Referral patterns and genetic testing outcomes in a contemporary hereditary renal cancer clinic.

OBJECTIVES: Multidisciplinary hereditary tumor clinics are a collaborative format to identify and treat patients with genetic cancer predispositions. The hereditary renal cancer clinic at Indiana University is comprised of a urologic oncologist, medical oncologist, clinical geneticist, and genetic counselor. The clinic holds regular tumor board meetings, where patient histories, pedigrees, imaging, pathology, and management plans are collectively reviewed and discussed. Here we report the contemporary experience for our hereditary renal cancer clinic, with description and analysis of referral patterns, patient profiles, and genetic testing outcomes. MATERIALS AND METHODS: A retrospective review of an IRB-approved, prospectively maintained database of patients seen in the hereditary renal cancer clinic was performed. Patient characteristics, genetic testing results, and disease characteristics were reported and analyzed. RESULTS: A total of 142 patients seen in clinics from January 2018 to June 2023 were included. Patient's median age was between 40 and 49 years old, and 88.7% were Caucasian. The most common reasons for referral were early-onset renal tumors (40%), known hereditary renal cancer syndrome (29%), and hereditary renal cancer syndrome screening (13%). Of those with a tissue diagnosis of renal cell carcinoma, 46.2% were clear cell subtype. The presence of nonrenal syndromic features concerning for hereditary renal tumor syndrome was predictive of pathogenic mutation identification (OR 13.45, P < 0.0001). Patient race and presence of multifocal tumors were not predictive of pathogenic mutation identification. When restricting analysis to patients with an established renal malignancy, high-grade tumor histology was predictive of a pathogenic mutation (OR 8.17, P = 0.012), though higher pathologic stage and nonclear cell histology were not. Referral for early-onset renal tumor (age < 45 years) predicted lower likelihood of pathogenic mutations (OR 0.10, P = 0.0002). FH gene mutations were the most commonly identified pathogenic mutations. Genetic testing of family members (cascade testing) was recommended to 9 patients seen in clinic; a pathogenic mutation was subsequently identified in all but one of these families. CONCLUSIONS: These findings are useful for referring physicians and patients in determining patient referral to hereditary cancer clinics, and for counseling patients undergoing genetic testing. Data from non-Caucasian patients and evolving implications of variants of unclear significance (VUS) may represent future research directions for hereditary renal cancer clinics.

Smoking among female daily smokers in Surabaya, Indonesia.

OBJECTIVES: Nationally representative studies suggest 1-2% of Indonesian women (2.3 million) smoke various tobacco products daily; however, in recent years, there has been concern that the tobacco industry has successfully increased female smoking. Our objective was to describe current cigarette smoking behaviors, past quit attempts, and intention to quit of female daily smokers in Surabaya, Indonesia. STUDY DESIGN: Survey. METHODS: Female daily smokers (n = 112) in Surabaya, Indonesia, the country's second largest city, were recruited to participate in a survey during 2018. Convenience sampling was utilized in two malls. Potential participants were intercepted in or near designated smoking areas and invited to the nearby data collection site. Survey items from Global Adult Tobacco Survey and the International Tobacco Control Policy Evaluation Project were utilized. RESULTS: Participants self-reported smoking 13.8 cigarettes per day (7.3 white machine-rolled cigarettes per day, 4.2 kreteks per day, and 2.4 roll-your-own cigarettes per day). Over 75% smoked their first cigarette within 30 min of waking. Over 53% had a heaviness of smoking index score suggesting moderate or high addiction. Approximately half (51%) did not attempt to quit smoking in the previous 12 months, and 55% planned to quit beyond 6 months or not at all. CONCLUSIONS: Our sample smoked five to six more cigarettes per day than female daily smokers in previous national surveys. Relative to previous studies, our data suggest an unexpected preference for white machine-rolled cigarettes and that there could be, at a minimum, pockets of increased smoking and addiction among female daily smokers in Indonesia.

Life events can trigger depressive exacerbation in the early course of schizophrenia.

Previous studies have linked life events with depression in chronic schizophrenia, but those studies had methodological limitations. Using a prospective research design and examining events that were clearly independent of the patients' illnesses, the authors sought to determine whether stressful life events could trigger depressive symptoms in the early course of schizophrenia. Schizophrenia patients (n = 99) were followed for 1 year from a point of outpatient stabilization. Life event interviews were conducted every 4 weeks and symptom assessments every 2 weeks. Survival analyses showed a significantly increased risk for an exacerbation of significant depressive symptoms following an independent life event. Of interest is that an analysis of competing risk showed that the odds of psychotic exacerbation following a major independent life event were not significantly greater than the odds of depressive exacerbation. The risk of depression and of psychosis after experiencing a stressful life event is significantly increased for the first month, but the risk period can extend to 3 months.

Role of the C(6)-hydroxy group in bicyclomycin: synthesis, structure, and chemical, biochemical, and biological properties.

Bicyclomycin (1) is a commercial antibiotic whose primary site of action in Escherichia coli is the transcription termination factor rho. A recent structure-activity relationship study of 1 showed that replacing the C(6)-hydroxy group with alkoxy and thioalkoxy substituents led to dramatic losses of inhibitory activity in rho biochemical assays. The origin for this structural specificity has been explored by the synthesis and chemical, biochemical, and biological evaluation of C(6)-amino- (13), C(6)-(hydroxylamino)-(14), and C(6)-mercaptobicyclomycin (15). These compounds, like 1, are capable of entering into hydrogen bond donor interactions with rho and are capable of undergoing C(6) ring opening to generate alpha, beta-unsaturated carbonyl, imine, or thione systems. The chemical reactivity of 13-15 was compared with that of 1. We observed that 1, upon treatment with EtSH under moderate and basic conditions, readily underwent C(6) hemiaminal bond cleavage followed by conjugate addition to beta-methylene-alpha-ketoamide 2 to give Michael addition adducts whereas 13-15 reacted by initial cleavage of the C(1)-O(2) bond. Biochemical and biological assays of 13-15 and related analogues demonstrated that the C(6) hydroxy group in 1 was essential for activity. We found that replacing the C(6)-hydroxy group in 1 with weaker hydrogen bond donors led to low inhibitory activities in the rho-dependent ATPase and transcription termination assays. None of the bicyclomycin derivatives exhibited antibiotic activity against E. coli W3350 cells at a 32 mg/mL concentration. The apparent specificity for the C(6)-hydroxy group in 1 suggests that an efficient hydrogen bond donor interaction from the C(6)-hydroxy group to rho or the C(6) hemiaminal bond cleavage to 2 or both is necessary for drug function.

Life events and schizophrenic relapse after withdrawal of medication.

Research with schizophrenic out-patients has shown that antipsychotic medication reduces relapse rates. This protective factor may operate partially by raising the threshold for relapse in the face of environmental stressors such as life events and high levels of familial expressed emotion. A prospective, longitudinal design was employed in the monthly collection of life-events data with 23 recent-onset schizophrenic out-patients. In a between-subjects ANOVA, a significantly higher frequency of independent life events was found in the month prior to a relapse for ten patients on medication, as compared with the analogous month for 13 drug-free patients. These findings suggest that neuroleptic medication may produce a prophylactic effect by raising a patient's threshold of vulnerability to relapse.

A prospective study of stressful life events and schizophrenic relapse.

In this prospective, longitudinal study, 11 recent-onset schizophrenic outpatients who met criteria for psychotic relapse or significant psychotic exacerbation during a 1-year period of standardized maintenance medication, and 19 patients who did not relapse during this follow-up period, were interviewed monthly regarding life events. As hypothesized, for relapsing patients, a significantly higher number of independent life events (those not the result of symptomatology or personal influence) occurred in the month preceding relapse. This increase was apparent relative to either the analogous month of a "nonrelapse" period in the same patient or the average number of independent events per month during a 1-year standardized medication period for nonrelapsing patients. The methodological advances of this design as well as the consistency of these findings with those of previous retrospective studies supports the hypothesis that life events may sometimes "trigger" schizophrenic episodes.

Acute mountain sickness, antacids, and ventilation during rapid, active ascent of Mount Rainier.

A double-blind randomized study of 45 climbers on Mt. Rainier was conducted to test the effectiveness of antacids in preventing acute mountain sickness. All 45 climbed to 3353 m, and 31 continued to the summit. Ten climbers listed acute mountain sickness as the reason for not attaining the summit. Of symptoms monitored throughout the climb, neither headache, nausea, dizziness, pounding heart, nor shortness of breath differed in severity between antacid-treated and placebo-treated groups. In both groups vital capacity decreased significantly with ascent (p less than 0.05), while peak flow (p less than 0.005) and minute ventilation (p less than 0.001) increased significantly. The 7 climbers with the most severe AMS symptom scores above 4000 m had significantly lower peak flow at sea level prior to ascent compared with the other 25 climbers who completed sea level tests (p less than 0.005). The results of this study fail to document efficacy for antacid use for the prevention of acute mountain sickness.