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Biomedical subjects

K Mitchell

Publications and source records attributed to K Mitchell.

At least 37 records · Page 2Linked to original sources
PubMed2001

Community-based HIV/AIDS education in rural Uganda: which channel is most effective?

A process evaluation was conducted to evaluate four channels (drama, video, community educators and leaflets) used in a community-based IEC (Information, Education and Communication) HIV/AIDS intervention in rural Uganda. Semi-structured interviews (n = 37) and focus groups (n = 3) were held with community members working as field staff. In addition, two questionnaire surveys (n = 105 and n = 69) and eight focus groups were conducted with the target community. Over 85% of the community had seen at least one drama or video show. They rated them as relevant and realistic. However, the messages 'taken home' were not always those intended by the plays. Access to community educators (CEs) was not equal. The CEs had a tendency to avoid the educated, rich and their older relatives. Those who had met with a CE rated them as knowledgeable and trustworthy, but felt they would rather be taught by a trained health worker. Around 80% of the community said they had seen the leaflets, but had not necessarily read them. Although appreciated by some as reference material, low literacy levels and a lack of reading culture meant that some leaflets may have gone astray. These findings suggest that a multi-channel approach may be required to overcome weaknesses inherent in individual channels.

Community Health Services↗
PubMed2001

The acceptability of urinary LCR testing for Chlamydia trachomatis among participants in a probability sample survey of sexual attitudes and lifestyles.

OBJECTIVES: To examine the factors that influence respondents' willingness to participate in urinary testing for Chlamydia trachomatis in a general population feasibility survey of sexual attitudes and lifestyles. METHODS: 199 sexually experienced, 18-44 year old participants, recruited as part of a larger (n=901) methodological study of sexual attitudes and lifestyles, were invited to provide a urine sample for chlamydial infection testing using ligase chain reaction (LCR) techniques. Analysis of the survey data and in-depth qualitative interviews were undertaken to explore the factors that influenced participants' decisions to participate. RESULTS: 143/199 (72%) participants agreed to provide a urine sample. The likelihood of providing a urine sample was reduced if other individuals were present in the home at the time of interview (OR 0.42, 95% confidence interval 0.20-0.90, p=0.03). Trust and rapport with the interviewer, understanding the aims of the test, sense of obligation, and perceived importance of the test were identified as additional influencing factors in the in-depth interviews. CONCLUSIONS: Survey respondents' uncertainty or embarrassment at participating in urine testing can be overcome if they are well informed, motivated by the potential health gain, and briefed by trained and confident interviewers.

Adolescent↗
PubMed2001

Analysis of the contribution of dydrogesterone to bone turnover changes in postmenopausal women commencing hormone replacement therapy.

Although gestagens have been reported to influence bone metabolism, whether these contribute to the beneficial effects of hormone replacement therapy (HRT) on the skeleton of postmenopausal women is currently unclear. To address this question, we compared changes in bone turnover markers after commencing HRT in 26 postmenopausal women randomized to receive 8 weeks of treatment with 2 mg estradiol daily or 2 mg estradiol plus 10 mg dydrogesterone daily. Serum and second morning void urine samples were obtained at baseline (twice) and after 1, 2, 4, and 8 weeks. Serum estradiol was measured by RIA, urinary total deoxypyridinoline (DPD) excretion by high pressure liquid chromatography, and serum osteocalcin and C-terminal procollagen peptide by enzyme-linked immunosorbent assay. The increase in serum estradiol after treatment with estradiol alone was slightly, but significantly, greater than that in the combination group (P = 0.04). Although estradiol suppressed urinary DPD excretion to a greater extent when given alone (P = 0.02), osteocalcin levels were significantly higher in this group than in women receiving combination therapy (P = 0.04). To assess the effect of dydrogesterone on the balance between formation and resorption in more detail, we subsequently compared the ratio between formation and resorption markers in the two treatment groups. We found that osteocalcin/DPD and C-terminal procollagen peptide/DPD ratios were significantly higher in women treated with estradiol alone (P < 0.0001 and P = 0.002, respectively), suggesting that dydrogesterone may reduce formation relative to resorption. These results suggest that gestagens may reduce estrogen's beneficial effects on the skeleton of postmenopausal women, as assessed over the first 8 weeks of replacement therapy.

Amino Acids↗
PubMed2001

Age-specific incidence of cancer in Kingston and St Andrew, Jamaica, 1993-1997.

A total of 4285 malignant neoplasms were recorded in Kingston and St. Andrew during the period 1993-1997, 2344 in females and 1941 in males. The crude incidence rate per 100,000 (CIR) for males was 121.6 and for females 129.2. Age standardized rates per 100,000 (ASR) were 156.7 and 176.7 for males and females respectively. In males, the leading sites for cancer were prostate (619 cases), bronchus (265 cases) and large bowel (144 cases) while in females the leading sites were breast (627 cases) cervix uteri (376 cases) and large bowel (204 cases). The crude and age standardized incidence rates have remained stable as compared to those for the previous five year period (1998-1992). The leading sites for both males and females have also been maintained in the same order but there was a marked increase in prostate cancer (ASR 56.4 versus 36). Invasive cervical cancer has shown no significant change in incidence (ASR 25.2 versus 26.3) but the rate for in-situ cancers has decreased (ASR 27.4 versus 43.8). The incidence of cancer of the female breast has remained relatively stable (ASR 43.2 versus 47.1). The trends exhibited by both prostate cancer and in-situ cervical cancer probably represent the influence of screening methods for prostate cancer and ablative management for low grade dysplastic lesions of the cervix uteri respectively.

Adult↗
PubMed2000

A comparison of apoptosis and necrosis induced by hepatotoxins in HepG2 cells.

7H-Dibenzo[c,g]carbazole (DBC), an N-heterocyclic aromatic hydrocarbon, is cytotoxic and carcinogenic in rodent liver. While DBC leads to necrotic lesions in the liver, the induction of apoptosis by DBC has not been investigated. The focus of this study was to determine the degree to which apoptosis and necrosis contributed to DBC cytotoxicity in a human hepatoma cell line (HepG2). To determine if these effects were unique to DBC, the results were compared to another hepatotoxin, aflatoxin B(1) (AFB(1)). DBC produced a distinct biphasic LDH release curve within 24 h of exposure. During the same time period lower concentrations of DBC (<10 microM) induced the formation of DBC-DNA adducts and increased p53 protein levels followed by apoptotic cell death. However, increasing the concentration of DBC to 80 microM led to lower DNA adduct and p53 protein levels. At this concentration, intracellular ATP levels were rapidly depleted followed by cell swelling and loss of membrane integrity consistent with necrotic cell death. In contrast to DBC, a biphasic LDH release curve was not observed for AFB(1). Instead, AFB(1) induced a concentration-dependent increase in apoptosis that reached two- to threefold higher levels than DBC. These results suggest that differences exist in the extent and type of cell death induced by DBC and AFB(1) at equimolar concentrations. Apoptosis and necrosis result from low and high concentrations of DBC, respectively, and may be dependent upon intracellular ATP levels.

Adenosine Triphosphate↗
PubMed2000

Expression of human papilloma virus E7 protein causes apoptosis and inhibits DNA synthesis in primary hepatocytes via increased expression of p21(Cip-1/WAF1/MDA6).

The impact of human papilloma virus (HPV16) E7 proteins and retinoblastoma (RB) antisense oligonucleotides upon mitogen-activated protein kinase (MAPK)-mediated inhibition of DNA synthesis via p21(Cip-1/WAF1/MDA6) (p21) was determined in primary hepatocytes. Prolonged activation of the MAPK pathway in p21(+/+) or p21(-/-) hepatocytes caused a large decrease and increase, respectively, in DNA synthesis. Either transfection with RB antisense oligonucleotides, expression of wild type E7, or RB binding mutant E7 (C24S) proteins increased p21 levels and reduced DNA synthesis in p21(+/+) hepatocytes. RB antisense oligonucleotides and E7 proteins increased apoptosis in p21(+/+), but not p21(-/-), hepatocytes. Expression of wild type E7 increased DNA synthesis above control levels in p21(-/-) cells, which was additive with prolonged MAPK activation. In contrast, expression of mutant E7 did not alter DNA synthesis above control levels in p21(-/-) cells and was supra-additive with prolonged MAPK activation. Antisense ablation of RB in p21(-/-) hepatocytes had a weak stimulatory effect upon DNA synthesis itself but enhanced the capacity of mutant E7 protein to stimulate DNA synthesis to the same level observed using wild type E7. The ability of prolonged MAPK activation to stimulate DNA synthesis in the presence of mutant E7 and antisense RB was additive. Collectively, the present data demonstrate that loss of RB function together with loss of p21 function plays an important role in the E7- and MAPK-dependent modulation of apoptosis and DNA synthesis in primary hepatocytes.

Animals↗
PubMed2000

The neurofibromatosis type 1 (Nf1) tumor suppressor is a modifier of carcinogen-induced pigmentation and papilloma formation in C57BL/6 mice.

There is increasing evidence implicating the human NF1 gene in epithelial carcinogenesis. To test if NF1 can play a part in skin tumor formation, we analyzed effects of the skin cancer initiator dimethylbenz-anthracene and/or the tumor promoter 12-O-tetradecanoyl-13-acetylphorbol on mice heterozygous for null mutations in Nf1 (Nf1+/-). Mice were on the C57BL/6 background, noted for resistance to chemical carcinogens. Nf1+/- mice (18 of 24) developed papillomas after treatment with dimethylbenzanthracene and 12-O-tetradecanoyl-13-acetylphorbol; papillomas did not develop in wild-type C57BL/6 mice nor Nf1+/- mice treated with 12-O-tetradecanoyl-13-acetylphorbol alone. All papillomas analyzed (six of six) had mutations in codon 61 of H-ras, demonstrating strong cooperation between the Nf1 GTPase activating protein for Ras, neurofibromin, and Ras-GTP. After exposure to 12-O-tetradecanoyl-13-acetylphorbol, Nf1+/- keratinocytes showed significant, sustained, increases in proliferation, implicating Nf1 in phorbol ester responsive pathways. Thus, Nf1 levels regulate the response of keratinocytes to 12-O-tetradecanoyl-13-acetylphorbol. Nf1+/- mice also showed a 2-fold increase in the development of pigmented skin patches stimulated by dimethylbenzanthracene; patches were characterized by hair follicles in anagen phase, implicating keratinocytes in the aberrant hyperpigmentation. Our results show that mutation in the Nf1 gene causes abnormal keratinocyte proliferation that can be revealed by environmental assaults such as carcinogen exposure. The data support a plausible role for NF1 mutation in human epithelial carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2000

Patient-initiated hospital follow-up for rheumatoid arthritis.

OBJECTIVES: To evaluate the clinical efficacy, cost and acceptability of a shared care system of patient- or general practitioner (GP)-initiated hospital review in rheumatoid arthritis (RA). METHODS: A 2-yr randomized controlled trial of routine rheumatologist-initiated review was compared with a shared care system. Shared care patients had no routine follow-up but patients or GPs initiated access to rapid review by the multidisciplinary team via a nurse-run helpline. Control patients had a rheumatologist-initiated medical review at intervals of 3-6 months. Clinical and psychological status, resource use, and patient and GP satisfaction and confidence were assessed. Three-monthly clinical data were assessed (blind) for safety monitoring, with failure set at a 20% increase in pain, disability or disease activity. RESULTS: Two hundred and nine established RA patients participated, of whom 182 were evaluable. Safety-net failures were not different between groups. Shared care patients had less pain (24 months, 3.9 cm on a 10-cm visual analogue scale vs 4.8 cm for controls; P: < 0.05), a smaller increase in pain over 2 yr (+ 0.4 cm vs +1.6 cm for controls; P: < 0.01), greater self-efficacy (6, 15, 18, 21 months, P: < 0.05), used 33.5% less resources (208 ponds sterling per patient per year vs 313 pound sterling for controls; P: < 0.001) and were more confident in the system (6, 9, 12, 18, 21, 24 months, P: < 0.01 to P: < 0.001). CONCLUSIONS: A patient-initiated system for hospital review over 2 yr offers some clinical benefit compared with the traditional system, using fewer resources and attracting greater patient confidence. Longer-term assessment of the system would be appropriate.

Aged↗
PubMed2000

In the steps of giants: the early geriatrics texts.

This article briefly reviews some of the major early geriatric textbooks of the last two centuries. Among the more important are books by George Day, Charcot, Nascher, Worcester, and Cowdry. Lord Amulree's book Adding Life to Years has become a watchword of modern geriatrics. It is of interest that during this time period the basic plea for high touch care of older patients and the lament that physicians have little knowledge of the needs of older patients has remained remarkably constant.

Geriatrics↗
PubMed2000

Effect of early emptying on quantitation and interpretation of liquid gastric emptying studies of infants and young children.

UNLABELLED: This study assesses the effect of emptying that occurs during feeding on quantitation and interpretation of liquid gastric emptying studies of infants and young children. METHODS: Forty-nine 99mTc-sulfur colloid liquid gastric emptying studies of 44 children (22 boys, 22 girls; mean age, 20 mo; age range, 2-46 mo) fed orally or by gastrostomy tubes were evaluated. Gastric residuals quantitated by 2 commonly used methods, the first of which does not account for early emptying and the second of which does, were compared. With the first method, residual relative to activity in the stomach at the start of imaging (Rg) was quantified by comparing activity in a region of interest (ROI) drawn about the stomach on the final image to activity in an ROI drawn about only the stomach at the start of imaging. With the second method, residual relative to total dose (Rt) was quantified by comparing activity in the same final ROI to activity in an ROI that included stomach and small bowel at the start of imaging. Studies were interpreted independently for Rg and Rt considering a value >70% as evidence of delayed emptying. RESULTS: Rt was lower than Rg by 15%-16% for the entire population, for patients fed orally, and for patients fed by gastrostomy tube. These differences reached statistical significance (P < 0.0001). In 31 of 49 studies, R1 was lower than Rg by > or =10%. In 8 studies, emptying classified as delayed on the basis of Rg was classified as nondelayed on the basis of Rt. Clinical decisions based on Rt did not require later management changes that would have indicated that treatment of gastric dysmotility had been postponed in any patient. CONCLUSION: Emptying that occurs during feeding should be factored into quantitation of liquid gastric emptying in infants and young children. Not recognizing and accounting for early emptying results in overestimated gastric residuals and can lead to classification of emptying as delayed in children whose residuals of the total administered dose are within a recognized range of normal.

Case-Control Studies↗
PubMed2000

Reproducibility of renal length measurements with 99mTc-DMSA SPECT.

UNLABELLED: Renal length measurements are used in evaluating several abnormalities of the pediatric genitourinary tract. This study assesses reproducibility of renal length measurements obtained with 99mTc-dimercaptosuccinic acid (DMSA) SPECT. METHODS: The lengths of 98 kidneys of 51 children (age range, 1-16 y; mean age, 5.4 y) who underwent 99mTc-DMSA SPECT were measured independently by 2 observers. Renal length was calculated by converting pixels between points at the superior and inferior renal margins on a summated coronal image to centimeters. Lengths were measured for kidneys as they appeared in situ and after realignment along their long axes. SPECT reconstruction, choice of display parameters, positioning of points used for measuring, and alignment were performed independently by each observer. Interobserver variability, interobserver correlation, and mean differences between observers' measurements (expressed as measurement of observer 2 - measurement of observer 1) were calculated. RESULTS: Correlation between the observers' measurements was highly significant for both nonaligned and aligned studies (r = 0.95 and 0.97, respectively; both, P < 0.0001). Interobserver variability expressed as 1 SD was 3.6 mm for nonaligned studies and 2.8 mm for aligned studies. The mean difference between the 2 observers' measurements for nonaligned studies was 2.0 +/- 4.8 mm (P < 0.0001) with a range of -11 to 14 mm. For aligned studies the mean difference between the 2 observers' measurements was -0.1 +/- 4.0 mm (P = 0.88) with a range of -20 to 10 mm. Differences between observers were not dependent on absolute renal length (P = 0.68 for nonaligned studies; P = 0.40 for aligned studies). CONCLUSION: The variability in renal length measurements determined by 99mTc-DMSA SPECT is similar to that reported previously using sonography. Because the interobserver differences in renal length are similar to annual renal growth rates during childhood, caution should be applied when incorporating renal length measurements determined by 99mTc-DMSA SPECT into management algorithms. Additional studies are required to further establish interobserver variability, to assess intraobserver variability, and to evaluate means of improving standardization.

Adolescent↗
PubMed2000

A phase II study of razoxane, an antiangiogenic topoisomerase II inhibitor, in renal cell cancer with assessment of potential surrogate markers of angiogenesis.

Renal cell carcinoma (RCC) is an angiogenic tumor resistant to standard cytotoxic chemotherapeutic agents. Although often responsive to immunomodulatory agents including interleukin 2 and IFN-alpha, the overall results in randomized Phase III studies are disappointing with only modest improvements in overall survival. This Phase II study evaluated the efficacy and tolerability of razoxane, an antiangiogenic topoisomerase II inhibitor, in 40 patients (32 men, 8 women; age: range, 31-76 years; median, 58 years) with inoperable RCC. Twenty patients received razoxane 125 mg p.o., twice a day for 5 days each week for 8 weeks (one cycle). This was repeated in patients with stable disease (StD), but was discontinued after 16 weeks if there was no evidence of an objective response. Because minimal toxicity was seen, subsequent patients (n = 20) were treated until progressive disease (PD) was documented. Of 38 evaluable patients, 11 (29%) had StD for a minimum of 4 months, and the remainder had PD. Median overall survival was 7.3 months. Duration of survival was significantly better in patients with StD compared with those with PD (P = 0.003). The effect of treatment on six potential surrogate serum/plasma (vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), urokinase plasminogen activator soluble receptor (uPAsr), E-selectin, vascular cell adhesion molecule-1 (VCAM-1) and von Willebrand's factor (vWF) and two urinary (VEGF and bFGF) markers of angiogenesis was evaluated before and after 1 cycle of treatment. Pretreatment serum VEGF and E-selectin levels above the median value were associated with a poor prognosis. Serum VCAM-1 levels and urinary VEGF levels rose significantly after one cycle in patients with PD but not in those with StD. Serum VEGF, bFGF, VCAM-1 and vWF, plasma uPAsr and urinary bFGF levels were significantly higher in PD patients compared with StD patients before and/or after 1 cycle of treatment. In conclusion, razoxane is an antiangiogenic agent that has minimal toxicity and that requires further evaluation in combination with other active agents in the treatment of RCC. Surrogate serum and urinary markers of angiogenesis may have a role to play in predicting disease response and overall survival in RCC.

Adult↗
PubMed1999

Phase II study of RC-160 (vapreotide), an octapeptide analogue of somatostatin, in the treatment of metastatic breast cancer.

RC-160 (octastatin/vapreotide) is a potent octapeptide analogue of somatostatin with growth inhibitory activity in experimental tumours in vitro and in vivo, including breast cancer. We evaluated the efficacy and tolerability of high-dose RC-160, 3 mg day(-1) on week 1 increased to 4.5 mg day(-1) for weeks 2-4 and subsequently 6 mg day(-1) until the end of treatment, administered by continuous subcutaneous infusion in the management of 14 women with previously treated metastatic breast cancer. The age range was 37-80 years (median 58.5 years) and performance status 0-2. The treatment was well tolerated with no dose reductions being required. No grade 3 or 4 toxicities were seen. Abscess formation developed at the infusion site in eight patients and erythema and discomfort was seen in a further three patients. A significant reduction in IGF-I levels occurred by day 7 and was maintained throughout the treatment. The lowest dose of RC-160 produced the maximal IGF-I response. Although there was no reduction in prolactin levels in patients whose baseline levels were normal, elevated prolactin levels found in three patients fell to within the normal range 7 days after commencing RC-160 treatment. A small but significant rise in fasting blood glucose levels was also recorded, the highest level on treatment being 7.6 mmol l(-1). No objective tumour responses were observed, all patients showing disease progression within 3 months of commencing treatment. These findings demonstrate that high-dose RC-160, administered as a continuous subcutaneous infusion, can reduce serum levels of the breast growth factors IGF-I and prolactin but is ineffective in the management of metastatic breast cancer. Encouraging preclinical anti-tumour activity and the favourable toxicity profile in patients suggest the merit of future studies combining RC-160 with anti-oestrogen, cytotoxic and anti-angiogenic agents.

Adult↗
PubMed1999

A pilot study of increasing dose intensity of epirubicin and ifosfamide in patients with small cell lung cancer by using recombinant granulocyte colony-stimulating factor.

The aim of this prospective study was to investigate the feasibility of increasing the dose intensity of chemotherapy in patients with small cell lung cancer (SCLC) by using recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF). Seventeen previously untreated patients (11 male, 6 female) were treated with ifosfamide (5.0 g/m2) and epirubicin (80 mg/m2) in two successive cohorts. Eight patients received chemotherapy every 2 weeks and r-metHuG-CSF 5 microg/kg given subcutaneously daily for 10 days (cohort A), and nine patients received chemotherapy at 10-day intervals with r-metHuG-CSF 5 microg/kg subcutaneously given daily for 7 days (cohort B). The relative dose intensity compared with the conventional 3-weekly regimen was 1.5 and 2.1 for cohorts A and B, respectively. Neutropenia-associated fever complicated two and five treatment courses in cohorts A and B, respectively. There were five episodes of grade 3/4 thrombocytopenia. There were no treatment delays in cohort A and one cycle was delayed in cohort B. One patient from each cohort was withdrawn due to toxicity. Grade 3/4 non-haematological toxicity, other than alopecia, was not observed. This study confirms that it is feasible to increase the relative dose intensity of ifosfamide and epirubicin in patients with SCLC to 2.1 by using r-metHuG-CSF and shortening the interval between treatment cycles.

Aged↗
PubMed1999

Oral rehydration solution for acute diarrhea prevents subsequent unscheduled follow-up visits.

BACKGROUND: Oral rehydration solutions (ORS) for the treatment of acute diarrhea remain an underutilized therapy in the United States, despite multiple clinical trials confirming their efficacy and safety. Economic barriers to their use have been identified. OBJECTIVE: To determine whether providing ORS to patients at the time of their office visit for acute diarrhea can increase ORS utilization and reduce unscheduled follow-up visits. DESIGN: Randomized, controlled clinical trial. SETTING: Seven health centers of a large health maintenance organization. PARTICIPANTS: Children (N = 479) 0 to 60 months of age with acute diarrhea (at least three watery or loose stools in the previous 24 hours for </=7 days). INTERVENTION: Prescription for 2 quarts of ORS filled for free at on-site pharmacy plus written instructions versus written instructions alone. PRIMARY OUTCOME MEASURES: Self-reported use of ORS; unscheduled follow-up visits in office, urgent care, and/or emergency department setting. RESULTS: Subjects in the intervention group were significantly more likely to use ORS after the initial office visit (85% vs 71%; RR: 1.19; 95% CI: 1.08-1.32). Of the standard treatment group subjects, 40 (17.3%) sought unscheduled follow-up care for diarrhea versus 27 (10.9%) of the intervention group subjects (RR: 0.63; 95% CI: 0.40-0.99). Subjects seeking unscheduled follow-up care tended to younger (15.7 vs 19.4 months old), have more stools (7.1 vs 6.2 stools), and more vomiting episodes (4.1 vs 3.0) in the 24 hours before initial evaluation than those not seeking unscheduled follow-up care. Multivariate analysis showed that randomization to the intervention group was associated with a 25% reduction in unscheduled follow-up visits for acute diarrhea. CONCLUSIONS: Providing ORS to families at the time of their office visit for acute diarrhea is associated with a significant increase in ORS use and substantially reduces the need for unscheduled follow-up visits. Health maintenance organizations should consider routine provision of ORS to children presenting with acute diarrhea.

Acute Disease↗