Review of kidney sections from a subchronic d-limonene oral dosing study conducted by the National Cancer Institute

d-Limonene administered by oral gavage at 150-2400 mg/kg/day in a subchronic (91-day) study conducted for the National Cancer Institute induced renal alterations in male rats at all dose levels, whereas kidneys of male mice, female rats and female mice were unaffected. The renal alterations were dose responsive, and were similar to changes observed as sequelae to oral or inhalation exposure to decalin, a model compound used in a volatile hydrocarbon toxicology programme. Decalin induces a nephrotoxic response unique to the male rat, but the primary response associated with decalin exposure--hyaline droplet formation within the cytoplasm of the epithelial cells of the proximal convoluted tubule--was not recognized in the kidneys of d-limonene-exposed male rats. A possible explanation for the absence of this primary response from kidneys of the d-limonene-treated male rats could be the 4-5-day interval between administration of the final dose and the killing of the animals.     

Informed consent policies governing medical students' interactions with patients

When medical students become involved in patient care, concerns are raised that have ethical and possibly legal implications. In order to determine compliance with the guidelines of the U.S. government and the Joint Committee on Accreditation of Hospitals pertaining to informed consent, the authors conducted a study of hospital administrators, medical school department chairpersons, and medical school deans (with response rates ranging from 82.3 to 95.1 percent) concerning policies on student involvement in patient care. The results show that only 37.5 percent of all responding teaching hospitals specifically informed patients that students would be involved in care. Only 51 percent of the responding medical schools that specifically gave their students instruction or guidance on initial patient interaction as a matter of policy insisted that their students introduce themselves as students and clarify their role in patient care. The authors conclude that medical educators' compliance with the ethical requirements of informed consent is incomplete.     

Renal and vestibular toxicity due to inhaled tobramycin in a lung transplant recipient.

Chronic rejection is the major hurdle to long-term survival after lung transplantation. Endobronchial infection with Pseudomonas aeruginosa is common in patients with chronic rejection and this may further contribute to deterioration of the allograft. Inhaled tobramycin is commonly used to treat P aeruginosa airways infection in patients with cystic fibrosis. The safety of inhaled tobramycin in transplant recipients, however, has not been established. We describe the first report of a lung transplant recipient who developed renal failure and vestibular injury after receiving inhaled tobramycin. We review the literature regarding the safety of inhaled tobramycin and discuss potential mechanisms that may promote systemic toxicity in transplant recipients.     

Complications Related to Dapsone Use for Pneumocystis Jirovecii Pneumonia Prophylaxis in Solid Organ Transplant Recipients

Dapsone, used for prevention of Pneumocystis jirovecii infections, has been reported to cause hemolytic anemia and methemoglobinemia; its tolerability in solid organ transplant recipients is not well described. We investigated dapsone-related adverse events in patients undergoing solid organ transplantation from 1999 to 2004. Transplant providers identified patients for the investigators who then reviewed the patients' hospital and outpatient records. Sixteen solid organ transplant recipients fit case definitions for dapsone-related hemolytic anemia (n = 11) or methemoglobinemia (n = 5). Median time from event to dapsone discontinuation was 15 days; all patients improved after drug discontinuation. G6PD enzyme activity was normal in all patients whose test results were available. Dapsone may be associated with hemolytic anemia or methemoglobinemia, even with normal G6PD levels. These events are often not promptly recognized, and drug discontinuation is delayed. Dapsone-related hemolytic anemia or methemoglobinemia should be considered in solid organ transplant recipients with unexplained anemia or hypoxia.     

Cardiac beta-adrenergic responsiveness is well preserved in moderate protein calorie malnutrition from semistarvation

Twenty-one dogs underwent instrumentation of the left ventricle with ultrasonic dimension to study the effects of acute protein-calorie malnutrition on the adrenergic responsiveness of the heart. This study allowed a chronic and dynamic measurement of the major cardiac axes and the ventricular wall thickness, which in turn can be used to derive sophisticated measurements of global and intrinsic left ventricular function. Of the 21 dogs, 11 received a protein- and calorie-deficient diet designed to achieve a mean weight loss from a baseline of 20-25% over a 4-week period. The other 10 dogs received a normal diet. Dogs were also randomized to receive either acute propranolol beta-receptor blockade (n = 9) or acute isoproterenol beta-receptor stimulation (n = 12) during their baseline studies. Of the nine dogs given propranolol, five were subsequently malnourished and four served as controls. Of the 12 given isoproterenol, six were rendered malnourished and six were controls. All dogs were studied at both baseline and 4 weeks and received drugs in an identical fashion during both studies. The significant changes with malnutrition consisted of decreases in heart rate, cardiac mass, and left ventricular wall thickness. The degree of change in stroke volume, ejection fraction, cardiac output, dp/dt, and Emax (index of left ventricular contractility), with the administration of propranolol or isoproterenol was unaltered by malnutrition. These data support the contention that moderate protein-calorie malnutrition is well tolerated in instrumented, unstessed dogs and that the left ventricle's capacity to respond to beta-stimulation and to tolerate beta-blockade is largely unimpaired.     

The burden of cutaneous disease in solid organ transplant recipients of color

Organ transplant recipients (OTRs) are at increased risk of cutaneous malignancy. Skin disorders in OTRs of color (OTRoC) have rarely been systematically assessed. We aimed to ascertain the burden of skin disease encountered in OTRoC by prospectively collecting data from OTRs attending 2 posttransplant skin surveillance clinics: 1 in London, UK and 1 in Philadelphia, USA. Retrospective review of all dermatological diagnoses was performed. Data from 1766 OTRs were analyzed: 1024 (58%) white, 376 (21%) black, 261 (15%) Asian, 57 (3%) Middle Eastern/Mediterranean (ME/M), and 48 (2.7%) Hispanic; and 1128 (64%) male. Viral infections affected 45.1% of OTRs, and were more common in white and ME/M patients (P < .001). Fungal infections affected 28.1% and were more common in ME/M patients (P < .001). Inflammatory skin disease affected 24.5%, and was most common in black patients (P < .001). In addition, 26.4% of patients developed skin cancer. There was an increased risk of skin cancer in white vs nonwhite OTRs (HR 4.4, 95% CI 3.5-5.7, P < .001): keratinocyte cancers were more common in white OTRs (P < .001) and Kaposi sarcoma was more common in black OTRs (P < .001). These data support the need for programs that promote targeted dermatology surveillance for all OTRs, regardless of race/ethnicity or country of origin.     

Release rates of polynuclear aromatic hydrocarbons from natural sediments and their relationship to solubility and octanol-water partitioning

Sediment efflux rates of six polynuclear aromatic hydrocarbons (PAHs) were determined employing a novel boundary-layer flux chamber which concentrates trace organics using solid phase extraction techniques. Sediment cores were collected from the Elizabeth River, Virginia and were monitored over a 48 h period for PAH fluxes into uncontaminated seawater. The observed flux rates were related to solubility and octanol-water partition coefficients (K_OW) of the PAHs. Flux rates for the six PAHs varied from 0.028 to 0.646 g/L/d on a concentration basis and 43.0 to 1,000 g/m²/d on an areal basis. The resulting flux rate coefficients (k₂) were determined to be well correlated to solubility (R²=0.82) and inversely related to K_OW (R²=0.75). The empirically determined sediment flux dynamics fit well with theoretical relationships that have been previously established for bioconcentration kinetics and octanol/water partitioning systems. Thus, it appears possible to predict flux rates of other hydrophobic organic chemicals from ambient sediment and water concentrations, K_OW information, and the proposed empirical models.