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Biomedical subjects

Paul A James

Publications and source records attributed to Paul A James.

At least 19 recordsLinked to original sources
PubMed2026

Impact of BRCA1/2 status on young women's sexual function, relationships, and reproduction after predictive genetic testing.

The experiences and outcomes for women identified with a BRCA1/2 pathogenic variant during young adulthood are qualitatively described but not well quantified. This study investigated the impact of BRCA1/2 status on women's reproduction, intimate partner relationships, and sexual functioning. Australian women aged 18-40 years who had predictive BRCA1/2 testing, received either a positive or negative result, and had no personal cancer history, completed an online survey that used a case-control design. Outcome measures included childbearing, use of reproductive technologies, relationship status, and sexual functioning. 579 women participated (62.0% with a BRCA1/2 PV; 38.0% without a BRCA1/2 PV). More women with a BRCA1/2 PV had children compared to those who did not (49.0% c.f., 40.5%; p = 0.045). BRCA1/2 status did not predict whether women were partnered at survey completion (Odds Ratio 1.20; 95% CI 0.80, 1.78) or their sexual functioning over the previous month (β-coefficient -0.08; 95% CI -1.15, 0.98). Women with a BRCA1/2 PV were more likely to have children after genetic testing (OR 1.83: 95% CI 1.05, 3.21) and were more likely to have a greater number of children after genetic testing (β-coefficient 0.41; 95% CI 0.10, 0.73) compared to women without a BRCA1/2 PV, after adjustment for confounders. Receiving a positive predictive BRCA1/2 result is associated with an increased likelihood of childbearing and having a greater number of children compared to receiving a negative predictive BRCA1/2 result. These findings contribute to the evidence base to inform long-term follow-up for women after predictive BRCA1/2 testing.

Humans↗
PubMed2006

Colorectal cancer testing among patients cared for by Iowa family physicians.

BACKGROUND: Colorectal cancer (CRC) can be largely prevented or effectively treated, yet about half of eligible Americans have not been screened. The purpose of this study was to examine patient and physician factors associated with documented CRC testing according to national guidelines. METHODS: Cross-sectional study where 511 randomly selected rural patients aged 55 to 80 years of 16 board-certified Iowa family physicians were enrolled in 2004. Patient survey and medical record information were linked with physician surveys. Predictors of CRC testing were examined using a regression procedure that accommodated random physician effects (2005-2006). RESULTS: Forty-six percent of patients were up-to-date with CRC testing in accordance with national guidelines. This percentage varied from 5% to 75% by physician (p < 0.0001). Of the patients who were up-to-date, 89% had colonoscopy, and 62% had symptoms prior to testing that could indicate CRC. The strongest univariate predictors other than symptoms were patient recollection of physician recommendation (odds ratio [OR] = 6.4, 95% confidence interval [CI] = 4.2-9.6) and physician documentation of recommendation (OR = 14.1, CI = 8.5-23.3). A multivariable regression model showed testing in accordance with guidelines significantly increased with government insurance (OR = 1.6, CI = 1.2-2.3), having a health maintenance visit in the preceding 26 months (OR = 2.4, CI = 1.4-4.1), family history of CRC (OR = 3.1, CI = 1.6-5.8), number of medical conditions (OR = 1.2 for each additional condition, CI = 1.1-1.3), high importance of screening to patient (OR = 2.6, CI = 1.5-4.5), patient satisfaction with doctor's discussions (OR = 3.3, CI = 2.2-4.8), physician trained in flexible sigmoidoscopy (OR = 2.3, CI = 1.6-3.4), and physician report of trying to follow American Cancer Society (ACS) guidelines (OR = 1.7, CI = 1.2-2.5). After excluding patients who had symptoms prior to screening, most of the ORs in the logistic regression analysis increased except that the number of medical conditions and physician trying to follow ACS guidelines became nonsignificant. CONCLUSIONS: Fewer than half of rural patients received CRC testing, and most of those tested had symptoms. Physician recommendations and the manner of presenting the recommendations greatly influenced whether patients were tested.

Aged↗
PubMed2006

The molecular genetics of non-ALS motor neuron diseases.

Hereditary disorders of voluntary motor neurons are individually relatively uncommon, but have the potential to provide significant insights into motor neuron function in general and into the mechanisms underlying the more common form of sporadic Amyotrophic Lateral Sclerosis. Recently, mutations in a number of novel genes have been associated with Lower Motor Neuron (HSPB1, HSPB8, GARS, Dynactin), Upper Motor Neuron (Spastin, Atlastin, Paraplegin, HSP60, KIF5A, NIPA1) or mixed ALS-like phenotypes (Alsin, Senataxin, VAPB, BSCL2). In comparison to sporadic ALS these conditions are usually associated with slow progression, but as experience increases, a wide variation in clinical phenotype has become apparent. At the molecular level common themes are emerging that point to areas of specific vulnerability for motor neurons such as axonal transport, endosomal trafficking and RNA processing. We review the clinical and molecular features of this diverse group of genetically determined conditions and consider the implications for the broad group of motor neuron diseases in general.

Adolescent↗
PubMed2006

Optimal selection of individuals for BRCA mutation testing: a comparison of available methods.

PURPOSE: Several methods have been described that estimate the likelihood that a family history of cancer is a result of a mutation in the BRCA1 or BRCA2 genes. We examined the performance of six different methods with the aim of identifying an optimal strategy for selecting individuals for mutation testing in clinical practice. PATIENTS AND METHODS: Two hundred fifty-seven families who had completed BRCA1 and BRCA2 mutation screening were assessed by six models representing the major methodologies used to assess the likelihood of a pathogenic mutation. The performance of each method as a selection criterion was compared with the result of mutation testing to produce sensitivity, specificity, and receiver operating curve data. The impact of incorporating breast cancer pathology data in the assessment was also analyzed. RESULTS: The highest accuracy was achieved by the Bayesian probabilistic model (BRCAPRO). The formal probabilistic methods were significantly more accurate than clinical scoring methods. The methods were further improved by the incorporation of information on breast cancer pathology (tumor grade and estrogen receptor/progesterone receptor status). The resulting combined probability figure was highly accurate when selecting individuals for BRCA1 testing. Some BRCA2 mutation carriers were missed by all of the models examined. CONCLUSION: Formal probabilistic models provide significantly greater accuracy in the selection of families for gene testing than the use of clinical criteria or scoring methods. The accuracy is further enhanced by incorporating information on the pathology of breast cancers occurring in the families.

Adult↗
PubMed2005

A mutation in the small heat-shock protein HSPB1 leading to distal hereditary motor neuronopathy disrupts neurofilament assembly and the axonal transport of specific cellular cargoes.

Distal hereditary motor neuronopathies (dHMNs) are a clinically and genetically heterogeneous group of disorders in which motor neurons selectively undergo age-dependant degeneration. Mutations in the small heat-shock protein HSPB1 (HSP27) are responsible for one form of dHMN. In this study, we have analysed the effect of expressing a form of mutant HSPB1 in primary neuronal cells in culture. Mutant (P182L) but not wild-type HSPB1 led to the formation of insoluble intracellular aggregates and to the sequestration in the cytoplasm of selective cellular components, including neurofilament middle chain subunit (NF-M) and p150 dynactin. These findings suggest a possible pathogenic mechanism for HSPB1 whereby the mutation may lead to preferential motor neuron loss by disrupting selective components essential for axonal structure and transport.

Axonal Transport↗
PubMed2005

Another case of interstitial del(12) involving the proposed cardio-facio-cutaneous candidate region.

Recent reports of patients with interstitial deletions involving the long arm of chromosome 12 have led to the proposal of a candidate region for the cardio-facio-cutaneous syndrome (CFCS) at (12)(q21.2q22). We now report a patient with an interstitial deletion, del(12)(q21.1q21.3) that overlaps the proposed critical region. The patient is an 11-year-old female with developmental delay. Her growth was normal but she is microcephalic with low set ears. In common with other patients with deletions in this region, she had fine, sparse head and eyebrow hair and a hyperkeratotic follicular rash, which involved her face and limbs. She does not have the diagnostic features of the CFC syndrome.

Abnormalities, Multiple↗
PubMed2005

The limited effect of screening for depressive symptoms with the PHQ-9 in rural family practices.

CONTEXT: Previous studies have found that routine screening for depression does not improve patient outcome unless it is combined with case management. However, these studies were conducted before the widespread use of SSRIs or in settings other than traditional primary care. PURPOSE: This study investigated whether screening for depressive symptoms improves outcomes for depressed patients seen in rural fee-for-service primary care offices. METHODS: Depression screening was conducted at 2 private rural clinics in Iowa using the PHQ-9. Patients with depressive symptoms were randomized to the control group or the intervention group, where providers were given completed PHQ-9 questionnaires at the baseline visit. The outcome PHQ-9 scores were assessed by telephone at 4, 10, and 24 weeks after the index visit. FINDINGS: A total of 861 patients were screened for depressive symptoms; 51 subjects enrolled in the trial. The intervention and control groups did not significantly differ with respect to changes in PHQ-9 scores at any of the 3 follow-up times. They also did not differ with respect to the proportion of subjects who were actively managed with medication or by referral to a mental health specialist: 46% vs 33% (P = .38) for all subjects and 50% vs 50% (P = .96) for subjects with major depression at baseline. CONCLUSIONS: Screening for depressive symptoms with the PHQ-9 in 2 rural medical clinics did not significantly increase physicians' active management of depression or lead to improved patient outcomes.

Adult↗
PubMed2004

Measuring adherence to practice guidelines for the management of hypertension: an evaluation of the literature.

Adherence to practice guidelines is frequently used as a measure of quality of care. Numerous studies have evaluated physician adherence to hypertension guidelines by prescription data, physician survey data, or medical record review. However, most have methodological limitations that might underestimate physician adherence. Accurate and meaningful characterization of adherence rests on evaluation of varied components of hypertension care, use of explicit validated performance measures, incorporation of implicit and explicit review, and linkage of process measures to blood pressure outcomes.

Guideline Adherence↗
PubMed2003

Severe musculoskeletal phenotype associated with an unbalanced t(6;10) translocation: clarification of the locus for this phenotype on distal 6p.

Larsen syndrome is a congenital condition consisting of multiple large joint dislocations associated with a distinctive facial appearance and frequently other abnormalities. The syndrome is probably genetically heterogeneous, with both dominant and recessive inheritance reported. Previously two cases have been reported where a Larsen-like syndrome was associated with unbalanced chromosomal translocations resulting in partial trisomy 1q and monosomy distal 6p. We now report a child with an unbalanced translocation resulting in a distal 6p deletion and partial trisomy 10q, who has Larsen-like features and has also severe developmental delay. A G-banded preparation revealed a karyotype 46,XX,der(6),t(6:10)(p25;q25.2) and the breakpoint at 6p25 was confirmed by FISH using YAC probes (between 6p25 at D6s477/F13A1 and 6p24 at 6WI13606). Our case provides further evidence for a Larsen-like locus at distal 6p and reduces the potential critical region.

Adult↗
PubMed2003

Familial mitral valve prolapse associated with short stature, characteristic face, and sudden death.

Mitral valve prolapse (MVP) is frequently a familial disorder but in few of these inherited cases it does form a prominent component of a multiple congenital anomaly (MCA) syndrome. We report a family in which eight individuals in four generations were affected by a dominantly inherited disorder involving MVP, short stature, a dolicocephalic face, broad forehead, posteriorly angulated ears, long philtrum, thin upper lip, high arched palate, and a small mandible. The proband presented with infective mastoiditis, bacterial endocarditis, and a supraventricular tachycardia. One other family member also had infective mastoiditis and bacterial endocarditis and both the proband's mother and grandmother died suddenly at the age of 30 and 25 years, respectively.

Adult↗
PubMed2003

CHARGE association and secondary hypoadrenalism.

Hypogonadotrophic hypogonadism is a well-described part of the CHARGE association. It has been suggested that more extensive defects of the pituitary function may occur, but this has not been reported in the medical literature. We report a patient with CHARGE association who, in addition to the cardinal manifestations, was found to have hypoadrenalism of pituitary/hypothalamic origin. The patient also has findings typical of the overlap of CHARGE and the 22q11 deletion syndrome, as well as an unusual cervical vertebral abnormality.

Abnormalities, Multiple↗
PubMed2003

Familial cerebro-costo-mandibular syndrome: a case with unusual prenatal findings and review.

Cerebro-costo-mandibular syndrome is characterized by the Pierre-Robin anomaly, multiple rib defects and the occasional occurrence of intellectual impairment. Over 60 cases have been reported, nearly half of which are familial. We report an infant and her father with typical features of CCMS. The child was diagnosed on prenatal ultrasound and was found to have the previously unreported prenatal finding of an omphalocoele. Twenty-eight cases of familial CCMS are reviewed. Families suggestive of autosomal recessive and autosomal dominant inheritance are not distinguishable on the basis of clinical manifestations.

Abnormalities, Multiple↗
PubMed2003

A model for diversity in admissions: a review of issues and methods and an experimental approach.

PURPOSE: The underrepresentation of certain minorities within medical education and the medical profession continues to be a problem. A review of the relevant research literature suggests current strategies are inadequate to address this important problem. Psychometric issues important in differentiating the unique concerns of medical education must be defined. SUMMARY: A new model that may attain diversity goals and meet standards related to validity and legality is presented. Admissions data describing applicants for one year at a large midwestern medical college are analyzed. The impact of selection techniques on both majority and underrepresented minority applicants is presented. CONCLUSION: The results of the analyses support further research designed to meet the quantitative objectives implied by diversity goals and suggests initiatives aimed at enhancing minority representation within medical education.

Cultural Diversity↗
PubMed2002

Complete overlap of PHACE syndrome and sternal malformation--vascular dysplasia association.

PHACE syndrome is the term applied to the association of posterior fossa brain abnormalities, hemangiomas, arterial anomalies in the cranial vasculature, coarctation of the aorta/cardiac defects, and eye abnormalities. An overlap with the sternal malformation/vascular dysplasia association has been described. We report an adult patient with complete manifestations of both conditions. As an adult she has demonstrated resolution of the hemangiomas and only mild intellectual difficulties.

Abnormalities, Multiple↗