Neonatal encephalopathy with neuronal vacuolar degeneration

Spontaneous augmented breaths (active sighs) reduced the tidal volume and inspiratory time of succeeding breaths; manual lung inflations (passive sighs) reduced the tidal volume but had little effect on inspiratory time. Sighs in air, whether active or passive, reduced tidal volume more than sighs in hyperoxia (100% oxygen or 33% oxygen in nitrous oxide) after both active and passive sighs (overall difference about 10%); the reduction in inspiratory time after a sigh was less affected by gas mixture. Calculated mean inspiratory flow was reduced after passive sighs, but active sighs were more likely to cause arousal, which complicated the analysis. Tidal volume was reduced after a sigh partly because of reduced peripheral chemoreceptor input, the main effect of which was to reduce inspiratory flow, and partly because inspiratory time was shorter. Although the chemoreceptors may affect inspiratory time after a sigh, the greater effect of active sighs compared with passive sighs makes it likely that the shortening was either part of the neural output that causes spontaneous sighs, or was caused by mechanoreceptor input not mimicked by manual lung inflation.     

Sudden infant death syndrome (SIDS): a case with accessory pathways and resorptive degeneration

The Australian Incident Monitoring Study in the intensive care unit (AIMS-ICU) is a national study established through nursing and medical collaboration to develop, introduce and evaluate an anonymous voluntary incident reporting system. To ensure incident monitoring results in improved patient safety, it is essential that reported incidents are followed up regularly. Local unit review meetings are an effective forum for discussion and review of reports amongst a wide group of practitioners from the intensive care unit (ICU). All staff should be invited to participate in order to suggest preventative strategies, report on incident follow up and explore national study findings. Ongoing momentum of the project is assisted by highlighting its positive contributions to patient care and safety via newsletters, poster displays and targeted correspondence. New staff require orientation to the reporting system and assurance regarding safety of data. The emphasis must focus on the system, not the individual.     

Paraneoplastic cerebellar degeneration with asymmetrical pan-cerebellar syndrome

INTRODUCTION: Paraneoplasic cerebellar degeneration is seen clinically as a pancerebellar condition which is usually symmetrical. Different families of tumours are associated with this, particularly (in view of its frequency) oat cell pulmonary carcinoma, gynecological tumours and Hodgkin's lymphoma. CLINICAL CASE: Signs of cerebellar atrophy were seen on MR and cortical hypoperfusion was seen on Single Photon Emission Computerized Tomography (SPECT). We present the case of a 76 year old woman who presented with an asymmetrical pancerebellar disorder of gradual onset, with positive anti-self antibodies and undifferentiated carcinoma of the breast. CONCLUSIONS: Paraneoplasic cerebellar degeneration should be suspected in a patient with symmetrical, progressive cerebellar disease. The syndrome characteristically starts with a slightly uncoordinated gait. This progresses over a period of weeks or months to an ataxic gait with incoordination of the limbs, dysarthria and frequently nystagmus with oscilloscopy. No satisfactory treatment has been found for DCP in spite of trials with vitamins, corticosteroids, plasmapheresis and immunoglobulin infusion. Slight improvement may be seen after treatment of the primary tumour.     

Progressive ocular toxoplasmosis in patients with acquired immunodeficiency syndrome

We studied two patients, a 43-year-old Hispanic man with a one-year history of acquired immunodeficiency syndrome (AIDS) and a 34-year-old Hispanic man with newly diagnosed AIDS. Both had necrotizing retinitis that progressed to panophthalmitis and orbital cellulitis. Toxoplasmosis was not diagnosed in the first patient early in the course of the disease. The second patient had a history of toxoplasmic retinochoroiditis. Despite anti-toxoplasmosis therapy, visual acuity deteriorated to no light perception in both patients. Diagnostic biopsy of the eye wall was performed on the first patient and enucleation of the globe on the second. Toxoplasmic panophthalmitis and orbital cellulitis were diagnosed in each patient by light microscopy and confirmed by electron microscopy. When patients with AIDS develop necrotizing retinitis, toxoplasmosis must be considered in the differential diagnosis, along with cytomegalovirus retinitis, progressive outer retinal necrosis, and syphilitic retinitis. Unlike cytomegalovirus retinitis, progressive outer retinal necrosis, and syphilitic retinitis, however, toxoplasmosis can cause a progressive intraocular infection, panophthalmitis, and orbital cellulitis in patients with AIDS.     

Aeromonas sobria infection with severe muscle degeneration in a patient with alcoholic liver cirrhosis

A 56-yr-old male who had been followed for alcoholic liver disease was admitted for abdominal pain and a high fever. Gastrointestinal endoscopy revealed bleeding esophageal varices that were treated by endoscopic sclerotherapy. Blood culture on admission was positive for Aeromonas sobria. Then skin bullas and ulcers and severe muscle degeneration developed. The patient died despite extensive treatment with antibiotics. A. sobria infection in patients with liver cirrhosis is rare.     

Absence of common trifunctional protein mutation in patients with Alpers disease

Occupational exposures were assessed in a case-control study on testicular cancer using self-administered questionnaires. In total, answers were obtained for 148 (91%) cases and 315 (87%) controls. Of the cases, 101 had seminoma and 47 had embryonal testicular cancer. An increased odds ratio (OR) was found for exposure to polyvinyl chloride (PVC) yielding an OR of 6.6 (95% confidence interval, 1.4-32). The risk increased further if cases with self-reported cryptorchidism or orchitis were excluded. Six of the 7 exposed cases had seminoma. Exposure to other types of plastics did not significantly increase the risk of testicular cancer.     

Progressive multifocal leukoencephalopathy in a patient with acquired immunodeficiency syndrome

We report a 28 year old heterosexual male with AIDS that presented with progressive motor disturbances and malaise. Light and transmission electron microscopy of a stereotaxic brain biopsy demonstrated a progressive multifocal leukoencephalopathy. This is a demyelinating infectious cerebral disease attributed to JC virus and must be considered in the differential diagnosis of central nervous system disturbances in AIDS patients.     

The pharmacokinetics of teniloxazine in healthy subjects and patients with hepatic cirrhosis

The single-dose and steady-state pharmacokinetics of teniloxazine, an investigational drug with antidepressant and anti-anoxic properties, were compared in 12 healthy volunteers and 12 cirrhotic patients, following oral administration of 80 mg teniloxazine maleate every 12 h for 7 days. In healthy volunteers, an increase in oral clearance, CLo (from a mean (s.d.) value of 14.6 (3.9) to 18.0 (6.6) ml min-1 kg-1; mean % ratio between the two values (95% CI), 123 (94-151)) and a significant shortening of t 1/2 (from 6.2 (2.7) to 4.8 (1.4) h; mean % ratio (95% CI), 78 (58-98)) were observed upon repeated administration, suggesting autoinduction of teniloxazine metabolism. In cirrhotic patients, the pharmacokinetic parameters of teniloxazine remained essentially invariant with time. Compared with normal subjects, CLo was about halved in cirrhotic patients, whereas t 1/2 was more than doubled. As a consequence of these modifications, the multiple-dose regimen resulted in a two-fold mean drug accumulation in cirrhotic patients, compared with virtually no accumulation in healthy volunteers. Although no adverse events were noted in either study group, it is suggested that maintenance doses for patients with liver dysfunction should initially be at the lower end of the therapeutic range.     

Hand-foot-uterus-(HFU) syndrome with hypospadias: the hand-foot-genital- (HFG) syndrome

Three brothers with the typical findings of the HFU-syndrome, but in addition with various degrees of hypospadias are reported. The family history otherwise was negative. The similarity of the "pattern-profile" of these cases with the mean pattern of the 11 previously reported ones is striking, as expressed by a product moment correlation of 0.83, 0.8 and 0.78 respectively. The widening of the concept of the HFU to that of a HFG-syndrome, as suggested by Poznanski et al, in 1974, is discussed.     

High-density lipoprotein aggregated by oxidation induces degeneration of neuronal cells

We have previously reported that high-density lipoprotein (HDL) exhibits antineuritogenic effects on chicken cerebral cells in culture. In the present study, we show the effects of HDLs, oxidized by UV irradiation or heating, on chicken cerebral neurons in culture. Both treatments produced several physical and chemical changes in the HDLs, i.e., formation of lipid peroxides, enlargement of HDL diameters, an increased exposure of the tryptophan groups of the apolipoprotein A-I to a more hydrophilic environment, formation of bityrosines, and cross-linking of apolipoprotein A-I. When these treatments were performed in the absence of EDTA, most of the modifications described above were more intense and HDLs formed a macroaggregate that displays a rosette-like structure. The aggregated HDLs produced neurodegeneration and death when added to both undifferentiated and differentiated cerebral neurons in culture. This process was accompanied by the disorganization of the cellular microtubular cytoskeleton and hyperphosphorylation of the microtubule-associated protein tau. Native HDL or HDLs treated in the presence of EDTA inhibited the neuritogenesis of undifferentiated neurons but did not show any significant effect on the differentiated neurons in culture. The effects on the cellular cytoskeleton and morphology of aggregated HDLs recall those of the fibrillar beta-amyloid peptide. The present results suggest that aggregated HDLs could participate in neurodegeneration associated with oxidative stress in the CNS.     

Par-4 is a mediator of neuronal degeneration associated with the pathogenesis of Alzheimer disease

Prostate apoptosis response-4 (Par-4) is a protein containing both a leucine zipper and a death domain that was isolated by differential screening for genes upregulated in prostate cancer cells undergoing apoptosis. Par-4 is expressed in the nervous system, where its function is unknown. In Alzheimer disease (AD), neurons may die by apoptosis, and amyloid beta-protein (A beta) may play a role in this. We report here that Par-4 expression is increased in vulnerable neurons in AD brain and is induced in cultured neurons undergoing apoptosis. Blockade of Par-4 expression or function prevented neuronal apoptosis induced by Ab and trophic factor withdrawal. Par-4 expression was enhanced, and mitochondrial dysfunction and apoptosis exacerbated, in cells expressing presenilin-1 mutations associated with early-onset inherited AD.     

Down-regulation of hepatic and renal 11 beta-hydroxysteroid dehydrogenase in rats with liver cirrhosis

Twenty-four crossbred primiparous sows were used to investigate the influence of insulin administration after weaning on the intrafollicular insulin-like growth factor i (IGF-I) system. Sows received 0.4 i.u. insulin kg-1 bodyweight or an equivalent volume of saline for 3 days (n = 5 insulin; n = 4 saline) or 5 days (n = 5 insulin; n = 6 saline) after weaning or served as untreated controls on day 1 (n = 4). The number and diameters of ovarian follicles were recorded, and fluid was aspirated from the 20 largest follicles for determination of oestradiol and IGF-I by radioimmunoassay and of insulin-like growth factor-binding proteins (IGFBPs) by western ligand blotting. The walls of the follicles were collected for mRNA analysis by RNase protection assay or granulosa cells were collected for estimation of apoptosis by flow cytometry. Insulin treatment resulted in smaller diameters of all follicles (P < 0.05) and tended (P < 0.07) to increase the number of follicles available on day 5 compared with saline-treated animals (19.8 versus 17.8). The concentration of oestradiol in follicular fluid from large (7-10 mm) follicles on days 3 and 5 was reduced (treatment by size class interaction; P < 0.05) by insulin treatment. Insulin also reduced intrafollicular concentrations of IGF-I at days 3 and 5 after weaning (treatment by day interaction; P < 0.02) while the amounts of IGFBP-3 and IGFBPs of molecular mass 30 and 22 kDa decreased from day 3 to day 5 in saline-treated animals only (treatment by day interaction; P < 0.05). Gene expression for IGF-I increased in saline-treated animals but decreased fourfold in insulin-treated sows from day 3 to day 5 (treatment by day interaction; P < 0.002). Gene expression for IGFBP-d decreased (P < 0.04) from day 3 to day 5, while expression of IGFBP-2 was unaffected by treatment or day. Overall, insulin influenced the IGF-I system in a manner consistent with slowing follicular growth and possibly allowed more follicles to become available for ovulation.