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P Major

Publications and source records attributed to P Major.

At least 19 recordsLinked to original sources
PubMed2006

Phase II study of erlotinib (OSI-774) in patients with metastatic colorectal cancer.

Erlotinib (Tarceva, OSI-774), a potent epidermal growth factor receptor tyrosine kinase inhibitor (EGFR), was evaluated in a phase II study to assess its activity in patients with metastatic colorectal cancer. In all, 38 patients with metastatic colorectal cancer were treated with erlotinib at a continuous daily oral dose of 150 mg. Radiological evaluation was carried out every 8 weeks and tumour biopsies were performed before treatment and on day 8. Of 31 evaluable patients, 19 (61%) had progressive disease and 12 (39%) had stable disease (s.d.). The median time to progression for those patients having s.d. was 123 days (range 108-329 days). The most common adverse events were rash in 34 patients and diarrhoea in 23 patients. Correlative studies were conducted to investigate the effect of erlotinib on downstream signalling. Tumour tissue correlations were based on usable tissue from eight match paired tumour samples pre- and on therapy, and showed a statistically significant decrease in the median intensity of both pEGFR (P=0.008) and phospho-extracellular signal-regulated kinase (ERK) (P=0.008) a week after commencement of treatment. No other statistically significant change in tumour markers was observed. Erlotinib was well tolerated with the most common toxicities being rash and diarrhoea. More than one-third of evaluable patients had s.d. for a minimum of 8 weeks. Correlative studies showed a reduction in phosphorylated EGFR and ERK in tumour tissue post-treatment.

Adult↗
PubMed2004

Clinical significance of isolated hippocampal volume asymmetry in childhood epilepsy.

This study defines the clinical characteristics and evolution of 16 epileptic children with hippocampal asymmetry (HA) without sclerosis on MRI. The association of a positive family history of epilepsy (11/16), low incidence of febrile seizures (2/16), and benign prognosis (seizure control in monotherapy in 11/16, mean follow-up = 4.3 years, range 1 to 10) suggest a different clinical presentation than patients with mesial temporal sclerosis. Genetic studies of these mostly French Canadian families should help confirm the existence of a distinct syndrome.

Adolescent↗
PubMed2002

Size at birth, adult intestinal calcium absorption and 1,25(OH)(2) vitamin D.

BACKGROUND: Adult bone mineral status is modified by early environmental influences, but the mechanism of this phenomenon is unknown. Intestinal calcium absorption and vitamin D metabolism are integrally involved in bone metabolism and may be programmed during early life. AIM: To examine the early-life influences on calcium absorption and its control in 322 post-menopausal female twins. METHODS: Intestinal calcium absorption was assessed by the stable strontium (Sr) method. Serum PTH, 25(OH) and 1,25(OH)(2) vitamin D were measured and recalled birth weight recorded. RESULTS: Fractional intestinal Sr absorption (alpha Sr) was correlated with serum 1,25(OH)(2) vitamin D (p<0.001), but not with 25(OH) vitamin D. Birth weight was inversely associated with serum 1,25(OH)(2) vitamin D (p=0.04), the association being independent of serum calcium, phosphate, creatinine and PTH. Birth weight was inversely correlated with alpha Sr (p=0.03), this association being independent of age, season, customary calcium intake and serum 25(OH) vitamin D; however, when serum 1,25(OH)(2) vitamin D was added into the model, the association became non-significant, suggesting that the association was partially mediated via serum 1,25(OH)(2) vitamin D. DISCUSSION: We found a significant inverse association between birth weight and intestinal calcium absorption that is partially explained by an association between serum 1,25(OH)(2) vitamin D and birth weight. This suggests a mechanism whereby the intra-uterine environment might affect adult skeletal status.

Aged↗
PubMed2001

Methodology for treatment evaluation in patients with cancer metastatic to bone.

BACKGROUND: Patients with cancer metastatic to bone experience several adverse and clinically important skeletal-related events, including pathologic fractures, vertebral compressions with fracture, the need for surgery to treat or prevent fractures, and the need for radiation therapy for the treatment of bone pain. We present appropriate methods for describing and modeling the clinical course of skeletal-related events and comparing treatments for such events. METHODS: On the basis of data from a recently completed randomized, placebo-controlled trial involving 380 breast cancer patients with bone metastases, we tested the validity of the "events-per-person-years" method, one of the most commonly used techniques, for the analysis of skeletal-related events. We then used more robust methods of analysis that are based on fewer assumptions, including a random-effects Poisson model, and contrasted the inferences about skeletal-related event rates and treatment effects for the different analytic methods. All statistical tests were two-sided. RESULTS: The events-per-person-years analysis underestimated substantially the variation in the data and is not appropriate to summarize the incidence rate of skeletal-related events. A random-effects Poisson model did provide a valid basis for analyzing such data. CONCLUSIONS: The underestimation of variability in data associated with the use of the events-per-person-years analysis leads to unduly narrow confidence intervals for complication rates and inflated false-positive error rates in treatment comparisons. A random-effects Poisson model provides a valid, robust basis for describing the clinical course of bone complications and evaluating treatment effects.

Bone Neoplasms↗
PubMed2001

Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials.

PURPOSE: Two identical, concurrent, parallel, multicenter, randomized, double-blind, double-dummy trials were conducted to compare the efficacy and safety of zoledronic acid and pamidronate for treating hypercalcemia of malignancy (HCM). PATIENTS AND METHODS: Patients with moderate to severe HCM (corrected serum calcium [CSC] > or = 3.00 mmol/L [12.0 mg/dL]) were treated with a single dose of zoledronic acid (4 or 8 mg) via 5-minute infusion or pamidronate (90 mg) via 2-hour infusion. A protocol-specified pooled analysis of the two parallel trials was performed. Clinical end points included rate of complete response by day 10, response duration, and time to relapse. RESULTS: Two hundred eighty-seven patients were randomized and evaluated for safety; 275 were evaluated for efficacy. Both doses of zoledronic acid were superior to pamidronate in the treatment of HCM. The complete response rates by day 10 were 88.4% (P = .002), 86.7% (P = .015), and 69.7% for zoledronic acid 4 mg and 8 mg and pamidronate 90 mg, respectively. Normalization of CSC occurred by day 4 in approximately 50% of patients treated with zoledronic acid and in only 33.3% of the pamidronate-treated patients. The median duration of complete response favored zoledronic acid 4 and 8 mg over pamidronate 90 mg with response durations of 32, 43, and 18 days, respectively. CONCLUSION: Zoledronic acid is superior to pamidronate; 4 mg is the dose recommended for initial treatment of HCM and 8 mg for relapsed or refractory hypercalcemia.

Adult↗
PubMed2001

Comparison of DNA sequencing of the protein A gene polymorphic region with other molecular typing techniques for typing two epidemiologically diverse collections of methicillin-resistant Staphylococcus aureus.

The aim of this study was to compare the recently developed typing approach for methicillin-resistant Staphylococcus aureus (MRSA) based on the DNA sequencing of the protein A gene polymorphic region (spaA typing) with a combination of three well-established molecular typing techniques: ClaI-mecA vicinity polymorphisms, ClaI-Tn554 insertion patterns, and SmaI pulsed-field gel electrophoresis (PFGE) profiles. In order to evaluate the applicability of this typing technique in different types of studies, two groups of MRSA clinical isolates were analyzed: a collection of 185 MRSA isolates circulating in Hungary recovered from 17 hospitals in seven cities during a 3-year period (1994 through 1996), and a selection of 53 MRSA strains isolated in a single hospital in Hungary between 1997 and 1998. The 238 MRSA clinical strains from Hungary were first classified in clonal types (defined as ClaI-mecA::ClaI-Tn554::SmaI-PFGE patterns), and 65 of the 238 strains, representing major MRSA clones and some sporadic clones, were further analyzed by spaA typing. Our results showed that the lineages most recently introduced in the hospital setting showed little variability in spaA types, whereas the MRSA clones circulating for a longer period of time and spread among several hospitals showed a higher degree of variability. The implementation of the spaA typing method was straightforward, and the results obtained were reproducible, unambiguous, and easily interpreted. This method seems to be adequate for outbreak investigations but should be complemented with other techniques in long-term surveillance or in studies comparing distant clonal lineages.

Amino Acid Sequence↗
PubMed2000

A phase I dose escalation study of the matrix metalloproteinase inhibitor BAY 12-9566 administered orally in patients with advanced solid tumours.

BACKGROUND: This phase I study was performed to evaluate the safety, tolerability, and efficacy of the oral matrix metalloproteinase inhibitor BAY 12-9566 in patients with advanced solid tumours, and to identify the maximum tolerated dose and dose for use in subsequent studies. PATIENTS AND METHODS: BAY 12-9566 was administered to 29 patients at doses ranging from 100 mg o.d. to 1600 mg (given either 400 mg q.i.d. or 800 mg b.i.d.). Blood samples for pharmacokinetic analyses were drawn on days 1-5, day 15 and days 29 and 30. Patients were continued on daily oral treatment of BAY 12-9566 until a dose limiting toxicity or tumour progression occurred. RESULTS: A maximum tolerated dose was not defined because plasma levels of BAY 12-9566 could not be sufficiently increased, even with escalating doses of drug. Pharmacokinetic analysis suggested that absorption was saturable at higher doses. The predominant toxicities related to drug were asymptomatic reversible effects on platelets and transaminases and mild anemia. There were no significant musculoskeletal toxicities. No objective responses were seen at the doses tested, but stable disease was observed in some patients based on tumour measurements. CONCLUSIONS: The recommended dose of BAY 12-9566 for further studies is 800 mg b.i.d. as this dose provides maximal plasma levels that can be achieved with a convenient dosing schedule for a chronically administered oral agent.

Administration, Oral↗
PubMed2000

Craniofacial asymmetry and temporomandibular joint internal derangement in female adolescents: a posteroanterior cephalometric study.

Unilateral or bilateral pathology of the osseous components of the temporomandibular joint (TMJ) can result in pronounced facial asymmetry because of dissimilar size and shape of the right and left sides of the mandible. To date, it is unknown whether abnormalities of the soft tissues of the TMJ are associated with greater than normal craniofacial asymmetry. In this study, we investigated the amount of craniofacial asymmetry in female orthodontic patients with unilateral or bilateral TMJ internal derangement (TMJ ID) relative to the amount in female patients without TMJ ID. The total sample consisted of 80 female adolescents. Bilateral TMJ magnetic resonance images were used as a database for objectively scoring the severity of TMJ ID. Craniofacial asymmetry was measured from posteroanterior cephalograms. Females with bilateral TMJ ID had significantly greater asymmetry in the vertical position of the antegonion. If the TMJ ID was more advanced on the right side, the ipsilateral ramus was shorter, resulting in significant asymmetry in this region. In all other craniofacial regions, the amount of asymmetry was not significant between females with normal TMJs and those with TMJ ID. The results indicate that a female orthodontic patient with bilateral TMJ ID or unilateral right TMJ ID may present with or develop a vertical mandibular discrepancy.

Adolescent↗
PubMed2000

A randomized controlled trial of vitamin D supplementation on preventing postmenopausal bone loss and modifying bone metabolism using identical twin pairs.

Vitamin D supplementation, when given with calcium, has been shown to increase bone mineral density (BMD) and reduce the incidence of hip fracture in elderly subjects. Despite its widespread use, the benefits of vitamin D supplementation in younger women and as a single agent are less clear. We performed a randomized co-twin, placebo-controlled, double-blind trial over 2 years to measure the effect of vitamin D3 supplementation on bone density and bone metabolism in young postmenopausal women. Seventy-nine monozygotic (MZ) twin pairs (mean age, 58.7 years; range, 47-70 years) were recruited. For each twin pair, one was randomized to 800 IU cholecalciferol/day for 2 years and the other was randomized to placebo. BMD was measured at the spine and hip and heel ultrasound at baseline, 12, 18, and 24 months. Samples were collected at 0, 3, and 6 months to measure serum calcium, 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), osteocalcin, and urinary deoxypyridinoline (DPD). In total, 64 pairs completed the study. No differences in baseline characteristics were seen between the groups. At 6 months, the treatment group had an increase in serum vitamin D [mean +/- SEM intrapair difference, 14.1+/-2.4 microg/liter (p < 0.001)]. There were no significant differences in other serum measurements or bone markers at 3 months or 6 months. At 24 months, no significant treatment effect was seen on BMD or calcaneal ultrasound change within pairs. Subanalysis of treatment response by vitamin D receptor (VDR) genotype revealed no significant difference in effect on BMD variables with treatment. On the basis of these results, vitamin D supplementation, on its own, cannot be recommended routinely as an osteoporosis prevention for healthy postmenopausal women with normal vitamin D levels under the age of 70 years.

Aged↗
PubMed2000

Rapid combined assay for Salmonella detection in food samples.

A rapid method was developed to detect salmonellae in food samples. The method gave a possibility to obtain results after 28 h 30 min. The preenrichment in buffered peptone water lasted for 6 h, the enrichment in Rappaport-Vassiliadis medium was applied for 18 h followed by PCR with INVA1-INVA2 primer pair, adapting Chiu and Ou's method. This procedure was suitable to demonstrate salmonella contamination at min. 10 cfu/25 g sample. Out of 18 samples there was a good agreement between the results of the conventional and rapid methods in case of 17 samples. PCR with SPVC1-SPVC2 primer pair informing about the presence of virulence plasmid was performed in separate tubes, because decreased sensitivity was observed in case of multiplex PCR.

Culture Media↗
PubMed1999

Placebo-controlled trial of 13-cis-retinoic acid activity on retinoic acid receptor-beta expression in a population at high risk: implications for chemoprevention of lung cancer.

PURPOSE: To establish the incidence of abnormalities in the expression of retinoic acid receptor-beta (RARbeta) in bronchial cells and determine the capacity of 13-cis-retinoic acid (13-CRA) to correct such abnormalities. PATIENTS AND METHODS: One hundred eighty-eight smokers had a medical indication for bronchoscopy and were studied with bronchial brushings. Bronchial brushing samples were obtained for cytology analysis and for molecular analysis. After RNA was extracted, RARbeta sequences were amplified by reverse transcriptase polymerase chain reaction and Southern blots were performed to assess RARbeta expression. Forty-four eligible individuals with diminished RARbeta expression consented to double-blind randomization to receive a placebo or 13-CRA 30 mg orally daily for 6 months. A second bronchoscopy was performed at the end of the treatment period. An analysis of variance was used to analyze changes in RARbeta expression before and after treatment. RESULTS: The 6-month treatment course was completed by 27 patients, and results were obtained for a total of 18 patients (eight patients treated with 13-CRA and ten treated with the placebo). In the placebo group, there was no difference between the results of RARbeta expression before and after treatment (P =.43). In the 13-CRA group, there was an upregulation of RARbeta expression at the end of 13-CRA treatment (P =.001). Cytologic changes were uncommon. Toxicities were primarily of grade 1. Palatal brushings were compared with bronchial brushings in 40 smokers. A perfect correlation of the results of RARbeta expression was obtained from 27 patients. CONCLUSION: RARbeta expression is frequently decreased in the bronchial epithelium of smokers and is upregulated at the end of 13-CRA treatment. These results support undertaking a phase III chemoprevention trial of 13-CRA treatment for lung cancer.

Analysis of Variance↗
PubMed1999

Magnetic resonance imaging and clinical assessment of temporomandibular joint pathology in ankylosing spondylitis.

OBJECTIVE: To evaluate temporomandibular joint (TMJ) articular disc position and osseous degenerative changes using magnetic resonance imaging (MRI) as well as clinical symptoms of temporomandibular disorders in patients with ankylosing spondylitis (AS). METHODS: A sample of 43 patients with AS (38 males, age 45.9+/-10.7 years) and 16 controls (all male, age 41.3+/-6.3 years) were studied. All subjects completed a self-administered questionnaire and underwent clinical examination and MRI survey. Recorded variables included disease characteristics, subjective neck and TMJ disorder symptoms, and axial mobility measurements. MRI variables included TMJ disc position and severity of osseous degenerative change. RESULTS: TMJ disorder symptoms of headache duration and frequency, TMJ pain duration and frequency, and painful jaw movement were more frequent in patients with AS (p < 0.05). Significant differences were also observed in MRI indices for disc displacement (AS, 0.89; controls, 0.36; p = 0.005) and degenerative changes (AS, 0.55; controls, 0.06; p = 0.01). A total of 50 (62%) joints in the AS group had disc displacement compared to 11 (34%) joints in the controls. A total of 16 (20%) joints in the AS group had degenerative change compared to 2 (6%) joints in the controls. CONCLUSION: TMJ internal derangement, degenerative changes, and subjective pain complaints are frequent in patients with AS. Physicians should be aware of potential TMJ involvement in these patients, which may require specific assessment and therapy.

Facial Pain↗
PubMed1998

Subtle physical activity poses a challenge to the study of heart rate.

In nonhuman primates, our understanding of the effect of physical activity upon heart rate, particularly activity involving only slight, nonlocomotor movements, is poor. However, before inferring that other factors affect an animal's heart rate, the effect of physical activity upon heart rate must be considered. This study describes this effect in five adult female and seven infant rhesus macaques (Macaca mulatta). Interbeat interval (IBI), the reciprocal function of heart rate, was monitored using radiotelemetry during six categories of physical activity. IBI varied between different activities. The largest observed mean decrease in IBI was by 45% of that when sitting still, during locomotion by adult females. However, even subtle physical activity, involving no movement from a sitting position, produced a large, significant reduction in IBI. The effect of activity upon IBI was different between adults and infants. The findings indicate that measures of physical activity that consider only locomotion are insufficiently sensitive to describe the relationship between physical activity and heart rate.

Animals↗
PubMed1998

Correlations between condylar characteristics and facial morphology in Class II preadolescent patients.

The aim of this retrospective study was to determine correlations between condylar characteristics measured from preorthodontic tomograms of preadolescents and their facial morphologic characteristics. The sample consisted of 136 patients displaying a Class II malocclusion, a vertical or horizontal skeletal growth tendency, and ranging in age between 10 years 0 months and 12 years 6 months for males and 9 years 0 months and 11 years 6 months for females. Two groups were established: the vertical group had 68 patients, 36 males and 32 females, (average pretreatment age, 11 years 0 months); the horizontal group also had 68 patients, 29 males and 39 females, their average pretreatment age was 10 years 9 months. The central cut of axially corrected lateral tomograms of the left and right temporomandibular joints for each group was randomized, blinded, and traced for condyle/fossa measurements including: anterior, superior and posterior joint space; condylar head and posterior condylar ramus inclination; condylar neck width; and condylar shape and condylar surface area. A logistic discriminant analysis with significance values set at p < 0.05 was used to determine the most reliable condylar characteristics to predict facial morphology. A cluster analysis was completed on the significant variables to form three clusters. Numeric ranges separating these clusters were then calculated. Chi-square tests measures of association were computed for significant variables and tested for associations between facial morphologic characteristics. Condylar head inclination and superior joint space proved to be significantly correlated to facial morphology (p values ranged from 0.010 to 0.018). Patients with vertical facial morphologic characteristics displayed decreased superior joint spaces and posteriorly angled condyles. Increased superior joint spaces and anteriorly angled condyles were significantly correlated to patients with a horizontal facial morphology. No significant correlations between the other condylar characteristics and facial morphology were determined.

Analysis of Variance↗
PubMed1998

Age limitation on provision of orthopedic therapy and orthognathic surgery.

Canadian orthodontists were surveyed by mail to determine the latest skeletal age at which they would recommend orthopedic therapy and orthognathic surgery and the earliest at which they would recommend orthognathic surgery. For the purposes of this introductory study, orthopedic therapy implied stimulation of physiologic response using appliance force, without specification of appliance type. Response rate from 512 orthodontists was 65% (n = 334), with the response rate by item varying from 92% to 95%. By Greulich and Pyle standards, the latest recommended age for orthopedic therapy was at 97% completion of skeletal growth (females 13.5 years, males 15 years), whereas the earliest recommended age for orthognathic surgery was when skeletal growth is 99% complete (females 14.9 years, males 16.5 years). Surgery would be recommended by 32% of respondents for a patient before the age of 8 years, if deformity is severe. For orthognathic surgery, respondents either perceived no age maximum or recommended 69 years, the maximum age on the questionnaire item. Orthodontists' traits influenced recommendations for timing treatment.

Adolescent↗
PubMed1997

Condyle displacement associated with premolar extraction and nonextraction orthodontic treatment of Class I malocclusion.

This study assessed condyle position change with premolar extraction and nonextraction orthodontic treatment in Class I malocclusions. Axially corrected pretreatment and posttreatment tomograms were obtained in 22 extraction and 13 nonextraction cases. Tomographic images were randomized and blinded for joint space measurement. A total of 27 linear anterior, superior, and posterior joint spaces were obtained from each tomogram and averaged. Comparisons of pretreatment and posttreatment joint spaces between groups were done by t test (pool variance estimate) with p < 0.05. Left and right anterior joint spaces were significantly increased during orthodontic treatment of the nonextraction group. No other significant changes in condyle position were determined in either group. There were no significant correlations between mean joint space changes with length of Class II elastic wear. There was no significant difference in condyle position change with extraction space closure using closing arch wires compared with elastic chain.

Adolescent↗