[Clinicopathological features of low-grade oncocytic renal tumor (CD117-negative, cytokeratin 7-positive): report of seven cases].

Objective: To explore clinicopathological features of low-grade oncocytic tumor (LOT) of the kidney and to analyze its relationship to hybrid oncocytic/chromophobe tumor (HOCT) of the kidney, renal oncocytoma (RO), and chromophobe renal cell carcinoma (chRCC). Methods: Seven LOTs were identified from the pathologic archives of two hospitals, including Xiangya Hospital (5 cases) and the Second Xiangya Hospital (2 cases) of Central South University between 2012 and 2019. Clinical data of the LOTs were collected. The tumor morphology was analyzed and immunohistochemistry was performed. Results: All LOTs occurred in adults, aged from 49 to 72 years (median 56.0 years, mean 60.7 years). The tumor size ranged from 2.5 to 6.0 cm (median 4.3 cm, mean 4.3 cm). There were three male and four female patients. Three cases occurred in the left kidney and four in the right. All the tumors were solitary lesions without the clinicopathologic background of Birt-Hogg-Dubé (BHD) syndrome or oncocytosis. Five patients had available follow-up data (follow-up period 23-95 months, median 69.0 months, mean 64.6 months) and all were alive without disease. Microscopically, all LOTs were well-circumscribed (7/7). Three LOTs were partly encapsulated. The tumors demonstrated a predominant growth pattern comprising prominently compact small nests surrounded by delicately branching thin-walled blood vessels, imparting an organoid architecture (7/7), but variable numbers of glandular or gland-like structures were often seen among the small nests (7/7). There were frequently areas with loose, edematous stroma, and the tumor cells exhibited reticular, trabecular, or single cell arrangements (6/7). Focal hemorrhage was also commonly present in both compact and loose areas (5/7). In addition, focally cystic formation and ossification occurred in the compact area of one case and in the loose area of another case. The tumor cells in LOT showed intermediate cytologic characteristics between RO and chRCC, including abundantly eosinophilic granular cytoplasm, ovoid to round nuclei with mostly smooth contours, discernable small nucleoli (RO features), frequently delicate perinuclear halos, and occasional binucleation (chRCC features). The tumors were typically CK7-positive and CD117-negative (7/7), and variable staining for PAX8 (5/7), P504s (2/7), and vimentin (1/7). They were negative for CK20, CD10 and FOXI1. All tumors retained SDHB immunostaining. Conclusions: LOT is a rare and indolent oncocytic renal tumor with homogeneously intermediate cytologic features between RO and chRCC. There are some clinicopathologic overlaps between LOT and sporadic HOCT. The distinctive morphology and immunophenotype of LOT suggest that it is potentially a distinct tumor entity.

Reporting of fatal adverse drug reactions.

OBJECTIVES: To review the reports of fatal adverse drug reactions (ADRs) submitted to the Ontario Medical Association Adverse Drug Reactions Monitoring Program between 1990 and 1994; to identify drugs associated with fatal outcomes; and to assess the causative role of the drug in these events and the completeness of the data in these reports. METHODS: Drug(s) identified on each ADR report as being responsible for the reaction were considered. Agents were classified by the Anatomical Therapeutic and Chemical classification system. The causality of each ADR report was evaluated by using an algorithmic rating scale. RESULTS: From the Ontario Medical Association database, 97 cases of ADRs that resulted in death were reviewed. One hundred fourteen medications were implicated as "suspect" drugs in the 97 deaths. The most commonly implicated drug classes were musculoskeletal agents, blood and blood-forming organ agents, and nervous system agents. Patients over 65 years of age comprised 60% of this series. After independent assessment as to causality, 13% of the cases were rated as probable, 86% were rated as possible and 1% were rated as doubtful. Seventy per cent of reports did not include information regarding medical history. Forty-two per cent of cases failed to provide adequate information to evaluate the feasibility of the time to onset of the ADR. The use of concomitant drugs was not reported in 12% of cases. CONCLUSIONS: The drugs most frequently implicated in fatal ADRs were consistent with those reported in other studies. Algorithmic causality assessments were of limited value in these reports. The completeness of the reports and adequacy of the information were poor. The type of reporting forms and information provided were not homogenous. There is a need to improve quality of reporting and harmonize reporting forms between monitoring bodies. The feasibility of unique data collection forms and obligatory reporting for fatal ADRs should be considered.

Utility scores for chronic conditions in a community-dwelling population.

OBJECTIVE: The objective of this study was to determine utility scores for various chronic conditions. DESIGN AND SETTING: This study is a descriptive analysis. Health Utilities Index (HUI) scores for 20 chronic conditions were examined from the National Population Health Survey (NPHS) from 1994 to 1995. PATIENTS AND PARTICIPANTS: 17,626 individuals were surveyed (54.3% women). Chronic conditions included: acne (requiring medication), Alzheimer's disease, arthritis/rheumatism, asthma, back problems excluding arthritis, chronic bronchitis or emphysema, cancer, cataracts, diabetes, epilepsy, food allergies, glaucoma, heart disease, high blood pressure, migraine headaches, other allergies, sinusitis, stroke, stomach/intestinal ulcers and urinary incontinence. INTERVENTIONS: Health Utilities Index-Mark III (HUI-Mark III) scores for patients with and without a NPHS-defined chronic condition were collected. Utility scores were examined according to age, gender and comorbidity. MAIN OUTCOME MEASURES AND RESULTS: 42.6% of individuals reported having no NPHS-defined chronic condition. The most commonly reported health conditions were allergies other than food (17.6%) and rheumatism/arthritis (16.5%). The mean HUI-Mark III scores for patients without a health state was 0.933 +/- 0.079. Individuals with Alzheimer's disease (0.580 +/- 0.263), stroke (0.676 +/- 0.230) and urinary incontinence (0.698 +/- 0.230) had the lowest overall HUI-Mark III scores. Utility scores decreased as age and as the number of comorbid conditions increased. CONCLUSIONS: This study provides health economists, researchers and policy-makers with a reference for health utilities of various chronic conditions, different age groups, gender and comorbidities.

[Study on regulators of the cell cycle in cutaneous squamous cell carcinoma].

In order to investigate the relationship between the regulators of cell cycle and cutaneous squamous cell carcinoma(SCC), we used an immunohistochemical staining technique to examine the expression of cyclin D1, p16 and Rb in the paraffin embedded skin cancer tissues of 30 patients with SCC. The positive percentage of cyclin D1, CDK4, p16 and Rb was 66.7%, 53.3%, 33.3%, and 36.7%, respectively. The overexpression of cyclin D1 and CDK4 could be observed frequently in low grade of differentiated cells, especially in marginal cells of the cancer nest. The results indicate that the aberrant expression of positive and negative regulators of the cell cycle may be involved in the carcinogenesis and evolution of SCC.

Efficacy and safety of neuroleptics in behavioral disorders associated with dementia.

BACKGROUND: Neuroleptics are commonly used to treat behavioral disorders associated with dementia. However, their safety and efficacy have not been well established in these patients. METHOD: A meta-analysis of randomized, controlled (either placebo or active drug), double-blind trials published since 1966 (N = 16; 499 treated, 112 active controls, and 123 placebo) was conducted. Data were collected on proportion of patients with clinically significant improvement, significant side effects, and dropout rates. RESULTS: Pooled mean percentages of patients who improved (95% CI): all neuroleptics, 64% (54% to 74%); low potency, 63% (54% to 72%); moderate potency, 70% (56% to 85%); moderate-high potency, 62% (49% to 75%); and high potency, 69% (49% to 90%). Thus, no differences in efficacy existed between different potencies of neuroleptics. Therapeutic effect (neuroleptic minus placebo) was only 26% (14% to 38%). Treatment-emergent side effects were more common for neuroleptics vs. placebo (mean difference = 25%, 13% to 37%), but pooled mean dropout rates were not different (mean difference = 4%, -7% to 14%). Neither weighting by clinical trial quality (3 raters; weighted agreement, 83% to 92%) nor exclusion of poor quality trials changed the results. CONCLUSION: Neuroleptics have small but significant efficacy over placebo in this population, and the efficacy rate is equivalent to the side effect rate. Comparing different neuroleptics shows they have similar efficacy, side effects, and dropout rates. Further study to determine more specific drug-responsive behaviors is needed to maximize benefits of these drugs.

Gender differences in adverse drug reactions.

The objective of this study is to identify gender-related differences in the types of symptoms and drugs reported to cause an adverse drug reaction. Patient data from the Sunnybrook Health Science Centre ADR Clinic for the period from April 1986 to May 1996 were reviewed. Of the 2,367 patients assessed, 74.1% were female. The mean age of the patients was 43 +/- 17 years. Drug classes most frequently reported to elicit an adverse event were general antiinfectives (60.4%), nervous system agents (21.5%), and musculoskeletal agents (3.7%). Skin-related reactions accounted for 49.0% of all reported adverse drug reactions. More than one agent was reported to be responsible for the adverse drug reaction(s) in 50% of the female patients, versus 33.1% of all male patients. Of the female patients, 47.6% were referred for skin or oral challenge testing, versus 41.6% of the male patients. Of the female patients, 6.2% tested positive to the agent compared with 6.1% of all male patients. These results support previous findings that female gender is a risk factor for the development of adverse drug reactions. Further work is required to elucidate the mechanisms explaining the differences observed between male and female patients.

Pancreatic insufficiency due to antituberculous therapy.

OBJECTIVE: To describe a case of chronic pancreatic insufficiency related to antituberculous therapy. CASE SUMMARY: A 57-year-old man developed rash, fever, and hepatitis (aspartate aminotransferase 369 IU/L, alanine aminotransferase 506 IU/L), 6 weeks after starting isoniazid, rifampin, ethambutol, and pyrazinamide. He also developed severe metabolic acidosis secondary to diabetic ketoacidosis and lactic acidosis (serum bicarbonate 7 mEq/L, glucose 1778 mg/dL, and lactate 4.0 mEq/L). Acute pancreatitis was diagnosed on the basis of a mildly elevated amylase concentration (392 U/L) and radiologic evidence of pancreatic inflammation. He developed pancreatic insufficiency with steatorrhea and an abnormal secretin test. He continues to require pancreatic enzyme replacement and insulin therapy. Rechallenge was not performed. DISCUSSION: Hypersensitivity syndromes have been reported for various drug therapies, including antituberculous agents. Hypersensitivity syndrome reactions are characterized by fever, rash, and internal organ involvement. Rifampin has been reported to cause acute pancreatitis in up to 2.7% of patients. Drug-induced chronic pancreatitis, however, is reported to be extremely rare. This is the first reported case of chronic pancreatic insufficiency occurring in the setting of a hypersensitivity syndrome reaction to antituberculous drugs. CONCLUSIONS: Chronic pancreatic insufficiency should be considered as a possible long-term sequelae of a hypersensitivity syndrome reaction to antituberculous therapy.

Seasonal prevalence of vitamin D deficiency in institutionalized older adults.

OBJECTIVE: To determine the prevalence and seasonal variation of vitamin D deficiency among older residents of long-term care facilities. DESIGN: Cross-sectional survey with 6-month follow-up. SETTING: Three long-term care facilities in Toronto. PATIENTS: Persons more than 65 years old, medically stable, who had resided in the facility for at least 6 months and had no conditions known to interfere with vitamin D metabolism. MEASUREMENTS: Information regarding demographics, past health, and medication use was collected. Mental and functional status were assessed by questionnaire. Venous blood samples were analyzed for alkaline phosphatase, calcium profile, albumin, intact parathyroid hormone, 25 hydroxyvitamin D (25OHD), and vitamin D binding protein in September 1994 and March 1995. In a subgroup of patients, bone specific alkaline phosphatase was measured, and dietary intake of vitamin D was assessed. RESULTS: A total of 155 subjects completed the study. The mean age of the subjects was 83.2 years (SD 7.1), and 47% were female. The mean 25OHD level in the March sample (39.9 nmol/L, SD 19.7) was significantly lower than the mean 25OHD level in the September sample (44.9 nmol/L, SD 16.9) (P = .001). The prevalence of vitamin D deficiency in the osteomalacic range (25OHD < 25 nmol/L) increased from 9% in the fall sample to 18% after the winter (chi 2 = 4.65, P = .03). The prevalence of borderline deficiency or hypovitaminosis D (25OHD < 40 nmol/L) increased from 38% in the fall sample to 60% in the spring sample (chi 2 = 14.9, P < .001). Dependence in transfers was associated with an increased risk of hypovitaminosis D, odds ratio 2.08 (95% confidence interval 1.08-4.01), dependence in ambulation 2.57 (1.26-5.23), and regular use of a wheelchair 2.17 (1.09-4.31). When entered into a forward conditional logistic regression model, only dependence in ambulation remained significant, with an adjusted odds ratio of 2.57 (95% CI: 1.26-5.18). CONCLUSIONS: Vitamin D deficiency and borderline vitamin D status are common among older residents of long-term care facilities in Canada. Even though this population has limited outdoor exposure, seasonal variation in the prevalence of deficiency remains significant. Evaluation of interventions to improve the status of vitamin D nutrition in this population is needed.

Drug-related mortality in Canada (1984-1994).

OBJECTIVE: To examine drug-related deaths due to adverse drug reactions between 1984 and 1994. DATA SOURCE: Voluntary reports of deaths due to adverse events as reported to the Adverse Drug Reaction Monitoring Program, Drugs Directorate, Health Protection Branch, Health Canada. METHODS: Drugs were classified according to the Anatomical, Therapeutic, Chemical (ATC) coding system. Descriptive statistics were utilized. RESULTS: One thousand four hundred and seventeen drug-related deaths were reported (700 male, 685 female, 32 unknown). The mean+/-SD age of patients was 54.6+/-21.7 years (range 1 month-97 years). In total, 2131 medications were implicated as suspect drugs (1.5+/-1.0, range 1-7). The most commonly reported categories of suspect drugs were the nervous system agents (50.6%), followed by cardiovascular system agents (9.0%), general antiinfectives for systemic use (8.8%) and musculoskeletal system agents (8.3%). One thousand and eighty-six deaths were classified as non-suicides. For non-suicide deaths, the most commonly reported suspect drugs were classified as nervous system agents (37.9%), followed by general antiinfectives for systemic use (12.3%), musculoskeletal system (11.5%) and cardiovascular system agents (10.2%). Three hundred and thirty-one (23.3%) reports were identified as suicides. For suicides, the most commonly reported suspect drugs were the nervous system agents (81.1%), followed by the respiratory system agents (8.5%) and the cardiovascular system agents (6.0%). CONCLUSION: Nervous system agents, musculoskeletal medications and general antiinfectives for systemic use figured prominently in deaths reported to HPB between 1984 and 1994.

The efficacy, safety and tolerability of antidepressants in late life depression: a meta-analysis.

BACKGROUND: To determine the efficacy, safety and tolerability of antidepressants in depressed elderly patients. METHODS: Search for randomized controlled double-blind studies evaluating atypical antidepressants (ATYPs), reversible inhibitors of monoamine oxidase-A, selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants in moderate/severe depressed patients > or = 60 years for > or = four weeks. The random effects model (single-arm; comparative) was used to aggregate efficacy, safety and dropout. RESULTS: No difference in single-arm aggregation of outcomes for four antidepressant classes. Comparative analyses showed no statistical difference between outcomes, except SSRIs had a higher response rate than ATYPs. CONCLUSION: Elderly show no differences in antidepressant class outcomes. LIMITATIONS: Heterogeneity and lack of power. CLINICAL RELEVANCE: There is little advantage for antidepressant classes over another in the aged.

Hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone associated with the use of selective serotonin reuptake inhibitors: a review of spontaneous reports.

OBJECTIVE: To review reported cases of hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with the use of selective serotonin reuptake inhibitors (SSRIs). DATA SOURCES: A search of MEDLINE for reports of hyponatremia and SIADH associated with the use of fluoxetine, fluvoxamine, paroxetine or sertraline published between January 1980 and May 1995. Unpublished reports of cases were requested from the pharmaceutical industry, the Ontario Medical Association, the Health Protection Branch of Health Canada, the US Food and Drug Administration and the World Health Organization. DATA SELECTION AND EXTRACTION: Spontaneous reports from postmarketing surveillance. DATA SYNTHESIS: A total of 736 cases of hyponatremia [corrected] and SIADH associated with SSRI use were reported. Fluoxetine was involved in 554 (75.3%) of the cases, paroxetine in 91 (12.4%), sertraline in 86 (11.7%) and fluvoxamine in 11 (1.5%). Reports of 30 cases were published. The remaining 706 cases were reported to monitoring bodies and the pharmaceutical industry. According to information in the published reports, the median time to onset of hyponatremia was 13 days (range 3 to 120 days). Most (83%) of the published cases involved patients 65 years of age or more, as compared with 74% of the unpublished cases. CONCLUSION: Elderly people may be at increased risk for hyponatremia associated with SSRI use. Physicians caring for elderly patients should be aware of this potentially serious but reversible adverse effect. Further research is required to determine the incidence of this adverse effect, the relative risk of hyponatremia and SIADH in different age groups and the risk associated with different SSRI drugs.

Falls among older people: relationship to medication use and orthostatic hypotension.

OBJECTIVE: To assess the risk of falls attributable to medication use and orthostatic hypotension. DESIGN: Prospective cohort study. SETTING: Two self-care, apartment-style residential facilities in the Toronto area. PARTICIPANTS: A total of 100 consecutive older volunteers (mean age = 83, range 62-96) who were independent in activities of daily living and able to stand unaided. MEASUREMENTS: Prescription medications used by each subject were documented at baseline. Blood pressure measurements were performed supine, immediately after standing, and after 5 minutes. Subjects reported falls weekly, by postcard, for a period of 1 year; nonreporters were contacted by telephone. RESULTS: Fifty-nine percent of subjects fell at least once during the 1-year follow-up. Antidepressant use was associated with an increase in the risk of experiencing one or more falls (RR = 1.6, P = .02). The use of other drug classes examined, including diuretics and sedative-hypnotics, was not associated with an increased risk of falling. Orthostatic hypotension was not predictive of falls. Surprisingly, there was an increase in the diastolic blood pressure of fallers, after 5 minutes, that was not seen in the nonfallers (3.3 vs -0.2 mm Hg, P = .05). Possible explanations for this previously unreported observation are explored. CONCLUSION: Patients using antidepressants should be followed closely because the risk of falls is increased. Previously reported relationships between benzodiazepines and diuretics and falls are not supported by the present findings. Clinical detection of orthostatic hypotension is unlikely to be useful in predicting future risk of falling.