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Biomedical subjects

R Hayward

Publications and source records attributed to R Hayward.

At least 37 records · Page 2Linked to original sources
PubMed1999

The present and future management of childhood craniopharyngioma.

Childhood craniopharyngiomas are rare tumours that present formidable difficulties in their treatment if cure is to be achieved without producing severe hypothalamic damage. Experience with our own cases suggests that the morbidity from an attempted radical removal can be predicted - allowing a treatment algorithm to be devised that combines both surgery (radical and "conservative") and radiotherapy (both external fractionated and intra-cyst instillations) in order to achieve long-term tumour control that is not at the expense of a severe functional disability.

Algorithms↗
PubMed1999

Sacral dysgenesis associated with terminal deletion of chromosome 7q: a report of two families.

UNLABELLED: Most cases of sacral dysgenesis are considered to be sporadic events. We present two families in whom the presence of associated clinical features prompted specific investigation of chromosome 7, leading to the identification of an underlying chromosome 7q deletion causing sacral dysgenesis. All affected individuals had microcephaly and developmental delay. Detailed cytogenetic studies confirmed that all three affected individuals had a deletion of chromosome 7q associated with their sacral dysgenesis, developmental delay and related problems. The three affected patients were studied clinically, radiologically and cytogenetically. Eleven unaffected individuals from the two families were also investigated by genetic studies, specifically evaluating chromosome 7. CONCLUSION: It is important that detailed family history, evaluation of associated malformations and the overall clinical picture be considered in identifying the underlying diagnosis in cases of anal stenosis/sacral agenesis. The cases we present demonstrate the value of detailed chromosome studies in such situations.

Abnormalities, Multiple↗
PubMed1999

Recombinant soluble P-selectin glycoprotein ligand-1 protects against myocardial ischemic reperfusion injury in cats.

OBJECTIVE: Neutrophils (PMNs) contribute importantly to the tissue injury associated with ischemia and subsequent reperfusion of a vascular bed. The effects of a recombinant soluble human form of P-selectin glycoprotein ligand-1 (rsPSGL.Ig) on PMN-endothelial cell interactions were investigated in a well established model of feline myocardial-ischemia reperfusion injury. METHODS: Cats were subjected to 90 min of myocardial ischemia followed by 270 min of reperfusion. RESULTS: Administration of rsPSGL.Ig (1 mg/kg) just prior to reperfusion resulted in a significant reduction in myocardial necrosis compared to that in cats administered a low affinity mutant form of rsPSGL.Ig (1 mg/kg) (16 +/- 3 vs. 42 +/- 7% of area-at-risk, P < 0.01). Cardioprotective effects were confirmed by significant (P < 0.05) reductions in plasma creatine kinase activity in cats treated with rsPSGL.Ig. Inhibition of PMN-endothelial cell interactions was evidenced by a significant attenuation in cardiac myeloperoxidase activity (P < 0.01) and reduced PMN adherence to ischemic-reperfused coronary endothelium (P < 0.001). In addition, rsPSGL.Ig treatment significantly (P < 0.01) preserved endothelium-dependent vasorelaxation in ischemic-reperfused coronary arteries. CONCLUSION: These results demonstrate that the administration of a recombinant soluble PSGL-1 reduces myocardial reperfusion injury and preserves vascular endothelial function, which is largely the result of reduced PMN-endothelial cell interactions.

Analysis of Variance↗
PubMed1999

Further evidence from two families that craniofrontonasal dysplasia maps to Xp22.

Craniofrontonasal dysplasia (CFND) is a rare X-linked disorder that maps to a 13-cM region on Xp22. Phenotypic features include craniosynostosis, hypertelorism and a broad nasal root with or without a bifid nasal tip. Multiple examples have been reported of males having a less severe phenotype than females. We report haplotype analyses in two CFND families over the critical region to which the gene has been mapped. In pedigree 1, a clinically unaffected male inherited the affected marker haplotype spanning the critical region. We suggest that this individual does have the CFND mutation, but has an extremely mild phenotype that is not detectable with clinical examination. Under the assumption that he is an unknown phenotype, a combined two-point LOD score of 1.68 at zero recombination was obtained, increasing the previously reported total to 5.61 (DXS8022). The data do not narrow down the critical region. This result stresses the importance of subjecting fathers of apparently sporadic cases to a highly critical medical examination and may also explain the unequal ratio of reported female-to-male cases.

Craniofacial Abnormalities↗
PubMed1999

Correlates of benzodiazepine abuse in methadone maintenance treatment. A 1 year prospective study in an Israeli clinic.

AIMS: This study addressed the following questions for patients after 1 year of methadone maintenance treatment (MMT); (1) What are the demographic features and past history of drug use of benzodiazepine (BZD) abusers? (2) Do BZD abusers abuse more heroin, cocaine and/or cannabis and do they receive a higher methadone dosage level? (3) Do BZD abusers suffer more from hepatitis C (HCV) and do they have more HIV/HCV risk-taking behaviors than non-abusers? (4) Do BZD abusers have more psychopathology and more emotional distress than non-abusers? DESIGN: All 148 patients who completed 1 year of MMT underwent random and twice-weekly observed urine analysis for various drugs of abuse, responded to self-report questionnaires (SCL-90-R; POMS; HIV/HCV risk-taking behaviors), interviews (ASI) and underwent testing for hepatitis C. Abuse in this study is defined as any use during the 12th month of treatment. FINDINGS: After 1 year of MMT, more BZD abusers (n = 63) were single, had spent time in prison, were unemployed and had at least one parent with an addiction problem or mental illness in comparison to non-abusers (n = 85). They had started using heroin and cocaine earlier and currently abused more cocaine, heroin and cannabis. They had significantly more psychopathology and negative mood. They had significantly more HCV and reported more HIV/HCV risk-taking behavior. IMPLICATIONS: We suggest that this group of patients is in need of more intensive pharmacological and psychological treatment.

Adult↗
PubMed1999

Effects of dietary protein on enzyme activity following exercise-induced muscle injury.

PURPOSE: The objective of this investigation was to determine the effects of varying levels of dietary protein on the postexercise increase in serum and muscle enzyme activity normally observed following exercise-induced muscle injury. METHODS: Serum creatine kinase (CK), serum aspartate aminotransferase (AST), and muscle glucose-6-phosphate dehydrogenase (G-6-PD) activities were measured in rats fed for 10 d on high (50%), normal (12%), or low (4%) protein diets following a single bout of eccentric exercise (treadmill running at 16 m.min(-1), -16 degrees incline, 90 min). RESULTS: The exercise intervention resulted in significant increases in serum CK and AST activities in all diet groups. Serum CK demonstrated peak activity immediately postexercise with increases reaching 910+/-94, 594+/-53, and 283+/-52 IU.L(-1) for animals on high, normal, and low protein diets, respectively. Similarly, peak postexercise AST activity for high, normal, and low protein diets reached 193+/-10, 147+/-3, and 162+/-9 IU.L(-1), respectively. The exercise intervention resulted in increases in muscle G-6-PD activity for all diet groups; however, LP rats demonstrated significantly lower values than NP or HP rats. CONCLUSIONS: These data show that dietary protein intake can significantly effect both serum and muscle enzyme activity following acute exercise-induced muscle injury.

Animals↗
PubMed1999

Acute mesenteric ischemia and reperfusion: protective effects of recombinant soluble P-selectin glycoprotein ligand-1.

The effects of recombinant soluble P-selectin glycoprotein ligand-1 (rsPSGL.Ig) were studied after 120 min of splanchnic artery occlusion and 120 min of reperfusion (SAO/R). SAO/R rats administered a low-affinity mutant form of rsPSGL.Ig exhibited signs of severe circulatory collapse with marked hypotension, a survival time of only 37+/-16 min, and significant increases in intestinal myeloperoxidase (MPO) activity (P<0.01). In addition, SAO/R rats given rsPSGL.Ig low-affinity mutant showed severe endothelial dysfunction characterized by a blunted vasorelaxation to the endothelium-dependent vasodilator acetylcholine in comparison to sham-operated controls (30+/-9% vs. 97+/-3%). Administration of rsPSGL.Ig (0.5 mg/kg) significantly improved mean arterial blood pressure and increased survival time to 107+/-13 min (P <0.01). rsPSGL.Ig treatment also resulted in a significant attenuation in both intestinal MPO activity as well as the SAO/R-induced decline in endothelium-dependent vasorelaxation of superior mesenteric artery rings (P<0.01). In addition, rsPSGL.Ig attenuated in vitro neutrophil adherence to thrombin-stimulated superior mesenteric artery endothelium to a comparable degree as a P-selectin monoclonal antibody. These data suggest that rsPSGL.Ig provides beneficial effects by preserving endothelial function and attenuating neutrophil-endothelial cell interactions in the splanchnic circulation following ischemia-reperfusion.

Acute Disease↗
PubMed1999

Unusual clustering of brain tumours in a family with NF1 and variable expression of cutaneous features.

Neurofibromatosis type 1 (NF1) is one of the commonest autosomal dominant disorders in man. It is characterised by café au lait spots, peripheral neurofibromas, Lisch nodules, axillary freckling, skeletal dysplasia, and optic glioma. Symptomatic brain tumours occur in 1.5-2.2% of patients with NF1. We report here a family where seven members developed brain tumours. Of these, three have a clinical history strongly suggestive of NF1, while two do not fulfil diagnostic criteria for the disorder. A splice site mutation in exon 29 of the NF1 gene was found in these two subjects. This lesion is thought to be disease causative since it creates a frameshift and a premature termination of the neurofibromin protein. Different hypotheses to explain the unusual recurrence of brain tumours in this family, such as the nature of the mutation or cosegregation of other predisposing genes, are discussed.

Adolescent↗
PubMed1998

Response of serum indicators of myocardial infarction following exercise-induced muscle injury.

The purpose of this investigation was to determine the response of three parameters used in the assessment of acute myocardial infarction (AMI) after a single bout of eccentric exercise designed to elicit skeletal muscle injury. Total creatine kinase (CK), CK-MB isoenzyme (CK-MB), and the leukocyte differential were determined after a 20-minute bench-stepping exercise in 21 men ranging in age from 30 to 45 years. Comparison of several criteria showed that the use of CK-MB or the relative lymphocyte percentage alone resulted in 11% and 1.8%, respectively, of data collection points exceeding cutoff values suggestive of AMI. However, the use of both parameters in combination completely eliminated false-positive results with no data collection points meeting the criterion. It is thus suggested that CK-MB activity in conjunction with the relative lymphocyte percentage may not only provide incremental value in the detection of AMI but also reduce the incidence of misdiagnosis associated with exercise.

Adult↗
PubMed1998

Ki-67 immunolabelling index is a prognostic indicator in childhood posterior fossa ependymomas.

Conventional histological evaluation and subclassification of childhood ependymomas poorly predict their biological behaviour. The Ki-67 labelling index (Ki-67 LI), a measure of growth fraction, correlates with the biological behaviour of several neoplasms, and this retrospective study tested the hypothesis that Ki-67 LI is a prognostic indicator in childhood posterior fossa ependymomas. Immunocytochemistry using an antibody to Ki-67 was undertaken on 5 microns sections of formalin-fixed, paraffin-embedded tissue from 74 cases of childhood (age < 16 years.) posterior fossa ependymoma. A Ki-67 LI was established by counting the proportion of labelled nuclei in more than 1000 cells from several histological fields. Several clinical and histological variables (including Ki-67 LI) potentially associated with survival were entered into univariate and multivariate analyses using a Cox proportional hazards model. Variables that showed a significant and independent association with survival were Ki-67 LI (P < 0.002), whether total surgical resection had been achieved according to operation records (P < 0.03), and whether no adjuvant therapy had been given (P < 0.01). Age, sex, and the presence of necrosis or microvascular proliferation did not correlate with survival. In our defined population of patients with ependymomas, Ki-67 LI is a strong prognostic indicator. We recommend that Ki-67 LI is used in the histological evaluation of childhood posterior fossa ependymomas during trials of novel adjunctive therapies.

Adolescent↗
PubMed1998

In sickness and in health: dilemmas of the person with severe mental illness.

In recent years, studies of person-disorder interactions, of problems of identity among discharged patients, and of subjective experiences of schizophrenia have made important contributions to our understanding of the posthospital fate of people with severe mental illness. Building on an earlier study of the experiences of a group of former mental patients in the community, this article attempts to highlight some of the issues and dilemmas that may arise for people with severe mental illness over time in their efforts to sustain a sense of identity and value that is not wholly defined or engulfed by mental illness.

Adaptation, Psychological↗
PubMed1998

Frontonasal dysplasia with optic disc anomalies and other midline craniofacial defects: a report of six cases.

The association of optic disc abnormalities with basal encephaloceles, specifically of the sphenoethmoidal type, and midline facial clefts has rarely been reported, although the association of midline facial clefts with encephaloceles is well described. We now report six cases of children, three males and three females, presenting with a sphenoethmoidal encephalocele, optic disc anomalies, midline facial clefting, hypertelorism, complete or partial agenesis of the corpus callosum, and endocrinological disturbances, including diabetes insipidus and pituitary dysfunction. This report underlines the importance of careful ophthalmic and endocrinological investigation of children with midline clefts associated with basal encephaloceles. These cases may represent a distinct entity within the spectrum of frontonasal dysplasia.

Abnormalities, Multiple↗
PubMed1998

Protein adsorption to hydrocephalus shunt catheters: CSF protein adsorption.

OBJECTIVE: To assess the quantity and nature of the proteins that adsorb to hydrocephalus shunt catheters after implantation, and to determine whether sufficient could accumulate to obstruct the catheter. DESIGN: Elution of proteins from 102 explanted shunt catheters, with protein assay and electrophoresis of the eluate, and scanning electron microscopy (SEM) of the catheters. RESULTS: The amount of protein elutable was extremely low, and significant protein, apart from a thin film, was not found on SEM. Qualitative analysis disclosed that most of the adsorbed protein was albumin. CONCLUSIONS: Protein deposition on hydrocephalus catheters does not occur in sufficient quantities to cause catheter obstruction.

Adsorption↗
PubMed1998

Cellular mechanisms of heparinase III protection in rat traumatic shock.

Pentobarbital-anesthetized rats subjected to traumatic shock developed a shock state characterized by marked hypotension to 65-70 mmHg, a survival time of 88 +/- 13 min, significant increases in ileal myeloperoxidase activity (P < 0.01), and severe endothelial dysfunction as evidenced by a significant (P < 0.01) decrease in vasorelaxation to endothelium-dependent dilators. Treatment with heparinase III (45 microg . kg-1 . min-1) 10 min posttrauma prolonged survival time to 223 +/- 19 min (P < 0.001), significantly attenuated ileal myeloperoxidase activity (P < 0.01), and significantly preserved endothelial function (P < 0.05). Intravital microscopy of the rat mesentery showed that infusion of heparinase III (45-67 microg . kg-1 . min-1) significantly (P < 0.01) attenuated both leukocyte rolling and adherence in the rat mesenteric microvasculature in response to NG-nitro-L-arginine methyl ester stimulation. Immunohistochemical localization of surface-expressed P-selectin on mesenteric venules showed that heparinase III infusion at 45-67 microg . kg-1 . min-1 significantly (P < 0.05) attenuated the increase in surface P-selectin expression. The beneficial effects of heparinase III are mediated at least in part by attenuating leukocyte-endothelial cell interactions via a P-selectin-dependent mechanism.

Anesthesia, General↗