Thiophene and benzodioxole appended thiazolyl-pyrazoline compounds: Microwave assisted synthesis, antimicrobial and molecular docking studies.

A novel series of thiophene and benzodioxole appended thiazolyl-pyrazoline derivatives have been designed, synthesized and evaluated against different bacteria and fungi. The antimicrobial activity of the synthesized compounds were screened using MIC method and were proved synthesized compounds 7o, 7r and 7t to show good antimicrobial activity against bacteria and fungi. In silico molecular docking studies revealed that all the synthesized molecules showed good binding energy toward the target receptor DNA topoisomerase IV, ranging from -10.42 to -11.66 kcal/mol.

Synthesis of new series of quinoline derivatives with insecticidal effects on larval vectors of malaria and dengue diseases.

Mosquito borne diseases are on the rise because of their fast spread worldwide and the lack of effective treatments. Here we are focusing on the development of a novel anti-malarial and virucidal agent with biocidal effects also on its vectors. We have synthesized a new quinoline (4,7-dichloroquinoline) derivative which showed significant larvicidal and pupicidal properties against a malarial and a dengue vector and a lethal toxicity ranging from 4.408 µM/mL (first instar larvae) to 7.958 µM/mL (pupal populations) for Anopheles stephensi and 5.016 µM/mL (larva 1) to 10.669 µM/mL (pupae) for Aedes aegypti. In-vitro antiplasmodial efficacy of 4,7-dichloroquinoline revealed a significant growth inhibition of both sensitive strains of Plasmodium falciparum with IC50 values of 6.7 nM (CQ-s) and 8.5 nM (CQ-r). Chloroquine IC50 values, as control, were 23 nM (CQ-s), and 27.5 nM (CQ-r). In vivo antiplasmodial studies with P. falciparum infected mice showed an effect of 4,7-dichloroquinoline compared to chloroquine. The quinoline compound showed significant activity against the viral pathogen serotype 2 (DENV-2). In vitro conditions and the purified quinoline exhibited insignificant toxicity on the host system up to 100 µM/mL. Overall, 4,7-dichloroquinoline could provide a good anti-vectorial and anti-malarial agent.

Risk of vascular access thrombosis in patients with systemic lupus erythematosus on hemodialysis.

INTRODUCTION: Anticardiolipin antibody is associated with increased risk of vascular access thrombosis (VAT) in hemodialysis (HD) patients. Systemic lupus erythematous (SLE) patients have a high prevalence of anticardiolipin antibodies, but it is not clear whether these patients are at high risk of developing vascular access thrombosis. METHODS: Thirty six SLE patients on HD, who had either an arterio-venous (AV) graft or AV fistula as vascular access, and were not on anticoagulation treatment, were retrospectively identified at Henry Ford Hospital. A similar number of patients without SLE, matched for age, sex, race and type of vascular access were selected as a control population. Vascular access thrombosis rate at one year was compared between two groups. RESULTS: Mean age at dialysis was 36+/-10 years in 36 SLE patients (28 females, 8 males) and was 38+/-6.4 years in 36 non-SLE patients (29 females, 7 males). Of all patients, 29/36 (80.5%) SLE and 27/36 (75%) non-SLE patients had AV grafts, whereas the rest had AV fistulas as vascular access (19.5% SLE and 25% non-SLE patients). Out of 36 SLE patients, 24 (66.6%) patients developed VAT at one year as compared to 14 (38.9%) patients in non-SLE group (p<0.05). The odds ratio of VAT in SLE patients was 3.1 (95% CI 1.2-8.2). CONCLUSION: SLE patients on hemodialysis are more likely to develop vascular access thrombosis as compared to non-SLE patients.

Clinicopathological Spectrum Of Gall Bladder Cancer In Kashmir - An Institutional Study.

Gallbladder cancer is a highly aggressive malignancy that usually presents at an advanced incurable stage. It is the fifth most common gastro-intestinal tumor and leads to approximately 2800 deaths in United States annually. This was a retrospective study carried out in the Department of Pathology, Sher-i-Kashmir Institute of Medical Sciences, a 650-bed super speciality hospital in Kashmir valley. We reviewed the histopathological records of all the patients who were diagnosed as carcinoma gallbladder from Dec 2009-Dec 2013. Gross findings and histopathological findings were noted from the departmental archival material and clinical records of the patients including the clinical presentation, laboratory investigations, radiological investigations, pre-operative diagnosis and intra-operative findings, were retrieved from the hospital records. We analyzed 57 cases of carcinoma gallbladder for their clinicopathological features It included 19 males and 37 females. In our study, adenocarcinomas accounted for 87.5% of total carcinomas. Incidentally, all but one patient where gall stones were found, adenocarcinomas were seen. We have 4 patients of squamous cell carcinoma. In our series we have a single case of small cell carcinoma which was positive for neuroendocrine markers. In our study, gall stones were seen only in 8 cases (14%) of the total cases.

Increased accumulation of lipoprotein and cholesterol in re-endothelialized rat carotid artery after laser damage.

The permeability characteristics of acute endothelial lesions and completely regenerated endothelium were investigated. The endothelium of rat carotid arteries was selectively damaged by laser irradiation. When [125I]LDL was injected 24 h later, the average [125I]LDL uptake in the damaged arteries was about 13 times the uptake by the non-irradiated, contralateral control arteries. Fourteen weeks after the irradiation, the vessel walls with regenerated endothelium had taken up twice as much [125I]LDL as the controls. Sixteen weeks after the irradiation, orally administered [3H]cholesterol was accumulated 5 times more by the irradiated than by the control vessel wall. These findings show that the adherent platelets contribute importantly to the LDL cholesterol accumulation by the vessel wall with acute endothelial lesion and that the regenerated endothelium promotes the accumulation of LDL cholesterol.

Comparison of uptake and degradation of low density lipoproteins by arteries and veins of rabbits.

The uptake and degradation of low density lipoproteins were compared in arteries and veins of rabbits in vivo. Rabbits were injected with low density lipoproteins labelled singly with 125I (125I-LDL) or doubly with 131I and with [125I]tyramine cellobiose (TC-LDL) which remains trapped intracellularly. After increasing times up to 24 h the largest vessels were perfused to remove blood, fixed in situ and excised. When the uptake of 125I-LDL by arteries and veins was compared on the basis of luminal surface area, there were no significant differences up to 3.5 h. When degradation rates of double labelled LDL were compared after 24 h on the same basis, the arteries contained significantly more TC label than the veins, but when the comparison was based on dry weights there were no significant differences. These results show that veins, like arteries, take up LDL from the circulating blood; and they suggest that the preferential accumulation of LDL in arteries susceptible to atherosclerosis may be accounted for, at least in part, by more degradation of LDL in arteries than in veins.

Effects of reserpine on expression of the LDL receptor in liver and on plasma and tissue lipids, low density lipoprotein and fibrinogen in rabbits in vivo.

The effects of administering reserpine (0.1 mg/kg) or 17alpha-ethinyloestradiol (2.5 mg/kg) to New Zealand White rabbits on low density lipoprotein receptors in liver, on plasma low density lipoprotein and fibrinogen and on plasma and tissue lipids were determined. Blood pressure and heart rate were also followed. The drugs were injected subcutaneously into conscious unrestrained rabbits for 5 days. On the 6th day homologous 125I-tyramine cellobiose labelled low density lipoprotein (125I-TC-LDL) was injected intravenously and 24 h later the animals were killed. Compared to controls, reserpine significantly increased LDL receptor expression in the liver by about threefold, and reduced total cholesterol in plasma, aorta and heart, without affecting plasma triglycerides. The reductions in plasma cholesterol and heart were due to decreases in both unesterified and esterified cholesterol. Similar effects were observed with oestrogen, except that there was no change in esterified cholesterol in aorta. In liver, a decrease of 24% in total cholesterol was due mainly to decreased esterified cholesterol. In adrenal glands total cholesterol increased by 25%. Reserpine significantly accelerated the plasma clearance of intravenously injected homologous 125I-TC-LDL and reduced its accumulation in aortic wall. Neither reserpine nor oestradiol affected blood pressure, haematocrit or plasma fibrinogen. The results suggest that reserpine is an affective anti-atherogenic drug capable of decreasing cholesterol in plasma, arteries and heart by increasing high affinity LDL receptors in the liver.

The nitric oxide synthesis inhibitor L-NAME produces anxiogenic-like effects in the rat elevated plus-maze test, but not in the social interaction test.

The effects of the nitric oxide synthase inhibitor, Nw-nitro-L-arginine methyl ester (L-NAME) were investigated in two animal models of anxiety: the elevated plus-maze and the social interaction test. In the elevated plus-maze, L-NAME (12.5-50 mg/kg) had an anxiogenic-like profile as indicated by dose-dependent reductions in the time spent on the open arms, open arm entries, the percentage of open arm entries and head dips, but there was no significant effect on the number of stretch attend postures. In contrast, L-NAME (12.5-50 mg/kg) failed to modify time spent in social interaction but did reduce a measure of vertical activity. The differential effects of L-NAME in the two anxiety paradigms are discussed.

Minor pediatric injuries.

Injuries are a common source of childhood morbidity and mortality. The initial evaluation should follow in a sequential fashion to determine the extent of injuries. Most minor injuries can be treated safely and cost-effectively in an office setting. The principles of wound care include adequate hemostasis, tissue debridement, removal of imbedded foreign bodies, and appropriate closure or coverage of the wound to optimize healing. Appropriate use of antibodies, tetanus prophylaxis, and rabies immunization will minimize complications. With proper selection and treatment, the outcome of children with minor injuries should be excellent.

Impact of bicycle helmet safety legislation on children admitted to a regional pediatric trauma center.

PURPOSE: The regional pediatric trauma center in Buffalo, NY, has been active in pediatric injury prevention programs, including community education and distribution of bicycle helmets, since 1990. Since June 1, 1994, the use of bicycle safety helmets for children under 14 years of age has been mandated by a state law in New York. The authors undertook this study to assess the impact of this legislation on the frequency of helmet use in children involved in bicycle crashes presenting to the regional pediatric trauma center, and to assess the impact of helmet use on the number and severity of head injuries. METHODS: Bicycle crash victims (n = 208) admitted to a regional pediatric trauma center from 1993 to 1995 were studied retrospectively. Head injuries were classified as concussion alone, skull fractures, intracranial hemorrhages (ie, epidural, subdural, and subarachnoid), cerebral contusions, or diffuse cerebral edema alone (without any other intracranial injury). Helmeted children (HC) were compared with nonhelmeted children (NHC) using chi2 and Fisher's Exact test. P value less than .05 was considered significant. RESULTS: Only 31 children (15%) wore helmets at the time of the crash. Helmet use increased from 2%, during the period of education alone, to 26% after the legislation went into effect (P < .00001). The proportion of children suffering head injuries was similar in both groups (HC, 68%; NHC, 61%; P = NS). However, the type of head injury was different. HC were more likely to sustain concussion alone (HC, 65%; NHC, 44%; P < .03). HC were less likely to have skull fractures (HC, 0%; NHC, 13%; P < .02), and exhibited a trend toward less intracranial hemorrhages (HC, 0%; NHC, 9%; P = NS), cerebral contusions (HC, 3%; NHC, 5%; P = NS), and cerebral edema (HC, 0%; NHC, 0.6%; P = NS). Excluding the isolated concussions, head injuries were noted in only one HC, compared with 30 NHC (P < .04). None of the three children who died wore helmets at the time of the crash, and all died of multiple head injuries. CONCLUSIONS: The bicycle helmet safety law resulted in a 13-fold increase in the use of bicycle helmets among the children admitted to a regional pediatric trauma center after bicycle crashes, but the helmet use remains inadequate. Helmet use reduced the severity of head injuries, and might have prevented deaths caused by head injuries.

Follow-up imaging studies in children with splenic injuries.

We undertook a retrospective study of pediatric blunt splenic injuries treated nonoperatively at our institution from 1990 to 1995 (n = 72) to assess the impact of serial computed tomography (CT) scans on the outcome. Median number of studies per child was three. The result showed that the appearance of the splenic injury remained unchanged or improved in 95% of the imaging studies obtained (116 of 122). Only one of five patients with an image suggesting a worsening splenic injury required operative intervention. There were no instances of missed injuries, delayed ruptures, or readmissions. We conclude that serial CT scans have limited follow-up value and should be used selectively.

Seroepidemiology of varicella-zoster in Pakistan.

The availability of safe and effective vaccines has renewed interest in the epidemiology of varicella worldwide. To date published data on the epidemiology of varicella in Pakistan is very scarce. Therefore, we conducted a study to determine the age-specific seroprevalence rate of varicella-zoster virus (VZV) antibodies in Pakistan. Between December 1997 and March 1998, 1,509 healthy volunteers aged between 1 month and 30 years were recruited from the Islamabad, Karachi, Lahore and Rawalpindi areas. Demographic information, socioeconomic status and past medical history were obtained by questionnaire. Serum samples were assayed for IgG antibodies against VZV by enzyme-linked immunosorbent assay. Overall 41.8% (600/1,435) of those tested were found to be seropositive for VZV antibodies. No difference was found in results obtained from the different cities. A higher seroprevalence was observed among women (45.2%) compared to men (39.6%). Seroprevalence rates increased with age and were 28.4% in those aged 0-5 years, 41.5% in the 6-10 year age group, 42.5% in the 11-15 year age group, 46.7% in the 16-20 year age group and 53.6% in those aged 21-30 years. Socioeconomic status was not a significant risk factor for VZV seropositivity. This is the first report of the seroepidemiology of VZV in Pakistan. The results indicate that seroprevalence of VZV increases with age in the Pakistani population studied. As in other tropical countries, there is greater susceptibility to varicella among the adolescent and young adult population. The results of this study suggest that these at-risk groups should be included in vaccination programs aimed at reducing the public health impact of varicella.

Acute myeloid leukemia-FAB classification and its correlation with clinico-haematological features.

The French-American and British (FAB) classification of 62 consecutive cases of acute myeloid leukemia was undertaken. AML-M2 was the commonest FAB type (32.26%), followed by M1 and M4 (22.58% each), M5 (8.6%) and M6 and M7 (1.61% each), respectively. One of the patients was diagnosed as AML-MO (not a FAB type). The mean age of M1, M2, M3 and M5 cases was between 25 and 29 years, whereas in M4 patients it was 45.6 years. AML-M2, M4 and M5 were commoner in males, M1 in females and M3 equal in both sexes. Feeling of weakness, easy fatiguability and pallor were invariably present in all FAB types. All the patients of M1 and M5, 85% of M2, 64% of M4 and 50% of M3 presented with fever. Bleeding manifestations were most frequent in M3 cases followed by M5, M1, M4 and M2, respectively. Hepatomegaly and splenomegaly were relatively less prominent features in M3 as compared to other FAB types. Amongst the haematological parameters, anaemia was more severe in M1, leucocytosis in M2 and thrombocytopenia in M3 cases as compared to other FAB types.

Hormone replacement therapy menopause with a better future--a survey of views on hormone replacement therapy (HRT).

OBJECTIVE: To assess the views and prescribing practices of doctors regarding hormone replacement therapy (HRT). METHODS: In April 1999, 103 doctors from a teaching hospital participated in a survey. Using a self-administered questionnaire, subjects were contacted at the departments of Internal Medicine, Family Medicine, Obstetrics and Gynaecology, and Orthopaedics. RESULTS: Seventy-two percent were below 40 years of age and 67% of the respondents were male. Most doctors believed that HRT decreases the risk of subsequent osteoporosis (97%), ischaemic heart disease (77%) and depression associated with menopause (64%). Doctors generally considered menopausal symptoms (90%), premature menopause (87%), surgical menopause (85%) and osteoporotic fracture (77%) as clear indications for hormone replacement therapy. Absolute contraindications to the therapy were stated as recent breast cancer (82%) and recent endometrial cancer (84%). Among the specialities covered, there were differing views on proposed duration of HRT. It was generally believed that a pelvic examination, cervical smear and mammography were pre-requisites when initiating and monitoring HRT. Majority (69%) felt that HRT should be offered to all menopausal women, assuming no contraindications and most (73%) did discuss HRT with their patients. However, less than 10% of the menopausal patients under their care were using HRT. Those doctors not in favor of universal offering of HRT (31%) considered unreliable patient follow up to be the main reason. Females were two times more likely to discuss HRT with their patients (p = .08). Doctors who discussed HRT with their patients were four times more likely to consider HRT for themselves or their spouses (p = .13). Gynecologists were eight times more likely to prescribe HRT than non-gynecologists (p = .001). CONCLUSION: Doctors are positively disposed to the universal offering, and use of HRT. Further studies are needed to understand a possible gap between perceived and actual prescribing practice.

Metastases to breast - A 29 year experience in a tertiary care hospital.

Metastatic lesions to the breast are unusual. We present a series of 26 cases of metastatic tumors to breast from extra-mammary sites over a period of 29 years. There were 14 female and 12 male patients, and their ages ranged from 28 to 70 years. The tumor was in the upper outer quadrant in 16 patients. All 26 cases noticed a mass in the breast and more than half of the patients complained of discomfort and pain. The mammary symptoms were present for more than 4 months in all patients. Of the 26 cases, 13 cases had metastatic adenocarcinoma, 12 cases had metastatic squamous cell carcinoma and one case had poorly differentiated carcinoma. On mammography, 16 patients showed high density lesions and on ultrasonography lesions were hypoechoic. Prognosis is poor but appears slightly improved since more refined chemo and immunotherapeutic regimens were available. The clinical, pathologic, and radiographic features of this problem are described.

Temporary inactive status on renal transplant waiting list: causes, risk factors, and outcomes.

Approximately 30% of all patients listed for a kidney transplant in the United States are on inactive status. The consequences of temporary inactivation and rates of transplantation in this group of patients have not been reported. We undertook a retrospective cohort study at our transplant center examining all patients listed between 2001 and 2007. We examined the rate of inactivation, risk factors, duration, and outcomes including transplantation rates and patient survival while on the waiting list and after transplantation. There were 436 patients included in the analysis; 322 (73.9%) were never inactivated and 114 patients (26.1%) were temporarily inactive. The most common causes for inactivation were cardiovascular and suspected malignancy. Time to reactivation was similar among different causes. Waiting times for transplantation (excluding time of inactivation) was 18.7 ± 0.9 versus 39.9 ± 2.3 months for active compared with temporarily inactive patients (log-rank P < .0001). Sixty-five percent of patients were reactivated within 24 months. Approximately one-third of patients were never reactivated. Patient survival was similar among both groups. Temporary inactivation is an independent risk factor for a prolonged waiting time even if time of inactivation is not accounted for. Effective strategies for monitoring patients temporarily inactive on the waiting list should be developed.