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Biomedical subjects

H Patel

Publications and source records attributed to H Patel.

At least 55 records · Page 3Linked to original sources
PubMed2001

The impact of fluid-dynamic-generated stresses on chDNA and pDNA stability during alkaline cell lysis for gene therapy products.

Extensive tests have been carried out to assess the impact of fluid-dynamic-generated stress during alkaline lysis of Escherichia coli cells (host strain DH1 containing the plasmid pTX 0161) to produce a plasmid DNA (pDNA) solution for gene therapy. Both a concentric cylinder rheometer and two stirred reactors have been used, and both the alkaline addition and neutralization stages of lysis have been studied. Using a range of shear rates in the rheometer, stirrer speeds in the reactors, and different periods of exposure, their impact on chromosomal DNA (chDNA) and pDNA was assessed using agarose gel electrophoresis, a Qiagen Maxiprep with a polymerase chain reaction (PCR) assay, and a Qiagen Miniprep purification with a UV spectrophotometer. Comparison has been made with unstressed material subjected to similar holding times. These tests essentially show that under all these conditions, <2% chDNA was present in the pDNA solution, the pDNA itself was not fragmented, and a yield of 1 mg/g cell was obtained. These results, together with studies of rheological properties, have led to the design of a 60-L, stirred lysis reactor and the production of high-quality pDNA solution with <1% chDNA after further purification.

Bioreactors↗
PubMed2001

Silver syndrome is not linked to any of the previously established autosomal dominant hereditary spastic paraplegia loci.

The hereditary spastic paraplegias are a clinically variable and genetically heterogeneous group of disorders characterized by progressive and lower limb spasticity and weakness. Silver syndrome (SS) is a particularly disabling autosomal dominant form of the disease in which there is associated wasting of the hand muscles. In view of the fact that genes for hereditary spastic paraplegia can produce highly variable phenotypes, the eight known autosomal dominant loci were investigated for linkage to Silver syndrome. Genotyping of these loci in two large multigenerational families was incompatible with linkage to any of these regions, suggesting that an additional locus is responsible for this syndrome.

Adult↗
PubMed2001

Effects of kaliuretic peptide on sodium and water excretion in persons with congestive heart failure.

Kaliuretic peptide, a 20-amino acid peptide hormone synthesized in the heart, enhances urine flow twofold, whereas atrial natriuretic peptide (ANP) enhances urine flow four- to 11-fold in healthy persons. The present investigation was designed to (1) determine whether kaliuretic peptide may have beneficial diuretic effects in persons with congestive heart failure (CHF), and (2) compare its beneficial effects with ANP in the treatment of CHF. Kaliuretic peptide (100 ng/kg body weight/min) given intravenously for 60 minutes to subjects with New York Heart Association class III CHF increased urine flow fourfold (p <0.001), which was maximal 212 hours after its infusion was stopped. Kaliuretic peptide enhanced sodium excretion threefold in subjects with CHF (p <0.01). Kaliuretic peptide increased the urinary excretion rate of potassium ion and fractional excretion of potassium 3.5- and twofold (p <0.05), respectively. ANP (same concentration) did not significantly enhance urine flow. ANP enhanced sodium excretion two- to sixfold in half of the CHF subjects, whereas it had no effect on sodium excretion in the other half. ANP did not significantly increase fractional excretion of sodium but did increase fractional excretion of potassium (p <0.05) during the first 20 minutes of its infusion. ANP-infused patients with CHF became hypotensive. None became hypotensive secondary to kaliuretic peptide. These data indicate that the diuretic properties of kaliuretic peptide in persons with CHF, as opposed to those of ANP, are not diminished (but rather are increased) compared with their effects in healthy persons. In patients with CHF, kaliuretic peptide causes a natriuresis-a feature not observed in those without sodium retention.

Adult↗
PubMed2001

Preventive health care, 2001 update: screening and management of developmental dysplasia of the hip in newborns.

OBJECTIVE: To review the effectiveness of, and make practice recommendations for, serial clinical examination and ultrasound screening for developmental dysplasia of the hip (DDH) in newborns. The effectiveness of selective screening of high-risk infants with hip and pelvic radiographs and treatment with abduction therapy are also examined. OPTIONS: Screening: serial clinical examination, ultrasound screening, radiographic evaluation. TREATMENT: abduction therapy. OUTCOMES: Rates of operative intervention, abduction splinting, delayed diagnosis of DDH (beyond 3-6 months), treatment complications and false diagnostic labelling. Long-term functional outcomes were considered important. EVIDENCE: MEDLINE was searched for relevant English-language articles published from 1966 to November 2000 using the key words "screening," "hip," "dislocation," "dysplasia," "congenital" and "ultrasound." Comparative and descriptive studies and key reviews were retrieved, and their bibliographies were manually searched for further studies. BENEFITS, HARMS AND COSTS: Because most infants will have spontaneous resolution of nonteratologic DDH, early identification and intervention results in unnecessary labelling of newborns as having the problem and unnecessary treatment. Ultrasound screening is a highly sensitive but poorly specific measure of clinically relevant DDH. Abduction splinting is associated with a variety of problems, and its effectiveness in treating DDH is not clearly known. At least 20% of infants requiring operative intervention have had splint therapy. The harms of labelling, repetitive investigations, unnecessary splinting and resource consumption associated with screening are substantial. VALUES: The strength of evidence was evaluated using the evidence-based methods of the Canadian Task Force on Preventive Health Care. RECOMMENDATIONS: There is fair evidence to include serial clinical examination of the hips by a trained clinician in the periodic health examination of all infants until they are walking independently (level II-1 and III evidence; grade B recommendation). There is fair evidence to exclude general ultrasound screening for DDH from the periodic health examination of infants (level II-1 and III evidence; grade D recommendation). There is fair evidence to exclude selective screening for DDH from the periodic health examination of high-risk infants (level II-1 and III evidence; grade D recommendation). There is fair evidence to exclude routine radiographic screening for DDH from the periodic health examination of high-risk infants (level III evidence; grade D recommendation). There is insufficient evidence to evaluate the effectiveness of abduction therapy (level III evidence; grade C recommendation), but good evidence to support a period of close observation for newborns with clinically detected DDH (level I evidence; grade A recommendation). However, there is insufficient evidence to determine the optimal duration of observation (level III evidence; grade C recommendation). VALIDATION: The members of the Canadian Task Force on Preventive Health Care reviewed the findings of this analysis through an iterative process. The task force sent the final review and recommendations to selected external expert reviewers, and their feedback was incorporated in the final draft of the manuscript. SPONSORS: The Canadian Task Force on Preventive Health Care is funded through a partnership between the Provincial and Territorial Ministries of Health and Health Canada.

Canada↗
PubMed2001

The Silver syndrome variant of hereditary spastic paraplegia maps to chromosome 11q12-q14, with evidence for genetic heterogeneity within this subtype.

The hereditary spastic paraplegias (HSPs) are a complex group of neurodegenerative disorders characterized by lower-limb spasticity and weakness. Silver syndrome (SS) is a particularly disabling dominantly inherited form of HSP, complicated by amyotrophy of the hand muscles. Having excluded the multiple known HSP loci, we undertook a genomewide screen for linkage of SS in one large multigenerational family, which revealed evidence for linkage of the SS locus, which we have designated "SPG17," to chromosome 11q12-q14. Haplotype construction and analysis of recombination events permitted the minimal interval defining SPG17 to be refined to approximately 13 cM, flanked by markers D11S1765 and D11S4136. SS in a second family was not linked to SPG17, demonstrating further genetic heterogeneity in HSP, even within this clinically distinct subtype.

Adolescent↗
PubMed2001

The theory and application of transition state pK(a) values: the reaction of papain with a series of trimethylene disulphide reactivity probes.

For many years methods to describe the structure of the transition state for a reaction have been sought. Most commonly these structures have been inferred from kinetic isotope effects. We report here for the first time the application of transition state pK(a) values to describe the relationship between molecular recognition and the transition state for the catalytic mechanism of papain. The background to the theory is presented and applied to the reactions of papain with a series of trimethylene disulphide reactivity probes. The common feature of these reactions is a loss in reactivity on ionization of the imidazolium cation for those probes containing molecular recognition features and an increase in reactivity on ionization of the electrostatic switch residue. The use of transition state pK(a) values enhances this information by providing details regarding the protonic distribution within the transition state. This has led to the reconsideration of the effect of the electrostatic switch ionization and the role of the hydrogen bond formed between the catalytic-site imidazolium cation and the leaving group of the reaction in the catalytic mechanism of papain.

Catalysis↗
PubMed2001

Measurement of MAP kinase activation by flow cytometry using phospho-specific antibodies to MEK and ERK: potential for pharmacodynamic monitoring of signal transduction inhibitors.

Cancer cells frequently show abnormal signaling via the mitogen activated protein kinase (MAP kinase) pathway due to increased activity of surface receptors for growth factors, or as a result of ras mutations. The development of potent anti-cancer agents that target this pathway prompts the need for analytical methods that allow pharmacodynamic monitoring of drug effects in patients during early phase clinical trial. We describe such a method, based on the activation of T-lymphocytes in undiluted peripheral blood using phorbol myristate acetate (PMA). Following rapid hypotonic lysis and formaldehyde fixation, activation of the MAP kinase pathway can then be demonstrated using phospho-specific antibodies that recognize the activated mediators MEK or ERK, followed by surface labeling with anti-CD3 to identify T-lymphocytes. This method was used to investigate the effects of a MEK inhibitor, U0126, and a new raf kinase inhibitor BAY 37-9751 in blood samples from normal donors. Dose-dependent inhibition of pERK activation was demonstrated for both agents. Furthermore, differential effects on pMEK activation allowed the molecular targets of the two inhibitors to be distinguished. In addition to monitoring drug effects in patients during treatment with inhibitors of the MAP kinase pathway, the general methodology described in this paper has the potential for wide application to the study of signal transduction at the single cell level using flow cytometry.

Blotting, Western↗
PubMed2001

P53 mutation and response to hepatic arterial floxuridine in patients with colorectal liver metastases.

PURPOSE: To establish the relationship between the number and site of p53 genomic mutations in metastatic colorectal cancer, and the response to hepatic arterial floxuridine. METHODS: Liver metastasis biopsies were collected, at the time of laparotomy for hepatic arterial cannulation. in 28 patients with metachronous colorectal liver metastases. p53 Gene mutations were assessed using reverse transcription, nested polymerase chain reaction, single strand conformational polymorphism and gene sequencing. Chemotherapy response was determined from computerised liver tomograms after 4 months of treatment. RESULTS: Liver metastasis p53 mutation was identified in 21 (75%), and p53 "hot spot" mutation in 11 (39%) patients. There was a significantly lower prevalence (Fisher's, P=0.001) of patients with p53 "hot spot"-mutated liver metastases in stable disease and partial response (5/22) than in progressive (6/6) disease groups. Significantly fewer (Mann-Whitney U, P=0.002) p53 "hot spot" mutations/biopsy were observed in liver metastases from stable disease and partial response (median 0, iqr. 0-0) than in progressive (median 1, iqr 1-2) disease patients. p53 "Hot spot"-mutated liver metastases were associated with significantly shorter survival times (logrank P=0.05) after hepatic arterial floxuridine. Significant response or survival-time differences by total or L2/L3 zinc-binding site p53 mutations were not detected. CONCLUSIONS: The results support a role for p53 "hot spot" mutations in colorectal liver metastasis resistance to fluorinated pyrimidines, and suggest that the presence of such mutations may be a contra-indication to treatment of colorectal liver metastases with hepatic arterial floxuridine.

Adult↗
PubMed2001

Measuring the water retention capacities (MRC) of different microcrystalline cellulose grades.

The ability of various types of microcrystalline cellulose (MCC) to hold water when subjected to an applied force has been assessed by a centrifuge technique. By considering the final percent of water retained after a standard centrifugation, as a function of the initial water content, a moisture retention capacity (MRC) can be determined. Statistical analysis of the results identified that it was possible to divide the nine samples of MCC into six sub-sets in terms of final moisture content retained. Those types which contained added polymer had by far the highest water level remaining. In terms of the MRC value, statistical analysis again sub-divided the celluloses into six sub-sets, although different from those for the final water content. Again those types containing added polymer gave much higher MRC values. As experiments were carried out with initial water/MCC ratios of different levels, statistical analysis of the influence of initial water content on the MRC values was undertaken with each type of MCC. The results showed a varying dependence on initial water level with the different types of cellulose. To provide a value of MRC which characterised the cellulose, the maximum value of MRC at the lowest initial water level was identified. Samples of MCC with low values of MRC have been shown previously to require less water for processing by extrusion/spheronization, while celluloses with a high MRC value appear better for the limitation of water movement during the process of extrusion/spheronization. The water retention must, however, also be considered in association with the rheological properties of the wet powder mass. Thus, while the Avicel RC591 had the highest MRC value, its rheological properties are so that the production of pellets with such a type can be less effective than with other types of MCC.

Algorithms↗
PubMed2001

Impact of PACS on the education of radiology residents: the residents' perspective.

RATIONALE AND OBJECTIVES: Because digital imaging and the picture archiving and communication system (PACS) are replacing radiographic film, the effect of PACS on residents' perceptions and their educational experience was investigated. MATERIALS AND METHODS: Residents taking part in large diagnostic radiology training programs at two hospitals were surveyed. Approximately 75% of radiographic studies were reviewed with the use of PACS at both hospitals. Survey topics included technical and didactic issues based on direct and indirect comparison with analog (conventional film) images. RESULTS: Fifty residents were polled (20 respondents). The majority has been using PACS for more than 1 year (14 of 20, 70%) to interpret 75%-100% of cases (11 of 20, 55%). The majority believed that PACS improved patient care (15 of 20, 75%) and their educational experience (15 of 20, 75%). A minority believed that increased patient throughput was harmful to the educational experience (five of 20, 25%) because it permitted attending radiologists to review cases too quickly (four of 20, 20%). Residents favored PACS over hard-copy images for ease of manipulation, resolution, and ability to see pathologic conditions and normal anatomic characteristics. CONCLUSION: Residents believe that PACS has positively affected their learning experience and does not negatively affect the quality of resident education.

Attitude of Health Personnel↗
PubMed2001

Detection and clinical significance of occult tumour cells in colorectal cancer.

BACKGROUND: A variety of techniques have been employed for the detection of occult tumour cells in the blood, bone marrow and lymph nodes of patients with colorectal cancer. This review examines the methods used, results obtained and the clinical significance of studies in this field. METHODS: A Medline literature search was performed using the terms colorectal cancer, minimal residual disease, micrometastasis, polymerase chain reaction, reverse transcriptase polymerase chain reaction and immunocytochemistry; further references were obtained from key articles. RESULTS: Immunocytochemical examination of bone marrow is the benchmark for detecting clinically significant occult disease. Larger standardized studies are required to confirm the prognostic significance of molecular assays for the detection of tumour cells in blood and bone marrow. The prognostic significance of lymph node tumour cells detected by either immunohistochemical or molecular methods awaits further affirmation. CONCLUSION: Standardization of terminology and techniques used, combined with large prospective clinical studies, is required if detection of occult residual disease is to become a prognostic marker for recurrence in colorectal cancer.

Biomarkers, Tumor↗
PubMed2001

Homozygosity at chromosome 8qter in individuals affected by mal de Meleda (Meleda disease) originating from the island of Meleda.

BACKGROUND: The inherited palmoplantar keratodermas (PPKs) are a clinically heterogeneous group of disorders characterized by thickening of the skin of the palms and the soles. These diseases also exhibit genetic heterogeneity and many autosomal dominant and recessive forms have been described. Mal de Meleda (Meleda disease, MD) is an autosomal recessive form of PPK first described on the Dalmatian island of Meleda. A gene for MD has recently been assigned to the most telomeric portion of chromosome 8q using two large Algerian families. OBJECTIVES: To determine whether the same gene underlies the skin disease in Meleda islanders. METHODS: We have examined five affected individuals originating from the Dalmatian island itself for 8qter homozygosity. RESULTS: This region was found to be homozygous in all five affected individuals but in none of the 20 other unaffected family members examined. CONCLUSIONS: The current study confirms the localization of a gene for MD to 8qter using samples from the island of Meleda, highlighting the clinical and genetic homogeneity of this condition.

Chromosomes, Human, Pair 8↗
PubMed2001

Penoplasty for buried penis in children: report of 50 cases.

PURPOSE: The authors report their experience with a large number of children with buried penis and describe their surgical technique. METHODS: Fifty consecutive cases of buried penis that occurred between 1993 and 1999 were analyzed by chart review. Age at the time of surgery was 11 months to 13 years. Each patient underwent elective surgical repair utilizing a surgical technique not described previously. The authors' technique avoids a circumferential incision at the base of the penis, decreasing postoperative edema. The authors also utilize a unique through and through vertical mattress suture at the base of the penis that firmly attaches the shaft skin to the underlying corpora. RESULTS: All patients had a good to excellent outcome with a low postoperative complication rate. One patient fell during the postoperative period and developed a wound dehiscence. Early in the series 3 patients underwent additional procedures for recurrent retraction (6%). All patients experienced some postoperative discomfort as expected. Edema, when present, was mild and resolved within an acceptable period of time. All patients had a good cosmetic result with increased visualization of the penile shaft. CONCLUSIONS: A surgical approach to the buried penis is warranted in most circumstances. There are psychological benefits to both the patients and the parents. Although the authors perform the procedure as early as 11 months, it can be performed safely at 3 months. The procedure reported here provides immediate excellent cosmetic results with a low complication rate. The authors do not recommend suprapubic lipectomy either alone or in combination with the buried penis procedure. Circumcision should be avoided in an infant with a definite diagnosis of buried penis.

Adolescent↗
PubMed2001

Female circumcision.

Female circumcision, more accurately known as female genital mutilation, is still a common practice in parts of Africa. This ritual genital operation can involve partial or complete excision of the clitoris and labia minora as well as infibulation (labial fusion). The case reported here involves a 16-year-old African girl with a complication of this mutilating procedure.

Adolescent↗
PubMed2001

Bifrontal decompressive craniectomy in the management of posttraumatic intracranial hypertension.

Bifrontal decompressive craniectomy has been used on an ad hoc basis for the treatment of post-traumatic intracranial hypertension for more than thirty years. In this observational study we report the clinical outcome and physiological effects of the procedure in a series of 26 patients with refractory intracranial hypertension treated on a protocol driven basis. Bifrontal decompressive craniectomy was associated with significant reductions in mean ICP from 37.5 to 18.1 mmHg (p = 0.003). In addition, craniectomy reduced the amplitude of ICP waves (p < 0.02) and increased compensatory reserve (p < 0.05). A favourable outcome was achieved in 69% of patients; 8% were severely disabled and 23% died. We conclude that this study provides pathophysiological evidence that bifrontal decompressive craniectomy significantly reduces posttraumatic intracranial hypertension and improves pressure dynamics. Our results support the continued use of bifrontal decompressive craniectomy in selected patients after head injury.

Adolescent↗
PubMed2001

Self antigen prognostic for human immunodeficiency virus disease progression.

We have recently found that an extracellular protein, alpha(1) proteinase inhibitor (alpha(1)PI; alpha(1) antitrypsin), is required for in vitro human immunodeficiency virus (HIV) infectivity outcome. We show here in a study of HIV-seropositive patients that decreased viral load is significantly correlated with decreased circulating alpha(1)PI. In the asymptomatic category of HIV disease, 100% of patients manifest deficient levels of active alpha(1)PI, a condition known to lead to degenerative lung diseases and a dramatically reduced life span. Further, HIV-associated alpha(1)PI deficiency is correlated with circulating anti-alpha(1)PI immunoglobulin G. These results suggest that preventing HIV-associated alpha(1)PI deficiency may provide a strategic target for preventing HIV-associated pathophysiology.

Acquired Immunodeficiency Syndrome↗