Edward Wasserman

Routine Immunohistology in Renal Diseases

Excerpt In 1907 it was suggested (1) that certain renal diseases may be caused by an immune reaction involving the glomerulus. This hypothesis has recently received renewed support. In 1951 we demo...

Occurrence and Nature of Glomerular Lesions after Group A Streptococci Infections in Children

Abstract A prospective study of renal involvement after group A streptococci infections was undertaken in 248 children who had weekly examinations for at least 6 weeks. Examination included urinaly...

Incidence of major congenital malformations in offspring of alcoholics and polydrug abusers

The incidence of major congenital malformations was compared in the offspring of mothers who abused alcohol only (group I), versus mothers who abused alcohol and opiates (group II) during pregnancy. In group I the percent of patients with malformations was 33, where as in group II it was 14. The prevalence of fetal alcohol syndrome was higher in blacks than Hispanics. Independent of race the alcohol-opiate combination seems less teratogenic to the fetus than alcohol alone.

Subclinical and overt acute glomerulonephritis in children following infections with group A streptococci

Fluorescein (FIT) labelled IgG fractions from patients with acute poststreptococcal glomerulonephritis (AGN) stain parts of the basement membrane and mesangium of glomeruli from the same patients, provided renal tissue is obtained early in the disease. Staining is abolished by preabsorbing the IgG fractions with disrupted streptococci isolated from patients with AGN. Non-nephritogenic streptococci do not reduce staining. These findings were applied in an epidemiologic survey of a pediatric population with group A streptococcal infections. During a 12-month period 178 children with group A streptococcal infections were followed with weekly examinations including urinalysis and determination of serum complement (CH50) and ASLO titers. Only children in whom these parameters were normal initially were kept in the study. 2 children developed typical AGN. 21 patients were asymptomatic but showed transient urinary abnormalities and decreased CH50. Their renal tissue showed glomerular lesions ranging from mild mesangial increase and endothelial cell proliferation to the characteristic changes seen in AGN. The glomeruli showed granular staining with FIT labelled anti-human IgG and β1C. Streptococci cultured from the children were preserved. Only bacteria isolated from patients with demonstrable glomerular lesions reduced the staining capacity of FIT labelled sera from patients with AGN. Streptococci obtained from patients without evidence of renal involvement failed to preabsorb. It appears that nephritogenicity of streptococci can be predicted. This study suggests that incidence of glomerular damage following group A streptococcal infections is greater than suspected.

MATERNAL DRINKING AND FETAL CLUBFOOT

We studied the prevalence of clubfoot in 129 patients with Fetal Alcohol Syndrome (FAS) or Alcohol Related Birth Defects (ARBD) aged 1-24 years. The mothers were all chronic alcoholics who abused ≥ 3 oz of absolute alcohol/day before and during pregnancy. They were divided in 2 groups: group I: alcohol abusers and group II: polydrug abusers (alcohol + narcotics ± cocaine). Group I comprised 55 mothers (40 blacks, 15 Puerto Ricans) and group II 30 (19 blacks, 11 Puerto Ricans). The socio-economic background, duration of alcoholism, average age at delivery and type of delivery were comparable in both groups.Four patients (all males, 2 blacks and 2 Puerto Ricans) were found to have talipes equinovarus, as well as other anomalies. Three had bilateral and one unilateral clubfoot. All four were seen in the nursery, where the deformities were corrected, and two were followed in clinic. Two mothers belonged to group I and two to group II.The occurrence of clubfoot in our study is significantly higher (P<0.01) than the accepted rate of 1.2/1,000.In the embryo marked equinovarus is a normal stage of development. In the newborn it means permanent growth arrest, which might have been caused by various agents: viruses, radiation, thalidomide, etc. Since narcotic addiction during pregnancy does not result in congenital malformations in the offspring we submit that alcohol, a known teratogen, should be added to the above list

802 TERMINAL LONG ARM DELETION OF CHROMOSOME 1, A CLINICALLY RECOGNIZABLE SYNDROME

We are reporting a one year old Hispanic female with terminal deletion of the long arm of chromosome 1 [del (1) (q43qter)], and reviewing all cases from the literature. With our patient there are 12 known (lq-) syndromes, of these seven were reported from the U.S.All patients had severe mental retardation, growth deficiency and unusual facial features; microcephaly, sparse fine hair, eye and ear malformations, flat nasal bridge with bulbous nose, carp-like mouth with tucked-in lower lip and micrognathia. Variable associated malformations of skeletal, cardiac, and genital systems were present in most.The typical facial dysmorphology along with the associated abnormalities makes (1q-) a clinically definable syndrome. Despite the striking similarities of the dysmorphic features in this syndrome, only three of the 12 known cases were diagnosed at birth by karyotyping. In half of the patients the physicians focused their attention on the respiratory problems occurring in the neonatal period, and the mental retardation was attributed to perinatal hypoxia. Two of the 12 cases were familial, while 10 were de novo deletions. Recognition of this syndrome is more significant in familial cases where a phenotypically normal parent with the balanced translocation may have several affected offspring necessitating genetic counseling and prenatal diagnosis

549 FAMILIAL FETAL ALCOHOL SYNDBOME INCIDENCE IN BLACKS AND HISPANICS

In a previous study we noted a higher incidence of fetal alcohol syndrome (F7AS) in blacks, vs. Hispanics. We new compared the incidence of familial FAS and alcohol-related effects (ARE) in black, (group I) and Hispanic (group II) patients, ranging in age from 1 day to 20 years. The average age of mothers at first visit was slightly higher in group II (31 vs. 28.6 in group I). The amount of alcohol abused during pregnancy (≥ 3 oz of absolute alcohol/day), average duration of alcohol abuse and socio-economic background (on public assistance, unwed mothers) were similar in both groups. Group I comprised 16 families with 39 children, 16 females and 23 males. Eleven families had 2 afflicted children, 4 families had 3 and one family had 5 afflicted children. FAS was diagnosed in 25 patients and ARE in 14. Group II comprised 7 families with 17 children, 10 females and 7 males. Five families had 2 afflicted children, one family had 3 and 1 family 4 afflicted children. FAS was found in 13 patients and ARE in 4. Though our clinic population is 65% Hispanic, familial FAS was significantly more frequent in blacks (P < .01). We conclude that for yet unexplained reasons single and multiple cases of FAS are more frequent in black than in Hispanic families.

ANTIBODY RESPONSE TO A GLOMERULONEPHRITIS RELATED STREPTOCOCCAL ANTIGEN

An antigenic protein can be isolated from the water soluble supernatant of disrupted group A streptococci. This antigen (Endostreptosin: ESS) can be detected in the glomeruli of patients with acute glomerulonephritis in the early days of the disease. ESS is not related to known streptococcal exozymes and is not excreted by intact streptococci. Antibody levels to this antigen were studied in 400 individuals of various ages using a microcomplement fixation test. Infants had usually negative titers. 41% of normal children were found to have moderately elevated (above 1:16) ESS antibody although 14% still had no ESS antibody. 90% of normal adults have low (less than 1:16) titers; only 3% have no detectable ESS antibody titer. Symptomatic and asymptomatic patients with acute glomerulonephritis have very high titers (up to 1:258). Patients with recent group A streptococcal infections without signs of nephritis also had consistently elevated titers, but titers were usually not as high as titers found in patients with acute glomerulonephritis. 61% of patients with lipoid nephrosis (minimal change disease) have no ESS antibody independent of activity of disease, steroid therapy, absence of proteinuria and years of remission. ASLO and streptozyme titers do not parallel ESS antibody levels. Penicillin therapy does not influence the emergence of titer elevation.

Routine Immunohistology as an Aid in the Diagnosis and Prognosis of Renal Diseases.

Excerpt Immunohistologic staining with fluorescein labelled antibodies against gamma globulin, type 12 streptococcal antigens, serum complement, as well as its components C′1 and C′3 (β1Cand β1A) w...