Malignant melanoma: girding our loins again.
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Adult↗
Biomedical subjects
G B Hill
Publications and source records attributed to G B Hill.
Novel inhibitors of prolyl 4-hydroxylase. 3. Inhibition by the substrate analogue N-oxaloglycine and its derivatives.
N-Oxaloglycine (3) is an alpha-ketoglutarate (1) analogue that is a competitive inhibitor of prolyl 4-hydroxylase (EC 1.14.11.2). A study of the structure-activity relationships of some other oxalo derivatives shows that substitution on the glycine moiety modulates activity stereoselectively and that if the omega-carboxylate is homologated or replaced by either acylsulfonamides or anilide, then activity is sharply reduced. This sensitivity to these changes is contrasted with the relative insensitivity of another putative alpha-ketoglutarate analogue, pyridine-2,5-dicarboxylic acid (2), and the implication is discussed that compounds of both series are unlikely to bind to prolyl hydroxylase in the same way even though both inhibit the enzyme competitively.
Amino Acid Sequence↗
Pelvic inflammatory disease: findings during inpatient treatment of clinically severe, laparoscopy-documented disease.
OBJECTIVES: We evaluated the relationship between clinically severe pelvic inflammatory disease and laparoscopic diagnosis and grading, comparative treatment with clindamycin plus cefamandole or doxycycline, and a management protocol for inpatient pelvic inflammatory disease treatment. STUDY DESIGN: Thirty-three patients who met our clinical criteria for severe pelvic inflammatory disease underwent diagnostic laparoscopy. Pelvic inflammatory disease patients were randomized to double-blind treatment with clindamycin plus cefamandole or doxycycline within our management protocol; postdischarge oral antibiotics were omitted. RESULTS: Laparoscopy confirmed pelvic inflammatory disease in 23 (70%) patients; 10 (44%) had mild pelvic inflammatory disease by laparoscopic grading. Laparoscopic grade alone predicted necessary duration of therapy to response: mild pelvic inflammatory disease, 2.3 +/- 0.5 days; moderate pelvic inflammatory disease, 2.7 +/- 1.5 days; and severe pelvic inflammatory disease, 3.9 +/- 1.5 days (p less than 0.05). Using the management plan presented, response rates for both antibiotic regimens were 100%. CONCLUSIONS: Clinical diagnosis and grading of severe pelvic inflammatory disease has poor specificity. Laparoscopic grading of severity of pelvic inflammatory disease seems accurate. Both clindamycin plus cefamandole and clindamycin plus doxycycline are equally effective regimens for treatment of pelvic inflammatory disease and did not require supplementation after discharge. Our management plan is objective and practical; daily bimanual examination is the most sensitive indicator of persistent disease.
Adult↗
Epidemiology of abdominal aortic aneurysm: the effect of differing definitions.
There have been several published definitions for abdominal aortic aneurysm (AAA), however, it is not known how different definitions affect what is reported. This paper presents an evaluation of three definitions taken from the literature on (a) aneurysm frequency, (b) prevalence rate and (c) prevalence ratio from an ongoing case-control study evaluating whether male siblings of patients with known AAA have a higher prevalence of aneurysms compared to a control group. Depending on the definition used, the frequency of AAA could vary from a low of five to a high of 23; the prevalence of AAA in siblings could range from 2.1 to 18.8. Changing definitions alters the prevalence ratio (risk of disease) in both magnitude and direction. On the one hand, male sibling of affected patients are at approximately one and a half times (1.6) greater risk of having an AAA compared to controls, whereas using a different definition they are at less than half the risk (0.3).
Aged↗
Eubacterium nodatum mimics Actinomyces in intrauterine device-associated infections and other settings within the female genital tract.
Eubacterium nodatum is an obligately anaerobic, gram-positive, branching rod that markedly resembles Actinomyces, particularly Actinomyces israelii, in its cellular and colonial characteristics. Its isolation from the female genital tract was examined for a study period in which use of intrauterine contraceptive devices (IUDs) was common, and additional characteristics of the organism were investigated. Fifteen genital isolates of E nodatum were all associated with the presence of a foreign body, usually an IUD (12 patients). Six of these 12 patients had presented with clinically severe pelvic inflammatory disease. The remaining six had signs and symptoms related to IUD use and/or had a report of probable Actinomyces (five patients) by a Papanicolaou smear, demonstrating that E nodatum can be mistaken for Actinomyces in a Papanicolaou-stained smear. The three other patients had different types of foreign bodies. The frequency of isolation from cultures associated with IUD use during the study period was five (6.4%) of 78 for Actinomyces versus the 12 (15.4%) of 78 for E nodatum. In vitro-prepared E nodatum was not demonstrated to cross-react with A israelii or A naeslundii antisera. Both E nodatum and A israelii were shown to adhere in vitro to an inanimate object, indicating their propensities to colonize a foreign body. The present data, with the previous reports of isolation of E nodatum from cases of lumpy jaw and severe periodontitis, suggest that it is an opportunistic pathogen very much like A israelii.
Actinomyces↗
Approaches to the design of anti-fibrotic drugs.
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Amino Acids, Dicarboxylic↗
Susceptibilities of anaerobic gram-negative bacilli to thirteen antimicrobials and beta-lactamase inhibitor combinations.
Thirteen antimicrobial agents and beta-lactamase inhibitor combinations were tested simultaneously for their in-vitro activity against a range of anaerobic Gram-negative bacilli with a standard reference agar dilution method. Overall, metronidazole, imipenem, ampicillin/sulbactam, ticarcillin/clavulanic acid and cefoperazone/sulbactam, followed by clindamycin, cefoxitin, and piperacillin, had the greatest activity. Cefotetan, ceftizoxime, and cefoperazone were moderately active, while ampicillin and penicillin were least active. Metronidazole was the only drug active against all strains, but only one strain was resistant to imipenem. Resistance was highest among certain members of the Bacteroides fragilis group, but was observed also among numerous other Bacteroides species. beta-Lactamase was produced by 94% of strains in the B. fragilis group, and by 64% of strains overall. The activities of clindamycin and cefoxitin were compared with those in previous surveys since 1982 at our institution. No clear evidence of increasing resistance was demonstrated, but the data emphasized the significant effects resulting from variations in susceptibility testing.
Ampicillin↗
Spiral gradient endpoint method compared to standard agar dilution for susceptibility testing of anaerobic gram-negative bacilli.
More efficient and reproducible alternative methods of performing agar dilution susceptibility testing are desirable, particularly for anaerobic bacteria. Anaerobes generally grow more reliably on solid media than they do in broth microdilution wells. A new method, the revised spiral gradient endpoint (SGE) method, was evaluated against the standard agar dilution (SAD) method by using a wide variety of anaerobic gram-negative bacilli (161 strains) and eight antimicrobial agents. For the SGE method, a spiral plater was used to set up a concentration gradient of an antimicrobial agent within an agar plate across which bacterial strains were inoculated as radial streaks. After incubation, the MIC of the antimicrobial agent was calculated from the radial endpoint location where bacterial growth ceased along the streak. The MICs for 90% of strains tested (in micrograms per milliliter) and the cumulative percentages of susceptible strains at the breakpoints for the SGE and SAD methods, respectively, and for all 161 strains were as follows: for metronidazole, 2 and 100 versus 2 and 100; for imipenem, 1 and 99 versus 0.5 and 98; for ampicillin-sulbactam, 8 and 97 versus 8 and 98; for clindamycin, 4 and 90 versus 4 and 91; for cefoxitin, 32 and 95 versus 32 and 95; for mezlocillin, 256 and 88 versus greater than 128 and 86; for ampicillin, greater than or equal to 256 and 51 versus greater than 64 and 51; and for penicillin (in units per milliliter), greater than or equal to 512 and 71 versus greater than 64 and 65. The excellent agreement of these data and the greater sensitivity reproducibility, and efficiency of the revised SGE method warrant further evaluations. Assuming that these advantages are confirmed, the revised SGE method should be a useful alternative test method when detailed susceptibility data are desired.
Agar↗
Canadian Cancer Statistics 1991.
During 1991, an estimated 109,000 new cases of cancer will be diagnosed in Canada (excluding non-melanoma skin cancer). Estimated cancer deaths in 1991 will total 56,700. Excluding non- melanoma skin cancer, over one in three Canadians will develop some form of cancer during their lifetime, while one in four men and one in five women will die from this disease. These statistics are discussed, as well as cancer risk factors, cancer in children, age and sex distribution of cancer, cancer survival rates, trends in cancer incidence and mortality since 1970, smoking and lung cancer, and cancer among the Inuit and Indians.
Adolescent↗
Epidemiology of prostatic cancer: a case-control study.
A population-based case-control study of prostatic cancer in Alberta was undertaken to determine the risk factors associated with the disease. Cases were 382 newly diagnosed prostatic cancer patients and 625 controls, group-matched to the anticipated age distribution of the cases, chosen at random from the health insurance roster. Subjects were interviewed in their homes by using a pre-tested questionnaire including questions related to ethnic group, education, puberty, marital history, family history, residence, water supply, smoking, and diet. Factors significantly related to the risk of developing prostatic cancer included ethnic group (British high, Ukrainian low), education (elementary high, university low), age at first marriage (early high, late low), family history (high risk for those with relatives with prostatic cancer), and increased masculinity among the children of cases. The results with respect to smoking, occupation, medical history, birthplace, residence, water supply, and diet were generally negative.
Canada↗
Bacterial vaginosis: diagnostic and pathogenetic findings during topical clindamycin therapy.
We examined subjective and objective correlates among 67 women with symptomatic bacterial vaginosis before and after treatment with intravaginal clindamycin or placebo. We found no preponderance of any sexual practices among these patients. Nine patients (13.4%) had had hysterectomy. Whereas odor and discharge were the most common symptoms, 30 patients (44.8%) also complained of vulvovaginal irritation. Symptoms correlated poorly with objective therapeutic outcome. On examination the diagnosis would have been missed in seven patients (10.4%) if the clinician relied on presence of an abnormal vaginal discharge to suggest bacterial vaginosis. Vaginal pH greater than 4.5 was found immediately after curative therapy in 59.6% of patients. Mobiluncus spp. morphotypes were 99.0% specific and 52.1% sensitive and proline aminopeptidase activity in vaginal fluid was 84.4% sensitive and 70.2% specific for diagnosis. Our Gram stain criteria yielded no false-negative results, 6.1% false-positive, and frequent indeterminate results after therapy. We found little evidence for sexual transmission of bacterial vaginosis. Recurrence after effective therapy was not predicted by vaginal pH elevation, positive or indeterminate Gram stain result, or positive proline aminopeptidase test.
Administration, Intravaginal↗
Spiral gradient endpoint: a new method of susceptibility testing.
The key to SGE is an instrument that deposits the antimicrobial agent in predetermined, decreasing concentrations in a spiral pattern on an agar plate. The bacterial inoculum is streaked radially from the center of the plate across the spiral. The drug concentration at the point in the spiral where bacterial growth ends is its MIC.
Anti-Bacterial Agents↗
Canadian cancer statistics 1990.
In 1990, an estimated 104,000 new cases of cancer (excluding non-melanoma skin cancer) will be diagnosed in Canada. The estimated number of deaths due to cancer in that same year will total 54,500. Just over one in three Canadians can expect to develop some form of cancer during their lifetime, and one in four men and one in five women will die from this disease. Almost 10% of women will develop breast cancer, while close to 8% of men will develop lung cancer. In 1990, lung cancer alone is expected to account for 17,300 newly diagnosed cancers (16.6% of the total), and 14,200 cancer deaths (26% of the total). Cancer will also take its toll as the fourth leading cause of death in children. This article explores additional statistics, trends in cancer incidence and mortality since 1970, cancer survival rates, and cancer mortality by income level. This article is based on material prepared by Statistics Canada for inclusion in Canadian Cancer Statistics 1990 (1), and developed in collaboration with the Canadian Cancer Society, Health and Welfare Canada, and provincial and territorial cancer registries.
Adolescent↗
Bacterial vaginosis: treatment with topical intravaginal clindamycin phosphate.
We tested topical intravaginal clindamycin phosphate at concentrations of 0.1, 1.0, and 2.0% in the treatment of 62 women with symptomatic bacterial vaginosis in a prospective, randomized, double-blind, placebo-controlled trial, and offered open-label treatment with 1.0% clindamycin to patients with persistent disease after blinded treatment. Blinded intravaginal clindamycin phosphate treatment cured bacterial vaginosis in 93.5% (43 of 46) of patients 4-7 days after therapy, compared with 25.0% (four of 16) of patients receiving placebo (P less than .001). One month later, 89.7% (35 of 39) of those who initially responded to clindamycin treatment showed persistent cure. There were no significant side effects.
Administration, Intravaginal↗
Risk of bladder cancer by source and type of tobacco exposure: a case-control study.
The association between tobacco use and risk of bladder cancer was investigated in a population-based case-control study conducted in Alberta and south-central Ontario, Canada, between 1979 and 1982. In all, 826 histologically-confirmed cancer cases and 792 randomly selected controls, individually matched to cases for age, sex, and area of residence, were recruited into the study. Compared to those who had never smoked cigarettes, males and females who had ever smoked cigarettes had a statistically highly significant 2-fold increase in risk of bladder cancer; for ex-smokers, the risk was intermediate between that for current smokers and never-smokers. There was a dose-dependent increase in risk of bladder cancer with total lifetime cigarette consumption, of similar magnitude for males and females. In males, risk increased with self-reported degree of inhalation in ex-smokers and in current smokers (statistically significant trend), while in females there was no association in current smokers, and a statistically significant inverse association in ex-smokers. Overall, risks of bladder cancer associated with lifetime consumption of plain and filter cigarettes were similar, and there was little evidence to suggest that switching from plain to filter cigarettes was beneficial. Neither passive smoking nor other forms of tobacco consumption (pipes, cigars, chewing tobacco, or snuff) were associated with altered risk of bladder cancer. The population attributable risk for cigarette smoking was about 47% in males and about 33% in females.
Adult↗
Pathologic prognostic factors for cutaneous malignant melanoma: the Western Canada Melanoma Study.
An analysis of data for histopathologic factors influencing survival was conducted on 798 cases of invasive cutaneous malignant melanoma. On univariate analysis, a number of factors influenced survival; however, when these factors were examined using a proportional-hazards model, sex and log of depth of penetration were the only factors governing survival. Moreover, these factors were only important in patients with lesions up to 4 mm in depth with no evidence of other disease. For patients with solitary lesions deeper than 4 mm, or patients with regional or distant disease, none of the factors examined in our study was of predictive value for survival assessment.
Adult↗
Serum vitamins A and E, beta-carotene, and selenium in patients with breast cancer.
A total of 89 subjects including 30 breast cancer patients with distal metastases, 29 patients with benign breast disease, and 30 healthy subjects were studied. Serum samples from these subjects were obtained from the National Cancer Institute (NCI) Breast Cancer Serum Bank, Bethesda. Serum concentrations of vitamin A and its transport proteins (prealbumin and retinol-binding protein [RBP]), beta-carotene, vitamin E, and selenium were determined. For each of these parameters the mean for the breast cancer patients was lower than that of the healthy subjects. The differences between healthy subjects and patients with either breast cancer or benign breast disease were, however, statistically significant only in the case of RBP (p less than 0.05). In the case of vitamin A and its transport proteins these differences were reduced by comparing the cancer patients with the benign breast disease patients rather than with the healthy controls. This indicates that the low serum levels for those three parameters may be merely a consequence of disease in general rather than a feature of cancer per se.
Breast Diseases↗
Selective screening for late stage breast cancer using a logistic model.
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Adult↗