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Biomedical subjects

P Anand

Publications and source records attributed to P Anand.

At least 91 records · Page 5Linked to original sources
PubMed1997

Neurotrophin-3-like immunoreactivity and Trk C expression in human spinal motoneurones in amyotrophic lateral sclerosis.

We have demonstrated neurotrophin-3 (NT-3)-like immunoreactivity and tyrosine kinase C (Trk C) receptor expression in motoneurones in postmortem amyotrophic lateral sclerosis (ALS) and control human spinal cord sections. We report that NT-3-like immunoreactivity in motoneurones is decreased in ALS when compared to control tissue. Trk C is expressed in low abundance in both control and ALS motoneurones. These findings are of importance in developing therapeutic strategies for ALS.

Aged↗
PubMed1997

Glial-derived neurotrophic factor in human adult and fetal intestine and in Hirschsprung's disease.

BACKGROUND & AIMS: Glial cell line-derived neurotrophic factor (GDNF) signals through the product of the ret proto-oncogene, which is known to be mutated in Hirschsprung's disease and other conditions with gut dysmotility. The aim of this study was to determine the presence of GDNF and its receptor component (RET) in human adult and developing intestine and to evaluate their distribution pattern in Hirschsprung's disease. METHODS: GDNF and RET were detected immunohistochemically, and GDNF was quantified by immunoassay in specimens of human adult and fetal colon and Hirschsprung's disease intestine. RESULTS: GDNF-like immunoreactivity was detected in all specimens. Immunostaining of GDNF was restricted to neural fiber-like structures across the gut wall and was similar to staining with markers of glia and Schwann cells. In contrast, RET immunoreactivity was found only in neural cell bodies. GDNF levels determined by immunoassay were higher in muscle than mucosal gut layers, and there was no difference between affected and unaffected segments of Hirschsprung's disease. CONCLUSIONS: GDNF is present in adult and fetal human gut, where it may play a neurotrophic role. Its staining pattern suggests that it is localized in glia or Schwann cells. There seems to be no difference of GDNF levels between affected and unaffected intestinal segments in Hirschsprung's disease.

Adult↗
PubMed1997

Increased nerve growth factor levels in the urinary bladder of women with idiopathic sensory urgency and interstitial cystitis.

OBJECTIVES: To determine whether nerve growth factor (NGF) is elevated in painful conditions of the urinary bladder (idiopathic sensory urgency, interstitial cystitis and painful chronic cystitis). PATIENTS AND METHODS: Sixteen women patients were recruited from the Urodynamic Clinic at The Elizabeth Garrett Anderson Hospital, London. Four each had idiopathic sensory urgency (mean age 34 years, range 24-51), chronic cystitis (mean age 51 years, range 40-79) and interstitial cystitis (mean age 41 years, range 29-53). Four women who had genuine stress incontinence on cystometry but with no irritative symptoms were used as controls (mean age 45 years, range 35-54). The levels of NGF were determined in bladder biopsies from all women and biopsy sections were immunostained to detect NGF. RESULTS: The levels of NGF were higher in samples from all three painful bladder conditions than in samples from controls. Immunostaining showed increased NGF expression in the urothelium, most marked in patients with idiopathic sensory urgency. CONCLUSIONS: The increased level of NGF may explain several clinical and pathological features in these conditions, including sensitization of nociceptor fibres and increased numbers of mast cells. We propose that anti-NGF treatment may be a rational and effective treatment in intractable bladder pain.

Adult↗
PubMed1996

Neurotrophins and peripheral neuropathy.

Endogenous nerve growth factor (NGF) levels were studied in patients with nerve trauma, diabetes mellitus and leprosy, the most common causes of human peripheral neuropathy. In diabetics, there was an early length-dependent dysfunction of small-diameter sensory fibres, with depletion of skin NGF and the sensory neuropeptide substance P. The NGF depletion correlated significantly with decreased skin axon-reflex vasodilatation, which is mediated by small sensory fibres at least partly via substance P release. Immunostaining showed depletion of NGF in keratinocytes in diabetic skin. In injured nerves, NGF levels were reduced when compared to intact nerve, except acutely distal to injury; NGF-immunostaining was seen in Schwann cells in distal segments, including neuromas. NGF levels were decreased in leprosy-affected skin and nerve. The role of neurotrophins in the rational treatment of human neuropathies is discussed e.g. loss of nociception and axon-reflex vasodilatation contribute to skin ulceration, a major and serious complication, for which NGF may provide prophylaxis.

Animals↗
PubMed1996

Nerve growth factor enhances nerve regeneration through fibronectin grafts.

Soluble fibronectin and nerve growth factor (NGF) promote axonal regeneration when placed in silicone tubes. We investigated the ability of orientated fibronectin mats to bind and release bioactive NGF and the possibility of augmenting axonal regeneration following axotomy by using fibronectin conduits impregnated with NGF. The release of NGF was quantified using a fluorometric ELISA and bioactivity confirmed with a neuronal culture bioassay. Immunohistochemical techniques and computerized image analysis were used to assess the rate and volume of axonal and Schwann cell regeneration. The delivery of NGF to the site of injury produced an increase in the rate (P < or = 0.007) and volume (P < or = 0.004) of both axonal and Schwann cell regeneration when compared to conduits of plain fibronectin. We conclude that the local delivery of NGF by impregnated fibronectin conduits enhances axonal regeneration.

Animals↗
PubMed1996

The role of endogenous nerve growth factor in human diabetic neuropathy.

Nerve growth factor (NGF) is trophic to sensory and sympathetic fibers. In animal models, NGF is depleted in diabetic nerves and NGF deprivation produces hypoalgesia. Exogenous NGF can reverse some of the pathological changes in diabetic nerves and NGF excess leads to hyperalgesia. We have quantified sensory and autonomic function in early diabetic polyneuropathy and correlated changes with levels of NGF and neuropeptides in affected skin. We describe an early length-dependent dysfunction of sensory small-diameter fibers, prior to dysfunction of sympathetic fibers, with depletion of skin NGF and the sensory neuropeptide substance P. We describe a significant correlation between NGF depletion and decreased skin axon-reflex vasodilation, mediated by small sensory fibers partly via substance P release. Immunostaining shows depletion of NGF in keratinocytes in diabetic skin. We propose that a decrease in endogenous skin-derived NGF influences the presentation of diabetic polyneuropathy, although metabolic or vascular abnormalities may be the cause of the neuropathy. As loss of nociception and axon-reflex vasodilation contribute to diabetic foot ulceration, early and prolonged NGF treatment at an appropriate dose may provide rational prophylaxis for this condition.

Adolescent↗
PubMed1995

Nerve growth factor levels in cultured human skin cells: effect of gestation and viral transformation.

Extracts of cultured human keratinocytes and fibroblasts were assayed for nerve growth factor-like immunoreactivity (NGF) by a specific enzyme-linked immunoabsorbant assay. NGF levels were higher in primary cultured keratinocytes than in freshly isolated keratinocytes or culture through multiple passages. Viral transformation of keratinocytes with the human papilloma virus (HPV16) significantly increased NGF levels, whilst transformation with the simian virus (SV40), which induces simple epithelial differentiation, reduced the concentration of NGF. Passaged epidermal keratinocytes contained more than twice as much NGF as did passaged fibroblasts. Oral keratinocytes and fibroblasts, and psoriatic fibroblasts, all from high turnover tissues, did not contain significantly different levels of NGF in culture than dermal keratinocytes or fibroblasts. Foetal fibroblasts contained five times as much NGF as did adult fibroblasts. These results suggest that basal keratinocytes are a major but not sole source of NGF in human skin, and that NGF may play a role in human skin development.

Adult↗
PubMed1995

Ciliary neurotrophic factor receptor expression in spinal cord and motor cortex in amyotrophic lateral sclerosis.

Ciliary neurotrophic factor (CNTF) is known to rescue motor neurones in animal models of injury and neurodegeneration and we have recently described regional changes of CNTF protein levels in spinal cord from patients with sporadic motor neurone disease of the amyotrophic lateral sclerosis (ALS) type. However, information is lacking about the CNTF receptor in this condition. We have therefore studied mRNA levels for the alpha subunit of the CNTF receptor (CNTFR alpha) and for CNTF itself in postmortem spinal cord and cerebral cortex in patients with sporadic ALS and matched controls. We report that in the spinal cord of ALS patients there is a marked increase in the hybridisation signal for CNTFR alpha subunit mRNA overlying motor neurones. In contrast, very little mRNA for CNTFR alpha subunit was found in the motor cortex and no differences were seen between ALS and controls. We were unable to detect any hybridisation signal for CNTF mRNA. Our findings provide evidence for regional differences in CNTF receptor expression in upper- and lower-motor neurones in ALS.

Aged↗
PubMed1995

Regional changes of ciliary neurotrophic factor and nerve growth factor levels in post mortem spinal cord and cerebral cortex from patients with motor disease.

Ciliary neurotrophic factor (CNTF) rescues motor neurons in animal models of injury and neurodegeneration, and disruption of the mouse CNTF gene results in motor neuron degeneration in mature adults. Glial cells increase nerve growth factor (NGF) expression in neuropathological conditions, and the sensory system can be affected in the amyotrophic lateral sclerosis (ALS) type of motor neuronic disease. We therefore studied CNTF and NGF levels in post mortem spinal cord and cerebral cortex from patients with ALS and matched controls. We report a marked decrease of CNTF in the ventral horn of spinal cord in ALS, with no change in cerebral motor cortex. In contrast, NGF levels were decreased in ALS cerebral motor cortex, where the corticospinal tract originates, but increased in the lateral column of spinal cord, which includes the region of corticospinal tract degeneration in ALS. Both CNTF and NGF levels were decreased in ALS dorsal spinal cord.

Aged↗
PubMed1995

Assessment of cutaneous sensory and autonomic axon reflexes in rheumatoid arthritis.

OBJECTIVE: To assess sensory function in skin overlying the joints of patients with rheumatoid arthritis, in relation to the pain and tenderness which commonly arises in structures not directly involved in the inflammatory process. METHODS: An intradermal injection of capsaicin 0.05 microgram in 10 microliters was made over the wrists and forearms of 40 patients with rheumatoid arthritis and 46 control subjects. Axon reflex vasodilatation was measured using laser Doppler flowmetry. Cholinergic sympathetic function was assessed by measuring axon reflex sweating induced by a single intradermal injection of nicotine 0.5 microgram in 0.1 ml. RESULTS: Capsaicin induced axon reflex vasodilation over the wrists was found to decrease with age in normal subjects (r = -0.62, p < 0.001). In patients with rheumatoid arthritis, capsaicin induced axon reflex vasodilatation was significantly greater over the wrists, but not the forearms, when compared with age matched normal controls (p < 0.01). A minimal correlation between axon reflex vasodilatation and visual analogue pain score was apparent in the rheumatoid group (r = -0.37, p < 0.05). Nicotine induced sweating responses were similar in the rheumatoid and normal groups, and both showed a linear age related decline. CONCLUSIONS: The results show a selective increase of capsaicin induced vasodilatation in skin overlying joints in patients with rheumatoid arthritis. This suggests that the activity of a sub-population of periarticular small sensory fibres is altered, which may explain, at least in part, some of the clinical findings in this disorder.

Adult↗
PubMed1995

Objectives, information and incentives in the NHS internal market.

In order to achieve and monitor success in the NHS internal market, it is important that information related to health care objectives is developed and used. The paper argues that these objectives are not always easy to specify but that four groups can be identified: efficiency, equity, quality and accountability/responsiveness. Although information management specialists have emphasised the construction and use of appropriate frameworks for planning information flows, whether appropriate information is used depends on the existence of incentives for its supply. Using concepts from game theory, the paper offers a non-technical examination of the incentives that the contracting environment imposes on the development of new information. The article concludes by suggesting that, for a variety of reasons, the incentives to produce information which would help monitor medical outcomes and related objectives, as distinct from inputs or activities, are often weak and sometimes perverse.

Cost-Benefit Analysis↗
PubMed1994

Effect of out-of-hospital albuterol inhalation treatments on patient comfort and morbidity.

STUDY OBJECTIVE: To determine the effect of the institution of out-of-hospital albuterol treatments for acute asthma on out-of-hospital time intervals emergency department (ED) morbidity. DESIGN: Retrospective chart and ambulance run report review. PARTICIPANTS: All patients who presented with a diagnosis of asthma on the ED record and ambulance run report during 1988 and 1990. RESULTS: Ninety patients treated prior to the routine use of nebulized albuterol (in 1988) and 86 patients treated during the period after the institution of nebulized albuterol (in 1990) were compared. Age, sex, scene and travel times, vital signs, peak expiratory flow rates, length of ED stay, hospitalizations, ED treatment, and mortality were recorded for each patient. Changes over time were determined using a cohort of asthma patients in each year as controls. Severity was recorded as low (less than 3) or high (3 or more) on a modified Fischl index for asthma. Groups were compared by F test, chi 2, or t test with P < .05 considered significant. Because there were differences for admission rates, first-hospital peak expiratory flow rates, and aminophylline use in control groups, the experimental groups could not be compared. No significant difference in travel interval, steroid use, albuterol treatments, or length of ED stay was determined in either the experimental or control group. Scene time (9.7 minutes versus 12.1 minutes) was significantly shorter in 1988 than in 1990 (difference, 2.4 minutes; 95% confidence interval, 0.2 to 4.6; P < .01). The percentage of patients with high initial severity of disease (85% versus 66%; P < .001) and the percentage of patients with first posttreatment peak expiratory flow rates of less than 120 L/min (77% versus 58%; P < .001) were significantly higher in 1988 than in 1990. There was no significant difference in scene time, severity scores, or first posttreatment peak expiratory flow rates in control groups. CONCLUSION: The institution of out-of-hospital use of nebulized albuterol increased scene time and increased first posttreatment peak expiratory flow rates significantly. There was a significant decrease in initial patient severity as measured on the modified Fischl index, although the validity of this index has not been established. It did not affect travel interval, length of stay in the ED, or medication use after ED presentation.

Acute Disease↗