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Biomedical subjects

R Garrick

Publications and source records attributed to R Garrick.

At least 19 recordsLinked to original sources

Laser Doppler flowmetry detection of endothelial dysfunction in end-stage renal disease patients: correlation with cardiovascular risk.

Prediction of cardiovascular (CV) complications represents the Achilles' heel of end-stage renal disease. Surrogate markers of endothelial dysfunction have been advocated as predictors of CV risk in this cohort of patients. We have recently adapted a noninvasive laser Doppler flowmetry (LDF) functional testing of endothelium-dependent microvascular reactivity and demonstrated that end-stage renal disease patients are characterized by profound alterations in thermal hyperemic responsiveness. We hypothesized that such functional assessment of the cutaneous microcirculation may offer a valid, noninvasive test of the severity of endothelial dysfunction and CV risk. To test this hypothesis, we performed a cross-sectional study, in which we compared LDF measurements to conventional risk factors, and performed a pilot longitudinal study. LDF studies were performed in 70 patients and 33 controls. Framingham and Cardiorisk scores were near equivalent for low-risk patients, but more divergent as risk increased. C reactive protein (CRP) levels and LDF parameters (amplitude of thermal hyperemia (TH), area under the curve of TH) showed significant abnormality in high-risk vs low-risk patients calculated using either Framingham or Cardiorisk scores. Patients who had abnormal LDF parameters showed increased CV mortality, however, had similar risk assessments (Framingham, Cardiorisk, CRP, and homocysteine) to those with unimpaired LDF tracings. In conclusion, LDF parameters of microvascular reactivity offer a sensitive characterization of endothelial dysfunction, which may improve CV risk assessment through incorporation into the Framingham or Cardiorisk algorithm.

Adult↗

Vascular neurofibromatosis affecting the internal carotid artery: a case report.

A patient with von Recklinghausen's disease presented with a right sixth nerve palsy. Investigations demonstrated unilateral dolichoectasia of the intracranial carotid artery and sphenoid wing dysplasia. This case demonstrates an association not previously documented, that of unilateral fusiform dilatation of the carotid artery with sphenoid wing dysplasia in the presence of classical neurofibromatosis.

Adult↗

Regulation of lipoxins (LX) and leukotriene B4 (LTB4) production in rat mesangial cells (MC).

In the present studies, an inverse relationship was observed between LTB4 and LXA4 formation when the concentration of LTA4 was increased from 50 microM to 250 microM. LTB4 was the major product at low concentration of LTA4 where as LXA4 was the major product at high concentration. This suggests that LTA4 hydrolase activity is present in MC and activated by low concentrations of LTA4. At high concentrations of LTA4, 15- or 12-lipoxygenase (LO) in MC may participat in LXs formation. Radioimmunoassays on HETEs MC activated with A23187 (3uM) were in the rank order of 15-HETE greater than 12-HETE greater than 5-HETE. Incubations of MC with 15-HPETE failed to produce any LX-like material. These results suggest that 1) 5-LO activity is not expressed in MC under these conditions, but LTA4 hydrolase activity is present in MC, 2) there are major activities of 12-LO and 15-LO in MC that are responsible for the generation of LXA4, LXB4 and HETES, 3) the production of LX and 12- or 15-LO products of AA may counterregulate the production of LTB4 and may modulate the response of the MC to inflammatory stimuli.

Animals↗

Eosinophilic meningitis: cause of a chronic pain syndrome.

Three tourists developed eosinophilic meningitis after visiting the Fijian Islands. Two had a severe and long lasting illness with chronic intractable pain. In one patient electrophysiological studies and MRI scan of the brain were abnormal and provided evidence of both radicular and cerebral parenchymal involvement by the most likely causative agent, Angiostrongylus cantonensis.

Adult↗

Transformation of leukotriene A4 to lipoxins by rat kidney mesangial cell.

Incubation of rat mesangial cells with leukotriene A4 in the presence of calcium ionophore A23187 led to a substrate dependent formation of lipoxin and its isomers. The major metabolite coeluted with authentic lipoxin A4 (LXA4) and lipoxin B4 (LXB4) in RP-HPLC system, and possessed a characteristic U.V. spectrum and C-value which were identical to authentic standards. GC/MS analysis on LXA4 further demonstrates that the mesangial cell derived LXA4 was identical to that reported by Serhan et al. (1) as LXA4 [5(S), 6,(R), 15(S)-trihydroxy7,9,13-trans-11-cis-eicosatetraenoic acid]. The formation of LXA4 was linear with substrate (LTA4) concentration. No similar products occurred in boiled controls. Incubation of mesangial cell with 15-HPETE failed to produce any lipoxin-like material. The absence of LX-like substance following incubation of 15-HPETE with mesangial cells suggested that 5-lipoxygenase activity is not expressed in mesangial cells under these conditions. The generation of LXA4 from LTA4 in mesangial cells suggested that there is an active 15- or 12- lipoxygenase activity in the kidney. The production of LX may play an important role in the regulation of renal function and the response to inflammatory stimuli.

Animals↗

The neurological features of early and 'latent' human immunodeficiency virus infection.

Neurological manifestations of unknown cause occurring in patients who become or are HIV antibody positive with presumed normal immune function have been described recently. This report adds a further six cases, all of whom had normal CD4+ cell counts either throughout the period of observation or after the episode of seroconversion. Three had an acute presentation, two in the context of documented seroconversion consisting of one of the following: an encephalitis, an ataxia, and confusion with neuralgic amyotrophy. Three had a subacute disorder occurring at a later phase of HIV infection but before opportunistic infections or neoplasms, and marked by a static mild cognitive deficit. This report extends the range of abnormalities that may be seen at seroconversion and documents the presence of a non-progressive cognitive deficit occurring in the latent phase of HIV infection.

AIDS Dementia Complex↗

Amelioration of systemic hypertension by converting enzyme inhibition in the renal ablation model.

Hypertension associated with a reduction in renal mass has been traditionally thought of as a volume-dependent state. Recent investigations suggest important roles for systemic and glomerular resistance vessels in the pathogenesis of systemic hypertension (SHT) and progression of end-stage renal disease. To examine this relationship, investigations were performed in two groups of rats maintained for 6 weeks following 5/6 renal ablation. Group A received converting enzyme inhibition (CEI) for 6 weeks. Group B received no treatment. Systolic blood pressure and weight of remnant kidney tissue were both increased in group B (P less than 0.01). BUN did not differ in groups A and B; however, renal PGI2 excretion was increased in group A (P less than 0.01). Renal morphology was preserved in group A, with little or no evidence of glomerular sclerosis. CEI prevents SHT and enhances renal PGI2 excretion in this model. The selective increase in PGI2 may mediate systemic and renal effects of this agent.

Angiotensin-Converting Enzyme Inhibitors↗

Gliomas presenting outside the central nervous system.

Tumours outside the central nervous system rarely prove to be intracranial glioma metastases. The mechanism of glioma metastasis has been thought to be related to dissemination of tumour cells either at the time of surgery or later through the surgical defect. However, 8 cases have been recorded to date in which metastases have occurred in the absence of surgery. This report details the clinical findings in 2 such patients. One presented with a pharyngeal mass that was found to be a metastasis from an anatomically remote parietal lobe astrocytoma. The other patient presented with a C8 nerve root tumour which was external to the dura. Biopsy revealed an astrocytoma that had metastasized from the roof of the lateral ventricle. Possible mechanisms of pathogenesis are discussed, including that of neural spread.

Astrocytoma↗

Lumboperitoneal shunting as a cause of visual loss in benign intracranial hypertension.

The causes of visual loss in benign intracranial hypertension are related to long standing papilloedema, ischaemic optic neuropathy or haemorrhage into a subretinal neovascular membrane. Decompression procedures generally preserve or improve visual acuity but surgical treatment with subtemporal decompression may lead to visual impairment. Such a deficit has been recorded in the past as occurring with ventriculography. Postulated mechanisms have included brain herniation, spasm of vessels supplying the visual cortices or retinal vascular disturbance. To our knowledge treatment with lumboperitoneal shunting has not previously been reported as leading to further significant visual loss in this condition. This report describes such an occurrence in a patient. Retinal vascular disturbance is postulated on the basis of several normal CT scans, normal CSF pressure measured after surgery and visual evoked responses suggesting retinal or optic nerve damage.

Adolescent↗

Bartter's syndrome: a unifying hypothesis.

The most proximate defect responsible for the pathogenesis of Bartter's syndrome remains uncertain. Although an abnormality in chloride reabsorption in the thick ascending limb of Henle has been postulated, renal clearance studies performed during oral water loading failed to disclose a reduction in fractional chloride reabsorption. We alternatively postulate that the underlying abnormality may reside in a generalized increase in cell sodium permeability. Elevated levels of cell sodium may secondarily stimulate Na-K-ATPase activity. In the cells of the distal nephron, stimulated Na-K-ATPase would lead to enhanced potassium secretion into the tubular fluid producing the characteristic potassium depletion. In addition, increased cell sodium influx may stimulate a sodium-calcium exchanger. If this process exists in vascular smooth muscle, it may result in reduction of cytosolic calcium activity. This effect and/or chronic potassium depletion may mediate the reduced vascular reactivity characteristic of this syndrome.

Adult↗

Evoked potential changes in clinically definite multiple sclerosis: a two year follow up study.

Visual, spinal and somatosensory evoked potentials were performed on 56 patients with clinically definite multiple sclerosis at the beginning and end of a 2 1/2 year follow-up period. At the initial examination one or both visual evoked potentials were abnormal in all but nine patients (84%), five of whom had abnormalities of either spinal or somatosensory evoked responses; that is, one or more abnormal results were obtained from 52 of 56 (91%) patients. At the final examination there were abnormalities of one or more evoked potentials in 55 of the 56 (98%) patients. There was an increase in latency of the components of the evoked responses over the period; reduction in latency in individual patients was exceptional. The change in these electrophysiological measurements correlated with the increase in clinical disability of the group of patients over the period of study.

Acoustic Stimulation↗

Transfer factor in treatment of multiple sclerosis.

A 2-year prospective double-blind trial of the treatment of multiple sclerosis patients with the leucocyte extract, transfer factor (TF), obtained from leucocytes of relatives living with the patient, was conducted. 60 patients with definite MS, of whom 58 completed the trial, were divided into two equal groups, one of which received TF and the other placebo. The groups were evenly balanced with respect to sex ratios, disability, duration of disease, ratio of moderate to severe cases, and HLA phenotype. Neurological, electrophysiological, and immunological assessments were done at the start of the trial and every 6 months thereafter. The results indicated that (1) TF retarded but did not reverse progression of the disease; (2) a significant difference between treatment and placebo groups was not apparent with 18 months after the start of the trial; and (3) treatment was effective only in those patients with mild to moderate disease activity.

Adolescent↗

Demyelination of the brain in tuberous sclerosis: computed tomography evidence.

Two patients with tuberous sclerosis are described in whom computed tomography of the head revealed areas of diffuse diminution of density suggestive of demyelination. Computed tomography is a sensitive test for the detection of intracerebral lesions in tuberous sclerosis, and the finding of areas of diminished density in the absence of evidence for tumor or ventricular obstruction correlates with the common histologic finding of diffuse demyelination. Serial studies with computed tomography are likely to determine whether such demyelination precedes the growth of hamartomas and calcification that characterize tuberous sclerosis.

Brain↗

Electrophysiological and immunological studies in optic neuritis.

Serial clinical and electrophysiological examinations and immunological investigations have been performed on 34 patients with primary optic neuritis. In 8 patients, the latency of visual evoked responses was normal after the resolution of clinical symptoms, and in a further 5 patients improvement in VER latency occurred although the response remained abnormal. In 17 patients, VER's abnormal and did not alter over the period of clinical recovery; in 4 patients there was a progressive increase in the latency of the VER's through both eyes although a satisfactory clinical recovery occurred. The frequency of histocompatibility antigens was similar in the group of ON patients to that in the normal population. Immunological function was normal in patients with ON as assessed by levels of immunoglobulins. T and B lymphocyte numbers and by lymphocyte blastogenesis in response to PHA and myelin basic protein. Three patients have developed multiple sclerosis, all of whom had either HLA-A3 or -B7 antigens; the clinical and electrophysiological pattern of recovery was different in each case.

Cerebrospinal Fluid Proteins↗

Spinal and cortical evoked potentials in multiple sclerosis.

Spinal and cortical sensory evoked potentials following stimulation of median and lateral popliteal nerves were performed in patients with definite multiple sclerosis in order to assess the usefulness of these procedures in the diagnosis and subsequent evaluation of multiple sclerosis. Abnormal SEP's were detected in 69% of patients. Abnormal spinal evoked potentials following median nerve stimulation were detected in 21 of 40 (52%) patients, and in a further 7 patients abnormalities were detected in cortical SEP's or in spinal SEP's when stimulating the lateral popliteal nerves. Close correlation was observed between the frequency of abnormal sensory signs or symptoms and the presence of electrophysiological abnormalities. When progress studies were performed a gradual deterioration was demonstrated in one or more SEP's of 12 of 24 patients.

Adolescent↗