Evaluation of the accuracy of aorta scan BVI 9600 in screening for abdominal aortic aneurysm.

OBJECTIVES: Despite a decreasing incidence of abdominal aortic aneurysm (AAA), the cost-effectiveness of AAA ultrasound screening can be improved by reducing the screening costs and increasing the uptake rates. The BVI 9600 (BVI) is a promising tool for this purpose as it is inexpensive and can detect AAA without a trained operator. This study aims to investigate whether the BVI can be used to detect AAA for the purpose of a low-cost outreach screening approach. METHODS: A total of 142 subjects had their abdominal aortae measured by five sonographers using the BVI and a conventional ultrasound machine. The examination included four anterior-posterior measurements at four equally spaced scanning locations from the xiphisternum to the umbilicus. The measurements produced by each machine were compared using Bland-Altman plots, followed by an analysis of the AAA detection performance. RESULTS: The BVI measured the aortic diameter to within 0.88-1.56 cm of the true diameter, exceeding the 0.5 cm "clinically acceptable difference" (CAD). Its accuracy was poorer when measuring the aneurysmal aortae (mean difference -0.56 cm, variability 1.72 cm) than normal aortae (mean difference 0.02 cm, variability 0.76 cm). Nine out of 52 aneurysms were not detected due to undersizing measurement and non-visualization of the aortae. CONCLUSIONS: At present, the BVI is not sufficiently accurate to detect AAA for screening purposes. A number of technical features require improvement.

Obesity and impaired venous function.

OBJECTIVES: The clinical severity of venous disease is often worse in obese patients. The objectives of this study were to compare lower limb venous physiology assessed by air plethysmography in a large group of obese and normal-weight patients; to consider the effect of posture on these measures and on foot vein pressure in a smaller cohort. METHODS: Venous function was assessed using air plethysmography and duplex scanning in 934 consecutive patients presenting for assessment of venous disease. These were grouped into obese or non-obese categories. A smaller group of twenty patients with a range of body weights were randomly selected from a database of patients with varicose veins. Foot vein pressures and femoral vein diameter were measured standing, sitting, lying and ambulating. RESULTS: Venous disease was more clinically severe in the obese limbs (CEAP C5&6 non-obese group 20.5%, obese group 35.4%, p<0.001 chi(2)). Venous reflux was worse in the obese but measures of muscle pump function were better. Residual volumes and fractions were better in the obese (mean residual volume, non-obese 60 SD 36, obese 50 SD 42, p<0.001 t test). In the smaller study group weight correlated with the diameter of the superficial femoral vein (r=0.50), ambulatory venous pressure (r=0.45), venous filling index (r=0.49) and the ejection volume (r=0.38, p<0.05). The foot venous pressure was significantly greater in the obese in all positions. CONCLUSION: The CEAP clinical stage of venous disease is more advanced in obese patients than non-obese patients with comparable anatomical patterns of venous incompetence. This may be the result of raised intra-abdominal pressure reported in previous studies, leading to greater reflux, increased vein diameter and venous pressures.

Factors affecting recurrence rates in superficial bladder cancer.

A prospective study of all patients with superficial bladder cancer diagnosed in Northern Alberta (population 1.2 million) from 1977 to 1983 was performed to establish patterns of recurrence. Of the 761 patients with all stages of bladder cancer at diagnosis, 642 were deemed to be free of disease after primary treatment consisting of transurethral resection, fulguration, or laser surgery. Follow-up of these patients showed that approximately two-thirds of first recurrences occur within 18 months of diagnosis and that more of these patients have died of unrelated causes (n = 73) than of bladder cancer (n = 34). Censored disease-free interval comparisons showed that initial recurrences occurred sooner in patients with multifocal rather than unifocal disease and also sooner in females than in males. Known risk factors (occupational exposure to chemicals and cigarette smoking) and suspected risk factors (coffee consumption and artificial sweetener use) had no effect on disease-free interval and are not related to tumor multiplicity.

Socioeconomic status, sunlight exposure, and risk of malignant melanoma: the Western Canada Melanoma Study.

In a study of 261 male melanoma patients and age-and sex-matched controls, a strong positive univariate association between socioeconomic status, as determined by usual occupation, and risk of melanoma was detected. This association, however, was substantially explained by host constitutional factors and occupational, recreational, and vacation sunlight exposure. The study demonstrated an increased risk of melanoma in draftsmen and surveyors and a reduced risk of melanoma in construction workers and individuals employed in the finance, insurance, and real estate industry even after control for the effect of host factors and sunlight exposure.

Risk factors for ocular melanoma: Western Canada Melanoma Study.

Between April 1, 1979, and March 31, 1981, 90 individuals in the four western provinces of Canada were diagnosed as having ocular melanomas. Of 87 age-eligible cases (age 20-79 yr), 65 (75%) were interviewed along with age- and sex-matched controls chosen at random from the provincial populations. Individuals with blue eyes had a significantly greater crude risk of ocular melanoma than those with brown eyes [odds ratio (OR)=3.0, P=.04]. Subjects with red or blonde hair were at higher risk of having ocular melanoma than those with black or dark-brown hair (OR=7.7, P=.03). Indoor workers appeared to be at elevated risk for ocular melanoma even after controlling for eye and hair color (OR=3.5, P=.006).

Chemical exposures, medical history, and risk of squamous and basal cell carcinoma of the skin.

The role of non-sunlight-related risk factors for squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) of the skin was investigated in a population-based, case-control study conducted among males in Alberta, Canada. In total, 180 SCC and 226 BCC cases and 406 randomly selected male controls, frequency matched by 5-year age groups to the cases, were interviewed by trained personnel using a standardized etiological questionnaire. Data were analyzed using conditional logistic regression techniques. After adjustment for age, skin and hair color, mother's ethnic origin, and sunlight exposure, elevated risks for SCC were seen in subjects exposed to insecticides [odds ratio (OR), highest tertile, 2.8; 95% confidence interval (CI), 1.4-5.6], herbicides (OR, highest tertile, 3.9; 95% CI, 2.2-6.9), and fungicides and seed treatments (OR, highest tertile, 2.4; 95% CI, 1.4-4.0), as well petroleum products, grease, and several other exposures. Elevated risks of BCC were seen in subjects exposed to fiberglass dust (OR, 2.0; 95% CI, 1.0-3.9) and dry cleaning agents (OR, 4.6 95% CI, 1.1-19.7). Prior nondiagnostic X-ray treatment for skin conditions increased risk of both cancers. Although solar UV radiation is known to be the major environmental exposure causing nonmelanocytic skin cancer, results of this study suggest that nonsolar factors may also be important.

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.

Archie Cochrane and his legacy. An internal challenge to physicians' autonomy?

Archibald L. (Archie) Cochrane was born in 1909 into a wealthy Scottish family, from which he inherited the advantage of a private income and the disadvantage of porphyria. Though a brilliant student, his medical training was interrupted by a lengthy psychoanalysis in Europe, and by service in a field ambulance unit in the Spanish Civil War. Eventually Cochrane qualified in medicine in 1938 and joined the R.A.M.C. in 1939. He was taken prisoner in Crete in 1941 and served the rest of the war as medical officer in various POW camps. Cochrane's post-war career with the Medical Research Council as a field epidemiologist in South Wales earned him the respect and admiration of a generation of British epidemiologists. However, Cochrane's international reputation is not based on his achievements as an epidemiologist, but on his 1971 monograph "Effectiveness and Efficiency. Random Reflections on Health Services," a biting scientific critique of medical practice. Cochrane died in 1988, but his name lives on in the Cochrane Collaboration, a network of researchers devoted to clinical trials, and the torch which he lit had been carried forward by the groups promoting evidence-based medicine. Some have looked askance at these developments, regarding them as a threat to the autonomy of physicians.

Community screening for dementia: the Mini Mental State Exam (MMSE) and Modified Mini-Mental State Exam (3MS) compared.

The objectives of this study were to assess whether Teng's modification of the Mini-Mental State Examination (MMSE) improves its performance as a screening test for cognitive impairment and dementia, and to replicate this comparison in French and English language groups, and for differing assumptions concerning the relative importance of false negative and false positive errors. Screening interviews were conducted with representative samples of people aged 65 or over, set in 36 communities in 10 Canadian provinces. There were 8900 community participants in the Canadian Study of Health and Aging, of whom 1600 also underwent an extensive clinical and neuropsychological examination. Sensitivity, specificity and areas under the receiver operating characteristic (ROC) curve for the original MMSE and modified version (the 3MS) were the main outcome measures. Results are reported for French and English versions of the tests. The results indicate the alpha internal consistency for the 3MS was 0.87, compared to 0.78 for the MMSE. The area under the ROC curve in identifying dementia was 0.93 for the 3MS and 0.89 for the MMSE (p < 0.001). There was less difference between the two tests in identifying all levels of cognitive impairment (AUC 0.80 versus 0.77, p < 0.01). The superiority of the 3MS appears more due to its extended scoring system than to its additional questions. The validity of the MMSE was comparable in English and French samples; results for the 3MS were inconsistent between the two samples, suggesting possible translation problems. In conclusion, the 3MS was superior to the MMSE, justifying the slightly greater burden for its administration and scoring. Neither test worked well in identifying lower levels of cognitive impairment.

Cigarette smoking and peripheral arterial occlusive disease.

BACKGROUND: The importance of cigarette smoking in the etiology of peripheral arterial occlusive disease is well known, but there have been few studies that have quantified this relationship. METHODS: A case-control study design was used in which the case subjects were men with a history of claudication for at least 1 year and abnormal findings on noninvasive blood flow studies or on arteriography; control subjects were men attending the same hospital for conditions other than cancer, with no history of cancer or vascular disease and with a normal ankle-brachial index. Case and control subjects were interviewed by a trained nurse interviewer using a pilot-tested questionnaire. Current smoking status was confirmed by serum cotinine level estimation. Univariate odds ratios for smoking and other potential risk factors were calculated, and their significance was tested by comparison with the chi-squared distribution. Logistic regression analysis was used to adjust the effect of smoking for confounding variables, and the regression equation was used to estimate the proportion of disease attributable to smoking. RESULTS: Of the patients approached, 94% of the eligible case subjects and 93% of the eligible control subjects agreed to participate. Recruitment ended with 102 cases of peripheral arterial occlusive disease and 99 controls. Most of the control subjects were attending clinics for other surgical specialties. Compared with men who had never smoked the relative risk was 7 for exsmokers and 16 for current smokers (p < 0.001). The relative risk increased directly with the lifetime number of cigarettes smoked, the chi-squared test for trend being highly significant (p < 0.001). Age, lipoprotein concentration, body mass index, and history of hypertension or heart disease were also significant risk factors. CONCLUSIONS: After adjustment for confounding variables the estimate of the fraction of disease attributable to smoking was 76%.

Experimental and clinical experience with hyperbaric oxygen in the treatment of clostridial myonecrosis.

At Duke University Medical Center, 49 patients with proved clostridial myonecrosis were treated with hyperbaric oxygen (HBO) during the past 10 years. Survival in patients with involvement confined to the extremities was 92.3 percent. Survival in patients with combined involvement of extremity and trunk was 53-3 percent, and with primary trunk involvement half of the patients survived. Survival for the entire series was 73.5 percent. Among the 28 patients receiving at least five HBO treatments, 24 survived. Extensive experimental studies were conducted during this same period including in vitro testing and in vivo experimental infections with C. perfringens. Data from the experimental models of gas gangrene indicate a therapeutic benefit with HBO by significantly decreasing both mortality and morbidity rates. The mechanism of action for this appears to be complex but probably includes a direct bactericidal action, bacteriostasis, inhibition of toxin production, and improvement in tissue oxygenation. In the absence of a controlled study, the therapeutic efficacy of HBO in the treatment of clostridial myonecrosis is not fully proved. Nevertheless HBO treatment can be recommended on the bases of sound experimental evidence and the results of favorable clinical experience. Mitigation of this severe but infrequent illness can best be accomplished through prevention, with strict adherence to the principles of wound care.

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.

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.

The latency period of carcinoma-in-situ of the cervix.

The age-specific incidence figures for gonorrhea and cervical carcinoma-in-situ in Alberta, Canada, have been correlated. The findings suggest that when reliable population-based data are available, changes in incidence and age distribution for gonorrhea can be regarded as predictive for comparable changes in incidence and age distribution for carcinoma-in-situ of the cervix with a delay in presentation of approximately five years. The latency period of carcinoma-in-situ of the cervix does not seem to vary considerably among different age groups. The results of the present study support the theory that a sexually transmitted infectious agent could be an etiologic factor in cervical cancer. Because gonorrhea rates in younger women indicate that they are engaging in earlier sexual activity with more partners, regular cervical screening should be encouraged to prevent a potential major increase of invasive cervical cancer.

Necrotizing fasciitis of vulvar origin in diabetic patients.

Necrotizing fasciitis is a rare, rapidly progressive, and often fatal infection of the superficial fascia and subcutaneous tissues. The integrity of the deep muscle fascia is usually not breeched, thus limiting the depth of involvement. Centrifugal spread within the planes of the superficial fascia and subcutaneous tissues is characteristic. Patients with diabetes mellitus constitute the group most vulnerable to necrotizing fasciitis, and a vulvar or perineal origin is associated with particularly high mortality. The authors report four such patients. Other apparent predisposing factors are advancing age, peripheral vascular disease, chronic debilitating illness, malnutrition, and possibly other states predisposing patients to immunodeficiency. None of these factors is an absolute prerequisite to the development of necrotizing fasciitis.

A trial of prophylactic cefamandole in extended gynecologic surgery.

A double-blind randomized trial of antibiotic prophylaxis was performed with 49 patients undergoing extended pelvic surgery for adenocarcinoma of the endometrium. In this series infections of the Hemovac drain site(s) were most common (8 of 10 infections); only 1 serious infection, pelvic cellulitis, occurred. Short-term perioperative cefamandole therapy significantly reduced infections and febrile morbidity in these patients as compared with patients who received a placebo. The average postoperative hospital stay for patients in the cefamandole group was 1 day less than for patients in the placebo group, but the difference was not statistically significant. The presence of 10 colony-forming units or more of a potential pathogen in lymph fluid collected through the Hemovac drains correlated with clinical infection. The low incidence of serious infection in this study precludes any conclusion regarding the impact of antibiotic prophylaxis in preventing serious infection after operation for gynecologic malignancy.

Intravenous metronidazole or clindamycin with tobramycin for therapy of pelvic infections.

Anaerobic bacteria are important pathogens in obstetric and gynecologic infections. As metronidazole has excellent in vitro activity against almost all clinically significant anaerobes, the newly available parenteral form of the drug was evaluated in a comparative study with clindamycin. Forty-seven patients with postpartum endomyometritis with or without wound infection, acute or chronic salpingo-oophoritis, tuboovarian abscess, postoperative pelvic cellulitis or wound infection, or other soft-tissue infection were included in the study. Initially 6 patients were treated with metronidazole, usually combined with tobramycin, in an open study. Subsequently, 41 patients were treated on a randomized schedule of either metronidazole or clindamycin, each combined with tobramycin. Anaerobic bacteria were isolated from 86% (37 of 43) of the patients who had positive cultures from sites cultured for aerobes and anaerobes. Anaerobic gram-negative rods and gram-positive cocci were the predominant isolates from infected tissues. Of the patients who received metronidazole, 96% (25 of 26) were considered clinically cured; the remaining patient initially responded but continued to have slight temperature elevations. There were no adverse reactions to this drug. Of the patients who received clindamycin, 100% were considered clinically cured. The excellent therapeutic response to intravenous metronidazole and the predominance of pathogenic anaerobes observed in these infections support its use in the treatment of infections of the female genital tract.

Antimicrobial susceptibility patterns of the Bacteroides fragilis group in the United States, 1989.

A national survey of Bacteroides fragilis group was continued in 1989 for the ninth consecutive year. Seven hundred thirty-nine isolates of B fragilis group from eight centers were tested for susceptibility to 14 antimicrobials. Sulbactam and clavulanic acid, beta-lactamase inhibitors, were tested at a constant concentration of 8 micrograms/ml and 2 micrograms/ml, respectively. Sulbactam was also tested in a fixed ratio of 1:2. Imipenem, ampicillin+sulbactam, and ticarcillin+clavulanic acid had resistance of less than 1% at breakpoints of 8 micrograms/ml, 16 micrograms/ml, and 64 micrograms/ml, respectively. At 32 micrograms/ml, resistance to cefoxitin, cefotetan, ceftizoxime, and ceftriaxone were 4%, 25%, 26%, and 46%, respectively. Clindamycin resistance was 10% at a breakpoint of 4 micrograms/ml. No isolates were resistant to chloramphenicol or metronidazole. Resistance for five B fragilis species to cefoxitin, ceftizoxime, and cefotetan varied greatly among both species and participating institutions. The addition of a beta-lactamase inhibitor increased the potency of the beta-lactam drugs tested as combinations. This finding suggests that beta-lactamase production is the major resistance factor in members of the B fragilis group.

Sunlight exposure, pigmentary factors, and risk of nonmelanocytic skin cancer. I. Basal cell carcinoma.

BACKGROUND AND DESIGN: Basal cell carcinoma (BCC) of the skin is the most common neoplasm in white populations, and solar radiation is generally accepted to be the dominant environmental risk factor for this disease. However, little information is available on the nature of the relationship between BCC and sunlight. The purpose of this study was to evaluate the nature of the relationship between sunlight exposure, pigmentary factors, and BCC of the skin. A population-based case-control study of 226 male patients with BCC diagnosed from January 1, 1983, through December 31, 1984, and 406 randomly selected male control subjects was conducted in Alberta, Canada. The study was conducted using a standardized questionnaire, administered in person by trained interviewers. Data were analyzed using conditional logistic regression methods. RESULTS: After controlling for other host and pigmentary factors, the risk of BCC was increased in subjects with light skin color and those who freckled in childhood. A history of severe sunburn in childhood also increased risk. Subjects of southern European ethnic origin were at significantly lower risk of BCC. Surprisingly, no association was seen between mean annual cumulative summer sunlight exposure and risk of BCC. A significantly increased risk of BCC was seen in subjects with increased recreational sunlight exposure in adolescence and childhood (age, 0 to 19 years), although an inverse relationship was seen with lifetime recreation exposure. The relationship with childhood sun exposure was most pronounced among sun-sensitive subjects whose skin tended to burn rather than tan in the sun. CONCLUSIONS: The lack of association between cumulative sun exposure and BCC contradicts conventional wisdom about the cause of this tumor, and the increased risk with sun exposure at age 0 to 19 years suggests that childhood and adolescence may be critical periods for establishing adult risk for BCC.

Sunlight exposure, pigmentation factors, and risk of nonmelanocytic skin cancer. II. Squamous cell carcinoma.

INTRODUCTION AND DESIGN: Squamous cell carcinoma of the skin (SCC), a common cancer in white populations, is related to sunshine exposure; however, relatively little information is available on how timing and character of exposure affect the relationship. The purpose of this study was to investigate the nature of the relationship of SCC to individual solar UV exposure after control for phenotype and pigmentary factors. All newly diagnosed cases of SCC were in men aged 25 through 79 years, ascertained in the province of Alberta from January 1, 1983, through December 31, 1984, who were approached for participation; 80% completed a standardized etiologic interview that was conducted in their homes by a trained interviewer. Control subjects were chosen at random from the Alberta Health Care Insurance Plan subscribers list, matched only by sex (male) and age (within a 5-year age group). The response rate among controls was 71%. RESULTS: Subjects with pale skin and red hair had an elevated risk of SCC. Subjects whose mother was of southern European ancestry had a reduced risk of SCC. After accounting for pigmentary factors, no association was seen between risk of SCC and cumulative lifetime sun exposure. However, a strong trend toward increasing risk was seen with increasing chronic occupational sun exposure in the 10 years prior to diagnosis. CONCLUSION: The results suggest that recent sun exposure (in the 10 years prior to diagnosis) may be important in accounting for individual risk of SCC.