirubinemia, has guidelines for its initiation but none for its discontinuation. In our study, phototherapy was begun at a mean age of 90 hours in 28 full-term and 30 preterm infants with indirect nonhemolytic hyperbilirubinemia. After three days, phototherapy was halted at a mean bilirubin concentration of 13.0 +/- 0.7 mg/dL in term and 10.7 +/- 1.2 mg/dL in preterm infants, levels higher than those used by other investigators. Bilirubin rebound then occurred at a mean of 12.5 hours to a level of 0.86 +/- 1.0 mg/dL in term and at a mean of 14.1 hours to a level of 0.83 +/- 0.56 mg/dL in preterm infants. No complications were observed nor was there a need for reinstitution of phototherapy. Based on these data, discontinuation of phototherapy at higher bilirubin concentrations and earlier home discharge than previously described appear harmless for both term and preterm neonates.

Bilirubin↗

Prevalence of minor congenital anomalies in newborns of diabetic mothers.

Minor congenital anomalies (MCA) were assessed in the offspring of 802 gestational diabetic mothers, 117 pre-gestational diabetic mothers, and 380 offspring born to normal mothers. The prevalence of infants with MCA ranged between 19.4% and 20.5% in the three groups without any significant difference between them. There was no correlation between the prevalence and type of MCA and the severity of the diabetic state. Neither was there any correlation between the prevalence or type of MCA and the appearance or type of major congenital anomalies.

Abnormalities, Multiple↗

Neonatal intestinal perforation due to congenital defects in the intestinal muscularis.

Congenital defect of the muscular layer of the small intestine is a rare cause of spontaneous bowel perforation in premature infants. During the last 12 years we have observed four similar cases. We describe the most recent one, a premature infant who developed two abdominal events. On her 2nd day of life, spontaneous perforation of the distal ileum due to focal absence of the muscular layer occurred. Several weeks later she developed the typical clinical and histological picture of necrotizing enterocolitis. The clinical and histological characteristics of the two different conditions are compared, and the 24 cases reported in the literature are discussed. We conclude that focal absence of intestinal musculature may be not such a rare entity as is commonly believed.

Female↗

Transient hepatic dysfunction in an infant of an epileptic mother treated with carbamazepine during pregnancy and breastfeeding.

OBJECTIVE: A case is reported of a carbamazepine (CBZ)-treated epileptic mother whose newborn presented with transient hepatic dysfunction characterized by direct hyperbilirubinemia and high concentrations of gamma-glutamyltransferase (GGT). DATA SOURCES: Information was obtained from case reports, clinical trials, and relevant bibliographic laboratory studies. DATA EXTRACTION: Data from case reports were evaluated and compared with those from our patient. The hepatotoxic reactions together with the microsomal enzymatic induction of CBZ were reviewed. DATA SYNTHESIS: A female infant born to an epileptic mother treated with CBZ throughout pregnancy and breastfeeding presented with transient direct hyperbilirubinemia and high concentrations of GGT. The characteristics of her transient hepatic dysfunction were: early appearance (during the first day of life); discrepancy between the normal liver enzymes and high GGT concentrations; slow decrease of GGT, which nevertheless remained at above-normal concentrations even after the complete disappearance of direct hyperbilirubinemia; and spontaneous resolution in spite of only occasional breastfeeding. The possible explanations of this transient hepatic dysfunction (like enzymatic induction) are discussed. CONCLUSIONS: CBZ-induced hepatic dysfunction in neonates appears to have different clinical expressions. Infants of epileptic mothers treated with CBZ throughout pregnancy and breastfeeding should be carefully monitored for possible adverse effects.

Adult↗

Clitoral length assessment in newborn infants of 30 to 41 weeks gestational age.

Clitoromegaly in the neonatal period is an important morphological sign. There are only few reports establishing an objective assessment of clitoral size. The present study establishes normal standards for clitoral length in healthy premature and full-term infants. The data are expressed at the same time in relation to both gestational age and birth weight, two variables which are strictly intercorrelated. Appropriate curves, which permit an easy and rapid objective determination of clitoral size, are presented.

Birth Weight↗

Regulation of the human immune response to ragweed pollen by immunotherapy. A controlled trial comparing the effect of immunosuppressive peptic fragments of short ragweed with standard treatment.

A new allergenic preparation consisting of peptic fragments of short ragweed has been tested for its clinical effectiveness. Such enzymatically derived fragments have been shown in prior murine studies to retain the T epitopes of the original allergen but to have a severe reduction in the number of B epitopes. Three groups of ragweed hayfever patients were placed on pre-seasonal immunotherapy. One group received a conventional ragweed preparation that had been enriched for antigen E (Amb a I), designated as Pool 2. The second group was given fragments of Pool 2 (fSRW) prepared by peptic digestion and the third group was injected with histamine as a placebo. Groups treated with the fSRW and Pool 2 had significantly reduced symptom-medication scores compared with the placebo-treatment group. However, fSRW-treated patients fared significantly better than Pool 2 patients (P less than 0.02). fSRW injections caused a significant rise in preseasonal specific IgG, antibodies as well as suppression of the seasonal anamnestic specific IgE increase. Similar, but not quite as marked changes occurred with Pool 2 treatment. fSRW was well tolerated and non-toxic. Thus, allergen modification by enzymatic degradation, as demonstrated here, appears to be a promising new approach for allergen immunotherapy.

Adult↗

Thoraco-abdominal enteric duplication with meningocele, skeletal anomalies and dextrocardia.

We describe an infant with an enteric thoraco-abdominal duplication arising in the proximal jejunum and associated with a dorsal meningocele, dextrocardia, agenesis of ribs and hypoplasia of the left arm. Diagnosis was reached post-operatively and the infant died of cytomegalovirus pneumonitis. Results of the postmortem examination are presented. Awareness of this rare malformation is required in order to reach a timely diagnosis and to plan a suitable operative approach.

Abnormalities, Multiple↗

Necrotizing enterocolitis after intravenous immunoglobulin treatment for neonatal isoimmune thrombocytopenia.

A male neonate of 38 weeks' gestation with isoimmune neonatal thrombocytopenia treated with high dose intravenous immunoglobulin (IVIG) developed necrotizing enterocolitis (NEC) at 3 days of age. The known maternal and neonatal risk factors for the development of this disease were excluded. The association between high dose IVIG and the appearance of thrombotic events might be another aetiological factor for occurrence of NEC in a newborn infant.

Enterocolitis, Pseudomembranous↗

Possible association between acetazolamide administration during pregnancy and metabolic disorders in the newborn.

Development of metabolic acidosis, hypocalcemia and hypomagnesemia in a preterm infant whose mother was treated with acetazolamide throughout pregnancy is described. These neonatal metabolic alterations possibly related to acetazolamide administration in pregnancy have not been previously described in the literature. The metabolic acidosis was transient and resolved spontaneously despite breast feeding and continued administration of acetazolamide to the mother. Hypocalcemia and hypomagnesemia resolved quickly with appropriate treatment with calcium gluconate and magnesium sulphate, respectively. At follow-up at ages 1, 3 and 8 months, the baby showed mild hypertonicity of the lower limbs requiring physiotherapy.

Acetazolamide↗

Modulation of the immune response to ragweed allergens by peptic fragments.

Fragments of short ragweed extract were prepared by peptic digestion and fractionated by molecular exclusion chromatography. We focused on fragmenting a ragweed fraction that was enriched for Amb aI. Digestion products in the molecular weight range of 5-15 kD (fSRW) were examined for their antigenic, immunogenic and immunosuppressive properties. fSRW was poorly immunogenic and unable to induce ragweed-specific PCA reactions in rat skin or to bind to anti-ragweed IgG antibodies. Intravenous administration of fSRW either prior to or after intraperitoneal immunization with a ragweed preparation resulted in a significant suppression of the immune response. T cells isolated from lymph nodes of mice immunized with ragweed were stimulated by fSRW in a lymphoproliferation assay. Moreover, T cells from mice injected with fSRW were immunosuppressive when transferred into mice immunized with intact ragweed antigens. Our data demonstrate that peptic fragments (fSRW) of ragweed lack B-cell determinants while retaining their T-cell immunoregulatory properties. Potentially these peptides are less likely to cause adverse reactions in allergen sensitive patients and thus offer a new approach to allergen immunotherapy.

Animals↗

Modulation of the immune response to allergens: phospholipase A degradation products suppress IgG and IgE response in mice.

Degradation products of phospholipase A2 (PLA2), the major allergen of honeybee venom, were prepared by peptic digestion of the enzyme and fractionated by molecular exclusion chromatography. The largest of the isolated products, P-1, was found to be a centrally nicked PLA2 molecule with a loss of several amino acids. It was examined for its antigenic, immunogenic and immunosuppressive properties. This peptic product was unable to block antigen-antibody reactions between PLA2 and anti-PLA2 antibodies and was incapable of inducing passive cutaneous anaphylaxis in rat skin sensitized with mouse anti-PLA2 IgE antibodies. BDF1 female mice injected intravenously with P-1 exhibited suppressed IgG and IgE anti-PLA2 responses to a subsequent PLA2 immunization. Intravenous administration of P-1 to mice with ongoing immune response to PLA2 resulted in decline of antigen-specific IgE titers. Transfer of splenic T cells from mice injected with P-1 into naive recipients caused profound suppression of the response to subsequent immunization with PLA2 indicating presence of PLA2-specific T suppressor cells. These results indicate that a degradation product of PLA2 prepared by peptic digestion lost antigenic and immunogenic properties of the intact enzyme but retained immunosuppressive properties, thus offering a novel approach to allergen immunotherapy.

Allergens↗

Neonatal ABO incompatibility. Complicated by hemoglobinuria and acute renal failure.

The authors present two infants with isoimmune hemolytic disease due to ABO incompatibility complicated by massive hemoglobinuria and secondary acute renal failure. This represents an incidence of 0.36% of all neonates with ABO hemolytic disease in the author's newborn population. Only two patients have been reported previously to have similar complications. Analysis of data of these four infants revealed the clinical characteristics of this complication of ABO incompatibility: 1) very low frequency; 2) early onset of hemoglobinuria (first voided urine) and of acute renal failure (first 2 days of life); 3) lack of correlation between the clinical presentation of hemolytic disease and appearance and severity of renal failure; 4) complete recovery of renal functions following intravenous fluid administration; and 5) normal renal radiologic investigations.

ABO Blood-Group System↗

New chromosome aberration: duplication of a large part of chromosome 4q and partial deletion of chromosome 1q.

We describe a preterm female infant with multiple anomalies who has a duplication of a large part of 4q and partial deletion of chromosome 1q. Her karyotype was interpreted to be 46,XX,-1,+der(1),t(1;4) (q44;q23 or 24)mat. She is the first patient with an unbalanced translocation involving chromosomes 4 and 1. There is a substantial amount of concordance between the phenotypic features of this patient and those described in the context of partial deletion 1q. The extensive duplication of 4q has no dominant clinical effects in the present infant. These facts support the general concept of much more deleterious effects of deletions versus duplications in human species.

Abnormalities, Multiple↗