Late solitary metastasis of a renal cancer to the contralateral adrenal gland

We report a case of metachronous metastasis from renal cell carcinoma to the contralateral adrenal gland detected one year after radical nephrectomy. The initial tumor was incidentally discovered in the setting of acute aortic dissection. A large left adrenal tumor was detected on CT follow-up at two years. Retrospectively, a hypervascular lesion was present on the first yearly CT examination. Adrenalectomy was performed. There is no evidence of recurrent disease at 12 months. The patient was also treated with oral steroids. Because of their location and of the particularities of available therapeutic options, and because these metastases can occur late, long-term sonographic and CT follow-up should be performed. The clinical, imaging, therapeutic and prognostic aspects of these lesions will be discussed.     

Positional occlusion of the descending scapular artery in transverse thoraco-brachial syndrome with neurologic symptoms

We report a thoracic outlet syndrome revealed by neurological complications. Angiography of the subclavian artery depicted an isolated positional occlusion of the descending scapular artery. This side branch of the subclavian artery is anatomically located close to and supplies the brachial plexus. Surgical treatment led to improvement of most symptoms and post-operative control angiography was normal. Not previously described, this sign illustrates the objective compression of the brachial plexus. Ischemia is perhaps intricated with compression, a well-known pathophysiological mechanism of neurological complications in this syndrome. This artery feeding the brachial plexus is usually ligated during surgical neurolysis but must be preserved in order to improve recovery of neurological function and prevent surgical failures.     

Sirolimus (rapamycin) potentiates cyclosporine in prevention of acute lung rejection

BACKGROUND: Cyclosporine-based immunosuppressive regimens (INN: ciclosporin) in human lung transplantation continue to result in a high incidence of acute cellular rejection. We investigated the use of sirolimus, a macrolide with structural similarity to tacrolimus, as monotherapy and in combination with cyclosporine in a rodent lung transplant model. METHODS: Orthotopic left lung transplantation was performed in Lewis recipients from Brown-Norway donor rats with syngeneic Lewis-to-Lewis controls. Open biopsies were performed on postoperative day 7, and the severity of acute lung rejection was graded by a pathologist blinded to the protocol. RESULTS: All recipients survived despite the amount of acute rejection seen on examination of the biopsy tissue. Lewis-to-Lewis isografts demonstrated near normal pulmonary architecture. Allogeneic recipients receiving high-dose cyclosporine (25 mg/kg) monotherapy showed mild to moderate acute rejection with some perivascular focal interstitial infiltrates. Recipients receiving low-dose cyclosporine (5 mg/kg) monotherapy or low- or high-dose sirolimus (0.5 or 2.0 mg/kg, respectively) monotherapy demonstrated massive cellular infiltration leading to necrosis and infarction and could not be graded. However, the addition of low-dose sirolimus (0.5 mg/kg) to low-dose cyclosporine (5 mg/kg) demonstrated a significant potentiating immunosuppressive effect, and the addition of high-dose sirolimus (2.0 mg/kg) to low-dose cyclosporine (5.0 mg/kg) demonstrated an even greater effect, with rejection scores better than those obtained with high-dose cyclosporine monotherapy and similar to those obtained with isografts. CONCLUSIONS: This study demonstrates that low-dose sirolimus has a cyclosporine-sparing effect and that a higher dose of sirolimus in combination with cyclosporine strongly protects lung allografts from acute cellular rejection. These results suggest that sirolimus may be indicated as an adjunct to current cyclosporine-based immunosuppressive regimens in clinical lung transplantation.     

Strategies for biological monitoring of exposure for contemporary-use pesticides

Pesticides are used on a massive scale in the United States. The widespread use of these pesticides has made it virtually impossible for the average person to avoid exposure at some level. Generally, it is believed that low-level exposure to these pesticides does not produce acute toxic effects; however, various cancers and other noncancer health endpoints have been associated with chronic exposure to several groups of pesticides. Therefore, it is imperative that well-designed studies investigate the potential relationship between contemporary pesticide exposure and health effects. For these studies to be accurate, reliable methods for determining individual exposure must be used. Biological monitoring is a useful tool for assessing exposure to some contemporary pesticides. As with any analytical method, biological monitoring entails many difficulties, but, in many instances, they can be overcome by the logical use of available information and information acquired in carefully designed studies. At the Centers for Disease Control and Prevention (CDC), we have acquired extensive experience in the development and application of specific techniques for biological monitoring of a variety of toxicants, including many of the contemporary-use pesticides. We have used these methods to measure the internal dose of pesticides received by people in acute and chronic incidents resulting from both environmental and industrial exposure. Additionally, we have established normative values, or reference ranges, of several pesticides based on measurements of their metabolites in the urine of randomly selected adults in the US population. These data have been successfully used to distinguish overt exposures from 'background' exposure. In this paper, we present several examples of the usefulness of biological monitoring in urine and blood and describe the difficulties involved with developing methods in these matrices. We also present a general strategy, considerations, and recommendations for developing biological monitoring techniques for measuring the internal dose of contemporary-use pesticides.     

Second-generation peptidomimetic inhibitors of protein farnesyltransferase demonstrating improved cellular potency and significant in vivo efficacy.

The synthesis and evaluation of analogues of previously reported farnesyltransferase inhibitors, pyridyl benzyl ether 3 and pyridylbenzylamine 4, are described. Substitution of 3 at the 5-position of the core aryl ring resulted in inhibitors of equal or less potency against the enzyme and decreased efficacy in a cellular assay against Ras processing by the enzyme. Substitution of 4 at the benzyl nitrogen yielded 26, which showed improved efficacy and potency and yet presented a poor pharmacokinetic profile. Further modification afforded 30, which demonstrated a dramatically improved pharmacokinetic profile. Compounds 26 and 29 demonstrated significant in vivo efficacy in nude mice inoculated with MiaPaCa-2, a human pancreatic tumor-derived cell line.     

Enhanced pulmonary epithelial replication and axial airway mucosubstance changes in F344 rats exposed short-term to mainstream cigarette smoke

Cigarette smoking is associated with respiratory diseases that may be caused by injury to specific pulmonary cells. The injury may manifest itself as site-specific enhanced cellular replication. In this study, rats were exposed either to mainstream cigarette smoke (CS; 250 mg total particulate matter/m(3)) or to filtered air (FA) for 6 h/day, 5 days/week, for 2 weeks. In one group, cells in S-phase were labeled over 7 days by bromodeoxyuridine (BrdU) released from implanted osmotic pumps (pump labeled), while another group received BrdU by injection 2 h prior to necropsy (pulse labeled). Morphometry showed that the type II epithelial BrdU labeling index (LI) was significantly elevated in the CS-exposed animals of both labeling groups. The axial airway and terminal bronchiolar LIs were enhanced by CS only in the pump-labeled group. In a third group (pulse labeled), 2 weeks of recovery following exposure to CS allowed a normalization in the type II LI. In the pump-labeled rats, the CS-induced elevation of the type II LI was greater than the LI elevation in conducting airways, suggesting that the parenchyma may have been injured more than the conducting airways. The terminal bronchiolar LI in the pump-labeled group, regardless of exposure, was significantly greater than the axial airway LI. Pump labeling, in contrast to pulse labeling, could therefore discern differences among replication rates of conducting airway epithelium in different regions of the lung. Mucosubstance (MS) within the axial airway epithelium was quantified by morphometry. The CS exposure did not increase the total number of MS-containing cells or the total number of axial airway epithelial cells, but there was a phenotype change in the MS cells. Neutral MS cells (periodic acid-Schiff-positive) were significantly decreased, while acid MS cells (alcian blue-positive) were slightly increased by CS exposure. Either cell replication and differentiation or differentiation alone may have changed the phenotype in the MS cell population.     

Cancer in the elderly

The objective of this study was to assess the patterns of cancer incidence of elderly populations on a geographic and ethnic basis. Internationally published incidence data was used to characterize the status of cancer in the elderly in selected world locations. Cancer sites reviewed are those common in the elderly. Incidence data was measured as published by the International Agency for Research Against Cancer and in appropriate statistical tests. The results indicate that the Western societies have a consistently higher proportion of cancer patients who are 65 and older, even when controlling for the age distribution factor. Also, the male/female ratio in the elderly is high due mainly to a relatively earlier occurrence of gynecological cancer. Three patterns characterizing a differentially retarding pattern of cancer incidence with age were found: i) a continuous increase, with some slowing pace of growth in the US and other Western countries. ii) a peak in the 75-79 age category followed by a decline. This is noted in less prosperous European populations, like the former Eastern Bloc countries. iii) a plateau, seen in developing countries like India or Gambia. Non-etiologic factors contributing to international cancer distribution variations among the elderly may include quality and frequency of diagnostic work-up. This is largely a reflection of a nation's healthcare system, as well as its social norms vis-a-vis the elderly. The positive global ageing trend promises increased cancer incidence and prevalence, and the need for greater resource allocation for the care of elderly cancer patients.     

Alteration of airflow and mucociliary transport in normal subjects

The effect that variation of nasal airflow has on the mucociliary clearance was studied in healthy volunteers. The nasal saccharin particle clearance time was found to have an inverse relationship with the nasal airflow.     

Marjolin's ulcer. The LSU experience

Skin cancers originating in areas of chronic injury (Marjolin's ulcers) are thought to behave in a more aggressive fashion than those due to other causes. The initial surgical treatment, especially the management of the regional lymph nodes, remains controversial. This review of 37 patients with Marjolin's ulcer evaluated the effectiveness of local surgical treatment at our center. Three of 18 patients treated with amputation developed recurrences and died of metastatic disease. Five of 16 patients treated by wide excision developed recurrences, two dying with metastatic disease, the remaining three apparently cured by additional surgery. Only six (17.6%) of the patients treated by "local" modalities, i.e., wide excision or amputation, developed subsequent regional node metastases. Recurrences following local excision tend to be local and can usually be managed by re-excision or amputation. It can be inferred from this study that prophylactic node dissections are not required in most patients with Marjolin's ulcers.