Pulmonary aspergilloma. Results of surgical treatment

Between 1953 and 1984, 53 patients (40 male and 13 female) underwent thoracotomy for treatment of pulmonary aspergilloma. The median age was 58 years (range 4 to 86 years). Either underlying lung disease or immunologic risk factors were present in 49 patients (92%). Twenty-one patients (31%) had simple aspergilloma and 32 (47%) had complex aspergilloma. The most common indication for operation was an indeterminate mass, hemoptysis, or severe cough. Lobectomy, wedge excision, and pneumonectomy were the most frequent operations. Complications occurred in 78% of patients with complex aspergilloma and in 33% of patients with simple aspergilloma (p = 0.002). Operative mortality was 5% (one death) in patients with simple aspergilloma and 34% (11 deaths) in patients with complex aspergilloma (p = 0.01). Cause of death was respiratory failure in four patients, underlying pulmonary disease in three, aspergillosis in two, and other conditions in three. At follow-up, 84% of operative survivors with simple aspergilloma were alive and well compared with 43% of those with complex aspergilloma. Although operative mortality in patients with complex aspergilloma was high, 67% of the survivors had a good long-term result in terms of absence of symptoms, but they frequently died of underlying disease. In contrast, operation in patients with simple aspergilloma was done with low risk, and approximately 90% of survivors had a good late result. Late appearance of contralateral disease did occur and argues for rigorous postoperative surveillance.     

Does an oral analgesic protocol improve pain control for patients with cancer? An intergroup study coordinated by the Eastern Cooperative Oncology Group

BACKGROUND: Cancer pain is highly prevalent and commonly undertreated. This study was designed to determine whether dissemination of a clinical protocol for pain management would improve outcomes in community oncology practices. PATIENTS AND METHODS: A pain management protocol was developed based on accepted guidelines. After baseline assessment, oncology practices were randomly assigned to 'analgesic protocol' (AP) sites, where oncologists implemented the guidelines in a group of lung or prostate cancer patients, or to 'physician discretion' (PD) sites, where customary treatment was continued. Patients treated on protocol and a comparison group of patients with pain due to breast cancer or myeloma were monitored for change in pain using the Brief Pain Inventory, and for change in other symptoms or mood. RESULTS: The protocol terminated early because of poor accrual. We compared groups using proportions of patients who had no or mild pain at follow-up. Although measures of protocol adherence did not suggest the occurrence of major practice change, the proportion of lung or prostate cancer patients with no or mild pain increased significantly from baseline for those treated at AP sites compared with those treated at PD sites. There was no significant difference between the breast and myeloma patients treated at AP sites versus those treated at PD sites. CONCLUSION: A protocol for cancer pain management can improve pain control. Diffusion of these benefits to other patients was not confirmed. Given the small sample size, these findings require confirmation in a larger trial.     

In vivo MRI of cancer cell fate at the single-cell level in a mouse model of breast cancer metastasis to the brain.

Metastasis (the spread of cancer from a primary tumor to secondary organs) is responsible for most cancer deaths. The ability to follow the fate of a population of tumor cells over time in an experimental animal would provide a powerful new way to monitor the metastatic process. Here we describe a magnetic resonance imaging (MRI) technique that permits the tracking of breast cancer cells in a mouse model of brain metastasis at the single-cell level. Cancer cells that were injected into the left ventricle of the mouse heart and then delivered to the brain were detectable on MR images. This allowed the visualization of the initial delivery and distribution of cells, as well as the growth of tumors from a subset of these cells within the whole intact brain volume. The ability to follow the metastatic process from the single-cell stage through metastatic growth, and to quantify and monitor the presence of solitary undivided cells will facilitate progress in understanding the mechanisms of brain metastasis and tumor dormancy, and the development of therapeutics to treat this disease.     

A series of potent HIV-1 protease inhibitors containing a hydroxyethyl secondary amine transition state isostere: synthesis, enzyme inhibition, and antiviral activity.

A series of HIV-1 protease inhibitors containing a novel hydroxyethyl secondary amine transition state isostere has been synthesized. The compounds exhibit a strong preference for the (R) stereochemistry at the transition state hydroxyl group. Molecular modeling studies with the prototype compound 11 have provided important insights into the structural requirements for good inhibitor-active site binding interaction. N-Terminal extension of 11 into the P2-P3 region led to the discovery of 19, the most potent enzyme inhibitor in the series (IC50 = 5.4 nM). 19 was shown to have potent antiviral activity in cultured MT-4 human T-lymphoid cells. Comparison of analogs of 19 with analogs of 1 (Ro31-8959) demonstrates that considerably different structure-activity relationships exist between these two subclasses of hydroxyethylamine HIV-protease inhibitors.     

Geriatric care on a ward without nurses

The Multiphasic Environmental Assessment Procedure (MEAP; Moos and Lemke, 1984) was used to assess three long-stay settings within a geriatric hospital, one of which is a non-nursing unit committed to the philosophy of residents viewing the setting as their own home. Findings suggest positive outcomes for residents on the nonnursing unit, and support the view that types of care fostering independence and personal responsibility of elderly residents in their setting may be associated with increased mental functioning and activity. The lack of trained nursing staff had no detrimental effect on any measure of resident life, and some specific caring practices on the unit may be interpreted as having a positive outcome for residents.     

Flexible Sigmoidoscopy Screening in an Industrial Setting

Little is known about the yield of colorectal cancer screening programs in an industrial setting. We therefore established a flexible sigmoidoscopy screening program at a chemical manufacturing plant and offered testing to all employees over the age of 40. After a Fleet enema preparation had been administered, a digital rectal examination and sigmoidoscopy were performed on each volunteer worker in the medical office of the plant. The plant had an average census of about 650 workers; 202 were screened during a 2-yr period. The mean (+/- SEM) age of participants was 52 +/- 0.4. Sixty-four employees had polyps (31.7%); data on follow-up colonoscopy were available in 69%. Colonoscopy revealed adenomatous polyps in 23 workers (53.5%), hyperplastic polyps in 10 (23%), and no evidence of neoplasia in 10 (23%). Seven workers did not arrange for follow-up colonoscopy and 12 individuals could not be contacted. No cancers were detected. In the 40- to 50-yr age group, polyps were detected in 19.5% of employees (25% adenomatous). Incidental findings were common, and included prostatic nodules, hemorrhoids, diverticulosis, and proctitis, among others. We conclude that screening sigmoidoscopy can be conveniently and economically performed at the workplace, with a high yield and good worker acceptance. The high yield suggests a possible association between polyp formation and work in a chemical plant. The finding of adenomatous polyps in the younger patients suggests that the threshold for flexible sigmoidoscopy at age 50 needs to be reassessed.     

Not an equal opportunity disease – a sex and gender-based review of colorectal cancer in men and women: Part II

This paper reviews the literature on colorectal cancer from a sex and gender-based perspective. Colorectal cancer is a major cause of death in the developed world, with rates increasing in developing countries. Although described by some writers as an ‘equal opportunity’ disease, it presents more risk to men than women. Both biological, or sex-linked factors, and gender-linked factors play a part in the aetiology of the disease, while gender differences in the use of screening and treatment also help shape the mortality gap between women and men for this condition. Without an appreciation of the part played by sex and gender in the risk of colorectal cancer, and without a gender-sensitive approach to screening in particular, it is possible that the mortality gap between men and women for this condition will widen in the future.     

Cytomegalovirus Disease in High-Risk Transplant Recipients Despite Ganciclovir or Valganciclovir Prophylaxis

The clinical patterns and predictors of cytomegalovirus (CMV) disease in kidney and/or pancreas transplant patients on ganciclovir (1.0 g po t.i.d.) or valganciclovir (450 mg po q.d.) prophylaxis were studied. This is a retrospective analysis of 129 transplant recipients. Median follow up was 12 months (range, 6-18 months). The overall incidence of CMV disease at 1-year post-transplant was 14% (4% tissue-invasive, 10% noninvasive). Seventeen of 18 patients were diagnosed with CMV after completion of 3 months' prophylaxis (median 8 weeks, range, 2-28 weeks). Induction treatment with thymoglobulin, and Donor +/Recipient - CMV status were the strongest predictors for the development of CMV disease. Cytomegalovirus incidence was not different between patients treated with ganciclovir or valganciclovir (15 vs. 17%, respectively). Valganciclovir (450 mg q.d.) is as effective as oral ganciclovir in CMV prophylaxis. High-risk individuals might require higher doses or longer duration of valganciclovir treatment.     

An animal model of chronic inflammatory pain: pharmacological and temporal differentiation from acute models.

Clinically, inflammatory pain is far more persistent than that typically modelled pre-clinically, with the majority of animal models focussing on short-term effects of the inflammatory pain response. The large attrition rate of compounds in the clinic which show pre-clinical efficacy suggests the need for novel models of, or approaches to, chronic inflammatory pain if novel mechanisms are to make it to the market. A model in which a more chronic inflammatory hypersensitivity phenotype is profiled may allow for a more clinically predictive tool. The aims of these studies were to characterise and validate a chronic model of inflammatory pain. We have shown that injection of a large volume of adjuvant to the intra-articular space of the rat knee results in a prolonged inflammatory pain response, compared to the response in an acute adjuvant model. Additionally, this model also results in a hypersensitive state in the presence and absence of inflammation. A range of clinically effective analgesics demonstrate activity in this chronic model, including morphine (3mg/kg, t.i.d.), dexamethasone (1mg/kg, b.i.d.), ibuprofen (30mg/kg, t.i.d.), etoricoxib (5mg/kg, b.i.d.) and rofecoxib (0.3-10mg/kg, b.i.d.). A further aim was to exemplify the utility of this chronic model over the more acute intra-plantar adjuvant model using two novel therapeutic approaches; NR2B selective NMDA receptor antagonism and iNOS inhibition. Our data shows that different effects were observed with these therapies when comparing the acute model with the model of chronic inflammatory joint pain. These data suggest that the chronic model may be more relevant to identifying mechanisms for the treatment of chronic inflammatory pain states in the clinic.