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Biomedical subjects

M Patel

Publications and source records attributed to M Patel.

At least 145 records · Page 8Linked to original sources

Ultrasonography of the rotator cuff. A comparison of ultrasonographic and arthroscopic findings in one hundred consecutive cases.

BACKGROUND: There has been limited acceptance of shoulder ultrasonography by orthopaedic surgeons in the United States. The purpose of this retrospective study was to determine the diagnostic performance of high-resolution ultrasonography compared with arthroscopic examination for the detection and characterization of rotator cuff tears. METHODS: One hundred consecutive shoulders in ninety-eight patients with shoulder pain who had undergone preoperative ultrasonography and subsequent arthroscopy were identified. The arthroscopic diagnosis was a full-thickness rotator cuff tear in sixty-five shoulders, a partial-thickness tear in fifteen, rotator cuff tendinitis in twelve, frozen shoulder in four, arthrosis of the acromioclavicular joint in two, and a superior labral tear and calcific bursitis in one shoulder each. All ultrasonographic reports were reviewed for the presence or absence of a rotator cuff tear and a biceps tendon rupture or dislocation. All arthroscopic examinations were performed according to a standardized operative procedure. The size and extent of the tear and the status of the biceps tendon were recorded for all shoulders. The findings on ultrasonography and arthroscopy then were compared for each parameter. RESULTS: Ultrasonography correctly identified all sixty-five full-thickness rotator cuff tears (a sensitivity of 100 percent). There were seventeen true-negative and three false-positive ultrasonograms (a specificity of 85 percent). The overall accuracy was 96 percent. The size of the tear on transverse measurement was correctly predicted in 86 percent of the shoulders with a full-thickness tear. Ultrasonography detected a tear in ten of fifteen shoulders with a partial-thickness tear that was diagnosed on arthroscopy. Five of six dislocations and seven of eleven ruptures of the biceps tendon were identified correctly. CONCLUSIONS: Ultrasonography was highly accurate for detecting full-thickness rotator cuff tears, characterizing their extent, and visualizing dislocations of the biceps tendon. It was less sensitive for detecting partial-thickness rotator cuff tears and ruptures of the biceps tendon.

Arthroscopy↗

Distance learning in the public health workplace.

The Master of Applied Epidemiology (MAE) Program implemented in Canberra to produce public health practitioners with specified competencies in the control of communicable diseases. Twenty one of the 24 months of training is distance learning defined as, 'where the learner is physically remote from the training institution'. During this time the trainees are in supervised employment in Public Health centres across the country. Here they learn directly from first hand experiences in the work place. They return to Canberra for short, intensive periods of interactive sessions with their peers and supervisors. Lessons learnt from conducting this program are discussed in this article. They include: all trainees are not suited to this form of training; the quality of support from the field supervisors is highly variable and their role in modelling crucial to the trainees performance; demands on the academic staff is high; and the frequency of contact between trainee and academic supervisor varies considerably. To date this program has made major contributions by enhancing communicable disease surveillance and control but it demands intensive resources to sustain, quality training, and support. This model of distance learning can be adapted in the Pacific both for graduate degree courses and also for continuing education for all levels of health professionals.

Adult↗

Service-oriented training in public health: a model for enhancing public health surveillance in the Pacific.

There is a need for a coordinated, sustainable, in-service, training programme in surveillance and other public health activities. This should be available for all levels of health personal throughout the Pacific. The model advocates continuing education and in-service training that immediately and directly enhances surveillance. Specific educational objectives for surveillance should be based on the needs of the work environment while the graduate degree training should include broader objectives integrated with established public health training courses. It is suggested that the Secretariat of the Pacific community (SPC) should provide the leadership by establishing a Centre for Coordinating Service-oriented Training in Surveillance and invite the University of PNG and the Fiji School of Medicine to incorporate training modules in surveillance into their degree programmes. Field support should be provided through the senior public health practitioners based in public health units and in health agencies throughout the region.

Humans↗

Discovery and structure-activity relationships of imidazole-containing tetrahydrobenzodiazepine inhibitors of farnesyltransferase.

2,3,4,5-Tetrahydro-1-(imidazol-4-ylalkyl)-1,4-benzodiazepines were found to be potent inhibitors of farnesyltransferase (FT). A hydrophobic substituent at the 4-position of the benzodiazepine, linked via a hydrogen bond acceptor, was important to enzyme inhibitory activity. An aryl ring at position 7 or a hydrophobic group linked to the 8-position through an amide, carbamate, or urea linkage was also important for potent inhibition. 2,3,4, 5-Tetrahydro-1-(1H-imidazol-4-ylmethyl)-7-(4-pyridinyl)-4-[2-(t rifluo romethoxy)benzoyl]-1H-1,4-benzodiazepine (36), with an FT IC(50) value of 24 nM, produced 85% phenotypic reversion of Ras transformed NIH 3T3 cells at 1.25 microM and had an EC(50) of 160 nM for inhibition of anchorage-independent growth in soft agar of H-Ras transformed Rat-1 cells. Selected analogues demonstrated ip antitumor activity against an ip Rat-1 tumor in mice.

3T3 Cells↗

A mechanism of paraquat toxicity involving nitric oxide synthase.

Paraquat (PQ) is a well described pneumotoxicant that produces toxicity by redox cycling with cellular diaphorases, thereby elevating intracellular levels of superoxide (O-(2)). NO synthase (NOS) has been shown to participate in PQ-induced lung injury. Current theory holds that NO reacts with O-(2) generated by PQ to produce the toxin peroxynitrite. We asked whether NOS might alternatively function as a PQ diaphorase and reexamined the question of whether NO/O-(2) reactions were toxic or protective. Here, we show that: (i) neuronal NOS has PQ diaphorase activity that inversely correlates with NO formation; (ii) PQ-induced endothelial cell toxicity is attenuated by inhibitors of NOS that prevent NADPH oxidation, but is not attenuated by those that do not; (iii) PQ inhibits endothelium-derived, but not NO-induced, relaxations of aortic rings; and (iv) PQ-induced cytotoxicity is potentiated in cytokine-activated macrophages in a manner that correlates with its ability to block NO formation. These data indicate that NOS is a PQ diaphorase and that toxicity of such redox-active compounds involves a loss of NO-related activity.

Animals↗

Synthesis and evaluation of analogs of Efavirenz (SUSTIVA) as HIV-1 reverse transcriptase inhibitors.

Efavirenz (SUSTIVA) is a potent non-nucleoside reverse transcriptase inhibitor. Due to the observation of breakthrough mutations of the reverse transcriptase enzyme during Efavirenz therapy, we sought to develop an optimized second generation series. To that end, SAR of the substituents on the aromatic ring was undertaken and the results are summarized here. The 5,6-difluoro (4f) and the 6-methoxy (4m) substituted benzoxazinones were determined to be equipotent, and as a result such substitution patterns will be incorporated in second generation scaffolds.

Alkynes↗

Isolation and structure of SCH 351633: a novel hepatitis C virus (HCV) NS3 protease inhibitor from the fungus Penicillium griseofulvum.

A new hepatitis C virus (HCV) protease inhibitor designated as Sch 351633 (1) was isolated from the fungus, Penicillium griseofulvum. Structure elucidation of 1 was accomplished by analysis of spectroscopic data, which determined compound 1 to be a bicyclic hemiketal lactone. Compound 1 exhibited inhibitory activity in the HCV protease assay with an IC50 value of 3.8 microg/mL.

Antiviral Agents↗

Mitochondrial disease in superoxide dismutase 2 mutant mice.

Oxidative stress has been implicated in many diseases. The chief source of reactive oxygen species within the cell is the mitochondrion. We have characterized a variety of the biochemical and metabolic effects of inactivation of the mouse gene for the mitochondrial superoxide dismutase (CD1-Sod2(tm1Cje)). The Sod2 mutant mice exhibit a tissue-specific inhibition of the respiratory chain enzymes NADH-dehydrogenase (complex I) and succinate dehydrogenase (complex II), inactivation of the tricarboxylic acid cycle enzyme aconitase, development of a urine organic aciduria in conjunction with a partial defect in 3-hydroxy-3-methylglutaryl-CoA lyase, and accumulation of oxidative DNA damage. These results indicate that the increase in mitochondrial reactive oxygen species can result in biochemical aberrations with features reminiscent of mitochondrial myopathy, Friedreich ataxia, and 3-hydroxy-3-methylglutaryl-CoA lyase deficiency.

Aconitate Hydratase↗

Developmental intervention for preterm infants diagnosed with periventricular leukomalacia.

Preterm infants with periventricular leukomalacia (PVL) were evaluated to determine whether multi-sensory stimulation is safe and to assess whether it improved neurobehavior and neurodevelopment. Thirty preterm infants with documented PVL were randomly assigned to control (n= 15) or experimental (Group E) (n= 15) groups at 33 weeks post-conceptional age. Group E infants received 15 minutes of auditory, tactile, visual, and vestibular (ATVV) intervention twice a day, five days a week, for four weeks during hospitalization. Repeated measures ANOVA demonstrated that Group E infants experienced significant increases in heart and respiratory rate and a 0.72% drop in hemoglobin saturation, coinciding with a significant behavioral state shift from sleep to alertness during intervention. No differences were identified in neurobehavioral function and neurodevelopment, indicating that Group E suffered no injury. Group E had an average hospital stay nine days shorter than that of controls, with the associated cost savings of $213,840. The earlier hospital discharge indicates that ATVV intervention promotes alertness without compromising physiologic status in vulnerable infants.

Analysis of Variance↗

Discordant retinoblastoma in monozygotic twins.

PURPOSE: We report cases of discordant retinoblastoma in twins confirmed to be monozygotic by DNA analysis. METHODS: Twin A demonstrated severe, bilateral, multifocal retinoblastoma, which was recalcitrant to external beam irradiation and chemoreduction. Twin B has not demonstrated retinoblastoma. DNA analysis was performed with polymorphic microsatellite markers to confirm monozygosity. Single-stranded conformation polymorphism and Southern blot analysis of the retinoblastoma gene were performed. RESULTS: Molecular genetic analyses confirmed monozygosity but failed to disclose a retinoblastoma gene mutation in either twin. CONCLUSIONS: The extreme phenotypic discordance may best be explained by an unidentified, postzygotic retinoblastoma gene mutation in early embryonic development of the affected twin.

Blotting, Southern↗

Benefit of intravenous antispasmodic (hyoscyamine sulfate) as premedication for colonoscopy.

BACKGROUND: We sought to determine whether premedication for colonoscopy with intravenous hyoscyamine sulfate (Levsin) was helpful from the standpoint of the colonoscopist and the patient. METHODS: One hundred sixteen adult patients were randomized to receive either 0.5 mg hyoscyamine sulfate intravenous (n = 57) or placebo (n = 59). After administration of study drug, patients were given meperidine and midazolam. Parameters measured included the time required to reach the cecum, total procedure time, and the endoscopist's perception of the adequacy of sedation, difficulty of insertion, and amount of colonic spasm on insertion and withdrawal. Patients were given a postprocedure questionnaire assessing their experience. RESULTS: In patients receiving hyoscyamine, there was a shorter cecal intubation time (median 9.2 vs. 12.9 minutes; p = 0. 01), shorter total colonoscopy time (median 20.5 vs. 25.0 minutes; p = 0.01), better patient sedation (p = 0.02), easier colonic insertion (p = 0.001), and less spasm on insertion (p = 0.01). No difference was found in the amount of spasm during withdrawal or the total dosages of meperidine or midazolam used. Patients receiving hyoscyamine sulfate reported being more comfortable during their procedures ( p < 0.001) and were more willing to repeat colonoscopy in the future (p = 0.0001). The only adverse effect seen during the study was a 27% incidence of sinus tachycardia that occurred in patients receiving hyoscyamine. CONCLUSIONS: Premedication with intravenous hyoscyamine sulfate was beneficial in terms of the time required for cecal intubation, total procedure time, adequacy of sedation, and scales of patient comfort. However, the high frequency of sinus tachycardia seen with the dose used in our study, which was extremely rapid in two patients, indicates the need for further study before the drug can be recommended as a routine premedication for colonoscopy.

Adolescent↗

Metalloporphyrin class of therapeutic catalytic antioxidants.

Metalloporphyrins have emerged as a novel class of catalytic antioxidants that scavenge a wide range of reactive oxygen species (ROS) such as superoxide, peroxide, peroxynitrite and lipid peroxyl radicals. Factors such as the type of metal centre, redox potential and electrostatic charge of the compounds are recognized as important determinants of their antioxidant activity and potency. These concepts have guided the development of metalloporphyrins with specific activities greater than those of the native superoxide dismutases. Several compounds in this class have been shown to be efficacious in a variety of in vitro and in vivo oxidative stress models of human diseases.

Antioxidants↗

Conformation and vasoreactivity of VIP in phospholipids: effects of calmodulin.

The purpose of this study was to determine the conformation and vasorelaxant effects of vasoactive intestinal peptide (VIP) self-associated with sterically stabilized phospholipid micelles (SSM) and whether calmodulin modulates both of these processes. Circular dichroism spectroscopy revealed that VIP is unordered in aqueous solution at room temperature but assumes appreciable a helix conformation in SSM. This conformational transition was amplified at 37 degrees C and by a low concentration of calmodulin (0.1 nM). Suffusion of VIP in SSM elicited significant time- and concentration-dependent potentiation of vasodilation relative to that elicited by aqueous VIP in the in situ hamster cheek pouch (P < 0.05). This response was significantly potentiated by calmodulin (0.1 nM). Collectively, these data indicate that exogenous calmodulin interacts with VIP in SSM to elicit conformational transition of VIP molecule from a predominantly random coil in aqueous environment to alpha helix in SSM. This process is associated with potentiation and prolongation of VIP-induced vasodilation in the in situ peripheral microcirculation.

Animals↗

A hybrid technique for spectroscopic imaging with reduced truncation artifact.

Traditionally, Fourier spectroscopic imaging is associated with a small k-space coverage which leads to truncation artifacts such as "bleeding" and ringing in the resultant image. Because substantial truncation artifacts mainly arise from regions having intense signals, such as the subcutaneous lipid in the head, effective reduction of truncation artifacts can be achieved by obtaining an extended k-space coverage for these regions. In this paper, a hybrid technique which employs phase-encoded spectroscopic imaging (SI) to cover the central portion of the k-space and echo-planar spectroscopic imaging (EPSI) to measure the peripheral portion of the k-space is developed. EPSI, despite its inherently low SNR characteristics, provides a sufficient SNR for outer high-spatial frequency components of the aforementioned high signal regions and supplies an extended k-space coverage of these regions for the reduction of truncation artifacts. The data processing includes steps designed to remove inconsistency between the two types of data and a previously described technique for selectively retaining only outer k-space information for the high signal regions during the reconstruction. Experimental studies, in both phantoms and normal volunteers, demonstrate that the hybrid technique provides significant reduction in truncation artifacts.

Artifacts↗