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Biomedical subjects

P Thomas

Publications and source records attributed to P Thomas.

At least 109 records · Page 6Linked to original sources
PubMed2002

Progression of actinic keratosis to squamous cell carcinoma of the skin correlates with deletion of the 9p21 region encoding the p16(INK4a) tumor suppressor.

Actinic keratoses (AKs) are pre-neoplastic lesions that can develop into squamous cell carcinomas (SCCs) of the skin. Often AK and SCC have commonly altered p53. A status of another tumor suppressor, the p16(INK4a), was reported for SCC but not for AK. A comparative study of SCC and AK human samples by loss of heterozygosity (LOH) analysis determined that the p16(INK4a/ARF) locus is less frequently altered in AKs than in SCCs. These LOH data highly correlated with immunohistochemical findings demonstrating the presence of p16(INK4a) in the AK skin samples but its absence in SCC lesions. Our results imply that progression of AK into SCC may involve inactivation of p16(INK4a).

Blotting, Western↗
PubMed2002

Treatments for secondary postpartum haemorrhage.

BACKGROUND: Secondary postpartum haemorrhage is any abnormal or excessive bleeding from the birth canal occurring between 24 hours and 12 weeks postnatally. In developed countries, two per cent of postnatal women are admitted to hospital with this condition, half of them undergoing uterine surgical evacuation; in developing countries it is a major contributor to maternal death. OBJECTIVES: To evaluate the relative effectiveness and safety of the treatments used for secondary postpartum haemorrhage. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (May 2001), the Cochrane Controlled Trials Register (The Cochrane Library, issue 2, 2001), MEDLINE (back to 1966) and EMBASE (back to 1988). The National Research Register was also searched. The reference lists of trial reports and reviews were searched by hand. Where possible, further sources were sought from the first named authors of the papers identified. SELECTION CRITERIA: All randomised or quasi randomised comparisons between drug therapies, surgical therapies and placebo or no treatment for the management of secondary postpartum haemorrhage occurring between 24 hours and three months following a pregnancy of at least 24 weeks gestation. DATA COLLECTION AND ANALYSIS: Reports of possibly eligible studies were scrutinised by two investigators. The third investigator acted as an advisor/arbitrator. MAIN RESULTS: Of the 45 papers identified, none met the inclusion criteria. REVIEWER'S CONCLUSIONS: No information is available from randomised controlled trials to inform the management of women with secondary postpartum haemorrhage. This topic may have received little attention because it is perceived as being associated with maternal morbidity rather than mortality in developed countries; it is only recently that the extent and importance of postnatal maternal morbidity has been recognised. A well designed randomised controlled trial comparing the various drug therapies for women with secondary postpartum haemorrhage against each other and against placebo or no treatment groups is needed.

Female↗
PubMed2002

Calcium phosphate apatites with variable Ca/P atomic ratio I. Synthesis, characterisation and thermal stability of powders.

Single phased apatitic calcium phosphate powders Ca(10-x)(PO4)(6-x)(HPO4)x(OH)(2-x) with Ca/P molar ratio ranging from 1.5 to 1.667 (0 < or = x < or = 1) were synthesised using wet method. Outside this compositional range the powders were biphasic mixtures composed of a calcium phosphate apatite and CaHPO4 (Ca/P < 1.5) or Ca(OH)2 (Ca/P > 1.667). Temperature and pH of synthesis were the preponderant parameters for the control of the precipitate composition. The precise determination of the chemical composition requires the use of several complementary techniques and thermal treatments of powders. These techniques include high resolution and high temperature X-ray diffractometry and FTIR spectroscopy and show that very small variations of the Ca/P molar ratio of the powder lead to great changes in powder composition and characteristics after thermal treatment.

Biocompatible Materials↗
PubMed2002

VATS is an adequate oncological operation for stage I non-small cell lung cancer.

OBJECTIVES: This study was designed to determine the long-term prognosis of video-assisted thoracic surgery (VATS) vs. open lung resections for patients with pathological stage I non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: The medical records of all patients who underwent lung resection for a pathological stage I NSCLC were reviewed for the period from 1990 to 1999, by screening of a database into which data were entered prospectively. There were 511 patients (430 males and 81 females) whose age averaged 63+/-10 years who underwent 515 lung resections. Our VATS experience began in 1993 with selected stage I patients, and since that date an average of one patient on four was managed with VATS. Lung resections consisted of 25 wedge resections or segmentectomies (seven VATS), 390 lobectomies (92 VATS), 19 bilobectomies (one VATS) and 81 pneumonectomies (ten VATS). Lymph node dissection was performed in all cases. RESULTS: There were significantly more females (P=0.01) and adenocarcinoma (P=0.02) in the VATS group (n=110) when compared to the open group (n=405). Tumour size averaged 4+/-2 cm in the open group and 3+/-2 cm in the VATS group (P=0.04). The distribution of T1/T2 tumours was 97/308 and 50/60, respectively (P=0.0001). At follow-up, cancer recurrence could be documented in 117 patients, with no difference of incidence between the two groups (22.5 vs. 24.5%; P=0.64). Estimated Kaplan-Meier 5-year survival rates, including the operative mortality as well as any cancer-related and unrelated death, were 62.8% (confidence interval (CI): 56.8-68.7%) vs. 62.9% (CI: 51.4-74.4%), respectively (P=0.60). The advent of VATS did not influence the patients' survival: 5-year survival rate was 63.9% (CI: 55.3-72.5%) for the period from 1990 to 1992, and 58.8% (CI: 51.7-65.9%) for the period from 1993 to 1999 (P=0.65). Subgroups survival analysis according to the T status did not show any statistically significant difference between the two groups. CONCLUSIONS: VATS lung resection with lymph node dissection achieved a 5-year survival similar to that achieved by the conventional approach. VATS is a valuable option for the management of selected patients with an early-stage NSCLC.

Adult↗
PubMed2002

[Contribution of ovarian and uterine color Doppler in medically assisted reproduction techniques (ART)].

Along the menstrual cycle and during pregnancy, small blood vessels proliferate within the uterus and the ovulating ovary. Angiogenic factors such as VEGF are involved in this phenomenon. In the ovulating ovary, neo-angiogenesis spreads progressively inside the dominant follicle wall and plays a role in the maintenance of the corpus luteum, under the influence of LH (or HCG during pregnancy). In ART, the measure of the blood flow is interesting since it correlates to the number and quality of harvested oocytes. Follicle hypoxia may impair chromosomal organization and separation within the oocyte. This neo-angiogenesis is also important in endometrium, in particular for embryo implantation. Ultrasounds with Doppler allow to estimate the endometrial receptivity, especially in IVF cycles. It is assumed that chance for ongoing pregnancy is almost zero if: endometrial thickness is < 8 mm; uterine pulsatility index (PI) is > 3. Doppler ultrasounds are a useful and even mandatory complement to standard vaginal ultrasonoghraphy in ART. It can be viewed as an indicator of the endometrial and follicular "well-being".

Endometrium↗
PubMed2002

Cyclic AMP-dependent protein kinase phosphorylation facilitates GABA(B) receptor-effector coupling.

GABA (gamma-aminobutyric acid)(B) receptors are heterodimeric G protein-coupled receptors that mediate slow synaptic inhibition in the central nervous system. Here we show that the functional coupling of GABA(B)R1/GABA(B)R2 receptors to inwardly rectifying K(+) channels rapidly desensitizes. This effect is alleviated after direct phosphorylation of a single serine residue (Ser892) in the cytoplasmic tail of GABA(B)R2 by cyclic AMP (cAMP)-dependent protein kinase (PKA). Basal phosphorylation of this residue is evident in rat brain membranes and in cultured neurons. Phosphorylation of Ser892 is modulated positively by pathways that elevate cAMP concentration, such as those involving forskolin and beta-adrenergic receptors. GABA(B) receptor agonists reduce receptor phosphorylation, which is consistent with PKA functioning in the control of GABA(B)-activated currents. Mechanistically, phosphorylation of Ser892 specifically enhances the membrane stability of GABA(B) receptors. We conclude that signaling pathways that activate PKA may have profound effects on GABA(B) receptor-mediated synaptic inhibition. These results also challenge the accepted view that phosphorylation is a universal negative modulator of G protein-coupled receptors.

Animals↗
PubMed2002

Obstetric anaesthetists' workload.

The current recommendation of one consultant session per 500 deliveries with full sessional cover for units over 3000 deliveries is arbitrary and is not based on workload. The Audit Commission has questioned the wide variability of anaesthetic staffing on labour wards. The aim of this study was to investigate whether there is a relationship between current workload and obstetric anaesthetic staffing in five maternity units. In 1998, a 2-week diary of workload in the participating obstetric units was assessed in terms of staffing and clinical and nonclinical activities. The busiest time was 08:00 to 12:30. The working patterns between consultants and trainees varied considerably. Time spent on nonclinical activity by consultants averaged 51%. Any calculation of consultant sessions will need to take into account nonclinical activities. Other factors requiring consideration are the number of high-risk cases, as well as the number and experience of trainees.

Anesthesiology↗
PubMed2002

Formal observations and engagement: a discussion paper.

Formal observation of patients at risk is extremely common in acute psychiatric facilities. Effectively a form of physical containment, observation is resource-intensive, makes significant personal demands upon staff and skews the focus of nursing care towards the small group of patients judged to be most at risk. For patients, the experience of being observed is often less than therapeutic and, in some cases, counter productive. In this paper, the authors draw upon a variety of perspectives, including that of a psychiatrist and a service user. It is argued that the practice of formal observation is ineffective and may actually contribute to the poor state of UK acute psychiatric inpatient units, in terms of direct patient care, clinical decision-making and appropriate risk management. In a recent 'commentary' within this journal, the authors offered 'engagement' as an alternative to observation. In this paper, the meaning of engagement is refined and presented as a process of emotional and psychological containment of distress. The paper concludes that inappropriate over-use of formal observation as a custodial and defensive practice can contribute to a sense of dehumanization and isolation within acute psychiatric patients; engagement may provide a genuine (i.e. not just linguistic) alternative.

Coercion↗
PubMed2002

Phase II randomized multicenter study evaluating a treatment regimen alternating docetaxel and cisplatin-vinorelbine with a cisplatin-vinorelbine control group in patients with stage IV non-small-cell lung cancer: GFPC 97.01 study.

BACKGROUND: The potential absence of cross-resistance between cisplatin and docetaxel in non-small-cell lung cancer (NSCLC) suggests that alternating regimens of cisplatin-based chemotherapy and docetaxel might increase the activity of chemotherapy in stage IV NSCLC. PATIENTS AND METHODS: Randomized, multicenter, non-comparative phase II study in patients with stage IV NSCLC (Eastern Cooperative Oncology Group performance status of 0-2). Patients randomized to alternating treatment group (A) received docetaxel 100 mg/m2 on days (D) 1 and 43 alternating with cisplatin 100 mg/m2 on D22 and vinorelbine 30 mg/m2 on D22, D29 and D36. Those randomized to the control group (B) received cisplatin 80 mg/m2 on D1, D22 and D43 and vinorelbine 30 mg/m2 once a week from D1 to D57. Treatment was continued for a further 6 weeks in the event of objective response or stabilization. RESULTS: Seventy patients were enrolled (group A: 38, group B: 32). More premature treatment discontinuations due to toxicity were observed in group A (median number of cycles: 3) than in group B (median number of cycles: 5). The intention-to-treat objective response rate was 10.8% [95% confidence interval (CI) 0.8% to 20.8%] in group A compared with 25% (95% CI 10% to 40%) in group B, the median time to treatment failure being 10.2 weeks and 17.3 weeks, respectively. The median survival and 1-year survival were 29.1 weeks and 39% in group A compared with 41.6 weeks and 42% in group B. Febrile neutropenia occurred in 5.9 and 4.9% of the cycles in group A and group B, respectively. Non-hematological toxicity was moderate in the two groups. CONCLUSIONS: The addition of docetaxel alternating with cisplatin-vinorelbine did not enhance the activity of this combination. The development of sequential regimens might be a more promising way of exploiting the absence of cross-resistance between these two drugs.

Adult↗
PubMed2002

Cloned genomic DNA of type 2 porcine circovirus is infectious when injected directly into the liver and lymph nodes of pigs: characterization of clinical disease, virus distribution, and pathologic lesions.

Infection of animals with a molecular viral clone is critical to study the genetic determinants of viral replication and virulence in the host. Type 2 porcine circovirus (PCV2) has been incriminated as the cause of postweaning multisystemic wasting syndrome (PMWS), an emerging disease in pigs. We report here for the first time the construction and use of an infectious molecular DNA clone of PCV2 to characterize the disease and pathologic lesions associated with PCV2 infection by direct in vivo transfection of pigs with the molecular clone. The PCV2 molecular clone was generated by ligating two copies of the complete PCV2 genome in tandem into the pBluescript SK (pSK) vector and was shown to be infectious in vitro when transfected into PK-15 cells. Forty specific-pathogen-free pigs at 4 weeks of age were randomly assigned to four groups of 10 each. Group 1 pigs served as uninoculated controls. Pigs in group 2 were each inoculated intranasally with about 1.9 x 10(5) 50% tissue culture infective doses of a homogeneous PCV2 live virus stock derived from the molecular clone. Pigs in group 3 were each injected intrahepatically with 200 microg of the cloned PCV2 plasmid DNA, and pigs in group 4 were each injected into the superficial iliac lymph nodes with 200 microg of the cloned PCV2 plasmid DNA. Animals injected with the cloned PCV2 plasmid DNA developed infection resembling that induced by intranasal inoculation with PCV2 live virus stock. Seroconversion to PCV2-specific antibody was detected in the majority of pigs from the three inoculated groups at 35 days postinoculation (DPI). Viremia, beginning at 14 DPI and lasting 2 to 4 weeks, was detected in the majority of the pigs from all three inoculated groups. There were no remarkable clinical signs of PMWS in control or any of the inoculated pigs. Gross lesions in pigs of the three inoculated groups were similar and were characterized by systemically enlarged, tan lymph nodes and lungs that failed to collapse. Histopathological lesions and PCV2-specific antigen were detected in numerous tissues and organs, including brain, lung, heart, kidney, tonsil, lymph nodes, spleen, ileum, and liver of infected pigs. This study more definitively characterizes the clinical course and pathologic lesions exclusively attributable to PCV2 infection. The data from this study indicate that the cloned PCV2 genomic DNA may replace infectious virus for future PCV2 pathogenesis and immunization studies. The data also suggest that PCV2, although essential for development of PMWS, may require other factors or agents to induce the full spectrum of clinical signs and lesions associated with advanced cases of PMWS.

Administration, Intranasal↗
PubMed2002

Comparison of molecular and biological characteristics of a modified live porcine reproductive and respiratory syndrome virus (PRRSV) vaccine (ingelvac PRRS MLV), the parent strain of the vaccine (ATCC VR2332), ATCC VR2385, and two recent field isolates of PRRSV.

The objectives of this study were to compare the molecular and biological characteristics of recent porcine reproductive and respiratory syndrome virus (PRRSV) field isolates to those of a modified live virus (MLV) PRRS vaccine and its parent strain. One hundred seventeen, 4-week-old pigs were randomly assigned to six groups. Group 1 (n = 20) served as sham-inoculated negative controls, group 2 (n = 19) was inoculated with Ingelvac PRRS MLV vaccine, group 3 (n = 20) was inoculated with the parent strain of the vaccine (ATCC VR2332), group 4 (n = 19) was inoculated with vaccine-like PRRSV field isolate 98-38803, group 5 (n = 19) was inoculated with PRRSV field isolate 98-37120, and group 6 (n = 20) was inoculated with known high-virulence PRRSV isolate ATCC VR2385. The levels of severity of gross lung lesions (0 to 100%) among the groups were significantly different at both 10 (P < 0.0001) and 28 days postinoculation (p.i.) (P = 0.002). At 10 days p.i., VR2332 (26.5% +/- 4.64%) and VR2385 (36.4% +/- 6.51%) induced gross lesions of significantly greater severity than 98-38803 (0.0% +/- 0.0%), 98-37120 (0.8% +/- 0.42%), Ingelvac PRRS MLV (0.9% +/- 0.46%), and negative controls (2.3% +/- 1.26%). At 28 days p.i., 98-37120 (17.2% +/- 6.51%) induced gross lesions of significantly greater severity than any of the other viruses. Analyses of the microscopic-interstitial-pneumonia-lesion scores (0 to 6) revealed that VR2332 (2.9 +/- 0.23) and VR2385 (3.1 +/- 0.35) induced significantly more severe lesions at 10 days p.i. At 28 days p.i., VR2385 (2.5 +/- 0.27), VR2332 (2.3 +/- 0.21), 98-38803 (2.6 +/- 0.29), and 98-37120 (3.0 +/- 0.41) induced significantly more severe lesions than Ingelvac PRRS MLV (0.7 +/- 0.17) and controls (0.7 +/- 0.15). The molecular analyses and biological characterizations suggest that the vaccine-like isolate 98-38803 (99.5% amino acid homology based on the ORF5 gene) induces microscopic pneumonia lesions similar in type to, but different in severity and time of onset from, those observed with virulent strains VR2385 and the parent strain of the vaccine. Our data strongly suggest that isolate 98-38803 is a derivative of Ingelvac PRRS MLV and that the isolate is pneumovirulent.

Animals↗
PubMed2002

[Confusional disorders and epilepsy].

Confusion in an epileptic patient raises several diagnostic possibilities: non convulsive status epilepticus, interictal or post-ictal psychosis, drug-induced confusion, confusion of another nature. Accurate diagnosis is based on clinical analysis, systematically completed by the practice and the repetition of emergency EEG.

Anticonvulsants↗
PubMed2002

Alzheimer's disease and vascular factors: facts and theories.

Although Alzheimer s disease is classified as a neurodegenerative dementia, in Alzheimer s dementia there is increasing evidence of an association with vascular risk factors and vascular pathology. These observations are supported by epidemiological and pathological studies. Vascular factors may play a significant role in the pathogenesis of Alzheimer s dementia. Further research is needed to explore this relationship. Modification of vascular risk factors could make a significant impact towards prevention and treatment of Alzheimer s disease, which is a distressing and prevalent condition in the community. This article considers the relationship of these vascular risk factors and potential mechanisms associated with the aetiopathogenesis of Alzheimer s dementia.

Aged↗
PubMed2002

Stroke prevention: missed opportunities?

Identification and modification of risk factors can prevent strokes. Certain previously unidentified risk factors for stroke can become apparent following admission with acute stroke. The aim of the study was to investigate the prior capture, identification and management of modifiable risk factors for stroke in patients admitted to a hospital following acute stroke. One hundred consecutive stroke patients admitted to a UK hospital were prospectively assessed for modifiable risk factors. The extent of pre-admission risk factor management was also determined. Pre-admission risk factors identified and effectively managed were hypertension in non-diabetics (28%), hypertension in diabetics (7%), previous cerebrovascular event (100%), diabetes (29%), smoking (50% counselled), atrial fibrillation (81%), hypercholesterolaemia (100%), excess alcohol (22% counselled) and obesity (52% counselled). Twenty-five new modifiable risk factors were identified following incident stroke. In conclusion, a significant number of patients admitted with acute stroke have their risk factors poorly identified and controlled in the community. Despite the trial evidence available, an evidence-practice gap exists and many stroke prevention opportunities are being missed.

Acute Disease↗
PubMed2002

[Management of adult refractory convulsive status epilepticus in the intensive care unit].

Patients with convulsive status epilepticus in whom first line treatment is not rapidly effective, or with a persistent delay in recovering consciousness must be admitted in an ICU even if assisted, mechanical ventilation is not performed. Continuous EEG monitoring performed in close collaboration with a neurophysiologist/epileptologist is mandatory to detect and treat subtle status epilepticus and to exclude post-anoxic encephalopathy. A number of drugs and anaesthetic agents have been proposed to control refractory status epilepticus. Midazolam and/or propofol have been recently recommended before performing general barbiturate anaesthesia. However, this approach is not rigorously assessed, because patients and series are heterogeneous, and controlled studies are difficult to design. Prognosis is closely related to the quality of initial management, to the development of subtle status epilepticus and, above all, to aetiology.

Anticonvulsants↗
PubMed2002

Knowledge of stroke symptoms and risk factors among at-risk elderly patients in the UK.

Assessing patient knowledge can help healthcare providers in planning measures directed at prevention, early identification and referral of patients. An incorrect understanding of stroke symptoms may delay patients seeking emergency help, thus missing the benefits of acute stroke treatments. Insufficient knowledge about stroke risk factors may affect risk factor control. We conducted a questionnaire-based interview among elderly patients at risk of stroke and assessed their baseline knowledge of stroke symptoms and risk factors. A large proportion were found to have an improper understanding of stroke symptoms and risk factors. Stress was considered the commonest risk factor for stroke. Most patients did not consider themselves to be at further risk of stroke. Further education is needed as part of stroke prevention strategies to remove misconceptions. Improved recognition of stroke symptoms when they occur will help when seeking emergency medical help.

Aged↗