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During the first year of operation, the New England Regional Hypothyroidism Screening Program determined the concentration of thyroxine (T4) levels in dried blood on filter paper from 129,028 infants born in Connecticut, Maine, Massachusetts, New Hampshire, and Rhode Island. Specimens from approximately 3,800 neonates were found to have levels of T4 below the lower limit of normal (<6.0 μg/dl) and were assayed for thyroidstimulating hormone (TSH) content. Levels of TSH were elevated (>20 μU/ml) in 31 infants, 23 of whom eventually proved to have unequivocal hypothyroidism. Based on these figures and including two hypothyroid infants who were not tested, the incidence of congenital hypothyroidism in the New England region is approximately 1:5,200 births. The estimation of T4 values supplemented by measurement of TSH values on specimens with low T4 values has proved to be a satisfactory approach to large-scale screening for congenital hypothyroidism.(JAMA 239:2348-2351, 1978)

The interaction of human blood platelets with influenza virus (PR-8) was studied in vitro and in vivo. It was found that "live" influenza virus was rapidly adsorbed onto human blood platelets at 4 C. and completely eluted at 37 C. "Dead" virus was adsorbed at 4 C. but not eluted at 37 C. unless the platelets were treated with RDE (receptor destroying enzyme). Adorption of virus also occurred at tem peratures above 4 C. (from 20 to 37 C.). However, while adsorption was maintained throughout incubation at 4 C., slow elution occurred after 30 to 90 minutes incubation at 26 to 37 C. Storage of the platelets for lengthy intervals at 4 C. or coating of the platelets with macromolecules did not interfere with virus adsorption. After one cycle of adsorption-elution, blood platelets could not adsorb virus again. Treatment with RDE greatly reduced virus adsorption. During the process of virus adsorption, prominent platelet clumping occurred. During elution, clumping remained unchanged, and gross alterations in morphology of the platelets were observed. In the process of virus adsorption-elution, large numbers of platelets were lysed. Comparative experiments were performed simultaneously with human red blood cells (RBC) and identical results were obtained as with blood platelets. However, the extent of adsorption of live virus was equal for platelets and RBC only when the relationship between platelet number and RBC number in the preparations used was 6:1. This suggested a direct proportion between the surface area of both platelet and RBC and the number of available virus receptors. Virus suspensions infused into rabbits produced a sharp and sustained drop of the platelet count. Survival of radioactively labeled platelets treated with virus prior to infusion was markedly shortened with live virus and was only slightly reduced with dead virus. It is suggested from these experiments that blood platelets, as other blood cells, may serve as carriers of viruses in the circulation and that in this process the platelets are damaged and partially destroyed.

Cooper, LouisZ. (New England Center Hospital, Boston, Mass.), Morton A. Madoff, and Louis Weinstein. Hemolysis of rabbit erythrocytes by purified staphylococcal alpha-toxin: I. Kinetics of the lytic reaction. J. Bacteriol. 87:127–135. 1964.—The hemolytic activity of purified staphylococcal alpha-lysin was found to be directly proportional to toxin concentration and inversely related to the log concentration of rabbit erythrocytes. Activity was directly proportional to the duration of lysin-red cell incubation until inactivating effects of heat and dilution became significant; this linear relationship was prolonged by incubation at a lower temperature and addition of bovine serum albumin. Study of the time course of hemolysis at different alpha-lysin concentrations revealed a family of sigmoid curves characterized by a prelytic lag phase and a period of rapid linear release of hemoglobin. The duration of prelytic lag varied inversely with the quantity of toxin, but the rate of hemolysis was directly proportional to toxin and red-cell concentrations. The presence of bovine serum albumin decreased the prelytic lag, prolonged the linear phase of the reaction, and increased total hemolysis. In the range of 25 to 46 C, the prelytic lag period became shorter with increase in temperature; at 48 to 52 C, it was markedly prolonged and hemolysis was strikingly diminished. As the incubation temperature was increased from 25 to 52 C, there was a decrease in the degree of maximal hemolysis, presumably due to thermal inactivation of alphalysin. The rate of hemolysis, when measured to 50% hemolysis, was optimal between 34 and 42 C but, when determined to the 10% level, was greatest between 40 and 46 C. The features of the hemolytic reaction suggest that staphylococcal alpha-toxin has the characteristics of an enzyme.

Madoff, MortonA. (New England Center Hospital, Boston, Mass.), Louis Z. Cooper, and Louis Weinstein. Hemolysis of rabbit erythrocytes by purified staphylococcal alpha-toxin. III. Potassium release. J. Bacteriol. 87:145–149. 1964.—The reaction between staphylococcal alpha-toxin and erythrocytes was characterized by rapid release of K+from the cells, early in the prelytic period; 50 to 75% of this loss occurred before leakage of hemoglobin was detectable. The addition of specific antitoxin early enough in the reaction to inhibit gross hemolysis also inhibited cation release. The presence of sucrose or polyethylene glycol prevented hemoglobin release, but was without effect on K+leak. These observations suggest that K+loss is a more specific indication of the progress of the reaction between alpha-toxin and erythrocytes than is the release of hemoglobin.

Madoff, MortonA. (New England Center Hospital, Boston, Mass.) and Louis Weinstein. Purification of staphylococcal alpha-hemolysin. J. Bacteriol. 83:914–918. 1962. — Staphylococcal alpha-toxin has been purified by metal-ion precipitation, column chromatography, and continuous-flow paper electrophoresis. The resultant preparation is highly unstable. A single line is obtained on agar-gel diffusion analysis against staphylococcal antiserum. Two bands, both associated with hemolytic activity and migrating cathodally at pH 8.4, are obtained on starch-gel electrophoresis. Levels of lytic, dermonecrotic, and lethal toxin activity maintain a constant relationship in the crude and purified materials, suggesting the unity of these effects.

Impairment of glomerular filtration rate (GFR), renal plasma flow (RPF), and maximal urinary concentrating capacity was noted in the surgical and medical survivors of a controlled study of colon bypass. Statistically similar, but slightly higher mean values for GFR and RPF were observed in nonedematous, nonencephalopathic cirrhotic patients who had recently recovered from a bout of hepatic decompensation. Patient selection is considered to be the most significant factor in explaining these clinical observations which differ from earlier published reports. The experimental findings did not support the concept of renal injury causally related to chronic use of neomycin sulfate or protein restriction. Clinical improvement in hepatic encephalopathy following colon bypass was unrelated quantitatively or qualitatively to the intestinal microflora.

Cooper, LouisZ. (New England Medical Center Hospital, Boston, Mass.), Morton A. Madoff, and Louis Weinstein. Heat stability and species range of purified staphylococcal α-toxin. J. Bacteriol. 91:1686–1692. 1966.—Heating of high-titer purified staphylococcal α-toxin at 60 and 80 C resulted in a double-sloped curve of inactivation of the hemolytic effect on rabbit erythrocytes. Early inactivation was less at the lower temperature, but activity persisted for a longer time at 80 C. Toxin inactivated at 60 C showed renewed activity when heated briefly at 80 C. A precipitate which formed during heating of α-toxin at 60 or 80 C yielded hemolytic activity when resuspended and heated at 80 but not at 60 C. Supernatant fluid of heat-precipitated toxin was heat-labile and did not regain activity when heated at 80 C. The results indicate that the “paradoxical effect” of heating of staphylococcal α-toxin is not due to a thermolabile inhibitor, but results from alteration of the toxin molecule to a heat-stable active form. Demonstration of renewed activity by 80 C heating of purified toxin requires potent toxin preparations and brief heating periods. Hemolysis of erythrocytes of several animal species by purified α-toxin was generally similar to that produced by impure toxin. Rabbit cells were most susceptible. Human and horse erythrocytes hemolyzed to less than 0.1% of the extent of rabbit cells. Blood cells of other species were intermediate in their response to the lytic effect of α-toxin.

The two patients whom we treated for systemic fungus infections with 5-fluorocytosine, an antifungal agent effective in experimental animal infection with Candida and cryptococci, had a satisfactory clinical response in association with therapy. One patient with Candida sepsis received 5-fluorocytosine for 21 days in a dose ranging from 2 to 4 gm daily. The other patient, with cryptococcal meningitis recurring after amphotericin B treatment, received 5-fluorocytosine in a dose of 2.25 to 9 gm daily for 50 days. There was little evidence of drug toxicity. The new agent deserves controlled clinical evaluation in systemic fungus infections.

Presents several criticisms of medical education, which are excerpted from an article reported in JAMA, volume 269, number 14.