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PubMed2006

Can discrete event simulation be of use in modelling major depression?

BACKGROUND: Depression is among the major contributors to worldwide disease burden and adequate modelling requires a framework designed to depict real world disease progression as well as its economic implications as closely as possible. OBJECTIVES: In light of the specific characteristics associated with depression (multiple episodes at varying intervals, impact of disease history on course of illness, sociodemographic factors), our aim was to clarify to what extent "Discrete Event Simulation" (DES) models provide methodological benefits in depicting disease evolution. METHODS: We conducted a comprehensive review of published Markov models in depression and identified potential limits to their methodology. A model based on DES principles was developed to investigate the benefits and drawbacks of this simulation method compared with Markov modelling techniques. RESULTS: The major drawback to Markov models is that they may not be suitable to tracking patients' disease history properly, unless the analyst defines multiple health states, which may lead to intractable situations. They are also too rigid to take into consideration multiple patient-specific sociodemographic characteristics in a single model. To do so would also require defining multiple health states which would render the analysis entirely too complex. We show that DES resolve these weaknesses and that its flexibility allow patients with differing attributes to move from one event to another in sequential order while simultaneously taking into account important risk factors such as age, gender, disease history and patients attitude towards treatment, together with any disease-related events (adverse events, suicide attempt etc.). CONCLUSION: DES modelling appears to be an accurate, flexible and comprehensive means of depicting disease progression compared with conventional simulation methodologies. Its use in analysing recurrent and chronic diseases appears particularly useful compared with Markov processes.

Journal Article↗
PubMed2003

Atrial high rate episodes detected by pacemaker diagnostics predict death and stroke: report of the Atrial Diagnostics Ancillary Study of the MOde Selection Trial (MOST).

BACKGROUND: Some current pacing systems can automatically detect and record atrial tachyarrhythmias that may be asymptomatic. We prospectively studied a 312-patient (pt) subgroup of MOST (MOde Selection Trial), a 2010-patient, 6-year randomized trial of DDDR versus VVIR pacing in sinus node dysfunction (SND). The purpose of the study was to correlate atrial high rate events (AHREs) detected by pacemaker diagnostics with clinical outcomes. METHODS AND RESULTS: Pacemakers were programmed to log an AHRE when the atrial rate was >220 bpm for 10 consecutive beats. Analysis was confined to patients with at least 1 AHRE duration exceeding 5 minutes. The 312 patients were median age 74 years, 55% female, and 60% had a history of SVT. 160 of 312 (51.3%) patients enrolled had at least 1 AHRE >5 minutes duration over median follow-up of 27 months. Cox proportional hazards analysis assessed the relationship of AHREs with clinical events, adjusting for prognostic variables and baseline covariates. The presence of any AHRE was an independent predictor of the following: total mortality (hazard ratio AHRE versus no AHRE and 95% confidence intervals=2.48 [1.25, 4.91], P=0.0092); death or nonfatal stroke (2.79 [1.51, 5.15], P=0.0011); and atrial fibrillation (5.93 [2.88, 12.2], P=0.0001). There was no significant effect of pacing mode on the presence or absence of AHREs. CONCLUSIONS: AHRE detected by pacemakers in patients with SND identify patients that are more than twice as likely to die or have a stroke, and 6 times as likely to develop atrial fibrillation as similar patients without AHRE.

Adult↗
PubMed2004

Treatment for spasticity in amyotrophic lateral sclerosis/motor neuron disease.

BACKGROUND: Spasticity commonly affects patients with motor neuron disease and it is likely to contribute to worsening muscle dysfunction, increased difficulty with activities of daily living and deteriorating quality of life. OBJECTIVES: The objective of this review is to systematically review all types of treatments for spasticity in amyotrophic lateral sclerosis, also known as motor neuron disease. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group specialised trials register (searched January 2003), MEDLINE (January 1966 to January 2003), EMBASE (January 1980 to January 2003), CINAHL (January 1982 to January 2003), AMED (January 1985 to January 2003) and LILACS (January 1982 to January 2003) for randomized controlled trials. We reviewed the bibliographies of the randomized trials identified, and contacted trial authors and known experts in the field. SELECTION CRITERIA: We included quasi-randomized or randomized controlled trials of participants with probable or definite amyotrophic lateral sclerosis according to the El Escorial diagnostic criteria (or a revised version) or the Airlie House revision. We would have included trials of physical therapy, modalities, prescription medications, non-prescription medications, chemical neurolysis, surgical interventions, alternative therapies. Our primary outcome measure was reduction in spasticity at three months or greater as measured by Ashworth (or modified Ashworth) spasticity scale. Our secondary outcome measures were: validated measures based on history, physical examination, physiological measures, measures of function, measures of quality of life, serious adverse events, and measures of cost. DATA COLLECTION AND ANALYSIS: We identified only one randomized controlled trial that met the inclusion criteria for this review. Two authors extracted the data. We also contacted the author of the paper and obtained further information not available in the published article. MAIN RESULTS: The included study was a trial of moderate intensity, endurance type exercise versus 'usual activities' in 25 patients with amyotrophic lateral sclerosis. At three months patients performing the 15 minute twice daily exercises had significantly less spasticity (mean reduction of 0.43 Ashworth grades versus an increase of 0.25 in controls), as measured by the Ashworth scale. REVIEWER'S CONCLUSIONS: Individualized, moderate intensity, endurance type exercises for the trunk and limbs may help to reduce spasticity in motor neuron disease. No other medical, surgical or alternative treatment and therapy has been evaluated in a randomized fashion in this patient population.

Amyotrophic Lateral Sclerosis↗
PubMed2006

Treatment for spasticity in amyotrophic lateral sclerosis/motor neuron disease.

BACKGROUND: Spasticity commonly affects patients with motor neuron disease. It is likely to contribute to worsening muscle dysfunction, increased difficulty with activities of daily living and deteriorating quality of life. OBJECTIVES: The objective of this review is to systematically review treatments for spasticity in amyotrophic lateral sclerosis, also known as motor neuron disease. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group trials register (January 2003 and January 2005), MEDLINE (January 1966 to February 2005), EMBASE (January 1980 to February 2005), CINAHL (January 1982 to February 2005), AMED (January 1985 to February 2005) and LILACS (January 1982 to January 2003). We reviewed the bibliographies of the randomized controlled trials identified, and contacted authors and experts in the field. SELECTION CRITERIA: We included quasi-randomized or randomized controlled trials of participants with probable or definite amyotrophic lateral sclerosis according to the El Escorial diagnostic criteria (or a revised version) or the Airlie House revision. We would have included trials of physical therapy, modalities, prescription medications, non-prescription medications, chemical neurolysis, surgical interventions, and alternative therapies. Our primary outcome measure was reduction in spasticity at three months or greater as measured by the Ashworth (or modified Ashworth) spasticity scale. Our secondary outcome measures were: validated measures based on history, physical examination, physiological measures, measures of function, measures of quality of life, serious adverse events, and measures of cost. DATA COLLECTION AND ANALYSIS: We identified only one randomized controlled trial that met our inclusion criteria. Two authors extracted the data. We also contacted the author of the paper and obtained information not available in the published article. MAIN RESULTS: The included study was a trial of moderate intensity, endurance type exercise versus 'usual activities' in 25 patients with amyotrophic lateral sclerosis. At three months patients performing the 15 minute twice daily exercises had significantly less spasticity overall (mean reduction of -0.43, 95% CI -1.03 to +0.17 in the treatment group versus an increase of +0.25, 95% CI -0.46 to +0.96 in control) but the mean change between groups was not significant (-0.68, 95% CI -1.62 to +0.26), as measured by the Ashworth scale. AUTHORS' CONCLUSIONS: The single trial performed was too small to determine whether individualised moderate intensity endurance type exercises for the trunk and limbs are beneficial or harmful. No other medical, surgical or alternative treatment and therapy has been evaluated in a randomized fashion in this patient population. More research is needed.

Amyotrophic Lateral Sclerosis↗
PubMed2006

Hyperhomocysteinemia and low plasma folate as risk factors for central retinal vein occlusion: a case-control study in a Chinese population.

PURPOSE: To determine whether hyperhomocysteinemia and low plasma folate are risk factors for central retinal vein occlusion (CRVO) in the Chinese population. METHODS: A matched case-control study was conducted between July 2004 and May 2005. The study cohort consisted of 64 individuals that had been diagnosed to have CRVO and 64 normal controls (matched for age, gender, hypertension, smoking and drinking habits). None of the cases or controls had a history of diabetes, glaucoma, medication or any other vascular events that might minimize the influence on plasma homocysteine levels. A cross-sectional analysis among the 64 cases was performed to compare the prevalence of hyperhomocysteinemia and low plasma folate among subjects with and without ischemia and subjects with age above 45 and below 45 years. Plasma homocysteine level was measured by means of high-performance liquid chromatography and plasma folate concentration by radioimmunoassay. RESULTS: The CRVO patients had a significantly higher homocysteine level (13.83+/-1.71 micromol/l) than the normal controls (8.05+/-0.58 micromol/l; p=0.003). The plasma folate levels were significantly lower in CRVO patients than in controls (5.62+/-0.39 ng/dl vs 7.23+/-0.60 ng/dl; p=0.032). A 1 micromol/l increase of plasma homocysteine level was associated with an odds ratio of 1.368. Hyperhomocysteinemia was defined as a homocysteine level of >14.97 micromol/l and was seen in 11 patients in the ischemic group, significantly more often than in the non-ischemic group (5 patients; p=0.030). CONCLUSIONS: The results suggest that hyperhomocysteinemia and low plasma folate are independent risk factors for CRVO and are associated with the development of CRVO in the Chinese population.

Adult↗
PubMed2005

Occurrence, hosts, morphology, and molecular characterisation of Pasteuria bacteria parasitic in nematodes of the family Plectidae.

Parasitic bacteria of the genus Pasteuria are reported for three Anaplectus and four identified and several unidentified Plectus species found in eight countries in various habitats. The pasteurias from plectids agree in essential morphological characters of sporangia and endospores as well as in developmental cycle with those of the Pasteuria species and strains described from tylenchid nematodes, but appear to be mainly distinguished from these by absence of a distinct perisporium in the spores and the endospores obviously not being cup- or saucer-shaped. The wide range of measurements and morphological peculiarities of sporangia and endospores suggest that probably several Pasteuria species have to be distinguished as parasites in Plectidae. From an infected juvenile of an unidentified plectid species the 16S rRNA gene sequence of Pasteuria sp. was obtained. Substantial sequence divergence from described Pasteuria species and its phylogenetic position on molecular trees indicate that this Pasteuria sp. could be considered as a new species. Preliminary results of the analysis of DNA phylogeny of Pasteuria spp. and their nematode hosts provide evidence for incongruence of their phylogenetic history and of host switching events during evolution of the bacterial parasites.

Animals↗
PubMed2000

The mouse lymphoma assay.

In this paper, the current status of the protocol for the Mouse Lymphoma Assay is discussed. A brief history describes the events leading to current protocol recommendations. Areas for further development such as cytotoxicity, 24-h treatments, acceptability criteria and statistical analysis are also considered. Recent guidelines are reviewed, and consensus issues from the Mouse Lymphoma workgroup assembled as part of the International Workshop on Genotoxicity Test Procedures (IWGTP) are included. There are two versions of the assay - soft agar and microwell - and both will be discussed. For assay procedures, the emphasis will be on a typical microwell protocol but an attempt will be made to highlight protocol variations between laboratories and between the microwell and agar versions of the assay.

Animals↗
PubMed2000

Homologous recombination between different genotypes of hepatitis B virus.

Phylogenetic analysis was used to examine the evolutionary relationships among 99 complete HBV sequences. Analysis revealed nine viral genomes clustered with different genotypes depending on genome region analyzed. This discordance indicated that recombination events occurred during HBV history. The putative breakpoints between genomes of different genotypes have been mapped. Six mosaic genomes representing B/C hybrids were isolated in East Asia and three A/D hybrids in Italy. At least some recombinant strains appear to be fully viable and possess high evolutionary potential. As a result, B/C recombinants overspread through the East Asia region. They were found among the isolates from Japan, China and Indonesia. Our results suggest that recombination is a significant and relatively frequent event in the evolution of HBV genome. A possible mechanism and the implications of recombination for the natural history of HBV, clinically important properties, and phylogenetic reconstruction are discussed.

DNA, Viral↗
PubMed1999

Identification of a novel mutation in a non-Jewish factor XI deficient kindred.

The role of factor XI (FXI) in blood coagulation has been clarified in recent years by descriptions of FXI-deficient patients who are prone to excessive bleeding after haemostatic challenge. We have studied a large kindred of an Italian FXI-deficient patient with a previously undescribed mutation. The propositus, a 68-year-old woman, presented with a cerebral thromboembolic event but had no history of bleeding (FXI activity 1.6 U/dl). A sensitive ELISA failed to detect FXI antigen in the propositus. Sequence analysis of the entire FXI gene revealed a TGG to TGC transversion in codon 228 of exon 7 (FXI-W228C). This missense mutation results in a Trp to Cys substitution within the third apple domain of FXI. We conclude that this novel mutation occurred in a structurally conserved region and may therefore have interfered with either chain folding and secretion or stability of FXI and was responsible for the inherited abnormality seen in this kindred. It is unclear why this kindred does not exhibit a bleeding tendency but it may correlate with a FXI-like antigen and factor IX binding activity expressed on platelets.

Aged↗
PubMed2004

A novel abundant family of retroposed elements (DAS-SINEs) in the nine-banded armadillo (Dasypus novemcinctus).

About half of the mammalian genome is composed of retroposons. Long interspersed elements (LINEs) and short interspersed elements (SINEs) are the most abundant repetitive elements and account for about 21% and 13% of the human genome, respectively. SINEs have been detected in all major mammalian lineages, except for the South American order Xenarthra, also termed Edentata (armadillos, anteaters, and sloths). Investigating this order, we discovered a novel high-copy-number family of tRNA derived SINEs in the nine-banded armadillo Dasypus novemcinctus, a species that successfully crossed the Central American land bridge to North America in the Pliocene. A specific computer algorithm was developed, and we detected and extracted 687 specific SINEs from databases. Termed DAS-SINEs, we further divided them into six distinct subfamilies. We extracted tRNA(Ala)-derived monomers, two types of dimers, and three subfamilies of chimeric fusion products of a tRNA(Ala) domain and an approximately 180-nt sequence of thus far unidentified origin. Comparisons of secondary structures of the DAS-SINEs' tRNA domains suggest selective pressure to maintain a tRNA-like D-arm structure in the respective founder RNAs, as shown by compensatory mutations. By analysis of subfamily-specific genetic variability, comparison of the proportion of direct repeats, and analysis of self-integrations as well as key events of dimerization and deletions or insertions, we were able to delineate the evolutionary history of the DAS-SINE subfamilies.

Animals↗
PubMed2000

Medical workforce planning in Australia.

The Australian Medical Workforce Advisory Committee (AMWAC) was established by the Australian Health Ministers' Advisory Council (AHMAC) in 1995 to provide information and analysis to AHMAC and the profession about the medical workforce to inform the policy process. This article provides a brief history of the events leading to the formation of AMWAC and of the work of this committee, particularly its approach to medical workforce planning and the outcomes of some of its research. The paper concludes that the forces leading to and maintaining workforce geographic and structural maldistribution are better understood as a result of AMWAC studies and the work of other stakeholders. Further research is required to improve understanding of the hospital medical workforce and the factors influencing the career decisions of young doctors and to monitor the impact of strategies to improve workforce distribution.

Australia↗
PubMed2004

Adult-onset epilepsy and history of childhood febrile seizures: a retrospective study.

BACKGROUND: Children with febrile seizures (FS) are at higher risk of developing epilepsy. There is robust literature on epilepsy with onset in childhood following FS but very little on the same issue in adults. AIMS: We intended to assess the association between adult-onset epilepsy and history of childhood FS. SETTINGS: The neurology clinic of a university hospital. DESIGN: A retrospective study. MATERIALS AND METHODS: Records of 101 consecutive adults (>14 years old) who were referred to our hospital with adult-onset seizures were reviewed and the patients and their families were interviewed to assess the medical history. STATISTICAL ANALYSIS: Chi-square test and Mantel-Haenszel method. RESULTS: Of the 101 patients, 9 were excluded for reasons of bacterial meningitis, recent head trauma, brain tumor, tricyclic antidepressants' overdose and missing reliable data of the childhood FS event. Thirty-one (33.7%) of the remaining 92 patients had history of FS in the childhood (71% men). Localization-related epilepsies were significantly associated with history of FS [Odds ratio: 3.29; (95% CI, 1.30-8.06)] ( (2)= 5.49, df = 1, P=0.012) when compared to other epilepsies and epilepsy syndromes. An initial unprovoked simple partial seizure was also significantly associated with a positive history of FS [Odds ratio: 8.05; (95% CI 2.88-22.45)] ( (2)= 15.86, df = 1, P< 0.001). CONCLUSIONS: Localization-related epilepsies and partial seizures seem to be associated with a history of FS in childhood. This warrants more investigation to understand the mechanism as well as a possible pathology common in both localization-related epilepsies and FS in the affected probands.

Adult↗
PubMed2004

Retrospective assessment of risk factors to predict tunneled hemodialysis catheter outcome.

PURPOSE: To identify factors that may influence the function, outcome, and complications associated with tunneled hemodialysis catheters. MATERIALS AND METHODS: Radiology reports and hemodialysis, medical, and Clinical Information System (computerized patient medical record system) records were retrospectively reviewed in 221 consecutive patients who underwent tunneled hemodialysis catheter placement by interventional radiologists between January 11, 1996 and January 13, 2000 at Dartmouth-Hitchcock Medical Center. Various patient characteristics (diabetes, smoking, hypertension, age, sex, atherosclerotic cardiovascular disease, history of cardiac catheterization, coumadin use, functional status, and obesity) were assessed for their relationship to the outcome of hemodialysis catheters. Catheter outcome was examined by calculating infection rate, thrombosis rate, fibrin formation rate, mechanical malfunction rate, and total complication rate. With these patient characteristics and outcome variables, multiple regression analysis was performed with STATA (College Station, TX) statistical analysis software. RESULTS: Of the 221 patients reviewed, 39 patients were lost to follow-up. Among the remaining 182 patients, 427 catheters were placed for a total number of 36994 catheter-days. For overall complication rate, multiple regression analysis revealed a statistically significant positive correlation only for hypertension (P =.032). Total complication rate was 0.76 events per 100 catheter-days (95% CI: 0.53-1.00) for patients with a documented history of hypertension and 0.27 events per 100 catheter-days (95% CI: 0.08-0.45) for patients without (P =.024, paired student t test). For patients with diabetes versus patients without, the infection rates were 0.34 episodes per 100 catheter-days (95% CI: 0.15-0.53) and 0.12 episodes per 100 catheter-days (95% CI: 0.06-0.18), respectively, (P =.011, paired student t test). Thrombosis rate for patients on coumadin was 0.13 events per 100 catheter-days (95% CI: -0.14-0.40), while thrombosis rate for patients not taking coumadin was 0.03 events per 100 catheter-days (95% CI: 0-0.05) (P =.036, paired student t test). CONCLUSION: Hypertension is a risk factor for poor outcome of tunneled hemodialysis catheters as measured by total complication rate requiring catheter removal or exchange. In this retrospective study, no other specific risk factors predicted an increased need for removal or exchange of tunneled hemodialysis catheters.

Adolescent↗
PubMed1989

Tallow and the time capsule: Claude Bernard's discovery of the pancreatic digestion of fat.

In 1848, Claude Bernard discovered that pancreatic secretion could emulsify and saponify fatty substances. He would eventually attribute these reactions to an enzyme that was later named 'pancreatic lipase'. This essay has three goals: 1) to examine Bernard's previously overlooked research on the pancreas; 2) to explore the equally ignored history of lipid digestion and metabolism; 3) to reconstruct Bernard's discovery of pancreatic lipase through a parallel analysis of his laboratory notebooks and his publications. This method reveals a discrepancy between the sequence and motivation of events as they were reported by Bernard in his publications and as they appear in his laboratory notebooks.

Animals↗
PubMed2006

A population-based and longitudinal study of sexual behavior and multidrug-resistant HIV among patients in clinical care.

BACKGROUND: Population-based and longitudinal information regarding sexual risk behavior among patients with multidrug resistant (MDR) HIV and their sexual partners is of great public health and clinical importance. OBJECTIVE: To characterize the HIV sexual risk behaviors of patients with and without drug-resistant HIV in the clinical care setting over time. MEASUREMENTS: 393 HIV-positive patients completed questionnaires of self-reported sexual risk behaviors at approximate 6-month intervals extending over 24 months. HIV viral load and genotypic drug resistance obtained during the same time points were matched to the behavioral data. Multidrug resistance was defined as having resistance to 2 or 3 antiretroviral (ARV) drug classes. RESULTS: In serial cross-sectional analyses, 393 patients (44% female and 79% heterosexual) contributed 919 matched behavioral and virologic results over the 24 months of data collection. Of these, 250 patients (64%) reported having sex during at least 1 survey period resulting in greater than 10,000 sexual events with more than 1000 partners. Unprotected sexual behavior was reported by 45% of sexually active patients, resulting in 34% of all sex events that exposed 29% of all partners. Of these patients with unprotected sexual events, 31% had HIV drug resistance--11.6% with resistance to 2 classes of ARVs (2-class), and 1.8% with 3-class ARV resistance at the time of a sexual risk event. Close to 1000 or 28% of all unprotected sexual events involved resistant strains (11% of these with resistance to 2 classes and 0.2% with 3-class resistance, exposing 20% of unprotected sexual partners to resistant HIV (8% to 2-class and 0.6% to 3-class resistance). In longitudinal analysis among the 78 patients who reported a cumulative total of 12 months of sexual history and had resistance testing, 38% reported engaging in unprotected sexual behavior. There was substantial and complex variation in the distribution of unprotected sexual events and in the detection of resistance over time. CONCLUSION: In this study of HIV sexual risk and resistance over time among HIV-infected patients in clinical care, a substantial proportion engaged in unprotected sex and had drug-resistant HIV, frequently exposing partners to 1- or 2-class resistant HIV strains. However, relatively few exposures involved 3-class resistance. The dynamics of sexual risk behavior and HIV drug resistance are complex and vary over time and urgently require both general and targeted interventions to reduce transmission of resistant HIV.

Adult↗
PubMed1998

Identification and classification of factitious disorders: an analysis of cases reported during a ten year period.

OBJECTIVE: The current article offers a new conceptualization of factitious disorders based on cases reported in the literature. METHOD: The current analysis examines twenty-nine cases of factitious disorder patients over the course of ten years (1986-1996). Cases were found through PSYCHLIT and MEDLINE searches. Patient variables examined include: demographics, occupational status, marital status, childhood history, extent of medical history, the presence of a borderline personality disorder, and presence of a psychosocial stressor prior to the onset of the factitious disorder. RESULTS: An examination of the cases found demographic patterns of illness presentation consistent with previous reviews of the disorder. From the examination emerged two distinct types of factitious presentations-one acute, one chronic. A two-dimensional approach is introduced in an attempt to understand various disease presentations. Cases were classified based on proposed Current Life Stress and Chronic Life Pattern dimensions. These dimensions are measures of the extent to which the patient's factitious presentation is in response to an immediate psychosocial stressor, or an action consistent with a long-term maladaptive behavior pattern resulting from an underlying character pathology. Three patient groups were identified based on estimated patient levels of each dimension. The three groups are: Stress Response, Life Response, and Mixed Response. CONCLUSION: Recommendations are made to increase the role of physicians in the detection of factitious patients, as well as to move toward a more uniform reporting of cases of factitious disorders in the literature.

Adolescent↗
PubMedDate not supplied

Predictors of depression in Thai women.

This cross-sectional correlational study examined the associations between depression and family history of depression, early loss of mother before age 11, number of stressful life events, women's role strains, interpersonal conflict, parental role strain, perceived stress, social support, and sense of belonging in 142 Thai women (77 depressed and 65 nondepressed). Results from chi-square tests and t tests revealed that compared to nondepressed women, depressed women were more likely to have a family history of depression and history of loss of mother before age 11; significantly higher stressful life events, parental role strain, interpersonal conflict, and perceived stress; and significantly lower interpersonal resources, perceived social support, and sense of belonging. Results from logistic regression, however, showed that only family history of depression, perceived stress, and sense of belonging predicted depression in Thai women. Results from path analysis showed that 66% of the variance of depression was explained by the proposed model. Perceived stress had the strongest direct effect on severity of depression. Family history of depression had both direct and indirect effects on severity of depression. Number of stressful life events, interpersonal conflict, parental role strain, perceived social support, and sense of belonging had indirect but not direct effects on severity of depression. Loss of mother before age 11 and interpersonal resources had neither direct nor indirect effects on severity of depression. Results from this study contributed significant information for understanding depression in Thai women and can help health care providers in Thailand to provide better care for depressed patients and prevent depression in Thai women.

Adult↗
PubMed1999

Are there low-penetrance TP53 Alleles? evidence from childhood adrenocortical tumors.

We have analyzed a panel of 14 cases of childhood adrenocortical tumors unselected for family history and have identified germline TP53 mutations in >80%, making this the highest known incidence of a germline mutation in a tumor-suppressor gene in any cancer. The spectrum of germline TP53 mutations detected is remarkably limited. Analysis of tumor tissue for loss of constitutional heterozygosity, with respect to the germline mutant allele and the occurrence of other somatic TP53 mutations, indicates complex sequences of genetic events in a number of tumors. None of the families had cancer histories that conformed to the criteria for Li-Fraumeni syndrome, but, in some families, we were able to demonstrate that the mutation had been inherited. In these families there were gene carriers unaffected in their 40s and 50s, and there were others with relatively late-onset cancers. These data provide evidence that certain TP53 alleles confer relatively low penetrance for predisposition to the development of cancer, and they imply that deleterious TP53 mutations may be more frequent in the population than has been estimated previously. Our findings have considerable implications for the clinical management of children with andrenocortical tumors and their parents, in terms of both genetic testing and the early detection and treatment of tumors.

Adaptor Proteins, Signal Transducing↗