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Biomedical subjects

R Grewal

Publications and source records attributed to R Grewal.

At least 19 recordsLinked to original sources
PubMed2005

A randomized prospective study on the treatment of intra-articular distal radius fractures: open reduction and internal fixation with dorsal plating versus mini open reduction, percutaneous fixation, and external fixation.

PURPOSE: To compare 2 methods of surgical treatment for displaced intra-articular fractures of the distal radius: open reduction and internal fixation with dorsal plating (Pi Plate; Synthes, Paoli, PA) versus mini open reduction with percutaneous K-wire and external fixation. METHODS: Patients with AO type C intra-articular distal radius fractures were randomized into 2 groups: open reduction and internal fixation and dorsal plating or external fixation and K-wires and mini-open reduction. Patients over the age of 70 years with any associated soft-tissue or skeletal injury to the same limb and pre-existing wrist arthrosis or disability were excluded from the study. Objective, subjective, and radiographic outcomes were assessed at 2 weeks, 4 to 6 weeks, 10 to 12 weeks, 6 months, and 1- and 2-year intervals. The minimum follow-up period was 6 months; the average follow-up period was 18 months. The principal outcome analyzed was the Disabilities of the Arm, Shoulder, and Hand score. Secondary outcomes included grip strength, range of motion, surgical procedure time, complications, and radiographic parameters. The groups were equal with respect to age, gender, fracture subtype, and number of workers' compensation cases. RESULTS: No significant difference was found in the Disabilities of the Arm, Shoulder, and Hand scores, our primary outcome. The dorsal plate group, however, showed a higher complication rate when compared with the external fixator group. The plate group had significantly longer tourniquet times when compared with the external fixator group. The plate group also had higher levels of pain at 1 year when compared with the external fixator group; however, this equalized after hardware removal. The external fixator group showed an average grip strength of 97% compared with the normal side and 86% in the dorsal plate group. CONCLUSIONS: At midterm analysis the dorsal plate group showed a significantly higher complication rate compared with the external fixator group; therefore enrollment in the study was terminated. The dorsal plate group also showed statistically significant higher levels of pain, weaker grip strength, and longer surgical and tourniquet times. Based on these results we cannot recommend the use of dorsal plates in treating complex intra-articular fractures of the distal radius.

Adult↗
PubMed2005

Rituximab for autoimmune haemophilia: a proposed treatment algorithm.

We previously reported durable complete responses following brief courses of rituximab and prednisone with or without cyclophosphamide in four patients with autoimmune haemophilia and inhibitor titres of 5-60 BU. We report here responses to this monoclonal anti-CD20 antibody in four additional patients, including two patients with inhibitor titres >200 BU. Factor VIII levels became normal 2-35weeks after 4 or 8 weekly doses of rituximab, brief courses of prednisone and in one patient immunoglobulin. Complete responses are ongoing at 10 months in two patients. Two patients relapsed: a patient whose initial inhibitor titre was 525 BU relapsed at 3.5 months and a long-term prednisone-dependent patient at 8.5 months. Both responded to second courses of rituximab and prednisone and are in remission. Our experience suggests that rituximab is a safe and effective addition to immunosuppression with prednisone and cyclophosphamide to treat autoimmune haemophilia, and may permit early discontinuation or even avoidance of these potentially toxic agents. High-titre inhibitor patients, however, may require multiple courses of rituximab or the addition of cyclophosphamide. Pending randomized studies, we propose an algorithm based on our experience and other reports for incorporating rituximab in the treatment of this rare disorder.

Aged↗
PubMed2001

Synthetic mannosides act as acceptors for mycobacterial alpha1-6 mannosyltransferase.

A series of synthetic mannosides was screened in a cell-free system for their ability to act as acceptor substrates for mycobacterial mannosyltransferases. Evaluation of these compounds demonstrated the incorporation of [14C]Man from GDP-[14C]Man into a radiolabeled organic-soluble fraction and analysis by thin layer chromatography and autoradiography revealed the formation of two radiolabeled products. Each synthetic acceptor was capable of accepting one or two mannose residues, resulting in a major and a minor mannosylated product. Both products from each acceptor were isolated and their mass was confirmed by fast-atom bombardment-mass spectrometry (FABMS). Characterization of each mannosylated product by exo-glycosidase digestion. acetolysis and linkage analysis by gas chromatography mass spectrometry of partially per-O-methylated alditols, revealed only alpha1-6-linked products. In addition. the antibiotic amphomycin selectively inhibited the formation of mannosylated products suggesting polyprenolmonophosphate-mannose (C15 50-P-Man) was the immediate mannose donor in all mannosylation reactions observed. The ability of synthetic disaccharides to act as acceptor substrates in this system, is most likely due to the action of a mycobacterial polyprenol-P-Man:mannan alpha1-6 mannosyltransferase involved in the biosynthesis of linear alpha1-6-linked lipomannan.

Carbohydrate Sequence↗
PubMed2000

Feasibility of partial A2 and A4 pulley excision: residual pulley strength.

We investigated residual digital flexor pulley strengths after 75% excision of the A2 and A4 pulleys. For direct pull-off tests, A2 and A4 pulleys from cadaveric fingers were tested by pulling on a loop of flexor digitorum profundus tendon through the pulley. For functional loading tests, fingers were positioned with the metacarpophalangeal joint flexed to 90 degrees for A2 testing, and with the proximal interphalangeal joint in 90 degrees flexion for A4 testing (with all other joints in full extension). Excision of 75% of A2 and A4 pulleys reduced pulley strengths determined by both testing methods. For the functional loading tests, which are more clinically relevant, mean tendon forces at failure after partial excision of A2 and A4 pulleys were 224 and 131 N respectively, which is sufficient to withstand flexor tendon forces expected during activities of daily living.

Analysis of Variance↗
PubMed2000

Ulnar nerve elongation and excursion in the cubital tunnel after decompression and anterior transposition.

We studied the elongation and excursion of cadaveric ulnar nerves during elbow flexion in control conditions and after in situ decompression and anterior subcutaneous transposition. We found that the normal nerve had the greatest elongation (23%) and excursion (14 mm) in the epicondylar groove. Decompression did not alter the excursion, but significantly reduced the elongation in the groove (6%) and increased it proximally (19%). After anterior subcutaneous transposition, the nerve segment which was originally in the groove elongated with elbow extension to the same extent as occurred with the normal nerve during flexion.

Aged↗
PubMed1999

Feasibility of partial A2 and A4 pulley excision: effect on finger flexor tendon biomechanics.

We investigated the effect of partial excision of the A2 and A4 digital pulleys, separately and in combination, on finger angular rotation and the energy for finger flexion. Statistically significant decreases in angular rotation resulted only after 50% and 75% excision of A2, A4, or A2 and A4 in combination. Work of flexion trends were weak and none of the changes were statistically significant. Although optimal finger function relies on the integrity of the A2 and A4 pulleys to maintain the efficiency of the digital flexor system, these data suggest that the A2 and A4 pulleys can be excised up to 25%, either separately or in combination, without significant effects on angular rotation. Decreases in total angular range of motion after 50% and 75% pulley excision were small, even for combined pulley excision (9 degrees +/- 3 degrees and 15 degrees +/- 5 degrees [mean +/- SD], respectively), and may be clinically acceptable.

Biomechanical Phenomena↗
PubMed1999

Passive and active rehabilitation for partial lacerations of the canine flexor digitorum profundus tendon in zone II.

The purpose of this study was to compare the effect of unrestricted active versus passive mobilization on the gliding function and structural properties (ultimate load and stiffness) of repaired and nonrepaired canine flexor digitorum profundus tendons following partial laceration at 1 week. Using a radiographic method, normalized tendon gliding of the flexor digitorum profundus tendon adjacent to the metacarpal bone and total joint rotation were shown to be significantly greater in passive than in active tendons. Each group differed from their control group, however, by an average of only 5%. Both rehabilitation (active vs. passive) and treatment (repair vs. nonrepaired) of the partial tendon laceration significantly affected gap formation. Both active rehabilitation and repair of the laceration significantly increased gap formation compared with passive rehabilitation and nonrepair of the partial laceration. Rehabilitation did not significantly affect the normalized ultimate loads and stiffness in the passive and active groups but the nonrepair groups displayed significantly higher ultimate loads and stiffness than the repair groups.

Animals↗
PubMed1999

Mapping of a new autosomal dominant spinocerebellar ataxia to chromosome 22.

The autosomal dominant cerebellar ataxias (ADCAs) are a clinically and genetically heterogeneous group of disorders. The clinical symptoms include cerebellar dysfunction and associated signs from dysfunction in other parts of the nervous system. So far, five spinocerebellar ataxia (SCA) genes have been identified: SCA1, SCA2, SCA3, SCA6, and SCA7. Loci for SCA4 and SCA5 have been mapped. However, approximately one-third of SCAs have remained unassigned. We have identified a Mexican American pedigree that segregates a new form of ataxia clinically characterized by gait and limb ataxia, dysarthria, and nystagmus. Two individuals have seizures. After excluding all known genetic loci for linkage, we performed a genomewide search and identified linkage to a 15-cM region on chromosome 22q13. A maximum LOD score of 4.3 (recombination fraction 0) was obtained for D22S928 and D22S1161. This distinct form of ataxia has been designated "SCA10." Anticipation was observed in the available parent-child pairs, suggesting that trinucleotide-repeat expansion may be the mutagenic mechanism.

Adolescent↗
PubMed1998

Targeted disruption of SHIP leads to hemopoietic perturbations, lung pathology, and a shortened life span.

SHIP is a 145-kD SH2-containing inositol-5-phosphatase widely expressed in hemopoietic cells. It was first identified as a tyrosine phosphoprotein associated with Shc in response to numerous cytokines. SHIP has been implicated in FcgammaRIIB receptor-mediated negative signaling in B cells and mast cells and is postulated to down-regulate cytokine signal transduction in myeloid cells. To define further its role in the proliferation and differentiation of hemopoietic progenitors, as well as its function in mature cells, we have generated embryonic stem cells and mice bearing a targeted disruption of both SHIP alleles. Here we show that although SHIP null mice are viable and fertile, they fail to thrive and survival is only 40% by 14 weeks of age. Mortality is associated with extensive consolidation of the lungs resulting from infiltration by myeloid cells. Increased numbers of granulocyte-macrophage progenitors are observed in both the bone marrow and spleen of SHIP-/- mice, perhaps as a consequence of hyper-responsiveness to stimulation by macrophage-colony stimulating factor, granulocyte-macrophage colony stimulating factor, interleukin-3, or Steel factor as observed in vitro. In contrast, numbers of bone marrow lymphoid and late erythroid progenitors (CFU-E) are reduced. Thus, homozygous disruption of SHIP establishes the crucial role of this molecule in modulating cytokine signaling within the hemopoietic system and provides a powerful model for further delineating its function.

Animals↗
PubMed1998

The effect of partial excision of the A2 and A4 pulleys on the biomechanics of finger flexion.

The purpose of this study was to investigate the effect of partial excision of the A2 and A4 pulleys on digital angular rotation and the energy required to flex the finger. Partial excision of A2 resulted in a statistically significant decrease in angular rotation of 3 and 5% after 50 and 75% excision, respectively. Partial excision of A4 failed to produce any significant differences in angular rotation. Combined partial excision of A2 and A4 resulted in a significant decrease of 5 and 8% after 50 and 75% excision, respectively. Significant differences in work of flexion occurred only after excision of 75% of the A2 pulley. Although optimal finger function relies on the integrity of the A2 and A4 pulleys which maintain the efficiency of the digital flexor system, these data suggest that 25% of the A2 pulley, up to 75% of the A4 and 25% of the A2 and A4 together can be excised without significant effects on angular rotation.

Biomechanical Phenomena↗
PubMed1998

The effects of multiple-strand suture methods on the strength and excursion of repaired intrasynovial flexor tendons: a biomechanical study in dogs.

This study was designed to determine the effects of in vivo multistrand, multigrasp suture techniques on the strength and gliding of repaired intrasynovial tendons when controlled passive motion rehabilitation was used. Twenty-four adult mongrel dogs were divided into 4 groups and their medial and lateral forepaw flexor tendons were transsected and sutured by either the Savage, the Tajima, the Kessler, or the recently developed 8-strand suture method. The tendon excursion, joint rotation, and tensile properties of the repaired tendons were evaluated biomechanically at 3 and 6 weeks after surgery. It was found that neither time nor suture method significantly effected proximal and distal interphalangeal joint rotation or tendon excursion when the 4 techniques were compared to each other. Normalized load value (experimental/control) was significantly affected by both the suture method and the amount of time after surgery, however. The Savage and 8-strand repair methods had significantly greater strength than did the Tajima method at each time interval (p < .05 for each comparison). In addition, the 8-strand method had significantly greater normalized load values than did the Savage method at each time interval (p < .05 for each comparison). Normalized stiffness (experimental/control) for the 8-strand repair method was significantly greater than that for the Tajima and Savage methods at 3 and 6 weeks after surgery (p < .05). In addition, the normalized stiffness values for the 6-week groups was significantly greater than those for the 3-week groups (p < .05). It was concluded that the method of tendon suture was a significant variable insofar as the regaining of tendon strength was concerned and that the newer low-profile 8-strand repair method significantly expands the safety zone for the application of increased in vivo load during the early stages of rehabilitation.

Animals↗
PubMed1997

Human acetyltransferase polymorphisms.

Conjugation of primary amino and hydroxylamino groups with acetate, catalyzed by acetyl CoA-dependent arylamine acetyltransferase (NAT) enzymes, may play an important role in the intricate series of metabolic pathways that produce or prevent toxicity following exposure to homo- and heterocyclic arylamine and hydrazine xenobiotics. Two independently regulated and kinetically distinct human acetyltransferases are now known to exist, namely NAT1 and NAT2. Interindividual variation in NAT2 function is associated with the classical isoniazid acetylation polymorphism which was discovered over forty years ago. At last count, fifteen variant alleles at the NAT2 gene locus have been linked to the isoniazid 'acetylator phenotype', and each of these can be identified in population studies using specific PCR-based genotyping tests. On the other hand, NAT1 shows kinetic selectivity for compounds whose disposition is unrelated to the classical isoniazid acetylation polymorphism. NAT1 expression is also phenotypically variable in human populations, at least in part due to allelic differences at the NAT1 gene locus. Nine NAT1 variant alleles have been described to date, of which NAT1* 14 and NAT1* 15 clearly produce defective NAT1 proteins and lead to functional impairment in the metabolism of NAT1-selective substrates both in vivo and in vitro. On the other hand, it has been reported that the NAT1* 10 variant associates with elevated NAT1 activity and increased risk for cancers of the bladder and colon. Because of the important toxicologic consequences of allelic variation in NAT1 and NAT2 function for the metabolic activation of arylamine and heterocyclic amine procarcinogens, further studies are needed to improve our understanding of the extent of NAT allelic variation, to determine the functional capacity of each variant gene product, and to develop accurate methods of detecting them in population and epidemiological studies.

Acetylation↗
PubMed1997

Isolation of chromosome 18-specific brain transcripts as positional candidates for bipolar disorder.

Several studies have proposed the existence of susceptibility loci for bipolar disorder on chromosome 18. To identify possible candidate genes for this disease, we isolated brain-expressed transcripts by direct cDNA selection on chromosome 18-specific biotinylated cosmid clones. Longer cognate cDNA clones of the selected cDNAs were isolated from a normalized infant brain cDNA library. Physical mapping by PCR on a panel of somatic cell hybrids was conducted by the use of primers derived from partial sequences on either the 5' or 3' ends of the clones. In our initial analysis, 48 cDNA clones were found to be chromosome 18-specific, mapping to different subchromosomal regions. Sequence redundancy among these clones yielded 30 unique transcripts, five of which were represented in previously known genes. Further sequencing of the remaining 25 unique cDNA clones confirmed the absence of significant homology to known genes, indicating that these transcripts represented novel genes. Mapping with the use of a radiation hybrid panel positioned the brain cDNAs to within = 100 to 1100 kb from reference sequence tag sites (STSs) and assembled them into six high resolution linkage groups. The majority of the transcripts were found to cluster to discrete locations on 18p and 18q, previously hypothesized as susceptibility regions for bipolar disorder, identifying them as positional candidate genes.

Bipolar Disorder↗
PubMed1997

Avulsion of the tibial tuberosity: muscles too strong for a growth plate.

PURPOSE: To ascertain whether there were significant knee extension strength differences between two adolescent male gymnasts (patient 1: age, 14.5 years; height, 159.3 cm; weight, 52.2 kg; patient 2: age, 15 years; height, 160.6 cm; weight, 54.8 kg) with avulsion of the tibial tuberosity associated with avulsion of the patellar tendon. CASE SUMMARY: Two adolescent male gymnasts underwent open reduction and internal fixation for avulsion of the tibial tuberosity associated with avulsion of the patellar tendon. Isometric extension strength of the contralateral uninjured knee and of the operated knee was significantly greater than for nonathletic adolescents of the same age (one-way analysis of variance [ANOVA], p = 0.001), and was at a higher part of normal strength than their gymnastic peers. DISCUSSION: A maximal contraction of the quadriceps is able to overcome the strength of the upper tibial epiphysis disrupting the extensor mechanism of the knee. RELEVANCE: Greater-than-usual strength, although normally of no undesired consequence, may play a role in avulsion injuries of major muscles.

Adolescent↗
PubMed1996

Tensile properties of the interosseous membrane of the human forearm.

The interosseous membrane is a structure deep in the forearm that joins the radius and the ulna. It is made up of membranous and ligamentous regions. Two main ligamentous structures have been described: a prominent central fiber group, the "central band," and a smaller proximal fibrous band, the "oblique cord." Many authors believe that the central band plays a biomechanical role in the normal and fractured forearm and that it may function much like a ligament. The objective of this study was to determine the tensile properties of the central band. Eighteen fresh frozen forearms from cadavers (45-70 years of age, both sexes) were used. A fiber bundle of the central band was subjected to a uniaxial tensile test to failure in a materials testing machine, and its tensile properties were calculated. Stiffness, ultimate load, and energy absorbed to failure were expressed as a function of specimen width. The central band structure had a stiffness of 13.1 +/- 3.0 N/mm per mm width and an ultimate load of 56.6 +/- 15.1 N per mm width (mean +/- SD). The tissue of the central band displayed a modulus of 608.1 +/- 160.2 MPa, ultimate tensile strength of 45.1 +/- 10.3 MPa, and strain at failure of 9.0 +/- 2.0%. This study demonstrated that the central band is comprised of strong tissue. The material properties of the central band compare with those of patellar tendon: modulus is 120% and ultimate tensile strength is 84% that of patellar tendon. As a structure, the interosseous membrane is stiff and capable of bearing high loads. Although load distribution across the central band is unknown, a 1.7 cm wide, evenly loaded homogenous portion of the central band would possess a stiffness comparable with that of the anterior cruciate ligament. The results of this study provide a basis for future analyses of radioulnar stability and load transfer.

Aged↗
PubMed1996

Does the internal thoracic artery graft delay the recovery of myocardial metabolism?

BACKGROUND: The left internal thoracic artery (LITA) bypass graft to the left anterior descending artery has greater long-term patency than a saphenous vein graft. However, surgeons may be reluctant to use the LITA graft in some patients because they are unable to deliver cardioplegia to the left anterior descending artery territory. METHODS: We compared the myocardial levels of high-energy phosphates and their metabolites in patients who received an LITA graft with those in patients who received a saphenous vein graft to the left anterior descending artery territory during elective coronary artery bypass grafting. Right and left ventricular biopsy specimens were obtained at three times: before aortic cross-clamping, after cross-clamp removal, and after 10 minutes of reperfusion. RESULTS: No differences were found between the LITA graft group and the saphenous vein graft group in any right ventricular metabolites. There was an improvement in myocardial protection over time and a higher proportion of LITA graft patients in the late time period (early group, 63% versus late group, 80%; p < 0.01). Within each time period, there were no differences between the LITA and saphenous vein graft groups. Among patients receiving cold antegrade cardioplegia, the myocardial levels of high-energy phosphates were better preserved in those receiving an LITA graft. CONCLUSIONS: Advances in myocardial protection have led to improved preservation of high-energy phosphate levels after cardioplegic arrest. In patients undergoing elective coronary artery bypass grafting, the use of an LITA graft does not adversely affect myocardial metabolism. Further investigations are required to determine the effects of the use of the LITA during urgent or emergent procedures.

Adenine Nucleotides↗
PubMed1996

Bundle pattern of the flexor digitorum profundus tendon in zone II of the hand: a quantitative assessment of the size of a laceration.

Assessing the cross-sectional area of a partial laceration of a flexor digitorum profundus tendon based on its width, using magnification and calipers, is often inaccurate. As the threshold for repairing a partial laceration for most surgeons is the involvement of 50% of the tendon area, an accurate method of naked-eye evaluation to detect a 50% (or larger, or smaller) laceration was developed. This assessment is based on the size of the radial and ulnar bundles in the tendon. The relative area of the two bundles at four levels in zone II in the index, middle, ring, and small fingers was measured. In the index and small fingers, the ulnar bundle had a mean area consistently greater than and the radial bundle consistently less than 50% of the total tendon area. In the middle finger, the mean areas of both bundles were close to 50% of the total tendon area, but the radial bundle was reduced at the level of the proximal interphalangeal joint and distally. In the ring finger, both bundles remained close to 50% of the total tendon area at all levels. The bundles involved in a laceration can be easily identified with the naked eye; the data provided by this study may improve the accuracy of partial laceration size assessment.

Aged↗