Efficacy of low-dose interferon with antiretroviral therapy in Kaposi's sarcoma: a randomized phase II AIDS clinical trials group study.

We wished to evaluate the efficacy and safety of a low and an intermediate daily dose of interferon-alpha2b (IFN-alpha2b) with didanosine in patients with acquired immunodeficiency syndrome (AIDS)-associated Kaposi's sarcoma (KS). HIV-seropositive subjects with biopsy-confirmed cutaneous KS were randomized to receive either a low (1 million IU) or an intermediate (10 million IU) dose of IFN-alpha2b once daily with twice daily doses of didanosine. Treatment assignment was stratified by CD4 count. Response, toxicity, changes in CD4 counts, and survival were evaluated. Sixty-eight eligible subjects were accrued, 35 to low-dose and 33 to intermediate-dose IFN-alpha2b. The response rate was 40% in the low-dose group (95% CI, 24-58) and 55% in the intermediate-dose group (95% CI, 36-72) (p = 0.338). The median response duration was approximately 110 weeks in both groups. Intermediate-dose IFN induced grade 3/4 neutropenia more often (21% vs. 3%, p = 0.048) and grade 3/4 toxicity faster (p = 0.0231) and necessitated treatment discontinuation earlier for drug-related toxicities (p = 0.0416) than low-dose IFN. There were no significant differences in survival between the treatment groups. Baseline CD4 count was the only significant factor predicting response. Once-daily low-dose and intermediate-dose IFN-alpha2b induced similar response rates, which were achieved without optimal antiretroviral therapy. The slightly higher response rate in the intermediate-dose group was offset by its significantly poorer tolerance. These findings justify the use of lower, well-tolerated IFN doses for treatment of KS with currently used antiretroviral regimens.     

Impact of Induction Chemotherapy and Preoperative Chemoradiotherapy on Operative Morbidity and Mortality in Patients with Locoregional Adenocarcinoma of the Stomach or Gastroesophageal Junction

Background Significant tumor downstaging has been achieved in patients with localized gastric or gastroesophageal adenocarcinoma by induction chemotherapy and preoperative chemoradiotherapy (CTX–CTXRT). However, the influence of CTX–CTXRT on operative morbidity and mortality has not yet been clarified. The aim of the present study was to document the frequency and nature of morbidity and mortality after surgery combined with CTX–CTXRT, and identify factors predictive of postoperative complications in patients with localized gastric or gastroesophageal adenocarcinoma. Methods A prospectively collected database on 71 consecutive patients who underwent CTX–CTXRT at M.D. Anderson Cancer Center between January 1997 and August 2004 was reviewed. Postoperative morbidity and mortality were investigated, and risk factors for overall complications were identified by multivariate logistic regression analysis. Results Overall morbidity and mortality rates were 38.0% (27 patients) and 2.8% (2 patients), respectively. Age greater than 60 years [relative risk 11.3 (95% confidence interval 2.50–50.6)] and body mass index (BMI) of 26 kg/m² or above [relative risk 4.08 (95% confidence interval 1.08–15.4)] were significant risk factors for overall complications. Conclusions CTX–CTXRT can be performed safely with an acceptable operative morbidity and a low operative mortality rate in patients with gastric or gastroesophageal cancer, with careful consideration of added risk associated with age and obesity.     

Francisella tularensis: possible agent in bioterrorism.

Francisella tularensis, the causative agent of tularemia, is a highly infectious gram-negative coccobacillus. Due to its high infectivity it is of major concern to public health officials as a possible biological weapon. Although accidental exposure can occur through arthropod bites, handling infected animals, or breathing in aerosols, cases are usually isolated and contained. In the event of an intentional exposure such as in a bioterrorist attack, inhalation of aerosols can result in devastating consequences with much causality. Although a vaccine is available, sufficient quantities may not be readily accessible in an actual attack. Therefore, it is very important for both medical professionals and public health officials to be prepared to contain and control the situation should it actually occur.     

Poxvirus-based vaccine therapy for patients with advanced pancreatic cancer

Purpose  

An open-label Phase 1 study of recombinant prime-boost poxviruses targeting CEA and MUC-1 in patients with advanced pancreatic cancer was conducted to determine safety, tolerability and obtain preliminary data on immune response and survival.     

Does the health status of chronically ill patients predict their judgements of the quality of general practice care?

Patients' health status as well as patients' judgements of care are used for assessing patients' perspectives, but the relation between those two concepts is unclear. In this study we explored whether health status predicts patients' judgements of the quality of general practice care. Hand-distributed and mailed surveys were performed by 28 general practitioners in The Netherlands. Chronically ill patients were approached when visiting the general practice or drawn from the practice registers. Health status was measured by WONCA/COOP charts, and patients' judgements by the CEP, a previously validated questionnaire. The response rate was 63% (n=762). When controlled for other patient characteristics, a poor overall health predicted less positive judgements of medical care, information, counselling, relation and communication, continuity of care and the organization of appointments (p[lessthan]0.01). Poor mental well-being predicted less positive judgements of the cooperation between care providers and a stronger need for more care (p[lessthan]0.001). The four other aspects of health status did not predict the patients' judgements. Judgements about the premises and the availability for emergencies were not predicted by health status. It can be concluded that a multidimensional approach should be used for interpreting the relations between patients' health status and their judgements of general practice care.     

Fast-phase instabilities in normally sighted relatives of congenital nystagmus patients—autosomal dominant and x-chromosome recessive modes of inheritance

Verification of inheritance in congenital nystagmus (CN) is only possible through the identification of more than one affected member in a family, since in a single case there are no accurate clinical differentiations between spontaneous and inherited CN. We performed electronystagmographic examinations (ENG) to search for abnormal involuntary eye movements as a sign of heredity in seemingly unaffected members of CN families.ENG registrations were performed under three test conditions: (1) with the subject fixating a target, (2) with the room lights off and (3) with closed eyes.Fifty normally sighted individuals (group (a) underwent the test procedure to provide a baseline of normality. Five CN families (three dominant, two sex-linked recessive) were tested as group (b). The eye movement recordings were analysed in terms of nystagmus intensity (amplitude x frequency of the involuntary saccade). In every one of the five families, abnormalities in seemingly non-affected members could be demonstrated: in four families, fastphase instabilities, in the fifth family a true (CN) (slowphase instability).All certain gene carriers were diagnosed correctly by the ENG.These findings indicate a method for detecting slightly affected members in dominant pedigrees and female gene carriers in sex-linked mode of transmission.     

Communication of BRCA1 and BRCA2 results to at-risk relatives: a cancer risk assessment program's experience

We describe results from a survey designed to assess patterns of communication within families shortly after an individual receives results of BRCA1 and BRCA2 mutation carrier status. Shortly after disclosure of BRCA1 and BRCA2 genetic test results, the proband was contacted by phone to administer the post disclosure survey. Questions asked included whether they had shared their results with their siblings or adult children, if there were difficulties in communicating the test results, and if there was any distress associated with the sharing of results. A total of 162 women who have received results from BRCA1 and BRCA2 genetic testing participated in the survey. The probands shared their results more often with their female than their male relatives (P < 0.001). Probands who had tested positive for a mutation in the BRCA1 or BRCA2 gene shared their results more often with their relatives than did probands who were not carriers (P = 0.002). Probands reported more often that their siblings rather than their adult children had difficulties understanding the results (P = 0.001). The probands who were carriers more often reported having difficulties explaining their results to their relatives (P < 0.001) and their relatives were upset on hearing the result more often than were the relatives of probands who were not carriers (P < 0.001). The probands who were carriers reported more often that they were upset explaining their results to their relatives than did the probands who were not carriers (P < 0.001). Individuals are disclosing their test results to their relatives. Probands who are BRCA1- or BRCA2-positive are more likely to experience difficulty and distress with the communication of their test results to family members.