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Biomedical subjects

P Patel

Publications and source records attributed to P Patel.

At least 163 records · Page 9Linked to original sources
PubMed1993

Altered ratios of beta-endorphin: beta-lipotropin released from anterior lobe corticotropes with increased secretory drive. I. Effects of diminished glucocorticoid secretion.

Previous studies have demonstrated that acute stress or ovine corticotropin-releasing hormone (oCRH) in vivo, or oCRH in vitro, stimulates release of beta-endorphin over beta-lipotropin from anterior pituitary corticotropes. This occurs despite the predominance of beta-lipotropin in corticotrope peptide stores. In vitro studies with primary anterior pituitary cultures suggested that chronic exposure to oCRH results in a shift towards more beta-lipotropin secretion into the media than with short-term exposure. The current studies explored whether increased secretory drive in vivo results in a similar shift towards more beta-lipotropin. We used removal of glucocorticoids by adrenalectomy or metyrapone blockade of corticosterone synthesis, to stimulate endogenous secretion of CRH and vasopressin. Both treatments resulted in shifts of the ratio of beta-endorphin: beta-lipotropin in plasma of experimental animals in comparison to the sham-treated control rats. In vitro testing with oCRH of anterior lobe cultures from adrenalectomized or metyrapone-treated rats demonstrated similar effects of these treatments on the ratio of beta-endorphin:beta-lipotropin. These changes occurred despite similar ratios of beta-endorphin:beta-lipotropin in anterior pituitary peptide stores.

Adrenalectomy↗
PubMed1993

Microsatellite polymorphisms at the glucokinase locus: a population association study in Caucasian type 2 diabetic subjects.

Glucokinase has a central role in glucose metabolism in pancreatic beta cells and hepatocytes and is an important candidate gene for Type 2 diabetes. Mutations of the glucokinase gene have been reported in Caucasian pedigrees with maturity-onset diabetes of the young and late-onset Type 2 diabetes. In population studies of American Blacks and Mauritian Creoles an association between alleles of a glucokinase polymorphism and Type 2 diabetes has been described. Two microsatellite polymorphisms (GCK 1 and GCK 2) flanking the glucokinase gene were investigated in Caucasian subjects. There was no significant linkage disequilibrium between the alleles of the two polymorphisms. The overall allelic frequencies for GCK 1 and the combined haplotyes did not significantly differ between 95 Type 2 diabetic and 76 normoglycaemic subjects. In an expanded cohort of 151 diabetic subjects the allelic frequencies at GCK 2 were also similar to controls. These results suggest that a single mutation of the glucokinase gene is not a common cause of Type 2 diabetes in English Caucasians.

Alleles↗
PubMed1993

Rapid HLA typing by multiplex amplification refractory mutation system.

AIMS: To detect HLA susceptibility and protective alleles associated with insulin dependent diabetes mellitus (IDDM) using a multiplex amplification refractory mutation system (ARMS). These include DR3 and DR4 alleles at the DRB1 locus, presence or absence of aspartic acid at position 57 (Asp-57) of the DQB1 locus, and presence or absence of arginine at position 52 (Arg-52) of the DQA1 locus. METHODS: The ARMS approach was used to design allele specific primers for the detection of the major susceptibility and protective alleles for IDDM. These include DR3 and DR4 alleles at the DRB1 locus, Asp-57 and non-Asp-57 at the DQB1 locus, and Arg-52 and non-Arg-52 alleles at the DQA1 locus. The allele specificity of each set of primers was first tested separately using DNA samples from 15 individuals previously typed for the DRB1, DQB1, and DQA1 loci using the sequence specific oligonucleotide (SSO) technique. The possibility of using multiplex ARMS for typing multiple susceptibility/protective alleles for IDDM was further investigated by testing various combinations of allele specific primers, thereby reducing the number of separate polymerase chain reactions required to type all these alleles. RESULTS: A "three-tube" system worked well and gave accurate results. Tube 1 contained ARMS primers for the detection of IDDM susceptibility alleles DR3 and DR4; tube 2 contained ARMS primers for the detection of susceptibility alleles non-Asp-57 and Arg-52; and tube 3 contained ARMS primers for the detection of the protective alleles Asp-57 and non-Arg-52. DNA samples typed with this ARMS method were in complete agreement with those obtained using the SSO technique. CONCLUSION: This method is rapid and has no requirement for radioactivity. It is an efficient method for population screening.

Alleles↗
PubMed1993

Selection of acute stroke patients for treatment of visual neglect.

Although visual neglect is a predictor of poor outcome after stroke, some patients regain independence, whilst others take up considerable rehabilitation resources. Intensive treatment of visual neglect is available and a knowledge of the predictive features in the recovery of these patients would be helpful in the early selection of patients for treatment. A study was therefore carried out to determine the prognosis of patients presenting with visual neglect at two to three days after stroke. Linear logistic regression showed that the initial degree of paralysis (measured by the Motricity Index), the severity of neglect (measured by the Visual Neglect Recovery Index) and the patient's age were the significant predictors of independence (Barthel score 20), mild dependence (Barthel 15-19), and moderate/severe dependence (Barthel 0-14) in surviving patients at three months and at six months. Regression equations correctly predicted 78% of outcomes, and had a sensitivity and specificity for "independence" of 84% and 90% respectively, and a sensitivity and specificity for "moderate/severe dependence" of 89% and 80%. It is suggested that these equations may be useful in selecting comparable groups of patients for randomised controlled trials of treatment of visual neglect.

Aged↗
PubMed1993

Beam profile analysis using GafChromic films.

GafChromic film dosimetry techniques were used to evaluate the beam profiles for each collimator of the Leksell Gamma Knife at the University of Kentucky Medical Center. At the conclusion of acceptance testing, representatives from Leksell exposed conventional films for beam profile processing and analysis in Sweden. At the same time, an inhouse technique using GafChromic films was utilized in the analysis of the beam profiles. GafChromic films were irradiated to 100 Gray to provide data in each of the three planes for each collimator size. The films were analyzed using a scanning helium-neon laser densitometer with a small aperture of 5-10 microns. The digitized density profiles were curve-fitted using a PC plotting algorithm. The curve-fitted density profiles were converted to relative dose using a standard calibration curve determined with a conventional cobalt-60 teletherapy beam. The results are in excellent agreement with the conventional film analysis reported by Leksell. The GafChromic method has proven to be an accurate and rapid method of analysis and could be easily incorporated into a quality assurance program.

Calibration↗
PubMed1993

A tissue equivalent phantom for stereotactic radiosurgery localization and dose verification.

A tissue equivalent head phantom was utilized in the stereotactic localization and dose verification of radiosurgery procedures with the Leksell Gamma Knife Unit at the University of Kentucky Medical Center. A radiation dose-dependent color-doped gel target was positioned within the head phantom and stereotactically localized using either angiography, CT, or MR techniques. Utilizing standard Gamma Knife treatment procedures, the head phantom was irradiated, which resulted in a color change of the gel tumor at the position of the treatment isocenter and thereby confirmed the localization procedure. Additionally, a radiation dosimeter (thermoluminescent dosimetry--TLD) was positioned within the head phantom and localized using an angiography frame and a standard radiation therapy simulator. The phantom skull measurements and the dosimeter coordinates were entered into the Leksell Gamma Knife dose planning computer (KULA) and an irradiation time for 40 Gy using the 18-mm collimator was determined. The TLD dose evaluations were relatively determined using a cobalt-60 calibration curve. The experimental dose verification results agreed well (+/- 4%) with computer dose estimates.

Algorithms↗
PubMed1993

Psychiatric morbidity in older people with moderate and severe learning disability. I: Development and reliability of the patient interview (PAS-ADD).

This paper describes the development of the PAS-ADD, a semistructured clinical interview for use specifically with patients with learning disabilities, based on items drawn from the PSE. The PAS-ADD includes a number of novel features including: parallel interviewing of patient and informant; a three-tier structure to provide a flexible interview appropriate to the patient's intellectual level; use of a memorable 'anchor event' in the patient's life to improve time focus; and simplified wording, improved organisation and lay out. Inter-rater reliability was investigated using an experimental design in which two raters viewed and re-rated videotaped PAS-ADD interviews which had been conducted by an experienced clinician. Reliability results compared favourably with those obtained in a major study of PSE reliability with a sample drawn from non-learning disabled individuals. Mean kappa for all items was 0.72. Other indexes of reliability were also good. In the current phase of development, the PAS-ADD is to be expanded to include further diagnostic categories, including schizophrenia and autism. The new version will be updated for use with ICD-10 criteria.

Aged↗
PubMed1993

Psychiatric morbidity in older people with moderate and severe learning disability. II: The prevalence study.

We present a prevalence study of psychiatric morbidity in people over 50 years of age with learning disability (LD), using a new semistructured clinical interview specifically for use with people who have LD (the 'PAS-ADD'). Assessment involved parallel interviewing of subject and informant, these two sets of information being combined to reach a final diagnosis using ICD-9 and DSM-III-R criteria. Detection of dementia involved interviews with informants, plus investigation of loss of cognitive function over a three-year period. The experimental sample was a mixed community and institutional group (n = 105), including, as far as possible, all people in a single administrative district (Oldham) matching the age and ability criteria. Prevalence of psychiatric disorder excluding dementia was 11.4% (n = 12), most of which were depression and anxiety. Seventy-five per cent of these cases were unknown to mental health services. However, immediate care staff were usually aware of the symptoms, although often unaware of their clinical significance. Prevalence of dementia was also 11.4% (n = 12), with a combined case prevalence of 21.0% (n = 22). The PAS-ADD proved a flexible interview, effective in use with people of varying linguistic level and intellectual ability: 61.9% (n = 65) of the sample were able to be interviewed, fully adequate clinical interviews being obtained with a group of 38 people whose mean IQ was only 39. In the remaining 38.1% (n = 40), diagnosis relied exclusively on informant data. Overall, the combination of subject and informant data was essential for sensitive case detection.

Aged↗
PubMed1993

Distribution of type II diabetes in nuclear families.

Type II diabetes has a substantial genetic component, but the mode of inheritance and the molecular basis of this inheritance are uncertain. This study documents the familial distribution of the disease in the parents and siblings of a consecutive series of type II diabetic subjects. We studied 66 first-degree relatives of 20 white subjects with type II diabetes and both parents alive. They were tested with a continuous infusion of glucose (5 mg.kg IBW-1.min-1) (n = 49) or FPG and hemoglobin A1c (n = 17). Seven probands had neither parent affected with diabetes or IGT, 10 had one parent affected (6 with diabetes and 4 with IGT), and 3 had both parents affected. The probands with affected and those with unaffected parents were phenotypically similar. These findings indicate that a sizable subgroup of type II diabetic subjects may have neither parent affected with a demonstrable abnormality of glucose tolerance. The assumption of autosomal dominance with complete penetrance is not supported, although it remains possible that a dominant gene of low penetrance may play a role in some pedigrees. Polygenic inheritance would appear likely, and genetic heterogeneity may occur. The inheritance of diabetic traits from phenotypically normal parents needs to be considered in the analysis of genetic linkage with type II diabetes.

Adult↗
PubMed1993

Dysgenesis of the corpus callosum: computed tomographic changes.

The CT findings in 32 cases of DCC are presented classifying them into three groups: Type I: Anatomical changes primarily due to callosal dysgenesis. Type II: Associated central nervous system anomalies. Type III: Incidental findings. The findings were compared with those of others. This study confirms that the CT findings which are of a high diagnostic index are those of Type I changes which include enlargement and elongation of the interventricular foramen, enlargement and continuity of the interhemispheric fissure with the third ventricle, which is invariably enlarged, elevation and anterior displacement of the third ventricle. Separation and parallelism of the lateral ventricle is also one of the most diagnostic features. Three rare syndromes (Soto's, Aicardi's and De Morsier's) and the rare occurrence of associated teratoma which were encountered as part of the associated congenital abnormalities are mentioned. The embryological basis of the CT findings is discussed.

Abnormalities, Multiple↗
PubMed1992

Linkage of type 2 diabetes to the glucokinase gene.

Maturity-onset diabetes of the young (MODY) is a subtype of type 2 diabetes that presents from the second decade and has an autosomal dominant mode of inheritance. We have investigated the glucokinase gene, a candidate gene for diabetes, in two MODY pedigrees. In a large 5-generation pedigree (BX) with 15 diabetic members, use of a microsatellite polymorphism revealed linkage of diabetes to the glucokinase locus on chromosome 7p. A peak lod score of 4.60 was obtained at a recombination fraction (theta) of zero. This finding suggests that a defective glucokinase gene contributes to the diabetes phenotype in this pedigree. This is not universal in MODY since linkage to the glucokinase locus was excluded in a second pedigree M (lod score = -7.36 at theta = 0). The affected members in pedigree BX were diagnosed either when young (in pregnancy or on screening) or when they presented symptomatically in middle and old age; most of them were treated by diet alone. Defects in the glucokinase gene may play an important part in the pathogenesis of type 2 diabetes.

Adolescent↗
PubMed1992

Large-scale purification of plasmid DNA by fast protein liquid chromatography using a Hi-Load Q Sepharose column.

The large-scale purification of plasmid DNA was achieved using fast protein liquid chromatography on a Hi-Load Q Sepharose column. This method allows for the purification of plasmids starting from crude plasmid DNA, prepared by a simple alkaline lysis procedure, to pure DNA in less than 5 h. In contrast to the previously described plasmid purification methods of CsCl gradient centrifugation or high-pressure liquid chromatography, this method does not require the use of any hazardous or expensive chemicals. More than 100 plasmids varying in size from 3 to 15 kb have been purified using this procedure. A Mono Q Sepharose column was initially used to purify plasmids smaller than 8.0 kb; however, a Hi-Load Q Sepharose column proved more effective with plasmids larger than 8 kb. The loading of plasmids larger than 8 kb on the Mono Q column resulted in a high back pressure and the plasmid DNA could not be eluted from the column. Thus, for routine purification we utilize the Hi-Load Q Sepharose column. Plasmids purified by this method had purity, yield, and transfection efficiency in mammalian cells similar to those of plasmids purified by CsCl density gradient centrifugation.

Centrifugation, Density Gradient↗
PubMed1992

Analysis of complex genetic systems by ARMS-SSCP: application to HLA genotyping.

We have developed a new method for analysis of complex genetic systems by a combination of the Amplification Refractory Mutation System (ARMS) and Single-Strand Conformation Polymorphism (SSCP) analysis: ARMS-SSCP. Thus, a complex allelic series is subdivided into a number of groups by ARMS followed by the identification of specific alleles using SSCP analysis. We have shown that the HLA alleles at the DRB3 and DQB1 loci were distinguishable from each other using ARMS-SSCP. In 36 individuals typed for the DRB3 and 48 individuals typed for the DQB1 loci, ARMS-SSCP results were in complete agreement with those obtained using the established method of sequence-specific oligonucleotide (SSO) hybridisation. With silver staining, ARMS-SSCP is a rapid, non-radioactive and reliable method which also offers the possibility for detecting new HLA alleles. We have demonstrated that ARMS-SSCP can be performed using fluorescent PCR primers, a feature which gives the method potential for automation.

Base Sequence↗
PubMed1992

Management of cervical lymph nodes in patients with head and neck cancer.

The status of the cervical lymph nodes is the single most important prognostic factor in head and neck cancer. Unfortunately, clinical assessment of the neck is not very accurate, although newer imaging techniques such as CT, MRI and ultrasound-guided fine needle aspiration cytology can be used to improve upon the results of clinical palpation alone. While diagnostic techniques remain less than 100% accurate, the risk of occult disease in the neck will remain. If this occurrence is judged to be greater than 15-20%, elective treatment to the neck may then be justified. When the neck is treated surgically, histological information can be gained which has both prognostic and therapeutic implications. Indications for the use of surgery and radiotherapy for the elective and therapeutic management of the neck and the results of such treatment are discussed.

Combined Modality Therapy↗
PubMed1992

Clinical experience with the low-resistance Groningen button.

Since its introduction in 1980, the standard Groningen button prosthesis has been of proven value for post-laryngectomy voice rehabilitation. Its relatively high airflow resistance has, however, been the cause of failure in achieving good post-laryngectomy tracheoesophageal shunt speech in some patients. The low-resistance Groningen button (LRGB) was therefore designed, thus reducing airflow resistance by 50% when compared to the standard device. The clinical performance of the LRGB, and the effect of prophylactic amphotericin, was assessed in 32 patients. The device lifetime, intratracheal phonatory pressures and patients' subjective acceptances of the prosthesis were recorded. Present findings showed that the majority of the patients preferred the LRGB as it required less effort to operate than the standard device. The intra-tracheal phonatory pressure was found to increase with time, but this change was prevented with the prophylactic use of amphotericin to inhibit concurrent colonization by Candida spp, which also helped to prolong the prosthesis lifetime.

Amphotericin B↗