Risk factors and long-term outcome in pituitary-dependent Cushing's disease.

Although transphenoidal pituitary microsurgery has become the treatment of choice in Cushing's disease, other procedures, such as bilateral adrenalectomy and pituitary irradiation, are currently in use in its management. Indeed, no treatment has proven to be fully satisfactory for this condition. The rates of cure and recurrence after pituitary surgery or irradiation and the incidence of Nelson's syndrome after bilateral adrenalectomy are still open issues. A population of 162 patients with pituitary-dependent Cushing's disease was studied at 1 institution and had a follow-up of at least 2 yr after treatment (median, 7 yr). Patients were divided in subgroups according to the type of treatment: transsphenoidal pituitary microsurgery, bilateral adrenalectomy, or pituitary irradiation. Survival analysis was employed to characterize the outcome of treatment in each subgroup. Predictive factors for success of pituitary surgery were also evaluated. The estimated cumulative percentage of patients remaining in remission after successful pituitary surgery (n = 79) was 93.7% after 2 yr, 80.6% after 5 yr, 78.5% after 7 yr, and 74.1% after 10 yr. Of 8 risk factors examined, the following attained statistical significance: age, clinical severity, presence of major depression, pre- and posttreatment urinary cortisol levels, and posttreatment ACTH level. Pituitary surgery was successful in 79 of 103 patients (76.7%). Surgical failure was significantly associated with lack of pituitary adenoma and the clinical severity and presence of major depression. Of patients treated by bilateral adrenalectomy (n = 63), the estimated cumulative percentage remaining free of Nelson's syndrome was 87.1% after 2 yr, 79.3% after 7 yr, and 71.2% after 10 yr. The occurrence of Nelson's syndrome was significantly related to the pretreatment urinary cortisol level and the presence of pituitary adenoma at previous pituitary surgery. After cure by pituitary irradiation (n = 23), the estimated cumulative percentage of patients remaining in remission was 100% after 2 yr, 81.8% after 5 yr, 71.6% after 7 yr, and 65.1% after 10 yr. Previous pituitary surgery, although unsuccessful, appeared to be a protective factor for relapse. The results indicate that relapse after cure by either pituitary surgery or irradiation is a considerable clinical problem that increases over time. Our findings ascribe new importance to the clinical presentation of patients and indicate subgroups that are at high risk for relapse after pituitary surgery or irradiation and for developing Nelson's syndrome after bilateral adrenalectomy.

Four-year outcome for cognitive behavioral treatment of residual symptoms in major depression.

OBJECTIVE: The authors' goal was to determine whether cognitive behavioral treatment of residual symptoms of depression might have a significant effect on relapse rate. METHOD: In an earlier study, 40 patients with primary major depressive disorder who had been successfully treated with antidepressant drugs were randomly assigned to either cognitive behavioral treatment of residual symptoms or standard clinical management. In both types of treatment, antidepressant drugs were gradually tapered and discontinued. In this study, a 4-year follow-up assessment was performed. RESULTS: Cognitive behavioral treatment resulted in a substantially lower relapse rate (35%) than did clinical management (70%). CONCLUSIONS: Cognitive behavioral treatment of residual symptoms reduces the risk of relapse in depressed patients, probably by affecting the progression of residual symptoms to prodromes of relapse.

Cognitive behavioral treatment of residual symptoms in primary major depressive disorder.

OBJECTIVE: Cognitive behavioral treatment has been used extensively in the acute phase of depression. The purpose of this study was to determine the applicability and effectiveness of this treatment modality in addressing the residual symptoms of primary major depressive illness. METHOD: The subjects were 40 patients with major depressive disorder who were successfully treated with antidepressant drugs. They were then randomly assigned to either cognitive behavioral treatment or clinical management of residual symptoms. In both subgroups, antidepressant drugs were tapered and discontinued. RESULTS: The group that received cognitive behavioral treatment had a significantly lower level of residual symptoms after drug discontinuation in comparison with the clinical management group. Cognitive behavioral treatment also resulted in a lower rate of relapse (15%) at a 2-year follow-up than did clinical management (35%), although this difference did not reach statistical significance. Most of the residual symptoms were found to have occurred also in the prodromal phase of illness. CONCLUSIONS: This preliminary study points to the potential clinical advantages of cognitive behavioral treatment targeted to the residual symptoms of depression.

Heroin nephropathy. A clinicopathologic and epidemiologic study.

The existence of a nephropathy secondary to intravenous narcotic use remains a matter of debate. To determine whether heroin use and renal disease are associated, a clinicopathologic and epidemiologic study was undertaken in the Buffalo Standard Metropolitan Statistical Area (Buffalo-SMSA). Over the past 10 years, 23 addicts presented with the nephrotic syndrome and/or renal insufficiency. All patients were black men 18 to 45 years of age. Kidney biopsies performed on 21 patients uniformly showed sclerosing glomerulonephritis. End stage renal disease (ESRD) developd in 15 of these patients. In the epidemiologic evaluation which spanned four and a half years, heroin use was highly correlated with both sclerosing glomerulonephritis and ESRD. A history of intravenous heroin use was found in 26 per cent of the new cases of sclerosing glomerulonephritis and in 13 per cent of the new cases of ESRD in patients aged 18 to 45 years (p less than 0.000001). This investigation confirms the existence of heroin-associated sclerosing glomerulonephritis in black men. Heroin use appears to be a major risk factor for ESRD in the Buffalo-SMSA.

Uptake of technetium-99m methylene diphosphonate by fractured and osteoporotic bone after a pulse dose of vitamin D3.

The effect of a pulse dose of Vitamin D3 on uptake of [99mTc]MDP by fractured and osteoporotic bone, respectively, was compared with D3's effect on uptake by normal bone in rats. At 4, 7, and 14 days, respectively, after femoral fracture, basal uptake was significantly (p less than 0.005) increased at the fracture site by 336.8, 276.1, and 183.5%, respectively, over the contralateral control site. D3-treated rats had lower uptakes than untreated controls at all three fracture sites and at 12 of 15 normal bone sites but analysis of variance showed the uptake differences were not significant. Cortisone-induced osteoporosis caused a significant (p less than 0.05) decrease in basal uptake. The decrease occurred in all nine bone areas studied. D3 caused a significant (p less than 0.05) increase (mean 16.2%) in uptake by these osteoporotic bones, but a significant (0.1 greater than p greater than 0.05) decrease (mean 13.0%) in uptake by the same bones in normal controls. Thus, D3 had an effect on uptake by the bone lesion, osteoporosis, that differed from D3's effect on uptake by fracture or normal bone.

Coffee, cigarette smoking, and bladder cancer in western New York.

The association between consumption of coffee and bladder cancer and the effect modification of cigarette smoking was investigated as part of a comprehensive case-control study. The study population consisted of 351 case patients with histologically confirmed transitional cell carcinomas of the bladder among white males and 855 white male control subjects selected from Erie, Niagara, and Monroe counties in New York from 1979 to 1985. Usual diet, coffee consumption, and cigarette use were estimated by comprehensive interviews using a detailed food frequency questionnaire. After adjustment for age, education, and dietary risk factors by multiple logistic regression, risk was found to increase with increasing pack-years of cigarette use with an odds ratio in the highest quartile of 2.7 (95% confidence interval, 1.8 to 4.0) when compared to the lowest quartile. Coffee consumption was associated with an increased risk for bladder cancer among the heaviest coffee drinkers after adjustment for cigarette smoking and other dietary risk factors (odds ratio, 2.1; 95% confidence interval, 1.3 to 3.2). The effect was more pronounced among nonsmokers, especially among those 65 years and older. These findings support the contention that coffee is a weak carcinogen.

Exercise, occupational activity, and risk of endometrial cancer.

We conducted a case-control study in western New York state among 232 women with newly-diagnosed endometrial cancer and 631 controls selected from the community. Physical activity was measured by participation in vigorous exercise and walking at four time periods: at age 16, and at 20, 10, and 2 years before the interview and by occupational activity based on a detailed lifetime history. Women who did a moderate amount of vigorous exercise at age 16 and at 20 years before the interview were at reduced risk as compared with those who reported no activity, with odds ratios (OR) (95% confidence intervals) of 0.51 (0.31-0.83) and 0.50 (0.29-0.89), respectively. However, there was no evidence of declining risk with greater amount of activity. At later times, 10 years and 2 years before the interview, being in the highest group with regard to vigorous activity was associated with a slightly but nor significant lower risk as compared with women who reported no activity; the adjusted OR were 0.72 (0.43-1.19) and 0.67 (0.42-1.09), respectively. Being in the highest category of miles walked at age 16 (i.e., > or = 15 miles per week) was associated with a slightly reduced risk as compared with not walking at all (OR 0.64 (0.26-1.16)), whereas the number of miles walked at other times was not related to reduced risk. Occupational physical activity was not related to the risk of endometrial cancer. Overall, these results indicate that physical activity at levels prevalent in this population has at most a modest relationship to reduced risk of endometrial cancer.

Trichomonas vaginalis and cervical cancer. A prospective study in China.

The relationship between Trichomonas vaginalis infection and cervical cancer was investigated prospectively in a cohort of 16,797 women aged 25 years or more who were followed from 1974 to 1985 within the framework of a cervical screening program in Jingan, China. Personal interviews were conducted by trained interviewers when the women first entered the screening program. At initial screening, 421 (2.51%) women had a positive cytologic diagnosis of T. vaginalis infection. Ninety-nine incident cases of pathologically confirmed squamous cell carcinoma were identified from the cohort, with a total of 140,018 person-years of observation. T. vaginalis infection was found to contribute to the risk of cervical cancer, as determined by crude estimates and after adjustment for potential confounding effects. In a multiple proportional hazards model, the relative risk for cervical cancer was 3.3 (95% confidence interval: 1.5 to 7.4) among women with T. vaginalis infection. Furthermore, in the multivariate analysis, increased risk of cervical cancer was associated with the following factors: number of extramarital sexual partners of both the subjects and their spouses, cigarette smoking, and irregular menstruation. Having a large number of negative Pap smears was associated with lower risk. This study suggests that there might be an association between T. vaginalis infection and the risk of cervical cancer, but only 4 to 5% of cervical cancer in Chinese women may be attributable to T. vaginalis infection.

Consumption of PCB-contaminated sport fish and risk of spontaneous fetal death.

Spontaneous fetal death has been observed among various mammalian species after exposure to polychlorinated biphenyls (PCBs). Our exposure-based cohort study assessed the relationship between consumption of PCB-contaminated Lake Ontario sport fish and spontaneous fetal death using 1820 multigravid fertile women from the 1990-1991 New York State Angler Cohort Study. Fish consumption data were obtained from food frequency questionnaires and history of spontaneous fetal death from live birth certificates. Analyses were stratified by number of prior pregnancies and controlled for smoking and maternal age. No significant increases in risk for fetal death were observed across four measures of exposure: a lifetime estimate of PCB exposure based on species-specific PCB levels; the number of years of fish consumption; kilograms of sport fish consumed in 1990-1991; and a lifetime estimate of kilograms eaten. A slight risk reduction was seen for women with two prior pregnancies at the highest level of PCB exposure (odds ratio = 0.36; 95% CI, 0.14-0.92) and for women with three or more prior pregnancies with increasing years of fish consumption (odds ratio = 0.97; 95% CI, 0.94-0.99). These findings suggest that consumption of PCB-contaminated sport fish does not increase the risk of spontaneous fetal death.

Nocturnal prolactin and cortisol secretion and recovery from melancholia.

Spontaneous prolactin and cortisol patterns were determined at 20 min intervals over 3 hr during the night in eight patients with melancholia, both during illness and after treatment with amitriptyline. Mean plasma prolactin levels were greater after recovery in the seven patients who responded to treatment. Mean cortisol secretion decreased upon recovery from melancholia, and such changes in two patients paralleled normalization of dexamethasone suppression test responses. The influence of assumptions of lack of interaction on the statistical significance of the analysis of variance with repeated measures for prolactin and cortisol values was evaluated.

Treatment responses in primary and secondary melancholia: a preliminary report.

Ten patients suffering from primary affective illness and melancholia were compared to 10 melancholic subjects whose depression was chronologically superimposed on a preexisting nonaffective psychiatric disturbance. Both groups displayed a satisfactory response to treatment with amitriptyline. Similar patterns of improvement were reported in the two groups, and there was a concordance of subjective and objective rating methods.

Prolactin, amitriptyline, and recovery from depression.

Spontaneous prolactin patterns were determined at 15-min intervals over 5 h in 13 patients, who were suffering from melancholia, during illness and after treatment with amitriptyline. Plasma prolactin levels were significantly greater at most sampling points after patients had recovered than during their illnesses. One patient, who did not recover, showed the opposite trend.

Endometriosis and body fat distribution.

OBJECTIVE: To examine the association of body fat distribution with risk of endometriosis in an effort to determine whether a specific somatotype is related to the disease. METHODS: We conducted a case-control study of 88 laparoscopically confirmed cases of endometriosis, identified in a specialty gynecologic practice in western New York, and 88 age-matched friend controls. Data were collected by standardized personal interview, and body measurements were taken in a standardized fashion by one interviewer. Risk of endometriosis associated with body fat distribution, as expressed by waist-to-hip and waist-to-thigh ratios, was assessed using logistic regression. RESULTS: For women under 30 years of age (45 cases, 46 controls), endometriosis was inversely related to both waist-to-hip ratio (odds ratio 6.18, 95% confidence interval [CI] 2.01-19.01) and waist-to-thigh ratio (odds ratio 3.64, 95% CI 1.23-10.78). This effect was not evident among women aged 30 years and older (43 cases, 42 controls). CONCLUSION: Our results suggest a specific somatotype with a predominance of peripheral body fat among women with endometriosis. This finding may provide information useful in both the diagnosis and understanding of the disease etiology.

Factors moderating the effect of oral sulfonylureas on free water clearance.

The effects of the antidiuretic agent chlorpropamide and the diuretic agent tolazamide on solute-free water clearance (CH2O) were compared in noninsulin-dependent diabetic patients undergoing water diuresis. Hyperglycemia (fasting serum glucose above 200 mg/dl) obscured the effects of these two sulfonylureas on CH2O. Thiazide or ethacrynic acid enhancement of chlorpropamide antidiuresis was also blunted by hyperglycemia and attendant osmotic diuresis. Thus, the low incidence of symptomatic hyponatremia during chlorpropamide treatment of diabetic patients may be explained by persistent hyperglycemia in such patients.

Cigarette smoking and risk of clinical relapse in patients with Crohn's disease.

Risk of clinical relapse among cigarette smokers and nonsmokers was examined in a cohort of 74 adult Crohn's disease (CD) patients who were identified and followed at monthly intervals for six months. We measured clinical activity by a weighted symptom index used previously. Relapse at any point during the study was defined by the index score exceeding 150. Approximately 50% of nonsmokers experienced clinical relapse during the study period. Current smokers experienced a relapse risk 1.6 times that of nonsmokers (P less than .01). The risk estimates correspond to mean overall clinical activity scores of 142 +/- 34 for smokers compared to 119 +/- 26 for nonsmokers. Adjustment for confounding effects did not substantially alter the association shown between cigarette use and clinical relapse. We observed no increase in the likelihood of relapse among former smokers. The statistically significant finding that current smoking increases the risk of relapse for CD patients is of clinical importance, given the high prevalence of smoking (42%) among CD patients in this sample.

Beta-endorphin responses to metyrapone and dexamethasone in depressed patients.

Controversy continues over the characteristics of beta-endorphin secretion in depression. Beta-endorphin plasma levels were measured in 30 drug-free male patients with a DSM-III-R major depressive disorder and 21 healthy controls. Depressed patients displayed significantly lower beta-endorphin plasma levels in baseline conditions, after the single dose metyrapone test, and after the dexamethasone suppression test. The activation of hypothalamic-pituitary-adrenal (HPA) axis in depression might be due, at least in part, to low levels of beta-endorphin. These results suggest that HPA axis dysregulation in depression may involve peptides other than ACTH.

Adulterants in heroin/cocaine: implications concerning heroin-associated nephropathy.

Heroin-associated nephropathy (HAN) is a complication of the intravenous use of heroin or cocaine. It has been postulated that one of the substances used to adulterate these drugs may be responsible for the renal injury. We examined data provided by the Drug Enforcement Administration (DEA) concerning the laboratory analysis of 12 366 samples of heroin/cocaine. These street-grade drugs were analyzed for the presence of various adulterants or secondary substances. Eleven adulterants were identified with a frequency of occurrence that exceeded 5%. Quinine, mannitol, lactose and procaine were the non-narcotic compounds most commonly found. Other substances found included caffeine, inositol, lidocaine, starches, methapyrilene, sucrose, acetylprocaine and dextrose. No specific substance including heroin or cocaine has yet been definitely implicated as causative of HAN. These data suggest that further animal research is needed to determine the effects of repeated intravenous injections of each of these commonly found substances on the kidney.

Sepsis syndrome and associated sequelae in patients at high risk for gram-negative sepsis.

We conducted a prospective surveillance study of 80 hospitals across the United States to determine the incidence of sepsis syndrome and its associated sequelae in hospitalized patients over age 18 years who were administered antibiotics for suspected or documented gram-negative infection. A sample of 1754 hospitalized patients were followed from onset of antimicrobial therapy to discharge or death. Mortality rates (MR) varied depending on the suspected source of sepsis syndrome. For patients in whom the syndrome was associated with community-acquired urinary tract infections, mortality was 20% (relative risk [RR] = 0.51, p < 0.05), for those with trauma 20.6% (RR = 0.51, p < 0.05), and patients with nosocomial respiratory tract infections 57.1% (RR = 1.66, p < 0.05). More than two complications occurred in 65.2% of patients under age 60 years (MR 31%), 40.8% of those age 60-80 (MR 42%), and 35.6% of patients older than 80 years (MR 33.3%, p > 0.05). Various patient populations had significant differences in both the incidence of the syndrome and its complications, and consequent mortality. Perhaps morbidity as well as mortality should be used as outcomes when testing the efficacy of innovative therapies for sepsis.

Hypochondriacal fears and beliefs in agoraphobia.

In order to evaluate hypochondriacal fears and beliefs in agoraphobia, the authors administered the self-rated Illness Attitude Scales to 18 agoraphobic patients. The patients reported hypochondriacal concerns similar to those of patients with hypochondriasis. After agoraphobia had been treated with exposure therapy in ten patients, hypochondriacal concerns did not differ significantly from those of normals. The findings suggest that hypochondriacal concerns are substantial in agoraphobia and that these wane when anxiety decreases.

Hypochondriacal fears and beliefs in DSM-III melancholia. Changes with amitriptyline.

The authors administered the Illness Attitude Scales, which identify hypochondriacal patients, to 20 nonpsychotic inpatients with DSM-III diagnosis of melancholia before and after 4 weeks of treatment with amitriptyline, and to a matched group of normals. Before treatment characteristic hypochondriacal responses occurred in over one-third of melancholics whereas after treatment the number was the same as in normals. The findings are in accord with the clinical observation that melancholia is one of the causes of hypochondriacal fears and beliefs and these tend to remit with recovery from depression.