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Biomedical subjects

P Khan

Publications and source records attributed to P Khan.

At least 19 recordsLinked to original sources
PubMed2001

Single-nucleotide polymorphism alleles in the insulin receptor gene are associated with typical migraine.

We have identified a migraine locus on chromosome 19p13.3/2 using linkage and association analysis. We isolated 48 single-nucleotide polymorphisms within the locus, of which we genotyped 24 in a Caucasian population comprising 827 unrelated cases and 765 controls. Five single-nucleotide polymorphisms within the insulin receptor gene showed significant association with migraine. This association was independently replicated in a case-control population collected separately. We used experiments with insulin receptor RNA and protein to investigate functionality for the migraine-associated single-nucleotide polymorphisms. We suggest possible functions for the insulin receptor in migraine pathogenesis.

Alleles↗
PubMed2000

Phase I and pharmacologic study of CT-2584 HMS, a modulator of phosphatidic acid, in adult patients with solid tumours.

CT-2584 HMS, 1-(11-dodecylamino-10-hydroxyundecyl)-3, 7-dimethylxanthine-hydrogen methanesulphonate, is a modulator of intracellular phosphatidic acid. We treated 30 patients as part of a Phase I and pharmacokinetic study to determine the maximum-tolerated dose of CT-2584 HMS, toxicity profiles, pharmacokinetic profile and antitumour effects at escalating dose levels. CT-2584 HMS was given as a continuous infusion for 6 hours for 5 consecutive days every 3 weeks. Plasma samples for pharmacokinetic studies were analysed using a validated high-performance liquid chromatographic assay. Mean C(max)and AUC values for each dose group were similar on days 1 and 5 and increases in plasma concentration (C(max)and AUC) appeared proportional to the dose. CT-2584 HMS had a mean elimination half-life of 7.3 hours. Values of V(d)and clearance were independent of dose and duration of treatment. Dose escalation was halted at 585 mg/m(2)because of malaise and lethargy, which was sometimes accompanied by nausea and headache. 26 patients were evaluable for response, one patient with pleural mesothelioma achieved a partial response to treatment confirmed by CT scanning. A dose level of 520 mg/m(2)daily x 5 days would be suitable for Phase II testing. Alternative schedules of CT-2584 HMS to overcome the limiting toxicity of malaise would be worthy of examination.

Adult↗
PubMed2000

Primary splenic angiosarcoma: case report and literature review.

Angiosarcoma of the spleen is a rare neoplasm. We describe the clinical findings of an index case at our institution and the results of a literature review of the topic. Generally, this cancer has a poor prognosis and prompt splenectomy offers the only cure, as the cancer is poorly responsive to adjuvant chemotherapy.

Combined Modality Therapy↗
PubMed2000

What role for the general practitioner in child protection?

BACKGROUND: New government guidance on cooperation in child protection confirms the importance of the general practitioner (GP) contribution. While research highlights the concerns of others about their role in the multi-agency process, relatively little is known about the views and experiences of GPs themselves. AIM: To examine the understanding that each of the key professional groups had of its own and each other's roles in child protection to identify those factors seen to enhance or inhibit the effective performance of these roles. METHOD: The research formed part of a larger investigation of the role of health professionals in child protection, which combined case study investigations of child protection networks in three health authority sites with a regional survey of Area Child Protection Committee members. RESULTS: A lack of correspondence was identified between GPs' perception and performance of their role in child protection and the expectations placed upon them by other child protection professionals and government guidance. CONCLUSION: The study identifies the need for more explicit discussion of the nature and extent of the GP role in local interagency child protection networks.

Child↗
PubMed1999

Development and validation of a sensitive solid-phase extraction and high-performance liquid chromatographic assay for the novel bio-reductive anti-tumor agent RH1 in human and mouse plasma.

A HPLC assay and solid-phase extraction technique from human plasma has been developed and validated for the experimental anticancer agent, RH1 (2,5-diaziridinyl-3-hydroxymethyl-6-methyl-1,4-benzoquinone) which is currently being evaluated by the CRC phase I/II committee. A 500 mg amino propyl solid-phase extraction cartridge was used to isolate RH1 from human plasma. Analysis was performed on a reversed-phase chromatography system using a 15 cm cyanopropyl column and isocratic elution with a 10% methanol-90% water (double distilled) solution. The lower limit of quantitation for RH1 was found to be 0.00375 microg/ml (3.75 ng/ml+/-8.3%) in water and following extraction from plasma. Recovery of >80%(+/-11.9%) was achieved over a five-day validation study. This method was used to carry out pre-clinical studies in BDF mice (standard strain of hybrid mice) at three dose levels (2, 5 and 10 mg/kg of RH1 in 0.9% (w/v) saline via an intraperotoneal injection). Standard Version of PC Winnonlin pharmacokinetic modelling software was used to model the data. A none-compartmental model was used to describe the disposition of RH1 in mice plasma. RH1 was rapidly eliminated from plasma with a mean plasma clearance of 23.4 ml/min, mean volume of distribution of 321.6 ml and mean t(1/2) alpha and beta decays of 4.8 and 9.6 min, respectively. RH1 in human and mouse whole blood and plasma was found to be stable up to 2 h.

Animals↗
PubMed1999

Development and validation of a high-performance liquid chromatographic assay using solid-phase extraction for the novel antitumor agent pancratistatin in human plasma.

The stability of the experimental anti-tumour agent pancratistatin in human plasma has been investigated. A solid-phase extraction technique and an HPLC assay with external standards have been developed and validated. Extraction was performed using C18 cartridges and HPLC, analysis was performed on a 15 cm Hypersil BDS column using isocratic elution with 13% acetonitrile and aqueous solution of 1% (w/v) acetic acid. The lower limit of quantification for pancratistatin in 5% DMF-95% water was found to be 0.58 ng/ml (+/-10.58%) and 2.3 ng/ml (+/-9.2%) following extraction from human plasma. Mean recovery of 89.4% (+/-4.73%) was obtained over the concentration range 0.0023-9.45 microg/ml for a five day validation study. Pancratistatin was stable at room temperature in light or dark for at least 15 days, in the refrigerator at 4 degrees C for at least 16 days and in the freezer at -20 degrees C or -80 degrees C for at least 28 days. Under all conditions monitored, % recovery of pancratistatin from human plasma was greater than 95% and no evidence of degradation had occurred. There also was no loss of pancratistatin after three cycles of freezing and thawing.

Amaryllidaceae Alkaloids↗
PubMed1999

Development and validation of a sensitive solid-phase extraction and high-performance liquid chromatography assay for the novel antitumour agent CT2584 in human plasma.

A HPLC assay and solid-phase extraction technique from human plasma has been developed and validated for the novel anticancer agent CT2584, 1-(11-dodecylamino-10-hydroxyundecyl)-3,7-dimethylxanthine, which has recently completed a phase I trial at the Christie Hospital, Manchester under the auspices of the CRC phase I/II committee. Following addition of CT2576, 1-(11-octylamino-10-hydroxylundecyl)-3,7-dimethylxanthine, as internal standard, a solid-phase extraction cartridge (100 mg cyanopropyl) was used to isolate the drug CT2584 from human plasma. Analysis was performed by reversed-phase chromatography. CT2576 was used as internal standard at a concentration of 4 microg ml(-1) for the quantification of CT2584 from plasma for the duration of this work. The lower limit of quantification for the drug CT2584 in buffer using this assay was found to be 0.0122 microM (0.008 microg ml(-1)) and 0.048 microM (0.027 microg ml(-1)) when extracted from human plasma.

Antineoplastic Agents↗
PubMed1998

High-performance liquid chromatographic assay for the novel antitumor drug, bryostatin-1, incorporating a serum extraction technique.

An HPLC assay incorporating a solid-phase extraction technique has been devised for bryostatin-1. Quantitation of bryostatin was found to be linear over the concentration range 0.012-25 microg/ml (0.2-25 ng on column) and was found to have a limit of detection of 0.2 ng on column, with a correlation coefficient of 0.9999. Following extraction of bryostatin over a range of concentrations from horse serum (0.012-25 microg/ml) and human serum (0.01-0.32 microg/ml) using a 100-mg C18 solid-phase extraction cartridge, extraction efficiencies consistently greater than 90% were obtained for extraction from horse serum and varied between 57 and 85% from human serum. However, on extending this work to blood samples from patients undergoing therapy with bryostatin-1, the drug was not detectable even at the maximum dose given, demonstrating the rapid loss of this agent from peripheral circulation.

Animals↗
PubMed1993

Pyrexia in hospitalised spinal cord injury patients.

To discover the frequency of pyrexia in spinal cord injury (SCI) patients in the Hospital for Medicine of the Locomotor System (HMLS/SARAH), a review study was undertaken. For a period of 3 months, all new episodes of fever were recorded. During the study 221.3 patients/month were observed. The age ranged from 14 to 60 years and time of lesion from 1 to 6,264 days: 85 patients were paraplegia or paraparetic, and 44 tetraplegic or tetraparetic. At the beginning of the study 10.8% of the patients had fever. During follow up, we observed a rate of 33.9 new incidences per 100 patients/month. In 77.3% only one cause was identified, and in 8% no cause could be defined. The commonest causes were urinary tract infection (UTI) (44.3%), and soft tissue infections (11.4%). Frequent causes of fever in the acute stage other than UTI were complications related to the initial trauma and thromboembolic disease (p < 0.05). These results demonstrate the high incidence of fever in patients with SCI, in addition to providing a useful approach for diagnosis and management.

Adolescent↗
PubMed1992

Traumatic injury to the spinal cord. Prevalence in Brazilian hospitals.

Traumatic spinal cord lesions have a worldwide high morbidity and mortality, and in many developed countries the problem has received special attention, based on epidemiological studies. In Brazil these studies have been restricted to institutional data. In 1988 a survey conducted by the Integrated System of Traumatology and Orthopaedics, covering 36 public hospitals from 7 Brazilian capitals, revealed a point prevalence of 8.6% (108 patients) with spinal cord injury, aged from 6-56 years; 81% were men. The most frequent causes were traffic accidents (42%), firearms (27%) and falling from heights (15%). The main complications were pressure ulcers (54%) and urinary infections (32%).

Adolescent↗
PubMed1991

Biochemical changes during the development of the miracidium of Gigantocotyle explanatum.

Analysis of various biochemical components during the development of the miracidium of G. explanatum showed marked changes, particularly in glycogen, protein and DNA levels. Though the total lipids remained more or less unchanged, alterations in the levels of cholesterol, triglycerides, free fatty acids, phospholipids and phospholipid fractions were also recorded. Such changes could be intrinsically programmed for the cellular differentiation and organogenesis in larval amphistomes.

Animals↗
PubMed1991

The expanded role of nurse case managers.

1. Effective nursing practice is responsive to the changing needs of clients. The community, rather than the hospital, has become the primary treatment setting in which the long-term mentally ill manage their daily activities. 2. The professional role of rehabilitative nurse case management can provide an opportunity for nurses to expand their roles and develop new career directions. 3. The primary nursing model provides an excellent foundation for acquiring the attitudes and skills necessary in the delivery of a comprehensive rehabilitative model of case management.

Hospital Departments↗
PubMed1990

Biochemical variations in Gigantocotyle explanatum and Gastrothylax crumenifer with respect to their seasonal reproduction.

Biochemical components, glycogen, protein, nucleic acids and lipid fractions were analysed every month from January to December 1986, in the liver and rumen amphistomes Gigantocotyle explanatum and Gastrothylax crumenifer, respectively. The results reveal a considerable seasonal variation. In the rumen amphistome the components reach their maximum level only once a year, whereas in the liver amphistome, more than one peak is observed in a year. In G. crumenifer the content of glycogen and nucleic acids increases before the onset of egg production while protein and lipids reach their maximum level during the egg production phase. The variations in biochemical components were associated with the reproductive cycles and gonad recrudescence of these parasites.

Animals↗
PubMed1989

Biochemical characterization of Taenia hydatigena cysticerci from goats and pigs.

Analysis of the major biochemical components of Taenia hydatigena cysticerci collected from goats and pigs showed marked differences, particularly in glycogen, protein, lipid and DNA levels. Differences were also detected in the levels of cholesterol, triglycerides, free fatty acids and phospholipids. Furthermore, the profile of phospholipid fractions revealed quantitative differences between the two species. It is concluded that the cysticerci of goat and pig origin probably represent two different strains and possibly follow the same pattern of speciation as reported in the related taeniid, Echinococcus granulosus.

Animals↗
PubMed1987

Light chain disease associated with the hyperviscosity syndrome.

The hyperviscosity syndrome refers to a group of symptoms and signs related to increased blood viscosity often produced by monoclonal immunoglobulins. It is most frequently associated with Waldenström's macroglobulinemia and, on occasion, with other immunoglobulins that are capable of forming highly polymerized molecules. This article is a report on the first case of pure light chain myeloma associated with the hyperviscosity syndrome. The hyperviscous plasma in this case is secondary to the unusual degree of aggregation of kappa light chain as demonstrated by high-resolution electrophoresis, serum immunofixation, and Sephadex g-200 (Pharmacia, Piscataway, NJ) column chromatography.

Bence Jones Protein↗
PubMed1985

Early organiform impairment test (OFIT). A new performance test for assessment of early cognitive impairment.

No satisfactory tests are available to a) document and b) monitor the short term effects of various pharmacological agents on early, and hopefully reversible, organic cognitive impairment in otherwise healthy individuals. A new test battery, Organiform Impairment Test (OFIT), is based on the clinical observation that impairment of the ability to operate simultaneously with a number of mental sets and stimuli is one of the first clinical manifestations in the early stages of organic brain pathology. This battery can be administered in 20-30 minutes and is partly automated. It has been standardized on 167 normal subjects in age ranges from 15 to 80 years. Any score below 50 on the battery in subjects under 80 years of age should be regarded with suspicion.

Adult↗