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Biomedical subjects

S M Hall

Publications and source records attributed to S M Hall.

At least 19 recordsLinked to original sources

The British Paediatric Surveillance Unit: activities and developments in 1990 and 1991.

The British Paediatric Surveillance Unit is a joint undertaking of the British Paediatric Association, the PHLS Communicable Disease Surveillance Centre and the Department of Epidemiology at the Institute of Child Health, London. It provides an active case reporting system which aims to facilitate the surveillance of rare childhood infections and other conditions. Cards with a menu of up to twelve reportable disorders are sent monthly to more than 1100 paediatricians throughout the United Kingdom and Ireland. The average response rate is 90%. Reported cases are followed up according to study protocols. Since its inception in 1986, the Unit has facilitated the study of a wide range of disorders, including HIV infection and AIDS, Reye's syndrome, Kawasaki disease, congenital rubella, neonatal herpes, congenital toxoplasmosis and acute rheumatic fever, and the number of new applications for surveys has increased in 1992-3. Several European paediatric organisations have expressed interest in setting up similar schemes in their own countries.

Adolescent

Listeriosis surveillance: 1991.

A total of 130 cases of listeriosis was reported in England, Wales and Northern Ireland in 1991. This represents a slight increase on the 1990 total of 118 reports but a marked decline compared with the peak incidence of reporting of 291 in 1988, which was part of an upsurge of cases between 1987 and mid 1989. Two epidemiological features of note in 1991 were the reappearance of a late summer-autumn peak in cases (commonly seen prior to 1987) and an increase in the number of reports among younger patients and children. The decline in listeriosis observed during the second half of 1989, which followed government health warnings about the consumption of pâté, and the continued low level of reporting since 1989 may be due to the disappearance of a common food source. However, in the light of the recent outbreak of listeriosis in France it is important that diagnostic vigilance and warnings about high risk foods are maintained.

Adolescent

Motor nerve biopsy in severe Guillain-Barré syndrome.

We undertook a biopsy of a terminal branch of the musculocutaneous nerve in a man with severe Guillain-Barré syndrome and very small distally evoked action potentials. The biopsy showed pronounced subperineurial edema, macrophage infiltration, and many axons that had been completely demyelinated, some associated with intratubal macrophages. The biopsy unequivocally identified the pathological process as primary demyelination, not axonal degeneration, and was more informative than previous reports of sural nerve biopsies in patients with Guillain-Barré syndrome.

Axons

Onset and evolution of pulmonary vascular disease in young children: abnormal postnatal remodelling studied in lung biopsies.

Pulmonary arterial structure was examined in lung biopsies from 26 children with severe pulmonary hypertensive congenital heart disease, aged 2 months-18 years, in whom the mean pulmonary arterial pressure was 55 (range 35-105) mmHg, using light, transmission, and scanning electron microscopy. Qualitative and quantitative techniques were applied and findings compared with those in age-matched controls. At 2 months, the smooth muscle cells showed hyperplasia, hypertrophy (mean cell diameter increased, P less than 0.001), and accelerated differentiation. In all pulmonary hypertensive cases aged less than 6 months, the contractile myofilament concentration was similar to the normal concentration at 6 months. Medial connective tissue was excessive for age. Smooth muscle cells within the intima (intimal proliferation) were first seen at 7 months, lying beneath a new internal elastic lamina. They showed a reduction in myofilament concentration in the more fibrotic lesions. In all cases, endothelial cells were abnormally thick (P less than 0.001) and elongated. Cytoskeletal remodelling was indicated by an increase in micro- and intermediate filament volume density (P less than 0.05 for both). The severity of endothelial damage was related to vessel size and position in the arterial pathway. These findings indicate that pulmonary vascular disease begins at or soon after birth with abnormal pulmonary vascular remodelling which leads to obliterative pulmonary vascular disease.

Adolescent

Regrowth of PNS axons through grafts of the optic nerve of the Browman-Wyse (BW) mutant rat.

We have examined the behaviour in vivo of regenerating PNS axons in the presence of grafts of optic nerve taken from the Browman-Wyse mutant rat. Browman-Wyse optic nerves are unusual because a 2-4 mm length of the proximal (retinal) end of the nerve lacks oligodendrocytes and CNS myelin and therefore retinal ganglion cell axons lying within the proximal segment are unmyelinated and ensheathed by processes of astrocyte cytoplasm. Schwann cells may also be present within some proximal segments. Distally, Browman-Wyse optic nerves are morphologically and immunohistochemically indistinguishable from control optic nerves. When we grafted intact Browman-Wyse optic nerves or 'triplets' consisting of proximal, junctional and distal segments of Browman-Wyse optic nerve between the stumps of freshly transected sciatic nerves, we found that regenerating axons avoided all the grafts which did not contain Schwann cells, i.e., proximal segments which contained only astrocytes; regions of Schwann cell-bearing proximal segments which did not contain Schwann cells; junctional and distal segments (which contained astrocytes, oligodendrocytes and CNS myelin debris). However, axons did enter and grow through proximal segments which contained Schwann cells in addition to astrocytes. Schwann cells were seen within grafts even after mitomycin C pretreatment of sciatic proximal nerve stumps had delayed outgrowth of Schwann cells from the host nerves; we therefore conclude that the Schwann cells which became associated with regenerating axons within the grafts of Browman-Wyse optic nerve were derived from an endogenous population. Our findings indicate that astrocytes may be capable of supporting axonal regeneration in the presence of Schwann cells.

Animals

Electron microscopic immunocytochemistry of GAP-43 within proximal and chronically denervated distal stumps of transected peripheral nerve.

Growth-associated protein, GAP-43 was initially described as a neuron-specific molecule thought to play a critical role in axonal growth and regeneration. However, it is also expressed in vitro in certain CNS glia, Schwann cell precursors and non-myelinating Schwann cells. In this paper, we report the subcellular localization of GAP-43 in vivo in chronically-denervated Schwann cells in the distal stumps of previously transected rat sciatic nerve. We have used a progressive lowering of temperature method combined with the non-polar acrylic resin Lowicryl HM20 and a post-embedding labelling regime to visualize the distribution of GAP-43, S-100 (marker for Schwann cells), RT97 and NF68 (markers for different subunits of the neurofilament molecule). We report that (1) the smallest calibre regrowing axons were GAP-43-positive, sometimes NF68-positive but always RT97-negative; (2) regenerating myelinated axons and larger unmyelinated axons (> 0.7 microns diameter) were NF68-positive, RT97-positive but GAP-43-negative; (3) cytoplasmic processes within Schwann cell basal lamina tubes in the distal stumps were S-100-positive, GAP-43-positive but RT97- and NF68-negative. The similar localization of GAP-43 within regrowing axons and denervated Schwann cells suggests that GAP-43 may function similarly in both situations, and may thus be involved in motility and/or elongation of axons and Schwann cells during regeneration.

Animals

GAP-43 is expressed by nonmyelin-forming Schwann cells of the peripheral nervous system.

Recently it has been demonstrated that the growth-associated protein GAP-43 is not confined to neurons but is also expressed by certain central nervous system glial cells in tissue culture and in vivo. This study has extended these observations to the major class of glial cells in the peripheral nervous system, Schwann cells. Using immunohistochemical techniques, we show that GAP-43 immunoreactivity is present in Schwann cell precursors and in mature non-myelin-forming Schwann cells both in vitro and in vivo. This immunoreactivity is shown by Western blotting to be a membrane-associated protein that comigrates with purified central nervous system GAP-43. Furthermore, metabolic labeling experiments demonstrate definitively that Schwann cells in culture can synthesize GAP-43. Mature myelin-forming Schwann cells do not express GAP-43 but when Schwann cells are removed from axonal contact in vivo by nerve transection GAP-43 expression is upregulated in nearly all Schwann cells of the distal stump by 4 wk after denervation. In contrast, in cultured Schwann cells GAP-43 is not rapidly upregulated in cells that have been making myelin in vivo. Thus the regulation of GAP-43 appears to be complex and different from that of other proteins associated with nonmyelin-forming Schwann cells such as N-CAM, glial fibrillary acidic protein, A5E3, and nerve growth factor receptor, which are rapidly upregulated in myelin-forming cells after loss of axonal contact. These observations suggest that GAP-43 may play a more general role in the nervous system than previously supposed.

Animals

Investigation of metabolic disorders resembling Reye's syndrome.

Ten per cent of patients initially reported with Reye's syndrome in the British Isles (1981-91) were subsequently found to have an underlying inherited metabolic disorder (IMD). There was also evidence to suggest that other cases may not have been recognised. The range of metabolic disorders that mimic Reye's syndrome is wide and specialist, often complex, investigations are required to make a specific diagnosis. Those patients presenting with Reye's syndrome-like illness but also with one or more clinical features suggestive of an IMD require particular attention and detailed investigation. Recommendations for specimen collection and investigation are presented.

Decision Making

Haemorrhagic shock encephalopathy syndrome in the British Isles.

The aetiopathogenesis of haemorrhagic shock encephalopathy syndrome (HSES) remains unclear and after concern that a novel environmental agent was the cause, the British Paediatric Association and the Public Health Laboratory Service Communicable Disease Surveillance Centre in 1983 initiated surveillance of this condition in the British Isles. After 1986 cases were ascertained via the British Paediatric Surveillance Unit 'active' reporting scheme; this report presents the findings for 1985-8. Sixty five patients were reported, of whom 52 satisfied the criteria for inclusion. Of those whose outcome was known, 24 (46%) died, 18 had severe neurological damage, and six survived apparently intact. Epidemiological features of note were: the median age of 15 weeks (range 3-140); statistically significant clustering of admission times suggesting a peak onset period at night; lack of geographic clusters, of secular trends and, except for a slight excess in winter months, of seasonality. Clinical and pathological features followed a highly consistent pattern, suggesting that HSES is an individual clinical entity distinguishable from conditions with similar presentations, such as septicaemia and Reye's syndrome. There was no microbiological or epidemiological evidence to support the emergence of a novel environmental agent. Many of the features of HSES were, however, the same as those described in heat stroke and we suggest that the two conditions are the same even though there is usually no history of overt overheating.

Age Factors

Transient ultrastructural injury and repair of pulmonary capillaries in transplanted rat lung: effect of preservation and reperfusion.

A donor lung is injured during preservation and is generally thought to be further injured by reperfusion on transplantation. Donor lungs from 15 adult male Lewis rats preserved by flush perfusion with cold Marshall's solution at 4 degrees C were examined by scanning and by quantitative transmission electron microscopy after 2, 4, or 7 h of storage at 4 degrees C and after transplantation (syngeneic) at 4 or 12 h (six animals per time interval). During preservation of the donor lung, capillary morphology changed rapidly. Both endothelial cells and type I pneumonocytes thinned (surface/volume ratio increased by 2 h in both; P less than 0.001). Pericapillary edema developed involving the blood-gas barrier. Basement membrane thickness increased significantly (P less than 0.001). Occasional breakage of the endothelial cell sheet occurred after 4 h of preservation, but even after 7 h of preservation there was no evidence of irreversible cell damage. The lamellar bodies of type II pneumocytes aggregated. Changes increased in severity with increase in preservation time. After transplantation, type I and type II pneumonocytes recovered after 12 h, but it took longer for the endothelial cell morphology to recover. Edema decreased rapidly during the first 4 h, despite the number of adherent neutrophils increasing 3-fold. The pulmonary capillaries of the transplanted lung showed no structural evidence of additional reperfusion injury, indicating a satisfactory method of preservation.

Animals

Weight gain prevention and smoking cessation: cautionary findings.

OBJECTIVES: Weight gain is a consistent sequela of smoking cessation. A successful intervention might attract smokers who fear weight gain. If the gain causes smoking relapse, such an intervention might reduce smoking relapse risk. METHODS: Using a sample of 158 smokers who completed a 2-week smoking treatment program, we compared an innovative weight gain prevention intervention with both a nonspecific treatment and standard treatment. Subjects were assessed on weight and smoking behavior and followed for 1 year. RESULTS: A disturbing, unexpected finding was that subjects in both the innovative and nonspecific conditions had a higher risk of smoking relapse than did standard treatment subjects. Some differences were observed between abstinent and smoking subjects in weight gain by treatment condition. CONCLUSIONS: Both active interventions may have been so complicated that they detracted from nonsmoking. Also, caloric restriction may increase the reinforcing value of nicotine, a psychoactive drug, thereby increasing smoking relapse risk. The magnitude of weight gain after smoking cessation may not merit interventions that increase smoking risk. Perhaps attitudinal modifications are the most appropriate.

Adult

Partner support, psychological treatment, and nicotine gum in smoking treatment: an incremental study.

Smokers (N = 99) were randomly assigned to one of three conditions: nicotine gum (NG), nicotine gum plus psychological treatment (NG-PT), and nicotine gum plus psychological treatment and partner support (NG-PT-PS). Data were collected at Weeks 0, 4, 12, 26, and 52 from study start. Contrary to expectations, NG-PT-PS and NG-PT failed to increase abstinence rates. Subjects who were closer to their support partners had significantly lower abstinence rates with NG-PT-PS than with the other conditions, although not significantly at Weeks 26 and 52. Treatments without partner participation (NG-PT and NG) were significantly more effective for subjects who had an extremely close support partner outside the treatment setting than for those who did not at all weeks. The role of social support in smoking treatment is discussed.

Adult

A study of neuropathy in HIV infection.

A prospective study of possible aetiological factors for neuropathy associated with HIV infection was performed in 80 patients and 28 homosexual controls. At entry to the study twelve patients (15 per cent) had evidence of a generalized neuropathy not due to any other cause and a further three patients developed symptomatic neuropathy during a mean (SD) follow-up of 20 (7.5) months. All but two of these neuropathies were of the distal symmetrical sensory type. Electrophysiology was consistent with an axonal pathology and nerve biopsy confirmed this as the major pathological change. Warming threshold was the diagnostic test most frequently abnormal, sometimes in the absence of other electrophysiological abnormalities. No association was seen with opportunistic infection (cytomegalovirus, herpes simplex, Pneumocystis pneumonia, toxoplasmosis, Cryptococcus infection or tuberculosis). HIV proviral DNA could not be detected in paraffin sections of peripheral nerve in six patients with neuropathy. The presence of the neuropathy did not show significant correlation with depression of the number of CD4+ T cells in the blood, impaired T cell function tests, or IgG, IgM, or IgA levels. Immune complexes containing C1q, but not those containing IgG, IgM, IgA or C3c, were significantly more common among neuropathic patients (p = 0.01).

AIDS-Related Opportunistic Infections

Human listeriosis and paté: a possible association.

OBJECTIVES: To study trends in human listeriosis and determine possible sources of infection. DESIGN: Descriptive analysis of laboratory reports of human listeriosis together with a survey of subtypes of Listeria monocytogenes isolated from patients and foodstuffs and an interview survey of patients to obtain food histories. SETTING: United Kingdom and Republic of Ireland 1985 to 1990. RESULTS: There was a near doubling in the incidence of human listeriosis in England, Wales, and Northern Ireland between 1985 and mid-1989 followed by a sharp decline. The upsurge in cases was caused largely by two strains of L monocytogenes, which accounted for 30-54% of the annual totals. These strains were less common before 1987 and after July 1989. A survey of paté in England and Wales in July 1989 showed that it frequently contained L monocytogenes. A similar survey in July 1990 showed a reduction in the proportions of samples contaminated. In 1989 patés from a single plant (manufacturer Y) were more likely to be contaminated by L monocytogenes and at higher levels than those from other producers. Most strains of L monocytogenes recovered from manufacturer Y's paté in 1989 were indistinguishable from those responsible for the 1987-9 upsurge in human listeriosis and were uncommon among isolates from patés from other manufacturers and from a wide range of other foodstuffs. Patients infected with the types of L monocytogenes found in paté were significantly more likely to have recently eaten paté than those affected by other strains. The start of the decline in numbers of cases of listeriosis coincided with government health warnings on paté consumption and the suspension of supplies from manufacturer Y. CONCLUSIONS: Contamination of paté was a likely contributory cause of the increase in the incidence of listeriosis between 1987 and 1989.

England