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Biomedical subjects

S Shafi

Publications and source records attributed to S Shafi.

At least 19 recordsLinked to original sources

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.

Aged↗

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.

Adult↗

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.

Animals↗

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.

Adrenal Glands↗

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.

Adolescent↗

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.

Child↗

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.

Bicycling↗

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.

Accidental Falls↗

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.

Animals↗

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.

Adolescent↗

[Factors affecting the trans-endothelial accumulation of atherogenic plasma proteins in artery walls].

Our experiments were done to find out whether there are factors which influence the passage of the two major "risk factor proteins" LDL and fibrinogen, other than their plasma concentrations, from the blood into the arterial walls, where their accumulation is associated with atherogenesis. The results suggest that administration of a remarkable variety of pressor agents over a few days accelerate the uptake of both proteins by arterial walls, and that, in contrast, the process is no faster in rats that have been spontaneously, i.e., genetically, hypertensive for about 3 months. Considering our experimental findings in relation to human atherosclerotic disease, it is interesting that the risk of coronary heart disease and stroke is increased more than additively when both LDL or fibrinogen levels and systolic or diastolic blood pressures are high (18,46). If our work should point to some mechanistic connection between blood pressure and the accumulation of atherogenic plasma proteins in arterial walls, it would provide, at least in principle, an explanation for the epidemiological facts.

Animals↗

Risk of hemorrhage and appropriate use of blood transfusions in pediatric blunt splenic injuries.

OBJECTIVE: To define changes in hematocrit (Hct) and the indications for blood transfusion in pediatric blunt splenic injury. DESIGN: Retrospective case series MATERIALS AND METHODS: All children with blunt splenic injuries from 1990 to 1995 were studied (n = 74). Transfusion practices were reviewed for the whole group. Thirty children with isolated splenic injuries who were not transfused were analyzed to document Hct changes (mean +/- 95% confidence intervals). MEASUREMENTS AND RESULTS: The Hct at presentation was 37 +/- 2%, which rapidly dropped to 31 +/- 2% (p < 0.05) within 24 hours. After remaining stable at that level for the next 5 days, the Hct rose to 33 +/- 4% on day 6 (p = not significant), 35 +/- 4% on day 7 (p = not significant), and 38 +/- 2% (p = not significant) on day 13 +/- 3. Fifteen children received transfusions, all but one of whom had suffered multiple injuries. The transfusion rate declined from 38% of children in 1990 to 10% in 1995. CONCLUSIONS: After the initial drop within the first 24 hours, the Hct remains stable and rises with time to reach the baseline by day 6. Transfusion rates have declined over time, and transfusions are now used almost exclusively in severely injured children with multiple injuries.

Blood Transfusion↗

Initial hepatic removal of chylomicron remnants is unaffected but endocytosis is delayed in mice lacking the low density lipoprotein receptor.

Two endocytic receptors, the low density lipoprotein (LDL) receptor (LDLR) and the LDLR-related protein (LRP), are thought to act in concert in the hepatic uptake of partially metabolized dietary lipoproteins, the chylomicron remnants. We have evaluated the role of these two receptors in the hepatic metabolism of chylomicron remnants in normal mice and in LDLR-deficient [LDLR (-/-)] mice. The rate of chylomicron remnant removal by the liver was normal up to 30 min after intravenous injection of chylomicrons into LDLR (-/-) mice and was unaffected by receptor-associated protein (RAP), a potent inhibitor of ligand binding to LRP. In contrast, endocytosis of the remnants by the hepatocytes, measured by their accumulation in the endosomal fraction and by the rate of hydrolysis of component cholesteryl esters, was dramatically reduced in the absence of the LDLR. Coadministration of RAP prevented the continuing hepatic removal of chylomicron remnants in LDL (-/-) mice after 30 min, consistent with blockade of the slow endocytosis by a RAP-sensitive process. Taken together with previous studies, our results are consistent with a model in which the initial hepatic removal of chylomicron remnants is primarily mediated by mechanisms that do not include LDLR or LRP, possibly involving glycosaminoglycan-bound hepatic lipase and apolipoprotein E. After the remnants bind to these alternative sites on the hepatocyte surface, endocytosis is predominantly mediated by the LDLR and also by a slower and less efficient backup process that is RAP sensitive and therefore most likely involves LRP.

Analysis of Variance↗

A quantitative method for cost reimbursement and length of stay quality assurance in multiple trauma patients.

OBJECTIVE: To develop a statistically valid method for trauma reimbursement and quality assurance (QA) length-of-stay filters. This is needed because diagnosis related group (DRG)-based trauma payment systems assume a random sampling of injury severities from a normally distributed population and thus result in economic disincentives to level I trauma centers. METHODS: 142 trauma patients with MVC blunt multisystem injuries (MSI) (ISS > or = 16) were studied concurrently during their hospital course. SETTING: Level I regional trauma center. OUTCOME MEASURES: Outcome measures were (dependent variables) length of stay (LOS) and state-approved hospital charges (COST). RESULTS: Mean acute care COST was $74,310, but the distribution of COST was log normal, rather than Gaussian normal as assumed by DRGs. The LOS for MSI was more than twice the average for all trauma (22 vs. 9 days), reflecting skewed severities of level I patients and was related to COST (r2 = 0.802; p < 0.0001). The ISS alone was a weak determinant of COST or LOS (r2 = 0.05; p < 0.0001). The best single determinant of COST and LOS was survival (r2 = 0.15; p < 0.0001): as it increased, it increased LOS. The most costly injuries (all p < 0.0001) involved the lower extremity (LE) or hip joint (HIP), whereas sepsis and pulmonary and surgical complications constituted the most costly complications (all p < 0.0001). Regression models that accounted for the log-normal distribution of the dependent variable and based on binary variables for survival, LE and HIP injuries, and the complications of sepsis, ARDS, pulmonary failure, MOFS, plus ISS, explained nearly two thirds of the variability in COST (r2 = 0.621; p < 0.0001) or LOS (r2 = 0.687; p < 0.0001) and the residuals were normally distributed. CONCLUSIONS: These models provide a valid method of reimbursement for MSI trauma for level I trauma centers, since the data imply that good care associated with survival from specific complications of MSI are the major determinants of COST, rather than the specific type of injury or the resultant ISS. Moreover, using survival and ISS plus the disease-related complications as determinants of LOS, this method can be applied to any U.S. region since local factors can be used to adjust hospital COST as a highly correlated function of LOS. This method also permits identification of LOS outliers for QA, taking into account the influence of injury complications.

Accidents, Traffic↗

Role of hepatic lipase in the uptake and processing of chylomicron remnants in rat liver.

The participation of hepatic lipase in the initial uptake and processing of chylomicron remnants was studied in the isolated, perfused rat liver. Hepatic lipase activity was either reduced by preperfusion of livers with heparin or inhibited with specific rat hepatic lipase antibodies. [3H]palmitate-labeled chylomicron remnants were recirculated through control and treated livers for 15 min; the livers were then flushed, homogenized, and endosome-rich fractions were isolated. Depletion of hepatic lipase activity by both methods reduced the uptake of chylomicron remnants and hydrolysis of their component triglycerides by perfused rat livers, but at the same time significantly increased the rate of endocytosis of those chylomicron remnants taken up. We conclude that hepatic lipase facilitates, but is not essential for, the initial uptake of chylomicron remnants by rat liver. Furthermore, endocytosis of chylomicron remnants does not require binding to hepatic lipase or the associated hydrolysis of remnant lipids.

Animals↗