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Biomedical subjects

G Singh

Publications and source records attributed to G Singh.

At least 109 records · Page 6Linked to original sources

Vaxfectin enhances antigen specific antibody titers and maintains Th1 type immune responses to plasmid DNA immunization.

Antigen specific immune responses were characterized after intramuscular immunization of BALB/c mice with 5 antigen encoding plasmid DNAs (pDNAs) complexed with Vaxfectin, a cationic lipid formulation. Vaxfectin increased IgG titers for all of the antigens with no effect on the CTL responses to the 2 antigens for which CTL assays were performed. Both antigen specific IgG1 and IgG2a were increased, although IgG2a remained greater than IgG1. Furthermore, Vaxfectin had no effect on IFN-gamma or IL-4 production by splenocytes re-stimulated with antigen, suggesting that the Th1 type responses typical of intramuscular pDNA immunization were not altered. Studies with IL-6 -/- mice suggest that the antibody enhancement is IL-6 dependent and results in a correlative increase in antigen specific antibody secreting cells.

Adjuvants, Immunologic↗

Sequence and crystal structure determination of a basic phospholipase A2 from common krait (Bungarus caeruleus) at 2.4 A resolution: identification and characterization of its pharmacological sites.

This is the first phospholipase A2 (PLA2) structure from the family of kraits. The protein was isolated from Bungarus caeruleus (common krait) and the primary sequence was determined using cDNA approach. Three-dimensional structure of this presynaptic neurotoxic PLA2 from group I has been determined by molecular replacement method using the model of PLA2 component of beta2-bungarotoxin (Bungarus multicinctus) and refined using CNS package to a final R-factor of 20.1 % for all the data in resolution range 20.0-2.4 A. The final refined model comprises 897 protein atoms and 77 water molecules. The overall framework of krait phospholipase A2 with three long helices and two short antiparallel beta-strands is extremely similar to those observed for other group I PLA2s. However, the critical parts of PLA2 folding are concerned with its various functional loops. The conformations of these loops determine the efficiency of enzyme action and presence/absence of various pharmacological functions. In the present structure calcium-binding loop is occupied by a sodium ion with a 7-fold co-ordination. The conformation of loop 55-75 in krait PLA2 corresponds to a very high activity of the enzyme. A comparison of its sequence with multimeric PLA2s clearly shows the absence of critical residues such as Tyr3, Trp61 and Phe64, which are involved in the multimerization of PLA2 molecules. The protein shows anticoagulant and neurotoxic activities.

Amino Acid Sequence↗

Quantification of matrix metalloproteinase activity in plasma of patients enrolled in a BAY 12-9566 phase I study.

The expression of matrix metalloproteinases (MMPs) is often associated with invasiveness or grade of tumours. Increased blood levels of MMP proteins, including MMP-1, MMP-2, MMP-3 and MMP-9 have been detected in various types of cancers. With the exception of one study, MMPs in serum and plasma have been determined using ELISA. In the present study we measured the activity of the MMPs found in human plasma samples using gelatin enzymography and fluorimetric degradation assays. We used plasma samples from healthy control subjects and cancer patients enrolled in a dose-finding study for the MMP inhibitor, BAY 12-9566, to assess the activity of MMPs found in plasma and screen for efficacy of the MMP inhibitor. BAY 12-9566 has inhibitory activity toward MMP-2, MMP-3 and MMP-9. Patients with advanced solid tumours were enrolled in our study and plasma was collected on day 1 before dosing and at steady-state of the drug on day 15. Our results show that BAY 12-9566 was effective in lowering the plasma gelatinolytic activity in the group of 29 patients when considering the data obtained from a fluorimetric gelatinase assay. The data obtained from gelatin enzymography, however, did not reach significance. The fluorimetric degradation assay could be a useful tool to screen plasma from cancer patients in other clinical trials assessing MMP inhibitors.

Adult↗

Studies on energetic compounds. Part 16. Chemistry and decomposition mechanisms of 5-nitro-2,4-dihydro-3H-1,2,4-triazole-3-one (NTO).

The present review deals with the chemistry and thermolysis of NTO and plausible decomposition pathways have been described. The decomposition of 5-nitro-2,4-dihydro-3H-1,2,4-triazole-3-one (NTO) induced by X-ray, UV, laser, photochemical irradiation has also been discussed. High-speed photographic studies of the impact responses of NTO are also included. The thermal decomposition of labelled NTO has also been described here. Methods of detection as well as safe disposal of NTO have also been mentioned.

Molecular Structure↗

Long-term morbidity, mortality, and economics of rheumatoid arthritis.

OBJECTIVE: To estimate the morbidity, mortality, and lifetime costs of care for rheumatoid arthritis (RA). METHODS: We developed a Markov model based on the Arthritis, Rheumatism, and Aging Medical Information System Post-Marketing Surveillance Program cohort, involving 4,258 consecutively enrolled RA patients who were followed up for 17,085 patient-years. Markov states of health were based on drug treatment and Health Assessment Questionnaire scores. Costs were based on resource utilization, and utilities were based on visual analog scale-based general health scores. RESULTS: The cohort had a mean age of 57 years, 76.4% were women, and the mean duration of disease was 11.8 years. Compared with a life expectancy of 22.0 years for the general population, this cohort had a life expectancy of 18.6 years and 11.3 quality-adjusted life years. Lifetime direct medical care costs were estimated to be $93,296. Higher costs were associated with higher disability scores. CONCLUSION: A Markov model can be used to estimate lifelong morbidity, mortality, and costs associated with RA, providing a context in which to consider the potential value of new therapies for the disease.

Antirheumatic Agents↗

Assessment of groundwater quality impacts due to use of coal combustion byproducts to control subsidence from underground mines.

Coal combustion byproducts are to be placed in an underground coal mine to control subsidence. The materials were characterized to determine potential groundwater impacts. No problems were found with respect to heavy or toxic metals. Coal combustion byproduct leachates are high in dissolved solids and sulfates. Chloride and boron from fly ash may also leach in initially high concentrations. Because the demonstration site is located beneath deep tight brine-bearing aquifers, no problems are anticipated at the demonstration site.

Air Pollutants↗

Nutritional composition of selected green leafy vegetables, herbs and carrots.

Six green leafy vegetables and herbs - spinach, amaranth, bengal gram, cauliflower, mint, coriander and carrots - were analyzed for moisture, protein, ascorbic acid, beta-carotene, total iron, ionizable iron (as % of total iron) in vitro iron (% of total iron), copper, manganese and zinc. Moisture content of the leaves and carrots varied from 75.1 percent (bengal gram) to 95.4 percent (carrot) and protein from 9.83 percent (carrots) to 30.9 (mint) percent. Ascorbic acid, beta-carotene, total iron and ionizable iron contents were at a maximum in case of bengal gram leaves whereas level of ionizable iron and in vitro iron as a percent of total iron was highest in carrots. Copper, manganese and zinc contents were maximum in spinach.

Amaranthus↗

Compression of femoral vein by the strap of a urine-collecting device in a spinal cord injury patient.

OBJECTIVE: To report an unusual cause of femoral vein compression in a spinal cord injury (SCI) patient. DESIGN: A case report of a SCI patient in whom the strap of a urinal produced compression of femoral vein. Setting Regional Spinal Injuries Centre, Southport, England. SUBJECT: A 65-year old male, who had sustained paraplegia at T-10 level 33 years ago, attended the spinal unit for a routine follow-up intravenous urography (IVU). He was wearing a urinal, which was held tightly over the penis by means of two straps coursing over the inguinal regions. MAIN OUTCOME MEASURES: IVU was performed by injecting 50 ml of Ultravist-300 via a 23-gauge butterfly needle inserted in a vein over the dorsum of the left foot. After completion of the injection, an X-ray of the pelvis was taken to evaluate the right hip. This showed contrast in the vena profunda femoris, circumflex femoral veins and inter-muscular veins with evidence of compression of proximal femoral vein. RESULTS: It was suspected that the strap holding the urinal was causing compression of the femoral vein. Therefore, a venogram was performed 5 days later, when the patient had discarded the urinal and the straps. This showed free flow of contrast through the left femoral and iliac veins. CONCLUSION: Compression of femoral vein by a strap holding the urinal was discovered serendipitously in this patient during a routine follow-up. Physicians and health professionals should bear in mind this rare complication when examining spinal cord injury patients who use this type of urine collecting device, and discuss with them alternative methods for urinary drainage.

Aged↗

Bilateral extracorporeal shock wave lithotripsy in a spinal cord injury patient with a cardiac pacemaker.

OBJECTIVES: To review the precautions to be observed before and during extracorporeal shock wave lithotripsy (ESWL) in spinal cord injury (SCI) patients with a cardiac pacemaker and the safety of bilateral ESWL performed on the same day. DESIGN: A case report of bilateral ESWL in a SCI patient with a permanent cardiac pacemaker. SETTING: The Regional Spinal Injuries Centre, Southport, the Lithotripsy Unit, the Royal Liverpool University Hospitals NHS Trust, Liverpool, and the Department of Cardiology, Manchester Royal Infirmary, Manchester, UK. SUBJECT: A 43-year-old male sustained a T-4 fracture and developed paraplegia with a sensory level at T-2. During the post-injury period, he developed episodes of asystole requiring implantation of a dual chamber (DDD) permanent pacemaker. Twenty-one months later, he developed a right ureteric calculus with hydronephrosis. A radio-opaque shadow was seen in the left kidney with no hydronephrosis. During right ureteric stenting, the ureteric stone was pushed into the renal pelvis. 1,500 shock waves were delivered to this stone on the right side, followed by ESWL to the left intra-renal stone with 1250 shock waves. RESULTS: The patient tolerated ESWL to both kidneys. The pacemaker was reprogrammed to a single chamber ventricular pacing mode at 30 beats per minute with a reduced sensitivity during lithotripsy. There were no untoward cardiac events during or after lithotripsy. The serum creatinine was 45 micromol/l before lithotripsy and 44 micromol/l two weeks after ESWL. CONCLUSION: SCI patients with a cardiac pacemaker may be able to undergo extracorporeal shock wave lithotripsy following temporary reprogramming of the pacemaker. Bilateral, simultaneous ESWL is safe in the vast majority of patients provided that there is no risk of simultaneous ureteric obstruction by stone fragments. However, it should be remembered that a decrease in renal function could occur following bilateral ESWL of renal calculi.

Adult↗

Occlusion of left common iliac vein by a distended urinary bladder in a male with paraplegia due to spinal cord injury.

STUDY DESIGN: A report of a male subject who sustained paraplegia at T-5 level due to spinal cord injury (SCI) 18 years ago, and in whom, occlusion of the left common iliac vein by a distended bladder was detected during a routine follow-up. OBJECTIVES: To illustrate a rare complication of chronic distension of the urinary bladder viz occlusion of the left common iliac vein, which persisted even after providing adequate bladder drainage by intermittent catheterisation. SETTING: Regional Spinal Injuries Centre, Southport, UK. METHODS: As part of a routine follow-up, we performed intravenous urography by injecting 50 ml of Ultravist 300 in a vein over the dorsum of the left foot. Opacification of collateral veins in the pelvis was seen in the 5- and 10-min films, which suggested iliac venous occlusion. In order to confirm the diagnosis, contrast was injected intravenously in the left foot and venography was performed. RESULTS: Venography revealed a distended left common iliac vein with contrast flowing into the right internal iliac vein through collateral veins in the pelvis; the right common iliac vein and inferior vena cava were patent. Duplex Doppler sonography showed compression of left common iliac vein by the posterior wall of a distended bladder with absence of blood flow through the compressed segment. Computerised tomography (CT) confirmed the diagnosis of extrinsic compression of the left common iliac vein against the promontory of sacrum by a distended bladder. CT excluded other causes for iliac vein occlusion. CONCLUSION: In a male subject with SCI, chronic bladder distension produced occlusion of the left common iliac vein. Health professionals caring for individuals with SCI should be aware that long-standing bladder distension could cause pressure effects upon adjacent structures in the pelvis.

Accidental Falls↗

Blunt trauma to scrotum in men with spinal cord injury after they had completed rehabilitation in a spinal unit.

STUDY DESIGN: A report of three men with spinal cord injury (SCI) who sustained blunt trauma to scrotum after they had completed rehabilitation in the spinal unit. OBJECTIVES: To raise awareness amongst health professionals regarding: (1) mechanism of scrotal trauma in men with SCI (2) need for prompt assessment of scrotal injury (3) measures to be taken by men with SCI and their carers to prevent injury to the scrotum. SETTING: Regional Spinal Injuries Centre, Southport, England. CASE REPORTS: (1) A 31-year-old with C-6 tetraplegia sustained traumatic haematocele as he squashed his right testis while he jumped on to a toilet seat in a hurry for bowel movement. (2) A 28-year-old male with T-7 paraplegia sat on his left testis while transferring on to a car seat. (3) A boxer dog jumped on to the scrotum of a 40-year-old male with T-8 paraplegia, while he was lying on his bed. CONCLUSIONS: Men with SCI are at high risk of sustaining trauma to scrotum during transfers. The scrotum may be squashed by the weight of the body during transfers, or the scrotum may be trapped between the thighs or under the torso. Men with SCI or their carers should check after each transfer that the scrotum is not trapped between the thighs or under the torso. The health professionals should encourage men with SCI to update their transfer skills at regular intervals in order to prevent trauma to the scrotum during transfers. Blunt trauma to scrotum requires prompt evaluation by ultrasonography so that appropriate treatment can be instituted without delay.

Accidents, Traffic↗

Community-care waiting list for persons with spinal cord injury.

OBJECTIVES: To disseminate the concept of community care waiting lists for spinal cord injury (SCI) patients with particular reference to carer support for management of neuropathic bladder by a regime of intermittent catheterisation. METHODOLOGY: The surgical waiting list focuses only on operative procedures, and ignores the wider requirements for ensuring satisfactory rehabilitation of people with spinal cord injury in the community. A community-care waiting list for individuals with spinal cord injury should include the following aspects of community care: (1) Home adaptation; (2) Provision of appropriate mobility needs (including wheelchair and cushion); (3) Equipment for comfortable living (including provision of hoist, pressure relieving mattress); (4) Psychological support for spinal cord injury patients and their partners; (5) Nursing home or residential care placement where appropriate; (6) Carer support for global management of complex needs associated with spinal cord injury (eg neuropathic bladder and bowel). RESULTS: Whereas full physical adaptation of the home can wait for some time after discharge, carer support for intermittent catheterisation is required from the first day after discharge from a spinal unit. Lack of such support means that some SCI patients are discharged with long-term indwelling urinary catheters, even though clean intermittent catheterisation is known to be the safest regime for managing the neuropathic bladder. Therefore, the absence of a community care waiting list means that best practice cannot be achieved for some tetraplegic subjects. CONCLUSION: We believe that a community care waiting list for bladder management will help to provide optimum care for neuropathic bladder and, hopefully, reduce the complications related to long-term indwelling catheters in spinal cord injury patients.

Adult↗

Doctor-patient communication: do people with spinal cord injury wish to receive written information about their medical condition from the physicians after an outpatient visit or after a readmission in the spinal unit?

STUDY DESIGN: A survey of spinal cord injury patients attending a follow-up clinic in a Regional Spinal Injuries Centre. OBJECTIVES: To investigate whether spinal cord injury patients wish to receive written information about any changes in their medical condition after an outpatient visit or, following readmission in a spinal unit. SETTING: Regional Spinal Injuries Centre, Southport, United Kingdom. METHODS: A questionnaire was developed to assess the following: (1) Whether spinal cord injury patients wished to receive written information about changes in their medical condition after an outpatient visit or following readmission in a spinal unit; and (2) Whether provision of such written information would cause needless anxiety to patients and/or their relatives/carers. RESULTS: A total of 128 adults with spinal cord injury filled in this questionnaire. One hundred and six persons (83%) wished to receive written information about any changes in their medical condition after an outpatient visit, whereas eight (6%) felt that provision of such written information was not required. 115 individuals with spinal cord injury (90%) preferred to receive a copy of the MRI scan report, with interpretation of the findings, while 11 (9%) would be happy not to receive such information. 115 persons with spinal cord injury (90%) felt that written information about their medical condition would be valuable for showing to a locum General Practitioner (GP), if necessary, who may not be acquainted with their medical status. Only eight (6%) did not perceive a need for written information to appraise a locum GP. One hundred and twenty-two persons with spinal cord injury (95%) did not feel that provision of written information would cause needless anxiety to them; only four (3%) felt the other way. One hundred and nineteen (93%) individuals with spinal cord injury wished to receive written information about changes in their medical condition after a readmission to the spinal unit, while six (5%) did not wish to receive such information. CONCLUSION: Although the vast majority of people with spinal cord injury reported they wished to receive written information, a small proportion of patients did not wish to receive such information. Acceptance of written information is not universal and clinicians must ensure that provision of written information to people with spinal cord injury should be tailored to the needs of individual patients.

Adult↗

Lumbrical muscle with an additional origin in the forearm.

BACKGROUND: Although variations in the attachments of the lumbrical muscles have been commonly reported, these have been seen mainly in the Caucasian population. The present study is the first reported case of such an anomaly in a Chinese cadaver in the literature. METHODS: The upper extremities of 26 Chinese (23 male and three female) cadavers were examined. RESULTS: Dissection of a male 66-year-old Chinese cadaver has revealed the rare case of a bipennate first lumbrical muscle with an additional origin extending from the distal part of the forearm. Its first origin arose from the flexor digitorum profundus in the hand distal to the flexor retinaculum. The intrinsic muscles in the hands of all the other cadavers were normal. CONCLUSIONS: An anomalous origin of the lumbrical from muscles in the forearm has the potential to cause compression of the median nerve in the carpal tunnel.

Aged↗

Sources of neuronal material for implantation.

The adult brain is an organ that does not have the natural ability to replace cells that have been lost through damage. Possible human interventions to rectify this situation include transplanting either developing neural tissue into the damaged host brain or transplantation of neural stem cells (cells that have the capacity to proliferate into neural cells and self-replicate) into the damaged area. Fetal or embryonic stem cells can be extracted and differentiated in vitro into the specific desired progeny (e.g. neurons). The neuronal stem cells themselves can be extracted from fetuses and multiplied in culture and then transplanted into the damaged brain. There is the possibility of dedifferentiation, in which cells of one type can be converted into a different cell type; for example, a differentiated blood cell could be de-differentiated back to its own hemopoietic stem cell and that stem cell could be converted into a neuronal stem cell which could then be differentiated into a neuron. It is probable that methods of generating large numbers of committed stem cells to treat conditions such as Alzheimer's disease will soon be increasingly common.

Animals↗