Apoptosis and delayed degeneration after spinal cord injury in rats and monkeys.

Apoptosis is a morphologically defined form of programmed cell death seen in a variety of circumstances, including immune cell selection, carcinogenesis and development. Apoptosis has very recently been seen after ischemic or traumatic injury to the central nervous system (CNS), suggesting that active cell death as well as passive necrosis may mediate damage after CNS injury. After spinal cord injury (SCI) in the rat, typical post-traumatic necrosis occurred, but in addition, apoptotic cells were found from 6 hours to 3 weeks after injury, especially in the spinal white matter. Apoptotic cells were positive for oligodendrocyte markers. After SCI in monkeys, apoptotic cells were found within remote degenerating fiber tracts. Both secondary degeneration at the site of SCI and the chronic demyelination of tracts away from the injury appear to be due in part to apoptosis. As cytokines have been shown to mediate oligodendrocyte death in vitro, it seems likely that chronic demyelination after CNS injury shares features with chronic degenerative disorders like multiple sclerosis.

Effects of static stretching on leg power during cycling.

AIM: This study investigated the effects of warm-up involving static stretching on leg power. It was expected that the inclusion of static stretching in the warm-up would decrease leg power. METHODS: Twenty-seven healthy volunteers (16 male, 11 female) participated in the study. A prospective, repeated measures design was implemented where volunteers underwent 2 testing sessions at least 24 hours apart. One testing session involved a control warm-up (5 min submaximal cycling) followed by 4 10-s leg power tests at 5, 20, 40 and 60 min postwarm-up. For the other testing session, the subjects performed 5 min of submaximal cycling followed by 15 min of lower body static stretching and then the four leg power tests. Relative peak power, time to peak power and relative total work were measured for each leg power test. RESULTS: Peak power and total work were significantly greater after the static stretching warm-up compared to the control warm-up on all power tests. Peak power was achieved more quickly for the static stretching warm-up compared to the control warm-up on the 5 min test only. CONCLUSIONS: A warm up that includes static stretching has beneficial effects on anaerobic power events in comparison to submaximal cycling alone.

Delayed wound healing in immunodeficient TGF-beta 1 knockout mice.

Previous studies showed that full-thickness wounds in transforming growth factor-beta1-deficient mice initially heal normally. Unfortunately, transforming growth factor-beta1 deficiency leads to a multifocal inflammatory disease affecting most organs of the body, which ultimately interferes with later stages of wound healing in these mice. As this inflammatory disease is eliminated in transforming growth factor-beta1-deficient mice lacking T and B cells (Tgfb1-/- Scid-/- mice), we hypothesized that wound repair in the latter would proceed normally, even at later stages of healing. Unexpectedly, Tgfb1-/- Scid-/- mice demonstrate a major delay of approximately 1 wk in each of the major phases of wound healing: inflammation, proliferation, and maturation. Immuno- deficient Scid-/- mice that have the wild-type Tgfb1 allele do not experience this delay in wound healing. One interpretation of these findings is that lymphocytes and transforming growth factor-beta1 affect compensatory pathways in wound healing. An alternative interpretation is that the delayed expression of Tgfb2 and Tgfb3 that occurs in the absence of transforming growth factor-beta1 results in the delayed wound healing, suggesting that transforming growth factor-beta2 and/or transforming growth factor-beta3 play important parts in wound healing.

The Nf1 tumor suppressor regulates mouse skin wound healing, fibroblast proliferation, and collagen deposited by fibroblasts.

Neurofibromatosis type 1 patients develop peripheral nerve tumors (neurofibromas) composed mainly of Schwann cells and fibroblasts, in an abundant collagen matrix produced by fibroblasts. Trauma has been proposed to trigger neurofibroma formation. To test if loss of the neurofibromatosis type 1 gene (Nf1) compromises fibroblast function in vivo following trauma, skin wounding was performed in Nf1 knockout mice. The pattern and amount of collagen-rich granulation bed tissue, manufactured by fibroblasts, was grossly abnormal in 60% of Nf1+/- wounds. Nf1 mutant fibroblasts showed cell autonomous abnormalities in collagen deposition in vitro that were not mimicked by Ras activation in fibroblasts, even though some Nf1 effects are mediated through Ras. Nf1+/- skin wound fibroblasts also proliferated past the normal wound maturation phase; this in vivo effect was potentiated by muscle injury. In vitro, Nf1+/- fibroblasts showed higher proliferation in 10% serum than Nf1+/+ fibroblasts. Macrophage-conditioned media or epidermal growth factor potentiated Nf1+/- fibroblast proliferation in vitro, demonstrating abnormal response of mutant fibroblasts to wound cytokines. Thus Nf1 is a key regulator of fibroblast responses to injury, and Nf1 mutation in mouse fibroblasts causes abnormalities characteristic of human neurofibromas.

Medicinal yeast extracts.

Alcoholic extracts of bakers' yeast (Saccharomyces cerevisiae) have been used for over 60 years in over-the-counter medications for the treatment of hemorrhoids, burns, and wounds. Although previous studies suggested that small peptides were responsible for the medical observations, the peptides were never resolved into separate fractions and identified. In the present report, a protein fraction was prepared by RPC18 chromatography of the extract which enhances wound closure in both diabetic and non-diabetic littermates. The peptides are active in nanomolar amounts and are 600 times more active than the initial extract. SDS-PAGE and N-terminal amino acid sequencing identified 4 polypeptides in the extract. Three of the proteins were small molecular weight stress-associated proteins: copper, zinc superoxide-dismutase, ubiquitin, and glucose lipid regulated protein (HSP 12). The fourth protein, acyl-CoA binding protein II, has not been previously associated with stress proteins.

Effects of aging on vasopressin secretion, water excretion, and thirst in man.

Disorders of water balance are common among elderly patients. A number of factors may contribute. Osmoreceptor-mediated release of AVP is increased, but the response to volume stimuli may be reduced. The capacity of the kidney to concentrate urine is reduced by age, but this impairment cannot be correlated with coincident loss of glomerular filtration (GFR); there may rather be a failure of cAMP response to AVP in aging kidneys. Free water clearance is reduced in the old in proportion to the loss of GFR. Thirst mechanisms are also significantly impaired in healthy as well as sick old people. This combination of factors renders old people particularly liable to develop disorders of water homeostasis during episodes of acute or chronic ill health.

Monoclonal antibody to carnosine synthetase identifies a subpopulation of frog olfactory receptor neurons.

A monoclonal antibody directed against the synthetic enzyme for the dipeptide carnosine was used on cryostat sections of olfactory epithelium from the grass frog Rana pipiens. A subpopulation of what morphologically resembled olfactory receptor neurons were immunolabelled by this antibody. Labelled cells were completely stained, including the cell body, axonal and dendritic processes, dendritic knobs and cilia-like projections from the knobs.

Distribution of NADPH-diaphorase reactivity in the spinal cord of metamorphosing and adult Xenopus laevis.

The histochemical NADPH-diaphorase reaction has identified distinct neuronal populations in the nervous system of several species. Considerable evidence suggests that NADPH-d is a neuronal nitric oxide synthase (NOS). We examined spinal cords of adult and metamorphosing Xenopus laevis (XL) for developmental differences in NADPH-d reactivity. In adult XL, labeling was found in all dorsal root ganglia (DRGs) and in their termination sites within the dorsal horn (cutaneous afferent field) and intermediate gray (muscle afferent field). Cell bodies in the intermediate gray regions containing the autonomic preganglionic neurons were labeled in thoracic and sacral sections. Neurons located in the medial (MMC) and lateral motor columns (LMC) of the ventral horn were also stained. In metamorphosing XL, reactivity was detected in neurons in the intermediate gray, in the MMC and in the LMC as in the adult. Additionally, primary motoneurons including those innervating tail musculature were labeled. Neurons in the DRGs were stained at all stages; in the dorsal horn, the density of staining reflected the development of the sensory afferent fields. The conservation of NADPH-d reactivity in adult and metamorphosing XL spinal neurons suggests that NOS may be involved in processes independent of developmental changes occurring in XL spinal cord.

Review of case definitions for nosocomial infection--towards a consensus. Presentation by the Nosocomial Infection Surveillance Unit (NISU) to the Hospital Infection Liaison Group, subcommittee of the Federation of Infection Societies (FIS).

As part of the preparatory work for a national surveillance scheme, consensus was sought on the case definitions for nosocomial infection. We compare six sets of case definitions for nosocomial urinary tract infection, surgical wound infection, bloodstream infection and pneumonia, and highlight areas of agreement and variation. We hope this will stimulate discussion among those with expertise and interest in surveillance and so contribute to the development of nationally agreed case definitions.

Trends in bacteraemia on the haematology and oncology units of a UK tertiary referral hospital.

As part of ongoing surveillance of infection in the haematology and oncology units at Belfast City Hospital, microbiologically documented bloodstream infections over three 12-month periods 1994/5, 1998/9 and 1999/00 were reviewed. Gram-positive organisms were the most common cause of blood stream infection in the haematology unit causing 66%, 56% and 64% of episodes of monomicrobial bacteraemia in 1994/5, 1998/9 and 1999/00, respectively. In haematology patients, enterococci have emerged as an important cause of bacteraemia, with increasing levels of glycopeptide resistance, and the 'non-fermenting Gram-negative rods other than Pseudomonas aeruginosa' are an increasingly common cause of monomicrobial and polymicrobial bacteraemia. In oncology patients, Gram-negative organisms (predominantly enterobacteriaceae) were more common than Gram-positive organisms, causing 50% and 54% of monomicrobial bacteraemia in 1998/9 and 1999/00, respectively. Changes in patient population, underlying diseases and chemotherapeutic agents may explain these findings. The spectrum of infection seen in haematology and oncology patients changes as management evolves. Ongoing co-operation between haematologists, oncologists and microbiologists is important to detect trends in epidemiology, which can be used to design empirical antibiotic regimens and guide infection control policies.

Species differences in amphibian olfactory neuron reactivity to a monoclonal antibody.

A monoclonal antibody immunostained a subpopulation of olfactory sensory neurons in cryostat sections of the olfactory mucosa of the grass frog, Rana pipiens, and the bullfrog, Rana catesbeiana. However, in the olfactory tissues of the African clawed frog, Xenopus laevis, only mucus and mucus-secreting components were stained, and no cell-specific immunoreactivity was seen in the tiger salamander, Ambystoma tigrinum. This antibody is a useful marker of olfactory neuronal subpopulations in some amphibians and illustrates the difficulties in cross-species immunocytochemistry.

Topical application of yeast extract accelerates the wound healing of diabetic mice.

Alcoholic extracts of yeast have been used as the active ingredient in medications under names such as "tissue or skin respiratory factor," Biodyne (Sperti Drug Co, Cincinnati, Ohio--now defunct), and live yeast cell derivative (LYCD). Beneficial clinical results from the use of LYCD have been reported for the treatment of burns, wounds, and hemorrhoids. The medicinal effects of LYCD have recently been localized to a protein fraction containing a mixture of several peptides. The effects of topical application of the peptide mixture on wounds were examined in diabetic mice, an animal model in which the healing process is disrupted and delayed. Full-thickness wounds were created on the backs of diabetic (DB) and nondiabetic (non-DB) mice. Half of the DB and non-DB mice were treated with 0.05 mL of LYCD after wounding and for 4 successive days. All other mice received vehicle. Wound areas were measured at Day 0 and at 2-day intervals. Mice were sacrificed at 3, 7, 10, 21, and 28 days postinjury. Differences in the extent and quality of healing appeared between DB mice receiving LYCD and DB mice receiving vehicle by day 10 (P < .0001). By 24 days postinjury, DB mice receiving LYCD had achieved 100% wound closure, whereas DB mice receiving vehicle had achieved only 31.4% wound closure. Histologic examination of wounds reflected improved wound healing in DB mice receiving LYCD as compared with those receiving vehicle. A topically applied yeast extract peptide mixture significantly attenuates wound closure and the degree of cellular reorganization of full-thickness excisional wounds of DB mice.

Eruptive xanthoma.

We recently had occasion to diagnose eruptive xanthoma. The significance of this cutaneous finding is that it is indicative of an underlying hypertriglyceridemic state. Appropriate dietary changes, correction of secondary factors, along with the addition of antihyperlipidemic drugs as required, will lower the plasma triglyceride level and allow the xanthomatous lesions to resolve.

Aquagenic urticaria.

Aquagenic urticaria is a rare form of physical urticaria characterized by small follicular wheals with an erythematous flare upon exposure to water. We describe typical lesions in a seven-year-old boy with aquagenic urticaria, cholinergic urticaria, and symptomatic dermatographism, who responded to treatment with ultraviolet B and oral antihistamines.

Effects of beta-hydroxy-beta-methylbutyrate and creatine monohydrate supplementation on the aerobic and anaerobic capacity of highly trained athletes.

AIM: The aim of this study was to investigate the effects of 6 wks oral supplementation of beta-hydroxy-beta-methylbutyrate (HMB) and a mixture of HMB and creatine monohydrate (HMBCr) on aerobic and anaerobic capacity in highly trained athletes. It was hypothesised that HMB and HMBCr would have positive effects on aerobic and anaerobic power. METHODS: A prospective study involving a repeated measures design was utilised where subjects underwent testing prior to, and immediately after, a 6 wks supplementation period. Elite, male rugby league players (n=27) were divided into 3 groups, a control group (n=6), a HMB group (3 g/d; n=10) and a HMBCr group (3 g/d HMB + 3 g/d Cr; n=11). Testing involved a multistage fitness test to determine aerobic power and a 60 sec maximal cycle test to determine anaerobic capacity. Peak power, total work and peak lactate levels were measured in the anaerobic cycle test. RESULTS: Two-way repeated measures ANOVA revealed no effect of HMB or HMBCr on any of the measured parameters in comparison to the control group. CONCLUSION: Aerobic and anaerobic ability of highly trained male athletes is unaffected by 6 wks oral supplementation with HMB or a combination of HMB and creatine monohydrate.

Hospital-based stroke care in Ireland: results from one regional register.

BACKGROUND: Most patients with acute stroke are admitted to hospital. If stroke services in this country are to be improved, we need accurate and reliable information about the types of stroke patients being admitted, their present management and outcome. AIMS: To examine the demography, severity, level of investigation, length of stay, mortality and discharge location of prospectively identified consecutive stroke admissions to three general hospitals in South East Dublin. RESULTS: Three hundred and twenty nine consecutive stroke admissions to three general hospitals in South East Dublin were registered using the European Stroke Database over 50 weeks. The mean age was 73.3 years, whilst 20.1% patients were under 65 years. Prior to admission, 90% of patients were community dwelling with 14.9% of patients being dependent in activities of daily living. 22.4% of patients had some depression in level of consciousness on admission. The overall mortality rate was 26.1% whilst 136 (41.3%) were discharged home, 50 (15.2%) went to institutional care and 45 (13.7%) went to non general hospitals secondary rehabilitation units. The mean length of stay was 31.3 days. The combined poor outcome measure (mortality plus percentage of patients discharged to institutional care), was lower in one hospital compared to the other two hospitals (29.3% versus 44.65%, p > or = 0.05) probably reflecting case mix. Stroke accounted for 4.2% of all bed days in the major general hospital in this area. The overall CT scan rate was 84.5%, with 18.2% of CT scans showing a haemorrhagic component and two patients (0.8%) having brain tumours. Carotid doppler examinations were carried out in 37% of patients. CONCLUSION: The results demonstrate the high mortality and prolonged hospital stay for stroke patients in this area and emphasise the need for co-ordinated stroke care and regular audit to ensure most effective use of hospital resources.