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Biomedical subjects

D Hunter

Publications and source records attributed to D Hunter.

At least 109 records · Page 6Linked to original sources

Complement factor H mRNA in Epstein-Barr virus-transformed B lymphocytes of a factor H-deficient patient: detection by polymerase chain reaction.

A Spanish family with a hereditary deficiency of factor H was identified in previous studies. The deficiency was subtotal as low amounts of a dysmorphic molecule with partial identity to factor H were detected in her serum. The aim of this study was to obtain further characterisation of her deficiency employing her immortalised lymphocytes. After purification of mRNA from her Epstein-Barr virus (EBV)-transformed lymphocytes and from Raji cells, and cDNA synthesis we succeeded in amplifying cDNA which codes for factor H domains 13-15 from both cell lines, using specific oligonucleotides. The amplified fragments were indistinguishable from the one which was amplified from the control cloned cDNA template. The failure to amplify the 3' end of the patient's factor H mRNA suggests that the mRNA is truncated, which is consistent with the characteristics of the dysmorphic protein. Thus, factor H mRNA was detectable in Raji cells and the patient's EBV-transformed lymphocytes. We suggest that immortalised B lymphocytes can be used for the study of a range of inherited complement deficiencies.

B-Lymphocytes↗

Validation of the Gail et al. model for predicting individual breast cancer risk.

BACKGROUND: The Gail et al. model is considered the best available means for estimating an individual woman's risk of developing breast cancer. Such estimates are useful in decision making on the part of women, in designing prevention trials, and in targeting screening and prevention efforts. PURPOSE: Our purpose was to evaluate the ability of the model to accurately predict individual breast cancer risk, using a large population independent of the one from which the model was derived. METHODS: We compared the number of cancer cases predicted by the model to the actual number of cases observed in the Nurses' Health Study. The study population was 115,172 women who did not have breast cancer at the beginning of the study. Questionnaires were sent to participants every 2 years, seeking data on risk factors and diagnoses of breast cancer. Follow-up compliance was 95% over the 12-year study period. RESULTS: The model over-predicted absolute breast cancer risk by 33% (95% confidence interval [CI] = 28%-39%), with the overprediction more than twofold among premenopausal women (95% CI = 1.9-2.2), among women with extensive family history of breast cancer (95% CI = 1.1-3.9), and among women with age at first birth younger than 20 years (95% CI = 1.3-4.7). The correlation coefficient between observed and predicted risk was 0.67, indicating that the model is less than satisfactory for ranking individual levels of breast cancer risk. Overprediction occurred at all deciles of predicted risk. CONCLUSIONS: The model's performance is unsatisfactory for estimating breast cancer risk for individual women aged 25-61 years who do not participate in annual screening. Lower mammography screening rates in the Nurses' Health Study may account for some, but not all, of the discrepancy between observed and predicted cases. IMPLICATIONS: A recent modification of the model by the tamoxifen trial investigators is likely to have provided accurate power calculations. This modified form of the model should be useful for planning other large, population-based studies.

Adult↗

A prospective study of cigarette smoking and risk of colorectal adenoma and colorectal cancer in U.S. women.

BACKGROUND: A positive correlation between smoking and colorectal cancer has been reported for men, but not for women, who began smoking in substantial numbers in the late 1940s and early 1950s. We hypothesized that smoking acts as an initiator of colorectal neoplasia and that an association with cancer in women has been missed because of the long period between initiation and diagnosis of cancer. PURPOSE: Our purpose was to assess the association between smoking and risk of colorectal adenoma and colorectal cancer in women and to estimate the minimum induction period between the onset of smoking and cancer diagnosis. METHODS: Our data came from the ongoing Nurses' Health Study, in which current and lifetime smoking histories and other potential confounding factors were assessed by questionnaire at baseline and at 2-year intervals. We documented 586 new cases of colorectal cancer from 1976 to 1990 from a group of 118,334 women and 564 new cases of adenoma among 12,143 women who had a first colonoscopy or sigmoidoscopy between 1980 and 1990. We then assessed the relative risk (RR) of small adenoma, large adenoma (> or = 1 cm), and colorectal cancer in terms of pack-years of smoking. RESULTS: The amount smoked in the prior 20 years was related to the prevalence of small adenomas (multivariate RR = 1.45; 95% confidence interval [CI] = 1.25-1.68; P < .0001) and less strongly with large adenomas (RR = 1.31; 95% CI = 1.17-1.47; P < .0001), adjusting for age, intake of saturated fat, dietary fiber, folate, and alcohol, body mass, family history of colorectal cancer, and pack-years of cigarettes smoked within the prior 20 years. Pack-years of cigarettes smoked more than 20 years in the past was associated with risk of large adenoma (multivariate RR for a 20 pack-year increment = 1.29; 95% CI = 1.01-1.64; P trend = .04), but not of small adenoma (RR = 1.11; 95% CI = 0.93-1.34). Cigarette smoking was unrelated to colorectal cancer until 35 years after smoking began, but then became progressively more strongly related with time. Among women who had started smoking more than 10 cigarettes per day 35-39 years in the past, the RR for cancer was 1.47 (95% CI = 1.07-2.01), progressing to 1.63 (95% CI = 1.14-2.33) after 40-44 years and 2.00 (95% CI = 1.14-3.49) after 45 years. CONCLUSIONS: Because the minimum induction period for colorectal cancer appears to be at least 35 years, an association between smoking and colorectal cancer in women may just now be showing up. IMPLICATIONS: Our findings suggest that cigarette smoking may be a previously unrecognized, preventable cause of colorectal cancer among women.

Adenoma↗

Intraureteral metallic self-expanding endoprosthesis (Wallstent) in the treatment of difficult ureteral strictures.

Intractable and recurrent ureteral stricture presents a continuous challenge to the urologist. We report on 5 patients with severe ureteral stricture who were successfully treated with self-expanding metallic stents. Ureteral stricture occurred at ureteroileal anastomotic sites after neoplasm resection in 2 cases, multiple upper ureteral strictures were related to multiple surgical procedures for correction of bladder exstrophy in 1 and a ureteral kink developed in 1. Treatment with transluminal balloon dilation provided poor results but self-expanding metallic stents were used successfully with no major complications. In the last patient the stent and the overlying ureter were removed due to recurrent reflux; the gross and histological ureteral changes are discussed in detail. The technical approach is described, alternative therapeutic options are considered and pertinent literature is reviewed.

Adult↗

Extradural infusion analgesia for postoperative pain relief.

We describe 4-yr experience providing extradural infusion analgesia in a district hospital for treatment of postoperative pain. A total of 770 patients recovering from major surgery were treated on general surgical wards between April 1989 and March 1993. The results of a retrospective audit showed that pain control, assessed with both a visual analogue scale (VAS score (0-10 cm)) and a verbal rating scale (VRS), was good. At rest, more than 80% of patients scored pain as absent or mild (VAS score 0-3) during the first 24 h, with only 4% experiencing severe pain (VAS score 7-10). On movement, 50% of patients had good pain control (VAS score 0-3) while 20% of patients experienced severe pain (VAS score 7-10). Minor complications such as emetic sequelae and pruritus were common; these conditions were mild and rarely required treatment. Hypotension (< 100 mm Hg) occurred in 34% of patients in the first 24 h. Ventilatory frequencies of 8 b.p.m. or less occurred in 2.6% of patients. Four patients (0.52%) developed severe respiratory depression. These patients demonstrated increased sedation but only one had a low ventilatory frequency. Three patients died while receiving extradural infusion analgesia.

Adolescent↗

Serologic survey and serum biochemical reference ranges of the free-ranging mountain lion (Felis concolor) in California.

Serum samples from 58 mountain lions (Felis concolor) in California (USA) were collected between April 1987 and February 1990. Nineteen serum samples were used for serum biochemistry determinations; the ranges were similar to reference values in domestic cats, captive exotic felidae and free-ranging mountain lions. A serological survey was conducted to determine whether antibodies were present against selected infectious agents. Fifty-four (93%) of 58 sera had antibodies against feline panleukopenia virus. Fifteen (68%) of 22, 16 (28%) of 58, 11 (19%) of 58, and 10 (17%) of 58 had serum antibodies against feline reovirus, feline coronavirus, feline herpes virus, and feline calicivirus, respectively. Twenty-three (40%) of 58 and 21 (58%) of 36 had serum antibodies against Yersinia pestis and Toxoplasma gondii, respectively. Only one of 22 sera had antibodies against the somatic antigen of Dirofilaria immitis. Feline leukemia virus and feline immunodeficiency virus antigens were not detected in any mountain lion's sera. All 58 sera samples were negative for antibodies to feline immunodeficiency virus and Chlamydia psittaci.

Animals↗

International experience and health sector reform: the challenge for developing health systems.

Health sector reform is a priority issue in many countries and there is great scope for an international exchange of experiences. We should not be amiss, however, to the problems and dangers of such international exchange. Focusing on the situation of developing countries, three critical problems are identified: tendencies to the universalism of a market approach, a one-way transmission of ideas, and the lack of policy analysis. In order to contribute to a more constructive process of international exchange, four recommendations are proposed in the areas of training and the approach to management, management research, strengthening health policy analysis, and developing new exchanges between countries.

Communication↗

Neurogenesis in the olfactory epithelium.

The initial step in the recognition of odors occurs when individual odorant molecules enter the nasal cavity and interact with the sensory endings of neurons located in the olfactory epithelium. These neurons are unique in several respects. First, they are directly accessible to the external environment. Second, perhaps because of their exposure to toxic substances in the environment, they degenerate and are replenished continuously from a population of stem cells at the base of the epithelium. Third, the sensory neurons born in the olfactory epithelium of adults retain the ability to differentiate and establish synaptic contact with target cells in the mature olfactory bulb. These unique features, which are conserved phylogenetically (for example, see Blaustein et al), provide substantial rationale for studying neuronal genesis and differentiation in the olfactory epithelium. We will summarize much of what is currently known about the development of the olfactory epithelium, the birth and differentiation of olfactory receptor neurons, and the molecular correlates of these events.

Animals↗

Pre-emptive analgesia from intravenous administration of opioids. No effect with alfentanil.

Forty patients undergoing total abdominal hysterectomy were randomly allocated to receive either 40 micrograms.kg-1 of alfentanil on induction of anaesthesia or 40 micrograms.kg-1 of alfentanil after the skin incision. Postoperative pain relief was provided with morphine from a patient-controlled analgesia system. The amount of morphine consumed in the operating theatre, while in recovery and for the first 24 h postoperatively was recorded. Pain scores were assessed at 24 h using a visual analogue scale. There were no differences found between the two groups for morphine consumption but the 'pre-emptive' group had significantly higher pain scores at rest. We conclude that there is no clinically useful pre-emptive analgesic effect with this dose of alfentanil and that therefore systemic opioid premedication is unlikely to decrease postoperative analgesic requirements through the mechanism of pre-emptive analgesia.

Adult↗

A prospective study of the association of serum neopterin, beta 2-microglobulin, and hepatitis B surface antigenemia with death in infants and children with HIV-1 disease.

A high percentage of HIV-1-infected infants and children in Romania are coinfected with hepatitis B virus. Little information is available on the impact of concurrent hepatitis B infection on the course of HIV-1 infection. We conducted a prospective cohort study over 1 year in a group of 68 HIV-1-infected infants and children to determine whether hepatitis B surface antigenemia, neopterin, and beta 2-microglobulin (B2M) predicted death. Among the 44 hepatitis B surface antigen-positive (HBsAg+) subjects at enrollment, 13 (30%) died during 1 year of follow-up. In comparison, two of 24 (8%) HBsAg-negative subjects died (RR = 7.7; p = 0.05). Higher initial serum concentrations of neopterin and B2M were negatively associated with survival. After stratifying by baseline clinical evidence of HIV-related disease, survival was negatively associated with HBsAg+ status (p = 0.04) in 33 children in stage P-2, adjusting for age, serum neopterin, and serum B2M levels. The results of this study suggest that serum neopterin is a marker for severity of clinical illness and that HBsAg+ status increases the mortality rate among children with clinical evidence of HIV infection.

Biopterins↗

Round table ... management development.

Management development in the NHS has reached a hiatus, yet there are no apparent moves from the centre to address this. The Journal brought together senior figures from the four dedicated management development providers in an informal round table discussion, chaired by Rob MacLachlan, to open the debate.

Administrative Personnel↗