Increased risk of primary hypothyroidism in preterm infants

Serum levels of thyroid stimulating hormone, thyroxine, triiodothyronine, free T4, thyroxine-binding globulin, reverse T3, and the TSH secretory areas and peak T3 after intravenous injection of 40 micrograms thyrotropin-releasing hormone were determined weekly from day 5 to 6 to 11 weeks of age in 42 unselected full-term and 61 preterm Belgian infants. The results on day 5 indicated a progressive deficit of thyroid function related to the degree of prematurity. In 92 infants this deficit progressively decreased with age and disappeared at 5 to 7 weeks. However, 11 infants developed biochemical evidence of overt but transient hypothyroidism. Belgian neonates are relatively iodine deficient, and this factor affects the constitution of iodine stores within the thyroid gland: (1) the urinary concentrations of iodine in the 103 infants studied in Belgium were markedly lower than in 30 infants from California; and (2) The iodine concentration of the thyroid gland in preterm infants who died during the 10 first days of life was almost three times lower in Brussels than in Toronto. The results indicate that, in Belgium, the effects of relative iodine deficiency on thyroid function are superimposed on and mask the physiologic state of tertiary hypothyroidism in prematurity.     

An epidemic of "childbed fever"

Postpartum infection remains a cause of considerable maternal morbidity and occasional maternal mortality. Puerperal sepsis mediated by what is now known as group A beta-hemolytic streptococci or Streptococcus pyogenes was once a common and lethal nosocomial scourge. Fortunately, multiple developments have decreased the incidence and ameliorated the clinical course of group A beta-hemolytic streptococcal postpartum sepsis. Despite these developments, epidemic group A streptococcal sepsis still jeopardizes modern mothers. We describe an epidemic of five women with group A beta-hemolytic streptococci-mediated postpartum infections which occurred at Mather Air Force Base Hospital, Sacramento, California. The remarkable, yet characteristic signs, symptoms, and clinical course of these patients are briefly reviewed along with the epidemiologic methods which led to the discovery of the common nosocomial source. Familiarization of the clinical aspects of these patients and the methods used to eradicate this epidemic will facilitate the protection and care of other women. Unfortunately, modern mothers still remain in jeopardy from "childbed fever."     

The diurnal variations of serum prolactin levels before and during pregnancy in normal and hyperprolactinemic patients

Although it seems likely that some patients with unexplained repeated abortions have early or subclinical autoimmune disease, there are no reports on the incidence of autoimmune serologic abnormalities in such patients by use of a series of tests. This diagnosis would suggest a treatable etiology for reproductive loss. We performed 11 serologic autoimmune tests in sera from 14 patients with three or more unexplained abortions (group II) and compared these results to those of 16 control patients with an established diagnosis for repeated abortions (group I). The groups were similar in age, gravidity, number of spontaneous abortions and live births, and in the interval from last abortion to serum sampling. A positive antinuclear antibody test plus at least one other positive test was found in four of 14 (29%) patients in group II (p less than 0.05). The tests that identified all these patients included levels of antinuclear antibody, antibodies to DNA or extractable nuclear antigen, and low levels of complement 3.     

A simple estimate of glomerular filtration rate in full-term infants during the first year of life

An estimate of glomerular filtration rate has been derived for children from body length (L, in centimeters) and plasma creatinine (Pcr, in milligrams per deciliter): GFR = 0.55 L/Pcr. The near universality of this estimate in children led us to seek a similar formula for estimating GFR in full-term infants during the first year of life. We measured Pcr in 137 healthy infants and performed creatinine clearance (Ccr) studies in 63 of them aged greater than or equal to 5 days. Beyond the first week, Pcr averaged 0.39 +/- 0.01 (0.10 SD) mg/dl. The estimate of GFR from 0.55 L/Pcr overestimated Ccr by 24% (P less than 0.001). Based on the calculation of a new constant from Ccr X Pcr/L, GFR was more accurately estimated from 0.45 L/Pcr (mean difference of Ccr - 0.45 L/Pcr = -0.4 +/- 3.7 (SE) ml/min X 1.73 m2) in full-term infants between 1 and 52 weeks of age. Because the constant 0.45 and Pcr do not change significantly during this period, GFR can be approximated at the bedside from body length of the healthy full-term infant (GFR = 0.45 L/0.39 = 1.1 L).     

A novel high-through-put assay for screening of pro-apoptotic drugs

Screening for anti-cancer substances iscommonly conducted using viability assays.An inherent problem with this approach isthat all compounds that are toxic andgrowth inhibitory, irrespective ofmechanism of action, will score positive.It would be beneficial to be able to screenfor compounds that specifically induceapoptosis. We here describe an ELISA-assaybased on a monoclonal antibody (M30) whichrecognizes a neo-epitope on cytokeratin 18exposed after cleavage by caspases duringapoptosis. We show that this assay detectsapoptosis in epithelial cells and that thesensitivity is sufficient for screening inthe 96-well format. We used the M30-ELISAassay to screen 500 low molecular weightcompounds from a chemical library from theNational Cancer Institute and identified 16drugs with strong pro-apoptotic activity,suggesting that the assay is a useful toolfor discovery of pro-apoptotic drugs.     

Interleukin-1beta converting enzyme (caspase-1) in intestinal inflammation

An imbalance of T helper cell type 1 (Th1) versus type 2 (Th2) polarization in favor of Th1 cell subsets appears to be a key pathogenic mechanism in chronic inflammatory bowel disease (IBD), in particular in Crohn's disease. The interferon gamma-inducing factor interleukin (IL)-18 acts in strong synergism with the Th1 polarizing cytokine IL-12. Recent studies provide evidence for the participation of IL-18 in the pathogenesis of IBD: IL-18 expression is increased in inflamed lesions of Crohn's disease patients and neutralization of IL-18 in different models of experimental colitis resulted in a dramatic amelioration of disease severity. IL-18 and IL-1beta are cleaved and thereby activated by the interleukin-1beta converting enzyme (ICE). Activation of ICE also occurs during different types of infectious colitis, and ICE expression and subsequent release of IL-1beta and IL-18 significantly contribute to intestinal inflammation. ICE knockout mice as well as mice treated with the ICE inhibitor pralnacasan are protected against experimental mucosal inflammation. Thus, inhibition of ICE represents an intriguing new target that requires further investigation in animal models.     

Sterol biosynthesis in Pneumocystis: unique steps that define unique targets

Pneumocystis lacks ergosterol, and several antimycotics that bind ergosterol in fungal membranes or inhibit its synthesis are ineffective against Pneumocystis pneumonia. The organism synthesizes C(28) and C(29) Delta(7) 24-alkylsterols, 24-alkyllanosterol derivatives, and Delta(5) 24-alkylsterols, which may be produced by modifying scavenged Delta(5) sterols. Mammals cannot desaturate C-22 and alkylate C-24 of sterols, thus, these processes are particularly attractive targets for antifungal drug development. Recent data indicate that C-22 desaturation is not, but C-24 alkylation is an attractive target in P. carinii. The P. carinii S-adenosyl-L-methionine:sterol C-24 methyl transferase (SAM:SMT) has unique properties; it prefers lanosterol as its sterol substrate.     

Ptosis postcardiac surgery: a case of pituitary apoplexy

We present a patient in whom ptosis and third cranial nerve palsy developed postcoronary artery bypass grafting, and discuss the management of pituitary apoplexy postcardiac surgery.