Critical illness polyneuromyopathy after artificial respiration.

Up to now, 71 critically ill patients have been reported with neuromuscular complications after artificial respiration. The authors review the literature and present data of a personal series of 22 patients all suffering from severe flaccid tetraparesis and muscle atrophy, which developed after an average of two weeks artificial respiration. The prognosis was relatively good in those surviving the primary disease. The multiconditional causes are discussed with emphasis on the combination of polyneuropathy and myopathy. Tumor necrosis factor (TNF), a key mediator of sepsis, which also has an influence on muscle and nerves, is mentioned as a possible cause of this illness.     

Evidence that 3α-hydroxy-5α-pregnan-20-one is a physiologically relevant modulator of gaba-ergic neurotransmission

3α-Hydroxy-5α-pregnan-20-one (HPO) is a progesterone metabolite which exhibits narcotic properties at high concentrations by interactions with the receptor for gamma-aminobutyric acid (GABA). The present investigation characterized low-dose effects of HPO on GABA_A receptor binding, by determining the allosteric properties of HPO on the in vitro binding of ³H-muscimol to membrane fractions from the cerebella of ovariectomized rats. A newly developed method for tissue preparation was used to wash out endogenous ligands interfering with the assay. HPO reduced the affinity of ³H-muscimol to GABA_A receptor sites by 52% and enhanced the number of accessible binding sites from 5.5±0.5 to 7.5±1.3 pmol/mg protein at subnanomolar (0.1 nM) HPO concentrations. The modulatory effects of HPO on GABA_A receptor binding provide evidence that this pregnane steroid might be a physiologically relevant modulator of GABAergic neurotransmission.     

Differences in the abilities of human tau isoforms to promote microtubule assembly.

Three isoforms of human tau protein were compared for their abilities to induce microtubule assembly. The three isoforms, tau 3 (tau containing three microtubule-binding domains), tau 4 (tau containing four microtubule-binding domains) and tau 4L (tau containing four microtubule binding domains plus a 58-amino-acid insert near the N-terminus) were expressed in E. coli and purified using ammonium sulfate precipitation, ion exchange, and size exclusion chromatography. All three isoforms induced microtubule assembly at micromolar concentrations and showed similar critical concentrations for assembly of 0.4-0.45 microM. However, tau 4 induced microtubule formation at a rate five- to tenfold faster than either tau 3 or tau 4L. The rate of microtubule elongation seen with tau 4 was twofold greater than with tau 3 or tau 4L, suggesting that the faster rate of microtubule assembly seen with tau 4 was due, at least in part, to faster elongation. Tau 4 induced a greater number of microtubules to form at steady state than did tau 3 or tau 4L. The microtubules generated with each tau isoform had similar steady-state length distributions and were equally susceptible to cold-induced disassembly. These results indicate that the additional microtubule-binding domain in tau 4 enhances microtubule assembly, while the 58-amino-acid insert negates the stimulatory effect of the fourth microtubule-binding domain.     

Multiple sclerosis patients have reduced HLA class II-restricted cytotoxic responses specific for both measles and herpes virus

It has been previously demonstrated that the generation of measles virus (MV)-specific cytotoxicity (CTL) is reduced in patients with multiple sclerosis (MS). By contrast, CTL specific for influenza virus (FLU) and mumps virus is normal. It is uncertain if reduced CTL is limited to MV in MS patients, or if reduced CTL may be found to other viruses as well. Since MV-specific CTL is predominantly restricted by HLA class II molecules, while FLU-specific and mumps-specific CTL have large HLA class I-restricted components, reduced MV-specific CTL may reflect a broader reduction in HLA class II-restricted CTL in patients with MS. To examine this question we studied the generation of CTL specific for herpes simplex virus type I (HSV). HSV-specific CTL, like MV-specific CTL is predominantly restricted by HLA class II molecules. We found that patients with MS had reduced generation of CTL to both MV and HSV. Most, but not all patients who had reduced generation of CTL to one virus also had a similar impairment with respect to the second virus. Some patients, however, had a reduction in the generation of CTL only to MV or to HSV. These findings extend our earlier observations regarding reduced MV-specific CTL in patients with MS to a second HLA class II-restricted virus, HSV. Such a reduction may reflect discrete impairments in immune function to separate viruses, possibly those that are associated with viral persistence, or may reflect a more generalized defect in HLA class II-restricted CTL.     

Differential ontogenesis of type I and II benzodiazepine receptors in mouse cerebellum

The ontogeny of type I and type II benzodiazepine binding sites was studied in mouse cerebellum by displacement of [3H]flunitrazepam binding by zolpidem, a ligand specific for the type I sites. Type I binding sites predominate throughout development and in the adult while type II sites account for 25% of total cerebellar benzodiazepine binding sites at birth and, during development, decrease to 10% or less in the adult. On a per cerebellum basis type II sites increase during the first postnatal week and then remain at a steady level while type I sites increase until adulthood. These results may indicate a specific localization of the type II sites (and of the corresponding alpha-protein subunits in the GABA/benzodiazepine receptor complex) in structures already present at birth and developing during a short early postnatal period. The affinity of zolpidem for its high affinity (type I) binding sites increases during cerebellar ontogeny, this increase possibly indicates an epigenetic (post-translational) 'maturation' process of the corresponding receptor molecule. Hill numbers indicate the existence of an additional binding site heterogeneity greater during development but still present in the adult; probably this is to be related to the simultaneous presence of different 'maturation' stages during development and with a certain variety of the final products.     

Emergency abdominal radiography

Plain abdominal radiographs are rarely diagnostic when the patient presents with acute abdominal pain. Emergency physicians, therefore, should be aware of the appropriate indications and limitations of abdominal films in this setting and should be skilled in their interpretation to exclude the rare cases of pneumoperitoneum, pneumobilia, hepatic-portovenous gas, small and large bowel obstruction, toxic megacolon, volvulus and intramural gas.     

Family history evaluation as a predictive screen for childhood hypercholesterolemia. Pediatric Practice Research Group

A study was conducted to evaluate the efficacy of family history factors as screening criteria for childhood hypercholesterolemia. When they were seen for routine care at one of eight office practices, 1005 prepubertal children underwent random serum cholesterol determinations. Parental and grandparental histories of cardiovascular risk factors and atherosclerotic complications prior to 55 years of age were also obtained. Of the initial group, 274 children had total cholesterol levels greater than or equal to 175 mg/dL, and 175 of these children returned for retesting after an overnight fast. A total of 88 children were found to have low-density lipoprotein-cholesterol (LDL-C) values greater than or equal to 90th percentile for age and sex. Maternal and paternal histories of hypercholesterolemia were significantly associated with elevated LDL-C (odds ratio = 7.3 and 2.9, respectively), but had extremely low sensitivities (0.09, 0.15) despite modest positive predictive values (0.42, 0.22). Grandparental histories of sudden death, peripheral vascular disease, and gout were associated with elevated LDL-C, but sensitivities and positive predictive values for all of these factors were less than 0.22. Family history factors most commonly recommended as criteria for cholesterol screening in children did not identify half of all the children with elevated LDL-C and did not selectively identify the most severely affected children. Adding information concerning the presence of childhood obesity did not result in appreciable improvement in LDL-C detection beyond that achieved by family history factors alone. It was concluded that if thorough identification of young children with elevated LDL-C is desired, inclusive population screening rather than a family history-based strategy would be the most effective approach.