Colonization and demographic expansion of freshwater fauna across the Hawaiian archipelago.

It is widely accepted that insular terrestrial biodiversity progresses with island age because colonization and diversification proceed over time. Here, we assessed whether this principle extends to oceanic island streams. We examined rangewide mtDNA sequence variation in four stream-dwelling species across the Hawaiian archipelago to characterize the relationship between colonization and demographic expansion, and to determine whether either factor reflects island age. We found that colonization and demographic expansion are not related and that neither corresponds to island age. The snail Neritina granosa exhibited the oldest colonization time (~2.713 mya) and time since demographic expansion (~282 kya), likely reflecting a preference for lotic habitats most prevalent on young islands. Conversely, gobioid fishes (Awaous stamineus, Eleotris sandwicensis and Sicyopterus stimpsoni) colonized the archipelago only ~0.411-0.935 mya, suggesting ecological opportunities for colonization in this group were temporally constrained. These findings indicate that stream communities form across colonization windows, underscoring the importance of ecological opportunities in shaping island freshwater diversity.

Characterization of a novel founder MSH6 mutation causing Lynch syndrome in the French Canadian population.

We identified an MSH6 mutation (c.10C>T, p.Gln4*) causing Lynch syndrome (LS) in 11 French Canadian (FC) families from the Canadian province of Quebec. We aimed to investigate the molecular and clinical implications of this mutation among FC carriers and to assess its putative founder origin. We studied 11 probands and 27 family members. Additionally 6433 newborns, 187 colorectal cancer (CRC) cases, 381 endometrial cancer (EC) cases and 179 additional controls, all of them from Quebec, were used. Found in approximately 1 of 400 newborns, the mutation is one of the most common LS mutations described. We have found that this mutation confers a greater risk for EC than for CRC, both in the 11 studied families and in the unselected cases: EC [odds ratio (OR) = 7.5, p < 0.0001] and CRC (OR = 2.2, p = 0.46). Haplotype analyses showed that the mutation arose in a common ancestor, probably around 430-656 years ago, coinciding with the arrival of the first French settlers. Application of the results of this study could significantly improve the molecular testing and clinical management of LS families in Quebec.

Assessment of fibromyalgia & chronic fatigue syndrome: a new protocol designed to determine work capability--chronic pain abilities determination (CPAD).

The objective was to design a protocol to assess work ability in people suffering ill-defined painful and disabling disorders, the outstanding prototype of which is fibromyalgia/chronic fatigue syndrome (FM/CSF).Following an extensive literature search, the mos appropriate components of current methods of assessment of physical and cognitive abilities were incorporated into the protocol, occasionally with appropriate modification to suit the specific requirements of the individual. The initial part of the assessment consists of a standard history taking, principally focusing on the patient's self-reported physical and cognitive abilities and disabilities, as well as the completion of established pain and fatigue scales, and relevant disability questionnaires. Following this, physical and cognitive abilities are objectively assessed on two separate occasions, utilizing computerized hand-held dynamometers, inclinometers, algometers, and force dynamometers. Specific work simulation tests using the industrial standards Methods-Time-Measurement testing are availed of, as is aerobic testing using the Canadian Aerobic Fitness Test (CAFT). Objective computerised neuro-cognitive testing are also utilised as an integral component of the assessment. All results are then subject to specific computerized analysis and compared to normative and standardised work-based databases. The designed system produces reliable, consistent and reproducible results. It also proves capable of detecting any inconsistencies in patient input and results, in addition to being independent of any possible assessor bias. A new protocol has been designed to determine the working capability of individuals who suffer from various chronic disabling conditions, and represents a significant step forward in a difficult but rapidly expanding area of medical practice.

Pyruvate dehydrogenase deficiency presenting as intermittent isolated acute ataxia.

OBJECTIVE: The aim of this study is to report and emphasize unusual presentations of pyruvate dehydrogenase (PDH) deficiency (OMIM 312170). METHODS: PDH activity and PDHA1 gene were studied in two siblings presenting with intermittent ataxia in childhood. Similar presentations in reported PDH-deficient patients were searched for using the Medline database. RESULTS: Both patients had PDH deficiency caused by a new mutation (G585C) in the PDHA1 gene, which is predicted to replace a highly conserved glycine at codon 195 by alanine. Although this mutation lies within the thiamine pyrophosphate binding domain, there was no thiamine responsiveness IN VIVO. The patients presented recurrent episodes of acute isolated ataxia in infancy. Both had normal blood and CSF lactate levels. Although symptoms initially resolved between episodes during the first decade, both patients subsequently worsened and developed progressive and severe encephalopathy, leading to death in their twenties. The spectrum of intermittent presentations in PDH deficiency includes episodic ataxia, intermittent peripheral weakness, recurrent dystonia and extrapyramidal movement disorders. CONCLUSIONS: PDH deficiency should be considered in patients with unexplained intermittent and recurrent acute neurological symptoms. Long-term prognosis and outcome remain uncertain. PDH deficiency can occur even with normal CSF lactate concentration.

Regulatory initiatives and framework in the USA: interventional radiology.

Therapeutic procedures using interventional radiology equipment as the imaging tool are often the only available treatment for serious, life-threatening conditions. Many of these procedures require extended periods of radiation exposure often at one location on the patient. As a result, the US Food and Drug Administration (FDA) continues to receive reports of radiation-induced injuries to the skin in patients undergoing some of these therapeutic procedures. The regulatory scheme applicable to interventional radiology equipment in the US is described including federal, state and local aspects, and the impact of professional and non-governmental organisations. Current activities within the FDA and other organisations which have or will affect the use, maintenance and manufacture of interventional radiology equipment are also described.

Uncertainties in estimates of lesion detectability in diagnostic ultrasound.

Statistical properties of estimates of focal lesion detectability for medical ultrasonic imaging systems are investigated. Analytic forms for bias and variance of estimates of detectability of a lesion consisting of fully developed speckle embedded within a speckle background are derived. Bias and variance of estimates of detectability are investigated using a computer simulation and experiments on tissue-mimicking phantoms. This work offers a systematic methodology for interpreting measurements on phantoms in order to assess lesion detectability. In addition, it provides useful results which may be used to improve design of phantoms and experiments for imaging-system performance assessment.

Clinical spectrum of infantile free sialic acid storage disease.

Infantile free sialic acid storage disease (ISSD) is a rare autosomal recessive metabolic disorder caused by a lysosomal membrane transport defect, resulting in accumulation of free sialic acid within lysosomes. Only a few cases have been described. We report on three new cases of ISSD with different modes of presentation: an infant with nephrotic syndrome, a case of fetal and neonatal ascites with heart failure, and a case of fetal ascites with esophageal atresia type III. From these patients and a review of the literature (27 cases total) we draw the following conclusions. 1) "Coarse facies," fair complexion, hepatosplenomegaly, and severe psychomotor retardation are constant findings in this disorder. 2) Nephrotic syndrome occurred in most cases (four in seven) in which renal evaluation was performed. Therefore, ISSD is an important cause of nephrosis in infants with a storage disorder phenotype. 3) Fetal/neonatal ascites or hydrops was the mode of presentation in 13 (60%) of 21 cases. Thus, ISSD enters in the differential diagnosis of hydrops fetalis with a storage disease phenotype. 4) Cardiomegaly was evident in nine cases. 5) Corneae were always clear, and albinoid fundi were reported in five cases. 6) Dysostosis multiplex was not prominent. 7) Bone marrow aspiration could be negative. 8) Death ensued in early infancy with a mean age of 13.1 months. All reported deaths were caused by respiratory infections.

Impact of a preceptor education board and computer network to engage community faculty at Dartmouth Medical School.

In 1994, as part of the Generalist Physician Initiative of The Robert Wood Johnson Foundation, Dartmouth Medical School established two programs to support and engage community-based teaching. The Preceptor Education Board and Community Computer Network were established to support a network of community-based preceptors and to facilitate communication between course directors at the school and community-based teachers. The board's mission is to organize, develop, and support a network of community-based primary care faculty, and to create and review community-based curricula. Through the board, community faculty members have made substantial contributions to curriculum, evaluation, faculty development, governance, and financing in community-based teaching. The Community Computer Network provides hardware, software, network systems, and support. Course directors and students have reported improved community-based educational experiences as a direct result of the Network. These two initiatives are dynamic and effective ways to improve the quality of community-based education and preceptors' morale. These efforts have strengthened the community faculty and their connection to the academic medical center.

Referrals for depression by primary care physicians. A pilot study.

BACKGROUND: Communication between primary care physicians (PCPs) and mental health providers (MHPs) is integral to the management of depressive disorders. Our study investigated referrals from PCPs to MHPs in a rural research network. METHODS: From April 1997 to September 1997, 5 family physicians tracked 6 weeks of referrals for depression and non-mental health problems and assessed the outcomes of these referrals after 3 months. The referrals were characterized by the nature and extent of communication between the PCP and the MHP and by the effectiveness of the consultation. RESULTS: Sixty-seven patients (44 with non-mental health disorders and 23 with depressive disorders) were identified and followed. Analysis of the initial referral process showed that the referring physicians felt a greater sense of urgency for the referrals for depression. Written evidence of the referral in the patient's chart at the 3-month survey was more common for non-mental health disorders. CONCLUSIONS: This pilot study demonstrates that there are communication barriers between PCPs and their mental health colleagues. Enhanced communication might improve satisfaction with the referral process. The details of the referral process need further study.

Alternative methods of obtaining the computed tomography dose index.

The most direct way of getting the value of the multiple scan average dose (MSAD) in computed tomography is to employ a pencil chamber for integration of a single scan dose profile. Because the active length of the pencil chamber is fixed, the measurement can represent the value of the MSAD from a different number of contiguous scans depending on the slice thickness. This characteristic makes it difficult to compare the value of MSAD using the pencil chamber to the information required by Federal regulations on the computed tomography dose index (CTDI). The CTDI, which is the MAD at the center of a set of 14 contiguous scans, is the dose descriptor used in the Federal Performance Standard. Two alternative methods were developed to make the CTDI measurements at the center of a CT dosimetry phantom. These alternative methods were compared to the results of thermoluminescent dosimeter (TLD) measurements from more than 20 different CT scanners. One alternative method involved the use of radio-opaque sleeves with the pencil chamber to limit the length of the single scan dose profile incident on the pencil chamber. In addition, the TLD data were also used to obtain a set of conversion factors for converting the results of a measurement with the pencil chamber without a radio-opaque sleeve to a value of the CTDI. The alternative methods of obtaining the CTDI agree on the average to better than 10% for all values of slice thickness on the different CT scanners.

A case of tyrosinaemia type I with normal level of succinylacetone in the amniotic fluid.

Prenatal diagnosis of tyrosinaemia type I can be achieved in cultured amniotic cells and in chorionic villus material by testing the activity of fumarylacetoacetate hydrolase and by DNA analysis, and in amniotic fluid by succinylacetone measurement. This specific metabolite can be measured either by gas chromatography-mass spectrometry or by delta-aminolevulinate dehydratase inhibition assay. In a series of 65 at-risk cases tested with the enzyme inhibition assay, one case out of the 18 with the disease had a normal level of succinylacetone. This case is presented.

Recommended specifications for new mammography equipment: report of the ACR-CDC Focus Group on mammography equipment.

The American College of Radiology has published a report that describes desirable features for new mammography x-ray units that will contribute to high-quality imaging. It encompasses all aspects of x-ray equipment performance including mechanical considerations, the x-ray tube focal spot and spectrum, generator performance, collimation, scatter rejection, and the automatic exposure control. The report is intended to provide guidance to equipment manufacturers and to purchasers of mammography systems with regard to basic performance levels that should be expected.

Comparison of beam-hardening and K-edge filters for imaging barium and iodine during fluoroscopy.

This study investigated the dose reduction performance of several beam-hardening and K-edge filter materials for the imaging of barium or iodine during fluoroscopy. A computer model was developed to simulate the effect of added filtration on entrance exposure rate (Xp), integral dose rate (Di), contrast (C), signal to noise ratio (SNR), imaging performance per dose (SNR2/Di), and tube load. The model incorporated the response characteristics, in both manual and automatic control modes of operation, of fluoroscopic systems to increasing or decreasing x-ray intensity at the input of the image intensifier. Input parameters to the computer model included choice of filter material and thickness, a barium or iodine test object, tube potential, phantom thickness, a CsI input phosphor, and a set of algorithms for controlling the fluoroscopic system. In all cases, the performance of systems with added filtration was judged with respect to a reference system operating under comparable conditions. In general, either beam-hardening or K-edge filters provided a significant reduction in entrance exposure and integral dose rates, but with an attendant increase in tube load. For a fluoroscopic system constrained to follow a representative automatic brightness control algorithm, added filtration provided a reduction in entrance exposure and integral dose rates for all phantom or uniformly distributed barium thickness. However, the imaging performance per dose, in some cases, decreased rapidly and was less than that of the reference system at large thicknesses. Only as change in the algorithm controlling the kVcp and mA operating points on the fluoroscopic system provided an imaging performance per dose greater than the reference system's at large thicknesses. The practical implementation of adding filtration to fluoroscopic systems is most simply accomplished with beam-hardening filters rather than K-edge filters. However, the systems with K-edge added filtration can provide slightly better performance when used over a limited range of phantom thicknesses such as the range normally associated with pediatric patients.

A biochemically distinct form of cytochrome oxidase (COX) deficiency in the Saguenay-Lac-Saint-Jean region of Quebec.

We report the results of biochemical and molecular investigations on a group of patients from the Saguenay-Lac-Saint-Jean region of Quebec who have an unusual form of cytochrome oxidase deficiency and Leigh disease. This group can be distinguished from the classical presentation of cytochrome oxidase deficiency with Leigh disease, by the severity of the biochemical defect in different tissues. The activity in skin fibroblasts, amniocytes, and skeletal muscle of cytochrome oxidase is 50% of normal, while in kidney and heart it is close to normal values. Brain and liver, on the other hand, have very low activities. The defect in activity appears to result from a failure of assembly of the cytochrome oxidase complex in liver, but levels of mRNA for both mitochondrially encoded and nuclear-encoded subunits in liver and skin fibroblasts were found to be the same as those in controls. The cDNA sequence of the liver-specific cytochrome oxidase subunits VIa and VIIa were determined in samples from patient liver and skin fibroblasts and showed normal coding sequence.

Genetic amniocentesis: a six-years experience in an isolated region of northeastern Quebec (Canada).

The indications, results and outcomes of 508 genetic amniocenteses performed during a 6-years period in Saguenay-Lac-St-Jean (SLSJ), a geographically isolated region of Quebec were reviewed. The geographical distribution of the residences showed that women living in urban communities were more likely to have an amniocentesis than those coming from rural communities. Advanced maternal age was the most frequent indication (62%) while a family history of hereditary disease was an indication in 9%, which is higher than in other published series. The rate of abnormal results in SLSJ was similar to those obtained in other series except for the rate found in amniocenteses done for hereditary diseases (4.3% versus 17.4-45.5%). All the pregnancies for which an abnormal result, but balanced translocations, was found were interrupted or ended spontaneously.

Definition of a small chromosomal rearrangement on chromosome 11p14 by molecular cytogenetics in situ hybridization.

Chromosomal in situ hybridization allows the detection and the definition of single copy DNA segments of very small size. In a particular case, we demonstrate the inactivity of this molecular cytogenetic technique. In this case, karyotype analysis revealed a chromosome 11p+. In situ hybridization of probes PBGD, D11S29, NCAM, and ETSI located at 11q23-qter shows that the extra chromosomal material on chromosome 11p+ is a duplication of the 11q23-qter region.

Canadian multicenter randomized clinical trial of chorion villus sampling and amniocentesis. chromosome mosaicism in CVS and amniocentesis samples.

Data on 1040 chorionic villus and 969 amniotic fluid samples were collected from women studied in the Canadian Multicentre Randomized Clinical Trial of Chorion Villus Sampling and Amniocentesis. Cytogenetic results were obtained from 98.0 per cent of chorionic villus samples and from 99.9 per cent of amniotic fluid samples. Level I mosaicism (a single cell with an abnormal karyotype) occurred frequently in both chorionic villus and amniotic fluid samples and appeared to have no clinical significance. Level II mosaicism occurred in 0.9 per cent of CVS mesenchyme and 1.5 per cent of amniotic fluid cultures and in general was not perceived to be of sufficient concern to warrant cytogenetic follow-up studies. Level III mosaicism was reported in 18 CVS cases (15 cytotrophoblast, 1 mesenchyme, and 2 with both cell methods) and in one amniotic fluid case. In all cases but one (fetus with trisomy 18), level III mosaicism was confined to the placenta. Maternal cell contamination occurring with a frequency of 6.4 per cent in the mesenchyme analyses was a concern. This study supports the final report of the Canadian Multicentre Randomized Clinical Trial of Chorion Villus Sampling and Amniocentesis. Cytogenetic analysis of chorionic villus samples appears to be an acceptable alternative to the analysis of amniotic fluid samples. However, because of mosaicism and maternal cell contamination concerns, the examination of both cytotrophoblast preparations and mesenchyme cultures from chorionic villus samples is recommended.

Assignment of the gene encoding the catalytic subunit C beta of cAMP-dependent protein kinase to the p36 band on chromosome 1.

A cDNA for the human catalytic subunit (C beta) of cAMP-dependent protein kinase (PKA) has been cloned from a testis cDNA library. In the present study, we have determined the chromosomal localization of this gene using a cDNA for C beta as a probe. Southern blot analysis of genomic DNA from human/mouse cell hybrids revealed that the presence or absence of a 20-kb XbaI fragment, which hybridized with the C beta probe, was concordant with the presence of human chromosome 1. In situ hybridization to metaphase chromosome confirmed the somatic cell hybrid data and regionally mapped the C beta gene of PKA to the p36 band on chromosome 1.