Immunotoxicity of aflatoxin B1 in rats: effects on lymphocytes and the inflammatory response in a chronic intermittent dosing study.

We investigated the effects of aflatoxin B1 (AFB1) on isolated splenic lymphocytes and the histo-morphologic changes in the spleens and liver of Fisher-344 male rats. Weaned animals were fed chow diets that contained 0, 0.01, 0.04, 0.4, or 1.6 ppm AFB1, using an intermittent dosing regimen (4 weeks on and 4 weeks off AFB1), for 40 weeks. An additional group of animals was fed the 1.6 ppm AFB1 diet continuously. The intermittent dosing regimen was designed to evaluate effects of cumulative dose and exposure for risk assessment comparisons. The percentages of T and B cells were affected as shown by flow cytometric analysis after the dosing cycles. The observed changes appeared to reverse or compensate to some extent after the off cycles. Lymphocytes were stimulated in culture for analysis of the production of IL-2, IL-1, and IL-6. Significantly increased production of IL-1 and IL-6 was seen in the second dosing cycle (12 weeks) and the second "off" cycle (16 weeks) at the higher doses. Inflammatory infiltrates were seen in the liver after eight weeks of continuous and intermittent dosing and were increased in size and number at 12 weeks in both 1.6 ppm dose groups correlating with the peak production of Il-1 and IL-6. We concluded that AFB1 effects on the immune system can be either stimulatory or suppressive dependent on a critical exposure window of dose and time. Immune cells in spleen such as T-lymphocytes and macrophages, both important mediators of inflammatory responses to tissue damage, were affected differently in the continuous and intermittent exposures to AFB1.     

Involvement of mitochondria in acetaminophen-induced apoptosis and hepatic injury: roles of cytochrome c,Bax, Bid,and caspases

The role of apoptosis in acetaminophen (AAP)-induced hepatic injury was investigated. Six hours after AAP administration to BALB/c mice, a significant loss of hepatic mitochondrial cytochrome c was observed that was similar in extent to the loss observed after in vivo activation of CD95 by antibody treatment. AAP-induced loss of mitochondrial cytochrome c coincided with the appearance in the cytosol of a fragment corresponding to truncated Bid (tBid). At the same time, tBid became detectable in the mitochondrial fraction, and concomitantly, Bax was found translocated to mitochondria. However, AAP failed to activate the execution caspases 3 and 7 as evidenced by a lack of procaspase processing and the absence of an increase in caspase-3-like activity. In contrast, the administration of the pan-inhibitor of caspases, benzyloxycarbonyl-Val-Ala-DL-Asp-fluoromethylketone (but not its analogue benzyloxycarbonyl-Phe-Ala-fluoromethylketone) prevented the development of liver injury by AAP and the appearance of apoptotic parenchymal cells. This correlated with the inhibition of the processing of Bid to tBid. The caspase inhibitor failed to prevent both the redistribution of Bax to the mitochondria and the loss of cytochrome c. In conclusion, apoptosis is an important causal event in the initiation of the hepatic injury inflicted by AAP. However, as suggested by the lack of activation of the main execution caspases, apoptosis is not properly executed and degenerates into necrosis.     

Posttraumatic concerns: a patient-centered approach to outcome assessment after traumatic physical injury

BACKGROUND: Approximately 2.5 million Americans are admitted to the hospital after traumatic physical injury each year. Few investigations have elicited patients' perspectives regarding posttraumatic outcomes. OBJECTIVE: To identify and categorize physically injured trauma survivors' posttraumatic concerns. RESEARCH DESIGN: Prospective longitudinal investigation; trauma survivors were interviewed during the post-injury hospitalization and again 1, 4, and 12 months after the trauma. SUBJECTS: Ninety-seven, randomly selected, English speaking, hospitalized survivors of motor vehicle-crashes or assaults. MEASURES: At the end of each interview patients were asked, "Of all the things that have happened to you since you were injured, what concerns you the most?" Using an iterative process and working by consensus, investigators categorized patient concerns in content domains. Concern domains were then compared with established measures of posttraumatic stress disorder (PTSD) symptoms and limitations in physical functioning. RESULTS: Seven categories of posttraumatic concerns were identified. During the course of the year, 73% of patients expressed physical health concerns, 58% psychological concerns, 53% work and finance concerns, 40% social concerns, 10% legal concerns, 10% medical concerns, and 20% uncodable concerns. Rater agreement on concern categorization was substantial (kappa = 0.72). The mean number of concerns expressed per patient gradually decreased over time (1 month mean = 1.51; 12 month mean = 1.26) and resembled the trajectories of PTSD symptoms and functional limitations. CONCLUSIONS: The concerns of physically injured trauma survivors are readily elicited and followed up during the course of the year after injury. Open-ended inquiry regarding posttraumatic concerns may complement standardized outcome assessments by identifying and contextualizing the outcomes of greatest importance to patients.     

'Hit by the wind' and temperature-shift panic among Vietnamese refugees

Surveying 60 Vietnamese patients with either current or past post-traumatic stress disorder, this article aims to phenomenologically characterize the syndrome of 'hit by the wind' in a multidimensional manner. This includes determining the patient conceptualization of the disorder, profiling 'hit by the wind' episodes suffered by patients in the previous month, and presenting case vignettes. Eighteen of the 60 patients (30%) suffered at least one episode of 'hit by the wind' in the last month; all 18 patients had at least one episode of 'hit by the wind' in the last month that met panic attack criteria. For the 18 patients, 33 episodes of'hit by the wind' that met panic attack criteria were experienced in the previous month. For these 33 episodes, the most frequently reported DSM-IV panic attack symptoms were chills (100%; 33/33) and dizziness (88%; 29/33). Flashbacks played a role in the 'hit by the wind' episodes for 5 of the 18 patients (28%). In the discussion, a model of how the syndrome of 'hit by the wind' generates panic is adduced; also, possible Chinese origins of the disorder are discussed.     

Patient benefit from functional and cosmetic rhinoplasty

The Glasgow Benefit Inventory, a validated post-interventional questionnaire, was used to determine patient benefit from septorhinoplasty according to indication (function, cosmesis or a combination) in 87 patients. We showed a very significant patient benefit from this procedure and have demonstrated that the benefit is greatest when cosmesis is an indication (P = 0.05).     

The effect of vomitoxin (Deoxnivalenol) on testicular morphology, testicular spermatid counts and epididymal sperm counts in IL-6KO [B6129-IL6 [TmlKopf] (IL-6 gene deficient)] and WT [B6129F2 (wild type to B6129-IL6 with an intact IL-6 gene)] mice.

The potential of vomitoxin (VT) to affect testicular morphology and testicular and epididymal sperm counts was assessed in three strains of mice: IL-6KO [B6129-IL6 (tmlKopf) (IL-6 gene deficient)], WT [B6129F2 (wild type to B6129-IL6 with an intact IL-6 gene)] and B6C3F1 mice in a 90-day feeding study. The treated mice received VT at a concentration of 10 ppm in their diet. The body weight of VT-treated animals was significantly reduced compared with control animals. Slight changes, not statistically significant, were observed in relative testis weight and testicular spermatid counts. Histological changes were not apparent in the testes of VT-treated animals. The diameter of the seminiferous tubules, the height of the seminiferous epithelium and the number of Sertoli cell nucleoli per cross-sectioned seminiferous tubule in the VT-treated groups were not significantly different from their respective untreated controls. The IL-6KO and B6C3F1 VT-treated mice had significantly reduced cauda epididymal weights compared with their respective controls. These changes were not attributed to decreased sperm counts and this finding suggests that VT may exert an adverse affect on the epididymis.     

Progression of hepatic neoplasia in medaka (Oryzias latipes) exposed to diethylnitrosamine.

Progression of hepatic neoplasia was assessed in medaka (Oryzias latipes) following aqueous exposure to diethylnitrosamine (DEN). Larvae (2 weeks old) were exposed to 350 or 500 p.p.m. DEN for 48 h, while adults (3-6 months old) were exposed to 50 p.p.m. DEN for 5 weeks. Fish were maintained as long as possible to determine malignant potential of resultant neoplasms. A total of 423 medaka with 106 hepatic neoplasms were examined. There were marked differences in tumor prevalence between exposure groups including: (i) higher prevalence of hepatocellular carcinomas in medaka exposed as adults (100% of hepatocellular tumors in adult-exposed medaka were malignant, while only 51.5% of larval hepatocellular tumors were malignant); (ii) higher prevalence of biliary tumors in medaka exposed as larvae (46.4% of all tumors in larval-exposed medaka were biliary versus 8.1% in adult-exposed fish); (iii) higher prevalence of mixed hepato-biliary carcinomas in adult-exposed medaka (24.3%) compared with those exposed as larvae (3%). In addition, a unique hepatocellular lesion termed 'nodular proliferation' was only observed in adult-exposed medaka. The lesion was characterized by small size (50-300 microm), complete loss of normal tubular architecture and variable megalocytosis. Nodular proliferation was distinct from preneoplastic foci of cellular alteration and may represent microcarcinomas. There was a step-wise increase in mean diameter with age (days post-exposure) from nodular proliferation (174 microm, 17 days) to hepatocellular carcinoma (1856 microm, 62 days) and mixed carcinomas (3209 microm, 93 days) in adult-exposed medaka. Metastasis was observed with 19 neoplasms and tumors with the highest metastatic potential were hepatocellular and mixed carcinomas. The most common form of metastasis was trans-coelomic, followed by direct invasion and distant metastasis, presumably via the vascular route. Differences in tumor prevalence between exposure groups were believed to be the result of length of DEN exposure rather than age of fish at the time of exposure. In larval medaka with brief (48 h) DEN exposure, neoplasms are thought to be the result of dedifferentiation of hepatic cells, with slow progression of foci of cellular alteration to benign and then malignant tumors. In contrast, with adult medaka and prolonged (5 week) DEN exposure, neoplasms are believed to result from initiation of committed stem cells and formation of microcarcinomas ('nodular proliferation'), before progressing to larger hepatocellular and then mixed carcinomas.     

The progress of awareness and acceptance of dying assessed in cancer patients and their caring relatives.

Awareness and acceptance of dying were assessed weekly by semistructured interviews in a randomized sample of 76 hospice cancer patients and caring relatives. During the final eight weeks of the study, patients' awareness showed only slight increase (about 42% fully certain) while relatives' certainty clearly progressed (from 53% to 81% certain). Depression was linked with greater awareness in relatives but not patients. Patients were more anxious if death seemed probable rather than certain or no more than possible. Acceptance usually increased, with 51% of patients and 69% of relatives becoming nearly/fully accepting. Many individuals diverged from the average progress of awareness and acceptance; 18% of patients and 24% of relatives showed fluctuating or falling acceptance. Patients' and relatives' levels of awareness were positively correlated (r = 0.46), as was acceptance (r = 0.47). Relatives accepted more if patients were over 70 years, weak, unable to concentrate or had a quality of life index (QLI) below five, but patients were more accepting if female and if the QLI was above five. Pain did not increase acceptance. Acceptance was described in terms of death's inevitability, faith and spiritual values, life's diminishing rewards, completing life, final benefits, humour, sharing, etc. Individuals often used more than one concept. Generalizing exact figures from this sample needs caution, but some patterns of progress, possible influential factors and ways of acceptance may apply widely.     

Anterior shoulder dislocation as a complication of surgery for burns

An example of anterior dislocation of the shoulder resulting from the positioning of a patient for skin grafting of burns is presented. Complications of positioning patients prone and with their arms abducted and practical measures for their avoidance are discussed.     

Combined effects of the mycotoxins aflatoxin B1 and cyclopiazonic acid on Sprague-Dawley rats

This study was conducted to determine whether exposure to cyclopiazonic acid (CPA) and aflatoxin B1 (AFB1) would alter the toxicity associated with exposure to either toxin individually. Groups of male rats were administered 0, 0.1 or 4.0 mg CPA/kg body weight/day intragastrically (three groups per dose level) for three consecutive days and 30 min after each of these CPA doses the rats were dosed by gavage with 0, 0.1 or 2.0 mg AFB1/kg body weight/day. Six of the 12 rats given each of these nine treatments were killed on day 4 after the initial dosing, and the rest were allowed a recovery period of 4 days prior to being killed. Weight loss in the three groups receiving 2.0 mg AFB1/kg/day occurred within 24 hr of the first doses. Feed consumption by these rats was about 60% of that in the other groups. By the end of the recovery period, rats in these three groups had lost an average of 31-38 g. Feed consumption throughout the recovery period by rats in the 2.0-mg AFB1 groups was about 50% of the control value, except in the group that also received the high dose of CPA, in which it was 75%. Gross pathological findings were primarily limited to rats in the high AFB1 group, and included icterus, shrunken liver and lesions in the kidney at the cortico-medullary junction. Microscopic changes were characteristic of aflatoxicosis in rats. Glycocholic acid assays indicated liver damage only in those groups that received the high AFB1 dose. We conclude that neither toxin potentiates the action of the other at the dose levels used in this study.