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Biomedical subjects

S S Mehta

Publications and source records attributed to S S Mehta.

At least 19 recordsLinked to original sources

A randomized, parallel study of the safety and efficacy of 45 mg primaquine versus 75 mg bulaquine as gametocytocidal agents in adults with blood schizonticide-responsive uncomplicated falciparum malaria [ISCRTN50134587].

BACKGROUND: The WHO recommends that adults with uncomplicated P. falciparum successfully treated with a blood schizonticide receive a single dose of primaquine (PQ) 45 mg as a gametocytocidal agent. An earlier pilot study suggested that 75 mg of bulaquine (BQ), of which PQ is a major metabolite, may be a useful alternate to PQ. METHODS: In a randomized, partial blind study, 90 hospitalized adults with Plasmodium falciparum malaria that was blood schizonticide-responsive and a gametocytemia of > 55/microl within 3 days of diagnosis were randomized to receive single doses of either PQ 45 mg or BQ 75 mg on day 4. We assessed gametocytemia on days 8, 15, 22 and 29 and gametocyte viability as determined by exflagellation (2 degrees end point) on day 8. RESULTS: On day 8, 20/31 (65%) primaquine recipients versus 19/59 (32%) bulaquine recipients showed persistence of gametocytes (P = 0.002). At day 15 and beyond, all patients were gametocyte free. On day 8, 16/31 PQ and 7/59 BQ volunteers showed gametocyte viability (p = 0.000065). CONCLUSION: BQ is a safe, useful alternate to PQ as a Plasmodium falciparum gametocytocidal agent and may clear gametocytemia faster than PQ.

Adolescent↗

Memokath stents for the treatment of detrusor sphincter dyssynergia (DSD) in men with spinal cord injury: the Princess Royal Spinal Injuries Unit 10-year experience.

STUDY DESIGN: Medical records review. OBJECTIVE: To assess the effectiveness of the Memokath (Engineers and Doctors A/S, Denmark) thermosensitive stent as a 'nondestructive' means of reducing bladder outlet resistance by treating detrusor sphincter dyssynergia (DSD) of neurogenic bladder dysfunction associated with spinal cord injury. SETTING: Spinal Injuries Unit, Sheffield, England. METHODS: A medical records review was performed to examine our experience of Memokaths over the last 10 years. During this time, 29 patients with spinal cord injury (17 tetraplegic and 12 paraplegic) underwent stenting of the external urethral sphincter either for prevention of dysreflexic symptoms, high residual urine volumes and subsequent urinary tract infection (UTI) or for protection of the upper tracts. RESULTS: A total of 33 stents were inserted into 29 men (25-77 years) with suprasacral spinal cord injury. Initial results showed that the Memokath was effective in almost all for relief of dysreflexic symptoms and elimination of DSD on pressure flow urodynamics. However, to date, 30 of the 33 stents have been removed. The overall mean working life of the Memokath was 21 months. Four stents were removed electively and 23 for complications, which included stent migration (seven) and blockage (14). Single-ended stents were more prone to migration, which was rare after 1 year (1-13 months, median 3 months, mean 5.5 months). Stent blockage by encrustation or prostatic ingrowth did not occur before 12 months (12-45 months, median 30, mean 27.9 months). CONCLUSIONS: In selected patients, temporary, thermo-expandable (Memokath) stents are effective in the treatment of DSD. The 'working life' of a Memokath stent is 21 months; however, complications do occur which may necessitate removal. Our overall experience with Memokath stents was disappointing. In future, Memokath stents will only be inserted after careful consideration in patients with prior 'failed' transurethral sphincterotomy or with caution in patients suitable for reconstructive surgery.

Adult↗

Three dimensional ultrasound and prostate cancer.

Three-dimensional ultrasound (3-D US) is a non-invasive method of producing whole volume images of solid structures. Early work on prostate imaging identified several advantages over 2-D imaging with a good ability to detect intraprostatic lesions. Several 3-D transrectal ultrasound (3-D TRUS) systems are now available for prostate imaging. Initial work using gray scale ultrasound appears promising with reported overall staging accuracies of up to 94%. These results were favourable when compared to other modalities for local staging of prostate cancer. Several adjuncts to 3-D gray scale TRUS have been investigated. A greater sensitivity for cancer detection has been achieved with the addition of power colour Doppler and contrast agents. Further clinical applications for 3-D TRUS include assessing placement of brachytherapy seeds and for cyroablation techniques. Computer enhancement with image registration has shown that 3-D US images can be manipulated to derive more information. Although the results of gray scale imaging alone or with adjuncts and post processing appear promising, these techniques remain largely experimental.

Equipment Design↗

Bioreductive metabolism of mitomycin C in EMT6 mouse mammary tumor cells: cytotoxic and non-cytotoxic pathways, leading to different types of DNA adducts. The effect of dicumarol.

The six DNA adducts formed in EMT6 mouse mammary tumor cells upon treatment with mitomycin C (MC) fall into two groups: (1) four guanine adducts of MC and (2) two guanine adducts derived from 2,7-diaminomitosene (2,7-DAM), the major reductive metabolite of MC. The two groups of adducts were proposed to originate from two pathways arising from reductive activation of MC: (a) direct alkylation of DNA and (b) formation of 2,7-DAM, which then alkylates DNA. The aim of this study was to test the validity of this proposal and to evaluate the significance of alkylation of DNA by 2,7-DAM. Treatment of the cells with 2,7-DAM itself yielded the same 2,7-DAM-guanine adducts as treatment with MC; however, 2,7-DAM was approximately 100-fold less cytotoxic than MC. The uptake and efflux of 2,7-DAM by EMT6 cells was comparable to that of MC, but 2,7-DAM alkylated DNA with higher efficiency than MC. These results validate the two proposed pathways and show that formation of 2,7-DAM-DNA adducts in MC-treated cells represents a relatively non-toxic pathway of reductive metabolism of MC. A selective stimulatory effect of dicumarol (DIC) on 2,7-DAM-DNA adduct formation in EMT6 cells treated with MC was also investigated. DIC had no effect on alkylation by MC in cell-free systems, nor did it have significant effects on adduct formation or cell survival for cells treated with 2,7-DAM. It is proposed that in the cell DIC stimulates a reductase enzyme located at subcellular sites where the activated MC species has no direct access to DNA and therefore is diverted into the non-cytotoxic pathway, which leads to the formation of 2,7-DAM and its adducts.

Animals↗

Bone material ultrasound velocity is predictive of whole bone strength.

In humans, bone strength is assessed indirectly by the noninvasive measurement of structure or mass. Recent clinical application of an ultrasonic critical-angle reflectometry technique (UCR) has demonstrated the measurement of the regional and directional distribution of mechanical stiffness. This study investigates the specific question: are these measurements of a local material level property predictive of the strength of whole bone? Maximum values of pressure wave velocity and breaking strength were recorded at two locations (midshaft and base of neck) on rat femurs from growing rats. The results demonstrate a strong empirical relationship between material-level ultrasound (US) velocity and whole bone mechanical strength. However, the US velocity at a specific bone site can be used to assess bone strength at that site only, explaining discrepancies in other published studies that negate a relationship between strength and US velocity. The results indicate an important role for US velocity measurement in clinical evaluation of bone health.

Animals↗

Determining an episode of care using claims data. Diabetic foot ulcer.

OBJECTIVE: Amid changes in the organization and financing of health care, health care decision makers are increasingly interested in episodes of care. We sought to determine an episode of care for diabetic foot ulcer using an administrative claims database. RESEARCH DESIGN AND METHODS: We used 1993-1995 claims data to assess resource utilization for privately insured patients with diabetic foot ulcers. Over a 26-week period, we determined the episode length by comparing differences in average daily charges and proportion of patients with charges before and after foot ulcer diagnosis. All 13 weeks before diagnosis were used to calculate baseline values. Significance was determined by CIs, which were calculated by a nonparametric bootstrap technique. Costs associated with the episode were also calculated. A sensitivity analysis using weeks with highest and lowest values as baseline was also conducted. RESULTS: Based on average daily charges, the episode of care for diabetic foot ulcer was 5 weeks. Using proportion of patients with charges, the episode was longer than 13 weeks. The cost for an episode of care ranged from $900 to $2,600. In the sensitivity analyses, episodes of care ranged from 1 to 13 weeks. CONCLUSIONS: Episodes of care can be defined by the period beginning with increased resource consumption and ending when resource consumption returns to baseline levels. With the growth of managed care and disease management programs, episode-of-care analysis may have an increasingly important role in health care provision and delivery.

Costs and Cost Analysis↗

Bone material elasticity in a murine model of osteogenesis imperfecta.

To investigate the source of bone brittleness in the disease osteogenesis imperfecta (OI), biomechanical properties have been measured in the femurs from a homozygous (oim/oim) mutant mouse model of OI, its heterozygous littermates, and wild-type animals. The novel technique of ultrasound critical-angle reflectometry (UCR) was used to determine bone material elasticity matrix from measurements of the pressure and shear wave velocity at different orientations about selected points of the bone specimens. This nondestructive method is the only available means for obtaining measurements of this nature from a single surface. The ultrasound pressure wave velocity showed an increased isotropy in the homozygous compared to the wild-type specimens. This was reflected in a significant decrease in the principal elastic modulus measured along the length of the oim/oim bones (E33) while the modulus along the width (E11) did not change significantly, compared to wild-type specimens. The Poisson's ratio, v12, also had a significantly increased value in oim/oim bones. Measurements of these parameters in heterozygous animals generally fell between those from homozygous and control mice. The differences in the elasticity components in oim/oim bones indicate an altered stress distribution and a modified elastic response to loads, compared to normal bone.

Animals↗

Treatment of hypertension in patients with comorbidities: results from the study of hypertensive prescribing practices (SHyPP).

Approximately 50 million people have hypertension. Many agents with differing efficacy, side effects, dosing schedules, and costs are available to treat hypertension. Joint National Committee (JNC) guidelines attempt to simplify this decision by recommending specific agents based on special considerations such as comorbidities. The objective of this study was to survey primary care physicians' antihypertensive prescribing practices and their treatment recommendations for patients with comorbidities. A direct mail survey was sent to a national random sample of 500 office-based primary care internists, family practitioners, and general practitioners. There were no significant differences between initial treatment recommendations at the time of the survey and those recommended before the survey. However, there were several therapeutic classes whose reported utilization for specific comorbidities significantly changed over 18 months. Angiotensin converting enzyme (ACE) inhibitors reportedly increased in patients with congestive heart failure and diabetes. In addition, the reported use of selective beta-blockers increased for patients with a history of myocardial infarction. Physicians did not follow JNC recommendations when initiating treatment in black patients, older patients, or those with mild renal failure. Younger physicians were more likely than older physicians to select agents consistent with guideline recommendations. Physicians did not adhere to JNC guidelines when initiating treatment in patients with comorbidities; however, more physicians are prescribing recommended agents today as compared to 18 months ago. Younger physicians were more likely to prescribe agents consistent with the guidelines. More direct efforts are needed to ensure awareness and compliance with these guidelines.

Adrenergic beta-Antagonists↗

Bone elasticity and ultrasound velocity are affected by subtle changes in the organic matrix.

The mechanical competence of bone can be studied through the measurement of the components of its material elasticity, a property which can vary both in magnitude and in dependence upon orientation (anisotropy). While it is known that the elasticity is largely determined by the mineral constituents of the bone matrix, it is nonetheless clear that it must be also dependent upon the remaining constituents of bone material. In this work, the influence of organic components on the elasticity is explored by altering specific constituents of the bone matrix to varying degrees. This study addresses two questions: first, are the resulting changes in elasticity strongly or weakly dependent upon direction, and second, are they substantially dependent upon the nature and magnitude of the induced matrix alteration? To answer these questions, we performed different chemical manipulations of the bone matrix and measured the changes in elasticity and velocity using the technique of ultrasound critical angle reflectometry. Altering the properties of the organic matrix resulted in substantial and complex changes in the elasticity of bone. The observed changes were strongly dependent upon direction, could not be explained by changes in density alone, and varied strongly with the specific chemical treatment of the matrix. Immersion in urea selectively affected protein components of the organic matrix and resulted in reversible changes in velocity and elasticity, while removal of collagen caused anisotropic decreases and removal of all organic matter caused a collapse of all components of the elasticity. In conclusion, this study confirms that the organic matrix exerts a profound influence on the elasticity and indicates that the measurement of elastic properties at multiple directions is necessary in the assessment of bone mechanical competence.

Animals↗

Analysis of cooked muscle meats for heterocyclic aromatic amine carcinogens.

A number of related heterocyclic amines that are mutagenic in bacterial test systems and carcinogenic in animals are formed during the cooking of food. The most commonly reported and abundant compounds are PhIP, MeIQx, DiMeIQx, IQ and A alpha C. Using analysis by solid-phase extraction and HPLC, amounts found in foods range from less than one ng/g for products from fast-food restaurants, up to 14 ng/g in commercially cooked products and over 300 ng/g for well done flame-grilled chicken breast meat. Interestingly, marinating meat for 4 h greatly reduces the amount of PhIP produced during cooking, but not MeIQx. Comparing mutagenic activity in meat samples to the mutagenic activity accounted for by the known heterocyclic amines shows that most samples have activity that cannot be accounted for by the aromatic amines we can currently identify. This suggests that additional compounds are present in these foods and need to be investigated, particularly those grilled over open flames.

Animals↗

Strategic options for brand-name prescription drugs when patents expire.

Pharmaceutical companies face a very hostile competitive environment from generic drugs once the patents on their brand name drugs expire. Depending on the country, such patents usually last 10-15 years but no sooner do the patents expire then copies of off-patent brand name drugs, called generics, are introduced, generally by smaller-size and lesser known companies, at significantly lower prices. As health care costs escalate all over the world, efforts to control medication costs have created a major market for generic prescription drugs, particularly in government funded hospitals and in dispensing general practitioner markets of the Asia Pacific and the third world. The world market for generics is estimated at US$20 billion, doubling in only five years and capturing over 30% of the market share. Because of adverse effects on sales and profitability due to the launching of generics, most research based companies that produce original brand-name patented drugs are forced to take counter measures to overcome this problem, particularly when R&D costs for new patents are skyrocketing. This paper develops a brief perspective on this problem and then examines the experiences of many multinational companies in the Singapore market in dealing with the problem. While several different approaches are identified, only one company experience appeared to work successfully and this is discussed in relative detail.

Commerce↗

Percutaneous transluminal excimer laser coronary angioplasty. Clinical report of six cases.

Six patients with 95% to 100% occluded atherosclerotic lesions underwent percutaneous transluminal excimer laser coronary angioplasty (PTELCA). Among them, 5 were male and 1 was female; their age ranged from 28 to 66 years. Four patients had LAD stenosis and 2 LCX lesions. Acute angiographic and clinical success was achieved in all patients but one, with a success rate of 83.3%. It was demonstrated that PTELCA is a safe and effective therapy for selected patients with coronary artery disease.

Adult↗

Intracoronary stent implantation via the brachial approach: a technique to reduce vascular bleeding complications.

To reduce the incidence of vascular complications of intracoronary stent implantation, we used the brachial approach. We attempted implantation of the Palmaz-Schatz stent via the brachial artery approach at 10 lesions in 9 patients. Stent delivery was successful at 8 lesions. Balloon angioplasty was successfully performed in the 2 failed cases, 1 of whom required surgical repair of the brachial artery. Intravenous anticoagulation was uninterrupted from the time of stent placement until therapeutic prothrombin times from oral warfarin therapy were obtained. Neither acute nor long-term major bleeding occurred in the 9 patients. There were no embolic events, myocardial infarctions, or deaths. One subacute thrombosis occurred, and the patient underwent bypass surgery. To evaluate the risks and benefits of the brachial approach, we compared these 9 patients with 41 who had stent placement by the femoral approach during the same period. Lesion characteristics were similar in these 2 groups. There were no significant differences in the success rate or angiographic outcome between the 2 groups. Seven (17%) patients in the femoral group had vascular access complications requiring surgery, compared with 1 (11%) in the brachial group. No patient in the brachial group required transfusion, compared with all 7 of the patients who had femoral vascular complications. The potential reduction in bleeding complications makes the brachial approach to stent implantation attractive in selected patients.

Aged↗

Palmaz-Schatz stent implantation in stenosed saphenous vein grafts: clinical and angiographic follow-up.

Balloon-expandable stents may reduce the restenosis rate following coronary angioplasty. To evaluate this potential in saphenous vein grafts, 26 patients with 30 discrete stenoses underwent conventional balloon dilation and successful Palmaz-Schatz stent implantation as part of a multicenter trial. All patients had resolution of their angina following the procedure. In a mean 5-month follow-up period, 14 patients (54%, 16 lesions) had repeat arteriography; two patients (14%) developed recurrent ischemia ascribed to their venous grafts from in-stent restenosis (2 of 16 lesions, 13%). Two asymptomatic patients (8%) died: one from cardiac arrest (stent patent) and one from stroke (no autopsy). The clinical recurrence rate (cardiac death, myocardial infarction, bypass surgery, repeat angioplasty, or symptom recurrence) was 15%. These preliminary results show trends toward an improved primary success rate with combined vein graft angioplasty/stenting and a lower restenosis rate in stented saphenous vein grafts, but continuing follow-up will be needed to verify these observations.

Aged↗

Holmium laser angioplasty after failed coronary balloon dilation: use of a new solid-state, infrared laser system.

A new solid-state laser system was used in a case of saphenous vein graft occlusion untreatable by standard very low-profile balloon angioplasty. The 2100 nm infrared pulsed thulium/holmium: YAG laser successfully recanalized an obtuse marginal bypass graft without complications. The holmium laser has several advantages over excimer systems and may prove an effective adjunct or alternative to coronary balloon angioplasty.

Aged↗