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Biomedical subjects

P Baker

Publications and source records attributed to P Baker.

At least 19 recordsLinked to original sources

Prevalence of the factor VLeiden mutation among autopsy patients with pulmonary thromboembolic disease using an improved method for factor VLeiden detection.

Activated protein C resistance caused by factor VLeiden mutation is the most common inherited predisposing cause of venous thromboembolism, including pulmonary embolism (PE). We studied whether the incidence of factor VLeiden is higher among patients with PE evident at autopsy than in the general population. Paraffin-embedded fixed tissue blocks from all autopsy patients with diagnosed pulmonary thromboembolic disease during a 4-year period were collected for DNA extraction. Extraction and molecular analysis of the DNA was performed with an improved technique with an internal control to determine the presence of factor VLeiden mutation. Analysis of 82 autopsy cases with PE yielded 5 patients who were heterozygotes. Seventy-seven of the 82 patients analyzed were normal, and no homozygotes for factor VLeiden mutation were identified. This yielded a positive rate of 6% overall and 7% among white patients, which is similar to the incidence of heterozygotes in the white population. This study indicates that routine determination of factor VLeiden mutation is not warranted for patients with PE diagnosed at autopsy.

Adolescent

Clinical characteristics of sudden death victims in heritable (chromosome 1p1-1q1) conduction and myocardial disease.

OBJECTIVES: The purpose of this study was to identify the clinical characteristics of family members at risk of sudden death. BACKGROUND: The significance of sudden death in heritable cardiac disorders with delayed expression is incompletely understood. Additional insights come from a four-decade experience of seven generations of a family of German origin with autosomal dominant (chromosome 1p1-1q1) cardiac conduction and myocardial disease. METHODS AND RESULTS: A total of 38 family members (20 males; 18 females) were identified with sudden death. Twenty-eight family members (mean age 48+/-8 years) from earlier generations had no pacemaker at the time of sudden death. In this group, 15 subjects were asymptomatic prior to sudden death. Ten family members with sudden death, from later generations, had chronically implanted pacemakers for high grade atrioventricular block. This group was older (mean age 57+/-2 years), with decreased functional status (New York Heart Association class II to IV), enlarged left atria, dilated left ventricles with reduced systolic function and documented ventricular fibrillation in three members. Twenty-eight family members with sudden death were descendants of sib lineages 2 or 6; 21 family members with sudden death were offspring of a parent who also suffered sudden death. CONCLUSION: Sudden death is an important late outcome in heritable (chromosome 1p1-1q1) cardiac conduction and myocardial disease. Pacemaker therapy is important for the treatment of symptomatic bradycardia, but it does not prevent sudden death. Family members who are beyond the third decade of life with reduced functional capacity, left ventricular dysfunction, pacemakers and who are the offspring of a parent with sudden death appear to be at greatest risk

Adult

Effect of catheter tip length and position on lesion volume in temperature controlled RF ablation in canine tricuspid valve annulus.

BACKGROUND: Radiofrequency (RF) energy has been delivered to the tricuspid valve annulus (TVA) in humans with both 4 mm and 8 mm long catheter tip electrodes to treat atrial flutter. However, lesion volume with temperature controlled RF delivery systems has not been previously characterized. METHODS: In 10 anesthetized canines, a single pulse of temperature controlled RF energy at a 70 degrees C set point, 30 second duration was delivered with either a 7 Fr/4 mm tip or a 7 Fr/8 mm tip electrode in a position both anterolateral and posteroseptal to the tricuspid valve annulus (TVA). Surface echocardiogram was obtained prior and after ablation. The animals were sacrificed after ablation and the lesions underwent gross and histological examination. RESULTS: Lesion size, tip temperature and power were related to tip electrode surface area (SA). Eight mm tips (SA = 59 mm2) tended to create significantly larger lesions than 4 mm tips (SA = 29 mm2). Median lesion volume was 22 vs. 1.5 mm3, respectively. Eight mm tips were also associated with higher power requirements and lower temperatures than 4 mm tips. Posteroseptal TVA lesions tended to be larger than anterolateral lesions. No significant complications were noted. CONCLUSIONS: Using temperature controlled RF ablation, large lesions may be safely created on the canine TVA using 7 Fr catheters with 8 mm long tips.

Animals

Autism and tuberous sclerosis complex: prevalence and clinical features.

This study employed a hierarchical assessment to detect the prevalence of autism in a clinic sample of individuals with tuberous sclerosis complex (TSC). After screening subjects with the Autism Behavior Checklist, subsequent evaluations with the Autism Diagnostic Interview, and direct clinical observation, the prevalence of autistic disorder in this sample of 20 subjects was conservatively estimated at 20%. Data suggest a possible association between both hypsarrythmia and TSC-related cardiac abnormalities with autism in this subgroup of TSC individuals. Implications of these findings for clinical practice and further research are discussed.

Adolescent

Upper limb disorder due to manual pipetting.

This case report describes the occurrence of non-specific upper limb symptoms, in a 47-year-old female scientific officer, associated, with manual pipetting. The discussion considers the difficulty of risk assessment and reduction for this common procedure.

Arm

Temperature controlled RF ablation in canine ventricle and coronary sinus using 7 Fr or 5 Fr ablation electrodes.

The safety and lesion volume of temperature controlled radiofrequency ablation (TCRFA) in the right ventricle (RV), left ventricle (LV), and coronary sinus (CS) comparing long 5 Fr to standard tip electrodes have not been previously reported. In 10 canines, TCRFA was delivered at a 70 degrees C set point for 30 seconds. Lateral and septal RV lesions were made with either a 5 Fr/5 mm or 7 Fr/4 mm tip. Lateral and septal LV lesions were made with either a 5 Fr/7 mm or 7 Fr/4 mm tip. Proximal and distal CS lesions were made with either a 7 Fr/4 mm, 5 Fr/5 mm or 5 Fr/7 mm tip. Gross and histologic examination of the lesions was completed. Lesion size, tip temperature and power required are related to electrode surface area (SA) when ablating in the RV, LV or CS. 5 Fr/7 mm tips (SA = 36 mm2) tended to create larger lesions than 7 Fr/4 mm tips (SA = 29 mm2) in the LV. 7 Fr4 mm tips tended to create larger lesions than 5 Fr/5 mm tips (SA = 26 mm2) in the RV. 7 Fr/4 LV lesions exceeded 7 Fr/4 mm RV lesions due to thicker LV walls. In the CS, 5 Fr/7 mm tips tended to create the largest lesions. In the RV, LV and CS, tips with larger SA tended to have lower temperatures and require higher power. No high temperature or high impedance shut-downs were observed. In conclusion, varying 5 Fr tip length can safely produce larger or smaller lesions compared to those created with 7 Fr/4 mm tips.

Animals

Glucose transport inhibitors protect against 1,2-cyclohexanedione-produced potassium loss from human red blood cells.

It has been suggested that the glucose transport system of human erythrocytes contains an arginine shield to prevent the leak of potassium through the transporter. To investigate this suggestion we treated human erythrocytes with the specific arginine reagent 1,2-cyclohexanedione. Under conditions which produce a covalent reaction between arginine and the reagent, a steady leak of potassium occurs. If glucose, maltose or the inhibitor phloretin are present during the reaction the extent of the leak is reduced. These findings support the view that arginines have a role in preventing potassium loss through the glucose transporter.

Arginine

A species-specific monoclonal antibody to Cynodon dactylon.

BACKGROUND: It is usually difficult to differentiate between the pollens of different grass species on the basis of their appearance under a microscope, as they often appear similar. Such distinctions are important when interpreting the clinical relevance of pollens in air samples as individuals can differ in their allergic responses to different grass species. As this allergenic distinction occurs at the level of presence and differences of epitopes on the allergens associated with different species, it could be anticipated that species-specific monoclonal antibodies could provide such distinctions between pollens. METHOD: Monoclonal antibodies raised against Cynodon dactylon were screened and characterised in ELISA assays and blotting, using a range of grass pollen extracts, to identify clones which were species specific. RESULTS: The most specific monoclonal raised to C. dactylon did not react at a level of greater than 1.2% to extracts of 10 other grass pollens in a direct ELISA assay and showed no detectable cross-reactivity in a particle blotting assay. CONCLUSION: It has been possible to produce a monoclonal antibody that is functionally species specific to C. dactylon.

Animals

Fetal development of Leydig cell activity in the mouse is independent of pituitary gonadotroph function.

During fetal development the testes secrete anti-Mullerian hormone and testosterone to induce formation of the male phenotype. Adult Leydig cells secrete testosterone under the control of LH, but the role of the fetal pituitary in regulating fetal Leydig cell function is unclear. To study the early relationship between pituitary and Leydig cell function, we have examined the development of fetal pituitary LH levels and Leydig cell function in normal mice and in hypogonadal (hpg) mice that lack GnRH and, thus, circulating gonadotropins. In normal and hpg mice, pituitary LH content was barely detectable until embryonic day 17 (E17), when levels began to increase significantly in both groups. Pituitary levels of LH in hpg mice were, however, only about 10% of normal at all ages. Full-length LH receptor transcripts were first detectable in fetal testes on E16 in both normal and hpg mice. In normal mice, levels of testicular messenger RNA (mRNA) encoding cytochrome P450 side-chain cleavage and 17alpha-hydroxylase increased from E13 to reach a peak around birth. In hpg mice, levels of mRNA encoding these enzymes were normal until around birth, at which time there was a significant decline. Levels of testicular mRNA encoding 3beta-hydroxysteroid dehydrogenase type I were similar in normal and hpg mice and showed little change during development. Intratesticular testosterone reached a peak on E18 in normal animals before declining again after birth. In hpg mice, intratesticular testosterone levels were normal throughout fetal development and on the day of birth, but were barely detectable by postnatal day 5. Results show 1) that fetal Leydig cell function in the mouse is normal in the absence of endogenous circulating gonadotropins; 2) that Leydig cells become dependent on gonadotropins shortly after birth; and 3) that pituitary LH synthesis can start in the absence of GnRH but is dependent on LH for a normal level of synthesis and secretion.

Animals

Hoarding and treatment response in 38 nondepressed subjects with obsessive-compulsive disorder.

OBJECTIVE: The authors studied factors associated with short-term treatment response in 38 nondepressed subjects with DSM-III-R obsessive-compulsive disorder (OCD). METHOD: The subjects completed 12 weeks of treatment with paroxetine (N = 20), placebo (N = 8), or cognitive-behavioral therapy (N = 10). Clinician and self-rated measures were gathered at baseline, during treatment, and after treatment. RESULTS: Seventeen (45%) subjects had "much" or "very much" improvement and achieved at least a 40% decrease in their total Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score. Responders had lower obsessive-compulsive scores on the Symptom Checklist 90-Revised, had a lower checking score on the Maudsley Obsessive-Compulsive Inventory, were less likely to have had prior drug therapy, and in general suffered more obsessive-compulsive symptoms. They were significantly less likely to have hoarding obsessions and corresponding compulsions. The latter finding was confirmed using multiple regression analysis. CONCLUSION: Hoarding is an important symptom that predicts poor treatment response in patients with OCD.

Age Factors

Laboratory evaluation in the diagnosis of Lyme disease.

PURPOSE: To provide a qualitative evaluation of the predictive value of the laboratory diagnosis of Lyme disease and to use the resultant data to formulate guidelines for clinical diagnosis. DATA SOURCES: A MEDLINE search of English-language articles or articles with English-language abstracts published from 1982 to 1996. DATA EXTRACTION: Sensitivity, specificity, and likelihood ratios were calculated, and a random-effects model was used to combine the proportions from the eligible studies. Prespecified criteria were used to determine which studies were eligible for analysis. DATA SYNTHESIS: Laboratory testing in general is not clinically useful if the pretest probability of Lyme disease is less than 0.20 or greater than 0.80. When the pretest probability is 0.20 to 0.80, sequential testing with enzyme-linked immunosorbent assay and Western blot is the most accurate method for ruling in or ruling out the possibility of Lyme disease. CONCLUSIONS: Laboratory testing is recommended only in patients whose pretest probability of Lyme disease is 0.20 to 0.80. If the pretest probability is less than 0.20, testing will result in more false-positive results than true-positive results; a negative test result in this situation effectively rules out the disease.

Bacteriological Techniques

The effect of delayed analysis or freeze-thawing on the measurement of natural anticoagulants, resistance to activated protein C and markers of activation of the haemostatic system.

We provide a centralised thrombophilia screening service with sample transfer by courier or first class mail, a practice common to many centres. Sample quality is of prime importance, thus we have assessed the effect of delayed sample handling upon the haemostatic variables within our thrombophilia profile. This comprises screening for familial natural anticoagulant deficiency and APC resistance (1-4), and acquired lupus anticoagulant (5,6). The effect upon hypercoagulable markers were also assessed to facilitate evaluation of these in prospective clinical studies (7).

Anticoagulants

Progress report. A randomized multicenter European study comparing adjuvant radiotherapy, 6-mo chemotherapy, and combination therapy vs no-adjuvant treatment in resectable pancreatic cancer (ESPAC-1).

CONCLUSION: The ESPAC-1 trial is the largest study of its kind in pancreatic cancer and should definitively address the question of the role of conventional methods of adjuvant treatment in pancreatic cancer. BACKGROUND: At the joint International Association of Pancreatology and the European Pancreatic Club meeting in Mannheim, Germany (June 12-15, 1996) a satellite meeting of the European Study Group for Pancreatic Cancer (ESPAC) met to discuss the progress of the ESPAC-1 trial. METHODS: A randomized multicenter study to address which, if any, of the following adjuvant treatments are of benefit in patients with resectable pancreatic cancer: radiotherapy (40 Gy with 5-FU as a sensitizing agent), 6 mo of chemotherapy (5-FU and folinic acid), or a combination of these treatments. RESULTS: From February 1994 to June 1996 (the time of the Mannheim meeting) 221 patients so far have been recruited into the three treatment arms and one control arm.

Adenocarcinoma

Renal artery dissection causing renal infarction in otherwise healthy men.

Arterial dissection is usually associated with pathological states such as malignant hypertension, severe atherosclerosis, severe trauma, Marfan syndrome, or Ehlers-Danlos syndrome. However, we report three cases in which renal artery dissection occurred in otherwise healthy, normotensive men. In two cases, the onset of symptoms of renal artery dissection was coincident with an unusual degree of physical activity. In the third case, the symptoms occurred while the patient was sitting but during a stressful business meeting. In each case, the patient experienced severe unilateral flank pain. Urolithiasis was suspected, but intravenous pyelography showed only ipsilateral impaired renal cortical perfusion, and the urinalyses showed no hematuria. The diagnosis of renal artery dissection was established by arteriography in two cases and by nephrectomy in one case. The latter case showed fibromuscular dysplasia by arteriography performed after the nephrectomy. The other two cases showed no evidence of fibromuscular dysplasia. We conclude that spontaneous renal artery dissection can occur in otherwise healthy individuals. Our experience and the reports of others indicate that this condition occurs mainly in men, conservative (nonsurgical) management is generally indicated, and the long-term prognosis is generally excellent. In some patients, an unusual degree of physical exertion might be the cause of renal artery dissection.

Adult