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Biomedical subjects

J D Ward

Publications and source records attributed to J D Ward.

At least 55 records · Page 3Linked to original sources
PubMed1997

Analysis of antibodies against components of the autonomic nervous system in diabetes mellitus.

Antibodies to autonomic nervous system structures have previously been detected using a complement fixation immunofluorescence test in the sera of patients with insulin-dependent diabetes mellitus (IDDM) and non-insulin dependent diabetes mellitus (NIDDM). These antibodies might play a role in the aetiology of autonomic neuropathy. Sera from 45 IDDM, 40 NIDDM and 52 control subjects were tested by immunofluorescence for antibodies to human sympathetic ganglia, human adrenal medulla and rabbit vagus nerve. The use of human sympathetic ganglia was compared with rabbit tissue for the detection of sympathetic ganglia antibodies; the results for these autonomic nervous system antibodies were also compared with results using an ELISA. There was no relationship between the presence of antibodies detected by ELISA and those detected by immunofluorescence, but of 14 IDDM patients with thyroid antibodies, 12 had autonomic nervous system antibodies detected by either immunofluorescence or ELISA (p < 0.005 compared to patients without thyroid antibodies). To further characterize the autoantigen(s), immunoblotting was performed. An adrenal antigen corresponding to 74 kDa was detected in sera from three patients, only one of whom had antibodies detectable by ELISA and immunofluorescence. One IDDM serum showed specific binding to a vagus nerve antigen corresponding to 33 kDa. No specific binding to sympathetic ganglia antigen was demonstrated. Antibodies against autonomic nervous system antigens are an inconsistent feature of diabetes, and appear more associated with coincidental autoimmunity against other organs such as the thyroid.

Adrenal Medulla↗
PubMed1997

Long-term effects of consumption of low-copper diets with or without supplemental molybdenum on copper status, performance, and carcass characteristics of cattle.

We used 42 Angus bull calves (7 mo of age) to determine long-term effects of low Cu diets with or without supplemental Mo on performance, carcass characteristics, and Cu status. Twenty-two bulls were injected with 90 mg of Cu 28 d before weaning. After weaning, injected steers were fed a diet supplemented with 7.5 mg of Cu/kg of DM; control steers received no supplemental Cu. At the end of the 40-d receiving phase, supplemental Cu was reduced to 5 mg/kg of DM. One half of the steers in each group were fed 5 mg of supplemental Mo/kg of DM following the receiving phase. The growing phase lasted 196 d. Steers were then switched to a high concentrate finishing diet for 49 d. Copper injection increased (P < .01) plasma Cu concentrations at weaning, and Cu-supplemented steers had greater (P < .05) plasma Cu, ceruloplasmin, superoxide dismutase activity (SOD), and liver Cu at the beginning of the growing phase. Supplemental Mo depressed plasma Cu, ceruloplasmin, and SOD during the growing and finishing phases in non-Cu-supplemented but not in Cu-supplemented steers. Copper supplementation increased DMI during the receiving (P < .05) and growing (P < .08) phases and increased (P < .08) ADG and gain:feed ratios during the finishing phase. Steers fed supplemental Cu produced carcasses with less (P < .06) backfat and slightly larger (P < .09) rib eye areas. The results of this experiment suggest that dietary Cu concentrations may alter cattle performance and carcass characteristics.

Abattoirs↗
PubMed1997

Effects of copper deficiency and copper deficiency coupled with high dietary iron or molybdenum on phagocytic cell function and response of calves to a respiratory disease challenge.

A study was conducted to determine the effects of supplementing a diet marginally deficient in copper (Cu) with iron (Fe), molybdenum (Mo), or Cu on phagocytic cell function and disease resistance of calves. Thirty-one calves were born to heifers fed a corn silage-based diet containing 4.5 mg of Cu/kg. Treatments consisted of 1) control (CON; no supplemental Cu, Fe, or Mo), 2) 600 mg of Fe added/kg (FE), 3) 5 mg of Mo added/kg (MO), or 4) 10 mg of Cu added/kg of DM (CU). Activity of superoxide dismutase was lower (P < .06) in neutrophils from MO vs CON or CU calves at 170 d of age. bactericidal activity of neutrophils from MO calves tended (P = .15) to be lower compared with those from CU calves at 70 d of age. Calves were inoculated intranasally with live infectious bovine rhinotracheitis virus (IBRV) 2 d after weaning, followed by intratracheal administration of Pasteurella hemolytica 5 d later. Iron- and Cu-supplemented calves exhibited higher (P < .01) body temperatures and lower (P < .06) feed intakes following IBRV inoculation compared with CON and MO calves. Copper-supplemented calves had higher levels of plasma tumor necrosis factor (TNF) than MO calves at weaning (P < .05) and tended to have higher plasma TNF (P = .11) than FE and MO calves 5 d after IBRV inoculation. These data indicate that dietary levels of Mo and Cu can affect body temperature and feed intake responses to disease by affecting TNF and perhaps other cytokines.

Aging↗
PubMed1997

The effects of copper deficiency with or without high dietary iron or molybdenum on immune function of cattle.

Two experiments were conducted to determine the effects of Cu deficiency with or without high dietary Mo or Fe on the specific immunity of calves. In Exp. 1, calves from 38 bred heifers, fed corn silage-based experimental diets from the last third of gestation until the calves were weaned, were used. Dietary treatments were control (no supplemental Fe, Mo, or Cu), 600 mg of supplemental Fe/kg of DM, 5 mg of supplemental Mo/kg of DM, and 10 mg of supplemental Cu/kg of DM. In Exp. 2, 18 Holstein bull calves were fed commercial milk replacer low in Cu for 49 d and then fed semipurified diets containing approximately 1.1 mg of Cu/kg of DM or diets supplemented with 5 mg of Mo or 10 mg of Cu per kilogram of DM for 126 d. Feeding diets not supplemented with Cu resulted in severe Cu deficiency in both experiments. During Exp. 1, control calves had higher (P < .10) secondary antibody response to pig erythrocytes than Cu-, Mo-, and Fe-supplemented calves. During Exp. 2, in vitro Cu supplementation decreased (P < .01) lymphocyte blastogenic response. In vivo cell-mediated response to phytohemagglutinin was decreased (P < .10) by Cu supplementation during Exp. 1 but was increased (P < .10) by Cu and Mo supplementation during Exp. 2. Copper deficiency and Cu deficiency coupled with high dietary Mo or Fe produced inconsistent immune function responses, indicating that Cu deficiency may not affect specific immune function of calves.

Analysis of Variance↗
PubMed1996

Arterio-venous shunting and proliferating new vessels in acute painful neuropathy of rapid glycaemic control (insulin neuritis).

Insulin neuritis, or painful neuropathy following rapid improvement in glycaemic control, is well recognised but its aetiology is unclear. An understanding of the processes involved in the genesis of acute painful neuropathy of rapid glycaemic control may give an insight into the early pathogenetic factors leading to diabetic nerve damage in general. We have identified five subjects with insulin neuritis including one who developed severe autonomic neuropathy following treatment with insulin. Subjects underwent: 1) assessment of neuropathic symptom and deficit scores; 2) quantitative sensory and electrophysiological studies and 3) sural nerve epineurial vessel photography and fluorescein angiography in vivo. The sural nerve photographs were independently graded by an ophthalmologist. All subjects with insulin neuritis presented with severe sensory symptoms but clinical examination and electrophysiological tests were normal except in the subject with the severe autonomic neuropathy in whom all the tests were abnormal. On nerve photography, there was an abundance of epineurial nutrient vessels although these showed severe abnormalities including arteriolar attenuation, tortuosity and arterio-venous shunting in all subjects. Proliferating neural 'new vessels' which bear striking similarities to those found in the retina and that were more leaky to fluorescein than normal vessels, were observed in three subjects. Venous distension and/or tortuosity was also observed in three subjects and this was most marked in the subject with severe autonomic neuropathy. This study shows that epineurial nutrient vessel anatomy is abnormal in subjects with acute painful neuropathy of rapid glycaemic control, a condition previously thought to be purely metabolic in origin. The presence of epineurial arterio-venous shunting and a fine network of vessels resembling the new vessels of the retina, may lead to a 'steal' effect rendering the endoneurium ischaemic. This process may be important in the genesis of neuropathic pain, and further supports the importance of vascular factors in the pathogenesis of diabetic neuropathy.

Acute Disease↗
PubMed1996

Elevated von Willebrand factor antigen predicts deterioration in diabetic peripheral nerve function.

We have studied the temporal relationship of plasma von Willebrand Factor (vWF), a marker of endothelial damage, with the development of complications in 63 young diabetic patients (56 of whom were insulin-dependent) who took part in a prospective study. Results are presented from baseline to follow-up. In the group as a whole, no significant changes were found in any autonomic function tests, temperature discrimination threshold or nerve conduction velocities. Median motor and peroneal latency were significantly increased, while median motor, peroneal motor and sural sensory potentials were significantly decreased at follow-up compared with baseline (p < 0.001). There was a significant fall in mean plasma vWF antigen and ristocetin co-factor activity in the entire group. Within the group, we identified eight patients whose peroneal motor and sural sensory conduction velocities had decreased by over 2 ms-1. In these patients (Group A), baseline vWF antigen and activity were significantly higher than in the rest of the patients (Group B), (p = 0.04) and vWF antigen was still significantly higher after 3 years (p = 0.02). There were no differences between the groups in incidence of retinopathy, urinary albumin excretion rate or macrovascular disease. To assess the influence of glycaemic control on vWF, we first compared a matched group (C) of diabetic patients with similar HbA1 to that of group A, but with normal nerve conduction velocities: vWF was still significantly higher in group A compared with group C (p = 0.02). Furthermore, hierarchical regression showed that vWF predicted deteriorating nerve function independently of glycaemic control or the type of diabetes. Endothelial dysfunction may be associated with development of peripheral neuropathy in young diabetic patients.

Adult↗
PubMed1996

Interleukin-1 receptor antagonist allele (IL1RN*2) associated with nephropathy in diabetes mellitus.

We have previously found association between an allele of the interleukin-1 (IL-1) receptor antagonist gene (IL1RN) and several inflammatory diseases, where IL-1 has been implicated in the inflammatory mechanism. We have now, therefore, tested the association of this specific allele (IL1RN*2) with complications of diabetes which have an inflammatory tissue component. We have tested the allele frequency of IL1RN*2 in 128 patients with insulin-dependent and 125 with non-insulin-dependent diabetes mellitus (NIDDM). There was a significant association between carriage of IL1RN*2 and diabetic nephropathy (P<0.001, Pcorrected<0.0012). The association was significant in both types of diabetes, but the observed increase was highest in NIDDM, rising to double the control levels. It appears that IL1RN*2 is a novel genetic marker of severity of inflammatory complications of diseases rather than a marker of disease susceptibility. If the DNA polymorphism is associated with altered gene function, new therapeutic interventions may be possible.

Adult↗
PubMed1996

Prevalence of diabetic peripheral neuropathy and its relation to glycaemic control and potential risk factors: the EURODIAB IDDM Complications Study.

The EURODIAB IDDM Complications Study involved the examination of 3250 randomly selected insulin-dependent diabetic patients, from 31 centres in 16 European countries. Part of the examination included an assessment of neurological function including neuropathic symptoms and physical signs, vibration perception threshold, tests of autonomic function and the prevalence of impotence. The prevalence of diabetic neuropathy across Europe was 28% with no significant geographical differences. Significant correlations were observed between the presence of diabetic peripheral neuropathy with age (p < 0.05), duration of diabetes (p < 0.001), quality of metabolic control (p < 0.001), height (p < 0.01), the presence of background or proliferative diabetic retinopathy (p < 0.01), cigarette smoking (p < 0.001), high-density lipoprotein cholesterol (p < 0.001) and the presence of cardiovascular disease (p < 0.05), thus confirming previous associations. New associations have been identified from this study - namely with elevated diastolic blood pressure (p < 0.05), the presence of severe ketoacidosis (p < 0.001), an increase in the levels of fasting triglyceride (p < 0.001), and the presence of microalbuminuria (p < 0.01). All the data were adjusted for age, duration of diabetes and HbA1c. Although alcohol intake correlated with absence of leg reflexes and autonomic dysfunction, there was no overall association of alcohol consumption and neuropathy. The reported problems of impotence were extremely variable between centres, suggesting many cultural and attitudinal differences in the collection of such information in different European countries. In conclusion, this study has identified previously known and new potential risk factors for the development of diabetic peripheral neuropathy.

Adolescent↗
PubMed1996

Paranodal structure in diabetic sensory polyneuropathy.

Observations have been made on the structure of the paranodal region at nodes of Ranvier in the sural nerve of patients with diabetic sensory polyneuropathy. The structure of the paranodes was examined with particular attention to the definition and assessment of axoglial dysjunction, which has been claimed to be a characteristic feature of both human and experimental diabetic neuropathy and which has been related to paranodal swelling. In the present series of cases it was not possible to confirm that axoglial dysjunction is a distinctive feature of diabetic polyneuropathy in fibres not undergoing active demyelination or wallerian-type degeneration, neither was excessive paranodal enlargement found.

Adult↗
PubMed1996

Ewing's sarcoma of the skull in an infant. A case report and review.

A 1-year-old female infant presented with a large 7-8 cm Ewing's sarcoma of the left parietal calvarium. It deeply indented the subjacent hemisphere. Wide surgical excision was followed by chemotherapy but not radiation. The patient was clinically free of tumor when she expired 9 months later of sepsis. Though primary Ewing's sarcoma of the skull is said to be relatively rare, we have tabulated 37 cases of this disorder, including the present one (we excluded mandibular tumors (> 100 cases) since they are not usually treated by neurosurgeons). The mean age was 11 years and of those available to follow-up, three quarters were tumor-free 6 months to 7 years postsurgery. The remainder survived an average of 21 months. Ewing's tumors of the calvarium generally grant a favorable prognosis following surgery and/or radiation and chemotherapy. Those at the base of the brain may be more difficult to eradicate. In addition to primary Ewing's tumors, metastases to the skull and the brain from other primary sources in the skeleton have been documented in several reports.

Chemotherapy, Adjuvant↗
PubMed1996

Bioavailability of copper proteinate and copper carbonate relative to copper sulfate in cattle.

Two experiments were conducted to determine the relative bioavailabilities of Cu proteinate, CuCO3, and CuSO4. In Experiment 1, 30 heifers that had been depleted of Cu were us 1. Treatments were control, Cu proteinate A, Cu proteinate B, CuCO3, and CuSO4. Sources provided 50 mg of Cu/d. Supplementation increased plasma Cu by d 21, but there were no differences among the sources. Heifers supplemented with Cu had greater liver Cu concentrations on d 21 than did controls. Heifers receiving CuCO3 had lower liver Cu concentrations than the other heifers. In Experiment 2, 40 heifers were fed diets containing 0.15% of added S and 5 mg of added Mo/kg of DM. Treatments were control, CuSO4, CuCO3, and Cu proteinate A. All sources provided 5 mg of added Cu/kg of DM. Controls and heifers supplemented with CuSO4 had declining plasma Cu concentrations. Supplementation with CuCO3 or Cu proteinate A maintained plasma Cu concentrations. Heifers supplemented with Cu proteinate A had smaller decreases in liver Cu concentrations than did heifers supplemented with other Cu sources. In the absence of high Mo, Cu proteinates were similar in bioavailability to CuSO4. In the presence of high Mo, Cu proteinate A appeared to have a greater bioavailability than CuSO4. Copper carbonate increased or maintained plasma Cu concentrations but was not stored in the liver efficiently.

Animals↗
PubMed1996

Ventriculostomy infections: the effect of monitoring duration and catheter exchange in 584 patients.

The investigators undertook a retrospective analysis of ventriculostomy infections to evaluate their relationship to monitoring duration and prophylactic catheter exchange. In 1984, the results of an epidemiological study of ventriculostomy-related infection were published. One of the conclusions of the paper was that the incidence of ventriculostomy-related infections rose after 5 days of monitoring. This led to the recommendation that catheters be prophylactically changed at 5-day intervals if prolonged monitoring was required. A recent randomized prospective study on central venous catheters showed no reduction in infection with prophylactic catheter exchanges. This has led the authors to reexamine their experience with ventriculostomy infections. Data on 584 severely head injured patients with ventriculostomies were prospectively collected in two data banks, The Traumatic Coma Data Bank and The Medical College of Virginia Neurocore Data Bank. These data were retrospectively analyzed for factors associated with ventriculostomy related infections. It was found that there is a relationship of ventriculitis to monitoring duration but it is not simple or linear. There is a rising risk of infection over the first 10 days, but infection then becomes very unlikely despite a population that continues to be at risk. Patients in whom catheters were replaced prior to 5 days did not have a lower infection rate than those whose catheters were exchanged at more than 5-day intervals. Based on these data, it is recommended that ventriculostomy catheters for intracranial pressure monitoring be removed as quickly as possible, and in circumstances in which prolonged monitoring is required, there appears to be no benefit from catheter exchange.

Adolescent↗
PubMed1996

Posttraumatic ventriculomegaly: hydrocephalus or atrophy? A new approach for diagnosis using CSF dynamics.

Cerebrospinal fluid (CSF) dynamics were correlated to the changes in ventricular size during the first 3 months posttrauma in patients with severe head injury (Glasgow Coma Scale score < or = 8, 75 patients) to distinguish between atrophy and hydrocephalus as the two possible causes of posttraumatic ventriculomegaly. Using the bolus injection technique, the baseline intracranial pressure (ICP), pressure volume index, and resistance for CSF absorption (R0) provided a three-dimensional profile of CSF dynamics that was correlated with ventricular size and Glasgow Outcome Scale (GOS) score at 3, 6, and 12 months posttrauma. Patients were separated into five different groups based on changes in ventricular size, presence of atrophy, and CSF dynamics. Group 1 (normal group, 41.3%) demonstrated normal ventricular size and normal ICP. Group 2 (benign intracranial hypertension group, 14.7%) showed normal ventricular size and elevated ICP. Group 3 (atrophy group, 24%) displayed ventriculomegaly, normal ICP, and normal R0. Group 4 (normal-pressure hydrocephalus group, 9.3%) had ventriculomegaly, normal ICP, and high R0. Group 5 (high-pressure hydrocephalus group, 10.7%) showed ventriculomegaly and elevated ICP with or without high R0. The GOS score in the nonhydrocephalic groups (Groups 1, 2, and 3) was better than in the hydrocephalic groups (Groups 4 and 5). It is concluded from these results that 44% of head injury survivors may develop posttraumatic ventriculomegaly. Posttraumatic hydrocephalus, as identified by abnormal CSF dynamics, was diagnosed in 20% of survivors and their outcome was significantly worse. This study demonstrates the importance of using CSF dynamics as an aid in diagnosis of posttraumatic hydrocephalus and identifying those patients who may benefit from shunt placement.

Atrophy↗
PubMed1995

Myelinated nerve fibre regeneration in diabetic sensory polyneuropathy: correlation with type of diabetes.

Observations were made on myelinated fibre regeneration in diabetic sensory polyneuropathy assessed in sural nerve biopsy specimens. These confirmed that regenerative clusters initially develop within abnormally persistent Schwann cell basal laminal tubes. The number of regenerating fibres, identified by light microscopy, was found to decline in proportion to the reduction in total myelinated fibre density. The relative number of regenerating fibres was significantly greater in patients with insulin-dependent as compared with those with non-insulin-dependent diabetes after correction for age. There was a slight negative correlation between the relative proportion of regenerating fibres and age, but this was not statistically significant. The progressive reduction in the number of regenerating fibres with declining total fibre density indicates that axonal regeneration fails with advancing neuropathy. The production of nerve growth factor (NGF) and NGF receptors by denervated Schwann cells is likely to be important for axonal regeneration. To investigate whether the failure of axonal regeneration could be related to a lack of NGF receptor production by Schwann cells, we examined the expression of p75 NGF receptors by Büngner bands immunocytochemically. In comparison with other types of peripheral neuropathy, p75 NGF receptor expression appeared to take place normally. It is concluded that failure of axonal regeneration constitutes an important component in diabetic neuropathy. Its explanation requires further investigation.

Adult↗
PubMed1995

Is ACE inhibition with lisinopril helpful in diabetic neuropathy?

Thirteen diabetic patients with hypertension (mean diastolic blood pressure 96.2 +/- 1.1 mmHg) were included in a study to assess the effects of lisinopril (20 mg day-1) on measures of nerve function. Patients had nerve conduction velocity (NCV), temperature discrimination threshold (TDT), and vibration perception threshold (VPT) measurements. At the end of 12 weeks of treatment with lisinopril, there was a significant improvement in median motor NCV (mean change +/- SEM 2.7 +/- 0.6 m s-1, p < 0.0001), median sensory NCV (2.1 +/- 0.9 m s-1, p = 0.03), peroneal motor NCV (1.0 +/- 0.4 m s-1, p = 0.03), and sural sensory NCV (1.9 +/- 0.7 m s-1, p = 0.01) values. There were also significant improvements in warm TDT and VPT. Diastolic BP decreased significantly, but there was no significant change in HbA1. Double blind controlled studies are now needed to confirm the effect of lisinopril on measures of nerve function.

Adult↗
PubMed1995

The cost of diabetic neuropathy.

Little information is available as to the exact financial cost of the clinical features of diabetic neuropathy. At least 20% of diabetic patients have a neuropathic problem consisting of either sensory pain and discomfort, foot ulceration or impotence. This represents a large load of clinical work in any diabetes service. Such patients should be offered thorough and sympathetic clinical facilities, from careful diagnosis and assessment through to treatment and counselling, to allow them to accept, and hopefully obtain improvement in, what is essentially an incurable clinical situation. Similarly, the emotional and financial costs to the patients of such a chronic condition have not been adequately assessed. It seems reasonable to suggest that such costs are high, and it is a general impression that patients with this problem do not receive adequate time and attention in many busy diabetes services.

Diabetic Neuropathies↗