Quantification of Iodine Leakage on Dual-Energy CT as a Marker of Blood-Brain Barrier Permeability in Traumatic Hemorrhagic Contusions: Prediction of Surgical Intervention for Intracranial Pressure Management.

BACKGROUND AND PURPOSE: Hemorrhagic contusions are associated with iodine leakage. We aimed to identify quantitative iodine-based dual-energy CT variables that correlate with the type of intracranial pressure management. MATERIALS AND METHODS: Consecutive patients with contusions from May 2016 through January 2017 were retrospectively analyzed. Radiologists, blinded to the outcomes, evaluated CT variables from unenhanced admission and short-term follow-up head dual-energy CT scans obtained after contrast-enhanced whole-body CT. Treatment intensity of intracranial pressure was broadly divided into 2 groups: those managed medically and those managed surgically. Univariable analysis followed by logistic regression was used to develop a prediction model. RESULTS: The study included 65 patients (50 men; median age, 48 years; Q1 to Q3, 25-65.5 years). Twenty-one patients were managed surgically (14 by CSF drainage, 7 by craniectomy). Iodine-based variables that correlated with surgical management were higher iodine concentration, pseudohematoma volume, iodine quantity in pseudohematoma, and iodine quantity in contusions. The regression model developed after inclusion of clinical variables identified 3 predictor variables: postresuscitation Glasgow Coma Scale (adjusted OR = 0.55; 95% CI, 0.38-0.79; P = .001), age (adjusted OR = 0.9; 95% CI, 0.85-0.97; P = .003), and pseudohematoma volume (adjusted OR = 2.05; 95% CI, 1.1-3.77; P = .02), which yielded an area under the curve of 0.96 in predicting surgical intracranial pressure management. The 2 predictors for craniectomy were age (adjusted OR = 0.89; 95% CI, 0.81-0.99; P = .03) and pseudohematoma volume (adjusted OR = 1.23; 95% CI, 1.03-1.45; P = .02), which yielded an area under the curve of 0.89. CONCLUSIONS: Quantitative iodine-based parameters derived from follow-up dual-energy CT may predict the intensity of intracranial pressure management in patients with hemorrhagic contusions.

The analgesic efficacy of continuous transversus abdominis plane block in renal transplant recipients.

BACKGROUND AND AIMS: Transversus abdominis plane (TAP) block is suitable for operations where parietal pain is a major cause of pain. Renal transplant recipients are ideally suited to gain maximum benefit from TAP block as the incision classically involves the lower abdomen. This study was conducted to evaluate the analgesic efficacy of continuous TAP block in transplant recipients. MATERIAL AND METHODS: In a prospective double-blind study, 40 chronic renal failure patients undergoing open renal transplant were randomly divided into two groups. At the end of surgery during closure, a multiorifice epidural catheter was placed in TAP plane. Study group (Group S) received Inj bupivacaine bolus 1 mg/kg (0.25%) followed by infusion 0.25 mg/kg (0.125%) through the catheter, whereas control group (Group C) received normal saline through the catheter. Inj pentazocine (0.3 mg/kg) was given as rescue analgesic at visual analogue score (VAS) > 3 in any group at rest or on movement. The analgesic efficacy was judged by VAS, time of first rescue analgesic, and total analgesic consumption in 24 h. RESULTS: Patients in Group S had significant lower VAS scores, longer time to first rescue analgesic (270 ± 347.96 vs. 42.85 ± 32.27 min) and lower pentazocine consumption (9.75 ± 13.95 vs. 56.42 ± 12.46 mg) in 24 h. There was significant sedation in Group C. CONCLUSION: The TAP catheter technique for postoperative pain control after renal transplant has proved to be effective in relieving the postoperative pain after renal transplant with less pentazocine requirement and less sedation.

Anesthetic management in parturients with chronic kidney disease undergoing elective Caesarean delivery: Our experience of nine cases.

In this retrospective study, we describe the anesthetic management and its implications in parturients with chronic kidney disease (CKD; n = 9), who underwent elective caesarean delivery. Nine parturients with CKD of various etiologies, who underwent elective Caesarean delivery, were included in this study. Spinal anest-hesia was administered in all parturients with normal coagulation profile through a 25-gauze spinal needle (Quincke) with 0.5% (H) bupivacaine in L2-3 space and T6 level was achieved. Hemodynamics and side effects such as nausea, vomiting, headache, and backache were record. The mean age was 28.22 ± 4.43 years. The mean levels of serum creatinine and serum potassium were 2.78 ± 1.29 mg/dl and 4.11 ± 0.46 meq/l, respectively. Mean baseline values of systolic blood pressure, diastolic blood pressure, and pulse rate were higher which decreased after spinal anesthesia. However, the incidence of hypotension, which required mephentermine treatment, was 11.1%. One patient had symptoms of nausea and vomiting/dizziness at the time of hypotension, which disappeared after treatment with 5 mg of intravenous mephentermine. Baseline value of PR remained high throughout the operation. Parturients with CKD with normal coagulation profile remained hemodynamically stable under spinal anesthesia with minimal side effects. However, a large number of studies are required to determine the safety of spinal anesthesia in this setting.

Intercity deceased donor renal transplantation: a single-center experience from a developing country.

In a developing country such as India, deceased donor renal transplantation (DDRTx) accounts for only about 1% of all renal transplants (RTx). Our institute initiated an intercity DDRTx in the year 2006, which significantly increased the number of RTx. We retrieved 74 kidneys from 37 deceased donors from various cities of Gujarat from January 2006 to December 2009. We transplanted the allografts in 66 recipients and a retrospective analysis of the donor profile and management and recipient outcome was performed. The mean age of the donors was 43.3 ± 18.8 years. The causes of death included road traffic accident in 51.35% of the donors and cerebrovascular stroke in 48.65% of the donors; 83.78% of the donors required ionotropes for hemodynamic stability in addition to vigorous intravenous fluid replacement. The average urine output of the donors was 350 ± 150 mL. The organs were perfused and stored in HTK solution. The mean cold ischemia time (CIT) was 9.12 ± 5.25 h. The mean anastomosis time in the recipient was 30.8 ± 8.7 min. 57.6% of the recipients established urine output on the operating table and 42.4% developed delayed graft function. At the end of 1 month after transplantation, the mean serum creatinine was comparable to the Ahmadabad city DDRTx, although the CIT was significantly longer in the intercity patients. Intercity organ harvesting is a viable option to increase the donor pool. Distance may not be an impediment, and good recipient outcome is possible in spite of prolonged CIT in case of proper harvesting and preservation.

Differential roles of MAPK-Erk1/2 and MAPK-p38 in insulin or insulin-like growth factor-I (IGF-I) signaling pathways for progesterone production in human ovarian cells.

Insulin and insulin like-growth factor-I (IGF-I) participate in the regulation of ovarian steroidogenesis. In insulin resistant states ovaries remain sensitive to insulin because insulin can activate alternative signaling pathways, such as phosphatidylinositol-3-kinase (PI-3 kinase) and mitogen-activated protein-kinase (MAPK) pathways, as well as insulin receptors and type 1 IGF receptors. We investigated the roles of MAPK-Erk1/2 and MAPK-p38 in insulin and IGF-I signaling pathways for progesterone production in human ovarian cells. Human ovarian cells were cultured in tissue culture medium in the presence of varying concentrations of insulin or IGF-I, with or without PD98059, a specific MAPK-Erk1/2 inhibitor, with or without SB203580, a specific MAPK-p38 inhibitor or with or without a specific PI-3-kinase inhibitor LY294002. Progesterone concentrations were measured using radioimmunoassay. PD98059 alone stimulated progesterone production in a dose-dependent manner by up to 65% (p<0.001). Similarly, LY294002 alone stimulated progesterone production by 13-18% (p<0.005). However, when used together, PD98059 and LY294002 inhibited progesterone production by 17-20% (p<0.001). SB203580 alone inhibited progesterone production by 20-30% (p<0.001). Insulin or IGF-I alone stimulated progesterone production by 40-60% (p<0.001). In insulin studies, PD98059 had no significant effect on progesterone synthesis while SB203580 abolished insulin-induced progesterone production. Either PD98059 or SB203580 abolished IGF-I-induced progesterone production. Both MAPK-Erk1/2 and MAPK-p38 participate in IGF-I-induced signaling pathways for progesterone production, while insulin-induced progesterone production requires MAPK-p38, but not MAPK-Erk1/2. These studies provide further evidence for divergence of insulin and IGF-I signaling pathways for human ovarian cell steroidogenesis.

Rosiglitazone and pioglitazone inhibit estrogen synthesis in human granulosa cells by interfering with androgen binding to aromatase.

The effects of rosiglitazone or pioglitazone (thiazolidinediones, TZDs) on estrogen production and aromatase activity in human ovarian cells were examined. Human granulosa cells were incubated in the tissue culture medium supplemented with androstenedione or testosterone, with or without insulin, TZDs, or type 1 17ß-hydroxysteroid-dehydrogenase (17ß-HSD) inhibitor. Estrogen concentrations in the conditioned medium, aromatase mRNA and protein expression in the cells and androgen substrate binding to aromatase were measured. With androstenedione as substrate, rosiglitazone or pioglitazone inhibited estrone production by up to 22% (p<0.012) while type 1 17ß-HSD inhibitor enhanced this effect of rosiglitazone or pioglitazone by 37% (p<0.001) and by 67% (p<0.001), respectively. With testosterone as substrate, rosiglitazone or pioglitazone inhibited estradiol production by 32% (p<0.001). With (3)H-testosterone as substrate, rosiglitazone or pioglitazone inhibited the (3)H-tritiated water release by the cultured cells by 45% and 35%, respectively, thus directly demonstrating inhibition of aromatase. Rosiglitazone or pioglitazone, however, had no significant effect on aromatase mRNA or protein expression. Rosiglitazone or pioglitazone inhibited (125)I-androstenedione and (125)I-testosterone binding to aromatase by 38% (p<0.001). It was concluded that rosiglitazone or pioglitazone inhibit estrogen synthesis in human granulosa cells by interfering with androgen binding to aromatase.

Vitamin D regulates steroidogenesis and insulin-like growth factor binding protein-1 (IGFBP-1) production in human ovarian cells.

Vitamin D Receptor (VDR) is expressed in both animal and human ovarian tissue, however, the role of vitamin D in human ovarian steroidogenesis is unknown. Cultured human ovarian cells were incubated in tissue culture medium supplemented with appropriate substrates, with or without 50 pM-150 pM or 50 nM-150 nM of 1,25-(OH)2D3, and in the presence or absence of insulin. Progesterone, testosterone, estrone, estradiol, and IGFBP-1 concentrations in conditioned tissue culture medium were measured. Vitamin D receptor was present in human ovarian cells. 1,25-(OH)2D3 stimulated progesterone production by 13% (p<0.001), estradiol production by 9% (p<0.02), and estrone production by 21% (p<0.002). Insulin and 1,25-(OH)2D3 acted synergistically to increase estradiol production by 60% (p<0.005). 1,25-(OH)2D3 alone stimulated IGFBP-1 production by 24% (p<0.001), however, in the presence of insulin, 1,25-(OH)2D3 enhanced insulin-induced inhibition of IGFBP-1 production by 13% (p<0.009). Vitamin D stimulates ovarian steroidogenesis and IGFBP-1 production in human ovarian cells likely acting via vitamin D receptor. Insulin and vitamin D synergistically stimulate estradiol production. Vitamin D also enhances inhibitory effect of insulin on IGFBP-1 production.

Development and in vitro evaluation of floating rosiglitazone maleate microspheres.

BACKGROUND: Various approaches have been used to retain the dosage form in stomach as a way of increasing the gastric residence time, including floatation systems; high-density systems; mucoadhesive systems; magnetic systems; unfoldable, extensible, or swellable systems; and superporous hydrogel systems. AIM: The objective of this study was to prepare and evaluate floating microspheres of rosiglitazone maleate for the prolongation of gastric residence time. METHOD: The microspheres were prepared by solvent diffusion-evaporation method using ethyl cellulose and hydroxypropylmethylcellulose. A full factorial design was applied to optimize the formulation. RESULTS: Preliminary studies revealed that the polymer:drug ratio, concentration of polymer, and stirring speed significantly affected the characteristics of microspheres. The optimum batch exhibited a prolonged drug release, remained buoyant for >12 hours, high entrapment efficiency, and particle size in the order of 350 microm. CONCLUSION: The results of 32 full factorial design revealed that the concentration of ethylcellulose 7 cps (X(1)) and stirring speed (X(2)) significantly affected drug entrapment efficiency, percentage release after 8 h and particle size of microspheres.

Effect of processing and sintering on controlled release wax matrix tablets of ketorolac tromethamine.

The objective of present study was to evaluate the effect of processing methods and sintering condition on matrix formation and subsequent drug release from wax matrix tablets for controlled release. Ketorolac tromethamine and compritol were processed with appropriate diluent using either dry blending, spray drying, partial melt granulation or melt granulation.The tablets were then sintered at 80 degrees . The sintered tablets were characterized by their physical parameters and in vitro dissolution tests. The micro-morphology and wettability of the tablets was also investigated. It was evident that different processing methods for identical formulation significant impact the release profile of drug. Sintering further retarded drug release and its effect was related to the manufacturing processes. Scanning electron microscopy showed that heat treatment redistributed the wax and formed a film-like structure covering drug and excipient particle. The contact angle of tablets made by dry blending, spray drying and partial melt granulation methods increased after sintering, while that of tablets made by melt granulation remained constant. Drug release from the wax tablets with or without heat treatment was best described by the Higuchi equation. Different processing methods produced different matrix structures that resulted in different drug release rates. Sintering retarded drug release mainly by decreasing the porosity of the matrix. Contact angle measurement and SEM analysis indicated that heat treatment caused the wax to melt, redistribute, coat the drug and diluents and form a network structure. Differential scanning calorimetry studies ruled out the occurrence of solid solution of the drug during sintering condition.

Combined epidural and general anesthesia for paediatric renal transplantation-a single center experience.

BACKGROUND: Appropriate anesthesia for pediatric renal transplantation requires stable intraoperative hemodynamics, optimal perfusion of the newly transplanted kidney and good analgesia during recovery. The aim of this study was to assess the preliminary application, success and safety of combined epidural and general anesthesia in pediatric renal transplantation in a small cohort. METHODS: We retrospectively reviewed the anesthesia records of 46 consecutive pediatric patients who received renal transplantation under combined epidural and general anesthesia from January 2003-2007. RESULTS: The mean patient age and weight were 13.2 +/- 2.4 years and 25.7 +/- 5.46 kg, respectively. The infused crystalloids, 20% albumin and red blood cell concentrates were 120 +/- 2 mL/kg to achieve a CVP of 13 to 15 mm Hg. Brisk diuresis was observed in all patients. Epidural tramadol (2 mg/kg) provided good postoperative analgesia in 89% patients. 15% patients developed radiological evidence of pulmonary edema, only one required mechanical ventilation for hypoxemia. Minor adverse effects were nausea and vomiting (17.5%) and convulsions (8.5%). No perioperative mortality or major morbidity was recorded. CONCLUSION: Epidural anesthesia is a useful adjunct to general anesthesia due to stable intraoperative haemodynamics and good postoperative analgesia.

Central pontine myelinolysis: sequele of hyponatremia during transcervical resection of endometrium.

Transcervical resection of endometrium is an alternative to hysterectomy for women with menorrhagia. The procedure involves the use of cutting loop diathermy to resect the endometrium while the uterine cavity is irrigated with 1.5% glycine which can absorb consequent fluid and electrolyte shifts. Severe hyponatremia leading to central pontine myelinolysis is an extremely rare complication of this procedure. We report a case of a young female undergoing transcervical resection of endometrium for menorrhagia, who developed central pontine myelinolysis but made a complete recovery after three months.

Cocaine withdrawal symptoms and initial urine toxicology results predict treatment attrition in outpatient cocaine dependence treatment.

This study evaluated the ability of cocaine withdrawal symptoms, measured by the Cocaine Selective Severity Assessment (CSSA) and initial urine toxicology results, to predict treatment attrition among 128 cocaine dependent veterans participating in a 4-week day hospital treatment program. The CSSA was administered and a urine toxicology screen was obtained at intake and at the start of the day hospital (about 1 week later). The combination of a positive urine toxicology screen and a high CSSA score at intake predicted failure to complete treatment. Urine toxicology results at the start of the day hospital, but not at intake, predicted failure to complete treatment. Among participants without other psychiatric illness, high CSSA scores at intake predicted failure to complete treatment. The presence of cocaine withdrawal symptoms and a positive urine toxicology screen are clinically useful predictors of treatment attrition.

The use of case vignettes for Addiction Severity Index training.

In an attempt to enhance the reliability of Addiction Severity Index (ASI) interviewer severity ratings (ISRs), we developed a set of eight ASI vignettes, fictionalized narrative case summaries that reproduced the quantitative ASI information in case report format. Each vignette has an ISR answer key, a consensus ISR of two expert ASI trainers for each problem area. Additionally, for four of the vignettes the rationale for the correct ISRs was operationalized. This report is a description of the ASI vignette packet, its use as a supplement to standard ASI training and the results of a pilot study to gauge its effectiveness in improving criterion validity of ISRs. Five ASI videotapes were also developed for the purposes of this investigation. There was limited evidence in this preliminary investigation that the addition of the ASI vignette packet to standard ASI training increased agreement with expert consensus ISRs. The ASI vignettes, relative to videotaped or live observed interviews, do however provide a brief means of assessing the adequacy of ASI interviewer skills with regard to ISRs.

Amantadine may facilitate detoxification of cocaine addicts.

The effectiveness of amantadine hydrochloride was evaluated in a double-blind placebo controlled drug trial. The subjects were 42 cocaine dependent men enrolled in a day hospital program. Twenty-one patients were prescribed 100 mg/bid of amantadine to be taken over 10.5 days and 21 were prescribed an equivalent amount of placebo. The primary outcome measures were the Addiction Severity Index at 1 month after study entry and urines during the drug trial (end of weeks 1 and 2) and 1 month after study entry. Urines obtained at the end of the drug trial (2 weeks) indicated that the subjects receiving amantadine (93%) were more likely (P = 0.040) to be free of cocaine than the placebo (60%) subjects. Urine toxicology data at 1-month follow-up again indicated that more of the amantadine subjects (83%) were free of cocaine than the placebo (53%) subjects (p = 0.049); although no differences were found in self-reports of cocaine or other substance use in the past 30 days. The urine findings provided preliminary indication that amantadine may have some effectiveness in reducing cocaine use in cocaine dependent patients.

Depression in hypertensive subjects.

168 patients attending hypertension clinic were randomly selected for the study. They were thoroughly investigated using E.C.G., X-ray chest, Urine analysis, Blood sugar, Blood urea, Serum cholesterol, Serum K, Serum Na, Scrum creatinine and Uric acid level. Detailed psychiatric case history and mental examination was carried out. Beck Rating Scale was used to measure the depression. 25% of hypertensive subjects exhibited depressive features and their mean score in Beck Rating scale is 21.76. The mean score of non-depressives is 4.46. All patients were receiving methyl dopa.25 mg. twice or thrice daily with thiazide diuretic. No significant difference in the incidence of depression with the duration of medication was observed.The hypertension was classified into mild, moderate and severe depending on the diastolic pressure. Depression was more frequent in severe hypertensives but not to the statistically significant level.Further hypertensives were classified into:1. Hypertension without organ involvement2. Hypertension with LVH only3. Hypertension with additional organ involvement4. Malignant hypertensionDepression was significantly more frequent in hypertensives with complications and also hypertensives in whom the B.P. remained uncontrolled. As all the patients were on the same drug, the drug effect is common to all; hence, the higher incidence of depression in hypertensives with complications is due to the limitation and distress caused by the illness.