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Biomedical subjects

M Cortina-Borja

Publications and source records attributed to M Cortina-Borja.

At least 19 recordsLinked to original sources

Prospective evaluation of urological effects of aging in chronic spinal cord injury by method of bladder management.

AIMS: Risk of treatment-related problems in spinal cord injury (SCI) mandates assessment of complication rates of different bladder management methods (BMMs). The current study evaluated aging-related complications of various BMMs over a 6-year period in a population with spinal cord injury for at least 20 years. MATERIALS AND METHODS: Clinical parameters were compared using a linear mixed effects model, controlling for various confounding variables, to establish complication trends with aging and their association with BMM. Results for people whose BMM was changed during the study were evaluated separately as well as in combination with the whole population. RESULTS: One hundred and ninety six people (mean age 57.4 and years post injury (YPI) 33) were evaluated on three occasions. Both age and YPI were significantly associated with rising complication rates regardless of BMM. The BMMs assessed differed in terms of complication rates. In comparison with balanced reflex voiding, straining was significantly better for renal structural abnormality. Intermittent catheterization was associated with significantly worse renal function, possibly for demographic reasons. Overall, 28.8% changed BMM during the study period, particularly, those using straining or balanced reflex voiding. The probability of change increased with age and YPI. Reasons for change of BMM were varied and there was no specific association between reason for change and BMM. CONCLUSIONS: Aging and duration of injury substantially influence urological complication rates, and BMM options differ in respect of prevalence and incidence of complications. At a late stage post injury there remains a high probability of change in BMM. The findings indicate the importance of long-term planning from the time of injury to minimize late complications.

Adult↗

Duration of the IgM response in women acquiring Toxoplasma gondii during pregnancy: implications for clinical practice and cross-sectional incidence studies.

We followed up a cohort of 446 toxoplasma-infected pregnant women to determine the median and variability of the duration of positive toxoplasma-IgM (immunoglobulin M) results measured by an immunofluorescence test (IFT) and an immunosorbent agglutination assay (ISAGA). IgM antibodies were detected for longer using the ISAGA test [median 12.8 months, interquartile range (IQR) 6.9-24.9] than the IFT (median 10.4, IQR 7.1-14.4), but the variability between individuals in the duration of IgM positivity was greatest for the ISAGA test. IgM-positive results persisted beyond 2 years in a substantial minority of women (27.1% ISAGA, 9.1% IFT). Variation in the duration of the IgM response measured by ISAGA and IFT limit their usefulness for predicting the timing of infection in pregnant women. However, measurement of IgM and IgG antibodies in a cross-sectional serosurvey offers an efficient method for estimating the incidence of toxoplasma infection.

Adult↗

Interpreting neonatal HIV seroprevalence data in Great Britain: the importance of differential fertility.

In order to derive more accurate estimates of HIV infection among the general population in Great Britain from unlinked anonymous neonatal seroprevalence data, the differential HIV and fertility patterns amongst groups of women were explored. The HIV risk in women was estimated using neonatal seroprevalence data and reports of diagnoses of HIV infection in pregnant women. Live birth rates were estimated using population data and these were supplemented using data from a prospective European cohort of HIV-infected pregnant women. HIV prevalence was higher in women born in sub-Saharan Africa (SSA) and injecting drug users (IDUs) (2.50% and 0.29% respectively in London) compared to other women (0.068%). Fertility was also higher in women born in SSA (OR 1.33 using population data), whilst IDUs were more likely to have had a previous termination (OR 1.48 using the European cohort of HIV-infected pregnant women data). We conclude that when unlinked anonymous neonatal seroprevalence data is used to estimate general population prevalence, adjustments need to be made for fertility differentials in population subgroups at varying risk of HIV.

Africa South of the Sahara↗

Naturally exposed populations differ in their T1 and T2 responses to the circumsporozoite protein of Plasmodium falciparum.

T-cell responses directed against the circumsporozoite protein (CS) of Plasmodium falciparum can mediate protection against malaria. We determined the frequency of T cells reactive to different regions of the CS in the blood of donors naturally exposed to P. falciparum by examining T1 (gamma interferon [IFN-gamma] ELISPOT assay), T2 (interleukin 4 [IL-4] ELISPOT assay), and proliferative T-cell responses. The proliferative responses were weak, which confirmed previous observations. The responses to the CS in the IL-4 and IFN-gamma ELISPOT assays were also weak (<40 responding cells per 10(6) cells), much weaker than the response to the purified protein derivative of Mycobacterium tuberculosis in the same donors. Moreover, a response in one assay could not be used to predict a response in either of the other assays, suggesting that although these assays may measure different responding cells, all of the responses are weakly induced by natural exposure. Interestingly, the two different study populations used had significantly different T1 and T2 biases in their responses in the C terminus of the protein, suggesting that the extent of P. falciparum exposure can affect regulation of the immune system.

Adolescent↗

Distribution of upper limb skin cancers in relation to arteriovenous fistula side in renal transplant recipients.

BACKGROUND: Renal transplant patients have an increased incidence of skin cancers, predominantly on sun-exposed surfaces. Clinical observation identified some patients with an increased number of viral warts, keratoses, and skin malignancies on the side of the arteriovenous fistula. METHODS: In a population of 980 patients who underwent transplantation in Oxford, we identified 68 patients with known fistula site who had developed cutaneous malignancies on the upper limbs. We compared the distribution of skin malignancies in relation to the side of the arteriovenous fistula with regard to histologically confirmed Bowen's disease, squamous cell carcinoma, basal cell carcinoma, and keratoacanthoma. RESULTS: No significant difference was found between the distribution of skin cancers, total malignancies or subgroups, in the fistula limbs compared with the nonfistula limbs. CONCLUSION: We have been unable to demonstrate that the presence of an arteriovenous fistula predisposes to the development of cutaneous malignancies.

Arm↗

Enhanced survival in Sandhoff disease mice receiving a combination of substrate deprivation therapy and bone marrow transplantation.

Sandhoff disease is a lysosomal storage disorder characterized by G(M2) ganglioside accumulation in the central nervous system (CNS) and periphery. It results from mutations in the HEXB gene, causing a deficiency in beta-hexosaminidase. Bone marrow transplantation (BMT), which augments enzyme levels, and substrate deprivation (using the glycosphingolipid biosynthesis inhibitor N-butyldeoxynojirimycin [NB-DNJ]) independently have been shown to extend life expectancy in a mouse model of Sandhoff disease. The efficacy of combining these 2 therapies was evaluated. Sandhoff disease mice treated with BMT and NB-DNJ survived significantly longer than those treated with BMT or NB-DNJ alone. When the mice were subdivided into 2 groups on the basis of their donor bone marrow-derived CNS enzyme levels, the high enzyme group exhibited a greater degree of synergy (25%) than the group as a whole (13%). Combination therapy may therefore be the strategy of choice for treating the infantile onset disease variants.

1-Deoxynojirimycin↗

Cardiac abnormalities and skeletal muscle weakness in carriers of Duchenne and Becker muscular dystrophies and controls.

Cardiac abnormalities, cardiomyopathy and skeletal muscle weakness have been described in female carriers of the Xp21 (Duchenne and Becker) muscular dystrophies (J Neurol 1975;209(4):279-285; Br Med J 1969;2:418-420; J AmMed Assoc 1996;275(17):1335-1338; Neurology 1980;30(5):497-501; Neuromusc Disord 1999;9:347-351; Arch Neurol 1989;46:673-675). We have screened volunteers from our Xp21 genetics register and found the prevalence of previously unrecognized, clinically relevant, abnormalities in this group to be less than previously reported. We studied 91 women (56 carriers and 35 controls), aged between 18 and 69 years, from our local population known to the Oxford Regional Genetics Register. Our study included controls, with the investigators being blind to the subject's genetic status. The prevalence of previously unrecognised cardiac abnormalities on echocardiogram and ECG was 18% (10/56). Seven percent (4/56) of carriers had cardiomyopathy, defined by significant LV dilatation and decreased shortening fraction. In most cases, subjects with abnormal cardiac findings were asymptomatic. Echocardiography was more frequently abnormal than electrocardiography, but in many subjects the measurements of left ventricular dimensions were only just outside the normal ranges. The prevalence of skeletal muscle weakness was 12% (7/56). It was usually recognized by the individual, although not previously volunteered, but was mild and did not substantially affect activities of daily living.

Adult↗

Encapsulated fish oil enriched in alpha-tocopherol alters plasma phospholipid and mononuclear cell fatty acid compositions but not mononuclear cell functions.

BACKGROUND: Several studies have reported that dietary fish oil (FO) supplementation alters cytokine production and other functional activities of peripheral blood mononuclear cells (PBMC). However, few of these studies have been placebo controlled and few have related the functional changes to alterations in PBMC fatty acid composition PATIENTS AND METHODS: Healthy subjects supplemented their diets with 9 g day-1 of encapsulated placebo oil (3 : 1 mix of coconut and soybean oils), olive oil (OO), safflower oil (SO), evening primrose oil (EPO) or FO [providing 2.1 g eicosapentaenoic acid (EPA) plus 1.1 g docosahexaenoic acid (DHA) per day] for 12 weeks; the capsules also provided 205 mg alpha-tocopherol per day. Blood was sampled at 4-weekly intervals and plasma and PBMC prepared. Plasma phospholipid and PBMC fatty acid composition, plasma alpha-tocopherol and thiobarbituric acid-reactive substance concentrations, plasma total antioxidant capacity, the proportions of different PBMC subsets, the proportions of PBMC expressing the adhesion molecules CD2, CD11b and CD54, and PBMC functions (lymphocyte proliferation, natural killer cell activity, cytokine production) were measured. All measurements were repeated after a 'washout' period of 8 weeks. RESULTS: The placebo, OO and SO capsules had no effect on plasma phospholipid or PBMC fatty acid composition. The proportion of dihomo-gamma-linolenic acid in plasma phospholipids was elevated in subjects taking EPO and was decreased in subjects taking FO. There was no appearance of gamma-linolenic acid in the plasma phospholipids or PBMC in subjects taking EPO. There was a marked increase in the proportion of EPA in the plasma phospholipids (10-fold) and PBMC (four-fold) of subjects taking FO supplements; this increase was maximal after 4 weeks of supplementation. There was an increase in the proportion of DHA in plasma phospholipids and PBMC, and an approximately 20% decrease in the proportion of arachidonic acid in plasma phospholipids and PBMC, during FO supplementation. Plasma concentrations of alpha-tocopherol were significantly elevated during supplementation in all subjects and returned to baseline values after the washout period. There were no effects of supplementation with any of the capsules on total plasma antioxidant activity or plasma thiobarbituric acid-reactive substances or on the proportion of different PBMC subsets, on the proportion of PBMC expressing adhesion molecules, on natural killer cell activity, on the proliferation of mitogen-stimulated whole blood cultures or PBMC, or on the ex vivo production of a range of cytokines by whole blood cultures or PBMC cultures stimulated by either concanavalin A or lipopolysaccharide. CONCLUSION: Supplementation of the diet with 3.2 g EPA plus DHA per day markedly alters plasma phospholipid and PBMC fatty acid compositions. The lack of effect of FO upon PBMC functions may relate to the level of alpha-tocopherol included in the supplements.

Adult↗

The effect of bladder outlet obstruction on tissue oxygen tension and blood flow in the pig bladder.

OBJECTIVE: To investigate the effect of partial bladder outlet obstruction on detrusor blood flow and oxygen tension (PdetO2) in female pigs. MATERIALS AND METHODS: Detrusor-layer oxygen tension and blood flow were measured using oxygen-sensitive electrode and radiolabelled microsphere techniques in five female Large White pigs with a partial urethral obstruction and in five sham-operated controls. The effects of chronic outlet obstruction on bladder weight, and cholinergic nerve density and distribution, are also described. RESULTS: In the obstructed bladders, blood flow and oxygen tension were, respectively, 54.9% and 74.3% of control values at low bladder volume, and 47.5% and 42.5% at cystometric capacity. Detrusor blood flow declined by 27.8% and 37.5% in the control and obstructed bladders, respectively, as a result of bladder filling, whilst PdetO2 did not decrease in the controls, but fell by 42.7% in the obstructed bladders. Bladder weight increased whilst cholinergic nerve density decreased in the obstructed animals. CONCLUSION: In pigs with chronic bladder outlet obstruction, blood flow and oxygen tension in the detrusor layer were lower than in control animals. In addition, increasing detrusor pressure during filling caused significantly greater decreases in blood flow and oxygen tension in the obstructed than in the control bladders.

Animals↗

Delayed symptom onset and increased life expectancy in Sandhoff disease mice treated with N-butyldeoxynojirimycin.

Sandhoff disease is a neurodegenerative disorder resulting from the autosomal recessive inheritance of mutations in the HEXB gene, which encodes the beta-subunit of beta-hexosaminidase. GM2 ganglioside fails to be degraded and accumulates within lysosomes in cells of the periphery and the central nervous system (CNS). There are currently no therapies for the glycosphingolipid lysosomal storage diseases that involve CNS pathology, including the GM2 gangliosidoses. One strategy for treating this and related diseases is substrate deprivation. This would utilize an inhibitor of glycosphingolipid biosynthesis to balance synthesis with the impaired rate of catabolism, thus preventing storage. One such inhibitor is N-butyldeoxynojirimycin, which currently is in clinical trials for the potential treatment of type 1 Gaucher disease, a related disease that involves glycosphingolipid storage in peripheral tissues, but not in the CNS. In this study, we have evaluated whether this drug also could be applied to the treatment of diseases with CNS storage and pathology. We therefore have treated a mouse model of Sandhoff disease with the inhibitor N-butyldeoxynojirimycin. The treated mice have delayed symptom onset, reduced storage in the brain and peripheral tissues, and increased life expectancy. Substrate deprivation therefore offers a potentially general therapy for this family of lysosomal storage diseases, including those with CNS disease.

1-Deoxynojirimycin↗

The size and fibre composition of the corpus callosum with respect to gender and schizophrenia: a post-mortem study.

In this study the cross-sectional area (in n = 14 female controls, 15 male controls, 11 female patients with schizophrenia, 15 male patients with schizophrenia) and fibre composition (in n = 11 female controls, 10 male controls, 10 female patients with schizophrenia, 10 male patients with schizophrenia) of the corpus callosum in post-mortem control and schizophrenic brains was examined. A gender x diagnosis interaction (P = 0.005) was seen in the density of axons in all regions of the corpus callosum except the posterior midbody and splenium. Amongst controls, females had greater density than males; in patients with schizophrenia this difference was reversed. A reduction in the total number of fibres in all regions of the corpus callosum except the rostrum was observed in female schizophrenic patients (P = 0.006; when controlling for brain weight, P = 0.053). A trend towards a reduced cross-sectional area of the corpus callosum was seen in schizophrenia (P = 0.098); however, this is likely to be no more than a reflection of an overall reduction in brain size. With age, all subregions of the corpus callosum except the rostrum showed a significant reduction in cross-sectional area (P = 0.018) and total fibre number (P = 0.002). These findings suggest that in schizophrenia there is a subtle and gender-dependent alteration in the forebrain commissures that may relate to the deviations in asymmetry seen in other studies, but the precise anatomical explanation remains obscure.

Aged↗

A quest for seasonality in presentation of leukaemia and non-Hodgkin's lymphoma.

The literature on presentation of seasonality of leukaemia fails to provide clear conclusions. Using the Data Collection Study organised by the Leukaemia Research Fund (LRF) Centre for Clinical Epidemiology, University of Leeds, this question was re-examined. This data has a high level of ascertainment and is population based. The results were mainly negative, there being no fit to a sinusoidal curve (Cosinor analysis) in any part of the data. Using normal approximation to Poisson there were individual months with positive findings. Such a method could not be specifically depended on to provide reliable conclusions, nevertheless, further work in this area is justified. Non-Hodgkin's lymphoma was also examined but again with mainly negative findings.

Acute Disease↗

Anomalies of cerebral asymmetry in schizophrenia interact with gender and age of onset: a post-mortem study.

In a post-mortem study of cerebral asymmetry in schizophrenia it was found that asymmetry of the length from the frontal pole to the central sulcus measured dorsally over the external surface of the brain on both hemispheres, showed a gender x diagnosis interaction (p = 0.002). Female controls had a left-greater-than-right asymmetry, and the male controls had a right-greater-than-left asymmetry. This pattern was reversed in schizophrenia. The converse effect was observed on a similar measure of the occipito-parietal lobes (p = 0.028). Significant changes were not seen in measures taken around the lateral surface of the hemispheres. Further, within the patient group, the frontal lobe asymmetry was related to age of onset such that leftward asymmetrical brains were associated with a later age of onset than rightward asymmetrical brains (p = 0.0463 for the females; p = 0.0162 for the males). The occipito-parietal asymmetry was not related to age of onset. We conclude that the asymmetry of the relative distribution of tissue between frontal and posterior regions of the hemispheres is altered in schizophrenia. The findings also suggest that there is an interaction between gender and cerebral asymmetry that is critical in determining age of onset.

Age of Onset↗

A seasonal variation in the incidence of ruptured abdominal aortic aneurysms.

OBJECTIVE: To discover whether there is a seasonal variation in the incidence of rupture of abdominal aortic aneurysms. DESIGN: Deaths per month due to rupture of abdominal aortic aneurysm were analysed retrospectively using a cosinor regression model. SETTING: England and Wales. SUBJECTS: 19,599 patients who died from rupture of abdominal aortic aneurysm between January 1991 and December 1995 according to death certification data. INTERVENTIONS: None. RESULTS: A seasonal variation in the incidence of rupture of abdominal aortic aneurysm occurs, with a peak in winter (p = 0.003). The ratio of rupture of abdominal aortic aneurysm in males and females decreased from more than 12 to 1 below age 60 years to less than 5 to 1 over age 80 years. CONCLUSIONS: There is a seasonal variation in the incidence of recorded deaths from abdominal aortic aneurysm in England and Wales, with a peak of deaths in the cold winter months. The underlying cause is unknown, but hypertension and tobacco smoking are predisposing factors to aortic aneurysm rupture. Exposure to tobacco smoke is known to be greater indoors in cold weather and there is a winter peak of blood pressure in hypertensive patients.

Age Factors↗

Seasonal variation in the incidence of Hodgkin's disease.

Earlier literature suggested there may be a seasonal rhythm of onset of Hodgkin's disease. This issue has been re-examined using population-based prospectively-collected data with high ascertainment levels. The Data Collection Study (DCS) of the Leukaemia Research Fund (LRF) Centre for Clinical Epidemiology (University of Leeds) generated the information used, which was based on a population of 13.5 million--about one quarter of England and Wales--over 10 years. The RYE histopathological classification was employed. The findings show that in patients with nodular sclerosing histopathology there was a highly significant circannual rhythm with a low amplitude (extent of seasonal variation) and a peak in March. A significant, but different, rhythm with a high amplitude and a peak in August was found in lymphocyte predominant Hodgkin's disease. However, this finding is less certain, due to smaller numbers and a lower significance level. The main conclusion is that there is a highly significant seasonality in nodular sclerosing Hodgkin's disease. The findings provide further evidence that nodular sclerosing and lymphocyte predominant may be two different diseases. The differing seasonality rhythms may provide aetiological clues.

Adolescent↗

A case-control study to examine any association between idiopathic detrusor instability and gastrointestinal tract disorder, and between irritable bowel syndrome and urinary tract disorder.

OBJECTIVE: To assess whether there are common malfunctions (e.g. of the autonomic nervous system and smooth muscle) that underlie disorders of the urinary and gastrointestinal tracts by determining whether there is an increased prevalence (i) of urinary symptoms in patients with irritable bowel syndrome (IBS) and (ii) of gastrointestinal symptoms in patients with idiopathic detrusor instability (IDI). PATIENTS AND METHODS: Questionnaires were sent to patients with a diagnosis of IBS or IDI who were seen in the Departments of Gynaecology, Gastroenterology and Urology at the John Radcliffe and Churchill Hospitals, Oxford, during the 3 year period 1993-1995. The questionnaires were also distributed to control patients who were recruited from the day-surgery unit of the Churchill Hospital. Of 236 questionnaires sent out, 168 replies were analysed; 64 from patients with IBS, 49 from patients with detrusor instability and 55 from controls. The questionnaire included questions about micturition and defecatory behaviour (frequency, regularity, urgency, continence, pain, and ease in passing urine and stools). RESULTS: Patients with IBS were more likely to experience certain urinary symptoms than controls (nocturia, urgency and some forms of urinary urge incontinence) and patients with IDI were as likely as patients with IBS to experience gastrointestinal symptoms more frequently than controls. Control patients showed an unexpectedly high probability of experiencing many of the gastrointestinal and urinary symptoms. CONCLUSIONS: The frequent occurrence of symptoms in control patients makes the significance of the results less clear, but the association between certain symptoms of urinary tract disorder and patients with IBS, and of symptoms of gastrointestinal tract disorder with patients with IDI, suggests that they may share some common underlying dysfunction.

Adult↗