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.

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.

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.

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.

Viral respiratory infections at the Hajj: comparison between UK and Saudi pilgrims.

A high incidence of respiratory infection, including influenza, has been reported at the Hajj in Mecca, Saudi Arabia. Reported rates of influenza have been higher among UK than among domestic pilgrims, but this could be explained by methodological differences among studies. Accordingly, the present study compared the frequencies of respiratory viruses among UK and Saudi pilgrims using the same study design. Pilgrims with upper respiratory tract symptoms were recruited from Mecca and the neighbouring valley Mina during the Hajj 2006. Nasal swabs were used for point-of-care influenza testing and real-time RT-PCR (rtRT-PCR) tests for influenza virus, rhinovirus, parainfluenza virus, adenovirus, human metapneumovirus and respiratory syncytial virus. Of 260 pilgrims investigated, 150 were from the UK and 110 were Saudi; of these, 38 (25%) UK pilgrims and 14 (13%) Saudi pilgrims had respiratory infections detectable by rtRT-PCR (p 0.01). In the UK group, there were 19 (13%) cases of rhinovirus infection, 15 (10%) cases of influenza virus infection, two (1%) cases of dual infections with influenza virus and rhinovirus, one (3%) case of parainfluenza virus infection, and one (1%) case of respiratory syncytial virus infection. Fifty-six (37%) UK pilgrims had been vaccinated against influenza virus, with the rates of influenza in the vaccinated and unvaccinated group being 7% and 14%, respectively (p 0.19). In the Saudi group, there were three (3%) cases of rhinovirus infection and 11 (10%) cases of influenza. Only four (4%) Saudi pilgrims had been vaccinated against influenza virus, and none of these was infected with influenza virus. Overall, a significantly higher proportion of the UK pilgrims had detectable respiratory infections (25% vs. 13%, p 0.01). Influenza rates were similar in both groups, but the reported rates of influenza vaccination differed.

Influenza and respiratory syncytial virus infections in British Hajj pilgrims.

Viral respiratory infections including influenza and respiratory syncytial virus (RSV) have been reported during the Hajj among international pilgrims. To help establish the burden of these infections at the Hajj, we set up a study to confirm these diagnoses in symptomatic British pilgrims who attended the 2005 Hajj. UK pilgrims with symptoms of upper respiratory tract infection (URTI) were invited to participate; after taking medical history, nasal swabs were collected for point-of-care testing (PoCT) of influenza and for subsequent PCR analysis for influenza and RSV. Of the 205 patients recruited, 37 (18%) were positive for either influenza or RSV. Influenza A (H3) accounted for 54% (20/37) of the virus-positive samples, followed by RSV 24% (9/37), influenza B 19% (7/37), and influenza A (H1) 3% (1/37). Of the influenza-positive cases, 29% (8/28) had recently had a flu immunisation. Influenza was more common in those who gave a history of contact with a pilgrim with a respiratory illness than those who did not (17 versus 9%). The overall rate of RSV was 4% (9/202). This study confirms that influenza and RSV cause acute respiratory infections in British Hajj pilgrims. Continuing surveillance and a programme of interventions to contain the spread of infection are needed at the Hajj, particularly when the world is preparing for an influenza pandemic.

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.

A model for the management of an atypical endophthalmitis outbreak.

PURPOSE OF STUDY: To present a model for the assessment, investigation, and management of an atypical outbreak of infectious endophthalmitis of indeterminate aetiology. METHODS: A published statistical model was used to determine when the case-load constituted an outbreak. Intraocular surgery was discontinued and a multidisciplinary infection control team was formed aimed at identifying potential causative factors among the following categories: environment around theatre, preoperative preparation, intraoperative theatre practices, intraoperative surgical practices, postoperative practices, equipment maintenance guidelines, cleaning/sterilization practices, and microbiological screening. RESULTS: Five cases of postoperative endophthalmitis developed following uncomplicated phacoemulsification cataract surgery by different surgeons over a 7-month period. Despite full investigation no single focus of infection could be determined. Four out of five cases were culture positive. Three grew Streptococcus viridans of different strains. The fourth culture grew Staphylococcus aureus. In the absence of a single causative factor, it was postulated the combined effect of multiple potential factors may have led to an increased bacterial load and subsequent infection rate. Improved practices were initiated including new cleaning protocols to combat the build-up of debris on phacoemulsification instruments. Cataract surgery was resumed with 3-monthly microbiological monitoring. There have been no further cases in the 12 months following the changes. CONCLUSION: Outbreaks of endophthalmitis typically present over a short time period and could often be attributed to a single infective cause. We present our experience of detecting and managing this cluster and recommend a 'ground-up' multidisciplinary model to manage future outbreaks of this devastating condition.

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.

Effect of reserpine treatment on low-density lipoproteins in arterial wall and internal organs of rats.

The effects were determined in rats of single injections of reserpine at increasing doses (0.5, 1.58, and 5.0 mg/kg) on low-density lipoprotein (LDL) and cholesterol in aortic wall, heart, liver, kidney, and adrenal gland. Catecholamine levels in plasma, heart, and liver, arterial blood pressure, and heart rate were also monitored. Reserpine was injected intraperitoneally, followed immediately by the administration of [3H]cholesterol by gavage. Twelve hours later, homologous 125I-tyramine cellobiose-labeled LDL (125I-TC-LDL) was injected intravenously. Twenty-four hours later, the rats were killed, and the radioactivities of aortic walls, heart, liver, kidney, and adrenal glands were determined. The results showed that after reserpine treatment the accumulation of both the 125I-TC label derived from LDL and total [3H]cholesterol was significantly reduced in aortic wall and heart, increased in liver, and unchanged in the kidney and adrenal gland. At higher doses (1.58 and 5.0 mg/kg), reserpine significantly accelerated the plasma clearance of radiolabelled LDL. Plasma noradrenaline in reserpine-treated animals decreased maximally (86%) by 12 h and by 61-71% at 36 h compared with the control. Plasma adrenaline increased transiently after injection of reserpine and then returned to the basal levels. Reserpine greatly decreased noradrenaline and adrenaline levels in heart and liver. Arterial blood pressure was decreased significantly (0.001 < p < 0.05) at 12 h by the two lower doses of reserpine and then returned to normal values over the next 24 h. The results indicate that reserpine decreases LDL cholesterol in artery wall and heart and increases it in liver. These findings suggest that reserpine could find a new use as a cholesterol-lowering drug for the prevention of atherosclerosis.

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.

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.

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.

A large outbreak of cryptosporidiosis associated with a public water supply from a deep chalk borehole. Outbreak Investigation Team.

Three hundred and forty-five confirmed cases were reported in a large waterborne outbreak of cryptosporidiosis in North Thames in the spring of 1997. The descriptive epidemiology, attack rates, a case control study, and the detection of oocysts in the water suggested strongly that the outbreak was associated with drinking unboiled tap water that originated from one deep chalk borehole. The 746,000 people living in the water distribution area were advised to boil their drinking water. Investigations did not reveal how oocysts entered the borehole. This is the first published report of a cryptosporidium outbreak caused by filtered borehole water and we believe it to be the largest outbreak due to groundwater to have been reported. Borehole supplies are regarded as relatively pure sources of water and this outbreak has implications for the future monitoring and treatment of drinking water extracted from boreholes.