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Biomedical subjects

J D Ward

Publications and source records attributed to J D Ward.

At least 91 records · Page 5Linked to original sources
PubMed1993

Abnormal microvasculature in diabetic neuropathy.

Microvascular abnormalities are prominent in the retina and kidney in diabetic subjects with the specific complications of the disease. It would not therefore be surprising to find similar changes in nerve, the other tissue prominently damaged in diabetes. A variety of biochemical abnormalities have been postulated as a cause of nerve damage but so far none has been reversed with any benefit to patients. It is now very clear that major structural and functional changes in the microvasculature occur in diabetic neuropathy and are probably involved in resulting nerve damage. Endothelial thickening of the endothelial basement membrane occurs, as does luminal occlusion caused by endothelial cell proliferation; human sural nerve is hypoxic; sural nerve epineurial arterioles are attenuated and involved in arteriovenous shunting associated with gross distension and tortuosity of veins; flow of fluorescein is impaired in neuropathic nerves and nerve conduction increment on exercise is impaired in neuropathy. Therapeutic intervention should now be directed at these gross abnormalities.

Animals↗
PubMed1993

Effect of continuous rotational therapy on intracranial pressure in the severely brain-injured patient.

OBJECTIVE: To determine the effect of continuous rotational therapy on the dynamics of intracranial pressure. DESIGN: A controlled, prospective evaluation of intracranial pressure during continuous rotation therapy. SETTING: Neuroscience intensive care unit in a university hospital. PATIENTS: A total of 58 severely brain-injured patients (Glasgow Coma Score of < or = 9) ranging in age from 14 to 81 yrs. INTERVENTIONS: All patients had intraventricular catheters placed to continuously monitor intracranial pressure and all patients were placed on continuous rotational therapy once stabilized. MEASUREMENTS AND MAIN RESULTS: Intracranial pressure data were measured in each patient during nonrotation and these data were compared with intracranial pressure data during rotation, thus allowing each patient to serve as their own control. In addition, the intracranial pressure during rotation (40 degrees from center) was further analyzed to determine the effect of angulation on the intracranial pressure. Analysis of computer-recorded intracranial pressure data showed no significant difference in intracranial pressure measured during rotation and nonrotation over the first 5 days postinjury. Minimal differences in intracranial pressure (< 1 to 2 mm Hg) were noted in right/center/left positions. It was also determined that intracranial pressure increased up to 6.5 mm Hg (p = .12) in patients who presented with a unilateral lesion on admission computed tomography when they rotated to the side of the lesion. However, these fluctuations did not promote additional intracranial pressure management. CONCLUSIONS: We conclude that the systemic benefits known to be derived from the use of continuous rotation therapy in the severely head-injured patient can be sustained without any deleterious effects on the intracranial pressure.

Adult↗
PubMed1993

Effect of copper level and source (copper lysine vs copper sulfate) on copper status, performance, and immune response in growing steers fed diets with or without supplemental molybdenum and sulfur.

One hundred twenty-six crossbred steers (218 kg initial BW) were used to determine the availability of Cu from copper lysine (CuLys) relative to CuSO4. Steers were assigned to pens (four replicates per treatment) based on BW and initial plasma Cu concentration and fed a corn silage-based diet supplemented with 0 or 5 ppm of Cu from either CuSO4 or CuLys. Half of the steers in each treatment were supplemented with 5 ppm of Mo and .2% S. Molybdenum and S supplementation increased (P < .10) growth rate during the first 21 d. Steers receiving CuSO4 gained more during the first 21 d than did control steers (P < .10) and steers receiving CuLys (P < .01). Growth, feed efficiency, and feed intake were not affected over the entire 98-d trial. Molybdenum and S supplementation decreased (P < .05) plasma Cu concentrations. Plasma Cu concentration was not affected by Cu source. Humoral immune response to ovalbumin was measured on d 7 and 77. Dietary treatment did not affect antibody production at either time. Cell-mediated immunity was measured in vivo on d 7 and 77 using phytohemagglutinin. In vivo cell reactivity was not affected by treatment on d 7 but was reduced (P < .10) by Mo and S supplementation on d 77. In vitro cell reactivity was measured on d 98 using a lymphocyte blastogenesis assay. Unstimulated lymphocytes from steers supplemented with Mo and S had lower (P < .10) uptakes of [3H]thymidine. There were no differences among treatments when lymphocytes were stimulated with pokeweed mitogen or phytohemagglutinin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗
PubMed1993

Comparison of copper lysine and copper sulfate as copper sources for ruminants using in vitro methods.

Two in vitro experiments were conducted to estimate the availability of Cu from Cu Lys compared with Cu from CuSO4. In experiment 1, a 24-h ruminal fermentation (alpha-cellulose substrate) containing either .1% added S or 2% added urea was performed with 4, 12, or 96 ppm of added Cu as either Cu Lys or CuSO4. Soluble Cu was measured at the end of the 24-h incubation, and concentrations were higher for Cu Lys with added urea (1.16 vs. .45 ppm), but no differences existed between sources of added S. In Experiment 2, 20 ppm of Cu added as either Cu Lys or CuSO4 with and without the addition of 10 ppm of Mo and .75% S were used in an vitro study designed to simulate digesta passage through the ruminant. A 24-h ruminal fermentation (orchardgrass substrate) was followed by a 2-h digestion in pepsin and HCl (pH 2.3) and then a 2-h digestion in NaHCO3 and pancreatin (pH 6.6). Soluble Cu concentrations were analyzed after each step. Molybdenum and S addition decreased soluble Cu after ruminal fermentation and tended to decrease soluble Cu concentrations after digestion of pancreatin and NaHCO3. The source of Cu did not affect soluble Cu concentrations. Results suggest that Cu from Cu Lys and CuSO4 behave similarly in the digestive tract of ruminants.

Animals↗
PubMed1993

Effect of THAM upon outcome in severe head injury: a randomized prospective clinical trial.

Although mortality and morbidity rates from head injury have been reduced substantially by improved prehospital interventions, intensive care, and aggressive management of intracranial pressure (ICP), successful treatment of the primary brain injury has been elusive. In experimental models, tromethamine (THAM) has been effective in treating head injury; this drug acts by entering the cerebrospinal fluid compartment, reducing cerebral acidosis and ICP, and reversing the adverse effects of prophylactic hyperventilation on early recovery. In this randomized prospective clinical trial, THAM was studied to determine if it had beneficial effects in the early management of severe head injuries and if the adverse effects of hyperventilation could be prevented. A total of 149 patients with severe head injury (Glasgow Coma Scale scores of < or = 8) were randomly assigned to either a control or a THAM group. Both groups of patients matched in terms of clinical parameters, including age, sex, number of surgical mass lesions, number in each Glasgow Coma Scale stratum, and first ICP measurement. All patients were treated by a standard management protocol, intubated, mechanically ventilated, and maintained in the pCO2 range of 32 to 35 mm Hg for 5 days. Tromethamine was administered as a 0.3-M solution in an initial loading dose (body weight x blood acidity deficit, average 4.27 cc/kg/hr) given over 2 hours, followed by a constant infusion of 1 ml/kg/hr for 5 days. Outcome was measured at 3, 6, and 12 months postinjury. Although analysis indicated no significant difference in outcome between these two groups at 3 months, 6 months, and 1 year, there was a difference regarding ICP. The time that ICP was above 20 mm Hg in the first 48 hours postinjury was less in patients treated with THAM (p < 0.05). Also, the number of patients requiring barbiturate coma was significantly less in the THAM group (5.48% vs. 18.4%, p < 0.05). The authors conclude that THAM ameliorates the deleterious effect of prolonged hyperventilation, may be beneficial in ICP control, and warrants further study as to the dosage and timing of administration.

Adolescent↗
PubMed1993

Neurologic consequences of hypoglycemia and pathogenic mechanisms involved in diabetic neuropathy.

Although the limitations of human experimental models of hypoglycemia have hampered investigation, it is generally accepted that a reversible deterioration in cognitive function occurs at a plasma glucose concentration of around 3.5 mmol/L, above the glycemic threshold for symptoms. It is unclear whether this threshold varies in those with hypoglycemia unawareness. Repeated severe hypoglycemia may cause chronic impairment although the clinical significance and the contribution of other factors remains unclear. There is increasing evidence that microvascular abnormalities are the major factor in the pathogenesis of peripheral neuropathy. This may be why there is still little experimental support from human clinical studies for the use of aldose reductase inhibitors in its treatment.

Blood Glucose↗
PubMed1992

Relationships between haemostatic factors and capillary morphology in human diabetic neuropathy.

We have examined haemostatic factors in 15 diabetic patients with peripheral neuropathy and 10 diabetic patients without clinical complications. Plasma and blood viscosity, fibrinogen, factor VIIIc, von Willebrand factor activity, spontaneous platelet aggregation and fibrinolytic activity were not significantly different between diabetic patients without clinical complications and diabetic patients with peripheral neuropathy. Platelet aggregation was enhanced in diabetic patients with neuropathy compared with those without complications. In the 15 patients with neuropathy and 3 without complications, who underwent biopsy of sural nerve, skin and muscle, associations were found between haemostatic variables and measures of nerve capillary pathology, notably: plasma fibrinogen and nerve capillary basement membrane thickness (r = 0.70, p < 0.001); thromboxane B2 production and nerve capillary basement membrane thickness (r = -0.61, p < 0.01); plasma fibrinolytic activity and endoneurial capillary lumen size (r = 0.60, p < 0.01) and endothelial cell outer perimeter (r = 0.65, p < 0.01). The main associations of skin and muscle capillary abnormalities were with measures of in vitro platelet aggregation, and the correlations found with nerve capillary measurements were not echoed in the overlying muscle and skin. The results are supportive of the involvement of haemostatic abnormalities in the pathogenesis of diabetic neuropathy.

Adult↗
PubMed1992

Exercise-induced conduction velocity increment: a marker of impaired peripheral nerve blood flow in diabetic neuropathy.

Severe microvascular disease exists at the stage of clinical diabetic neuropathy. A non-invasive test that will identify those diabetic subjects who will eventually develop neuropathy is essential for early intervention. Sural sensory conduction velocity was recorded (x3) in 12 non-neuropathic diabetic subjects, 15 diabetic subjects with established neuropathy and 16 age-matched normal control subjects, before and after exercise to 80% age/sex predicted maximum heart rate. Fixed sural electrodes were used. Subcutaneous temperature was recorded by a needle thermocouple placed near the sural nerve. Sural sensory conduction velocity increased significantly after exercise in normal subjects (p less than 0.01, mean increase 5.07 m/s) and non-neuropathic diabetic subjects (p less than 0.02, mean increase 3.99 m/s) but not in neuropathic subjects (mean increase 0.99 m/s). Subcutaneous temperature rose significantly in normal subjects (p less than 0.01, mean increase 2.07 degrees C) and non-neuropathic diabetic subjects (p less than 0.001, mean increase 2.52 degrees C) but not in neuropathic subjects (mean increase 0.15 degree C). However, sural sensory conduction velocity increased by 1.2 m.s-1.degree C-1 following direct warming of the limb in six neuropathic subjects which was comparable to that of normal and non-neuropathic subjects (1.49 and 1.48 m.s-1. degree C-1). The impairment of exercise conduction increment in diabetic neuropathy suggests impaired nerve blood flow in diabetic neuropathy.

Adult↗
PubMed1992

Diabetes care.

Providing good quality diabetes care is complex but achievable. Many aspects of the care do not require high tech medicine but, rather, good organisation. Diabetes is a costly disease, consuming 1500 pounds per diabetic patient per year versus 500 pounds on average for a non-diabetic member of the population in health service costs. Investment now in good quality diabetes care is sound: patients will benefit from a better quality of life associated with a reduced incidence of the complications of diabetes and the direct costs to the health service in treating these complications and the indirect costs to employers will be reduced. Physical and clinical assessments--measurements of blood glucose and glycosylated haemoglobin concentrations, weight, and blood pressure and assessment of eyes, kidneys, feet, and heart--are clearly important, but quality must include consideration of people and their reactions to life and diabetes--a lifelong entanglement--for which much more support should be provided.

Diabetes Mellitus↗
PubMed1991

Neutrophil aldose reductase activity as a potential marker for neuropathy and cataract in diabetes.

Aldose reductase activity can be measured in the neutrophil and it has been proposed that this may be a marker for risk of complications in diabetes. We have studied aldose reductase activity in neutrophil, nerve, and lens in diabetic patients undergoing sural nerve biopsy or cataract extraction. A correlation was demonstrated between lens and neutrophil aldose reductase activity (r = 0.53, p = 0.01) but no correlations were demonstrated between nerve aldose reductase activities and nerve morphometry, nerve function or neutrophil aldose reductase activity. No significant difference was found between neutrophil aldose reductase activities in groups of patients with severe neuropathy, or cataract, or no complications (24 (interquartile range 16-32) vs 24 (16-40) vs 24 (16-40) nmol NADPH min-1 10(8)-cells-1). In a group of 56 Type 1 diabetic patients screened within 6 years of diagnosis, multiple regression analysis failed to show any relationship between neutrophil aldose reductase activity and abnormalities of neurophysiological function. These results suggest that neutrophil aldose reductase activity cannot be used as a marker for the development of cataract or neuropathy in diabetes.

Action Potentials↗
PubMed1991

Activation of coagulation in diabetes mellitus in relation to the presence of vascular complications.

To examine the relationship between diabetic vascular disease and haemostasis, a set of sensitive assays has been used to assess in vivo activation of coagulation in 62 diabetic patients (41 Type 1 and 21 Type 2), aged 19-68 years, who had been screened for the presence of complications. Fibrinopeptide A, an index of thrombin activity, was significantly increased in diabetic patients compared with control subjects (p less than 0.05), in both plasma (with complications mean 8.04 +/- 11.87 (+/- SD); without complications 7.21 +/- 10.13; control subjects 2.11 +/- 1.40 micrograms l-1) and urine (with complications mean 1.48 +/- 0.74; without complications 1.35 +/- 0.62; control subjects 0.98 +/- 0.39 micrograms l-1). Activated factor VII (VIIa ratio 1.21 +/- 0.39; 1.13 +/- 0.23; 1.01 +/- 0.11) and fibrinogen (3.15 +/- 0.59; 3.11 +/- 0.69; 2.70 +/- 0.57 g l-1) were also elevated in diabetic patients with and without complications (VIIa p less than 0.05, fibrinogen p less than 0.01). The only difference between Type 1 and Type 2 patients was in fibrin degradation products (Type 1 0.28 +/- 0.18; Type 2 0.40 +/- 0.18 mg l-1, p less than 0.01). Plasma levels of fibrin degradation products were elevated in diabetic patients (p less than 0.05 vs control subjects), and correlated with age (r = 0.44, p less than 0.01) but were unrelated to the presence of complications. There were no significant differences in any coagulation variables between diabetic patients with and without complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

The effects of diet and insulin therapy on coagulation factor VII, blood viscosity, and platelet release proteins in diabetic patients with secondary sulphonylurea failure.

The effect of intensified dietary measures and subsequently insulin therapy upon haemorheological measures were studied in Type 2 diabetic patients with secondary sulphonylurea failure. Coagulation factors VIIc and VIIIc, fibrinogen, plasma viscosity, whole blood viscosity, beta-thromboglobulin, platelet factor 4, von Willebrand factor, and euglobulin clot lysis time were measured at baseline, after 3 months intensified dietary therapy and after 4 months insulin therapy. During intensified dietary therapy there was a significant fall in serum cholesterol (p less than 0.05) and a small decrease in weight, but no significant change in blood glucose control. Factor VIIc levels fell significantly (1.22 (SE 0.07) vs 1.42 (0.08) u ml-1, p less than 0.01), and plasma viscosity and whole blood viscosity (23 s-1) also improved (both p less than 0.05). Insulin therapy was instituted with either continuous subcutaneous insulin therapy or twice daily injections of soluble and isophane (NPH) insulin. During this period glycosylated haemoglobin improved (mean (SE) 49.5 (1.4) vs 65.0 (2.1) mmol-HMF mol-Hb-1, p less than 0.001; normal range 29-39 mmol-HMF mol-Hb-1) as did serum triglyceride (p less than 0.01), but weight increased (p less than 0.001). The only haemorheological changes with insulin were increased levels of the platelet release proteins beta-thromboglobulin (37 (3) vs 28 (2) micrograms l-1, p less than 0.01) and platelet factor 4 (median 7.5 (range 3.0-18.0) vs 4.5 (2.0-10.5) micrograms l-1, p less than 0.01).

Adult↗
PubMed1991

Neutrophil aldose reductase activity and its association with established diabetic microvascular complications.

Direct investigation of the polyol pathway is rarely possible in studies of human diabetes. A spectrophotometric assay has been developed for the measurement of aldose reductase and sorbitol dehydrogenase activity in the neutrophil. Neutrophil aldose reductase activity was increased in patients with Type 1 diabetes with complications (median 40 (interquartile range 28-48) u, where 1 unit of enzyme activity = nmol NADPH min-1 10(8)-cells-1) compared with those without complications (20 (16-36) u, p less than 0.01) and normal control subjects (20 (8-36) u, p less than 0.01). In Type 2 diabetes, patients with complications also had higher aldose reductase activity (40 (28-52) u) than those without complications (24 (16-36) u, p less than 0.01). There were no differences between patients without complications and normal control subjects. Sorbitol dehydrogenase activity was decreased in diabetic patients (p less than 0.02) but not significantly different between diabetic patients with and without complications.

Aldehyde Reductase↗
PubMed1991

Randomized trial comparing continuous subcutaneous insulin infusion and conventional insulin therapy in type II diabetic patients poorly controlled with sulfonylureas.

OBJECTIVE: To compare the effects of continuous subcutaneous insulin infusion (CSII) and conventional insulin therapy (CIT) in patients with poorly controlled sulfonylurea-treated diabetes mellitus. RESEARCH DESIGN AND METHODS: Twenty-five patients aged 40-65 yr and poorly controlled with sulfonylureas and without severe diabetic complications comprised the study group. Five patients left the study (3 achieved satisfactory glycemic control without insulin, 1 defaulted, 1 developed ketonuria). Ten patients were treated with CSII and 10 with CIT. Outpatient treatment consisted of CIT (twice-daily injections of regular and NPH insulin) or CSII (basal infusion and prandial boluses of regular insulin). RESULTS: Glycosylated hemoglobin improved with both methods of insulin delivery (P less than 0.01), but 8 of 10 CSII-treated patients achieved satisfactory glycemic control (HbA1 less than 50 mmol hydroxymethylfurfural/mol Hb), whereas only 3 of 10 CIT-treated patients achieved this (P less than 0.05). Weight gain, insulin dosage, and prevalence of hypoglycemia were similar in the two groups. Retinal deterioration occurred in one CSII-treated patient and three CIT-treated patients, but there were no episodes of infusion site infection or metabolic decompensation. Patients' satisfaction with treatment improved during insulin therapy (P less than 0.02), and significant changes in beliefs about diabetes and its treatment were observed in CSII-treated patients (P less than 0.05). CONCLUSIONS: Glycemic control improved with both methods of insulin treated patients achieved satisfactory glycemic control (HbA1 less than 50 mmol hydroxymethylfurfural/mol Hb), whereas only 3 of 10 CIT-treated patients achieved this CSII. Patients' satisfaction with treatment improved during insulin therapy.

Adult↗
PubMed1991

Adverse effects of prolonged hyperventilation in patients with severe head injury: a randomized clinical trial.

There is still controversy over whether or not patients should be hyperventilated after traumatic brain injury, and a randomized trial has never been conducted. The theoretical advantages of hyperventilation are cerebral vasoconstriction for intracranial pressure (ICP) control and reversal of brain and cerebrospinal fluid (CSF) acidosis. Possible disadvantages include cerebral vasoconstriction to such an extent that cerebral ischemia ensues, and only a short-lived effect on CSF pH with a loss of HCO3-buffer from CSF. The latter disadvantage might be overcome by the addition of the buffer tromethamine (THAM), which has shown some promise in experimental and clinical use. Accordingly, a trial was performed with patients randomly assigned to receive normal ventilation (PaCO2 35 +/- 2 mm Hg (mean +/- standard deviation): control group), hyperventilation (PaCO2 25 +/- 2 mm Hg: HV group), or hyperventilation plus THAM (PaCO2 25 +/- 2 mm Hg: HV + THAM group). Stratification into subgroups of patients with motor scores of 1-3 and 4-5 took place. Outcome was assessed according to the Glasgow Outcome Scale at 3, 6, and 12 months. There were 41 patients in the control group, 36 in the HV group, and 36 in the HV + THAM group. The mean Glasgow Coma Scale score for each group was 5.7 +/- 1.7, 5.6 +/- 1.7, and 5.9 +/- 1.7, respectively; this score and other indicators of severity of injury were not significantly different. A 100% follow-up review was obtained. At 3 and 6 months after injury the number of patients with a favorable outcome (good or moderately disabled) was significantly (p less than 0.05) lower in the hyperventilated patients than in the control and HV + THAM groups. This occurred only in patients with a motor score of 4-5. At 12 months posttrauma this difference was not significant (p = 0.13). Biochemical data indicated that hyperventilation could not sustain alkalinization in the CSF, although THAM could. Accordingly, cerebral blood flow (CBF) was lower in the HV + THAM group than in the control and HV groups, but neither CBF nor arteriovenous difference of oxygen data indicated the occurrence of cerebral ischemia in any of the three groups. Although mean ICP could be kept well below 25 mm Hg in all three groups, the course of ICP was most stable in the HV + THAM group. It is concluded that prophylactic hyperventilation is deleterious in head-injured patients with motor scores of 4-5.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1991

Management of head injury. Prehospital care.

The care of the patient begins at the moment of injury, and thus, prehospital care is crucial in the overall treatment of the patient. This article discusses the basic principals involved in prehospital care, including the importance of timing, emergency medical training, and resuscitation at the scene. It discusses how the patient is evaluated, the types of transportation available, and the appropriate destination for the patient depending on his or her injuries.

Brain Injuries↗