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Biomedical subjects

J Hall

Publications and source records attributed to J Hall.

At least 163 records · Page 9Linked to original sources

Folic acid for the prevention of congenital anomalies.

UNLABELLED: Paediatricians need to be aware of the broad implications that sufficient maternal folic acid intake has on the wellbeing of the embryo and fetus. There is now strong evidence that adequate periconceptional maternal folic acid supplementation during critical periods of organ formation is associated with reduction in both the occurrence and recurrence of neural tube defects, congenital heart defects (particularly conotruncal heart defects), obstructive urinary tract anomalies, limb deficiencies, orofacial clefts and congenital hypertrophic pyloric stenosis. Inadequate maternal folic acid intake is associated with preterm deliveries, intra-uterine growth retardation, placental abruption and infarction, while maternal folic acid supplementation is associated with a reduction in preterm deliveries and intra-uterine growth retardation. Recently adequate folic acid intake in adults has been associated with a reduction in adult cardiovascular disease and some cancers. A common mutation in the 5,10 methylenetetrahydrofolate reductase gene has been identified which produces a thermolabile variant of 5,10 methylenetetrahydrofolate reductase with reduced enzyme activity. The common mutation is a risk factor both for neural tube defects and adult cardiovascular diseases. Folic acid acts to increase the activity of the variant methylenetetrahydrofolate reductase thereby reducing plasma homocysteine levels. However the polymorphism does not explain all of the protective effects of folic acid. CONCLUSION: Primary prevention of birth defects by adequate periconceptional folic acid supplementation is a major public health opportunity and has wide implications in reducing both mortality and morbidity due to birth defects and several adult diseases. It follows that there would also be a curbing of health care costs related to those disorders.

Adult↗

Nevoid basal cell carcinoma syndrome in a black child.

Nevoid basal cell carcinoma syndrome (NBCCS) is rare in black persons. We describe an 11-year-old black boy with NBCCS who presented with exotropia and a painful, expanding, cystic mass in the left posterior alveolar ridge. Further examination revealed odontogenic keratocysts with palmar and plantar pitting. Less than 5% of reported patients with NBCCS are black. To our knowledge, this is the first report of a black patient with NBCCS presenting with exotropia and an impacted molar displaced into the orbit by an odontogenic keratocyst.

Basal Cell Nevus Syndrome↗

The role of enterocytes in gut dysfunction.

Stem cells in the intestinal epithelium give rise to enterocytes, goblet cells, enteroendocrine cells, and Paneth cells. Each of these cell lines plays a role in cytoprotection of the intestinal mucosa. In particular, it has been demonstrated that mature enterocytes can act as antigen presenting cells. Parenteral and enteral nutrition are used to nourish critically ill patients. However, these regimens are unfortunately associated with gut atrophy. Glutamine, the preferred intestinal nutrient, reverses this gut atrophy and plays a key role in maintaining the barrier function of the gut. Specific nutrients (putrescine, spermidine, spermine) have been used to modulate intestinal adaption. In addition, ornithine has been shown to act as a regulator of intestinal adaption. In this review, we discuss the relationship between the biology of enterocytes and failure of the gut barrier.

Animals↗

Asthma-related prescribing patterns with four different corticosteroid inhaler devices.

Four types of corticosteroid inhaler devices are available in New Zealand for first-line treatment of asthma, including two aerosol systems [Autohaler (3M Healthcare Ltd, Loughborough, U.K.; 3M Pharmaceuticals (Australia Pty Ltd, Sydney, Australia) and MDI (Glaxo Wellcome PLC, Ware, U.K.)] and two dry powder systems [Diskhaler (Glaxo Wellcome) and Turbuhaler (Astra AB, Sodertalje, Sweden)]. Rates of asthma-related health care consumption and treatment outcomes associated with use of the different inhalers are unknown. In this retrospective survey, asthma-related primary health care consultation and prescription patterns were compared in a large general practice population for each corticosteroid inhaler device prescribed as first-line treatment. An electronic search of a computerized clinical database yielded the medical records of 5704 patients with physician-diagnosed asthma who were prescribed either the Autohaler, Diskhaler, MDI or Turbuhaler as their sole corticosteroid inhaler device in the previous 12 months. The mean daily inhaled corticosteroid dose was lowest for the Autohaler (569 micrograms day-1; 95% CI: 538-605), followed by the Diskhlaer (638 micrograms day-1; 95% CI: 609-670) and MDI (665 micrograms day-1; 95% CI: 638-673), and was highest for the Turbuhaler (990 micrograms day-1; 95% CI: 954-1029, P < 0.001). A relatively high proportion of patients aged 19-49 years in the Turbuhaler and Diskhaler groups (29% and 23%, respectively) received at least one inhaled corticosteroid prescription including a daily dose greater than 1500 micrograms compared with the MDI group (4%). In the Diskhaler group the mean daily inhaled corticosteroid dose prescribed for adult patients was similar to that for the Turbuhaler group (904 micrograms day-1 and 1058 micrograms day-1, respectively). These data suggest that in New Zealand the dry powder corticosteroid inhaler devices are prescribed for adults at significantly higher doses than the aerosol inhaler devices. Clinical databases of this type yield valuable information on drug utilization in large patient populations and usefully assess clinical prescribing practices.

Adolescent↗

Rhabdomyosarcomas and radiation hypersensitivity in a mouse model of Gorlin syndrome.

Gorlin (or nevoid basal cell carcinoma) syndrome is characterized by a variety of clinical problems including generalized overgrowth of the body, cysts, developmental abnormalities of the skeleton and a predisposition to benign and malignant tumors. The syndrome results from germline mutations of the human homolog of the drosophila segment polarity gene patched (ptc). Here we report that mice heterozygous for ptc develop many of the features characteristic of Gorlin syndrome and that they exhibit a high incidence of rhabdomyosarcomas (RMS), the most common soft-tissue sarcoma in children. The downstream signalling partner of ptc, gli1, was overexpressed in all RMSs analyzed, indicating that abnormal signalling of the ptc-gli1 pathway may be common for the various tumors associated with the syndrome. igf2, implicated in the formation of RMSs, was also overexpressed, suggesting cross-talk between the ptc and igf2 pathways in tumorigenesis. Developmental defects in Gorlin syndrome resemble those induced by ionizing radiation. We show that ptc heterozygous mice exhibit increased incidence of radiation-induced teratogenesis. This suggests a role for ptc in the response to ionizing radiation and provides a model for both the systemic (developmental) and stochastic (cancer) abnormalities observed in Gorlin syndrome.

Animals↗

Influence of ischaemia-reperfusion injury on CD44 expression in rat small intestine.

BACKGROUND: CD44 is an adhesion molecule expressed by neutrophils and lymphocytes which is involved in cell-cell and cell-matrix binding. In this study, the effect of ischaemia-reperfusion injury on CD44 messenger RNA (mRNA) and cell surface immunohistochemical expression of CD44 in the rat small intestine was evaluated. METHODS: Wistar rats (n=16) were randomized to either serve as controls (sham surgery) or to be subjected to a standardized ischaemia-reperfusion injury (suprarenal aorta occluded for 1 h followed by 1 h of reperfusion). Standardized segments of jejunum were harvested after ischaemia-reperfusion injury (ischaemic and reperfused samples) to measure the mucosal protein and DNA content, mRNA expression of CD44 and the immunohistochemical expression of CD44. RESULTS: Reperfusion significantly damaged the jejunal mucosa, e.g. mucosal protein content was lower after reperfusion compared with that in the control group (z=-2.31, P=0.02) and the ischaemic samples (z=-2.52, P=001). The expression of cell surface CD44 protein was also significantly decreased after ischaemic injury (z=-1.99, P=0.04); this coincided with a decrease in the amount of cytoplasmic CD44 mRNA within isolated enterocytes (z=-2.31, P=0.02). CONCLUSION: Ischaemia-reperfusion injury decreases the expression of CD44 within the jejunal mucosa. This may contribute to the failure of the gut barrier after such injury.

Animals↗

Frozen-thawed epididymal sperm is effective for intracytoplasmic sperm injection: implications for the urologist.

OBJECTIVE: To evaluate the pregnancy potential of frozen-thawed surgically retrieved epididymal sperm when used with intracytoplasmic sperm injection (ICSI). PATIENTS AND METHODS: From August 1994 to January 1997, 20 thawed samples of sperm from 19 patients, surgically retrieved and frozen after percutaneous or open epididymal aspiration, were used for ICSI. The results were compared with those obtained using fresh sperm obtained at the same procedure. RESULTS: Of the specimens of surgically retrieved sperm which had been frozen, stored and thawed, 15 had sufficient motile sperm for use with ICSI. The fertilization, cleavage and pregnancy rates in those cycles were similar to the same couples' previous cycle using fresh sperm from the same collection and to the overall results in the NURTURE ICSI programme obtained with fresh epididymal sperm. CONCLUSION: Scrotal exploration for diagnostic testicular biopsy and/or reconstructive surgery without having access to sperm-freezing and storage facilities could represent a lost opportunity for the patient.

Adult↗

Failure to detect Chlamydia pneumoniae in atherosclerotic plaques of Australian patients.

Chlamydia pneumoniae is a recently reported, but common, respiratory tract pathogen. The organism has been detected by electron microscopy, immunocytochemistry, polymerase chain reaction (PCR) and recently culture within atherosclerotic plaques, suggesting a possible association between C. pneumoniae infection and atherosclerosis. Interestingly this association has not been found by all researchers. We examined 17 carotid endarterectomy specimens, 16 carotid arteries and 16 coronary arteries from autopsy specimens. They were examined by PCR for the presence of C. pneumoniae. In none of the 49 atherosclerotic samples examined was C. pneumoniae detected. The sensitivity of our PCR assay was rigorously tested and found to detect consistently fewer than ten elementary bodies. The association between C. pneumoniae and atherosclerosis is intriguing but has not yet been demonstrated in Australian patients.

Arteriosclerosis↗

The p53-mediated DNA damage response to ionizing radiation in fibroblasts from ataxia-without-telangiectasia patients.

PURPOSE: To assess the functionality of the p53-mediated pathway, activated by the ataxia-telangiectasia gene product (ATM) in response to ionizing radiation, in cells derived from four ataxia-without-telangiectasia patients. These patients exhibit cerebellar ataxia and cellular abnormalities that are compatible with the diagnosis of ataxia-telangiectasia (AT), but the telangiectasias normally seen in AT patients are absent. MATERIALS AND METHOD: Protein and RNA extracts were prepared from primary fibroblast cultures non- or exposed to 5 Gy of ionizing radiation in order to monitor the modulation in p53 and ATM protein levels by immunologic techniques and WAF1/Cip1(p21) mRNA by Northern blotting. RESULTS: A sub-optimal response in terms of increased levels of p53 and the transcriptional activation of WAF1/Cip1(p21) was see in the ataxia-without-telangiectasia fibroblast cultures examined over a 4 h period post-irradiation when compared with normal fibroblast cultures. The ATM protein was expressed at much reduced levels in the ataxia-without-telangiectasia and the classical AT fibroblast cultures examined when compared with normal fibroblast cultures. CONCLUSIONS: Despite the milder clinical phenotypes observed in these ataxia-without-telangiectasia patients and the presence of low levels of ATM protein in the fibroblast cultures, their response to ionizing radiation quantitatively resembles that reported in fibroblast cultures established from classical AT patients.

Ataxia↗

Correlation between intracellular cAMP content, kinematic parameters and hyperactivation of human spermatozoa after incubation with pentoxifylline.

Various compounds have been used in the attempt to improve sperm motility, including pentoxifylline (PF), a methylxanthine derivative. It has been postulated that PF, being a phosphodiesterase inhibitor, increases sperm kinematic parameters and the number of spermatozoa exhibiting hyperactivated motility by raising the intracellular content of cAMP, a molecule involved in the generation of sperm energy. However, it has not been clarified whether the biological effects of PF on sperm motility correlate with its ability to increase intracellular cAMP levels. To examine this relationship, the kinematic parameters, hyperactivation, and intracellular cAMP content were evaluated in motile spermatozoa, obtained by discontinuous Percoll gradient and swim-up from 21 normozoospermic semen samples, incubated without and with PF for 0, 1, 2, and 4 h. PF increased beat cross frequency after 1 and 2 h of incubation, curvilinear velocity and lateral head displacement (ALH) after 4 h, and hyperactivation after 1, 2, and 4 h, and decreased linearity (LIN) after 1 h of incubation. The intracellular cAMP content of spermatozoa incubated with PF increased at all time-points examined. Both intracellular cAMP content and increase in hyperactivation in response to PF decreased with the length of incubation. In the absence of PF, cAMP content was unchanged and was correlated significantly only with ALH and the percentage of spermatozoa with hyperactivated motility. Following incubation with PF, cAMP content correlated with hyperactivation and all sperm kinematic parameters, with the exception of LIN and straightness. These findings suggest that the beneficial effects of PF on sperm kinematic parameters and hyperactivation are related to its ability to increase intracellular cAMP content.

Cyclic AMP↗

The origin, effects and control of air pollution in laboratories used for human embryo culture.

Testing shows that most laboratories conducting human gamete and embryo culture have air quality and sources of contamination that exceed the levels measured in homes, businesses and schools. The sources of these contaminants have been shown to be either from activities outside the laboratory, or emitted from materials used in the facility, such as compressed gas, cleaning and sterilizing agents, plastic and stored materials. Both the laboratory structure and the air handling systems may affect the air composition. The significance of these findings is being validated by the accumulation of field case studies and now by assay procedures. Products given off by road sealant were shown to have accumulated in one of the examined laboratories, adjacent to a large re-surfaced parking area. Aldehydes such as acrolein, hexanal, decanal, pentanal and others were detected at elevated concentrations that were statistically significant. Since it is not appropriate to add potentially suspect chemicals to human embryos, we used a mouse-model to study the effect of acrolein. The growth of mouse embryos was significantly affected after acrolein was added at different concentrations to the culture environment. The physiological effect was noted at concentrations in the low ppm range. The testing end-point of embryo death must still be considered to be a crude basis for evaluating toxicological effects, since it involves addition of compounds to culture media and unprotected growth until the blastocyst stage. The findings may, however, support observations of decreased pregnancy rate following exposure of human embryos to aldehydes or other adverse conditions. With proper engineering and material selection, it is possible to reduce such contamination. The usefulness of this approach for controlling aldehydes has been demonstrated by decreasing levels in the laboratory to below those of the outside air.

Acrolein↗

The influence of ischemia/reperfusion injury on the jejunum.

Ischemia/reperfusion injury (IRI) after free tissue transfer of the small intestine results in transmural tissue damage. This study examined the effects of IRI on the jejunum. Wistar rats served either as controls (N=10) or underwent clamping of the infrarenal aorta for 1 hour followed by 1 hour of reperfusion (N=10). Both ischemia and reperfusion reduced the protein and deoxyribonucleic acid content of the jejunal mucosa (p < 0.05). Myeloperoxidase activity in the jejunal mucosa remained relatively low. The expression of leukocyte function-associated antigen 1 and intercellular adhesion molecule 1 (ICAM-1) on the surface of mucosal cells was not altered significantly by the ischemic insult, but was reduced after the period of reperfusion (p < 0.05). This coincided with an increase in messenger ribonucleic acid (mRNA) for ICAM-1 within isolated mucosal cells (p < 0.05). The specific activity of glutaminase in isolated jejunal mucosal cells was diminished after ischemia and reperfusion (p < 0.05), and this was not associated with an appreciable change in glutaminase mRNA expression. These results have identified some molecular mechanisms underlying IRI of the small intestine that are possible candidates for therapeutic intervention.

Animals↗

Taking a count: the evaluation of genetic testing.

While some forms of genetic testing have been available for decades, the progress of the Human Genome Project will expand the possibilities for testing. Evaluation of genetic testing is warranted because health care services have an opportunity cost and thus the benefits of testing must be assessed against the costs. However, genetic testing raises new methodological difficulties in taking into account the full range of costs, benefits and risks. The conventional approach to evaluating new technologies is to assess their benefits in terms of health outcomes only, and to consider the effects on the individuals being tested. Like any test, the product of genetic testing is information. Any subsequent health outcome gain depends on the effectiveness of any intervention which results from the information. Assessing the benefits in terms of health outcomes only excludes consideration of any value, both positive and negative, attached to information. The special feature of genetic testing is that the information obtained has implications for family members. This information may have value to relatives individually and may affect family interactions. Information also has value at a social level; it may affect social relationships and interactions. As the possibilities for genetic testing expand, it is likely that testing programs will be subject to economic evaluation. Until the methods and measures used can validly take this range of effects into account (and into a count of benefits), then the results of evaluation studies will be, at best, incomplete and, at worst, misleading.

Cost-Benefit Analysis↗

An NMR study of ligand binding by maltodextrin binding protein.

Proton NMR spectra of maltodextrin binding protein from Escherichia coli were used to monitor conformational changes that accompany ligand binding. Chemical shift changes associated with the binding of different maltodextrins to maltodextrin binding protein were studied using one-dimensional difference spectra. Line-shape analysis of an isolated upfield methyl resonance was used to measure the kinetics of maltose binding at several temperatures. Maltose and linear maltodextrins caused similar changes to the upfield protein spectrum with no detectable differences between alpha and beta sugar anomers. Binding of a cyclic ligand, beta-cyclodextrin, caused smaller chemical shift changes than binding of linear maltodextrins. Two maltodextrin derivatives were also studied. Both maltohexaitol and maltohexanoic acid gave one-dimensional difference spectra that were intermediate between those of linear maltodextrins and beta-cyclodextrin. The methyl resonances at -1 and -0.35 ppm were assigned to leucine 160 on the basis of homonuclear COSY and TOCSY experiments and theoretical chemical shift calculations using the X-ray crystal structure of maltodextrin binding protein.

Bacterial Proteins↗

Tinea nigra palmaris: differentiation from malignant melanoma or junctional nevi.

Tinea nigra usually presents as a brown to black macule on the palmar or plantar skin and is sometimes misdiagnosed as a malignant melanoma or as a junctional nevus, prompting unnecessary surgical procedures and anguish for the patient. Superficial scraping of the skin for microscopic inspection with potassium hydroxide reveals pigmented hyphae, easily confirming the diagnosis of tinea nigra.

Diagnosis, Differential↗