The association between cigarette smoking and selected HIV-related medical conditions

OBJECTIVE: To clarify the effect of cigarette smoking on the development of conditions associated with HIV infection. DESIGN: Prospective and retrospective cohort study, with interview and examination twice a year since 1988. METHODS: Data on 516 HIV-infected men from cohorts of homosexual and bisexual men in San Francisco, Denver and Chicago, who were repeatedly interviewed and examined between 1988 and 1992, were analysed. After excluding men who did not have well-defined dates of seroconversion and those who were classified as ex- or intermittent smokers, 232 men remained for analysis: 106 were smokers and 126 were non-smokers. Univariate and Kaplan-Meier survival analyses were performed to assess the relationship between cigarette smoking and loss of CD4+ T-lymphocytes, diagnosis of any AIDS-defining illness, and specific diagnosis of Kaposi's sarcoma, Pneumocystis carinii pneumonia (PCP), oral candidiasis, hairy leukoplakia, and community-acquired pneumonia. RESULTS: By univariate analyses, cigarette smoking was not associated with clinical AIDS, loss of CD4+ cells, Kaposi's sarcoma or PCP, but was significantly associated with oral candidiasis [relative risk (RR), 1.32; 95% confidence interval (CI), 1.02-1.70], hairy leukoplakia (RR, 1.51; 95% CI, 1.15-1.99), and community-acquired pneumonia (RR, 2.62; 95% CI, 1.30-5.27). Dose-response effect was also evident for these three conditions (all P < 0.01). Kaplan-Meier survival analysis indicated no association between cigarette smoking and time of progression to clinical AIDS, Kaposi's sarcoma (KS), or PCP (P = 0.62, 0.54 and 0.11, respectively) but showed that cigarette smokers developed oral candidiasis, hairy leukoplakia, and pneumonia more quickly than non-smokers (P = 0.031, 0.006 and 0.009, respectively). CONCLUSIONS: Cigarette smoking was not associated with an increased likelihood or rate of developing KS, PCP or AIDS, but was associated with developing community-acquired pneumonia, oral candidiasis, and hairy leukoplakia in these HIV-infected men.     

Incidence of bacterial pneumonia in HIV-positive patients treated with preventive co-trimoxazole or pentamidine

BACKGROUND: Besides Pneumocystis carinii bacterial pathogens represent the most common aetiology of pulmonary infections in HIV-positive patients. However, the impact of PCP prophylaxis on the incidence of bacterial pneumonia in HIV-positive patients using pentamidine or co-trimoxazole is still unknown. PATIENTS AND METHODS: We analysed retrospectively the data of 80 consecutive HIV-positive patients with a CD4-cell count < 300/microliter. The total observation period was 1993 patient months. Type and duration of chemoprophylaxis, frequency of bacterial pneumonia, PCP, extrapulmonary bacterial infections and cerebral toxoplasmosis were documented in a standardised manner. For statistical analysis we used the Kaplan-Meier test for the time to a recurrence of the various infections under both prophylaxis regimens and the Odds ratio for determination of the relative risk. RESULTS: We followed up 47 patients inhaling 300 mg pentamidine monthly for a total of 1133 months and 33 patients taking 480 mg co-trimoxazole per day p.o. for a total of 860 months. There were no statistically significant differences between the two groups in respect of demographic parameters, stage and therapy of HIV infection and distribution of risk groups. We found seven bacterial pneumonias in the co-trimoxazole group and 13 in the pentamidine group (not significant); the most common causative organisms were S. pneumoniae (n = 4), S. aureus (n = 3) and H. influenzae (n = 3). Furthermore, in the pentamidine group 12 PCP and nine cases of toxoplasma encephalitis were observed, whereas none of these infections occurred in the co-trimoxazole group (p < 0.05). Two of the patients taking co-trimoxazole and 15 of those inhaling pentamidine had extrapulmonary bacterial infections (p < 0.05), the most frequently identified pathogen being S. aureus (n = 7). The two prophylaxis groups did not differ significantly with regard to laboratory data, course and therapy of the bacterial pneumonias. CONCLUSION: There was no significant influence of chemoprophylaxis on the incidence of bacterial pneumonia in patients with advanced HIV-disease in our study. Since S. pneumoniae represents the most common causative agent, we suggest immunisation with a polyvalent pneumococcal vaccine at an early stage of HIV-infection.     

Myocardial infarction in critically ill patients presenting with gastrointestinal hemorrhage: retrospective analysis of risks and outcomes

OBJECTIVES: To determine the frequency of and risk factors for myocardial infarction (MI) in patients admitted to an ICU with GI hemorrhage, and the effects of MI on mortality and length of stay. METHODS: A retrospective review of the medical records of patients admitted to our ICU with GI hemorrhage was conducted. Charts were reviewed for various demographic, laboratory, and outcome parameters. Patients were categorized as having MI, not having MI, or inadequate data to allow classification. RESULTS: Two hundred thirty admissions to the ICU for GI hemorrhage were reviewed. One hundred thirteen cases had serial creatine phosphokinase (CK) measurements with isoenzymes allowing diagnosis of MI. In these 113 cases, patients' mean age was 67.4+/-1.3 years and the mean APACHE II (acute physiology and chronic health evaluation) score was 10.9+/-0.6. The in-hospital mortality rate was 13/113 (11.5%). Patients who did not survive had a higher admission APACHE II score (15.8+/-2.0 vs 10.2+/-0.5; p = 0.02), lower initial systolic BP (104.5+/-4.4 vs 121.2+/-3.2 mm Hg; p = 0.005), and a longer length of ICU stay (8.3+/-1.8 vs 4.0+/-0.4 days; p = 0.04) than those who survived. Sixteen of 113 patients met enzymatic and ECG criteria for MI. One patient complained of chest pain and nine of 16 had shortness of breath and/or dizziness. Patients with MI had significantly more cardiac risk factors (2.4+/-0.2 vs 1.6+/-0.1; p = 0.006), lower presenting hematocrit (26.0+/-1.3 vs 30.5+/-0.8; p = 0.007), and lower lowest hematocrit in the first 48 h (22.3+/-0.9 vs 25.1+/-0.6; p = 0.01), and tended to have a longer ICU stays (7.9+/-2.2 vs 4.0+/-0.4 days; p = 0.09) than those without MI. Patients who had MI were not more likely to die during hospitalization (risk ratio = 1.8; 95% confidence interval, 0.6 to 5.8). CONCLUSIONS: Myocardial infarction occurs frequently in patients admitted to intensive care with GI hemorrhage. A clinical history of and multiple risk factors for coronary artery disease may help identify patients who are at increased risk of MI, which tends to be associated with a higher acuity of illness and in-hospital mortality. Prospective studies are required to further substantiate these associations.     

Effect of testosterone replacement on whole body glucose utilisation and other cardiovascular risk factors in males with idiopathic hypogonadotrophic hypogonadism

BACKGROUND: Excessive testosterone in males or estrogens in females could explain their differences in coronary heart disease event rates. As a contraceptive testosterone is likely to be used at large scale the role of testosterone in increasing the risks of coronary heart disease needs investigation. AIM: To look at the role of testosterone in development of insulin resistance and other cardiovascular risk factors. DESIGN: Prospective, before-after study on ten male subjects with idiopathic hypogonadotrophic hypogonadism pre- and post-testosterone replacement therapy; outcome measures: anthropometry, lipoprotein profile and M value (whole body glucose disposal rates on standard hyperinsulinemic euglycemic clamp; at insulin infusion rate: 40 mU x (m-2)). RESULTS: Pre-treatment serum testosterone was 0.43 (0.515) ng x mL(-1), LH was 1.29 (0.08) IU x L(-1), and FSH was 1.54 (0.08) IU x L(-1). None had glucose intolerance. After replacement testosterone levels increased to 9.4 ng x mL(-1) (p=0.0005); weight increase of 5.0 kg (p=0.140), body mass index increase of 1.2 kg x m(-2) (p=0.28), and the change in waist to hip ratio (p=0.31) were not statistically significant. M-value (mg x kg x min(-1)) did not change after testosterone therapy (5.86 [0.72] vs 5.29 [0.82], p=0.62). Insulin levels (mU x L(-1)) achieved during the clamps were 89.5 (14.2) before and 146 (32.2) after androgen therapy (p=0.127). There was no change in glucose area under curve (mg x min x dL(-1)) (14406 [502.2] vs 12557 [826.5], p=0.312). On testosterone replacement therapy total and LDL cholesterol levels (mg x dL(-1)) declined (122.5 [13.4] vs 91.6 [5.0], p=0.04; 65.9 [9.9] vs 39.4 [7.3], p=0.05); Ratio of total cholesterol to HDL ratio also decreased significantly (p=0.05). Changes of serum triglycerides (p=0.25) and HDL cholesterol (p=0.19) did not attain statistical significance. CONCLUSIONS: Insulin sensitivity does not decrease on testosterone replacement therapy of male subjects with idiopathic hypogonadotrophic hypogonadism. Testosterone replacement was associated with decrease in other cardiovascular risk factors.     

Clearance of Pneumocystis carinii cysts in acute P carinii pneumonia: assessment by serial sputum induction

STUDY OBJECTIVES: To determine the feasibility of repeat sputum induction in acute Pneumocystis carinii pneumonia (PCP) and to define the rate of clearance of P carinii cysts from the respiratory tract of HIV-seropositive patients with acute PCP. DESIGN: Prospective cohort evaluation. SETTING: University medical center. PARTICIPANTS: Twenty-four HIV-seropositive subjects with acute PCP. MEASUREMENTS: Sputum induction for P carinii 2, 3, 4, and 6 weeks after initial diagnosis, and follow-up for 1 year. RESULTS: Eighty-eight percent of subjects had residual cysts at 2 weeks, 76% at 3 weeks, 29% at 4 weeks, and 24% at 6 weeks postdiagnosis. A prior AIDS-defining illness (p = 0.033) or prior PCP (p = 0.004) predicted relapse within 6 months, but persistent cysts at 3 weeks did not; 8 of 16 sputum-positive subjects and 1 of 5 sputum-negative subjects experienced a relapse within 6 months (p = 0.34). Secondary prophylaxis with trimethoprim-sulfamethoxazole was associated with a reduced risk of relapse. CONCLUSIONS: Serial sputum induction coupled with direct fluorescent antibody staining is a feasible, noninvasive method of respiratory tract surveillance for the eradication of P carinii during and after acute PCP. Three-quarters of HIV-seropositive patients with acute PCP have persistent cysts in their lungs at the end of antimicrobial treatment, despite clinical recuperation, but only one quarter have residual cysts 6 weeks postdiagnosis. A prior AIDS-defining illness and prior PCP are positively associated, and subsequent trimethoprim-sulfamethoxazole prophylaxis is negatively associated, with relapse within 6 months, while persistent organisms at 3 weeks do not appear to be a significant predictor of relapse risk.     

Is autonomic neuropathy a risk factor for severe hypoglycaemia? The EURODIAB IDDM Complications Study

The hypothesis that diabetic patients with autonomic neuropathy are at increased risk of severe hypoglycaemia was examined in an epidemiological study of over 3000 IDDM patients in Europe (EURODIAB IDDM Complications Study). Autonomic function was assessed by two standard cardiovascular tests: change in heart rate and systolic blood pressure on standing. Severe hypoglycaemia was defined as an attack serious enough to require the help of another person. Compared to patients (68%) reporting no attacks in the last year, those reporting one or more attacks were older (34.0 +/- 10.7 vs 32.1 +/- 9.9 years, mean +/- SD, p < 0.0001), had had diabetes for a longer period (16.6 +/- 9.5 vs 13.8 +/- 9.1 years, p < 0.0001), had better glycaemic control (HbA1c 6.4 +/- 1.8 vs 6.9 +/- 1.9%, p < 0.0001) and were more likely (p = 0.002) to have abnormal responses to both autonomic tests (13.0 vs 7.7%). A single abnormal autonomic response was not associated with an increased risk of severe hypoglycaemia. The odds ratio for severe hypoglycaemia in people with abnormal responses to both autonomic tests, compared to those with normal responses, was 1.7 (95% confidence interval 1.3, 2.2) after controlling for age, duration of diabetes, glycaemic control and study centre. In conclusion, a combined autonomic deficit in heart rate and blood pressure responses to standing is associated with only a modest increase in the risk of severe spontaneous hypoglycaemia. Although the increase in risk is not large, severe hypoglycaemia was a frequently reported event in this study. IDDM patients with deficient autonomic responses who strive for tight glycaemic control may therefore be at particular risk of severe hypoglycaemia.     

Oral manifestations of human immunodeficiency virus-infected patients in Taiwan

To understand the characteristic clinical features of human immunodeficiency virus (HIV)-related oral lesions and determine the prevalence of various oral lesions in HIV-infected patients in Taiwan, we conducted a cross-sectional study of 207 HIV-infected patients at the Taipei Municipal Institute for Venereal Disease Control. Overall, 108 (52.2%) patients had at least one oral lesion. The most common oral manifestation of HIV infection among these 207 patients was oral hairy leukoplakia (OHL, 29.5%), followed by candidiasis (12.1%), xerostomia (10.6%), aphthous ulcers (8.7%), and linear gingival erythema (5.8%). Less frequently encountered oral lesions included leukoplakia (1.9%), papilloma (1.4%), necrotizing ulcerative periodontitis (1.0%), Kaposi's sarcoma (1.0%), herpes simplex (0.5%), Burkitt's lymphoma (0.5%), and parotid gland enlargement (0.5%). Thirty-one (15%) patients had multiple oral lesions. Patients with oral candidiasis or multiple oral lesions had significantly lower mean CD4 lymphocyte counts and CD4/CD8 lymphocyte ratios than those without any oral lesions (p < 0.05). Chi-square analysis revealed that patients with CD4 lymphocyte counts below 200 cells/mm3 were more prone to have OHL (p < 0.002), oral candidiasis (p < 0.001) and multiple oral lesions (p < 0.001). Those with CD4/CD8 lymphocyte ratios below 0.4 were more likely to have OHL (p < 0.02), oral candidiasis (p < 0.01) and multiple oral lesions (p < 0.02) than those with higher counts. In conclusion, the occurrence of oral lesions, especially OHL and oral candidiasis, is fairly common in Taiwanese HIV-infected patients.     

Cardiovascular prevention, primary or secondary, in high risk patients

Two groups of patients admitted to hospital consecutively for coronary artery disease in 36 university hospital departments were interrogated about the advice received and followed concerning cardiovascular prevention both before the clinical onset of the disease (Group I), those with disease of less than one month duration (primary prevention), or after this period (Group II), those with disease for over six months (secondary prevention). The follow-up of risk factors or medical advice concerning prevention (dietary and/or treatment) was more common, and compliance to the advice was better, in secondary prevention. However, in both groups, with the exception of hypertension, the diagnosis and follow-up of the risk factors were incomplete with 19% vs 41% (p < or = 0.001) of serum cholesterol levels unmeasured before the onset of clinical disease; during the last 5 years, 41% vs 12% (cholesterol, p < or = 0.001) and 27% vs 9% (serum glucose, p < or = 0.001) were not checked. At least one measure of prevention had been advised to 66% vs 80% (p < or = 0.001) of patients and the measures taken concern 53 vs 75% (p < or = 0.001) of patients: serum cholesterol 27% vs 51% (p < or = 0.001), hypertension 32% vs 36% (NS) and serum glucose 14% vs 21% (p < or = 0.05). Compliance with advice was mediocre with regards to diet and cholesterol lowering drugs. A large proportion of patients in both groups had higher than recommended levels, including those on diet or treatment. These observations, confirmed in France and abroad, suggest that cardiovascular prevention should be better organised.     

Stage I corpus cancer: is teletherapy necessary?

OBJECTIVE: Our aim was to evaluate the perioperative morbidity after hysterectomy and lymphadenectomy as primary treatment of endometrial cancer and to analyze the recurrence and survival of patients classified as having surgical stage I disease who did not receive adjunctive teletherapy. STUDY DESIGN: Over a 10-year interval 444 patients underwent extensive surgical staging for corpus cancer. Perioperative events were recorded prospectively. Outcome events were updated after the last year of study. RESULTS: After patients with high-risk histologic types of cancer were excluded, 396 patients were evaluable. The risk of extrauterine disease, detected in 21.8% of patients, increased with increasing lack of tumor differentiation. The associated surgical morbidity, including blood loss (mean 336 ml), surgical site infection (3.5%), thromboembolic events (1.5%), and urinary injury (0.6%), and deaths (0.6%) did not differ from those in reports of women undergoing lesser operative procedures. Late complications, including lymphocyst (1.2%), leg edema (1.8%), and hernia (2.9%), were infrequent. Recurrence and survival analysis indicated a calculated 5-year survival of 97% of all patients with surgical stage I disease. There was a significant survival difference related to grade and stage for women in whom disease was confined to the uterus. Overall survival in patients with stage IA (100%) was significantly different (p < 0.0001) from that of patients with stage IB (97%) and stage IC (93%). All recurrences included a distal component. CONCLUSION: Extensive surgical staging including lymphadenectomy can be performed safely. Our results suggest that the risk of pelvic recurrence is not increased and the risk of survival is not compromised in those women not receiving adjunctive teletherapy.     

Serial prognostic capabilities of electrocardiographic indices of infarcted and hibernating myocardium in predicting short- and long-term outcome following coronary artery bypass surgery

Concentrations and ex vivo production of interleukin 1 beta (IL-1), tumour necrosis alpha (TNF), interleukin 6 (IL-6), interleukin-1 receptor antagonist (IL-1RA) and TNF soluble receptors (sTNF-receptors, P55 and P75) were measured in bronchoalveolar lavage (BAL) fluid and blood in 23 HIV-seropositive (HIV+) patients with Pneumocystis carinii pneumonia (PCP) and compared with values found in healthy HIV-seronegative (HIV-) controls and asymptomatic HIV+ subjects. Concentrations of the proinflammatory cytokine IL-1 beta were increased in BAL fluid of HIV+ patients with PCP (184 +/- 47 pg mL-1) compared with undetectable levels in healthy control subjects (P = 0.0001). In plasma of these patients higher concentrations of the anti-inflammatory cytokine IL-1RA were found during acute PCP than after recovery (2.1 +/- 0.7 vs. 0.5 +/- 0.2 ng mL-1, P = 0.01). No correlations could be found between cytokine concentrations and clinical severity of the infection. Corticosteroid treatment did not influence cytokine concentrations in BAL or blood, nor did it suppress the production in alveolar cells. In whole-blood cultures, however, lipopolysaccharide (LPS)-stimulated production was significantly suppressed for IL-1 (1.3 vs. 5.5 ng mL-1, P = 0.009) and for IL-6 (0.6 vs. 2.5 ng mL-1, P = 0.01). The overall data show that in HIV+ patients with PCP (similar to what we had found previously in HIV-patients with PCP) proinflammatory cytokines are more prominently present in BAL, whereas anti-inflammatory reaction is predominant in the circulation.     

Mechanical debulking versus balloon angioplasty for the treatment of true bifurcation lesions

OBJECTIVES: The purpose of this study was to compare the immediate angiographic and long-term results of debulking versus balloon angioplasty for treatment of true bifurcation lesions. BACKGROUND: Previous studies have shown true bifurcation lesions to be a high risk morphological subset for percutaneous transluminal coronary angioplasty (PTCA). Although atherectomy devices have been used to treat bifurcation lesions, no studies have compared the outcomes of these alternative treatment modalities. METHODS: Between January 1992 and May 1997, we treated 70 consecutive patients with true bifurcation lesions (defined as a greater than 50% stenosis in both the parent vessel and contiguous side branch) with conventional PTCA (n = 30) or debulking (with rotational or directional atherectomy) plus adjunctive PTCA (n = 40). Paired angiograms were analyzed by quantitative angiography, and clinical follow-up was obtained in all patients. RESULTS: Acute procedural success was 73% in the PTCA group and 97% in the debulking group (p = 0.01). Major in-hospital complications occurred in two patients in the PTCA group and one in the debulking group. Treatment with atherectomy plus PTCA resulted in lower postprocedure residual stenoses than PTCA alone (16+/-15% vs. 33+/-17% in the parent vessel, and 6+/-15% vs. 39+/-22% in the side branch; p < 0.001 for both comparisons). At 1 year follow-up, the incidence of target vessel revascularization (TVR) was 53% in the PTCA group as compared with 28% in the debulking group (p = 0.05). Independent predictors of the need for repeat TVR were side branch diameter >2.3 mm, longer lesion lengths, and treatment with PTCA alone. CONCLUSIONS: For the treatment of true bifurcation lesions, atherectomy with adjunctive PTCA is safe, improves acute angiographic results, and decreases target vessel revascularization compared to PTCA alone. The benefits of debulking for bifurcation lesions were especially seen in lesions involving large side branches.     

Preterm birth and cerebral palsy. Predictive value of pregnancy complications, mode of delivery, and Apgar scores

BACKGROUND: Preterm infants are at 8 times higher risk than term infants for pre- and perinatal brain damage, resulting in cerebral palsy. In this paper we have analysed the influence of prenatal and birth-related risk factors on cerebral palsy in preterm infants. METHODS: In a register-based study, 175 preterm singleton infants with cerebral palsy, born in 1982-86, were compared with 687 controls matched by gestational age and year of birth. RESULTS: Statistically significant higher rates in cases were found in parity > or = 3 (22% vs. 16%, p < 0.05), Cesarean section (67% vs. 56%, p < 0.01), and low Apgar scores at 1 minute (45% vs. 36%, p < 0.05). By multivariate analyses, two variables remained statistically significant: parity > or = 3 (adjusted OR = 1.53 (95% CI 1.00-2.34), p < 0.05) and Cesarean section (adjusted OR = 1.57 (95% CI 1.07-2.32), p < 0.05). CONCLUSIONS: Pregnancy complications preceding preterm birth did not imply a higher risk of cerebral palsy. Delivery by Cesarean section was a prognostic factor for developing cerebral palsy, and the predictive value of Apgar scores was highly limited.     

Risk factors for postherpetic neuralgia

BACKGROUND: The risk factors for postherpetic neuralgia (PHN), the most common complication of herpes zoster, have not been well established. OBJECTIVE: To elucidate the risk factors for PHN. METHODS: Automated medical, claims, and pharmacy records of a health maintenance organization were used to identify cases of PHN and obtain data on risk factors. A case-base design was used to assess the impact of various patient, disease, and treatment factors on the prevalence of PHN 1 and 2 months after developing zoster. RESULTS: There were 821 cases of herpes zoster that met all eligibility criteria. The prevalence of PHN more than 30 days after onset of zoster was 8.0% (95% confidence interval [CI], 6.3%-10.1%) and 4.5% (95% CI, 3.2%-6.2%) after 60 days. Compared with patients younger than 50 years, individuals aged 50 years or older had a 14.7-fold higher prevalence (95% CI, 6.8-32.0) 30 days and a 27.4-fold higher prevalence (95% CI, 8.8-85.4) 60 days after developing zoster. Prodromal sensory symptoms and certain conditions associated with compromised immunity were also associated with PHN. Systemic corticosteroids before zoster and treatment of zoster with acyclovir or corticosteroids did not significantly affect the prevalence of PHN. CONCLUSIONS: Increased age and prodromal symptoms are associated with higher prevalence of PHN 1 and 2 months after onset of zoster. Overall, systemic acyclovir appears not to confer any protection against PHN, although benefit among elderly patients cannot be excluded.     

A multifactorial analysis of melanoma: prognostic histopathological features comparing Clark's and Breslow's staging methods

A multifactorial analysis was used to identify the dominant prognostic variables affecting survival from a computerized data base of 339 melanoma patients treated at this institution during the past 17 years. Five of the 13 parameters examined simultaneously were found to independently influence five year survival rates: 1) pathological stage (I vs II, p = 0.0014), 2) lesion ulceration (present vs absent, p = 0.006), 3) surgical treatment (wide excision vs wide excision plus lymphadenectomy, p = 0.024), 4) melanoma thickness (p = 0.032), and 5) location (upper extremity vs lower extremity vs trunk vs head and neck, p = 0.038). Additional factors considered that had either indirect or no influence on survival rates were clinical stage of disease, age, sex, level of invasion, pigmentation, lymphocyte infiltration, growth pattern, and regression. Most of these latter variables derived their prognostic value from correlation with melanoma thickness, except sex which correlated with location (extremity lesions were more frequent on females, trunk lesions on males). This statistical analysis enabled us to derive a mathematical equation for predicting an individual patient's probability of five year survival. Three categories of risk were delineated by measuring tumor thickness (Breslow microstaging) in Stage I patients: 1) thin melanomas (<0.76 mm) were associated with localized disease and a 100% cure rate: 2) intermediate thickness melanomas (0.76-4.00 mm) had an increasing risk (up to 80%) of harboring regional and/or distant metastases and 3) thick melanomas (>/=4.00 mm) had a 80% risk of occult distant metastases at the time of initial presentation. The level of invasion (Clark's microstaging) correlated with survival, but was less predictive than measuring tumor thickness. Within each of Clark's Level II, III and IV groups, there were gradations of thickness with statistically different survival rates. Both microstaging methods (Breslow and Clark) were less predictive factors in patients with lymph node or distant metastases. Clinical trials evaluating alternative surgical treatments or adjunctive therapy modalities for melanoma patients should incorporate these parameters into their assessment, especially in Stage I (localized) disease where tumor thickness and the anatomical site of the primary melanoma are dominant prognostic factors.     

Characteristics of patients less than 45 years of age compared with older patients undergoing coronary artery bypass grafting

BACKGROUND: Coronary artery disease (CAD) was not recognized as common among young patients until the study by Yater in 1948. Subsequent studies further elucidated the nature of the disease, which had become more apparent in the younger groups. HYPOTHESIS: The study was undertaken to determine the prevalence of risk factors and severity of coronary disease among young patients aged < or = 45 years undergoing coronary artery bypass grafting (CABG) compared with older patients. METHODS: In all, 112 young patients aged < or = 45 years (Group 1) and 798 older patients aged > 45 years (Group 2) were analyzed for trends to hypertension, smoking, diabetes, family history of heart disease, hypercholesterolemia, obesity, and history of previous myocardial infarction (MI). The severity of disease was examined in terms of number of diseased vessels, vessel size, number of grafts performed, performance of endarterectomies, and left ventricular function. RESULTS: Group 1 had a higher incidence of positive family history (68.5 vs. 51.2%, p < 0.05), and lower incidences of hypertension (62.7 vs. 81.5%, p < 0.05), obesity (42.9 vs. 83.9%, p < 0.05), and history of previous MI (54.5 vs. 94.6%, p < 0.05). Group 2 had a higher incidence of left main disease (22.6 vs. 11.4%, p < 0.05). The distribution of the affected vessels of the young patients was most commonly the left anterior descending (90.4%) followed by the right coronary (79.8%) and circumflex arteries (69.2%). Group 2 had more grafts per patient (3.82 vs. 3.37, p < 0.05). The size of the diseased vessels measured intraoperatively was similar (1.56 vs. 1.58 mm, p = NS) in both groups. Endarterectomy was performed almost three times more often in Group 1 patients (8.2 vs. 3.0%, p < 0.05). Operative mortality was less in Group 1 mean (1.8 vs. 6.3%, p < 0.05). Group 2 had a greater mean left ventricular ejection fraction (53.8 vs. 49.7%, p < 0.05). CONCLUSION: Compared with the older population, patients < or = 45 years of age who underwent CABG had (1) a higher incidence of positive family history of CAD, (2) a higher likelihood of requiring an endarterectomy, and (3) lower operative mortality rate despite a slightly poorer ventricular function.     

Effects of antibiotic treatment in the subset of common-cold patients who have bacteria in nasopharyngeal secretions

BACKGROUND: Upper-respiratory-tract infection is one of the main causes of overuse of antibiotics. We have found previously that bacteria such as Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae can be isolated from the nasopharyngeal secretions of a substantial proportion of adults with upper-respiratory-tract infections. We have assessed the efficacy of co-amoxiclav in patients with common colds but no clinical signs of sinusitis or other indications for antibiotics. METHODS: Between January, 1992 and March, 1994, 314 patients who presented to our outpatient clinic with common colds were enrolled in the double-blind, placebo-controlled study. They were randomly assigned 5 days' treatment with co-amoxiclav (375 mg three times daily) or identical placebo. Clinical examinations were done at enrolment and on day 5-7 to assess outcome (cured, persistent symptoms, worse symptoms). Seven patients were excluded after randomisation, seven did not have nasopharyngeal aspiration, and 12 did not return for followup assessment. FINDINGS: Of 300 patients with nasopharyngeal aspirates, 72 had negative bacterial cultures, 167 had cultures positive only for bacteria unrelated to respiratory infections, and 61 had cultures positive for H influenzae, M catarrhalis, or S pneumoniae. At 5-day follow-up of these culture-positive patients, the distribution of outcome was significantly better among co-amoxiclav-treated (n=30) than placebo-treated (n=28) patients (cured 27 vs 4%; persistent symptoms 70 vs 60%; worse symptoms 3 vs 36%; p=0.001). Patients on co-amoxiclav also scored their symptoms significantly lower than patients on placebo (p=0.008). Among culture-negative patients (n=230), the outcome distribution did not differ between the treatment groups (p=0.392). INTERPRETATION: The majority of patients with upper-respiratory-tract infection do not benefit from antibiotics and side-effects are frequent. However, for the subgroup whose nasopharyngeal secretions contain H influenzae, M catarrhalis, or S pneumoniae, antibiotics are clinically beneficial.     

Diabetes mellitus and morbidity and mortality risks after coronary artery bypass surgery

Of 1025 patients (912 men, 113 women) who underwent coronary artery bypass grafting and were followed up for a mean of 7.4 years, 45 (4.4%) had diabetes mellitus. Norwegian population is 1.8-2%). Early mortality was not significantly greater among diabetics than in non-diabetics (2.2 vs. 3.1%, odds ratio--OR-0.44, confidence interval--CI- 0.05-3.56). Diabetic patients had no increased risk of perioperative myocardial infarction (OR = 0.87, CI 0.36-2.10) or of low-output syndrome necessitating intraortic balloon pumping (OR = 0.42, CI 0.55-3.05), and no excess incidence of late non-fatal myocardial infarction (relative risk = 0.69, CI 0.10-1.28) or late chronic heart failure (OR = 2.50, CI 0.5-11.0). Long-term mortality was increased in the diabetic patients (relative risk 1.87, CI 1.60-2.14). Thus diabetes did not entail heightened risk of early mortality, perioperative myocardial infarction or low-output syndrome. Nor was there excess risk of recurrent angina pectoris, late non-fatal myocardial infarction or chronic heart failure among the diabetic patients, but the late mortality risk was increased.     

Molecular analysis of glycogen storage disease type Ib: identification of a prevalent mutation among Japanese patients and assignment of a putative glucose-6-phosphate translocase gene to chromosome 11

BACKGROUND: Varicella pneumonia that results in respiratory failure or progresses to the institution of mechanical ventilation carries a significant morbidity and mortality despite intensive respiratory support and antiviral therapy. There has been no reported study of the role of corticosteroids in life-threatening varicella pneumonia. DESIGN AND METHODS: This was an uncontrolled retrospective and prospective study of all adult patients with a diagnosis of varicella pneumonia who were admitted to the ICUs of the Johannesburg group of academic hospitals in South Africa between 1980 and 1996. Patient demographics, clinical and laboratory features, necessity for mechanical ventilation, and complications were reviewed. The outcome and therapy of varicella pneumonia was evaluated with particular reference to the use of corticosteroids. Patients with comorbid disease and those already taking immunosuppressive agents were excluded. Key endpoints included length of ICU and hospital stay and mortality. MEASUREMENTS AND RESULTS: Fifteen adult patients were evaluated, six of whom received corticosteroids in addition to antiviral and supportive therapy. These six patients demonstrated a clinically significant therapeutic response. They had significantly shorter hospital (median difference, 10 days; p<0.006) and ICU (median difference, 8 days; p=0.008) stays and there was no mortality, despite the fact that they were admitted to the ICU with significantly lower median ratios between PaO2 and fraction of inspired oxygen than those patients (n=9) who did not receive corticosteroid therapy (86.5 vs 129.5; p=0.045). CONCLUSION: When used in addition to appropriate supportive care and early institution of antiviral therapy, corticosteroids appear to be of value in the treatment of previously well patients with life-threatening varicella pneumonia. The observations presented in this study are important and should form the basis for a randomized controlled trial, as no other relevant studies or guidelines are available.     

Weekly fluconazole for the prevention of mucosal candidiasis in women with HIV infection. A randomized, double-blind, placebo-controlled trial. Terry Beirn Community Programs for Clinical Research on AIDS

BACKGROUND: Candidiasis is a frequent complication of infection with the human immunodeficiency virus (HIV); however, few data exist about the natural history, prevention, and treatment of mucosal candidiasis in women. OBJECTIVE: To evaluate the safety and effectiveness of weekly fluconazole prophylaxis for mucosal candidiasis in women infected with HIV. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: 14 sites participating in the Community Programs for Clinical Research on AIDS (CPCRA). PATIENTS: 323 women with HIV infection and CD4+ cell counts of 300 cells/mm3 or less. INTERVENTION: 200 mg of fluconazole per week or placebo. Open-label fluconazole for candidiasis prophylaxis was permitted after two oropharyngeal or vaginal episodes or one esophageal episode. MEASUREMENTS: Development of mucosal candidiasis, clinical and in vitro resistance of Candida species to fluconazole, survival, and adverse events. RESULTS: After a median follow-up of 29 months, 72 of 162 patients receiving fluconazole and 93 of 161 patients receiving placebo had at least one episode of candidiasis (relative risk [RR], 0.56 [95% Cl, 0.41 to 0.77); P < 0.001). Weekly fluconazole was effective in preventing oropharyngeal candidiasis (RR, 0.50 [Cl, 0.33 to 0.74]; P < 0.001) and vaginal candidiasis (RR, 0.64 [Cl, 0.40 to 1.00]; P = 0.05) but not esophageal candidiasis (RR, 0.91 [Cl, 0.48 to 1.72]; P > 0.2). Relative risks were similar for women who had a history of mucosal candidiasis (RR, 0.5 [Cl, 0.35 to 0.75]) and those who did not (RR, 0.69 [Cl, 0.35 to 1.34]). Absolute risk reduction for patients with a history of infection was 25.6 per 100 person-years, which is more than twice the reduction of 11.2 per 100 person-years seen in patients with no history of infection. This difference reflects the higher risk of patients who previously had an infection. Candida albicans was not usually resistant to fluconazole in vaginal specimens in clinical or in vitro settings; such resistance occurred in less than 5% of patients in each group. CONCLUSIONS: Weekly fluconazole (200 mg) seems to be safe and effective in preventing oropharyngeal and vaginal candidiasis. This regimen has a useful role in the management of HIV-infected women who are at risk for recurrent mucosal candidiasis.     

Changing patterns of infections in patients with AIDS: a study of 279 autopsies of prison inmates and nonincarcerated patients at a university hospital in eastern Texas, 1984-1993

Reports on autopsies of 279 persons infected with human immunodeficiency virus (HIV) were reviewed retrospectively to determine changes in survival rates and infections and to identify differences between prison inmates and nonincarcerated patients. The 78 cases from 1984 through 1988 were compared with 201 from 1989 through 1993, on the basis of use of antiretroviral therapy and (after 1988) prophylaxis against Pneumocystis carinii pneumonia (PCP). Risk factors for HIV infection were homosexuality/bisexuality (30%), injection drug use (IDU; 22%), transfusion (5%), heterosexual contact (4%), and combinations of the above or unknown factors (38%); 95% of patients were males and 41% were state prison inmates in Texas. IDU was more common and homosexuality/ bisexuality was less common among inmates than among nonincarcerated patients. Mean survival time was 12 months in the first period studied and 23 months in the later period (P < .05). Cytomegalovirus infection was the most common type in both periods. The number of cases of PCP declined and the number of cases of bacterial infections increased significantly in the later period. Tuberculosis was significantly more common in inmates than in nonincarcerated patients. Tuberculosis and disseminated histoplasmosis (noted at autopsy) and deaths due to disseminated Mycobacterium avium complex and histoplasmosis were significantly more common among injection drug users than among homosexuals/bisexuals. Invasive candidiasis was more common in homosexuals/ bisexuals and in those who survived > 3 years. Antiretroviral therapy, prophylaxis for PCP, and risk factors for HIV infection appear to influence the mortality rate and prevalence of certain infections found at autopsy.