Search PubMed⌕ Search

Biomedical subjects

N Patel

Publications and source records attributed to N Patel.

At least 145 records · Page 8Linked to original sources
PubMed1999

Relationship of Ki-67 labeling index to DNA-ploidy, S-phase fraction, and outcome in prostate cancer treated with radiotherapy.

BACKGROUND: Our purpose was to evaluate the relationship of Ki-67 labeling index (Ki67-LI) to deoxyribonucleic acid (DNA) ploidy, S phase fraction (SPF), other clinical prognostic factors, and clinical outcome for patients with prostate cancer treated by external beam radiotherapy. METHODS: Tissue was retrieved from 42 patients who underwent transurethral resection of the prostate before treatment with external beam radiotherapy between 1987-1993. DNA histogram profiles were classified as diploid (diploid + near-diploid) and nondiploid (tetraploid + aneuploid). Immunohistochemical staining of Ki-67 by the MIB-1 monoclonal antibody was used to calculate Ki67-LI. Median patient follow-up was 62 months. Treatment failure was defined as two consecutive rises in serum prostate-specific antigen (PSA) or clinical evidence of disease recurrence. RESULTS: The mean and median Ki67-LIs were 3.1 and 2.4, respectively (range, 0-12.4). Mean Ki67-LI values were significantly associated with higher stage, Gleason score, and pretreatment PSA. Nondiploid tumors had significantly higher Ki67-LIs, as did patients who failed radiotherapy over the follow-up period. SPF was not significantly correlated with Ki67-LI. As a categorical variable, the most significant relationships were seen when Ki67-LI was subdivided into thirds around the median (Ki67-LI </=1.5%, Ki67-LI >1.5-3.5%, and Ki67-LI >3.5%). This trichotomous variable correlated significantly with pretreatment PSA (P = 0.0008), tumor stage (P = 0.016), Gleason score (P = 0.024), and treatment failure (P = 0.0015), but not with DNA-ploidy (P = 0.15). In actuarial univariate analyses, Ki67-LI appeared to be a more significant predictor of patient outcome (P = 0.003) than DNA-ploidy (P = 0.035). CONCLUSIONS: The Ki67-LI correlated with known prognostic factors such as pretreatment PSA, tumor stage, and Gleason score, and was also weakly related to DNA-ploidy. In comparison to DNA-ploidy, Ki67 LI seems to be a better correlate of treatment outcome.

Aged↗
PubMed1999

OB-BP1/Siglec-6. a leptin- and sialic acid-binding protein of the immunoglobulin superfamily.

We report the expression cloning of a novel leptin-binding protein of the immunoglobulin superfamily (OB-BP1) and a cross-hybridizing clone (OB-BP2) that is identical to a recently described sialic acid-binding I-type lectin called Siglec-5. Comparisons to other known Siglec family members (CD22, CD33, myelin-associated glycoprotein, and sialoadhesin) show that OB-BP1, OB-BP2/Siglec-5, and CD33/Siglec-3 constitute a unique related subgroup with a high level of overall amino acid identity: OB-BP1 versus Siglec-5 (59%), OB-BP1 versus CD33 (63%), and OB-BP2/Siglec-5 versus CD33 (56%). The cytoplasmic domains are not as highly conserved, but display novel motifs which are putative sites of tyrosine phosphorylation, including an immunoreceptor tyrosine kinase inhibitory motif and a motif found in SLAM and SLAM-like proteins. Human tissues showed high levels of OB-BP1 mRNA in placenta and moderate expression in spleen, peripheral blood leukocytes, and small intestine. OB-BP2/Siglec-5 mRNA was detected in peripheral blood leukocytes, lung, spleen, and placenta. A monoclonal antibody specific for OB-BP1 confirmed high expression in the cyto- and syncytiotrophoblasts of the placenta. Using this antibody on peripheral blood leukocytes showed an almost exclusive expression pattern on B cells. Recombinant forms of the extracellular domains of OB-BP1, OB-BP2/Siglec-5, and CD33/Siglec-3 were assayed for specific binding of leptin. While OB-BP1 exhibited tight binding (K(d) 91 nM), the other two showed weak binding with K(d) values in the 1-2 microM range. Studies with sialylated ligands indicated that OB-BP1 selectively bound Neu5Acalpha2-6GalNAcalpha (sialyl-Tn) allowing its formal designation as Siglec-6. The identification of OB-BP1/Siglec-6 as a Siglec family member, coupled with its restricted expression pattern, suggests that it may mediate cell-cell recognition events by interacting with sialylated glycoprotein ligands expressed on specific cell populations. We also propose a role for OB-BP1 in leptin physiology, as a molecular sink to regulate leptin serum levels.

Amino Acid Sequence↗
PubMed1999

Non-invasive diagnosis of hepatic cirrhosis by transit-time analysis of an ultrasound contrast agent.

BACKGROUND: Hepatic cirrhosis is accompanied by several haemodynamic changes including arterialisation of the liver, intrahepatic shunts, pulmonary arteriovenous shunts, and a hyperdynamic circulatory state. We postulated that the hepatic first pass of a bolus of an ultrasound contrast agent injected into a peripheral vein is accelerated in patients with cirrhosis. We investigated this first pass in patients with diffuse liver disease and in normal controls to assess whether it provides useful differential diagnostic information. METHODS: We enrolled 15 patients with biopsy-proven cirrhosis, 12 patients with biopsy-proven non-cirrhotic diffuse liver disease, and 11 normal controls. We carried out continuous spectral doppler ultrasonography of a hepatic vein from 20 s before to 3 min after a peripheral intravenous bolus injection of 2.5 g Levovist. The intensity of the doppler signal was measured and used to plot time-intensity curves. FINDINGS: Patients with cirrhosis showed a much earlier onset of enhancement (arrival time; mean 18.3 s) and peak enhancement (mean 55.5 s) than controls (49.8 s and 97.5 s) or patients with non-cirrhotic diffuse liver disease (35.8 s and 79.7 s). All patients with cirrhosis had an arrival time of the bolus of less than 24 s, whereas the arrival time was 24 s or more in 22 of the 23 other participants. Peak enhancement was higher in patients with cirrhosis (mean 48.7 units) than in the other two groups (12.5 and 12.3 units, respectively). We found highly significant differences between the patients with cirrhosis and each of the other two groups for all variables (p<0.005), whereas we found no significant differences between non-cirrhotic patients and controls. INTERPRETATION: Our preliminary study suggests that analysis of liver transit time of a bolus of ultrasound contrast agent provides useful information about haemodynamic changes in patients with cirrhosis. Measurement of the arrival time of the bolus allows discrimination of patients with cirrhosis from controls and from patients with non-cirrhotic diffuse liver disease, and has potential as a non-invasive test for cirrhosis.

Adult↗
PubMed1999

Morphological development of beta(1-40) amyloid fibrils.

The Alzheimer's disease-related peptide beta(1-40) amyloid self-associates to form fibrils exhibiting a morphology characteristic of amyloidogenic proteins. The mechanism of this fibrillization process has yet to be fully elucidated. In this study we have immobilized the beta(1-40) amyloid to flat gold surfaces using thiol-based self-assembled monolayers. Atomic force microscopy reveals the presence of spherical units of beta(1-40) amyloid immediately following the initiation of fibrillization. Short fibrillar structures, termed nascent fibrils, which appear to be formed by the association of these units are also present at this time point. At later time points extended, branching networks of fibrils are observed. Some fibrils exhibit a more beaded appearance and greater axial periodicity than others. No nascent fibrils are seen to be present. We believe that these data identify an early fibril structure which could act as an intermediate in beta-amyloid fibrillization. The oligomeric units of which these nascent fibrils are comprised are also determined.

Amino Acid Sequence↗
PubMed1999

Quantitative measurement of long range nuclear Overhauser enhancement.

Measurement of nuclear Overhauser enhancement is one of the mainstays of structural studies of molecules in solution. Measurements, particularly over long distances, are often compromised by spin diffusion. A robust and accurate method for measuring nuclear Overhauser enhancements that are largely free of spin diffusion effects is presented. The effects of using imperfect radiofrequency pulses are considered and experimental data are presented for Amphotericin B.

Magnetic Resonance Spectroscopy↗
PubMed1999

Maze learning impairment is associated with stress hemopoiesis induced by chronic treatment of aged rats with human recombinant erythropoietin.

Mean cell volume (MCV) of erythrocytes has been reported to increase with age in humans, and to be negatively correlated with memory performance in humans and rats. We evaluated hematological changes in 21-mo old male Fischer 344 rats undergoing a 3-mo twice weekly subcutaneous injection of human recombinant erythropoietin (EPO). A baseline hematocrit (HCT) was obtained initially and repeated at monthly intervals to determine the effectiveness of EPO treatment. At 24-mo of age and after 3 mo EPO treatment, the rats were tested for their ability to learn a 14-unit T maze. Following maze testing, blood was drawn for hematologic analyses, including HCT, MCV, maximum swollen cell volume (MCVS), mean cell transit time (MCTT), and the membrane shear modulus of elasticity (G), the latter a derived measure of the relative elasticity of the red cell membrane. After 1 mo EPO treatment, HCT significantly increased compared to saline-injected controls. After 2 mo treatment, HCT began to decline but remained elevated above baseline levels even after 3 mo treatment. After 3 mo EPO treatment, MCV was significantly lower in EPO-treated rats compared to controls. These changes imply altered hemopoiesis to produce cells which undergo shrinkage associated with accelerated cellular aging. The lower MCV would have predicted a shorter MCTT which instead was unchanged. This observation suggested the presence of an additional factor contributing to the MCTT. The G, which measures the membrane contribution to deformability, very significantly increased with EPO treatment. This finding indicates an increased contribution of membrane properties to the MCTT after EPO treatment, which cancels the expected decrease in MCTT for smaller cells. After 3 mo of EPO treatment, aged rats exhibited significantly impaired maze learning compared to controls. A relationship between, changes in erythrocyte membrane properties and impaired function was indicated by a significant correlation (r=0.67, p <0.04) between G and errors in the 14-unit T-maze. These findings suggest that stress-induced erythropoiesis produces accelerated aging in the red blood cell population that may have functional implications (i.e., impaired learning ability).

Aging↗
PubMed1999

Stimulated acoustic emission to image a late liver and spleen-specific phase of Levovist in normal volunteers and patients with and without liver disease.

Quantitative studies were performed to investigate liver- specific uptake of the microbubble Levovist, using stimulated acoustic emission (SAE), which can detect microbubbles even when stationary or slow-moving. These comprised studies of biodistribution comparing the liver and kidney in five normal volunteers, reproducibility in 34 patients, comparison between cirrhotics and controls (n = 9 each) and maximal depth of effect at different frequencies (180 measurements in 31 patients). Stimulated acoustic emission lasted beyond 30 min, with strongly liver-specific properties in each volunteer and was highly reproducible. No difference in the amount of SAE in the superficial liver was seen between cirrhotic and normal livers, but attenuation was higher in cirrhotics. This demonstrates a frequency-dependent effect on liver SAE penetration. We conclude that the liver uptake of Levovist lasts over 30 min, is reproducible, occurs even where diffuse liver disease is present and can be used to assess tissue attenuation in a novel fashion.

Adult↗
PubMed1999

Modified use of the arrow-trerotola percutaneous thrombolytic device for the treatment of thrombosed hemodialysis access grafts.

PURPOSE: To assess the safety and efficacy of using the Arrow-Trerotola percutaneous thrombolytic device (PTD) as the sole means of mechanical thrombolysis in hemodialysis access grafts, including in situ treatment of the arterial plug. PATIENTS AND METHODS: Fifty consecutive patients (22 women, 28 men; mean age, 58 years; mean graft age, 29 months), in whom mechanical thrombolysis of a thrombosed hemodialysis access graft using the PTD was planned, were included in the study. In all patients, the PTD was used to treat the arterial plug in situ at the arterial anastomosis, instead of using a Fogarty catheter to reposition the plug, as indicated in the PTD product labeling. Prospective data collection included demographic information, technical details of the procedure, immediate outcomes, and complications. Patients were followed for 3 months using definitions and data forms that were identical to those used in the original clinical trial of the PTD. A sample of procedures drawn from the PTD clinical trial database (n = 54) served as control. RESULTS: Immediate technical patency was 100%. Complications included arterial embolization (6% versus 2% control; P = NS; all successfully treated with backbleeding); venous rupture (6% versus 2% control; P = NS); and sepsis (n = 1), probably due to occult graft infection. Adjunctive therapy with an Adherent Clot catheter was needed in two procedures (4%). Three month patency using life-table analysis was 42% (versus 39% control; P = NS). The number of subsequent interventions (surgical/percutaneous) to the arterial limb of the graft did not differ from the PTD trial, and no native arterial stenoses were detected during the follow-up period. CONCLUSIONS: The PTD is safe and effective when used as the sole means of mechanical thrombolysis of hemodialysis grafts. Treating the arterial plug in situ with the PTD eliminates the need for a Fogarty or Adherent Clot catheter in 96% of procedures. A slight increase in arterial embolic complications was observed but these were easily treated with backbleeding.

Adult↗
PubMed1999

Randomized comparison of high-flow versus conventional hemodialysis catheters.

PURPOSE: To evaluate short-term flow rates achieved with a new split-tip polyurethane hemodialysis catheter. PATIENTS AND METHODS: This was a prospective, randomized, nonblinded study. Patients referred for a tunneled-dialysis catheter received either a conventional silicone (Bard Hickman 13.5 F) if randomized to the control group, or a split-tip, high-flow polyurethane (MedComp AshSplit 14.5 F) catheter if randomized to the study group. Effective flow rates (QbEff) and recirculation were measured with use of ultrasonic dilution at pump settings (Qb) of 200, 300, 350 and 400 mL/min, as well as maximum Qb (QbMax, up to 500 mL/min) sustainable for at least 3 minutes. Measurements were repeated weekly for 6 weeks. Procedure times and initial and late complications were recorded. RESULTS: Twelve patients were enrolled in each group, 11 and eight completed the study in the test and control groups, respectively. Insertion complications, limited to the split-tip group, included asymptomatic air embolus (n = 1), prolonged tunnel bleeding (n = 2), and kinking (n = 2). Recirculation in both groups was low (mean < 6% at all flow rates). QbMax was 499 mL/min in the Ash group and 470 mL/min in the Hickman group. A repeated measures analysis of variance was used. Adjusted (for week) mean effective flow rates (Qbeff, mL/min) were as follows: at Qb = 200, Ash = 211, Bard = 211, P = .93; at Qb = 300, Ash = 301, Bard = 292, P = .28; at Qb = 350, Ash = 341, Bard = 314, P = .03; at Qb = 400, Ash = 375, Bard = 329, P = .01; at QbMax, Ash = 422, Bard = 359, P = .0005. CONCLUSION: Both catheters delivered flows within the acceptable range indicated by the Dialysis Outcomes Quality Initiative. The split-tip catheter is capable of higher flow rates (Qb and QbEff) compared with the conventional catheter, which may allow more efficient dialysis. Insertion complications appear to be higher with the new design.

Blood Flow Velocity↗
PubMed1999

Advancement in the zone of calcified cartilage in osteoarthritic hands of patients detected by high definition macroradiography.

OBJECTIVE: High definition macroradiography permits the advancement in the zone of calcified cartilage (described as a ZCC step) to be detected in osteoarthritic (OA) hand joints of patients. The pattern of their incidence and distribution was determined and compared to the joint space width (JSW) measurement. DESIGN: Macroradiographs, x5 magnification, were obtained of the OA hands of 44 patients at baseline and at 18 months. The incidence of ZCC steps, identified as an advancement in the mineralized cartilage front into articular cartilage, was assessed at each articular surface. JSW was measured and was used to determine the difference in JSW between hands and groups of joints with and without ZCC steps at both X-ray visits. RESULTS: ZCC steps were only found at the convex articular surfaces in 42 (48%) of hand joints in 28 (64%) patients. Here, ZCC steps were present in 36 joints in the non-dominant hand compared to 30 joints in the dominant hand. In the former, they were present in 22 DIP, six PIP and eight MCP joints and in 12 DIP, 8 PIP and 10 MCP joints in the dominant hand. By 18 months new ZCC steps had formed in 15 hands with and 17 hands without previous ZCC steps. At both X-ray visits no statistically significant difference in JSW was found between the hands and joint groups with and without ZCC steps. CONCLUSION: Although ZCC steps and JSW loss were greater at the PIP joints, supporting a mechanical hypothesis for ZCC formation, their presence in joints, where JSW was larger, and their greater incidence in the non-dominant PIP joints, suggest that factors associated with vascular changes, related to subchondral bone remodeling, are responsible.¿copy¿

Aged↗
PubMed1999

Physical map of the region surrounding the ataxia-telangiectasia gene on human chromosome 11q22-23.

Ataxia telangiectasia (A-T) is an autosomal recessive disease affecting multiple systems, including the development of the cerebellum and thymus. This results in a progressive cerebellar ataxia with onset between 1-3 years, telangiectasia occurs within the subsequent 3-5 years. We localized the A-T gene by linkage analysis to chromosome 11q22-23, between the markers D11S384, and D11S535, and constructed a series of contigs using three BACs and twelve cosmids, spanning a region of approximately 400 kb. We developed a set of sequence-tagged site (STS) markers from the ends of the BACs and cosmids. The A-T gene was isolated from within this region. It is now possible to precisely orient specific BACs, cosmids, and STSs with respect to the exons of the A-T gene (ATM). We anticipate that this information will be useful for further studies of functional domains and regulatory elements within the ATM gene, as well as for other genes in this region. In addition, these clones can be used for FISH studies of deletions, translocations and for loss of heterozygosity in various tumors.

Ataxia Telangiectasia↗
PubMed1999

Age is no contraindication to thyroid surgery.

BACKGROUND: There is increased risk of surgical treatment in elderly patients, but little has been written on the safety and efficacy of thyroid surgery in this group. OBJECTIVE: To determine if there is an increased risk of morbidity and mortality of thyroid surgery in patients over 75 years old. PATIENTS AND METHODS: During the period 1986-96, 1631 patients aged 50 and over underwent 1673 procedures by two surgeons in our unit. We retrospectively compared indications for surgery, procedures, pathology complications and mortality in three groups: 50-60-year-olds (725 patients), 61-74-year-olds (685 patients) and those aged 75 years and over (221 patients) RESULTS: The main indication for surgery in all three groups was compression or risk of malignancy. Total thyroidectomy was the main procedure performed. Although benign multinodular goitre was the commonest diagnosis, the over-75-year-olds had fewer benign multinodular goitres than the 61-74 group and more malignancy than the other two groups. There was no significant difference in mortality between the three groups. CONCLUSIONS: Surgery in patients over 75 is as safe as in younger patients with no increase in morbidity and mortality. Benign multinodular goitre is the most common indication for surgery.

Age Factors↗
PubMed1999

A patient-benefit evaluation of unilateral congenital conductive hearing loss presenting in adulthood: should it be repaired?

OBJECTIVE: To evaluate subjective and objective outcomes of surgical therapy in congenital conductive hearing loss (HL) presenting in adulthood. The impact of hearing restoration on quality of life (QOL) for these patients may differ from those with acquired HL. STUDY DESIGN: Retrospective review of five patients treated surgically. METHODS: Standard audiometry was completed. Patients completed a subjective questionnaire as well as subjective (open-set) questions. A seven-point Likert scale was used for closed-set responses with 1 representing the worst possible outcome and 7 being best. RESULTS: The average four-frequency improvements in pure-tone average and air-bone gap were 18 dB (range, 7-29 dB) and 16 dB (range, 2-30 dB), respectively. An average score was obtained for each closed-set question. The highest-scoring items were for overall improvement of QOL (average score, 6), followed by perceived improvement in hearing (average score, 5.6). Other positive responses were improved ability to use the telephone (four of five patients) and improved localization of sound (four of five patients). Negative subjective responses included prolonged dysequilibrium in two of five, prolonged adjustment period in three, and dysgeusia in one patient. CONCLUSION: Important components of outcome are likely to escape our review if only objective measures are used to evaluate surgical outcomes. These results suggest that improved hearing in this population provides specific improvements in lifestyle and is perceived as a significant improvement in overall QOL.

Adult↗
PubMed1999

Emergency magnetic resonance imaging of cervical spinal cord injuries: clinical correlation and prognosis.

OBJECTIVE: The goal of this study was to determine the prognostic and clinical value of magnetic resonance imaging (MRI) performed within hours after cervical spinal cord injuries in human patients. METHODS: Fifty-five patients with acute cervical vertebral column and spinal cord injuries underwent MRI as part of their initial treatment at the University of Michigan Medical Center. All images were obtained within 21 hours after injury (mean, 7.8 h) and were interpreted by an attending neuroradiologist who was blinded to the clinical status of the patients. Neurological function at presentation and in long-term follow-up examinations was compared with MRI characteristics assessed immediately after the injury. RESULTS: The presence and rostrocaudal length of intra-axial hematoma, the rostrocaudal length of spinal cord edema, the presence of spinal cord compression, and spinal cord compression by extra-axial hematoma were each significantly associated with poor neurological function at presentation and in long-term follow-up examinations. Although the best single predictor of long-term improvement in neurological function was the neurological function at presentation, four MRI characteristics, i.e., the presence of intra-axial hematoma, the extent of spinal cord hematoma, the extent of spinal cord edema, and spinal cord compression by extra-axial hematoma, provided significant additional prognostic information. MRI data demonstrated spinal cord compression for 27 of 55 patients (49%), leading to emergency surgery. Among patients who underwent imaging after restoration of normal vertebral alignment using closed cervical traction, 13 of 26 (50%) underwent emergency surgery for treatment of persistent, MRI-demonstrated, spinal cord compression. CONCLUSION: Emergency MRI after spinal cord injury provides accurate prognostic information regarding neurological function and aids in the diagnosis and treatment of persistent spinal cord compression after vertebral realignment.

Adolescent↗
PubMed1999

Diclofenac-associated hepatitis.

This patient, who had a history of osteoarthritis, had severe hepatitis 5 weeks after being started on diclofenac for increasing pain in the joints. A week before the onset of hepatitis, the patient complained of upper gastrointestinal symptoms and was treated for gastritis. Seven days later, she had full-blown, severe hepatitis. Diclofenac was immediately stopped, leading to a complete restoration of liver functions over the course of the next few months. We highlight the importance of having a high index of suspicion for hepatic side effects of diclofenac and emphasize the need for increased awareness of this rare but potentially serious problem. We also review relevant literature regarding incidence and management.

Alanine Transaminase↗