A prospective study of concurrent cyclophosphamide/methotrexate/5-fluorouracil and reduced-dose radiotherapy in patients with early-stage breast carcinoma

BACKGROUND: Concurrent administration of chemotherapy and radiotherapy has the potential advantage of delaying neither treatment and providing radiation sensitization. However, the optimal approach to concurrent treatment in women with early-stage breast carcinoma remains undefined. We present updated results of a prospective protocol of concurrent cyclophosphamide/methotrexate/5-fluorouracil (CMF) and reduced-dose radiotherapy, focusing on tumor control and patient tolerance. METHODS: One hundred twelve women with AJCC Stage I or Stage II breast carcinoma with 0-3 positive axillary lymph nodes were enrolled in a prospective single-arm study of concurrent CMF and reduced-dose radiotherapy (39.6 gray [Gy] to the whole breast, 16-Gy boost). A high proportion of women had risk factors associated with an increased risk of local disease recurrence, including age <40 (32%), close or positive margins (37%), or lymphatic/vascular invasion (51%). The median follow-up period was 94 months. RESULTS: The 5-year overall survival rate was 94%. By 60 months, 5 patients (4%) experienced local disease recurrence and 19 patients (17%) experienced distant metastasis. There were no isolated regional lymph node recurrences. Local disease recurrence occurred in 1 of 25 patients (4%), 1 of 16 patients (6%), and 3 of 70 patients (4%) with positive, close (<1 mm), and negative margins, respectively. One patient developed acute myelogenous leukemia. An additional patient developed Grade 2 pneumonitis. Cosmetic results were not recorded uniformly for all patients and therefore could not be reliably analyzed. CONCLUSIONS: Concurrent CMF and reduced-dose radiotherapy resulted in a low level of late toxicity and excellent local tumor control, despite the large proportion of patients with substantial risk factors for local disease recurrence. Future studies of concurrent regimens, particularly in patients at high risk of local disease recurrence, are warranted.     

Multiple substance use disorders in juvenile detainees

OBJECTIVE: To estimate the 6-month prevalence of multiple substance use disorders (SUDs) among juvenile detainees by demographic subgroups (sex, race/ethnicity, age). METHOD: Participants were a randomly selected sample of 1,829 African American, non-Hispanic white, and Hispanic detainees (1,172 males, 657 females, aged 10 to 18). Patterns and prevalence of DSM-III-R multiple SUDs were assessed using the Diagnostic Interview Schedule for Children Version 2.3. The authors used two-tailed F and t tests with an alpha of .05 to examine combinations of SUDs by sex, race/ethnicity, and age. RESULTS: Nearly half of the detainees had one or more SUDs; more than 21% had two or more SUDs. The most prevalent combination of SUDs was alcohol and marijuana use disorders (17.25% females, 19.42% males). Among detainees with any SUD, almost half had multiple SUDs. Among detainees with alcohol use disorder, more than 80% also had one or more drug use disorders. Among detainees with a drug use disorder, approximately 50% also had an alcohol use disorder. CONCLUSIONS: Among detained youths with any SUD, multiple SUDs are the rule, not the exception. Substance abuse treatments need to target detainees with multiple SUDs who, upon release, return to communities where services are often unavailable. Clinicians can help ensure continuity of care by working with juvenile courts and detention centers.     

Regulation of myoplasmic Ca(2+) in genetically obese (ob/ob) mouse single skeletal muscle fibres

The present study examined whether calcium handling in skeletal muscle fibres from ob/ob mice was abnormal compared to normal mice. Simultaneous measurements of free myoplasmic calcium and force were made in mouse single intact muscle fibres at rest, during repetitive stimulation and for 30 min afterwards. Fibres were subjected to two bouts of intermittent tetanic contractions 1 h apart. The first bout consisted of 50 tetani only, while during the second bout stimulation was continued until force fell to 40% of control. During a bout of 50 repeated contractions, muscle fibres from ob/ob mice were unable to maintain basal calcium and tetanic calcium transients. During a second series of contractions, muscle fibres from ob/ob mice showed a marked improvement in calcium handling compared to the first series but still fatigued more rapidly than control fibres. It is concluded that calcium handling in skeletal muscle fibres from ob/ob mice is abnormal compared to fibres from normal mice and this contributes to premature fatigue.     

Sensitization of thermotolerant SCK cells to hyperthermia and freezing with reduction of intracellular pH: implications for cryosurgery

BACKGROUND AND OBJECTIVES: During cryosurgery, cells frozen slowly at the outer part of the ice ball undergo severe dehydration and are subject to solute effects injury, which may be caused in part by protein denaturation. This study was undertaken to determine whether heat shock proteins (HSPs), the molecular chaperones that stabilize proteins against denaturation, have a protective effect on cells during slow freezing. In addition, we aimed to determine whether acidic conditions, similar to those found in many solid tumors, would effect this protection. METHODS: SCK cells were frozen at 5 degrees C/min to -10 degrees C or -20 degrees C before or after induction of thermotolerance, and at neutral or low pH conditions. Lethal damage was determined by clonogenics. RESULTS: Clonogenic survival was decreased by 50% in thermotolerant cells frozen to -10 degrees C after culture in acidic conditions (pH 6.6) compared with non-thermotolerant cells cultured at neutral pH. Induction of thermotolerance alone or low pH alone did not significantly sensitize SCK cells to freezing. All treatment groups were equally susceptible to killing when frozen to -20 degrees C. CONCLUSIONS: Our results show that induction of thermal tolerance does not protect SCK cells against subsequent freezing injury and that a low pH environment actually sensitizes these cells to freeze injury.     

Conservative management of Paget disease of the breast with radiotherapy: 10- and 15-year results

BACKGROUND: At 5-year follow-up, patients with Paget disease of the breast who were treated with breast-conserving surgery (BCS) and radiotherapy (RT) had excellent results. The current report provides 10- and 15-year rates of tumor control in the breast, as well as disease-free and overall survival rates following BCS and RT in a cohort of patients with Paget disease presenting without a palpable mass or mammographic density. METHODS: Through a collaborative review of patients treated with BCS and RT from seven institutions, 38 cases of Paget disease of the breast presenting without a palpable mass or mammographic density were identified. All patients had pathologic confirmation of typical Paget cells at time of diagnosis. Thirty-six of 38 patients had a minimum follow-up greater than 12 months and constitute the study cohort. Ninety-four percent of patients underwent complete or partial excision of the nipple-areola complex and all patients received a median external beam irradiation dose of 50 Gy (range, 45-54 Gy) to the whole breast. Ninety-seven percent of patients also received a boost to the remaining nipple or tumor bed, a median total dose of 61.5 Gy (range, 50.4-70 Gy). RESULTS: With median follow-up of 113 months (range, 18-257 months), 4 of 36 patients (11%) developed a first recurrence of disease in the treated breast only. Two of the four recurrences in the breast were ductal carcinoma in situ (DCIS) only and two were invasive with DCIS. Two additional patients had a recurrence in the breast as a component of first failure. Actuarial local control rates for the breast as the only site of first recurrence were 91% at 5 years (95% confidence interval [CI], 80-100%) and 87% (95% CI, 75-99%) at both 10 and 15 years. Actuarial local control rates for breast recurrence, as a component of first failure, were 91% (95% CI, 80-100%), 83% (95% CI, 69-97%), and 76% (95% CI, 58-94%) at 5, 10, and 15 years, respectively. No clinical factors were identified as significant predictors for breast recurrence. Five-, 10- and 15-year actuarial rates for survival without disease of 97% (95% CI, 90-100%) and 5-, 10-, and 15-year actuarial rates of overall survival of 93% (95% CI, 84-100%) at 5 years and 90% (95% CI, 78-100%) at 10 and 15 years were reported. CONCLUSIONS: These data confirm excellent rates of local control, disease-free survival, and overall survival at 10 and 15 years following BCS and RT for Paget disease of the breast. This study continues to support the recommendation of local excision and definitive breast irradiation as an alternative to mastectomy in the treatment of patients with Paget disease presenting without a palpable mass or mammographic density.     

Risk factors associated with rosacea

Background Although rosacea is a common disease, the cause of disease is still a mystery –Helicobacter pylori infection, genetic predisposition, climatic factors, and detrimental habits are implicated as triggers of rosacea. Objective The aim of current study is to evaluate several suspected risk factors coincidently. Methods Patients with rosacea from a dermatology clinic and skin‐healthy controls from an randomly selected employees' population enrolled the study. Skin status were evaluated by one and same dermatologist. Participants were queried for age, gender, sun‐reactive skin type, and detrimental habits using a questionnaire; blood samples for detecting Helicobacter pylori serostatus were collected. Results Totally 145 skin‐healthy controls and 172 subjects either with flushing episodes or established rosacea included the study. In multivariate analysis, rosacea patients had significantly higher chance to have photosensitive skin types (OR 1.75; 95% CI 1.01–3.04; P < 0.05), positive family history to rosacea (OR 4.31; 95% CI 2.34–7.92; P < 0.0001) or previous smoking status (OR 2.01; 95% CI 1.07–3.80; P < 0.05) comparing with skin‐healthy controls. There were no statistically significant differences either in gender, Helicobacter pylori serostatus, caffeine intake, alcohol consumption, occupational environment, or education level between rosacea patients and controls. Conclusion Rosacea is foremost associated with familial predisposition. There is no association between Helicobacter pylori infection and rosacea in current study.