Samuel P. Gotoff

Secondary and prolonged fevers in bacterial meningitis.

The course of 88 patients with bacterial meningitis was reviewed to determine theincidence, etiology, and significance of secondary and prolonged fevers. Twenty-eight per cent developed secondary fever, and prolonged fever was noted in 9 per cent. Phlebitis, drug fever, and unrelated infections were the major established causes of complicating fevers. Fever was not due to an inadequate response to antimicrobial therapy in this series. The differential diagnosis of fevers complicating the course of bacterial meningitis is emphasized to avoid improper management.

Relationship of neonatal IgM values to congenital abnormalities and mental retardation

A controlled prospective study was performed in 3 hospitals to determine whether an elevated cord serum IgM concentration would identify infants with intrauterine infections who would later manifest sequellae of these infections. IgM values were 17 mg. per cent or greater in 1.6 per cent of 4,285 cord serum specimens. The incidence of elevated IgM concentrations was significantly greater in a lower class, predominantly Negro population than in a Caucasian, middle class community. There was no increase in the incidence of congenital malformations or neuromotor abnormalities in infants with elevated cord serum IgM values. The results of this and other studies militate against the routine screening of cord serum IgM levels to detect subclinical intrauterine infection.

Deficient Serum Opsonic Activity for Macrophage Function in Newborn Infants

Summary Circulating serum opsonic or phagocytosis promoting activity relative to Kupffer cell function was deficient on a group comparison basis in newborn infants (1–9 days old) as compared to that manifested by serum from healthy adult controls. This early pattern of opsonin levels in the newborn was not significantly affected by sex or race, although a tendency for lower opsonin activity to be exhibited by serum from newborn males was noted. These findings suggest that hypo-opsonemia in the newborn infant may mediate altered R.E. function and increased susceptibility to systemic infection.

Risk factors in early-onset neonatal group B streptococcal infections

Newborn infants with “early-onset” disease due to group B beta hemolytic streptococcus were studied over a 40-month period. Clinical presentations included asymptomatic bacteremia, mild transient illness, respiratory distress, meningitis, and overwhelming sepsis. Chronologically, 19 were ill at birth; 11 became ill after a symptom-free period; and four were asymptomatic. Sixty-eight percent of the cases weighed less than 2500 grams, and 59 percent were born to mothers whose amniotic membranes were ruptured for over 20 hours. The overall “early-onset” attack rate was 1.9/1000 live births, but the rates increased markedly with decreasing birth weight, i.e., for infants weighing > 2.5 kg, 0.8/1000; 2-2.5 kg, 5/1000; 1-2 kg, 11.2/1000; and .5-1 kg, 66/1000 live births, respectively. Similarly, the attack rates increased with the duration of ruptured membranes, from 0.7/1000 for 0-9 hrs, 1/1000 for 10-19 hrs, 17/1000 for 20-29 hrs, to 21/1000 for > 30 hrs. All 15 of the deaths occurred in the low birth weight infants who were critically ill from birth. These results suggest that the management of “early-onset” disease should begin prior to delivery and focus on high risk groups. The colonized gravid woman in premature labor or with prolonged ruptured membranes is clearly at risk, and a controlled study of penicillin prophylaxis appears indicated.

TRANSSPHENOIDAL REMOVAL OF PITUITARY MICROADENOMAS IN THE TREATMENT OF CHILDHOOD CUSHING'S DISEASE

The morbidity of adrenalectomy and high incidence of post-adrenalectomy Nelsons syndrome in children with Gushings disease suggests that alternative methods of treatment would be especially useful in childhood. Two boys (patient 1, 6 9/12; patient 2, 15 yrs) with classic Cushings disease and no evidence of pituitary adenoma on skull x-ray or pneumoencephalogram failed to respond to cyproheptadine (0.25-0.5 ng/kg). Transsphenoidal pituitary exploration and removal of a pituitary microadenoma induced complete clinical resolution in both patients. Fasting plasma cortisol levels were low (3.8, 6.2 ug/dl), and the response to insulin-induced hypoglycemia was poor (10.4, 7.1 μg/dl) 2-4 months post-operatively. GH response to insulin-induced hypoglycemia returned to normal (pre-1.3 vs. post-26.8 ng/ml), and ACTH levels rose appropriately during hypoglycemia in patient 1. Patient 2 displayed a nocturnal rise in growth hormone (pre-3.6 vs. post-6.7 ng/ml), normal prolactin (13.5 ng/ml) and increased gonadotropins (pre FSH 2.8 LH 2.3 vs. post FSH 12.8 LH 13.2 mIU/ml) associated with progressive sexual maturation. T-4 and T-3 were normal in both patients postoperatively, as were other tests of pituitary function. We suggest that transsphenoidal pituitary exploration should be the initial therapy of choice in childhood Cushings disease.

DETECTION OF TYPE-SPECIFIC ANTIBODY TO GROUP B STREPTOCOCCI |[lpar]|GBBHS|[rpar]| BY THE |[ldquo]|LONG CHAIN REACTION|[period]||[rdquo]|

Since the lack of transplacental antibody to GBBHS appears to constitute a major determinant of susceptibility to neonatal infection and presently available methods for detecting antibody are cumbersome and time-consuming, a rapid test for antibody would be advantageous for screening populations at risk. Accordingly, we have adapted the streptococcal “long chain reaction” to measure antibody to GBBHS type Ia in human sera and correlated the results with those previously obtained by mouse protection and bactericidal assays (Clin. Res., 24:578A, 1976).A mid-log phase inoculum of GBBHS-Ia in Todd-Hewitt broth is incubated with the serum sample for three hours. Smears are made, and the length of 100 streptococcal chains is evaluated microscopically. Hyperimmune anti-GBBHS-Ia rabbit sera and six human sera which protected mice against a LD90 challenge with GBBHS-Ia and opsonized GBBHS-Ia in the in vitro bactericidal assay produced significantly (p<0.001) longer streptococcal chains than heterologous rabbit antisera and 18 human sera which were neither mouse protective nor opsonically active. The “long chain reaction” was demonstrable with a 1:1000 dilution of hyperimmune sera and with 1:32 dilutions of human sera. This simple, sensitive, and rapid method provides a semiquantitative test for antibody to GBBHS.

Cell-mediated Immune Response in vitro

Studies of the mechanism of cell-mediated immune responses have been hampered by the lack of in vitro systems. While the inhibition of macrophage migration model had advanced our understanding of delayed hypersensitivity reacions, the technique is complex and cumbersome. We have recently developed a simple test ofr measuring cell-mediated immune responses which depends on the aggregation of peritoneal exudate cells (PEC) in suspension cultures.PEC from guinea pigs with delayed hypersensitivity aggregate when the cells are cultured with the appropritate antigen. Diphtheria toxoid, PPD, egg albumin and keyhole limpet hemocyanin have been used in this system. Aggregation appears at 6 h and reaches a maximum at 24–25 h which is comparable to the time course of cutaneous delayed hypersensitivity reacions. This in vitro model also correlates with another cell-mediated response, allograft rejection. PEC from strain 13 guinea pigs previously grafted with skin from strain 2 animals aggregate in the presense of strain 2 cells. Aggregation does not occur with mixtures of PEC from guinea pigs of the same strain or different strains without prior grafting.Peripheral blood leukocytes, spleen cells or lymph mode cells from sensitized animals cultured with antigen synthesize a factor which causes aggregation of PEC from nonsensitive guinea pigs. The aggregating cells are macrophages, and the titer of macrophage aggregation factor (MAF) is determined by serial dilution. Macrophage aggregation in vitro provides a simple semiquantitative test fro cell-mediated immune reacions and permits further analysis of the mechanism involved.Studies of the mechanism of cell-mediated immune responses have been hampered by the lack of in vitro systems. While the inhibition of macrophage migration model had advanced our understanding of delayed hypersensitivity reacions, the technique is complex and cumbersome. We have recently developed a simple test ofr measuring cell-mediated immune responses which depends on the aggregation of peritoneal exudate cells (PEC) in suspension cultures.PEC from guinea pigs with delayed hypersensitivity aggregate when the cells are cultured with the appropritate antigen. Diphtheria toxoid, PPD, egg albumin and keyhole limpet hemocyanin have been used in this system. Aggregation appears at 6 h and reaches a maximum at 24–25 h which is comparable to the time course of cutaneous delayed hypersensitivity reacions. This in vitro model also correlates with another cell-mediated response, allograft rejection. PEC from strain 13 guinea pigs previously grafted with skin from strain 2 animals aggregate in the presense of strain 2 cells. Aggregation does not occur with mixtures of PEC from guinea pigs of the same strain or different strains without prior grafting.Peripheral blood leukocytes, spleen cells or lymph mode cells from sensitized animals cultured with antigen synthesize a factor which causes aggregation of PEC from nonsensitive guinea pigs. The aggregating cells are macrophages, and the titer of macrophage aggregation factor (MAF) is determined by serial dilution. Macrophage aggregation in vitro provides a simple semiquantitative test fro cell-mediated immune reacions and permits further analysis of the mechanism involved.

Sustained-release aspirin in children

Serial plasma salicylate levels were measured in children with acute rheumatic fever following a single dose and maintenance therapy with different regimens of regular and sustained-release aspirin preparations. The plasma salicylate levels were comparable following a single equivalent dose of regular and sustained-release aspirin preparations except for the 2 hour level when regular aspirin gave higher levels. With maintenance sustained-release aspirin tablets given every 8 or 12 hours, plasma salicylate levels were comparable to those obtained with regular aspirin given 5 times daily. Preliminary results of a double-blind, crossover study of 13 children with juvenile rheumatoid arthritis suggest that a sustained-release aspirin preparation given every 8 hour is as effective as regular aspirin tablets given 5 times daily in suppressing symptoms of arthritis.