Association between plasma homocysteine and extracranial carotid arterial disease in older persons

The data demonstrate that high plasma homocysteine levels and low plasma folate and vitamin B12 levels are associated with a higher prevalence of 40% to 100% extracranial carotid arterial disease (ECAD) in older men and women. Elevated plasma homocysteine levels were observed in 45% of the older men with 40% to 100% ECAD versus 20% of the older men with 0% to 39% ECAD, and in 40% of the older women with 40% to 100% ECAD versus 18% of the older women with 0% to 39% ECAD.     

Randomized trial of alternating versus sequential radiotherapy/chemotherapy in limited-disease patients with small-cell lung cancer: a European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group Study

PURPOSE: To evaluate the effectiveness of alternating or sequential schedules of cyclophosphamide, doxorubicin, and etoposide (CDE) chemotherapy and irradiation in patients with previously untreated small-cell lung cancer (SCLC). MATERIALS AND METHODS: A total of 335 eligible patients were randomized between five courses of CDE chemotherapy followed by thoracic irradiation 50 Gy in 20 daily fractions (S) and the same total dose of chemotherapy and irradiation split into four courses of five daily fractions delivered on days 14 to 21 of the second and subsequent chemotherapy courses (A). Patients had a median age of 61 years (range, 33 to 75); 224 (66%) were male; the Eastern Cooperative Oncology Group (ECOG) performance status (PS) was 0 or 1 in 311; and 254 had weight loss less than 10%. RESULTS: The overall median survival duration was 15 months, with 62% (95% confidence interval [CI], 57% to 67%) 1-year, 25% (95% CI, 20% to 30%) 2-year, and 14% (95% CI, 10% to 18%) 3-year survival rates. There was no significant difference between the arms. The median survival time was 14 months in A and 15 months in S. One-year survival was 60% in A (95% CI, 53% to 67%) and 64% in S (95% CI, 57% to 71%); 2-year survival was 26% in A (95% CI, 19% to 33%) and 23% in S (95% CI, 16% to 30%); and 3-year survival was 12% in A (95% CI, 6% to 18%) and 15% in S (95% CI, 9% to 21%). World Health Organization (WHO) grade 3 and 4 neutropenia occurred in 90% of A and 77% of S patients (P < .001) and WHO grade 3 and 4 thrombocytopenia in 33% of A and 20% of S patients (P < .001). Rates of other acute and late toxicities were similar in both arms. Hematologic toxicity compromised treatment dose delivery; less than 50% of A patients received greater than 95% of prescribed chemotherapy and 77% their full radiation course, compared with 60% and 93% for arm S (P < .009). Local relapse was the site of first failure in 60% of all patients and 75% of these suffered an in-field relapse; no difference could be seen between the two arms. CONCLUSION: This trial failed to confirm the superiority of an alternating schedule of delivery. For this combination of chemotherapy and irradiation, hematologic toxicity compromised treatment delivery and could have contributed to the overall result. The poor rates of local control are disappointing and require intensification of the radiation therapy strategy.     

The plasma protein binding and distribution of etomidate in dog, rat and human blood

The interactions of etomidate and its major metabolite (R 28 141) with plasma proteins were studied by equilibrium dialysis with a multiple cell system. A 4% human serum albumin solution was able to bind 78.5% of the etomidate, and 60.5% of R 25 141, whereas a 1.5% human gamma globulin solution bound etomidate for not more than 3% and did not bind R 28 141 at all. The association constants and free binding energies for the binding of etomidate and R 28 141 to human serum albumin were determined. Plasma protein binding of etomidate was 75.4% in the dog and 76.5% in man; in rat plasma 79.5% of the radioactivity was bound to the plasma proteins, however the etomidate was partly hydrolyzed, even in the presence of sodium fluoride. In the rat 29.7% was distributed to the blood cells, 55.9% bound to plasma proteins and 14.4% was present in plasma water; in the dog the distribution percentages were 42.1%, 43.7% and 14.2% respectively, and in man 37.7%, 47.6% and 14.7% respectively. The major metabolite of etomidate was distributed for 26.3% to the human blood cells, 47.4% was bound to plasma proteins and 26.2% was present in the plasma water; its plasma protein binding amounted to 64.3%. Etomidate was bound at or in the blood cells, whereas R 28 141 was not.     

Use of the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI) to assist with triage of patients with chest pain or other symptoms suggestive of acute cardiac ischemia. A multicenter, controlled clinical trial

BACKGROUND: Approximately 6 million U.S. patients present to emergency departments annually with symptoms suggesting acute cardiac ischemia. Triage decisions for these patients are important but remain difficult. OBJECTIVE: To test whether computerized prediction of the probability of acute ischemia, used with electrocardiography, improves the accuracy of triage decisions. DESIGN: Controlled clinical trial. SETTING: 10 hospital emergency departments in the midwestern, southeastern, and northeastern United States. PATIENTS: 10689 patients with chest pain or other symptoms suggestive of acute cardiac ischemia. INTERVENTION: The probability of acute ischemia predicted by the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI), either automatically printed or not printed on patients' electrocardiograms. MEASUREMENTS: Emergency department triage to a coronary care unit (CCU), telemetry unit, ward, or home. Other measurements were the bed capacity of the CCU relative to that of the telemetry unit; training or supervision status of the triaging physician; and patient diagnoses and outcomes based on clinical, electrocardiographic, and creatine kinase data. RESULTS: For patients without cardiac ischemia, in hospitals with high-capacity CCUs and relatively low-capacity cardiac telemetry units, use of ACI-TIPI was associated with a reduction in CCU admissions from 15% to 12%, a change of -16% (95% CI, -30% to 0%), and an increase in emergency department discharges to home from 49% to 52%, a change of 6% (CI, 0% to 14%; overall P=0.09). Across all hospitals, for patients evaluated by unsupervised residents, use of ACI-TIPI was associated with a reduction in CCU admissions from 14% to 10%, a change of -32% (CI, -55% to 3%); a reduction in telemetry unit admissions from 39% to 31%, a change of -20% (CI, -34% to -2%); and an increase in discharges to home from 45% to 56%, a change of 25% (CI, 8% to 45%; overall P=0.008). Among patients with stable angina, in hospitals with high-capacity CCUs, use of ACI-TIPI was associated with a reduction in CCU admissions from 26% to 13%, a change of -50% (CI, -70% to -17%), and an increase in discharges to home from 20% to 22%, a change of 10% (CI, -29% to 71%; overall P=0.02). At hospitals with high-capacity telemetry units, use of ACI-TIPI was associated with a reduction in telemetry unit admissions from 68% to 59%, a change of -14% (CI, -27% to 1%), and an increase in emergency department discharges to home from 10% to 21%, a change of 100% (CI, 22% to 230%; overall P=0.02). Among patients with acute myocardial infarction or unstable angina, use of ACI-TIPI did not change appropriate admission (96%) to the CCU or telemetry unit at hospitals with high-capacity CCUs or telemetry units. CONCLUSIONS: Use of ACI-TIPI was associated with reduced hospitalization among emergency department patients without acute cardiac ischemia. This result varied as expected according to the CCU and cardiac telemetry unit capacities and physician supervision at individual hospitals. Appropriate admission for unstable angina or acute infarction was not affected. If ACI-TIPI is used widely in the United States, its potential incremental impact may be more than 200000 fewer unnecessary hospitalizations and more than 100000 fewer unnecessary CCU admissions.     

Sensitivity of Streptococcus agalactiae and Staphylococcus aureus to antibiotics in the Slovak Socialist Republic in the year 1974

In 1974, the State veterinary institutes in the Slovak Socialist Republic studied the sensitivity of 4420 strains of Streptococcus agalactiae and 1056 strains of Staphylococcus aureus to eight antibiotics. The strains were isolated from milk samples obtained from dairy cows suffering from mastitis. 100 per cent of the strains of Streptococcus agalactiae was sensitive to ampicillin, 99.23% to erythromycin, 98.70% to oxytetracycline, 93.02% to bacitracin, 90.77% to chloramphenicol, 41.97% to penicillin, 12.39% to neomycin, 9.73% to streptomycin. As to the strains of Staphylococcus aureus, 98.68 were sensitive to chloramphenicol, 98.50% to ampicillin, 97.92% to erythromycin, 94.98% to oxytetracycline, 93.85% to neomycin, 92.67% to bacitracin 87.50% to streptomycin, and 46.24% to penicillin. The results are discussed in relation to the use of antibiotics in the treatment of mastitis in dairy cows.     

Chondrodysplasia in Australian Dexter cattle

To evaluate the current prevalence of initial and acquired resistance to the main antituberculosis drugs in Yaounde, isolates of M. tuberculosis complex obtained from sputum cultures of 602 adult patients with pulmonary tuberculosis (516 new cases and 86 old cases) consecutively admitted into the tuberculosis centre of H?pital JAMOT from July 1994 to December 1995 were studied. The susceptibility of isolates to the major antituberculosis drugs was tested by the indirect proportion method. The overall resistance rate (1 or more drugs) was 35.2%, with initial resistance 31.8% (164 of 516) and acquired resistance 55.8% (48 of 86). Initial resistance to streptomycin was the most frequent (20.5%), followed by isoniazid 12.4%), thiacetazone (5.6%), rifampicine (0.8%) and ethambutol (0.4%). Initial resistance was noted as 25% to 1 drug, 5.8% to 2 drugs, 0.8% to 3 drugs and 0.2% to 4 drugs. Acquired resistance to isoniazid was the most frequent (45.3%), followed by streptomycin (40.7%), rifampicine (30.2%), thiacetazone (10.5%) and ethambutol (9.3%). Acquired resistance was found as 13.9% to one drug, 19.8% to 2 drugs, 12.8% to 3 drugs and 9.3% to 4 drugs. A combined resistance to rifampicine and isoniazid in the same patient was noted in 0.8% of the new cases and in 26.7% of the old cases. These high rates af antituberculosis drug resistance in Yaounde underline the urgent need to reestablish a tuberculosis control programme in Cameroon.     

Unrelated donor bone marrow transplantation for children with acute leukemia

PURPOSE: To test the use of unrelated donor bone marrow transplantation (URD BMT) to cure children with high-risk acute leukemias. PATIENTS AND METHODS: Between June 1985 and December 1994, 50 children with acute leukemia (15 acute myelogenous leukemia [AML], 35 acute lymphoblastic leukemia [ALL]; 22 greater than second complete remission [CR]) received BMT from a URD at the University of Minnesota. Ages ranged from 0.9 to 17.5 years (median, 8.8). Median follow-up is 2.1 years (range, 1 to 7.3). Thirty patients (60%) received bone marrow fully matched at HLA-A,B and DRB1; 20 (40%) received bone marrow with a major or minor mismatch at a single HLA-A or B locus. RESULTS: The median time to neutrophil engraftment was day 24 (range, 14 to 42 days) in those receiving matched and day 25 (range, 15 to 32 days) in those receiving mismatched marrow (P = .35). The incidence of grades III to IV graft-versus-host disease (GVHD) was 23% (95% confidence interval [CI], 7% to 39%) in matched and 32% (95% CI, 8% to 52%) in HLA-mismatched patients (P = .57). The incidence of chronic GVHD was 50% (95% CI, 28% to 72%) in matched and 57% (95% CI, 23% to 91%) in mismatched patients (P = .80). Disease-free survival for patients with ALL is 37% (95% CI, 21% to 53%) at 1 year and 30% (95% CI, 15% to 46%) at 2 years; for patients with AML, 53% (95% CI, 28% to 78%) at 1 year and 33% (95% CI, 6% to 60%) at 2 years. CONCLUSION: URD BMT is an effective treatment for children with poor-prognosis acute leukemia and should be considered for all high-risk patients. Early referral of patients is strongly recommended.     

Effect of long-term NO synthase inhibition on cyclic nucleotide content in rat tissues

The Cyto-Shuttle (Cancer Diagnostics, Inc., Fairfax, VA) monolayer preparation method was compared to our routine cytocentrifuge method in 129 fluid cytology cases. A single sample from each case was split and prepared by each method. The Cyto-Shuttle preparation was superior to the cytocentrifuge preparation in 51% of cases, equal to it in 38%, and inferior to it in 11%: bronchial wash/lavage (45 cases), 38%, 49%, 13%; body cavity fluid (39 cases), 72%, 15%, 13%; urine (18 cases), 56%, 44%, 0%: peritoneal washing (16 cases), 44%, 44%, 12%; and miscellaneous (11 cases), 36%, 55%, 9%. Cyto-Shuttle preparations were superior due to decreased background and increased number of cells per slide; fixation and morphology were generally equivalent to cytocentrifuge preparations.     

Gross periostitis ossificans in mandibular osteomyelitis. Review of the English literature and radiographic variation

BACKGROUND: Although the airway epithelium participates in inflammation and repair, the circadian expression of epithelial cell markers involved in these processes has not been investigated. OBJECTIVE: We sought to determine whether expression of CD51 (vitronectin and fibronectin receptor), CD54 (intercellular adhesion molecule-1), HLA-DR (activation marker), CD29 (beta1 integrin), CD49b (collagen receptor), and CD11b (complement receptor) exhibit a circadian rhythm in asthma. METHODS: Eleven patients with nocturnal asthma (NA), 9 subjects with nonnocturnal asthma (NNA), and 10 control subjects underwent bronchoscopy at 4 PM and 4 AM in a random order 1 week apart, with brushing of the proximal and distal airways. The percentage of cells staining for a particular marker was determined. RESULTS: At 4 PM, HLA-DR in the proximal airways and CD54 in the distal airways was significantly greater in control subjects as compared with asthmatic subjects (HLA-DR, control subjects: 10.0% [range, 5.0% to 21.0%]; NNA: 8.0% [range, 4.0% to 14.5%] NA: 3.5% [range, 2.0% to 6.0%], P = .01; CD54, control subjects: 17.0% [range, 8.0% to 25.0%], NNA: 8.0% [range, 5.3% to 11.5%], NA: 7.0% [range, 4.0% to 15.0%], P = .O;). At 4 AM, CD51 in the distal airways was significantly greater in patients with NA as compared with patients with NNA and control subjects (control subjects, 23.0% [range, 13.8% to 30.5%]; NNA, 32.0% [range, 13.0% to 35.0%]; NA, 40.0% [range, 23.0% to 50.0%], P = .05). Expression of CD51 in the distal airways correlated with the degree of airway obstruction (r = -0.57, P = .001). Control subjects exhibited significant circadian variation in the expression of HLA-DR in the proximal airways and CD54 in the distal airways. CONCLUSION: The increased CD51 at night in patients with NA may be related to increased airway inflammation and repair processes in response to injury. The circadian changes in CD54 and HLA-DR in control subjects require further study to determine their significance. (J Allergy Clin     

Indicators of hospital treatment and the organization and management of injuries and diseases in armed combat in 1991 and 1992

Efficiency of organisation of management of the injured and diseased in combat operations in 1991/2 and results of hospital treatment are studied. The questionnaire was established for collection of data about stationary treatment of the wounded and diseased in 7 military and 15 civilian medical institutions. Data about 9.243 injured of whom only 5.57% were civilians are especially analysed. In most cases injuries were inflicted by mine-explosive devices (48.77% in combat and 6.27% in non-combat operations), then those inflicted by bullets (38.58% in combat and 8.02% in non-combat operations). Self-inflicted injuries occurred in 5.79% in combat and 10.32% in non-combat operations. Injuries inflicted in non-combat operations were found in a high percentage (46.60). They mostly occurred in the open air (41.26%). Injuries of extremities are predominant (64.70%), then injuries of the head and neck (17.90%), thorax (9.90%), abdomen and pelvis (7.50%). Young men (20-24 years old) were commonly injured but the older ones (over 40 years) have been also frequently injured (18.30%). Evacuation of the wounded and diseased was performed mainly by ambulances (about 60%) or helicopters (16%), especially to the medical institutions far in the country (to M.M.A. up to 60%). The first aid was given within the first ten minutes after injury in 55.00% and within 30 minutes in 65.58% of cases. Mutual aid was most frequently applied (33.12%) and then first aid given by general practitioners (32.12%). Surgical treatment was provided one hour after injury to every fourth wounded (24.08%) and after six hours to more than one third of the wounded (31.88%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Pathogenic potential of Gardnerella vaginalis on the female urogenital system

The prevalence of certain characteristics of genital discharge like (a) watery variety in sexually transmitted disease (STD) clinic 34% and in gynaecology clinic 26.6%, (b) fishy odour in STD clinic 29.2% and in gynaecology clinic 12.2% and (c) pH > 4.5 in STD clinic 53.6% and in gynaecology clinic 43% was notable. On the other hand, occurrence of "clue cells" (in STD clinic 41.4% and in gynaecology clinic 39.5%) did not show difference in the aforesaid clinics. The preponderance of watery discharge in the STD clinic appears to be related to G vaginalis (in STD clinic 26.8% and in gynaecology clinic 9.3%). It is intriguing to note that G vaginalis was isolated from leucorrhoea (in STD clinic 19.5% and in gynaecology clinic 9.3%) and inapparent (in 10%) cases and normal (in 4.2%) cases. Single infection with G vaginalis in one particular case had profuse watery discharge, pH > 4.5 and there was occurrence of "clue cells". Likewise, in multiple infections revealing G vaginalis (29 cases) as one of the potential agents, 78.5% had profuse, 53.8% watery discharge of which 53.5% had "clue cells" and 81% had pH > 4.5. In mixed type of infections, the U urealyticum (53.8%) and M hominis (30.6%) were conspicuous in bacterial vaginosis. Cervicitis, erosion cervix or urethral syndrome were unrelated to G vaginalis. All cases of G vaginalis infection responded to metronidazole with remission of leucorrhoea in 25.9% cases.     

Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium

The contribution of BRCA1 and BRCA2 to inherited breast cancer was assessed by linkage and mutation analysis in 237 families, each with at least four cases of breast cancer, collected by the Breast Cancer Linkage Consortium. Families were included without regard to the occurrence of ovarian or other cancers. Overall, disease was linked to BRCA1 in an estimated 52% of families, to BRCA2 in 32% of families, and to neither gene in 16% (95% confidence interval [CI] 6%-28%), suggesting other predisposition genes. The majority (81%) of the breast-ovarian cancer families were due to BRCA1, with most others (14%) due to BRCA2. Conversely, the majority of families with male and female breast cancer were due to BRCA2 (76%). The largest proportion (67%) of families due to other genes was found in families with four or five cases of female breast cancer only. These estimates were not substantially affected either by changing the assumed penetrance model for BRCA1 or by including or excluding BRCA1 mutation data. Among those families with disease due to BRCA1 that were tested by one of the standard screening methods, mutations were detected in the coding sequence or splice sites in an estimated 63% (95% CI 51%-77%). The estimated sensitivity was identical for direct sequencing and other techniques. The penetrance of BRCA2 was estimated by maximizing the LOD score in BRCA2-mutation families, over all possible penetrance functions. The estimated cumulative risk of breast cancer reached 28% (95% CI 9%-44%) by age 50 years and 84% (95% CI 43%-95%) by age 70 years. The corresponding ovarian cancer risks were 0.4% (95% CI 0%-1%) by age 50 years and 27% (95% CI 0%-47%) by age 70 years. The lifetime risk of breast cancer appears similar to the risk in BRCA1 carriers, but there was some suggestion of a lower risk in BRCA2 carriers <50 years of age.     

Do interventions that improve immunisation uptake also reduce social inequalities in uptake?

OBJECTIVE: To investigate whether an intervention designed to improve overall immunisation uptake affected social inequalities in uptake. DESIGN: Cross-sectional small area analyses measuring immunisation uptake in cohorts of children before and after intervention. Small areas classified into five groups, from most deprived to most affluent, with Townsend deprivation score of census enumeration districts. SETTING: County of Northumberland. SUBJECTS: All children born in country in four birth cohorts (1981-2, 1985-6, 1987-8, and 1990-1) and still resident at time of analysis. MAIN OUTCOME MEASURES: Overall uptake in each cohort of pertussis, diphtheria, and measles immunisation, difference in uptake between most deprived and most affluent areas, and odds ratio of uptake between deprived and affluent areas. RESULTS: Coverage for pertussis immunisation rose from 53.4% in first cohort to 91.1% in final cohort. Coverage in the most deprived areas was lower than in the most affluent areas by 4.7%, 8.7%, 10.2%, and 7.0% respectively in successive cohorts, corresponding to an increase in odds ratio of uptake between deprived and affluent areas from 1.2 to 1.6 to 1.9 to 2.3. Coverage for diphtheria immunisation rose from 70.0% to 93.8%; differences between deprived and affluent areas changed from 8.6% to 8.3% to 9.0% to 5.5%, corresponding to odds ratios of 1.5, 2.0, 2.5, and 2.6. Coverage for measles immunisation rose from 52.5% to 91.4%; differences between deprived and affluent areas changed from 9.1% to 5.7% to 8.2% to 3.6%, corresponding to odds ratios of 1.4, 1.4, 1.7, and 1.5. CONCLUSION: Despite substantial increase in immunisation uptake, inequalities between deprived and affluent areas persisted or became wider. Any reduction in inequality occurred only after uptake in affluent areas approached 95%. Interventions that improve overall uptake of preventive measures are unlikely to reduce social inequalities in uptake.     

Clinical and histopathological aspects of 113 necrotizing malignant melanomas of the choroid. 1. Clinical and histological features of necrotizing choroidal melanomas

BACKGROUND: Tumor necrosis may reflect a destructive immune reaction. Systematic and statistically significant comparative clinico-histopathologic studies have not yet been reported. PATIENTS AND METHODS: 113 necrotizing choroidal melanomas (NCM) recruited from 701 enucleated globes 1967-1988 were resectioned, stained and compared to 100 choroidal melanomas without necrosis (CM), and data of 74 patients with a follow-up of more than 10 years were evaluated. RESULTS: Statistically significant characteristics of NCM were: patient age < 60 yrs. for NCM 27.4%, CM 46%; patient age in men for NCM was 64 yrs on average (CM: 58 yrs.), in women for NCM 67 yrs. (CM: 59 yrs.). Time elapsed between first symptoms and enucleation was < 12 months in 15.9% of NCM (89% for CM), and > 12 months in 23.9% of NCM (11% in CM). Mixed or epitheloid cell tumors was seen in 54.9% of NCM and 49% of CM, spindle cell tumors in 36.3% of NCM and 51% in CM. Advanced tumor stages T3 and T4 were present in 45.1% resp. 36.3% of NCM compared to 37% resp. 16% in CM. Scleral invasion was documented in 67.3% of NCM and 37% of CM, extrascleral dissemination in 43% of NCM and 16% of CM. Secondary glaucomas were seen in 62.2% of NCM and 6% CM, a penetration through Bruch's membrane in 61.0% of NCM and 46% of CM. Intratumoral hemorrhage was noted in 68.14% of NCM and 24% of CM, extratumoral bleeding in 23.9% of NCM and 0% CM. Inflammatory reactions in tumors were observed in 96.7% of NCM harboring > 30% necrosis compared to 5% in CM, and extratumoral in 94.5% of NCM and 0% of CM. Intraocular extratumoral necrosis was seen in 23.9% of NCM and 0% of CM. There were no significant differences in the degree of pigmentation of the 90.3% pigmented NCM or of the 94% pigmented CM, neither in the tumor localization, being constantly behind the equator in 87% of cases. Survival of patients with NCM patients was 5 years and 9 months on average (5-year mortality rate 41.9%), and 74.3% were deceased from metastatic spread. CONCLUSIONS: Significant clinical and histopathological differences between necrotizing and non-necrotizing malignant melanomas of the choroid can be identified. The inflammatory reaction of NCM must be further elucidated, particularly with respect to the nature of tumor-infiltrating lymphocytes.     

Lack of cross-tolerance to short-term linsidomine in forearm resistance vessels and dorsal hand veins in subjects with nitroglycerin tolerance

BACKGROUND: Therapy with nitroglycerin is widely used in the treatment of angina pectoris, but development of tolerance is a major problem. Nitrovasodilators other than nitroglycerin may be less prone to induce vascular tolerance. This investigation was designed to test whether the alternative nitric oxide donor linsidomine maintains its vasodilator effects in the presence of nitroglycerin tolerance. METHODS: We tested the vascular effects of nitroglycerin and linsidomine (SIN-1) in forearm resistance arteries (venous occlusion plethysmography) and hand veins (venous compliance technique) using a randomized, double-blind placebo-controlled regimen in 33 healthy subjects (age range, 22 to 38 years; mean age, 26 years) before and after 7 days of assignment to either 1 week of nitroglycerin administration (0.83 mg/hr) for induction of tolerance or placebo administration. RESULTS: Vascular responses of both vascular beds to nitroglycerin (in veins: mean difference, 42.3%; confidence interval [CI], 3% to 81.7%; p < 0.05; in arteries: mean difference, 65.0%; CI, 38.9% to 91.1%; p < 0.01) but not to linsidomine (in veins: mean difference, -13.8%; CI, -53.5 to 25.8%; not significant; in arteries: -19.7%; CI, -33.7% to -5.6%; not significant) were attenuated in the nitroglycerin patch group, whereas the placebo group showed no differences to either nitroglycerin (in arteries: mean difference, -7.5%; CI, -44.6% to 29.6%; in veins: -10.6%; CI, -58.2% to 36.9%) or linsidomine (in arteries: 4.5%; CI, -12.8% to 21.7%; in veins: -13.1%; CI, -4.5% to 29.8%). CONCLUSION: These results suggest that short-term administration of sydnonimines can overcome the loss of vascular relaxation associated with long-term nitroglycerin therapy.     

Epidemiology of community-acquired Pseudomonas aeruginosa infections in children

The epidemiology of community-acquired Pseudomonas aeruginosa infections in children during a one-year period (January through December 1993) was evaluated. A total of 6,859 clinical samples, each one representing a separate individual with suspected infection, were cultured. Pseudomonas aeruginosa was isolated from 218 children with various infections occurring in the following order of frequency: chronic suppurative otitis media, 76.3%; appendicitis/peritonitis, 10.3%; osteomyelitis, 8.9%; skin or soft tissue infection, 6.3%; acute conjunctivitis, 3.0%; and urinary tract infection, 0.1%. A variety of O serogroups were identified: O1 (15.2%), O6 (14.7%), O11 (12.4%), O10 (11.5%), O3 (10.6%), O5 (5.1%), and O9 (4.6%). Other serogroups and nontypable strains were recovered at a frequency of 11.2% and 14.7%, respectively. Nontypable strains predominated in chronic otitis media (18.9%), while serogroups O1 (18.3%), O6 (17.5%), and O11 (17.5%) were recovered most frequently among the typable isolates. Susceptibility of Pseudomonas aeruginosa to antipseudomonadal agents was extremely high. The rate of susceptibility to ceftazidime was 99.6%, to azlocillin 98.6%, to piperacillin 98.2%, to aztreonam 97.3%, to gentamicin and netilmicin 97.7%, and to ciprofloxacin 99.1%. All isolates were susceptible to tobramycin, imipenem, and amikacin. The results might suggest that community-acquired Pseudomonas aeruginosa infections in children can be treated successfully with any antipseudomonadal antibiotic.     

Factors affecting long term survival following resection for lung cancer

BACKGROUND: Survival following pulmonary resection for primary lung cancer is considered to be principally dependent on the clinical stage of the disease. A study was undertaken to verify this and to identify other contributing factors. METHODS: The case records of all patients who underwent surgery for lung cancer over a two year period between January 1987 and December 1988 were reviewed retrospectively. RESULTS: One hundred and forty-seven lobectomies and 60 pneumonectomies were performed with 2.8% and 5.3% operative mortality, respectively. Squamous carcinoma was the commonest pathology (60%) followed by adenocarcinoma (30%). The overall five year survival was 45.5% (95% CI 44.1% to 57.9%). There were 123 patients with stage I disease, 40 with stage II, and 37 in stage IIIa with five year survival of 59.4% (95% CI 50.8% to 68%), 30% (95% CI 15.9% to 44.1%), and 16.2% (95% CI 3.5% to 31%), respectively. There were no differences in survival with respect to sex, extent of resection, or cell type. In patients with stage II disease the five year survival of those with T1 lesions (50%, 95% CI 37.3% to 62.9%) was better than those with T2 (28.1%, 95% CI 16.9% to 39.3%). Of eight patients over the age of 70 with stage IIIa disease none survived more than 24 months. CONCLUSIONS: Stage at operation is the most accurate predictor of long term survival in early lung cancer and surgery remains an effective treatment, particularly in stage I and II disease. Further study is needed to assess the prognostic value of subdividing stage II disease into T1 and T2 lesions. Major resection for locally advanced disease in older patients may be relatively ineffective.     

Development and testing of a quality of life model for long-term female cancer survivors

OBJECTIVES: To document the effects of pelvic radiotherapy on bowel, bladder, and sexual function, as reported by the patient. METHODS: A confidential questionnaire was distributed to 202 prostate cancer patients. Mean age was 70 years (range, 49 to 87) and mean follow-up was 33 months (range, 12 to 72). Radiation was given by a standard four field box technique on a linear accelerator to 60 to 66 Gy over 6.5 weeks. Treatment was limited to the prostate and seminal vesicles for small well-differentiated tumors, but otherwise included internal and external iliac nodes. RESULTS: Responses were obtained from 192 patients (95%). No or mild change in bowel function was reported by 64% of patients, 25% reported moderate change, and 11% reported severe change. Rectal urgency was a concern for 20%, and 5% reported fecal soiling in the preceding 6 months. Hematochezia at least once a week was reported by 9% and daily by 5%. Frequent hematochezia decreased from 17% in the second and third post-treatment years to 4% after 3 years (P = 0.02). Transfusions or laser surgery for proctitis was required by 4%. No patient required a colostomy for rectal complications. Urinary stream was unchanged or improved for 83%. Nocturia was unchanged or improved in 70%. Some form of protection for urinary incontinence was required by 2%, and 0.5% noted frequent hematuria and 2% moderate to severe dysuria. Potency prior to radiotherapy was reported by 82% and was lost following radiotherapy in 35%. Technical factors, including treatment volumes and total dose, did not correlate to the risk of moderate or severe complications. CONCLUSIONS: The sequelae of pelvic radiotherapy as viewed from the patient's perspective reveal a major alteration in bowel function in 11%, significant bladder symptoms in 4%, and loss of potency in 35%.     

Short-term oral endothelin-receptor antagonist therapy in conventionally treated patients with symptomatic severe chronic heart failure

BACKGROUND: The vasoconstrictor peptide endothelin-1 (ET-1) is important for increased vascular tone in patients with chronic heart failure, but the effects of endothelin-receptor blockade in addition to conventional triple therapy are unknown. METHODS AND RESULTS: Thirty-six men (mean age+/-SD, 55+/-8 years) with symptomatic heart failure (NYHA class III; left ventricular ejection fraction, 22.4+/-4.5%) despite treatment with diuretics, digoxin, and ACE inhibitors received, in a double-blind and randomized fashion, either additional oral bosentan (1.0 g BID; n=24) or placebo (n=12) over 2 weeks. Hemodynamic and hormonal (plasma ET-1, norepinephrine, renin activity, and angiotensin II) measurements were obtained before and repeatedly for 24 hours after administration of bosentan on days 1 and 14. Bosentan was discontinued in 1 patient with symptomatic hypotension, and 2 patients (bosentan group) declined hemodynamic investigations on day 14. Compared with placebo, bosentan on day 1 significantly decreased mean arterial pressure (difference from baseline over 12 hours [95% CIs], -13.9% [-16.0% to -11.7%]), pulmonary artery mean (-12.9% [-17. 4% to -8.3%]) and capillary wedge (-14.5% [-20.5% to -8.5%]) pressures, and right atrial pressure (-20.2% [-29.4% to -11.0%]). Cardiac output increased (15.1% [10.7% to 19.7%]), but heart rate was unchanged. Both systemic (-24.2% [-28.1% to -20.3%]) and pulmonary (-19.9% [-28.4% to -11.4%]) vascular resistance were reduced. After 2 weeks, cardiac output had further increased (by 15. 2% [10.8% to 19.6%]) and systemic (-9.3% [-12.3% to -6.4%]) and pulmonary (-9.7% [-16.3% to -3.1%]) vascular resistances further decreased compared with day 1. Heart rate remained unchanged. Plasma ET-1 levels increased after bosentan, but baseline levels of the other hormones were unchanged. CONCLUSIONS: Additional short-term oral endothelin-receptor antagonist therapy improved systemic and pulmonary hemodynamics in heart failure patients who were symptomatic with standard triple-drug therapy. Further investigations are warranted to characterize the effects of long-term endothelin-receptor antagonist therapy on symptoms, morbidity, and mortality in such patients.     

Effects of antiglaucoma drugs and corticosteroids on the cellular glucose uptake in cultured porcine corneal endothelial cells

In this study, various commercially used antiglaucoma drugs and corticosteroids were investigated in their effects on porcine corneal endothelial cells especially in cellular glucose uptake. Cellular glucose uptake directly affects the pumping efficiency in corneal endothelial cells. Following the cells' treatment with various antiglaucoma eyedrops for 100 min, the 3H-2-deoxyglucose uptake in cultured porcine corneal endothelial cells was affected by betaxolol from 3.1% (1.6 mM), 181% (0.16 mM) to 158% (0.016 mM), by timolol from 93% (0.79 mM), 227% (0.079 mM) to 151% (0.0079 mM), by carteolol from 141% (3.4 mM), 180% (0.34 mM) to 97% (0.034 mM), by levobunolol from 80% (1.5 mM), 98% (0.15 mM) to 90% (0.015 mM), by dipivefrin from 116% (0.2 mM), 176% (0.02 mM) to 108% (0.002 mM) and by pilocarpine from 115% (9.6 mM), 210% (0.96 mM) to 210% (0.096 mM) when the cells were compared with a control medium. In the presence of various corticosteroids, the glucose uptake in corneal endothelial cells was affected by fluorometholone from 160% (0.26 mM), 139% (0.026 mM) to 107% (0.0026 mM), by dexamethasone from 85% (0.25 mM), 117% (0.025 mM) to 109% (0.0025 mM) and by betamethasone from 95% (0.25 mM), 96% (0.025 mM) to 99% (0.0025 mM). These results show that the commercial eyedrops of antiglaucoma drugs and corticosteroids will not decrease the cellular glucose uptake in cultured porcine corneal endothelial cells except when incubated with high concentrations of betaxolol, levobunolol and dexamethasone.