Doxorubicin pharmacokinetics: the effect of abnormal liver biochemistry tests

We studied variability in doxorubicin pharmacokinetics in 24 patients with abnormal liver biochemistry tests. Blood samples were collected after the first cycle of single-agent doxorubicin given as an i.v. bolus and plasma levels were measured by high-performance liquid chromatography. The relationship between doxorubicin clearance (dose/AUC) and liver biochemistry tests (AST, bilirubin, albumin, alkaline phosphatase and indocyanine green clearance) was investigated. Patients with a raised bilirubin level had reduced doxorubicin clearance, but there was no clear relationship between the extent of this elevation and the reduction in doxorubicin clearance. Doxorubicin clearance was lower in patients with an isolated increase in AST than in those with normal liver biochemistry, but this difference was not statistically significant. Nevertheless, there was a significant correlation between reduced doxorubicin clearance and both raised serum AST levels and low indocyanine green clearance. These pharmacokinetic data suggest that current dose reductions based solely on the extent to which bilirubin is elevated may not be optimal. Received: 20 October 1997 / Accepted: 20 January 1998     

Gunshot wounds to the facial nerve.

OBJECTIVE: This paper presents our experience with gunshot wounds to the temporal bone and discusses facial nerve lesions, surgical indication, surgical timing, and other findings. STUDY DESIGN: We performed a retrospective review of patients treated for facial nerve lesion after gunshot injury to the temporal bone. SETTING: The study was performed in the Otolaryngology Department of the University of Sao Paulo Medical School, Sao Paulo, Brazil. PATIENTS: Ninety-eight patients treated between 1988 and 1999 were analyzed. INTERVENTION: Facial nerve lesions, bullet locations, and surgical techniques were analyzed. Patients were monitored for 2 years. RESULTS: Gunshot trauma to the temporal bone presented considerable tissue loss resulting from the abrasion effect and severity of the impact. The third segment of the facial nerve was most affected, and the bullet was typically found lodged in the mastoid tip. Postoperative infection was common. Such cases required revision surgery, resulting in worse cosmetic outcomes than in cases of closed trauma. CONCLUSIONS: Surgical exploration of the facial nerve should be performed as soon as possible, since long delays increase the chance of traumatic neuroma and more pronounced scarring around the facial nerve. Open mastoidectomy with meatoplasty is the surgical technique recommended for repairing the mastoid and the facial nerve. In the majority of cases, a cable graft is necessary. Since nerve lesion in proximity to the stylomastoid foramen and extratemporal facial nerve is common, these areas must be explored carefully.     

High dose chemotherapy and autologous stem cell transplantation as adjuvant therapy for primary breast cancer patients with four or more lymph nodes involved: long-term results of an international randomised trial.

BACKGROUND: The purpose of this study was to assess whether a short course of anthracycline containing chemotherapy followed by high dose therapy with autologous stem-cell support improves disease-free and overall survival as compared with conventional, anthracycline containing chemotherapy, in patients with primary breast cancer and four or more histologically involved lymph nodes. PATIENTS AND METHODS: Two hundred and eighty one patients entered into a randomised clinical trial were allocated to receive standard, conventional treatment (5-fluorouracil, epirubicin and cyclophosphamide-FEC for six cycles) or FEC for three cycles followed by high dose therapy consisting of cyclophosphamide, thiotepa and carboplatin and stem cell rescue (HDT). To be eligible, patients had to be free of overt metastatic disease and be < or =60 years of age. Analyses were according to intention to treat. RESULTS: At a median follow up of 68 months, 118 patients have experienced a relapse or death from breast cancer (62 in the FEC followed by HDT arm and 56 in the conventional FEC arm) and a total of 100 patients have died (54 in the FEC followed by HDT arm and 46 in the conventional FEC arm). No significant difference was observed in relapse-free survival [hazard ratio 1.06, 95% CI 0.74-1.52, p = 0.76] or overall survival [hazard ratio 1.18, 95% CI 0.80-1.75, p = 0.40]. Five patients died from treatment related causes, three as a consequence of HDT and two in the conventional FEC arm. CONCLUSIONS: At the present time, no benefit has been observed from replacing three cycles of conventional chemotherapy with the HDT regimen described here. Patients should continue to receive conventional chemotherapy as adjuvant therapy for breast cancer.     

Oral shedding of HSV-1 and EBV and oral manifestations in paediatric chronic kidney disease patients and renal transplant recipients

Objective: Previous research demonstrated that salivary shedding of HSV-1 and EBV occurs often in adult renal transplant recipients, but there is a lack of studies on the presence of them in the saliva of paediatric population. Therefore, the objective of this study is to describe oral characteristics and to compare the shedding profile of HSV-1 and EBV in the saliva of children with renal transplant to that of chronic kidney disease patients and controls.

Methods: This is a cross-sectional study involving 100 children, being 25 renal transplant recipients, 25 chronic kidney disease patients and 50 healthy children. Demographic and oral clinical characteristics were assessed. Saliva samples were collected and submitted to screening for EBV and HSV-1 by using nested polymerase chain reaction technique. Fisher’s exact, Pearson’s chi-square and Kruskal–Wallis tests were used for statistical analysis at a significance level of 5%.

Results: Oral shedding of HSV-1 (28%) and EBV (60%) were significantly higher in renal transplant recipients compared to the other groups. Single vesicles in the oral mucosa were statistically associated with the presence of HSV-1 (p?=?.035). In children with chronic kidney disease, there was a higher prevalence of pale oral mucosa (32%) and enamel hypoplasia (40%) compared to paediatric renal transplant recipients and controls. Dental calculus (36%), candidiasis (8%), drug-induced gingival overgrowth (16%), mouth blisters (8%), xerostomia (12%) and salivary gland enlargement (20%) were more common in paediatric renal transplant recipients.

Conclusions: Therefore, it can be concluded that salivary shedding of HSV-1 and EBV in paediatric patients was more often found in renal transplant recipients than in the renal failure and control children. Transplanted recipients showed more oral manifestations than renal failure and control children did.     

Influence of history of smoking on the physical capacity of older people

Among the elderly, smoking is related to death and it contributes to disability associated with chronic diseases. This study aims to verify the influence of a history of smoking on the physical capacity of elderly people, and its relationship with the gender. Elderly people beginning to practice physical activity reported questions about their smoking history and underwent a physical evaluation, consisted by hemodynamic data (blood pressure, heart rate and maximum oxygen consumption), body mass index (BMI), muscular strength, flexibility and balance. Mann-Whitney test and Spearman's test was used to data analysis. The sample consisted of 127 subjects, among whom 26.8% were ex-smokers. There were a higher number of nonsmoking women (p < 0.001) than others, and women smoked fewer packets per day (p = 0.047). Among the women, those ex-smokers were younger and more flexible in comparison with those nonsmokers (p < 0.05). Among the men, the ex-smokers were older and walked more slowly than nonsmokers (p < 0.05). There was a correlation between the BMI and duration of smoking time. Smoking cessation benefits the elderly, since the physical variables showed no long-term harm associated with the history of smoking when compared with those of elderly without this habit.