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Biomedical subjects

S Ryder

Publications and source records attributed to S Ryder.

At least 37 records · Page 2Linked to original sources

Analysis of hospitalization rates by electoral ward: relationship to accessibility and deprivation data.

The objective of this paper is to investigate the relevance of access to hospital services in explaining utilization rates at a District Health Authority level in the UK. In order to test the hypothesis that access is important, it is necessary to develop a means of scoring access factors and then combining these scores with other more recognized influences on hospitalization rates e.g. deprivation measures. Acknowledging that hospitalization rates are not merely products of a population's socio-economic characteristics, the effect of accessibility to hospital services for the resident population is investigated through the derivation of an access score using both private and public transport from electoral ward of residence. Deprivation and accessibility to services were both found to be significant factors in determining hospitalization rates at electoral ward level. The chosen supply variable--number of GPs--was not found to be significant in any of the models developed using linear regression techniques. To conclude, it appears that access plays an important role in determining hospitalization rates within a given population. If high hospitalization rates are accepted as an indicator of effectively met demand then policy makers may have to consider increasing the accessibility of hospital services.

Catchment Area, Health↗

Mannose binding protein gene mutations associated with unusual and severe infections in adults.

A defect in opsonisation can cause a common immunodeficiency. A mutation in mannose binding protein (MBP) caused by point mutations in the MBP gene will lead to such a defect. This type of syndrome can cause recurrent infections in infants between 6 and 18 months of age but is not generally believed to predispose to adult infections. We looked at 4 patients with severe and unusual infections in whom MBP gene mutations were the only identified cause of immunodeficiency and one patient with combined MBP and IgA deficiency. We analysed the MBP genotypes of all the patients in whom we suspected an immunodeficiency because of their clinical history. Infections seen were recurrent skin abscesses, chronic cryptosporidial diarrhoea, meningococcal meningitis with recurrent herpes simplex, and fatal klebsiella lobar pneumonia. Both sexes were affected and ages ranged from 15 to 56 years. Two patients were homozygous for codon 54 mutations, one patient had codon 52 and codon 54 mutations and was phenotypically homozygous, and two patients were heterozygous for codon 54 mutations. Individuals homozygous for MBP mutations are unusual in the general population (approximate frequency 0.3%). The occurrence of three homozygotes for MBP mutations among these five infected patients suggests that MBP deficiency may confer a life-long risk of infection.

Adolescent↗

Glial cell transplants that are subsequently rejected can be used to influence regeneration of glial cell environments in the CNS.

Transplantation of glial cells into demyelinating lesions in CNS offers an experimental approach which allows investigation of the complex interactions that occur between CNS glia, Schwann cells, and axons during remyelination and repair. Earlier studies have shown that 1) transplanted astrocytes are able to prevent Schwann cells from participating in CNS remyelination, but that they are only able to do so with the cooperation of cells of the oligodendrocyte lineage, and 2) transplanted mouse oligodendrocytes can remyelinate rat axons provided their rejection is controlled by immunosuppression. On the basis of these observations, we have been able to prevent the Schwann cell remyelination that normally follows ethidium bromide demyelination in the rat spinal cord by co-transplanting isogeneic astrocytes with a potentially rejectable population of mouse oligodendrocyte lineage cells. Since male mouse cells were used it was possible to demonstrate their presence in immunosuppressed recipients using a mouse Y-chromosome probe by in situ hydridisation. When myelinating mouse cells were rejected by removal of immunosuppression, the demyelinated axons were remyelinated by host oligodendrocytes rather than Schwann cells, whose entry was prevented by the persistence of the transplanted isogeneic astrocytes. The oligodendrocyte remyelination was extensive and rapid, indicating that the inflammation associated with cell rejection did not impede repair. If this host oligodendrocyte remyelination was prevented by local X-irradiation, the lesion consisted of demyelinated axons surrounded by processes from the transplanted astrocytes. By this approach, it was possible to create an environment which resembled the chronic plaques of multiple sclerosis. Thus, these experiments demonstrate that in appropriate circumstances the temporary presence of a population of glial cells can alter the outcome of damage to the CNS.

Animals↗

Monocyte recruitment into the scrapie-affected brain.

The recruitment of monocytes into the scrapie-affected brain was investigated in female mice reconstituted with male bone marrow, using a Y-chromosome-specific probe and F4/80 immunocytochemistry. Recruitment of monocytes could be demonstrated in six out of eight animals and the number of recruited cells correlated with the severity of vacuolation in most, but not all, animals. The proportion of microglia derived from recruited monocytes varied between individual animals, did not correlate with the increase in cellularity (glia) in affected areas of brain and did not affect the length of incubation period. Thus, it is unlikely that the recruitment of monocytes is a pivotal event in the development of early pathological changes in scrapie. The morphology of recruited cells in scrapie lesions, as revealed by F4/80 immunoreactivity, was indistinguishable from that of activated resident microglia.

Animals↗

[Venezuelan equine encephalitis. Determination of antibodies in the human population of Municipio Mirand, Estado Zulia, Venezuela].

With the purpose of determining antibodies prevalence against Venezuelan Equine Encephalitis Virus in the population of Puertos de Altagracia and Sabaneta de Palmas of Miranda county, Zulia State, Venezuela, 199 subjects were studied: 57 from Puertos de Altagracia and 142 from Sabaneta de Palmas. They were classified in older (42.78%) and younger (57.2%) than 15 years. The blood specimens were processed for Hemagglutination Inhibition Test using EEV antigen Goajira strain at pH 6.5. We found that all 57 specimens from Puertos de Altagracia were negative, whereas of 142 specimens from Sabaneta de Palmas 17 were positive (11.97%). Of these, one was from a subject less than 15 years-old (5.85%) and 16 from individuals more than 15 years-old (94.15%). Positive titers were higher than 1:160 in 80% of cases. Being Sabaneta de Palmas one of the most affected areas in the 1962 epidemic in the Miranda county and keeping the affected ones high positivity with elevated titers, we conclude that this population could represent an enzootic zone similar to Paez county where a similar situation, of high positivity and elevated titers, many years after the last epidemic occurred in that area, has been described.

Adolescent↗

Massive haemorrhage due to ulcerative colitis presenting as melaena.

We present a patient with known ulcerative colitis who presented with massive lower gastrointestinal bleeding in the form of melaena. Extensive investigations indicated that the source of blood loss was only from the colon, was attributable to the colitis, and settled when the colitis was treated with steroids. Melaena may be due to blood loss from the colon.

Acute Disease↗

A proposal for the classification of field placement errors in radiotherapy.

There is an increasing awareness of the high frequency of field placement errors occurring in radiotherapy. If such errors are to be rectified systematically to provide a sustainable improvement in field placement accuracy over a course of treatment, the origins of the errors require unambiguous identification. From an examination of the procedures taking place between the exposure of the prescription and treatment films, we propose resolving field placement errors into four groups: patient motion, entrance field location, field shape or size, and beam direction. We also suggest means by which the components of clinically observed field placement errors may be resolved in practice.

Classification↗

Ion exchange chromatography of purified colonic mucus glycoproteins in inflammatory bowel disease: absence of a selective subclass defect.

Previous reports of a selective mucin subclass defect in ulcerative colitis have been reassessed using high performance chromatography (Superose 6 and Mono Q) for mucin purification and fractionation coupled with analysis of the fractions obtained using a combination of enzyme linked lectin and mucin antibody assays. Mucin samples purified from snap frozen rectal biopsy specimens obtained from patients with ulcerative colitis (n = 12), Crohn's disease (n = 5), and non-inflammatory bowel disease control subjects (n = 9) were subject to ion exchange chromatography using a continuous 0-0.35 mol/l NaCl salt gradient with a final 2.5 mol/l NaCl step. In all samples the major proportion (mean (SD) 86.7 (8.9)%) of the mucin detectable by wheat germ agglutinin binding eluted between 0.15 and 0.35 mol/l NaCl with no significant difference in elution profile between ulcerative colitis and control subjects. Significant elution of glycoprotein at less than 0.15 mol/l NaCl did occur, however, when a lower molecular weight mucin containing fraction which contained concanavalin A positive (glucose or mannose containing) material was analysed similarly. Similar ion exchange profiles were obtained when (3H)N-acetylglucosamine labelled mucins were studied after tissue culture of rectal biopsy specimens. No significant alteration in the ion exchange profile of purified mucins in ulcerative colitis has been shown in these studies. It is possible that the previously reported relative depletion of mucin subclass IV (eluting with 0.20 mol/l NaCl) may simply have reflected mucin depletion.

Chromatography, Ion Exchange↗

[Antibodies against Venezuelan equine encephalitis in the human population of the Mara district of the state of Zulia, Venezuela].

Antibodies against Venezuelan Equine Encephalitis Virus (VEEV) were studied in the human population of Mara District, Zulia State, Venezuela. Two hundred thirty nine blood samples were taken from the towns of San Rafael de Mara, Santa Cruz de Mara, La Sierrita-4 Bocas, Carrasquero, Isla de San Carlos e Isla de Toas, during june, july and september, 1988. Donors samples were classified by age, sex and serological titres. Eighty nine were less than 15 years old (37.2%) and 150, over 15 years old (62.7%). From the 239 samples, 224 were negative (93.7%) and 15 positive (6.3%). Our results indicate that must of the population from the studied towns were negative for VEEV antibodies and being exposed to the disease.

Adolescent↗

[Antibodies against the Venezuelan equine encephalitis virus in the population of the Páez District of the Zulia Venezuela State].

With the purpose of knowing the presence of antibodies against Venezuelan Equine Encephalities virus (EEV), after the continuous outbreaks produced by this virus we studied 192 sera (112 children and 80 adults), from the towns of Carretal, Cojoro and Paraguaipoa (Páez District), between the months of March and October 1986. The samples were analyzed using the hemagglutination inhibition test by the Clarke and Casals technique, using VEE virus antigen Guajira strain. We found that from 192 samples, 161 were negative 84%. This negativity was observed mainly on the infant population where it reached 97%. Negativity in adults was 65%. These results demonstrate that there has been no viral activity since the last outbreak in 1973, due probably to the epidemiological controls done on that zone and that the percentage of positivity of those older than 15 years has maintained the same level since the last survey on 1973.

Adolescent↗

Effect of tolrestat on red blood cell sorbitol levels in patients with diabetes.

The effect of the aldose reductase inhibitor, tolrestat, on red blood cell (RBC) sorbitol levels was studied in 23 patients with diabetes after oral dosing with tolrestat, 25 or 100 mg b.i.d. The mean (+/- SE) RBC sorbitol levels (measured 12 hours after the preceding dose) after 3, 7, and 13 days of dosing decreased after both dose levels. After 25 mg tolrestat the RBC sorbitol levels fell from 25.1 +/- 4.0 to 20.0 +/- 5.7 nmol/gm hemoglobin (21%) and after 100 mg tolrestat the level fell from 26.7 +/- 3.7 to 11.4 +/- 1.7 nmol/gm hemoglobin (57%; P less than 0.001). This latter RBC sorbitol concentration is similar to levels in individuals without diabetes. At both dosage levels the maximum decrease in RBC sorbitol levels occurred after only 3 days of dosing. Tolrestat had no effect on plasma glucose or hemoglobin A1 concentrations. The overall mean plasma unbound drug concentration measured 12 hours after 100 mg tolrestat (11.7 +/- 3.0 ng/ml; 3.3 X 10(-8) mol/L) was similar to the median inhibitory level (3 X 10(-8) mol/L) of tolrestat for sorbitol accumulation in human RBCs incubated in a high-glucose medium. Our results demonstrate the systemic bioavailability of tolrestat and its aldose reductase inhibitory activity in erythrocytes of patients with diabetes.

Administration, Oral↗

Tolrestat kinetics.

The kinetics of tolrestat, a potent inhibitor of aldose reductase, were examined. Serum concentrations of tolrestat and of total 14C were measured after dosing normal subjects and subjects with diabetes with 14C-labeled tolrestat. In normal subjects, tolrestat was rapidly absorbed and disappearance from serum was biphasic. Distribution and elimination t 1/2s were approximately 2 and 10 to 12 hr, respectively, after single and multiple doses. Unchanged tolrestat accounted for the major portion of 14C in serum. Radioactivity was rapidly and completely excreted in urine and feces in an approximate ratio of 2:1. Findings were much the same in subjects with diabetes. In normal subjects, the kinetics of oral tolrestat were independent of dose in the 10 to 800 mg range. Repetitive dosing did not result in unexpected cumulation. Tolrestat was more than 99% bound to serum protein; it did not compete with warfarin for binding sites but was displaced to some extent by high concentrations of tolbutamide or salicylate.

Absorption↗

Human Venezuelan equine encephalitis virus infection and diabetes in Zulia State, Venezuela.

Venezuelan equine encephalitis (VEE) virus has been implicated as producing alterations in glucose metabolism in animals. We performed oral glucose tolerance tests and measured serum immunoreactive insulin responses in 13 patients who were infected by VEE virus during an epidemic in 1969, in Zulia State, Venezuela. No significant alterations in the glucose tolerance test were found. Sera of 86 diabetic outpatients and 98 control individuals with normal glycemia at a local hospital were tested for antibodies to VEE virus by hemagglutination inhibition. No statistically significant difference was found between the two groups; 10.4% of the diabetic patients had detectable antibodies against VEE virus, compared to 7.1% of controls. Seventy-three percent of the diabetics with antibodies were individuals over 40 yr old, whose diabetes could be catalogued as insulin independent. The results of these studies indicate no relationship of VEE virus infection to subsequent diabetes.

Adolescent↗