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Biomedical subjects

E Campbell

Publications and source records attributed to E Campbell.

At least 19 recordsLinked to original sources

Androgen, estrogen, and progesterone receptors in normal and aging prostates.

Testicular hormones regulate the growth and development of the prostate. The presence of androgen receptors in prostatic tissue and their importance in the normal development of the prostate has been established. Age-related changes in the hormonal milieu, and perhaps steroid hormone receptor profile, could set in motion pathological changes leading to the onset of benign prostatic hyperplasia (BPH) or prostate cancer which primarily affect older men. The accumulation of dihydrotestosterone with age, the reawakening of the inductive potential of the prostatic stroma, the altered rate of apoptosis with age, and the age-related changes in the ratio of testosterone:estrogen have all been implicated in the etiology of BPH. In addition to androgen receptors, several studies have documented the presence of estrogen and progesterone receptors in BPH and prostate cancer. So far, most studies have focussed on the correlation between the presence/absence of steroid hormone receptors and response to hormonal therapy. The molecular mechanisms by which these steroid hormone receptors regulate the onset or progression of BPH and prostate cancer are not yet clear. The chronological changes in the levels and distribution of steroid hormone receptors in normal prostatic tissue and the effect of such changes on the synthesis of growth factors, growth factor receptors, and oncogenes should be investigated.

Aging

Inadequacy of visual alarms in helicopter air medical transport.

BACKGROUND: Air medical programs use medical equipment primarily designed for hospital and/or ground transport settings. Many of these medical devices are equipped with auditory alarms of malfunction or deteriorating clinical status. The high ambient noise requires visual scanning of medical devices to detect alarm conditions in the helicopter cabin. PURPOSE: To evaluate the adequacy of visual scanning for alarm conditions in the helicopter air medical environment. METHODS: The helicopter transport program used in this study is staffed with two medical crewmembers. Flight nurse response time (RT) to a visual alarm was assessed during 25 air medical patient flights. RT was measured using a battery powered dual timer device with a red LED visual alarm placed in a fixed position among the medical instruments. The device was activated at a random time point unknown to the medical crew during each patient flight. RT was defined as the elapsed time from activation of the alarm until it was physically switched off by the flight nurse. RESULTS: RT was surprisingly lengthy for the study population with a mean RT of 81.2 +/- 78.4 s (95% CI 48.8-113.5 s). The variability of RT was also surprising ranging from 3 s to > 5 min. CONCLUSION: RT to visual alarms in the air medical environment is lengthy and quite variable. Recognition of malfunction of medical equipment or early signs of clinical instability prior to clinical deterioration cannot be assured by visual scanning for alarm conditions. Alternative alarming systems should be considered and investigated for air medical transport.

Air Ambulances

Loin pain-hematuria syndrome: how effective is renal autotransplantation in its treatment?

OBJECTIVES: To evaluate our experience with renal autotransplantation in the management of loin pain-hematuria (LPH) syndrome after relatively long follow-up (30 to 35 months). METHODS: Four patients with LPH syndrome of 3 to 18 years' duration underwent technically successful autotransplantation. All patients preoperatively had normal radiologic investigations, including renal arteriography and biopsy. All required narcotic analgesia for pain control. Patients were followed for 30 to 35 months. RESULTS: All 4 patients were pain and narcotic free for 6 months postoperatively. At 18 months after surgery, 3 of the 4 had recurrence of the pain and at 30 months, 2 required nephrectomy. Only 1 patient of 4 had sustained pain relief at 35 months. CONCLUSIONS: Renal autotransplantation certainly offers temporary relief from LPH syndrome, but in our experience this was not durable in the majority of our patients.

Adult

A phase II trial of DaunoXome, liposome-encapsulated daunorubicin, in patients with metastatic adenocarcinoma of the colon.

CONTEXT: Liposomal encapsulation of drugs can potentially ameliorate toxicities and improve acute and chronic tolerance. The increased uptake of liposomes by colon adenocarcinoma cell lines may enable DaunoXome to circumvent the p-glycoprotein-mediated anthracycline resistance of colon cancer cells. PURPOSE: To determine if DaunoXome, liposome-encapsulated daunorubicin, has clinical activity in patients with adenocarcinoma of the colon who failed treatment with a 5-fluorouracil containing regimen. METHOD: In a Phase II trial, patients with metastatic adenocarcinoma of the colon, whose disease has progressed after receiving one 5-fluorouracil-containing regimen, were treated with DaunoXome 100 mg/m2 repeated every 3 weeks. RESULTS: In this trial 16 patients received 45 courses of therapy. No objective tumor responses were seen. Hematologic toxicities consisted of neutropenia (grade 3 and 4), grade 2 anemia, and grade 2 thrombocytopenia. Nonhematologic toxicities were mild and manageable. Of the 16 patients, 5 experienced flushing, shortness of breath, chest tightness, and back pain during DaunoXome infusion, which resolved with infusion interruption, diphenhydramine, and meperidine. CONCLUSIONS: DaunoXome is generally well tolerated at a dose of 100 mg/m2 every 3 weeks. Toxicities are mild and reversible. On this schedule DaunoXome does not have significant clinical activity in patients with metastatic adenocarcinoma of the colon who have progressed after one 5-fluorouracil-containing regimen.

Adenocarcinoma

Assignment of a human DNA double-strand break repair gene (XRCC5) to chromosome 2.

The Chinese hamster ovary (CHO-K1) cell mutant XRS-6 is defective in rejoining of DNA double-strand breaks and is hypersensitive to X-rays, gamma-rays, and bleomycin. Radiation resistance or sensitivity of somatic cell hybrids constructed from the fusion of XRS-6 cells with primary human fibroblasts strongly correlated with the retention of human chromosome 2 isozyme and molecular markers. Discordancies between some chromosome 2 markers and the radiation resistance phenotype in some of the hybrid cells suggested the location of the X-ray repair cross complementing 5 (XRCC5) gene on the p arm of chromosome 2. Introduction of human chromosome 2 by microcell-mediated chromosome transfer into the radiation-sensitive XRS-6 cells resulted in hybrid cells in which the radiation sensitivity was complemented. The chromosome 2p origin of the complementing human DNA in the microcell hybrids was supported by fluorescent in situ hybridization analysis of human metaphases using human DNA amplified from the hybrids by inter-Alu-PCR as chromosome-painting probes. XRCC5 is therefore provisionally assigned to human chromosome 2p.

Animals

The effects of patterned urge-response toileting (PURT) on urinary incontinence among nursing home residents.

OBJECTIVE: To test an individualized form of habit training for urinary incontinence (UI) among long-stay cognitively and/or physically impaired elderly nursing home residents over time. DESIGN: Randomization of subjects occurred by nursing home unit. Baseline wet checks were done hourly for one 24-hour period at 3-week intervals over 12 weeks followed by 72 hours of continuous electronic monitoring to establish precise voiding patterns for each subject. The 12-week intervention period was administered by indigenous staff after they attended a 4-hour UI educational program. Subjects were followed an additional 12 weeks to determine the extent of maintenance of the intervention among staff and subjects. SETTING: Four non-profit nursing homes; west, mid-west, east coast. PATIENTS: Consent was obtained from 154 (71%) who met primary inclusion criteria. Forty-one failed the secondary inclusion criteria leaving 113 who entered the 37-week study. Eighty-eight completed the study (experimental = 51, control = 37); all were physically and/or mentally impaired, averaged age 85, and had either urge or urge/stress UI. RESULTS: UI was significantly decreased during the 3-month period (P less than 0.001). Eighty-six percent showed improvement over baseline while one-third improved 25% or more over their baseline UI rate. The control group's UI increased during the same period of time. The volume of UI among the experimental group also decreased (P less than 0.005) while the control group's UI volume increased. CONCLUSIONS: The training program was effective in reducing UI though compliance among nursing staff averaged only 70% of the prescribed toileting times. The success of this approach is similar to other recently described behavioral programs but achieved the reduction using only regular nursing staff. This individualized approach supports the recent regulatory thrust to individualize care to promote and maintain functional abilities and autonomy.

Activities of Daily Living

Localization in human interleukin 2 of the binding site to the alpha chain (p55) of the interleukin 2 receptor.

Human interleukin 2 (IL-2) analogs with defined amino acid substitutions were used to identify specific residues that interact with the 55-kDa subunit (p55) or alpha chain of the human IL-2 receptor. Analog proteins containing specific substitutions for Lys-35, Arg-38, Phe-42, or Lys-43 were inactive in competitive binding assays for p55. All of these analogs retained substantial competitive binding to the intermediate-affinity p70 subunit (beta chain) of the receptor complex. The analogs varied in ability to interact with the high-affinity p55/p70 receptor. Despite the lack of binding to p55, all analogs exhibited significant biological activity, as assayed on the murine CTLL cell line. The dissociation constants of Arg-38 and Phe-42 analogs for p70 were consistent with intermediate-affinity binding; the Kd values were not significantly affected by the presence of p55 in binding to the high-affinity IL-2 receptor complex. These results confirm the importance of the B alpha-helix in IL-2 as the locus for p55-receptor binding and support a revised model of IL-2-IL-2 receptor interaction.

Amino Acid Sequence

Tissue expanders in children.

Tissue expanders are particularly applicable in the pediatric population. They are extremely well tolerated by children and can withstand the everyday play and trauma unique to children. Over the past 2 years, we have used 26 tissue expanders in 17 pediatric patients. Fifteen of the 17 patients successfully underwent reconstructive surgery with the aid of expanders. The expander became exposed in two patients, necessitating removal. In each of these patients, a more complicated and less satisfactory method of reconstruction was performed.

Adolescent

Issues in implementing clinical research in nursing home settings.

Researchers at four nursing home sites experienced similar problems in the informed consent process when they attempted to access a frail, cognitively impaired population to conduct a collaborative, quasi-experimental two year clinical trials study on urinary incontinence. In addition, similar institutional barriers were experienced in these geographically distant and dissimilar nursing homes. The study involved working closely with indigenous licensed nursing and nurse aide staff to implement the independent variable, an individualized toileting prescription. Successful strategies used to overcome barriers in conducting the research will be described.

Aged

Does infant feeding method influence maternal postpartum weight loss?

We conducted a retrospective study of 411 women to determine whether a significant relationship existed between method of infant feeding (breast vs bottle) and postpartum weight loss at 6 weeks and 12 months. In addition to method of infant feeding, the variables parity, gravidity, mode of delivery, maternal age, maternal prepregnancy weight, infant sex, and payment status (whether receiving assistance from the Aid to Dependent Children [ADC] program) were studied in terms of their association with weight loss. In general, no consistent relationship was found between method of infant feeding and postpartum weight loss. However, in the ADC group at 6 weeks and in the non-ADC group at 12 months, nonlactating women had lost more weight than had their lactating counterparts, in spite of the theoretical energy deficiency of breast-feeding women. Women who gained more weight during pregnancy consistently lost more weight following delivery, regardless of their prepregnancy weight. These results indicate that infant feeding method was not related to differences in postpartum weight loss between lactating and nonlactating counterparts.

Adolescent

Breast self-examination and breast examination by a health care provider: prevalence and predictors of screening in a randomly selected sample of Australian women.

Professional organizations recommend the practice of monthly breast self-examination (BSE), and examination of the breasts by a health care provider every three years for women up to the age of 40 and annually thereafter. These practices were examined in a randomly selected sample of 1454 women. Only 39% (95% confidence interval [CI], 36%-42%) of the sample reported monthly BSE. Women were more likely to examine their breasts each month if they had found a breast lump, believed they were likely to get breast cancer, were not single, or were frequent users of general practitioners. Only 51% (95% CI, 45%-53%) of women under the age of 40 reported receiving three-yearly breast examinations; of those women aged 40 or more, 31% (CI, 27%-35%) of those with no additional risk factors and 35% (95% CI, 27%-42%) of those with at least one additional risk factor reported annual examinations. Women were more likely to have received a breast examination in the past three years if they had previously had a breast lump, were not single, had reached a higher educational level, were more frequent users of general practitioners, had private health insurance, or were described as other than ill or retired. There was a substantial association between BSE and breast examination by a health care provider with 25% (95% CI, 23%-27%) practising BSE and being screened by a health care provider. Thirty-five per cent (95% CI, 32%-38%) of women were not being screened by either method. The implications of the results for health education campaigns are discussed.

Adolescent

A distinct human testis and brain mu-class glutathione S-transferase. Molecular cloning and characterization of a form present even in individuals lacking hepatic type mu isoenzymes.

mu-Class glutathione S-transferases (GSTs) were identified in all 13 human testes and 28 brains examined; even subjects whose livers were devoid of mu-GSTs expressed extrahepatic GSTs of this class. Testes and brains from individuals with mu-class GSTs in their livers had additional forms that also reflected the liver phenotypes. An isoenzyme with an isoelectric point of 5.2, which was a major GST in testis and present as well in cerebral cortex but not detected in any livers, was identified and purified. Sequence analysis of peptides derived by cleavage of the testicular mu-class GST by Achromobacter protease I revealed distinct aspects of primary structure not found previously in any mammalian mu-class GSTs. These unique features included a blocked and extended amino terminus and 3 additional residues (Pro-Val-Cys) at the carboxyl terminus. This structure was confirmed by molecular cloning and sequencing of cDNAs derived from human testis and brain libraries. In the coding region the mRNA of the brain-testis mu-class GST was 75% homologous with that of the liver form, and its 3'-untranslated sequence was mostly divergent, indicating that it is the product of a separate gene. Distinct catalytic and structural properties of the testis-brain mu-class GSTs suggest that these GSTs may be uniquely involved in blood-barrier functions common to both organs.

Adolescent

Clinical and histopathologic findings in adults with the nephrotic syndrome.

The clinical and histopathologic findings in 225 Irish adults with nephrotic syndrome were reviewed. Membranous nephropathy was the most common lesion found (28%), followed by proliferative glomerulonephritis (17%), and focal sclerosing glomerulonephritis (16%). Minimal change disease was the least frequent cause for idiopathic nephrotic syndrome (12%). The major secondary cause of nephrotic syndrome was amyloidosis (13%). The patients were analysed for the predictive value of the level of renal function, presence or absence of hypertension, and the degree of proteinuria. It was not possible to determine the nature of the underlying lesion giving rise to the nephrotic syndrome using any of these variables. There was also no significant difference between primary and secondary glomerular disease with regard to these factors. It is concluded that renal biopsy remains the only definitive method of establishing the underlying lesion causing idiopathic nephrotic syndrome.

Adolescent

The rate of rise of corticotrophin releasing factor and endogenous digoxin-like immunoreactivity in normal and abnormal pregnancy.

Maternal plasma concentrations of corticotrophin releasing factor (CRF) and endogenous digoxin-like immunoreactivity (EDLI) were estimated in 80 normal and 88 abnormal pregnancies which were sampled sequentially from 24 weeks gestation to delivery. A slope was fitted for each woman's antenatal EDLI and CRF values, both of which rose significantly during gestation, and the mean of the slopes for the normal and abnormal groups for each value compared. There was no evidence of significant mean differences between groups for EDLI but there was evidence of a significant mean difference for CRF (P less than 0.05). After adjustment for other variables which may affect pregnancy outcome, the slopes for CRF were found not to be significantly related to outcome.

Corticotropin-Releasing Hormone