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Biomedical subjects

S Vaidyanathan

Publications and source records attributed to S Vaidyanathan.

At least 55 records · Page 3Linked to original sources

Protocol of a prospective cohort study of the effect of different methods of drainage of neuropathic bladder on occurrence of symptomatic urinary infection, and adverse events related to the urinary drainage system in spinal cord injury patients.

BACKGROUND: To present a protocol of a prospective, cohort study in which four groups of spinal cord injury (SCI) patients will participate. (Patients with indwelling urethral catheter; patients who perform intermittent catheterisation without wearing a penile sheath; patients who perform intermittent catheterisation and wear penile sheath as well; and patients with penile sheath drainage). OBJECTIVES: (1) What is the incidence of symptomatic urinary infection in men with spinal cord injury who use different types of bladder drainage? (2) Which are predisposing factors for the occurrence of symptomatic urinary infection in men with spinal cord injury who practise different methods of bladder drainage? (3) What is the incidence of catheter and urinary drainage system-related adverse events in the four groups of SCI patients? PATIENTS: The criteria for inclusion are as follow: (1) Male patients with neuropathic bladder due to spinal cord injury, who are registered with the Regional Spinal Injuries Centre, Southport, England. (2) Age: 18 years or above. (3) Patients who are willing to give informed consent for participation in the study. (4) Patients willing to be contacted every two weeks by a staff of the spinal unit for 36 months. (5) Patients who are willing to maintain an accurate record of adverse events related to urinary catheter and urinary drainage system and predisposing factors for the occurrence of symptomatic urinary infection. (6) Patients, who are stabilised in a particular method of bladder drainage, and therefore, unlikely to make a permanent change in the method of bladder drainage (e.g. from penile sheath drainage to the use of long-term indwelling catheter) during a foreseeable future. METHODS: The participants will be observed for a period of 36 months. A staff of the spinal injuries unit will contact the participants by telephone every two weeks on a mutually agreed day and time. The information obtained during this standardised telephonic interview conducted once in two weeks will be entered in a database. When a participant develops symptom(s) suggestive of urinary infection, he will undergo urine and blood tests, and imaging studies of the urinary tract. CONCLUSION: This study will provide information regarding the occurrence of symptomatic urinary infection, predisposing factors for development of urinary infection, and adverse events related to urinary catheter and urinary drainage system in SCI patients using different methods of bladder drainage.

Adult↗

Assessment of near-infrared spectral information for rapid monitoring of bioprocess quality.

Access to real-time process information is desirable for consistent and efficient operation of bioprocesses. Near-infrared spectroscopy (NIRS) is known to have potential for providing real-time information on the quantitative levels of important bioprocess variables. However, given the fact that a typical NIR spectrum encompasses information regarding almost all the constituents of the sample matrix, there are few case studies that have investigated the spectral details for applications in bioprocess quality assessment or qualitative bioprocess monitoring. Such information would be invaluable in providing operator-level assistance on the progress of a bioprocess in industrial-scale productions. We investigated this aspect and report the results of our investigation. Near-infrared spectral information derived from scanning unprocessed culture fluid (broth) samples from a complex antibiotic production process was assessed for a data set that incorporated bioprocess variations. Principal component analysis was applied to the spectral data and the loadings and scores of the principal components studied. Changes in the spectral information that corresponded to variations in the bioprocess could be deciphered. Despite the complexity of the matrix, near-infrared spectra of the culture broth are shown to have valuable information that can be deconvoluted with the help of factor analysis techniques such as principal component analysis (PCA). Although complex to interpret, the loadings and score plots are shown to offer potential in process diagnosis that could be of value in the rapid assessment of process quality, and in data assessment prior to quantitative model development.

Anti-Bacterial Agents↗

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↗

Improved pharmacokinetic properties of a polyethylene glycol-modified form of interferon-beta-1a with preserved in vitro bioactivity.

Interferon therapies suffer from a relatively short half-life of the products in circulation. To address this issue we investigated the effects of polyethylene glycol modification (PEGylation) on the pharmacokinetic properties of human interferon (IFN)-beta-1a. PEGylation with a linear 20-kDa PEG targeted at a single site on the N-terminal amine had no deleterious effect on its specific activity in an in vitro antiviral assay. In monkeys, PEG IFN-beta-1a treatment induced neopterin and beta2-microglobulin expression (pharmacodynamic markers of activity). Systemic clearance values in monkeys, rats, and mice decreased, respectively, from 232, 261, and 247 ml/h/kg for the unmodified IFN-beta-1a to 30.5, 19.2, and 18.7 ml/h/kg for the PEGylated form, while volume of distribution values decreased from 427, 280, and 328 ml/kg to 284, 173, and 150 ml/kg. The decreased clearance and volume of distribution resulted in higher serum antiviral activity in the PEG IFN-beta-1a-treated animals. In the rat, a more extensive set of dosing routes was investigated, including intraperitoneal, intratracheal, and oral administration. Bioavailability for the PEG IFN-beta-1a was similar to the unmodified protein for each of the extravascular routes examined. For the intraperitoneal route, bioavailability was almost 100%, whereas for the oral and intratracheal routes absorption was low (<5%). In rats, subcutaneous bioavailability was moderate (28%), whereas in monkeys it was approximately 100%. In all instances an improved pharmacokinetic profile for the PEGylated IFN-beta-1a was observed. These findings demonstrate that PEGylation greatly alters the pharmacokinetic properties of IFN-beta-1a, resulting in an increase in systemic exposure following diverse routes of administration.

Animals↗

At-line monitoring of a submerged filamentous bacterial cultivation using near-infrared spectroscopy.

The use of near infra-red spectroscopy (NIRS) to monitor a submerged filamentous bacterial bioprocess was investigated. An industrial strain of the filamentous bacterium Streptomyces fradiae was cultured in a 12 litre stirred tank reactor (STR) using a complex medium. This mycelial 4 phase (oil, water, gas and solid) system produced highly complex and variable matrices, therefore monitoring such a complex fluid with NIRS represented a considerable challenge. Nevertheless, successful models for four key analytes (methyl oleate, glucose, glutamate and ammonium) were built at-line (rapid off-line) using NIRS. In the present study, the methods used to formulate, select and validate the models for the key analytes are discussed, with particular emphasis on how the model performance can be critically evaluated. Since previous reports on NIRS in monitoring bioprocesses have either involved simpler matrices, or, in filamentous systems, have not discussed how NIRS models can be critically assessed, the emphasis in the present study on providing an insight into the modelling process in such a complex matrix, may be particularly important to the applicability of NIRS to such industrial bioprocesses.

Journal Article↗

Interaction of dexrazoxane with red blood cells and hemoglobin alters pharmacokinetics of doxorubicin.

PURPOSE: The mechanism of the cardioprotective action of dexrazoxane against doxorubicin cardiotoxicity is not fully understood. It has been suggested that its hydrolysis product, ICRF-198, chelates and removes free iron and iron associated with doxorubiciniron complex and, therefore, prevents the formation of free radical, lipid peroxidation and cardiotoxicity. Dexrazoxane is also known to inhibit topoisomerase II, to prevent the inactivation of cytochrome c oxidase by Fe3+ -doxorubicin and to increase the levels of transferrin receptor (trf-rec) mRNA and cellular iron uptake. This sequestration of iron and its effect on cellular iron homeostasis may also contribute to its protective effect against doxorubicin cardiotoxicity. The present project was designed to investigate the interaction of dexrazoxane with hemoglobin and red blood cells and the subsequent effect on the pharmacokinetics and toxicodynamics of doxorubicin. METHODS: In an in vitro investigation the binding of doxorubicin (0.5-25 microg/ml) to red blood cells, erythrocyte ghosts and hemoglobin in the presence of dexrazoxane was evaluated. In an in vivo study female Sprague Dawley rats were pretreated with 100 mg/kg of dexrazoxane by intravenous injection 1 h before the injection of 14C-doxorubicin (specific activity 0.4 microCi/mg, 10 mg/kg). The time-course of doxorubicin associated with blood cells and plasma was evaluated with simultaneous characterization of doxorubicin and its metabolites in the bile and urine. The serum concentration ofendothelin was measured as a biomarker of cardiotoxicity in separate groups of animals. RESULTS: The in vitro data indicated that dexrazoxane inhibited the binding of DOX to red blood cells in a concentration-dependent manner. At 1 microg/ml it reduced the binding of doxorubicin to red blood cells by about 30% and at 100 microg/ml by about 60%. It had no effect on the association of doxorubicin with erythrocyte ghosts. The investigation of binding of doxorubicin to hemoglobin revealed the existence of two distinct binding sites and dexrazoxane reduced the association constant of doxorubicin with the low-affinity and high-capacity class of binding sites significantly. The pharmacokinetic analysis showed that pretreatment with dexrazoxane (100 mg/ kg) reduced the area under plasma concentration-time curve of doxorubicin, its mean residence time and plasma clearance significantly. Similar reductions were also shown with the pharmacokinetic analysis of doxorubicin associated with blood cells. The biliary and urinary elimination of unchanged doxorubicin increased significantly. The pretreatment reduced the serum concentration of endothelin from about 20 ng/ml to about 12 ng/ ml. The per cent of this reduction was proportional to the reduction in the AUC of blood cells. CONCLUSION: The cardioprotective effect of dexrazoxane is due, in part, to its interaction with hemoglobin and red blood cells and this interaction modifies the pharmacokinetics of DOX.

Animals↗

Effect of tamoxifen pretreatment on the pharmacokinetics, metabolism and cardiotoxicity of doxorubicin in female rats.

UNLABELLED: The purpose of this study was to examine the effect of tamoxifen pretreatment on the metabolism and pharmacokinetics of doxorubicin. We tested the hypothesis that the pretreatment would counteract the side effects of doxorubicin and modify the disposition of the drug. The concentration-time profiles of doxorubicin in plasma and blood cells were determined in conjunction with the cumulative amount of renal and hepatobiliary elimination of unchanged drug and metabolites following a 10-day tamoxifen pretreatment at a dose of 1 mg/kg per day. Furthermore, under the same experimental protocol the serum concentration-time profile of endothelin was determined as a biomarker of toxicity. METHODS: Female Sprague Dawley rats (225-275 g). pretreated orally for 10 days with corn oil or tamoxifen in corn oil (1 mg/kg per day), received 14C-doxorubicin (specific activity 0.4 microCi/mg, 10 mg/kg) intravenously. Plasma, blood cells, bile and urine were collected periodically and analyzed for doxorubicin and its metabolites. Four other groups of animals received the same pretreatment and non-labeled doxorubicin. Their serum samples were analyzed for endothelin. Two additional groups were also used to examine the effect of tamoxifen on the in vitro metabolism of doxorubicin by the cytosolic enzyme aldo-keto reductase. RESULTS: Tamoxifen pretreatment reduced the total protein of the cytosolic fraction by 50% and reduced the formation of doxorubicinol both in vitro and in vivo. The pretreatment resulted in a notable increase in the area under plasma and blood cells concentration-time curves of doxorubicin and a significant reduction in mean residence time, apparent volume of distribution and serum endothelin levels. CONCLUSIONS: We attributed the increase in the area under the curves of plasma and blood cells following tamoxifen pretreatment to a reduction in the uptake of doxorubicin by peripheral tissues. This conclusion was consistent with the reduction in the volume of distribution of plasma, mean residence time and higher availability of the parent compound for excretion. An interesting observation was that the increase in concentration of doxorubicin in plasma was not concomitant with an increase in concentration of doxorubicinol. The levels of this toxic metabolite and its corresponding biliary rate constant were reduced by approximately 50%. The results demonstrate that tamoxifen, in addition to being a modulator of P-glycoprotein and counteracting the effects of doxorubicin at the cellular level, also alters the metabolic profile of doxorubicin either by inhibiting the formation of the toxic metabolite doxorubicinol or by reducing the enzyme responsible for the biotransformation. The change in metabolism may well be a contributing factor to reduction of serum endothelin levels.

Animals↗

Dosage of once-daily gentamicin in spinal cord injury patients.

INTRODUCTION: In patients with spinal cord injury (SCI), serum creatinine does not accurately reflect the level of renal function. Therefore, in SCI patients, the dose of potentially nephrotoxic drugs should be adjusted on an individual basis from the estimated creatinine clearance. CASE REPORT: A 41-year-old male with tetraplegia due to cervical spinal cord injury underwent extended pyelolithotomy for staghorn calculus in the right kidney. The blood urea level was 9.9 mmol/l; creatinine was 112 umol/l (reference range: 0-135). We were conscious of this patient's renal disease, and therefore, administered only 3 mg/kg of gentamicin (240 mg) instead of the standard dose of 5 mg/kg body weight. Despite taking this precaution, the gentamicin level measured 22.5 h after the initial dose, was in the potentially toxic range 3.3 mg/l. CONCLUSION: We recommend that even the first dose of gentamicin in the once-daily regimen, which is 5 mg/kg, should be individualised in SCI patients based on age, sex, weight, height, level of spinal cord injury, and renal function.

Adult↗