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Biomedical subjects

J D Ward

Publications and source records attributed to J D Ward.

At least 37 records · Page 2Linked to original sources
PubMed2000

Central nervous system leiomyosarcoma in patients with acquired immunodeficiency syndrome. Report of two cases.

Leiomyosarcomas (LMSs) of the central nervous system are extremely rare; however, they are becoming more prevalent in immunocompromised patients. The authors present the cases of two patients with acquired immunodeficiency syndrome: one with LMS of the thoracic vertebral body and the other with LMS originating from the region of the cavernous sinus. The epidemiological and histological characteristics of LMS and its association with latent Epstein-Barr virus are discussed, as well as the treatments for this neoplasm.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Contribution of edema and cerebral blood volume to traumatic brain swelling in head-injured patients.

OBJECT: The pathogenesis of traumatic brain swelling remains unclear. The generally held view is that brain swelling is caused primarily by vascular engorgement and that edema plays a relatively minor role in the swelling process. The goal of this study was to examine the roles of cerebral blood volume (CBV) and edema in traumatic brain swelling. METHODS: Both brain-tissue water and CBV were measured in 76 head-injured patients, and the relative contribution of edema and blood to total brain swelling was determined. Comparable measures of brain-tissue water were obtained in 30 healthy volunteers and CBV in seven volunteers. Brain edema was measured using magnetic resonance imaging, implementing a new technique for accurate measurement of total tissue water. Measurements of CBV in a subgroup of 31 head-injured patients were based on consecutive measures of cerebral blood flow (CBF) obtained using stable xenon and calculation of mean transit time by dynamic computerized tomography scanning after a rapid bolus injection of iodinated contrast material. The mean (+/- standard deviation) percentage of swelling due to water was 9.37+/-8.7%, whereas that due to blood was -0.8+/-1.32%. CONCLUSIONS: The results of this study showed that brain edema is the major fluid component contributing to traumatic brain swelling. Moreover, CBV is reduced in proportion to CBF reduction following severe brain injury.

Adolescent↗
PubMed1999

A new minimally invasive technique to show nerve ischaemia in diabetic neuropathy.

AIMS/HYPOTHESIS: Experimental studies have shown that abnormalities of nerve microcirculation are important factors in the pathogenesis of diabetic neuropathy but there have been few clinical studies. We have applied microlightguide spectrophotometry to measure intravascular oxygen saturation (HbO2%) and blood flow in human sural nerve. METHODS: We studied ten patients with mild-moderate sensory motor diabetic neuropathy, nine patients without neuropathy and nine control subjects. We took 300 measurements of oxygen saturation under direct visual control through a 1.9 mm rigid endoscope over three regions of the nerve. Spectrophotometric measurements of nerve fluorescence were taken after an intravenous injection of sodium fluorescein and the rate of increase in nerve fluorescence (rise time) was used as an indicator of nerve blood flow. RESULTS: Nerve oxygen saturation was reduced in patients with neuropathy compared with control subjects (67.1 +/- 2.2% vs 76.7 +/- 2.1%, p = 0.006). Fluorescein rise time was prolonged in patients with neuropathy compared with the control group (48.5 +/- 7.0 s vs 14.0 +/- 3.1 s, p = 0.001) suggesting impaired nerve blood flow. There was a correlation between rise time, nerve oxygen saturation, glycaemic control and sural nerve sensory conduction velocity (p < 0.01). CONCLUSION/INTERPRETATION: The combination of microlight-guide spectrophotometry and micro-endoscopy provides a valuable minimally invasive technique for clinical investigation of nerve microcirculation. We have shown reduced nerve oxygenation and impaired blood flow in diabetic neuropathy and these findings strongly support a central role of microvascular disease in the pathogenesis of diabetic neuropathy.

Diabetic Neuropathies↗
PubMed1999

Diabetic neuropathic pain in a leg amputated 44 years previously.

The mechanism of neuropathic pain in the diabetic limb is far from clear. Phantom limb pain likewise is of obscure aetiology. The development of typical pain in an absent leg in a patient with diabetes many years after the amputation stimulates thought as to the mechanism, not only of neuropathic pain, but also of phantom limb pain. A 58-year-old man was diagnosed with type 2 diabetes 44 years after having undergone left below knee amputation for congenital AV malformation, at the age of 13. Eight months before the diagnosis of diabetes he began to complain of pain in the leg on the amputated side-pain very similar to that described in typical diabetic neuropathy. This was followed by similar pain in the right leg. MR scan of the spine revealed a small syringohydromyelia of the thoracic cord in addition to a prolapse of disc at L(5)/S(1) level on the left side, which was first noted 5 years previously. There were no other features of S(1) compression. The typical neuropathic character of the pain involving both the amputated and the intact limbs that developed with the diagnosis of type 2 diabetes suggest that the neuropathic pain may originate from centres higher than peripheral nerves.

Amputation, Surgical↗
PubMed1999

Digital imaging: an accurate and easy method of measuring foot ulcers.

AIMS: A progressive reduction in the area of foot ulcer on serial measurement is traditionally done by tracing the margin of the ulcer on a transparent film and counting the number of squares on a graph paper underneath. We set out to use and validate the measurement of foot ulcers using a digital imaging technique and compare this with the traditional method. METHODS: Thirty diabetic foot ulcers (18 patients) were studied over 10 weeks. Each ulcer was traced by three independent observers with a pen over a flexigrid Opsite film and digital photographs were taken. Each observer calculated the area of an ulcer first using a 1-mm2 graph paper and then with the computer software. For each ulcer we calculated the mean area using measurements from all the observers. We then calculated the deviation from this mean for each observer. RESULTS: There was significantly less interobserver variation using the digital image than the traditional method with mean coefficient of variation (CV) 16% vs. 27%; P = 0.05. CONCLUSIONS: The digital imaging method was faster and easier to use and the patients preferred it, as it was a noncontact method. In addition it also provides a photographic record for comparison.

Diabetic Foot↗
PubMed1999

Combined microlightguide spectrophotometry and microendoscopy for measurement of oxygen saturation in peripheral nerves.

Microlightguide measurements of the spectral composition of backscattered light may be used to determine local tissue oxygen saturation and monitor tissue perfusion using intravenous injection of fluorescein dye as a contrast agent. We have used a combination of microlightguide spectrophotometry and microendoscopy to measure intravascular oxygen saturation (HbSaO2%) and monitor blood flow in the sciatic nerve of 12 healthy male Sprague-Dawley rats. The microlightguide and endoscope combination is a relatively new measurement technique. The aims of this study were to determine whether microlightguide spectrophotometry and microendoscopy could be used to measure HbO2 and blood flow in peripheral nerves and to compare the measurements made using the flexible lightguide with the endoscope-lightguide combination. We found no significant difference between the two types of measurement over similar regions of the nerve. mean SaO2% values 77.1% (95% CI = 75.4-78.8) and 78.8% (95% CI = 77.5-80.1) respectively. During a period of hypoxia there was a similar fall in both arterial and nerve oxygen saturation. Following injection of fluorescein, the rate of increase in nerve fluorescence was used as a measure of perfusion. The combination of microlightguide spectrophotometry and microendoscopy allows the exact site of measurement to be directly visualized. The minimally invasive nature of this technique may allow its application to the study of peripheral nerves in human subjects in conditions such as diabetic neuropathy where vascular factors are thought to have an important role in aetiology.

Animals↗
PubMed1999

Early identification of diabetic foot ulcers that may require intervention using the micro lightguide spectrophotometer.

OBJECTIVE: Adequate tissue oxygenation is known to be essential for the healing of diabetic foot ulcers, but hypoxia has also been shown to be a potent stimulus for growth. There are no studies looking specifically at ulcer oxygen levels during the healing process. We measured the serial microvascular oxygen saturation (SaO2) of the foot ulcer, the ulcer margin, and a control site using the Erlangen micro lightguide spectrophotometer (EMPHO II; Bodenseewerk Geratetechnik, Erlangen, Germany) to study serial changes during healing. RESEARCH AND DESIGN METHODS: Studied over 9 months were 14 patients with neuropathy with a total of 24 foot ulcer sites. Of these patients, four (seven ulcers) had significant ischemia as determined by the ankle-brachial pressure index (ABPI) and transcutaneous oxygen tension. RESULTS: Of 21 ulcer sites with serial measurements, only 13 ulcers healed. In those ulcers, a significant reduction (P<0.05) in SaO2 occurred with healing. SaO2 dropped from 58% at initial presentation (mean area 2.6 cm2) to 47% at midsize (mean area 1.2 cm2 at 5.2 weeks) and finally reduced to 45% just before it healed. Similar trends were also seen around the margin of the ulcers (initial 49%, midsize 45%, and final 41%; P = 0.1). However, there were no such changes on the control sites (43, 40, and 40%; P = 0.5) or within the eight ulcers that did not heal (46, 42, and 53%; P = 0.2). CONCLUSIONS: Serial microvascular oxygen measurements may be used to identify at an early stage those ulcers that are unlikely to heal and, therefore, need surgical intervention.

Aged↗
PubMed1999

The effects of low-copper diets with or without supplemental molybdenum on specific immune responses of stressed cattle.

Angus bull calves (n = 42; 7 mo of age; 254 kg initial BW) were used to investigate the effects of dietary Cu and Mo on immune function of stressed cattle. Randomly selected calves (n = 22) were injected with 90 mg of Cu as Cu glycinate 28 d before weaning and castrated at weaning. These calves received 7.5 and 5 mg of supplemental Cu/kg of DM during a 41-d receiving phase and a 196-d growing phase, respectively. The remainder of the steers received no supplemental Cu during the experiment. Copper-supplemented steers had adequate Cu status at weaning, whereas unsupplemented calves were marginally Cu-deficient. Cell-mediated response to intradermal injection of phytohemagglutinin was not affected by dietary treatment during the receiving phase. During the growing phase, half of the steers in each Cu treatment were given 5 mg of supplemental Mo/kg of DM. Copper supplementation increased (P<.05) humoral response to ovalbumin injected on d 133 of the growing phase. On d 168 of the growing phase, calves receiving only supplemental Mo were severely Cu-deficient based on plasma and liver Cu concentrations. The other treatment groups had adequate Cu status. Before feeding on d 168 of the growing phase, half of the steers were loaded onto trailers and transported 2.5 h, and they remained on the trailers an additional 9.5 h. Humoral response to porcine erythrocytes (PRBC) and delayed-type hypersensitivity (DTH) to dinitrochlorobenzene was tested at the end of the stress period. There was a Cu x stress interaction for humoral response to PRBC, with Cu decreasing antibody titers in unstressed calves and increasing titers in stressed steers. Stressed steers had lower (P = .03) ADG during the 28 d following stress. The results of this study indicate that Cu deficiency and 5 mg of supplemental Mo/kg of DM do not dramatically alter the specific immunity of stressed cattle.

Animal Feed↗
PubMed1999

Improving prognosis in type 2 diabetes. Diabetic neuropathy is in trouble.

Painful sensory syndromes and the anesthetic foot result in much clinical morbidity and patient unhappiness in diabetes. As yet, a satisfactory and fundamental therapy is not available to us to help patients. Effective blood glucose control and vigilant screening programs for foot problems are all we have to offer. Clinical observation of neuropathic syndromes and measures of nerve function have not led to significant understanding of pathogenesis. The primary source of understanding of pathways to nerve damage come from animal studies, despite the fears that the model in diabetes in no way reflects the human situation. Therapeutic hope at the moment from such animal work must focus on the interference of pathways known to lead to neural blood-flow abnormalities and a variety of metabolic abnormalities, as well as the possibility that addition of nerve growth factor will assist repair and regeneration. The understanding of these multiple pathways in the animal model underlines the likely enormous complexity in the final picture of understanding in diabetic neuropathy. Modern imaging techniques such as magnetic resonance imaging should, in the future, allow more significant investigation of the human subject.

Aldehyde Reductase↗
PubMed1998

Central pontine myelinolysis and ataxia: an unusual manifestation of hypoglycaemia.

Hypoglycaemia is common in people with diabetes who aim to achieve good blood glucose control. Severe hypoglycaemia presents with evidence of neurological dysfunction, such as inability to concentrate, confusion, seizures, and coma. Such disturbances are reversible on correction of the hypoglycaemia. Infrequently there may be a focal neurological deficit and we report one such case presenting with cerebellar symptoms following an episode of severe hypoglycaemia. A magnetic resonance scan showed features consistent with the presence of central pontine myelinolysis. The symptoms resolved within a few months with only minimal residual neurological deficit.

Adult↗
PubMed1998

Correlations between brain tissue oxygen tension, carbon dioxide tension, pH, and cerebral blood flow--a better way of monitoring the severely injured brain?

BACKGROUND: The ideal method for monitoring the acutely injured brain would measure substrate delivery and brain function continuously, quantitatively, and sensitively. We have tested the hypothesis that brain PO2, pCO2, and pH, which can now be measured continuously using a single sensor, are valid indicators of regional cerebral blood flow (CBF) and oxidative metabolism, by measuring its product, brain pCO2. METHODS: Twenty-five patients (Glasgow Coma Score < or = 8) were studied. A Clark electrode, combined with a fiber optic system (Paratrend 7, Biomedical Sensors, Malvern, PA) was used to measure intraparenchymal brain PO2, pCO2, and pH. Data were averaged over a 1-h period before and after CBF studies. Regional CBF was measured around the probe, using stable xenon computed tomography. Regression analyses and Spearman Rank tests were used for data analysis. RESULTS: Regional CBF and mean brain PO2 were strongly correlated (r=0.74, p=0.0001). CBF values < 18 mL/100 g/min were all accompanied by brain PO2 < or = 26 mm Hg. The four patients with a brain PO2 < 18 mm Hg died. Brain pCO2 and pH, however, were not correlated with CBF (r=0.36, p=0.24 and r=0.30, p=0.43, respectively). CONCLUSIONS: Until recently, substrate supply to the severely injured brain could only be intermittently estimated by measuring CBF. The excellent intra-regional correlation between CBF and brain pO2, suggests that this method does allow continuous monitoring of true substrate delivery, and offers the prospect that measures to increase O2 delivery (e.g., increasing CBF, CPP, perfluorocarbons etc.) can be reliably tested by brain PO2 monitoring.

Blood Flow Velocity↗
PubMed1998

An evidence-based approach to management of increased intracranial pressure.

Current treatment of many conditions associated with elevated ICP of the brain involves stabilization and oxygenation with maintenance of adequate perfusion of cerebral tissue, while maintaining an acceptable ICP. As an example of a standard protocol that is in concordance with what is already known about a patient with a severe head injury, the first priority is radiographic screening for a surgical lesion. Further treatment, as shown by the previously outlined studies, includes keeping the patient normothermic, normoglycemic, and normocapnic, and placing an indwelling ICP monitor. Acutely elevated ICP is treated with mannitol, and if this fails, patients are routinely sedated, paralyzed, and mildly hyperventilated, while repeat radiology is obtained to rule out a further surgical lesion. Hypothermia, aggressive hyperventilation, and barbiturate coma continue to be used and are reserved for intractable ICP elevation, or as warranted based on a specific patient (Table 2).

Barbiturates↗
PubMed1998

Physiological analysis of Rasmussen's encephalitis: patch clamp recordings of altered inhibitory neurotransmitter function in resected frontal cortical tissue.

Rasmussen's encephalitis (RE) is a progressive, rare childhood disease characterized by severe epilepsy, hemiplegia, dementia, and inflammation of the brain. While one mechanism underlying the pathogenesis of RE has been hypothesized to be mediated by production of excitotoxic GluR3 autoantibodies to the AMPA receptor, other neuropathological etiologies have also been indicated. Whole-cell patch clamp recordings of GABA(A) receptor mediated responses were conducted in neurons acutely isolated from an RE patient, and compared to properties of non-focal human temporal cortical neurons. RE neurons appeared similar anatomically to control cortical neurons. Significant differences in GABAergic responses were evident between RE and control neurons. GABA was significantly more potent in RE than in control cortical neurons (EC50 of 13 microM vs 23 microM, respectively). In addition, the overall efficacy of GABA was significantly decreased in RE neurons, associated with a decrease in postsynaptic GABA current density in RE neurons (5.1 pA/microm2) in comparison to controls (9.2 pA/microm2). Augmentation of GABA responses by the benzodiazepine, clonazepam (CNZ), was significantly reduced in RE in comparison to control neurons (34% vs 99% augmentation at 100 nM). The RE-associated reduced functional efficacy and altered pharmacology of neuronal GABA(A) receptors is consistent with overall disinhibition in RE neurons, and could contribute to the generation of the severe epileptic activity evident in this disorder.

Cell Size↗
PubMed1998

Factors affecting excitatory amino acid release following severe human head injury.

OBJECT: Recent animal studies demonstrate that excitatory amino acids (EAAs) play a major role in neuronal damage after brain trauma and ischemia. However, the role of EAAs in patients who have suffered severe head injury is not understood. Excess quantities of glutamate in the extracellular space may lead to uncontrolled shifts of sodium, potassium, and calcium, disrupting ionic homeostasis, which may lead to severe cell swelling and cell death. The authors evaluated the role of EEAs in human traumatic brain injury. METHODS: In 80 consecutive severely head injured patients, a microdialysis probe was placed into the gray matter along with a ventriculostomy catheter or an intracranial pressure (ICP) monitor for 4 days. Levels of EAAs and structural amino acids were analyzed using high-performance liquid chromatography. Multifactorial analysis of the amino acid pattern was performed and its correlations with clinical parameters and outcome were tested. The levels of EAAs were increased up to 50 times normal in 30% of the patients and were significantly correlated to levels of structural amino acids both in each patient and across the whole group (p < 0.01). Secondary ischemic brain injury and focal contusions were most strongly associated with high EAA levels (27+/-22 micromol/L). Sustained high ICP and poor outcome were significantly correlated to high levels of EAAs (glutamate > 20 micromol/L; p < 0.01). CONCLUSIONS: The release of EAAs is closely linked to the release of structural amino acids and may thus reflect nonspecific development of membrane micropores, rather than presynaptic neuronal vesicular exocytosis. The magnitude of EAA release in patients with focal contusions and ischemic events may be sufficient to exacerbate neuronal damage, and these patients may be the best candidates for treatment with glutamate antagonists in the future.

Amino Acids↗