Nancy H. Holland

IMMUNOGLOBULIN LEVELS FROM THE NEWBORN PERIOD TO ADULTHOOD AND IN IMMUNOGLOBULIN DEFICIENCY STATES

Beta-2A globulin and the 7S and 19S gamma globulins are the major proteins of the serum derived from the immune system. Collectively they have been termed the immunoglobulins. The 19S gamma globulin, also known as the gamma-1 macroglobulin, the 82 macroglobulin or 82M, has been the subject of intensive study in recent years. The rheumatoid factor as well as a variety of antibodies fall into this protein group, and abnormally high levels are found in Waldenstroems macroglobulinemia. Less is known about 82A globulin (gamma 1-A). It is like gammaglobulin in that it has a sedimentation constant of 7S, but contains more carbohydrate (1). Recent observations imply that it is the carrier of the reaginic activity of the serum (2). All of immunoglobulins are easily detectable in normal adult serum by immunoelectrophoretic analysis. 82A and 82M are absent in cord serum, and in agammaglobulinemia all three immunoglobulins are absent or in greatly reduced concentrations. Other antibody deficiency states have been described in which only one or two immunoglobulins are in low concentration (3-6). The present paper reports the levels of the immunoglobulins in cord serum and in the serum of infants, children, and adults as determined by a method based on a combination of immunoelectrophoretic analysis and the quantitative precipitin reaction (7). The data reveal a variable rate of maturation of the synthetic mechanisms for these proteins that is not apparent from semi-quantitative estimates based on simple immunoelectrophoretic analysis of serum. Also reported are the

IgA nephropathy: long-term prognosis for pediatric patients.

OBJECTIVE The determination of the ultimate prognosis for patients with IgA nephropathy diagnosed in childhood requires long-term follow-up of identified patients. The purpose of this study was to obtain such follow-up for patients from two centers where the disease has been diagnosed for more than 20 years. METHODS Clinical data at the apparent onset of symptoms and renal histologic data were obtained for 103 patients in whom IgA nephropathy was diagnosed before age 18 years. Clinical status at last follow-up was obtained from office records or from direct contact with the patient. Predicted kidney survival was determined by the Kaplan-Meier method. Follow-up of more than 10 years from the time of biopsy was available for 40 of the patients. RESULTS Fourteen of the patients have progressed to end-stage renal disease; three others have progressive chronic renal insufficiency as defined by an estimated creatinine clearance of less than 50 ml/min per 1.73 m2. Severity of the renal histologic findings and the degree of proteinuria at the time of biopsy were associated with poor outcome. For all patients, predicted kidney survival from the time of apparent onset was 94% at 5 years, 87% at 10 years, 82% at 15 years, and 70% at 20 years. Age at clinical onset and gender were not associated with poor outcome, but black race and severity of renal histologic findings were. CONCLUSION With follow-up into adulthood, the outcome for pediatric patients with IgA nephropathy appears to be as serious as that reported in adult patients. Follow-up of a pediatric patient with persistent clinical findings should be maintained after the patients care is transferred to a physician caring for adults.

IgA Nephropathy: Presentation, Clinical Course, and Prognosis in Children and Adults

Eighty-two patients, 56 male and 26 female, biopsied since 1972 had IgA nephropathy. At the time of kidney biopsy, 24 patients were children and 58 were adults. In both groups the clinical course was documented in sufficient detail to allow prediction of disease outcome. Twenty-six (45%) of the adult patients had chronic renal insufficiency either at first evaluation or subsequently. Fourteen eventually required chronic hemodialysis. Hypertension as the initial sign of disease was seen more frequently in patients with chronic renal insufficiency. Adult males were more likely to have chronic renal insufficiency. The life table method was used to predict age at initiation of dialysis and kidney survival from date of onset of clinically apparent disease. Thirty-five percent of the male patients were predicted to require dialysis by age 40. Kidney death was predicted at 10 years from onset for 33% of male and 22% of all patients biopsied as adults. While all patients with progressive disease had over 2.0 g/24 h urinary protein excretion at least once, many individuals with serum creatinine concentration below 1.5 mg/dL showed marked fluctuation in degree of proteinuria, often exceeding 2.0 g/24 h. Thus, in some cases, degree of proteinuria was not a reliable predictor of outcome.

Prevention and management of acute hyperuricemia in childhood leukemia

Massive and rapid destruction of neoplastic cells following institution of corticosteroid therapy is reported in 5 children with acute lymphoblastic leukemia. Severe hyperuricemia resulting from cellular breakdown was prevented by prophylactic regimens with the use of either allopurinol or mannitol diuresis. Intravenous fluids, urinary alkalinization, and mannitol diuresis were successful in reversing severe uric acid nephropathy already present in one patient and hemodialysis reversed renal shutdown secondary to acute uric acid nephropathy in another patient.

Hematuria in Childhood: Significance and Management

Of 164 children presenting with gross or microscopic hematuria during a 5-year period 111 (68 per cent) were proved by clinical features or renal biopsy to have glomerulonephritis. Extraglomerular origin of hematuria was documented in only 25 (15 per cent). No definite diagnosis could be made in the remaining 28 (17 per cent) with isolated hematuria but the clinical picture was similar to that of the patients with mild glomerular lesions. Followup in 59 of 68 children confirms previous reports that isolated hematuria in childhood is usually a benign condition. Although excretory urography, urine cultures and serum complement measurements should be done to eliminate uncommon causes of hematuria, invasive studies, such as renal biopsy and cystoscopy, are not indicated routinely.

Decreased gentamicin half-life during peritoneal dialysis

Previous l i t e ra ture citation of local oral toxicity is almost nonexistent for this re la t ively low toxicity ant i biotic. Kude r p r e s e n t e d t he un toward react ions in 20 525 cases r e p o r t e d to Lilly Labora tor ies . 1 Only six pa t ien ts expe r i enced stomatit is or glossitis. A pr ior his tory of chronic al lergic d isorders in 548 ch i ld ren d id not increase t h e inc idence of e ry thromycin toxicity: no cases of oral inflammatory disease, and only a 2.9 p e r c e n t inc idence of all side effects. In t he only o t h e r r e l a t e d r epo r t , a fixed, bullous erupt ion occu r red on t he lip and tongue of one pa tient receiving e ry th romycin . 3 Local d i rec t toxicity of t he table ts is r e m o t e and not likely, since topical e ry th romycin is a r a r e sensit izer. For e x a m p l e , t o p i c a l a p p l i c a t i o n of e r y t h r o m y c i n in pe t ro la tum failed to p r o d u c e react ions in 60 stasis u lcer pat ients . 4 T h e r e f o r e , l i n g u a l b u c c a l g i n g i v a l u l c é r a t i o n was caused by ery thromycin , since no o t h e r cause was found, and recha l lenge p r ec ip i t a t ed the react ion. This case represen t s a r a re , idiosyncratic, id iopathic react ion, p r e viously un repo r t ed .

Immunologic reactions and Australia Antigenemia in Down's Syndrome☆

Abstract Immunologic studies were done in sixty institutionalized patients with Downs syndrome (DS) and compared with age and sex matched mentally retarded (MR) controls. In the DS group there was a significant increase in gamma globulins, IgG and IgA. Au antigenemia was found in 27 per cent of DS patients and in none of the controls. In contrast to previous reports there was no evidence of decreased delayed hypersensitivity to PPD, histoplasmin or dermatophytin in DS subjects. There were, however, significantly fewer positive skin tests to mumps antigen. These studies confirmed the previously reported changes in serum proteins and increased prevalence of Australia antigenemia in DS. The results of skin testing and in vitro lymphocyte stimulation (reported elsewhere) did not demonstrate a generalized defect in cellular immunity in DS. The decrease in positive mumps skin reactions and Australia antigenemia may reflect an unusual defect in the handling of viral infections.

501 INCIDENCE OF MINIMAL LESION NEPHROSIS IN EASTERN KENTUCKY

The etiology of minimal lesion nephrosis (MLN), the most common cause of nephrotic syndrome in children, is unknown. The only incidence data on MLN have been extrapolated from population surveys of nephrotic syndrome in childhood performed over 20 years ago. These studies estimated the incidence of MLN at 1.5 cases per year per 100,000 children, ages 1-9. New cases of MLN occurring during the years 1970-1979 were identified by survey of area pediatricians and by medical record review of 9 hospitals in the area most likely to care for children. Total population of the study area in 1974 was 1.1 million with 187,000 children, ages 1-9. Thirty-five cases of MLN were identified with onset after first and before tenth birthday. Criteria for identification were initial response to daily steroids (33 pts) with complete clearing of proteinuria in <1 month or initial non-response (2 pts) with both renal biopsy and subsequent clinical course compatible with MLN. Incidence of MLN in the study area was 1.9 cases per year per 100,000 children, ages 1-9. However, in one rural 5-county area the incidence was 4.7 cases per year per 100,000. Whether this cluster of cases is epidemiologically meaningful or a statistical artifact is uncertain. Further refinement of the distribution and demographics of cases in the high rate area may provide clues to the etiology of MLN and continuing surveillance of area will enable us to assess the reliability of the finding.

Progress in Pyelonephritis.

This record of the second international symposium on pyelonephritis documents recent investigations of the prevalence, etiology, and significance of urinary tract infections. Although some parts of the book such as that related to the renal lesion caused by analgesic abuse will be of little concern to most pediatricians, other sections will be of considerable interest. The frequency of bacteriuria in the female population is emphasized by a number of surveys of school children, pregnant women, and family constellations. Methods of detecting bacteriuria are reviewed, and the superiority of quantitative urine cultures over chemical tests and smears is again apparent. The possibility of differentiating bladder from renal infections by an increase in specific antibody titer and loss of concentration ability in the latter is suggested. A large proportion of urinary tract infections are shown to be caused by a few nephropathogenic serotypes of Escherichia coli , but the frequency of infection with