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Biomedical subjects

M Joshi

Publications and source records attributed to M Joshi.

At least 19 recordsLinked to original sources

Exploiting the bootstrap method for quantifying parameter confidence intervals in dynamical systems.

A quantitative description of dynamical systems requires the estimation of uncertain kinetic parameters and an analysis of their precision. A method frequently used to describe the confidence intervals of estimated parameters is based on the Fisher-Information-Matrix. The application of this traditional method has two important shortcomings: (i) it gives only lower bounds for the variance of a parameter if the solution of the underlying model equations is non-linear in parameters. (ii) The resulting confidence interval is symmetric with respect to the estimated parameter. Here, we show that by applying the bootstrap method a better approximation of (possibly) asymmetric confidence intervals for parameters could be obtained. In contrast to previous applications devoted to non-parametric problems, a dynamical model describing a bio-chemical network is used to evaluate the method.

Algorithms↗

Ultrasound spectrum in intraductal papillary neoplasms of breast.

Intraductal papillary neoplasms (IPNs) of breast form a wide spectrum of pathological changes with benign intraductal papilloma occupying one end of the spectrum and papillary carcinoma at the other end. Intraductal papillomas are known to occur anywhere within the ductal system and are broadly classified into central and peripheral types. Intraductal papillary carcinoma is an uncommon ductal malignancy forming papillary structures, and these lesions characteristically lack the myoepithelial layer present in benign papillary neoplasms. Three basic patterns of IPNs are recognized on ultrasound - intraductal mass with or without ductal dilatation, intracystic mass and a predominantly solid pattern with the intraductal mass totally filling the duct. Benign papillomas are known to exhibit calcifications which tend to be extremely dense and coarse. IPNs are highly vascular tumours and have a propensity to bleed spontaneously. A distinct vascular pedicle is identified within the central core of IPNs, with branching vessels arborising within the mass. In an older age group, presence of a large solid component and evidence of spontaneous intracystic bleed are more suggestive of papillary carcinomas than benign papillomas. We have serially studied 42 cases of intraductal papillary neoplasms with sonomammography and mammography from 2001 to 2004.

Adult↗

Anterior cruciate ligament insufficiency: does delay in index surgery affect outcome in recreational athletes.

The aim of the study was to see if delay in anterior cruciate ligament (ACL) reconstruction affects post-reconstruction outcome in recreational athletes. Sixty-two recreational athletes who had arthroscopic ACL reconstructions using quadruple hamstring grafts between 1997 and 2000 were retrospectively evaluated. Patients with less than 2 years' follow-up, those with multi-ligament injuries, reconstructions for previous failed repairs, those whose injury date was unknown, those with pre-injury Tegner activity level greater than 7 (competitive athletes) and those lost to follow-up were all excluded. Forty-six patients (38 males) were entered. The mean follow up was 38 months and the mean time from injury to index ACL reconstruction was 27 months. Apart from two revisions there were no other significant complications. Forty-one (89%) patients were evaluated in a review clinic. There was a significant improvement in the post-reconstruction Lysholm scores and an improvement in the Tegner scores. The Spearman's correlation coefficient between postoperative Lysholm score and the delay until surgery was -0.18 and the correlation coefficient between postoperative Tegner scores and the delay until surgery was 0.14. Thirty-five patients returned to sporting activity. Thirty-seven rated their knee as being normal or nearly normal and 35 said that their knee function was as they had expected it to be. Late ACL reconstruction does not adversely affect the outcome in recreational athletes. ACL reconstruction should be offered to these patients as there is a significant improvement in the knee function and patients are satisfied with the results.

Adolescent↗

Laparoscopic total extraperitoneal repair versus anterior preperitoneal repair for inguinal hernia.

Laparoscopic inguinal hernia repair is still not the gold standard for repair although mesh implantation is unequivocally accepted as an integral part of any groin hernia repair. The aim of the study was to compare the results of anterior preperitoneal (APP) mesh repair with totally extra peritoneal (TEP) repair for inguinal hernias. The prospective study was conducted on 241 patients with 247 hernias (from January 2000 to June 2004). Anterior preperitoneal repair was done in 121 patients and 120 patients were subjected to TEP repair. Repair in both groups was done by using Prolene mesh of size 6x4 in. or 6x6 in. intraoperative and postoperative parameters and complications were recorded and the patients were followed up to 1 year post-surgery. For both unilateral and bilateral inguinal hernias, mean operative time was significantly more in patients of TEP repair as compared to APP repair (P<0.001) and significantly more patients had peritoneal tears in the TEP group (P<0.001). Patients undergoing TEP repair, however, had significantly less postoperative pain (P<0.05) and postoperative hospital stay (P<0.05) and return to work was significantly earlier is this group (P<0.01 and P<0.001). There was no difference in the recurrence rate between the two groups. Patients with inguinal hernias undergoing laparoscopic repair recover more rapidly, and have less incidence of postoperative pain. But it takes significantly more time to perform than APP repair and also the incidence of peritoneal tear is higher.

Adolescent↗

A randomized controlled trial comparing the accuracy of general diagnostic upper gastrointestinal endoscopy performed by nurse or medical endoscopists.

BACKGROUND AND STUDY AIMS: Rising demand for general diagnostic upper gastrointestinal endoscopy in the UK is outgrowing the capacity of doctors to provide this service within a reasonable time. One solution is to train nurses to carry out the procedure, but it is not known whether nurses can perform general diagnostic upper gastrointestinal endoscopy as competently as doctors. PATIENTS AND METHODS: A randomized controlled non-inferiority trial compared the adequacy and the accuracy of diagnostic upper gastrointestinal endoscopies performed by five medical and two nurse endoscopists. The videotaped procedures were assessed by a consultant gastroenterologist blinded to the identity of the endoscopist. RESULTS: 641 patients were randomly allocated (before attendance and consent procedure) to endoscopy carried out either by a doctor or a nurse. Of these, 412 were enrolled and 367 (89 %) were included in the analysis. An adequate view was obtained throughout in 53.4 % (93/177) of doctor endoscopies and 91.6 % (174/190) of nurse endoscopies (difference 38.2 %, 95 % CL 30.5 %, 47.2 %). In adequately viewed areas, the mean agreement between doctor and expert was 81.0 % and between nurse and expert it was 78.3 % (difference between the means 2.7 %, 95 % CL - 1.0 %, 6.4 %). There was no difference between doctors and nurses in the rate of biopsy performance (90.4 % and 91.1 %, respectively, P = 0.862). Nurses took longer (8.1 minutes vs. 4.6 minutes, P < 0.001) and used intravenous sedation more often (57.6 %, P = 0.027). Adequacy of view correlated positively with endoscopy duration ( P < 0.001), but diagnostic accuracy correlated inversely with duration ( P < 0.001). Neither adequacy or accuracy correlated significantly with use of intravenous sedation. CONCLUSIONS: In endoscopies performed by nurses, the proportion of adequate examinations was much higher than that found for doctors. In areas with an adequate view, there is no significant difference in accuracy between nurses and doctors. Nurses can provide an accurate general diagnostic upper gastrointestinal endoscopy service as competently as doctors.

Clinical Competence↗

Formulation and evaluation of Nanostructured Lipid Carrier (NLC)-based gel of Valdecoxib.

Nanostructured Lipid Carrier (NLC)-based topical gel of Valdecoxib was formulated with the aim of faster onset yet prolonged action for the treatment of inflammation and allied conditions. NLCs prepared by microemulsion template technique were characterized by photon correlation spectroscopy for size. Drug encapsulation efficiency was determined using Nanosep centrifugal device. The nanoparticulate dispersion was suitably gelled and characterized with respect to drug content, pH, spreadibility, rheology, and in-vitro release. Safety of the NLC-based gel was assessed using primary skin irritation studies, and efficacy was confirmed using pharmacodynamic study, namely the Aerosil-induced Rat Paw edema model. The developed NLC-based gel showed faster onset and elicited prolonged activity up to 24 hours.

Animals↗

A case control study in the Indian subcontinent ethnic population on the effect of return visits and the subsequent development of tuberculosis.

SETTING: A local government area in North West England with a significant population of Indian subcontinent (ISC) ethnic origin and a high incidence of tuberculosis. OBJECTIVE: To assess whether return visits to the ISC are associated with an increased risk of developing clinical tuberculosis. METHODS: Analysis of data prospectively obtained from ISC patients diagnosed with TB in 1998-2002 (cases) and age and sex matched ISC patients in two local GP practices (controls). RESULTS: There is at best weak evidence of association between case status and whether individuals have had a repeat visit to the subcontinent within 3 years of notification in this cohort; odds ratio 1.26 (95% CI (0.95, 1.76)); Fishers exact test P=0.09.

Adult↗

Nutritional status and wound healing in open fractures of the lower limb.

Forty-three patients averaging 28.2 (range 16--74) years with open fractures of the lower limbs were studied prospectively for 40 weeks using anthropometrical, biochemical and haematological parameters to ascertain their relationship to wound healing following injury. Nearly half (21/43) of the patients were malnourished at admission and the number increased to 22 a week after injury. Dietary advice and better food intake improved nutritional status with only 13 patients remaining malnourished at the 40th week. Wound healing was earlier when creatinine-height index was normal throughout the course of treatment and was delayed when serum albumin level was low.

Adolescent↗

Prevalence of HCV and HIV/HCV co-infection among volunteer blood donors and VCT clients.

OBJECTIVE: To determine the prevalence of HCV infection and HCV/HIV co-infection among voluntary blood donors at the National Blood Transfusion Centre and clients at the Kenyatta National Hospital HIV-Voluntary Counseling and Testing (VCT) Centre. DESIGN: A prospective cross-sectional descriptive study. SETTING: Kenyatta National Hospital, a tertiary referral and teaching hospital and the National Blood Transfusion Services Centre, Nairobi. SUBJECTS: Volunteer blood donors and VCT attendants. RESULTS: The prevalence of HCV/HIV co-infection among 6154 blood donors in the NBTSC was very low, at 0.02. The HIV prevalence among the 353 KNH HIV-VCT clients was 9.3%, none of the clients tested positive for HCV. The incidence of risk factors in the persons with HCV and/or HIV infection(s) was low. CONCLUSION: The prevalence of HCV infection among pre-screened volunteer blood donors was low. However the current practice of screening all donated blood for HCV remains indispensable to prevent its transmission to blood recipients.

Adolescent↗

Prevalence of HCV and HCV/HIV co-infection among in-patients at the Kenyatta National Hospital.

OBJECTIVE: To determine the prevalence of HCV and HCV/HIV co-infection among medical in-patients at the Kenyatta National Hospital. DESIGN: Prospective cross-sectional descriptive study. SETTING: Kenyatta National Hospital, a tertiary referral and teaching hospital, in-patient department SUBJECTS: HIV/AIDS and HIV negative in-patients at KNH medical wards. RESULTS: Among 458 HIV/AIDS medical in-patients, the prevalence of HCV was 3.7% while in the 518 HIV negative patients, it was 4.4%. The prevalence of co-infection with HCV and HIV was 3.7%. The incidence of risk factors in persons with HCV and/or HIV infection(s) was low. CONCLUSION: This study found the prevalence of HCV infection among medical in-patients to be similar in HIV positive and HIV negative group of patients. The co-infection rates were low, as were the risk factors for transmission of these infections.

Adolescent↗

Analgesic effect of expressed breast milk in procedural pain in term neonates: a randomized, placebo-controlled, double-blind trial.

AIM: To assess the effectiveness of expressed breast milk (EBM) in reducing pain due to venepuncture, in term neonates, as measured by behavioural and physiological observations. METHODS: This randomized, placebo-controlled, double-blind trial involved 81 full-term neonates, up to 4 wk of postnatal age, who needed venepuncture for blood investigations. Two minutes before the venepuncture, in the intervention arm, 40 babies received 5 ml of EBM, while 41 babies in control group received 5 ml of distilled water (DW) as placebo. Two observers who were blinded to the intervention recorded the physiological (heart rate and oxygen saturation) and behavioural parameters [duration of crying and modified Neonatal Facial Coding Scores (NFCS)] after the venepuncture. RESULTS: There was no difference in the baseline characteristics of the neonates in the two groups. The duration of crying was significantly shorter in babies fed EBM [median 38.5 s, interquartile range (IQR) 9.5-57.5 s] than in those fed DW (median 90 s, IQR 28-210 s). The mean duration of crying in EBM group was shorter by 70.7 (95% confidence interval 36.6-104.9) s. The modified NFCS at 0, 1 and 3 min was significantly lower (p < 0.01) in the EBM than in the DW group. The change in heart rate and oxygen saturation was significantly lower in the EBM group and returned to baseline values sooner than in the DW group. CONCLUSION: Feeding 5 ml of EBM before venepuncture is effective in reducing symptoms due to pain in term neonates.

Analgesia↗

The Lancaster experience of 2.0 to 2.5 mg/kg intramuscular ketamine for paediatric sedation: 501 cases and analysis.

OBJECTIVES: To report the experience of using intramuscular ketamine 2.0 or 2.5 mg/kg for minor painful procedures in children in a medium sized district general hospital accident and emergency department. To demonstrate the safety and acceptability of ketamine and determine if the incidence of adverse effects is related to dose or other variables. METHODS: Prospective data collection and analysis using Statsdirect and SPSS software. RESULTS: 501 consecutive cases were collected from August 1996 to April 2002. A total of 310 children received 2.0 mg/kg and 191 received 2.5 mg/kg. Twenty six received a second dose. In seven cases oxygen saturation fell below 93%, three of these fell below 90%. There was one case of laryngospasm. Eight cases received airway suctioning, five of these were mouth or lip wounds. Seventeen per cent vomited in recovery or at home for which one child required admission. Muscle hypertonicity was observed in 6.8%, disturbed sleep or nightmares in 2%. The median time to discharge was 85 minutes. Ninety seven per cent of parents' experiences were "the same as" or "better than" expected. No children suffered any lasting or troublesome complications. CONCLUSIONS: 2.0 - 2.5 mg/kg intramuscular ketamine sedation is a safe and acceptable technique when used within a defined protocol. Lower dose ketamine (2 mg/kg) warrants further study in view of potentially less airway complications and quicker discharge times than previously reported.

Child↗

Cardiovascular risk factor profile of black Africans undergoing coronary angiography.

BACKGROUND: Coronary artery disease (CAD) is a growing epidemic on the African continent. It remains uncertain whether the risk factors identified as contributing to CAD in white populations contribute to a similar extent to CAD incidence in black populations. No data of the local population exists that is based on the coronary angiogram (CA). OBJECTIVES: To analyse the relationship of conventional cardiovascular risk factors with presence of CAD in black Africans. DESIGN: This was a dual-armed study, consisting of retrospective and prospective comparative arms. SUBJECTS: Black Africans who underwent coronary angiography. SETTING: Nairobi Hospital, Cathereterization laboratory. MAIN OUTCOME MEASURES: The conventional risk factors: age, male gender, hypertension, obesity, smoking, diabetes mellitus, dyslipidaemia, alcohol use and interventricular septum (IVS) hypertrophy, as a marker of LVH. RESULTS: One hundred and sixty nine patients fulfilled the inclusion criteria; 144 in the retrospective arm and 25 in the prospective. The larger retrospective arm showed that the group with CAD, compared to the normal group, was significantly older, with a higher mean age of 54.4 years compared to 49.8 years (P=0.005); had significantly more males, with a male to female ratio of 5.5:1 compared to 2.3:1 (P=0.045); had a very significantly larger proportion of diabetics (38.5% compared to 12%, P=0.0002), and also had a significantly larger proportion of patients with dyslipidaemia (67.3% compared to 35.9%, P=0.0003). The percentage of hypertensives was high in both groups, with (65.4%) in the CAD group and 62% in the Normal group being hypertensive (P=0.68). The percentage of smokers was small in both groups, being 15.4% and 13% respectively. Smoking, increased BMI, alcohol use, and increased IVS were each found to be distributed equally in both groups. In addition, the Waist hip ratio (WHR) and waist circumference (WC) did not differ significantly between the two groups studied. CONCLUSIONS: The risk factors found to be most strongly associated with presence of angiographically-detected CAD in the population studied were diabetes mellitus, dyslipidaemia, age and male gender. There was a high prevalence of hypertension, with equal distribution in both groups under study; hence this risk factor was not discriminatory for CAD. There was a low prevalence of cigarette smoking in this particular study; it was not predictive of presence of CAD.

Black People↗

In vitro propagation of Saussurea obvallata (DC.) Edgew.--an endangered ethnoreligious medicinal herb of Himalaya.

This is the first report of a micropropagation protocol for Saussurea obvallata (DC.) Edgew. (Asteraceae), a rare, threatened and near-endemic medicinal herb of the Indian Himalayan region. Multiple shoots were formed from epicotyle explants on Murashige and Skoog (MS) medium supplemented with 1.0 microM kinetin and 0.25 microM alpha-naphthaleneacetic acid. A maximum of five shoots were obtained from one explant in a 75-day culture period. The effect of subsequent subcultures on shoot formation was also studied. After 100% in vitro rooting was obtained in half-strength MS supplemented with 2.5 microM indole-3-butyric acid, the plantlets were transferred to ex vitro conditions. Following a 15-day in vitro rooting period and 12 days of ex vitro acclimatization, 66.7% of the plantlets had established in the field. Application of this protocol has the potential to substantially reduce the pressure on natural populations.

Adenine↗

Auditory function following spinal analgesia. Comparison of two spinal needles.

BACKGROUND AND OBJECTIVE: Auditory impairment is among the lesser known complications of spinal analgesia. The aim of the present study was to determine the degree of vestibulocochlear dysfunction in patients undergoing spinal analgesia for lower abdominal surgery. METHODS: Eighty patients who had received spinal analgesia for lower abdominal surgery were studied. Males were undergoing inguinal herniorraphy and the females tubectomy. Audiograms were performed before operation and on the second and seventh postoperative days. Hearing levels were measured from 250 Hz-8 kHz. In Group 1 (n = 40) a 22-gauge, cutting type of spinal needle (Howard Jones) was used. In Group 2 (n = 40) a 25-gauge, non-cutting spinal needle (Whitacre) was used. RESULTS: Hearing loss >10 dB was noticed in three patients in Group 1 and none in Group 2. The mean hearing level was more reduced in Group 1 patients. CONCLUSIONS: Use of cutting type spinal needle is associated with a greater decrease in mean hearing levels compared to the non-cutting type.

Abdomen↗

Apoptosis versus necrosis during cold storage and rewarming of human renal proximal tubular cells.

BACKGROUND: A recent clinical study demonstrated that in renal allografts preserved in the cold apoptosis occurred soon after reperfusion. The mode of cell death during cold storage is generally considered necrotic. Whether apoptosis occurs as a part of cold storage is uncertain. The objective was to determine in human renal tubular cells whether apoptosis is specific for rewarming or it also occurs during cold storage and whether it could be modified. METHODS AND RESULTS: Cold storage (4 degrees C) of primary human renal proximal tubular epithelial (RPTE) in University of Wisconsin (UW) solution up to 48 hr caused a time-dependent increase in cell death measured by lactic dehydrogenase (LDH) release and vital dye exclusion methods. Transmission electron microscopy (TEM) demonstrated that cell death in the cold was necrotic, involving considerable mitochondrial disruption, and was not apoptotic. The TUNEL assay that provides a specific, quantitative measure for apoptosis showed no increase in TUNEL-positivity during flow cytometry of cells stored in cold: 37 degrees C, 0.23+/-0.14%; 24 hr cold, 0.23+/-0.1%; 48 hr cold, 1.79+/-0.58%. Annexin-V staining, a sensitive method for detecting early apoptosis, similarly showed no increase in positively stained cells during cold storage. Addition of antioxidants 2-methyl aminochroman and deferoxamine to UW solution inhibited necrotic cell death and preserved mitochondrial structure. In contrast to cold storage alone, rewarming (37 degrees C for 24 hr) of cold stored cells, however, resulted in significant apoptosis (TUNEL positive: 48 hr cold: 2+/-0.6%, 48 hr cold and 24 hr rewarming: 54+/-17%), which was confirmed by the TEM based on typical apoptotic features. Addition of 2-MAC and DFO significantly inhibited rewarming-induced apoptotic cell death (plus 2-MAC: 3+/-1%, plus DFO: 3+/-2%). CONCLUSION: Our study in human tubular cells provides evidence that cold storage per se does not result in apoptosis, but is primarily necrotic. However, rewarming is associated with significant apoptosis in the presence of ongoing necrosis, speculatively due to the activation of the apoptotic enzymic process of sublethally injured cells. Inclusion of antioxidants in the storage solution confers protection against both cold storage and rewarming-induced necrosis and apoptosis.

Adenosine↗

Dry powder inhalation of liposomal Ketotifen fumarate: formulation and characterization.

The purpose of the experiment was to formulate and characterize the dry powder inhalation (DPI) formulation of liposomally entrapped anti-asthmatic drug, Ketotifen fumarate (KF). Liposomes composed of saturated egg phosphatidyl choline (EPC) and cholesterol (CHOL) were prepared by lipid film hydration and sonicated to have the desired size (<5 microm). Process variable such as vacuum, presonication hydration, postsonication hydration, purification and lamellae composition, were optimized for encapsulation efficiency of KF. Liposomal dispersion was blended with cryoprotectant (sugar) in varying bulk and mass ratios and assessed for its influence on retention of encapsulated drug on lyophilization. Characterization of liposomal dispersion was done for size, lamellarity, entrapped volume and oxidation index. DPI formulation was characterized for angle of repose, compressibility index, dispersibility and respirable fraction (British Pharmacopoeia, apparatus A). Process optimization revealed that a vacuum, 20 in.; presonication hydration, 60 min; postsonication hydration, 2 h and purification by dialysis gave maximum encapsulation efficiency. Sucrose was found to be the most suitable cryoprotectant at bulk strength of 500 mM and mass ratio of lipid/sugar, 1/12. Blending of sorbolac before lyophilization showed better retention of encapsulated KF (97.92+/-0.54%). In the preparation of sonicated MLVs, the presence of nitrogen atmosphere, alpha-tocopherol and EDTA could not totally eliminate EPC oxidation, expressed as the change in oxidation index from 0.427+/-0.01 to 1.510+/-0.01. The respirable fraction of the developed formulation (21.59+/-1.53%) is comparable with the control (26.49+/-1.52%). From studies, it may be concluded that an optimal bulk and mass ratio of sucrose, relative to the size of liposomes is necessary for effective cryoprotection. In this investigation, DPI of liposomal KF was successfully prepared and delivered to the required site in the lungs.

Administration, Inhalation↗

Emergence of axons from distal dendrites of adult mammalian neurons following a permanent axotomy.

The distinctive features of axons and dendrites divide most neurons into two compartments. This polarity is fundamental to the ability of most neurons to integrate synaptic signals and transmit action potentials. It is not known, however, if the polarity of neurons in the adult mammalian nervous system is fixed or plastic. Following axotomy, some distal dendrites of neck motoneurons in the adult cat give rise to unusual processes that, at a light microscopic level, resemble axons (Rose, P.K. & Odlozinski, M., J. Comp. Neurol., 1998, 390, 392). The goal of the present experiments was to characterize these unusual processes using well-established ultrastructural and molecular criteria that differentiate dendrites and axons. These processes were immunoreactive for growth-associated protein-43 (GAP-43), a protein that is normally confined to axons. In contrast, immunoreactivity for a protein that is widely used as a marker for dendrites, microtubule-associated protein (MAP)-2a/b, could not be detected in the unusual distal arborizations. At the electron microscopic level, unusual distal processes contained dense collections of neurofilaments and were frequently myelinated. These molecular and structural characteristics are typical of axons and suggest that the polarity of adult neurons in the mammalian nervous system can be disrupted by axotomy. If this transformation in neuronal polarity is common to other types of neurons, axon-like processes emerging from distal dendrites may represent a mechanism for replacing connections lost due to injury. Alternatively, the connections formed by these axons may be aberrant and therefore maladaptive.

Animals↗