Progressive multifocal leukoencephalopathy in an HIV-infected child.

Progressive multifocal leukoencephalopathy is an infection of the immunosuppressed, especially of AIDS, patients. The disease is caused by the JC virus and is exceptionally rare in children. The diagnosis is based on MRI and on the detection of JC virus DNA in the cerebrospinal fluid. Progression is relentless in most cases. The only treatment of proven benefit is restoration of the immune system by highly active antiretroviral therapy. We report the case of a 15S-year-old HIV-infected boy. After several months of fatigue he developed apathy, head tilt, diplopia, motor apraxia and unsteady gait. Physical examination revealed mild cerebellar signs. MRI showed a 30-mm large, non-enhancing, hyper-intense area in the right cerebellar hemisphere and the middle cerebellar peduncle. JC virus DNA was detected in the cerebrospinal fluid. Two weeks later the MRI showed progression. The patient's condition rapidly worsened and he died four months after the onset of the disease. Autopsy revealed widespread lesions of the cerebellar hemispheres and the brainstem. The case presented is peculiar owing to the young age of the patient, the unusual localization and the unifocal nature of the lesion.

The apical shaft of CA1 pyramidal cells is under GABAergic interneuronal control.

Dendrites of pyramidal cells perform complex amplification and integration (reviewed in Refs 5, 9, 12 and 20). The presence of a large proximal apical dendrite has been shown to have functional implications for neuronal firing patterns (13) and under a variety of experimental conditions, the largest increases in intracellular Ca2+ occur in the apical shaft.(4,8,15,16,19,21-23) An important step in understanding the functional role of the proximal apical dendrite is to describe the nature of synaptic input to this dendritic region. Using light and electron microscopic methods combined with in vivo labeling of rat hippocampal CA1 pyramidal cells, we examined the total number of GABAergic and non-GABAergic inputs converging onto the first 200microm of the apical trunk. The number of spines associated with excitatory terminals increased from <0.2 spines/microm adjacent to the soma to 5.5 spines/microm at 200microm from the soma, whereas the number of GABAergic, symmetric terminals decreased from 0.8/microm to 0.08/microm over the same anatomical region. GABAergic terminals were either parvalbumin-, cholecystokinin- or vasointestinal peptide-immunoreactive. These findings indicate that the apical dendritic trunk mainly receives synaptic input from GABAergic interneurons. GABAergic inhibition during network oscillation may serve to periodically isolate the dendritic compartments from the perisomatic action potential generating sites.

Screening and surveillance. OSHA's medical surveillance provisions.

The OSH Act requires OSHA to include provisions for medical examinations of employees in its standards. However, the specific test and examinations criteria are not outlined in the OSH Act. Instead, each standard has specific medical surveillance requirements. These are specific to the adverse health effects triggered by exposure to the hazardous substance. The OSHA uses the term medical surveillance to refer to its employee examination and testing provisions. Most occupational health professionals call this activity employee screening and reserve the term surveillance for aggregate analysis of population data. It is important to remember this distinction when referring to OSHA standards. Many standards are challenged in court resulting in changes to medical surveillance provisions of the standards. Some court decisions support OSHA's language. In either case, the court often sets precedents for future standards.

Glutathione status in retinopathy of prematurity.

This study examines the glutathione status of red blood cells in patients with retinopathy of prematurity (ROP) both in vivo and after an in vitro oxidative challenge. Fifty ROP patients of different ages (between 6 weeks and 6 years), born prematurely (gestational age: 28.7 +/- 1.3 weeks; birth weight: 1210 +/- 313 g; mean +/- SD) suffering either from active ROP (<3 months old; n = 12) or from a visual handicap due to preceding ROP (3 months-6 years; n = 38) as well as control patients of similar age and maturity (n = 56) were included. Infants with active disease have the lowest levels of reduced glutathione (GSH), the highest levels of oxidized form (GSSG), the highest GSSG/GSH ratios and the greatest fall in GSH after an in vitro oxidative challenge. After an in vitro oxidative stress, defective glutathione recycling was found in patients with preceding ROP and was suggested as a factor predisposing to oxidative hemolysis. The glutathione redox ratio was warranted as a biochemical screen for active ROP in premature infants.

Free radical formation in infants: the effect of critical illness, parenteral nutrition, and enteral feeding.

BACKGROUND/PURPOSE: An increase in free radical activity has been observed in patients suffering from a variety of illnesses and has been correlated with disease severity. Free radical production is increased by the administration of total parenteral nutrition (TPN) and may be linked to its adverse effects. Some of the complications of TPN can be ameliorated by partial enteral feeding. The aim of this study was to investigate free radical activity during critical illness and during the administration of parenteral nutrition. METHODS: Three groups of surgical infants were studied: (1) control infants (n = 8) before minor surgery, (2) stable infants on the ward recovering from a major operation (n = 24), (3) critically ill infants in the neonatal intensive care unit (NICU, n = 28). Fourteen patients in the ward and 17 patients in NICU were receiving parenteral nutrition. Of the 31 patients on TPN, 9 were also receiving minimal enteral feeding (3% to 24% of total calorie intake). Plasma malondialdehyde (MDA), an index of free radical activity, was measured in all 60 infants. The Paediatric Risk of Mortality (PRISM) score was obtained on NICU patients. The cytokines tumor necrosis factor (TNF-alpha) and interleukin 6 (IL-6) were measured in 25 patients. RESULTS: Plasma MDA was significantly higher in (1) the stable patients on the ward compared with control patients (P < .001) and (2) patients in NICU compared with stable patients in the ward (P < .001). Parenteral nutrition was associated with higher levels of plasma MDA both in stable patients in the ward and critically ill infants in NICU. There was no correlation between the PRISM score and MDA. In patients not receiving TPN there is a correlation between MDA and TNF-alpha (r = 0.54, P = .02) and between MDA and IL-6 (r = 0.74, P = .001). The level of free radical activity in patients on TPN is not changed by partial enteral feeding. CONCLUSIONS: Critical illness causes a rise in free radical production. Parenteral nutrition causes a significant elevation in free radical activity in both stable infants in the ward and critically ill infants in NICU. The addition of minimal enteral feeding to parenteral nutrition does not reduce free radical activity. We hypothesize that the parenteral nutrition solution directly initiates free radical production.

Medial septal and median raphe innervation of vasoactive intestinal polypeptide-containing interneurons in the hippocampus.

Vasoactive intestinal polypeptide-immunoreactive interneurons are known to form three anatomically and neurochemically well-characterized neuron populations in the hippocampus. Two of these establish synaptic contacts selectively with other GABAergic cells (interneuron-selective cells), whereas the third type innervates pyramidal cell bodies and proximal dendrites like a conventional basket cell. Our aim was to examine which of the vasoactive intestinal polypeptide-containing interneuron populations are among the targets of GABAergic septohippocampal and serotonergic raphe-hippocampal pathways. Anterograde tracing with Phaseolus vulgaris leucoagglutinin combined with double immunocytochemistry for vasoactive intestinal polypeptide was used at the light and electron microscopic levels. Our results show that both interneuron-selective cells and vasoactive intestinal polypeptide-containing basket cells receive synaptic input from the medial septum and median raphe nucleus. The GABAergic component of the septohippocampal pathway establishes multiple contacts on both cell types. In the case of the raphe-hippocampal projection, single or double contacts were more frequent on vasoactive intestinal polypeptide-positive interneuron selective cells (76%), whereas multiple contacts predominated on basket cells (83%). The extrinsic GABAergic innervation of interneuron-selective cells in the hippocampus indicates a complex interaction among GABAergic systems, which might ensure the timing and rhythmic synchronization of inhibitory processes in the hippocampus. On the other hand, our results suggest that the serotonergic effect on perisomatic inhibition is exerted via vasoactive intestinal polypeptide-containing basket cells that are functionally distinct from their parvalbumin-positive relatives, which appear to escape control of serotonergic as well as local interneuron-selective cells.

Total parenteral nutrition directly impairs cytokine production after bacterial challenge.

BACKGROUND/PURPOSE: Previous studies have shown that total parenteral nutrition (TPN) influences host immunity, but the mechanism is unclear. This study explored the effect of TPN solution on neutrophil phagocytosis and whole-blood cytokine production in response to coagulase-negative staphylococci in vitro challenge. METHODS: Blood samples were taken from five enterally fed infants (age <6 months) and six healthy adults. Samples were incubated for 45 minutes with four isovolemic solutions: (A) control (saline), (B) TPN (0.1 microL/mL of blood), (C) TPN (1 microL/mL), (D) TPN (10 microL/mL). Solution C (1 microL/mL) corresponded to TPN-blood ratio used in clinical practice. After incubation, blood was challenged with coagulase-negative staphylococci. Neutrophil phagocytosis was measured by flow cytometry after 40 minutes of bacterial challenge, and tumour necrosis factor alpha (TNF-alpha) was measured by enzyme-linked immunosorbent assay (ELISA) after 2 hours of bacterial challenge. RESULTS: In infant blood, TNF-alpha production after coagulase-negative staphylococci challenge was impaired after the addition of a "physiological" dose of TPN solution (1 microL/mL of blood) as well as "supranormal" doses (10 microL/mL of blood). In adult blood, a similar effect was observed only after the addition of a supranormal dose of TPN. In both the infant and adult blood, there was no direct effect of TPN solution on neutrophil phagocytosis. CONCLUSIONS: These results suggest that infants are more susceptible than adults to TPN-related depression of cytokine production. The level of proinflammatory cytokines may be important in the host defence against bacterial infection.

Distinct interneuron types express m2 muscarinic receptor immunoreactivity on their dendrites or axon terminals in the hippocampus.

In previous studies m2 muscarinic acetylcholine receptor-immunoreactive interneurons and various types of m2-positive axon terminals have been described in the hippocampal formation. The aim of the present study was to identify the types of interneurons expressing m2 receptor and to examine whether the somadendritic and axonal m2 immunostaining labels the same or distinct cell populations. In the CA1 subfield, neurons immunoreactive for m2 have horizontal dendrites, they are located at the stratum oriens/alveus border and have an axon that project to the dendritic region of pyramidal cells. In the CA3 subfield and the hilus, m2-positive neurons are multipolar and are scattered in all layers except stratum lacunosum-moleculare. In stratum pyramidale of the CA1 and CA3 regions, striking axon terminal staining for m2 was observed, surrounding the somata and axon initial segments of pyramidal cells in a basket-like manner. The co-localization of m2 with neurochemical markers and GABA was studied using the "mirror" technique and fluorescent double-immunostaining at the light microscopic level and with double-labelling using colloidal gold-conjugated antisera and immunoperoxidase reaction (diaminobenzidine) at the electron microscopic level. GABA was shown to be present in the somata of most m2-immunoreactive interneurons, as well as in the majority of m2-positive terminals in all layers. The calcium-binding protein parvalbumin was absent from practically all m2-immunoreactive cell bodies and dendrites. In contrast, many of the terminals synapsing on pyramidal cell somata and axon initial segments co-localized parvalbumin and m2, suggesting a differential distribution of m2 receptor immunoreactivity on the axonal and somadendritic membrane of parvalbumin-containing basket and axo-axonic cells. The co-existence of m2 receptors with the calcium-binding protein calbindin and the neuropeptides cholecystokinin and vasoactive intestinal polypeptide was rare throughout the hippocampal formation. Only calretinin and somatostatin showed an appreciable degree of co-localization with m2 (20% and 15%, respectively). Using retrograde tracing, some of the m2-positive cells in stratum oriens were shown to project to the medial septum, accouting for 38% of all projection neurons. The present results demonstrate that there is a differential distribution of m2 receptor immunoreactivity on the axonal vs the somadendritic membranes of distinct interneuron types and suggest that acetylcholine via m2 receptors may reduce GABA release presynaptically from the terminals of perisomatic inhibitory cells, while it may act to increase the activity of another class of interneuron, which innervates the dendritic region of pyramidal cells.

Distribution of toxic and radiation components in air particulates.

The concentrations of several toxic heavy metals and volatile organic compounds (VOCs) in various types of Hungarian fly-ash fine particulates were investigated by means of instrumental neutron activation analysis, X-ray fluorescence analysis and gas chromatography, coupled with mass spectrometry. Within a power station, particulate samples were taken from the boiler zone (BO), from the electrostatic dust filter chamber (FI) and from the flue-gas at the top of the stack (ST). Enrichment rates of the toxic metals both in FI and ST particulate fractions related to the BO concentrations were calculated to enable the temperature dependence on the adsorption of the toxic components to be studied. In addition, both the total amounts of the VOCs and their partial distributions in accordance with the number of carbon atoms were also studied in fly-ash particulates. From them, 31 organic species were identified and determined. Since Hungarian brown coals have high uranium and thorium contents, the specific radioactivities of the daughter isotopes of both the 232Th and 238U decay series were also measured and are discussed.

Hemangioblastoma of the optic nerve.

A 43-year-old woman presented with progressive loss of vision in the right eye. Magnetic resonance imaging (MRI) showed a prominently enhancing lesion of the optic nerve, thought preoperatively to represent an optic nerve meningioma or optic neuritis. Histological examination of the excised tumor showed this lesion to be hemangioblastoma. Her family history was unremarkable. However, subsequent review of the preoperative MRIs and postoperative imaging studies showed two small cerebellar lesions, probably hemangioblastomas, and renal, pancreatic, and adnexal cysts, establishing the diagnosis of von Hippel-Lindau disease.

Characterization of human type I and type II IMP dehydrogenases.

Human IMP dehydrogenase, a target for anticancer and immunosuppressive chemotherapy, exists as two isoforms, types I and II. Nonfusion sequences of each isoform were overexpressed in an IMP dehydrogenase-deficient strain of Escherichia coli and purified to homogeneity. Both recombinant isoforms were tetramers, which was in agreement with the subunit structure of the native mammalian enzyme. The results of initial velocity and product inhibition studies were consistent with an Ordered Bi Bi kinetic mechanism for both isoforms. Substrate affinities were similar for types I and II with Km values of 18 and 9.3 microM, respectively, for IMP, and 46 and 32 microM, respectively, for NAD.kcat values were 1.5 and 1.3 s-1 at 37 degrees C for types I and II, respectively. Xanthosine 5'-monophosphate and NADH inhibited the two isoforms with identical inhibition patterns and inhibition constants. Mycophenolic acid, however, inhibited the type II enzyme with a 4.8-fold lower K than the type I. Selective inhibitors of the inducible type II isoform may mitigate toxicity caused by inhibition of the constitutively expressed type I isoform.

Purified fibronectin administration to patients with severe abdominal infections. A controlled clinical trial.

Subnormal plasma fibronectin (Fn) levels are found in patients with severe abdominal infections (SAI). The repletion of Fn has been postulated to have therapeutic benefit by virtue of its opsonic, reticuloendothelial system (RES) stimulating effects. A controlled, prospective trial of Fn administration was performed in patients with SAI to assess its use as an adjunct to standard procedures of intensive care. Thirty-three SAI patients were given daily doses of 0.8 g of purified Fn on days 1-5 following admission to the ICU, whereas 34 control patients received no Fn. All patients received the clinical care, antibiotics, and pharmacologic agents appropriate to their individual needs. The admission status and laboratory profiles of the two patient groups (+ and -Fn) were comparable on admission to the study. No side effects of the Fn preparation were observed. As judged by subgroup averages, the Fn replacement regimen was effective in elevating Fn levels to within normal range from day 2 onwards, as measured by immunological and functional assays. The estimated intravascular recovery of Fn averaged 82% in those patients who survived, yet only 52% in the nonsurvivors. Ultimate hospital mortality was 9/33 (27.3%) in the +Fn group versus 13/34 (38.2%) in the -Fn group (p = 0.244, Fisher's exact test). Although ultimate mortality was not significantly changed by the administration of Fn, the Fn treated patients appeared to survive longer than did the control patients. This trend was confirmed through the analysis of expected survival curves (D = 3.12, 0.1 greater than p greater than 0.05). When compared to the survivors, the ultimate nonsurvivors entered the study with statistically higher group averages of bilirubin and creatinine concomitant with lower averages of Fn, antithrombin III, C4, C3, C3b-INH, and transferrin. These differences persisted throughout the 11-day monitoring period; differences between survivors and nonsurvivors with respect to platelets, plasminogen, B-1-H, alpha-2-macroglobulin, and prealbumin appeared during the same period. Dramatic differences between the +Fn and -Fn treatment groups were not seen. Other than Fn, the Fn recipients only developed higher levels of the acute phase reactants C4, C3b-INH, B-1-H and alpha-1-antitrypsin (p less than 0.05) than did their non-Fn treated counterparts. In the present study, we again found a highly significant pattern of correlations between the absolute levels as well as the changes of Fn and other plasma proteins.(ABSTRACT TRUNCATED AT 400 WORDS)

Antithrombin III and related parameters in surgical patients receiving blood components.

We examined the intra- and postoperative behavior of antithrombin III (AT), factor V, VIII, and fibrinogen in 27 elective surgical patients without evidence of disseminated intravascular coagulation (DIC) and treated according to the concept of blood component therapy inaugurated at our hospital in 1975. The intraoperative depletions of AT and fibrinogen were proportional to the transfusion volumes and correlated significantly. AT, fibrinogen, and especially factor V and VIII were significantly mobilized during surgery. A greater intraoperative depletion of AT was significantly associated with a faster recovery during the first 24 postoperative h. The AT activity was virtually stable over a period of 4 weeks in CPD-adenine red cell concentrates; fresh frozen plasma and whole blood are thus not essential as a source of AT. The application of our concept did not increase the frequency of thromboembolic complications, despite the fact that the intraoperative AT values fell below the presumed 'critical' level of 60-70% in some patients. The probable reasons are the brief duration of such levels, the simultaneous depletion of coagulation-promoting plasma constituents (e.g. fibrinogen), and the use of antithrombotic prophylaxis. Our results suggest no reasons for a routine use of fresh frozen plasma in patients with a loss and replacement of less than about 75% of their blood volume.

Pregnancy associated with hypergonadotropic hypogonadism.

A case of a 30-year-old female with secondary amenorrhea and relative hypergonadotropic hypogonadism is presented. The patient demonstrated persistently elevated levels of gonadotropins in spite of clinical and laboratory evidence of estrogen production. Laparoscopic directed biopsy revealed a total absence of ova, but in spite of this finding, conception ensued. Variations in ovarian sensitivity throughout the female reproductive period and in certain pathologic states are discussed, as well as the apparent limitation of single laparoscopic directed biopsies for confirming the diagnosis of premature menopause. Finally, the theoretical use of exogenous estrogen to induce ovulation in patients with the ovarian insensitivity syndrome is discussed.