An objective way to predict remission and relapse in Cushing disease using Bayes' theorem of probability.

OBJECTIVE: In this study on patients with Cushing disease, post-transsphenoidal surgery (TSS), we attempt to predict the probability of remaining in remission, at least for a year and relapse after that, using Bayes' theorem and the equation of conditional probability. The number of parameters, as well as the weightage of each, is incorporated in this equation. DESIGN AND METHODS: The study design was a single-centre ambispective study. Ten clinical, biochemical, radiological and histopathological parameters capable of predicting Cushing disease remission were identified. The presence or absence of each parameter was entered as binary numbers. Bayes' theorem was applied, and each patient's probability of remission and relapse was calculated. RESULTS: A total of 145 patients were included in the study. ROC plot showed a cut-off value of the probability of 0.68, with a sensitivity of 82% (range 73-89%) and a specificity of 94% (range 83-99%) to predict the probability of remission. Eighty-one patients who were in remission at 1 year were followed up for relapse and 23 patients developed relapse of the disease. The Bayes' equation was able to predict relapse in only 3 out of 23 patients. CONCLUSIONS: Using various parameters, remission of Cushing disease can be predicted by applying Bayes' theorem of conditional probability with a sensitivity and a specificity of 82% and 94%, respectively. This study provided an objective way of predicting remission after TSS and relapse in patients with Cushing disease giving a weightage advantage to every parameter.

Detection of Pre-clinical Involvement of the Second Eye in Viral Acute Retinal Necrosis Using Optical Coherence Tomography.

PURPOSE: To report the detection of retinitis in the second eye of a patient with viral acute retinal necrosis (ARN), before the appearance of clinical change, using swept-source optical coherence tomography. RESULTS: A 63 year-old male developed right-sided varicella-zoster virus (VZV) ARN, confirmed with aqueous sampling. High-dose intravenous aciclovir caused renal impairment and was suspended for two-days. One day later, left eye macular SS-OCT revealed focal retinal thickening and disruption of retinal architecture without clinically detectable retinitis. The patient was asymptomatic. Aqueous sampling was VZV PCR positive. He received bilateral foscarnet injections and renal adjusted dose of aciclovir. The left OCT signs improved with full restoration of retinal layers. CONCLUSIONS: We report for the first time the use of OCT to detect pre-clinical second eye retinitis during ARN. Prompt diagnosis and combined systemic and intensive local antiviral therapy resulted in a favourable structural and functional outcome.

Footrot on a sheep breeding farm in the Himalayan state of Jammu and Kashmir.

In the present study ovine footrot was detected clinically on a sheep farm in the Himalayan state of Jammu and Kashmir. Dichelobacter nodosus was confirmed by culture and polymerase chain reaction (PCR) using species-specific 16S ribosomal RNA primers. When cultured, the organism appeared as flat colourless colonies having a fine granulated structure with irregular margins, and showing characteristic Gram-negative rods with swollen ends. Detection by PCR from cultured bacteria resulted in amplification of a 783 base pairs (bp) product. Serogrouping by multiplex PCR using group (A-I)-specific primers revealed the presence of serogroup B-specific bands of 283 bp.

Effectiveness of Interventional Strategies in Modulating Knowledge and Attitude of Health Care Professionals for Promoting Organ Donation: A Study in Tertiary Care Public Hospital of North India.

OBJECTIVE: To evaluate the impact of interventional "educational module" on knowledge and attitude regarding organ donation amongst resident doctors and nurses in the Institute of National Importance. STUDY DESIGN: Interventional and prospective. METHODS: We devised an interactive educational module covering various aspects of organ donation through a series of audiovisual lectures and information booklets. Resident doctors and nurses posted in those areas of the 1948-bedded Postgraduate Institute of Medical Education and Research (PGIMER), where head injury patients were treated and were subject to intervention using this module. The pre and postinterventional scores of their knowledge and attitude regarding organ donation were compared to find out impact of the intervention. RESULTS: A total of 242 nurses and 87 resident doctors participated in this research. Higher knowledge score was observed preintervention amongst doctors as compared to nurses. Significant improvement was seen in total knowledge scores of both groups postintervention. Doctors had better scores for the "concept of organ donation," while nurses were more familiar with "procedures and protocols." Both had low knowledge about "clinical criteria for brain death" and "legal issues" preintervention which improved significantly postintervention. The positive impact of intervention was also observed on attitude in both categories. A significant impact of intervention was observed on overall propensity of doctors and nurses to promote organ donation, for pledging their own organs and for counseling of the patient/attendants on this cause. CONCLUSION: Scientifically designed educational modules have a promising role in improving awareness and attitude of health care professionals regarding organ donation and their propensity to be prospective donors, effective counselors, and advocates of organ donation.

Carcinogenesis studies of cresols in rats and mice.

Cresols, monomethyl derivatives of phenol, are high production chemicals with potential for human exposure. The three isomeric forms of cresol are used individually or in mixtures as disinfectants, preservatives, and solvents or as intermediates in the production of antioxidants, fragrances, herbicides, insecticides, dyes, and explosives. Carcinogenesis studies were conducted in groups of 50 male F344/N rats and 50 female B6C3F1 mice exposed to a 60:40 mixture of m- and p-cresols (m-/p-cresol) in feed. Rats and mice were fed diets containing 0, 1500, 5000, or 15,000 ppm and 0, 1000, 3000, or 10,000 ppm, respectively. Survival of each exposed group was similar to that of their respective control group. Mean body weight gains were depressed in rats exposed to 15,000 ppm and in mice exposed to 3000 ppm and higher. A decrease of 25% over that of controls for the final mean body weight in mice exposed to 10,000 ppm appeared to be associated with lack of palatability of the feed. A marginally increased incidence of renal tubule adenoma was observed in the 15,000-ppm-exposed rats. The increased incidence was not statistically significant, but did exceed the range of historical controls. No increased incidence of hyperplasia of the renal tubules was observed; however, a significantly increased incidence of hyperplasia of the transitional epithelium associated with an increased incidence of nephropathy was observed at the high exposure concentration. The only significantly increased incidence of a neoplastic lesion related to cresol exposure observed in these studies was that of squamous cell papilloma in the forestomach of 10,000-ppm-exposed mice. A definitive association with irritation at the site-of-contact could not be made because of limited evidence of injury to the gastric mucosa at the time of necropsy. However, given the minimal chemical-related neoplastic response in these studies, it was concluded that there was no clear evidence of carcinogenicity in male rats or female mice exposed to the cresol mixture.

Emergencies in HIV medicine--part I.

Human immunodeficiency virus (HIV) infection is now a chronic manageable disease due to which is it imperative for reviewing various medical emergencies which an individual case may encounter. Emergencies may occur at any stage of the disease. HIV infection is associated with several opportunistic infections/malignancies that may be life threatening and need quick intervention by health care workers. These emergencies could be related to opportunistic infections that are seen at presentation or that occur as the immune system gets weaker, or may be HIV induced diseases like enteropathy and wasting, diarrhea leading to dehydration and its sequel, neurological complication like PML etc. and from complications resulting from use of anti-HIV medication like lactic acidosis, pancreatitis, bone marrow suppression and may include the immune reconstitution syndromes.

Emergencies in HIV--part 2.

In a short span of two and a half decades, HIV/AIDS has emerged as second largest killer disease that has affected mankind. The triple drug antiretroviral therapy (ART) has ensured a reasonably good quality of life to HIV infected individuals. Human immunodeficiency virus (HIV) infection is associated with several opportunistic infections/malignancies that may be life threatening and need quick intervention by health care workers. These emergencies could be related to opportunistic infections that are seen at presentation or that occur as the immune system gets weaker, or may bedue to HIV itself per se. The emergencies could also result from use of antiretroviral drugs like lactic acidosis, pancreatitis, bone marrow suppression and may include the immune reconstitution syndromes. The emergencies due to the opportunistic conditions and HIV per se had been dealt with in detail in the part 1, and this part describes various emergencies that could be encountered due to the administration of the anti retroviral treatment. Some patients may present due to emergencies as a result of co-administration of antiretroviral drugs with drugs used for treatment of some opportunistic infections like ATT etc.

Brainstem abscess: the nonsurgical management.

The brainstem is an unusual location for a pyogenic abscess. Stereotactic aspiration or microsurgical drainage may be required in antibiotic refractory cases. Prolonged antibiotic therapy, along with symptomatic treatment may provide successful outcome. We report a case of cerebellar and brainstem abscess, managed successfully with prolonged antibiotic administration.

Carcinogenesis studies of benzophenone in rats and mice.

Benzophenone, an aryl ketone, is used primarily as a photoinitiator and fragrance enhancer. Groups of 50 male and 50 female F344 rats and B6C3 F1 mice were fed diets containing 0, 312, 625, and 1250 ppm benzophenone for 105 weeks. Survival of males exposed to 1250 ppm benzophenone was significantly less than that of controls. There was a positive trend in the incidence of renal tubule adenoma in male rats; these neoplasms were accompanied by significantly increased incidences of renal tubule hyperplasia. Increased incidences of mononuclear cell leukemia were observed in male rats exposed to 312 or 625 ppm benzophenone and in female rats exposed to 625 ppm benzophenone. Liver lesions observed included significantly increased incidences of hepatocytic centrilobular hypertrophy in all exposed groups of rats. In mice, survival of all exposed groups was generally similar to that of the control groups. In male mice, there were significantly increased incidences of hepatocellular adenoma in the 625 and 1250 ppm groups. In female mice, the incidences of hepatocellular adenoma in the 625 and 1250 ppm groups were higher than expected after adjusting for the lower body weights in these groups. The incidences of kidney nephropathy in exposed groups of female mice, as well as the severity of nephropathy in exposed groups of males, were significantly increased. The incidences of metaplasia of the olfactory epithelium were significantly increased in 1250 ppm mice. Rare histiocytic sarcomas were observed in female rats and mice in the 625 and 1250 ppm groups. Under the conditions of these 2-year studies, there was some evidence of carcinogenic activity of benzophenone in male F344/N rats based on increased incidences of renal tubule adenoma. There was equivocal evidence of carcinogenic activity of benzophenone in female F344/N rats based on the marginal increased incidences of mononuclear cell leukemia and histiocytic sarcoma. There was some evidence of carcinogenic activity of benzophenone in male B6C3F(1) mice based on increased incidences of hepatocellular neoplasms, primarily adenoma. There was some evidence of carcinogenic activity of benzophenone in female B6C3F(1) mice based on increased incidences of histiocytic sarcoma; the incidences of hepatocellular adenoma in female B6C3F(1) mice may have been related to benzophenone exposure.

Sedimentation of a circular disk in power law fluids.

The continuity and momentum equations have been solved numerically for the two-dimensional steady flow of power law fluids over a thin circular disk oriented normal to the direction of flow. Extensive results on the individual and total drag coefficients are obtained as functions of the power law flow behavior index (0.4 < or = n < or = 1.0), Reynolds number (1 < or = Re < or = 100) and the blockage ratio, disk-to-cylinder diameter ratio (0.02 < or = e < or = 0.5), which can be used to estimate the settling velocity of a circular disk. The numerical predictions of drag are consistent with the scant experimental results available in the literature.

Ischemic Colitis Caused by Intra-Aortic Balloon Pump Counterpulsation.

Intra-aortic balloon pump counterpulsation (IABP) has been shown to prolong life in critically ill cardiac patients. However, complications including distal emboli, balloon rupture, bleeding, limb loss, and bowel ischemia continue to be associated with them. We present a case of a 56-year-old male who suffered bowel ischemia as a result of a malpositioned IABP. While the benefit of such devices in critically ill patients is not disputed, patients as well as clinicians should be aware of the potential side effects and patients undergoing IABP placement should be monitored for complications.

Assessment of Ethnicity in Indian Population using Tooth Crown Metric Dental Traits.

BACKGROUND: Tooth crown dimensions vary between different ethnic groups, providing insights into the factors controlling human dental development. This present study compares permanent mesiodistal (MD) and buccolingual crown dimensions between four ethnic groups, highlighting patterns of tooth size between these groups and considers the findings in relation to genetic and environmental influences. MATERIALS AND METHODS: MD and buccolingual tooth crown dimensions were recorded using digital vernier calipers on dental casts derived from four different human population: Iranians, Hindus, Muslims, and Christians. RESULTS: Obtained measurements were subjected to statistical analysis. The Christian sample was found to have the largest teeth overall, whereas the Iranian sample generally displayed the smallest MD and buccolingual crown dimensions (P < 0.001). Comparisons of coefficients of variation for teeth within each class showed that the later-forming teeth displayed greater variation in MD size than the earlier-forming teeth. CONCLUSION: The different patterns of tooth size observed between the study samples are thought to reflect differences in the relative contributions of genetic and environmental influences to dental development between the four population. Using a standardized methodology, significant differences in MD and buccolingual crown dimensions have been demonstrated between four human ethnic groups. There were also distinct differences in the patterns of crown size between the groups, with the later-forming teeth in each type generally showing greater size variation.

Comparison of maternal sera, cord blood, and neonatal sera for detecting presumptive congenital syphilis: relationship with maternal treatment.

The incidence of congenital syphilis has increased rapidly over the past few years. Most infected mothers and their newborns are asymptomatic at birth and diagnosis depends on serologic testing during pregnancy and at delivery. This study was initiated to compare maternal sera, cord blood, and neonatal sera for detecting presumptive congenital syphilis and to assess the role of maternal treatment (administration of penicillin to the mother at least 1 month before delivery) on the serologic results at the time of delivery. The serologic results from all live deliveries complicated by a positive maternal and/or neonatal test for syphilis during a 12-month period were compared using chi 2 analysis and multiple comparisons for proportions. Of 3306 livebirths, 73 (2.2%) were complicated by a positive maternal or neonatal serology. At delivery, the serologic test was positive in 68 (94%) of 72 maternal sera, 30 (50%) of 60 cord sera, and 43 (63%) of 68 neonatal sera. In the absence of maternal treatment, 95% of the maternal sera, 66% of the cord blood samples, and 86% of the neonatal sera were positive. If the mother had been treated, 94% of maternal sera, 36% of cord sera, and 39% of neonatal sera were positive. Cord blood and neonatal sera appear to be inferior to maternal sera for detecting prenatal exposure to syphilis. Cord serology is also inferior to neonatal serology at 2 to 3 days of age. The most effective way to identify newborns at risk for congenital syphilis is to obtain a maternal serologic diagnosis during pregnancy and to test maternal and neonatal sera at delivery.

Intestinal absorption and metabolism of xenobiotics.

There are five possible processes of intestinal absorption of xenobiotics. These are active transport, passive diffusions, pinocytosis, filtration through "pores," and lymphatic absorption. The passive diffusion is major process for transport of foreign chemicals across the intestine. Though the lymphatic absorption of drugs is not of any major therapeutic significance, the uptake of toxic chemicals such as 3-MC, benzpyrene, and DDT through lymphatics may enhance their toxicity, since they are distributed to other organ systems in the body without being metabolized by liver. A number of factors such as diet, motility of intestine, interference with gastrointestinal flora, changes in the rate of gastric emptying, age of the animal, and dissolution rate of xenobiotic can alter the rate of absorption of chemicals. Liver is the major site of metabolism of xenobiotics, but the contribution of intestinal metabolism of xenobiotic can influence the overall bioavailability of chemicals. The xenobiotic metabolizing enzymes located in endoplasmic reticulum of intestine possess biochemical characteristics similar to that of liver. In general, the rate of metabolism of xenobiotics by intestinal microsomal preparation is lower than that observed with similar hepatic microsomal preparations. The in vitro intestinal metabolism of xenobiotics is affected by several factors including age, sex, diurnal variations, species, and nutritional status of the animal. The intestinal xenobiotic metabolizing enzymes are stimulated by the pretreatment of animals with foreign chemicals, but this depends on the route of administration of chemicals, drug substrate and the animal species used. Rabbit intestinal drug metabolizing enzymes seem to be resistant to induction by foreign chemicals.

An overview of prechronic and chronic toxicity/carcinogenicity experimental study designs and criteria used by the National Toxicology Program.

Since the establishment of the National Toxicology Program (NTP), there have been gradual changes in strategies to evaluate the overall toxicity of chemicals as well as their carcinogenic potential. The spectrum of toxicologic information sought on selected chemicals has been broadened by the multidisciplinary approach to evaluating chemicals. This paper describes the scientific rationale and experimental processes used by NTP in designing studies. Also, an outline of current NTP protocols are given for prechronic and chronic toxicity/carcinogenicity studies.

Development and validation of a cellular transplant model for leukemia in Fischer rats: a short-term assay for potential anti-leukemic chemicals.

The efficacy of a leukemia cell transplant model to measure potential chemotherapeutic activity was tested with five different chemicals that had previously been evaluated in 2-year studies. Leukemic spleen cells from Fischer rats were injected subcutaneously into syngeneic recipients and the effects of chemical treatment on tumor progression were evaluated at 70 days post-transplant. The data from the short-term assay were in all cases correlated with the trends reported for mononuclear cell leukemia in 2-year studies, where two chemicals were reported to decrease the incidence and three chemicals were reported to increase the incidence of leukemia. Short-term treatment with the two chemicals which caused negative trends for leukemia (2-ethoxyethanol or ethylene glycol monoethyl ether; 4-hexylresorcinol) delayed and/or reduced tumor growth in the transplant model in a dose-related fashion, as exhibited by reduction or elimination of splenomegaly and leukoblastosis, and a reversal in the depression of red blood cell indices or platelet counts. By contrast, the rate of tumor progression was increased in the short-term assay of the three chemicals which previously caused increased trends for leukemia in 2-year studies (pyridine; 2,4,6-trichlorophenol, dichlorvos). The severity of the mononuclear cell leukemia in the transplant recipients, as measured by histopathological examination of spleen and liver, was correlated with the changes in tumor growth rates. The in vivo leukemia transplant model is a short-term assay that could be used to screen a variety of potential chemotherapeutic agents, or to study structure-activity relationships within one class of chemicals.

Comparative gavage subchronic toxicity studies of o-chloroaniline and m-chloroaniline in F344 rats and B6C3F1 mice.

ortho-Chloroaniline (o-CA) andmeta-chloroaniline (m-CA) are chemical intermediates for pigment production in the textile industry. Comparative subchronic gavage studies were conducted to determine the effect of structure on toxicity.o-CA orm-CA was administered to 10 animals/sex/species in deionized water at dosages of 0, 10, 20, 40, 80, and 160 mg/kg for 13 weeks. Blood samples for clinical pathology were collected after 3 and 23 days in rats and at study termination (Day 93) in rats and mice. No mortalities occurred that could be directly attributed to treatment. Transient clinical signs of toxicity observed after dosing included cyanosis in rats and ataxia and tremors in mice. Methemoglobin formation was directly related to dosage (rats and mice) and duration of treatment (rats). At study termination, Heinz body formation in erythrocytes in association with decreased hemoglobin, hematocrit, and red blood cell count was a prominent treatment-related effect. Enlarged spleens (gross necropsy observation) and increased spleen weight were treatment effects of each chemical in both species. Microscopic lesions typical of increased red blood cell production were found in hematopoietic tissues (bone marrow, spleen, and liver), while lesions due to increased red cell destruction were found in these tissues and also the kidneys (rats). Microscopic changes were more frequently seen and severe, and involved more body organs, in rats than mice, and in m-CA-treated animals thano-CA-treated animals. Sex differences in lesion incidence/severity were not evident.

Toxicology and carcinogenesis studies of p,p'-dichlorodiphenyl sulfone in rats and mice.

p,p'-Dichlorodiphenyl sulfone (DDS) is used as a starting material in the production of polysulfones and polyethersufones, a family of thermoplastics. DDS was studied because of its high production volume and use. In toxicology studies, 10 Fischer 344 rats and 10 B6C3F1 mice/sex/group were fed diets containing 0, 30, 100, 300, 1,000 or 3,000 ppm DDS for 14 weeks. All animals survived until the end of the studies. Mean body weights of groups exposed to 300 ppm or greater were significantly decreased. Liver and kidney in rats and liver in mice were the major target organs of DDS toxicity. Dose-related increases in liver weights and incidences of centrilobular hepatocyte hypertrophy were observed in DDS-exposed groups. Nephropathy was seen in male and female rats only at and above 300 ppm. Neurotoxicity evaluations were negative in DDS-treated animals. Clinical chemistry and hematology parameters were minimally affected. In the 2-year toxicity and carcinogenicity studies, 50 rats and 50 mice/sex/group were fed diets containing 0, 10 (male rats), 30, 100, or 300 ppm DDS for 104 to 105 weeks. Survival of exposed groups was not affected. There were no clinical signs of toxicity related to DDS exposure. Final mean body weights were 2-17% lower in DDS-treated groups. Liver was the only target organ of DDS-induced toxicity. The incidence of centrilobular hepatocyte hypertrophy in mice and rats, and the incidence of bile duct hyperplasia and centrilobular degeneration in female rats was significantly greater than in controls. A no-observed-adverse-effect level (NOAEL) of 30 ppm DDS in the diet (1.5 mg/kg body weight) was established for rats. DDS was not carcinogenic in these studies.

Hematological effects in F344 rats and B6C3F1 mice during the 13-week gavage toxicity study of methylene blue trihydrate.

Methylene blue trihydrate is used widely as a dye and therapeutic agent. Methylene blue was administered by gavage to 30 animals/sex/dose group in a 0.5% aqueous methylcellulose suspension at doses of 0, 25, 50, 100, and 200 mg/kg. Blood samples from 10 animals/sex/dose group were collected at the end of study weeks 1, 6, and 13. Methylene blue treatment resulted in methemoglobin formation and oxidative damage to red blood cells, leading to a regenerative anemia and a variety of tissue and biochemical changes secondary to erythrocyte injury. An early change was a dose-related increase in methemoglobin, where the response of rats and mice was similar in magnitude. Mice appeared to be more sensitive than rats to the formation of Heinz bodies and the development of anemia that was characterized by a decrease in hemoglobin, hematocrit, and erythrocyte count. Splenomegaly was apparent in all treated mice and in the 100 mg/kg (males only) and 200 mg/kg rats at necropsy. There was a dose-related increase in absolute and relative spleen weight for both species. Microscopic examination revealed increased splenic hematopoiesis in all mice treatment groups and in rats at the 50 mg/kg dose level and above. Splenic congestion and bone marrow hyperplasia were also observed in these rat-dose groups. Mice at the higher doses showed hematopoiesis in the liver and accumulation of hemosiderin in Kupffer cells. These gross and microscopic findings are consistent with the development of hemolytic anemia. A dose-related increase in the reticulocyte count during study weeks 6 and 13 suggested a compensatory response to anemia.