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Biomedical subjects

R Day

Publications and source records attributed to R Day.

At least 109 records · Page 6Linked to original sources
PubMed1997

Dominantly inherited cerebral dysplasia: arachnoid cyst associated with mild mental handicap in a mother and her son.

We report a mother and son who each presented in infancy with hypotonia and global developmental delay. Subsequently, in both subjects, mild mental handicap was diagnosed in association with temporal lobe arachnoid cysts. Mendelian inheritance of this phenotype seems likely and macroscopic cerebral dysplasia in general may be underdiagnosed in people with familial, mild mental handicap.

Adult↗
PubMed1997

Prohormone convertases in mouse submandibular gland: co-localization of furin and nerve growth factor.

Nerve growth factor (NGF) in mouse submandibular glands (SGs) is generated from a 35-kD precursor by proteolytic enzymes that have yet to be identified. Prohormone convertases (PCs) cleave the NGF precursor in vitro, and in this study we questioned whether PCs could process salivary NGF in vivo. mRNA coding for PC2 (but not PC1) was detected on Northern blots of SG mRNA and also by in situ hybridization within parasympathetic neurons of intralobular ganglia. Northern blot and in situ hybridization analyses also detect mRNA coding for furin. In SGs of male mice, furin mRNA levels are high at birth and remain high throughout development. In glands from female mice, levels decline during postnatal development and are lower in adults than in newborns. Immunocytochemistry detects furin immunoreactivity in pro-acinar and ductal cells of glands from newborn and pubescent mice. In glands of adults, furin immunoreactivity is detectable in acinar cells but highest levels are present in NGF-containing granular convoluted tubule cells. These data, taken together with those from previous studies, suggest that furin is a candidate processing enzyme for NGF in mouse submandibular glands.

Animals↗
PubMed1997

Does capsaicin affect the thermal sensation of males during immersion in 18 degrees C and 22 degrees C?

Animals respond to acute local or systemic administration of capsaicin with strong nociceptive reactions. The present investigation examined the thermal sensation in males who were given capsaicin (CAP, 2 mg x kg(-1) body weight) vs a placebo (PL, a maltodextrin capsule) before immersion in cold water. Seven Caucasian males ages 20-28 years were immersed in 18 degrees C and 22 degrees C twice (PL vs CAP) for 120 minutes. The following were examined: metabolism (VO2; L x min(-1)), rectal temperature (Tre; degrees C), and thermal sensation (TS). For VO2 there were no significant differences between treatments (PL vs CAP) when the variables were pooled jointly over the two immersion temperatures (18 degrees C and 22 degrees C) and across time. However, for Tre there were significant differences detected across time (p = 0.01) when Tre was pooled jointly across two treatments and two immersion temperatures. Postanalysis of variance revealed specific significant differences between 5 minutes (mean +/- SE; 37.2 +/- 0.07) and 120 minutes (36.0 +/- 0.09). For TS, there was a trend (p = 0.0699) which demonstrated differences between immersion temperatures only when TS was pooled jointly over the two treatments and across time, whereby TS was lower in 18 degrees C (6.2 +/- 0.5) than in 22 degrees C (3.7 +/- 0.6). From these data it appears that although Tre differed across time and temperature, respectively, a CAP feeding did not affect differentially the TS and metabolic response of males during acute cold water immersion.

Adult↗
PubMed1997

Socialization into nursing: nursing students as learners.

In this article, we describe how the functionalist and interactionist approaches to socialization are exemplified in the learning experiences of nursing students in a 4-year baccalaureate program. A qualitative longitudinal exploratory research design was used to study the socialization of baccalaureate nursing students in a large western Canadian university. The findings suggest that student learning reflects a combination of functionalist and interactionist approaches, with the relative emphasis of each approach varying over the 4 years. In the first year, functionalist learning predominates as students learn the "ideal." In second and third year, students are confronting and adapting to reality, which requires a more interactionist approach. Fourth year students look beyond their practice situation as they anticipate and prepare for a reality beyond the student world. This article concludes with implications for nursing education.

Adaptation, Psychological↗
PubMed1997

A pharmacological approach to acute pain.

A wide variety of analgesic drugs and techniques is available for the management of acute pain. Nurses are frequently expected to make choices in analgesic therapy. A good understanding of the actions of available drugs is needed by nursing and medical staff to provide optimum pharmacological pain relief. Education of health professionals is essential to promote the effective management of acute pain.

Acute Disease↗
PubMed1997

Efficacy of cisplatin, 5-fluorouracil, and paclitaxel regimen for carcinoma of the esophagus.

Eighteen patients with esophageal carcinoma (16 adenocarcinoma, two squamous cell carcinoma) were treated with two cycles of induction chemotherapy consisting of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) 175 mg/m2 (3-hour infusion), cisplatin 20 mg/m2/d x 4 days, and 5-fluorouracil 1 g/m2/d (continuous infusion x 4 days) separated by a 28-day interval before surgical resection. After resection, patients received two more cycles of the same regimen. A thorough staging evaluation was performed before patients were enrolled in the study. The salient chemotherapy toxicities included grade 3 nausea (two patients), grade 3 vomiting (two patients), grades 3 and 4 diarrhea (one patient each), and grades 3 and 4 neutropenia (two and 10 patients, respectively). No deaths occurred due to toxicity. Surgical resection was attempted in all 18 patients (100%) after two cycles of induction chemotherapy. Esophageal resection was successfully completed in 17 patients. Liver metastases were noted at laparotomy in the one patient who subsequently did not undergo esophageal resection. Surgical complications were minor, and no postoperative deaths occurred. Fifteen patients received two additional cycles of the paclitaxel/5-fluorouracil/cisplatin regimen postoperatively, two received only one cycle, and one refused further therapy. Of 15 patients alive, 14 show no evidence of disease. The 1-year actuarial survival rate of this group of patients is 82%. In conclusion, the paclitaxel/5-fluorouracil/cisplatin combination is well tolerated and is an active regimen in esophageal carcinoma.

Adenocarcinoma↗
PubMed1996

cDNA structure, tissue distribution, and chromosomal localization of rat PC7, a novel mammalian proprotein convertase closest to yeast kexin-like proteinases.

By using reverse transcription-coupled PCR on rat anterior pituitary RNA, we isolated a 285-bp cDNA coding for a novel subtilisin/kexin-like protein convertase (PC), called rat (r) PC7. By screening rat spleen and PC12 cell lambda gt11 cDNA libraries, we obtained a composite 3.5-kb full-length cDNA sequence of rPC7. The open reading frame codes for a prepro-PC with a 36-amino acid signal peptide, a 104-amino acid prosegment ending with a cleavable RAKR sequence, and a 747-amino acid type I membrane-bound glycoprotein, representing the mature form of this serine proteinase. Phylogenetic analysis suggests that PC7 represents the most divergent enzyme of the mammalian convertase family and that it is the closest member to the yeast convertases krp and kexin. Northern blot analyses demonstrated a widespread expression with the richest source of rPC7 mRNA being the colon and lymphoid-associated tissues. In situ hybridization revealed a distinctive tissue distribution that sometimes overlaps with that of furin, suggesting that PC7 has widespread proteolytic functions. The gene for PC7 (Pcsk7) was mapped to mouse chromosome 9 by linkage analysis of an interspecific backcross DNA panel.

Amino Acid Sequence↗
PubMed1996

Psychosocial and biological aspects of acute brief psychoses in three developing country sites.

This study explored biological as well as psychosocial contributions to the incidence of acute brief psychoses in three developing country sites. The samples were taken from the five year follow-up data of the International Pilot Study of Schizophrenia sites in Ibadan, Nigeria and Agra, India, and from the Determinants of Outcome of Severe Mental Disorders rural Chandigarh site. Baseline narratives of the cases and controls were reviewed and rated for presence or absence of three exposures: fever, departure from or return to parental village (women), and job distress (men). Results showed an association between fever and acute brief psychosis in all three sites. There was an association between acute brief psychosis and departure from or return to the parental village among women in all sites, and among men, an association between job distress and acute brief psychosis was noted in Ibadan and Agra. These findings suggest that psychosocial and biological factors such as these three exposures merit further research to clarify their roles in the etiology of acute brief psychoses.

Acute Disease↗
PubMed1996

Differential modulation of prohormone convertase mRNA by second messenger activators in two cholecystokinin-producing cell lines.

Regulation of prohormone convertase expression was studied in two neuropeptide-producing cell lines, the human neuroepithelioma cell line SK-N-MCIXC and the rat medullary thyroid carcinoma cell line WE 4/2. The cells were treated with the phosphodiesterase inhibitor isobutyl-methylxanthine and the tumor-promoting phorbol ester, phorbol-12-myristate-13 acetate, activators of the cyclic AMP (cAMP) and protein kinase C (PKC) second messenger pathways, respectively. mRNA levels of prohormone convertase 1 (PC1), prohormone convertase 2 (PC2), and furin were determined after 3- and 6-h treatments, using Northern analysis. Activation of both cAMP and PKC pathways increased PC1, but not PC2 or furin mRNA levels in SK-N-MCIXC cells. Activation of the cAMP pathway increased PC1, PC2, and furin mRNA levels in WE 4/2 cells, whereas activation of the PKC pathway did not change prohormone convertase mRNA levels in this cell line. These results indicate that prohormone convertases may be differentially regulated by cAMP and PKC mechanisms and regulation may be tissue specific.

1-Methyl-3-isobutylxanthine↗
PubMed1996

Anomalous perceptual asymmetries for negative emotional stimuli in the psychopath.

This study tested the hypothesis that when processing negative emotional material, psychopaths, compared with nonpsychopaths, would rely less on connotative-emotional processes based in the right hemisphere and more on denotative-linguistic processes based in the left hemisphere. Psychopathic and nonpsychopathic inmate groups, defined by their scores on the Psychopathy Checklist--Revised (R. D. Hare 1985), completed 2 analogous tachistoscopic tasks (words and faces). Accuracy and reaction times of inmates' responses in identifying which of 2 bilaterally presented stimuli (1 neutral and 1 emotional) was the emotional stimulus were measured. Significant lateral processing differences between the 2 groups emerged on the word task but not on the face task, providing partial support for the experimental hypothesis. Psychopaths also showed lower generalized emotional responsivity than nonpsychopaths on the Affect Intensity Measure.

Adult↗
PubMed1996

Cortical visual dysfunction in children: a clinical study.

Damage to the cerebral cortex was responsible for impairment in vision in 90 of 130 consecutive children referred to the Vision Assessment Clinic in Glasgow. Cortical blindness was seen in 16 children. Only 2 were mobile, but both showed evidence of navigational blind-sight. Cortical visual impairment, in which it was possible to estimate visual acuity but generalised severe brain damage precluded estimation of cognitive visual function, was observed in 9 children. Complex disorders of cognitive vision were seen in 20 children. These could be divided into five categories and involved impairment of: (1) recognition, (2) orientation, (3) depth perception, (4) perception of movement and (5) simultaneous perception. These disorders were observed in a variety of combinations. The remaining children showed evidence of reduced visual acuity and/ or visual field loss, but without detectable disorders of congnitive visual function. Early recognition of disorders of cognitive vision is required if active training and remediation are to be implemented.

Adolescent↗
PubMed1996

Hydroxychloroquine relative bioavailability: within subject reproducibility.

Six healthy volunteers received hydroxychloroquine sulphate 200 mg orally on four occasions (three tablets, one solution). Maximum hydroxychloroquine blood concentration (Cmax; range 135-422 ng ml-1) and time to maximum (tmax; range 1.5-7.0 h) for the three tablet doses showed significant differences between subjects (P < 0.009; between subject coefficients of variation (CVs) 34% and 27%, respectively). There were no within subject differences in Cmax (P = 0.32; mean within subject CV 11%), Cmax corrected for weight (P = 0.28) or tmax (P = 0.35; mean within subject CV 16%). Truncated areas under the hydroxychloroquine blood concentration-time curve of the three tablets were different between (P = 0.0001) but not within subjects (P = 0.13). Again, between subject CV (38%) was more than three times the mean within subject CV (12%). Bioavailability was not limited by tablet formulation. The significant variability in relative bioavailability between but not within individuals indicated that individualising dosing to target concentrations associated with optimal outcomes may minimise variability in response.

Adolescent↗
PubMed1996

Prohormone convertase PC5 is a candidate processing enzyme for prorenin in the human adrenal cortex.

We isolated a cDNA clone encoding the human prohormone convertase PC5 from human adrenal gland mRNA. The deduced protein sequence would encode a 915 amino acid preproPC5 that shares a very high degree of homology with previously cloned rat and mouse homologues. PC5 mRNA was detected in multiple human tissues, including the brain, adrenal and thyroid glands, heart, placenta, lung, and testes. PC5 mRNA was undetectable in the liver and was present at lower levels in skeletal muscle, kidney, pancreas, small intestine, and stomach. Co-transfection of human PC5 and human prorenin expression vectors in cultured GH4C1 cells led to secretion of active renin. The activation of human prorenin by PC5 depended on a pair of basic amino acids at positions 42 and 43 of the prorenin prosegment and occurred only in cells containing dense core secretory granules. Human PC5 was colocalized with renin by immunohistochemistry in the zona glomerulosa of the adrenal gland, suggesting that it could participate in the activation of a local renin-angiotensin system in the human adrenal cortex.

Adrenal Cortex↗
PubMed1996

Localization of sites of enhanced expression of endothelin-1 in the kidney of DOCA-salt hypertensive rats.

Although the role of endothelin-1, a potent vasoconstrictor peptide, in hypertension remains unclear, there is evidence of its involvement in deoxycorticosterone acetate (DOCA)-salt hypertensive rats, in which enhanced vascular production of endothelin-1 has been documented. The study presented here examined endothelin-1 gene expression in the kidney in DOCA-salt hypertensive rats by in situ hybridization histochemistry. A high specific activity 35S-labeled complementary RNA probe was used. Significant increases in abundance of endothelin-1 mRNA transcripts were found in the endothelium of renal vessels, and in capillary endothelial and mesangial cells of glomeruli of the remaining kidney of DOCA-salt hypertensive rats, in comparison with unilaterally nephrectomized control rats. Enhanced expression of the endothelin-1 gene in the kidney of DOCA-salt hypertensive rats may participate in abnormalities of renal function in this model of hypertension, and thus contribute to the development and maintenance of elevated blood pressure.

Animals↗
PubMed1996

Chemoradiotherapy in non-small cell lung cancer: paclitaxel/carboplatin/radiotherapy in regionally advanced disease.

Based on superior results observed with combined-modality therapy over radiotherapy alone and on the authors' previous work with carboplatin and standard daily thoracic radiotherapy in patients with advanced, unresectable non-small cell lung cancer, a phase II study was designed to incorporate radiosensitizing doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) into the carboplatin/radiotherapy regimen, to improve the therapeutic index and define the toxicities. Thirty-two patients have been entered. Paclitaxel 45 mg/m2/wk was administered over 3 hours prior to carboplatin (100 mg/m2/wk) and thoracic radiotherapy (1.8 Gy/d 5 days a week; total dose, 60 to 65 Gy). No grade 4 toxicities occurred. Seven patients had chemotherapy doses delayed because of grade 3 neutropenia, and one patient had grade 3 mucositis/esophagitis that required hospitalization. Median survival has not yet been reached, and all patients are being followed. These preliminary data demonstrate the feasibility of combined concurrent chemoradiotherapy, with acceptable toxicities. Further investigation is needed to optimize carboplatin dosage with adaptive control using formulas based on pharmacokinetics and pharmacodynamics. Full-dose induction chemotherapy regimens to maximize the systemic effects of chemotherapy should precede concurrent chemoradiotherapy in future studies.

Adult↗
PubMed1996

Carmustine and streptozocin in refractory melanoma: an attempt at modulation of O-alkylguanine-DNA-alkyltransferase.

The activity of the enzyme O6-alkylguanine-DNA-alkytransferase (AGAT) protects cells from the cytotoxic effects of alkylating agents. This Phase II trial was designed to assess the efficacy of a strategy designed to modulate the resistance to carmustine (BCNU) mediated by AGAT using streptozocin (STZ) in patients with advanced refractory melanoma. Seventeen patients who had failed prior chemotherapy were treated with STZ at 500 mg/m2 daily for 4 days with BCNU at 150 mg/m2 on day 3. Peripheral blood lymphocytes for assay of AGAT activity levels were collected prior to therapy and following the third dose of STZ. There were two partial responses in the 15 patients evaluable for response (13%). Most patients received only a single cycle of therapy due to rapidly progressive disease. Two patients developed fatal pulmonary toxicity, and one developed myelodysplasia. Other toxicities included transient rises in liver function tests. AGAT levels decreased by a mean of 53% in 9 patients but actually increased over baseline in 3 patients while on therapy. Based on these data, BCNU and STZ are not an effective combination for the therapy of advanced refractory melanoma, and pulmonary toxicity due to this combination appears to be increased compared with BCNU alone. STZ is not an effective modulator of AGAT activity when given on this schedule. New strategies designed to deplete AGAT activity using O6-benzylguanine or temozolomide should be explored with careful attention to the possibility that this approach may potentiate both the toxicity and efficacy of BCNU.

Adult↗
PubMed1995

An application of decision theory to patient screening for an autologous tumour vaccine trial.

Patients are eligible for accrual onto a phase I autologous tumour vaccine clinical trial if their resected and dissociated tumour achieves a minimum viable cell count. Because tumour pre-processing and cell count determination are expensive, there has been developed a screening procedure based on tumour mass to screen out those tumours unlikely to yield sufficient viable cells. If theta is the ratio of the expected benefit of an accrual onto the study to the cost of tumour pre-processing and cell counting, then we maximize long-run benefit by pre-processing and counting only those tumours whose masses exceed a cutoff mc, such that Pr(sufficient tumour cells masses = mc) = 1/theta. We derive algorithms for estimating mc and evaluate them under a variety of assumptions concerning the cell count/mass relationship. These include explicit equations for mc under parametric assumptions as well as more general algorithms based on non-parametric smoothing techniques. We show that when theta deviates substantially from 2, these methods outperform simple inverse interpolation.

Adenocarcinoma↗