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Biomedical subjects

L Martin

Publications and source records attributed to L Martin.

At least 37 records · Page 2Linked to original sources

[Paraneoplastic pemphigus: a pustular form during chronic lymphoid leukemia].

BACKGROUND: Paraneoplastic pemphigus is an autoimmune disease of the skin and mucosa described in 1990. The condition is generally associated with lymphoma or chronic lymphoid leukemia. Lesions are often misleading, masquerading as polymorphous erythema or lichen. We report a case of paraneoplastic pemphigus with pustulous skin lesions. CASE REPORT: A 52-year-old man developed over a few weeks time erosive lesions of the oral cavity and lips associated with papulous skin lesions. Secondarily, large-sized pustules, sometimes a hypopion, were observed associated with bullae. The diagnosis of paraneoplastic pemphigus was confirmed by direct immunofluorescence that evidenced IgG deposits within the keratinocytes and along the basal membrane and by indirect immunofluorescence on rat bladder that evidenced circulating antibodies. This paraneoplastic pemphigus was the inaugural sign of chronic lymphoid leukemia. DISCUSSION: Skin lesions described in paraneoplastic pemphigus include: erosion, vesicles, bullae, and psoriasiform, lichen-like, plate-like or vegetative formations. To our knowledge, this is the first report of a pustulous form; clinically similar to Hallopeau pustulous pemphigus.

Anti-Inflammatory Agents↗

Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of the metabolic syndrome.

Recent research has emphasized the importance of the metabolic cluster, which includes glucose intolerance, dyslipidemia, and high blood pressure, as a strong predictor of the obesity-related morbidities and premature mortality. Fundamental to this association, commonly referred to as the metabolic syndrome, is the close interaction between abdominal fat patterning, total body adiposity, and insulin resistance. As the initial step in identifying major genetic loci influencing these phenotypes, we performed a genomewide scan by using a 10-centiMorgan map in 2,209 individuals distributed over 507 nuclear Caucasian families. Pedigree-based analysis using a variance components linkage model demonstrated a quantitative trait locus (QTL) on chromosome 3 (3q27) strongly linked to six traits representing these fundamental phenotypes [logarithm of odds (lod) scores ranged from 2.4 to 3.5]. This QTL exhibited possible epistatic interaction with a second QTL on chromosome 17 (17p12) strongly linked to plasma leptin levels (lod = 5.0). Situated at these epistatic QTLs are candidate genes likely to influence two biologic precursor pathways of the metabolic syndrome.

Blood Glucose↗

"Open" structures of MurD: domain movements and structural similarities with folylpolyglutamate synthetase.

UDP-N-acetylmuramoyl-l-alanine:d-glutamate (MurD) ligase catalyses the addition of d-glutamate to the nucleotide precursor UDP-N-acetylmuramoyl-l-alanine (UMA). The crystal structures of Escherichia coli in the substrate-free form and MurD complexed with UMA have been determined at 2.4 A and 1.88 A resolution, respectively. The MurD structure comprises three domains each of a topology reminiscent of nucleotide-binding folds. In the two structures the C-terminal domain undergoes a large rigid-body rotation away from the N-terminal and central domains. These two "open" structures were compared with the four published "closed" structures of MurD. In addition the comparison reveals which regions are affected by the binding of UMA, ATP and d-Glu. Also we compare and discuss two structurally characterized enzymes which belong to the same ligase superfamily: MurD and folylpolyglutamate synthetase (FGS). The analysis allows the identification of key residues involved in the reaction mechanism of FGS. The determination of the two "open" conformation structures represents a new step towards the complete elucidation of the enzymatic mechanism of the MurD ligase.

Adenosine Triphosphate↗

Differences in the contents of total sugars, reducing sugars, starch and sucrose in embryogenic and non-embryogenic calli from Medicago arborea L.

The total sugars, reducing sugars, starch and sucrose in embryogenic and non-embryogenic calli from explants (cotyledons, petioles, hypocotyls and leaves) obtained from Medicago arborea L. seedlings were evaluated. Total sugars were the major components in the calli and no significant differences between embryogenic and non-embryogenic calli were observed. In contrast, important differences between the embryogenic and non-embryogenic calli were observed for reducing sugars, the highest levels being observed in embryogenic calli. The highest starch levels were found in non-embryogenic calli developed in MS medium. During the development of somatic embryogenesis very low starch levels in the callus were found. During the first months of culture, no significant differences in the sucrose content were found between calli that produced embryos and those that did not. The most important differences in sucrose were seen between calli transferred to medium F0, which had the greatest embryogenic capacity, and those transferred to medium F6, which inhibited embryogenesis. In the latter case, an increase in sucrose was observed.

Journal Article↗

Genetic manipulation of the rabbit heart via transgenesis.

BACKGROUND: Transgenesis using cardiac-specific expression has been valuable in exploring cardiac structure-function relationships. To date, cardiac-selective studies have been confined to the mouse. However, the utility of the mouse is limited in certain, possibly critical, aspects with respect to cardiovascular function. METHODS AND RESULTS: To establish the potential validity of transgenic methodology for remodeling a larger mammalian heart, we explored cardiac-selective expression in transgenic rabbits. The murine alpha- and beta-cardiac myosin heavy chain gene promoters were used to express a reporter gene, and transgene expression was quantified in cardiac, skeletal, and smooth muscles as well as in nonmuscle tissues. Although neither promoter exactly mimics endogenous patterns of myosin heavy chain expression, both are able to drive high levels of transgene expression in the cardiac compartment. Neither promoter is active in smooth muscle or nonmuscle tissues. CONCLUSIONS: Directed organ-specific expression is feasible in a larger animal with existing reagents, and cardiac-selective transgenic manipulation is possible in the rabbit.

Animals↗

RANK is the intrinsic hematopoietic cell surface receptor that controls osteoclastogenesis and regulation of bone mass and calcium metabolism.

We have generated RANK (receptor activator of NF-kappaB) nullizygous mice to determine the molecular genetic interactions between osteoprotegerin, osteoprotegerin ligand, and RANK during bone resorption and remodeling processes. RANK(-/-) mice lack osteoclasts and have a profound defect in bone resorption and remodeling and in the development of the cartilaginous growth plates of endochondral bone. The osteopetrosis observed in these mice can be reversed by transplantation of bone marrow from rag1(-/-) (recombinase activating gene 1) mice, indicating that RANK(-/-) mice have an intrinsic defect in osteoclast function. Calciotropic hormones and proresorptive cytokines that are known to induce bone resorption in mice and human were administered to RANK(-/-) mice without inducing hypercalcemia, although tumor necrosis factor alpha treatment leads to the rare appearance of osteoclast-like cells near the site of injection. Osteoclastogenesis can be initiated in RANK(-/-) mice by transfer of the RANK cDNA back into hematopoietic precursors, suggesting a means to critically evaluate RANK structural features required for bone resorption. Together these data indicate that RANK is the intrinsic cell surface determinant that mediates osteoprotegerin ligand effects on bone resorption and remodeling as well as the physiological and pathological effects of calciotropic hormones and proresorptive cytokines.

Animals↗

Feeding schedules in hospitals for newborn infants.

BACKGROUND: Regular breastfeeding times have been thought to help establish routines and promote infant digestion, while frequent breastfeeding has been recommended to enhance breastfeeding and infant growth. OBJECTIVES: The objective of this review was to assess the effects of frequent breastfeeding compared with less frequent breastfeeding in the early days after birth. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register. SELECTION CRITERIA: Randomised and quasi-randomised trials comparing on demand or frequent breastfeeding (two or three hourly) schedules in hospital compared with four hourly restricted feeds. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data were extracted independently by two reviewers. MAIN RESULTS: Three trials involving 400 women were included. There were significant methodological limitations in some of the studies. Compared to two hourly, three hourly or on demand breastfeeding, restricted (less frequent four hourly breastfeeding) was associated with greater discontinuation of breastfeeding by four to six weeks postpartum (relative risk 1.53, 95% confidence interval 1.08 to 2.15). Restricted breastfeeding was associated with increased incidence of sore nipples (relative risk 2.12, 95% confidence interval 1.22 to 3.68), engorgement (relative risk 2.10, 95% confidence interval 1.25 to 3.21) and the need to give additional (formula) feeds (relative risk 3.14, 95% 1.24 to 8.00). REVIEWER'S CONCLUSIONS: There appear to be a number of disadvantages from restricting breastfeeding to a four hourly schedule in the first few days after birth. More frequent or on demand breastfeeding is associated with fewer complications and longer duration of breastfeeding.

Breast Feeding↗

Interventions for influencing sleep patterns in exclusively breastfed infants.

BACKGROUND: The difference between night and day may be reinforced in young babies by offering a 'focal feed' between 10pm and midnight and gradually lengthening the intervals between night-time feeds by a variety of other activities (such as nappy changing, re-swaddling and walking with the infant). OBJECTIVES: The objective of this review was to assess the effects of using a structured training programme to teach exclusively breastfed infants to sleep through the night by eight weeks old. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register. SELECTION CRITERIA: Acceptably controlled trials of a structured programme accentuating the difference between night and day compared with no intervention in first time parents of singleton babies, with mothers intending to exclusively breastfeed their infants for at least eight weeks post-partum. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data were extracted independently by two reviewers. MAIN RESULTS: One trial involving 33 couples was included. More infants in the treatment group were sleeping throughout the night by eight weeks of age than in the control group (odds ratio 0.04, 95% confidence interval 0.01 to 0.21). REVIEWER'S CONCLUSIONS: There is some evidence to show that first time parents using a structured sleeping programme can teach their babies to sleep through the night by eight weeks of age.

Breast Feeding↗

Follow-up of steroid-resistant nephrotic syndrome: tubular proteinuria and enzymuria.

The aim of this study was to examine the compromise of proximal tubule cells in steroid-resistant nephrotic syndrome patients with a histologic diagnosis of focal segmental glomerulosclerosis (FSGS) through assessment of the urinary levels of beta 2-microglobulin (beta 2M) and N-acetyl-beta-D-glucosaminidase (NAG) during active disease and remission over a follow-up period of 3 years. We studied 34 children with nephrotic syndrome: 12 with steroid-resistant nephrotic syndrome (SRNS) and massive proteinuria, 7 with steroid-dependent nephrotic syndrome (SDNS) and 15 with steroid-sensitive nephrotic syndrome (SSNS). Of the SSNS patients, 8 children were in remission (RM) and 7 were in relapse (RL). Seven healthy children were included as controls. Urinary beta 2M, measured by enzyme-linked immunosorbent assay, was significantly increased in the SRNS group as compared to the SDNS group (P < 0.01), SSNS in remission (P < 0.01), and controls (P < 0.01). There were no differences between the SRNS group and SSNS in relapse. Analysis of urinary N-acetyl-beta-D-glucosaminidase (U-NAG) by colorimetric assay showed significantly higher values in the SRNS group of patients than in SDNS, SSNS, and control groups. A positive correlation between U-NAG and proteinuria was demonstrated (r = 0.73, P < 0.01). The SRNS group of patients (n = 12, 11 with a histologic diagnosis of FSGS and one with diffuse mesangial proliferation) was treated with the same protocol of i.v. methylprednisone and oral cyclophosphamide. Long-term follow-up showed a progressive decrease in U-beta 2M and U-NAG excretion to control values in the 3rd year, except in one patient who did not respond to the treatment. In the FSGS patients, evaluation of the contribution of structural interstitial histological abnormalities, including each of the histological parameters considered in interstitial scarring to the functional tubule abnormalities assessed by beta 2M and NAG excretion, was performed by multiple regression analysis. The r2 values for beta 2M and NAG were 53.99%, P = 0.19, and 57.90%, P = 0.14, respectively; neither was significant. We conclude that: (1) proximal tubule cell dysfunction, partially affected by massive albuminuria, may account for the higher values of beta 2M and NAG excretion in the SRNS patients and (2) urine beta 2M and NAG levels are not helpful in identifying histological evidence of structural tubulointerstitial damage in children with steroid-resistant nephrotic syndrome.

Acetylglucosaminidase↗

A pilot survey of aberrant drug-taking attitudes and behaviors in samples of cancer and AIDS patients.

The clinical assessment of drug-taking behaviors in medically ill patients with pain is complex and may be hindered by the lack of empirically derived information about such behaviors in particularly medically ill populations. To investigate issues surrounding the assessment of these behaviors, we piloted a questionnaire based on the observations of specialists in pain management and substance abuse. This preliminary questionnaire evaluated medication use, present and past drug abuse, patients' beliefs about the risk of addiction in the context of pain treatment, and aberrant drug-taking attitudes and behaviors. This instrument was piloted in a mixed group of cancer patients (N = 52) and a group of women with HIV/AIDS (N = 111). Reports of past drug use and abuse were more frequent than present reports in both groups. Current aberrant drug-related behaviors were seldom reported, but attitude items revealed that patients would consider engaging in aberrant behaviors, or would possibly excuse them in others, if pain or symptom management were inadequate. Aberrant behaviors and attitudes were endorsed more frequently by the women with HIV/AIDS than by the cancer patients. Patients greatly overestimated the risk of addiction in pain treatment. We discuss the significance of these findings and the need for cautious interpretation given the limitations of the methodology. This early experience suggests that both cancer and HIV/AIDS patients appear to respond in a forthcoming fashion to drug-taking behavior questions and describe attitudes and behaviors that may be highly relevant to the diagnosis and understanding management of substance use among patients with medical illness.

Acquired Immunodeficiency Syndrome↗

Tollip, a new component of the IL-1RI pathway, links IRAK to the IL-1 receptor.

Interleukin-1 (IL-1) is a proinflammatory cytokine that elicits its pleiotropic effects through activation of the transcription factors NF-kappaB and AP-1. Binding of IL-1 to its receptor results in rapid assembly of a membrane-proximal signalling complex that consists of two different receptor chains (IL-1Rs), IL-1RI and IL-1RAcP, the adaptor protein MyD88, the serine/threonine kinase IRAK and a new protein, which we have named Tollip. Here we show that, before IL-1beta treatment, Tollip is present in a complex with IRAK, and that recruitment of Tollip-IRAK complexes to the activated receptor complex occurs through association of Tollip with IL-1RAcP. Co-recruited MyD88 then triggers IRAK autophosphorylation, which in turn leads to rapid dissociation of IRAK from Tollip (and IL-1Rs). As overexpression of Tollip results in impaired NF-kappaB activation, we conclude that Tollip is an important constituent of the IL-1R signalling pathway.

Adaptor Proteins, Signal Transducing↗

Inherited palmoplantar keratoderma and sensorineural deafness associated with A7445G point mutation in the mitochondrial genome.

We report a French pedigree with members having an inherited combination of non-epidermolytic palmoplantar keratoderma (NEPPK) and sensorineural deafness. The penetrance of both features was incomplete. Additional ectodermal defects were absent. The expression of numerous epidermal proteins (keratins, fillagrin, cornified envelope proteins, intercellular junction proteins including connexin 26, and loricrin) defined with immunolabelling was normal in the proband. The combination was shown to be associated with the A7445G point mutation in the mitochondrial genome (mtDNA). This mutation is responsible for a subtype of NEPPK which is so far the only mtDNA mutation-associated keratoderma.

Adolescent↗

Comparison of critical swimming velocity and velocity at lactate threshold in elite triathletes.

The purpose of this study was to determine whether the critical swimming velocity (Vcrit) corresponds to the velocity at lactate threshold (V-LT) in elite triathletes. Eight elite triathletes (5 male, 3 female; age 26 +/- 4 years; height 1.7 +/- 0.1 m and body mass 75 +/- 4 kg) participated in the study. Vcrit, defined as the speed that could theoretically be maintained indefinitely without exhaustion, was expressed as the slope of a regression line between swimming distance covered and the corresponding times of five time trials over 100, 200, 400, 800 and 1500m and all combinations of these. Lactate threshold (LT) was determined by visual inspection as the point of first inflection of the lactate-work rate curve following 5 x 300 m swims of increasing velocity which were paced using the Aquapacer (Challenge and Response, Inverurie, Scotland). Velocities of the 300 m swims were -10, -5, 0, +5 and +10% of the average 100m pace from a 1500 m time trial. Vcrit was similar regardless of the combination or number of time trials used in the linear regression. For all subjects Vcrit was significantly faster (p <0.05) than V-LT (1.23 +/- 0.11 m x s(-1) and 1.15 +/- 0.10 m x s(-1) respectively). Blood lactate concentrations were also significantly higher (p < 0.05) at Vcrit (3.0 +/- 1.0 mM) than at LT (1.9 +/- 0.4 mM). Results from the present study demonstrate that Vcrit can be calculated from any two time trials in triathletes, however Vcrit did not represent V-LT in triathletes. Since Vcrit is faster than V-LT it is unlikely to be sustained indefinitely and consequently the notion of Vcrit should be re-evaluated in light of these findings.

Adult↗

Reproducibility of diurnal variation in sub-maximal swimming.

Swimming training is characterised by the use of early morning and evening training sessions. The purpose of the present study was to investigate if the physiological and kinematic responses to swimming a typical training set are affected by time of day. Seven male collegiate swimmers (age 22 +/- 4 years; height 1.8 +/- 0.1 m; mass 82.1 +/- 4.1 kg) completed a standardised 600 m warm up followed by a 10 x 100 m sub-maximal freestyle set twice a day (06:30-08:00 h and 16:30-20:00 h) on three separate days. Swimming speed was controlled precisely throughout (limits of agreement multiplied/divided 1.00) using a new pacing device (Aquapacer, Challenge and Response, Inverurie, Scotland). Oral temperature (To), heart rate (HR), minute ventilation (VE), oxygen uptake (VO2), carbon dioxide expired (VCO2), respiratory exchange ratio (RER), capillary blood lactate (Bla), and glucose (BGL) were measured at rest and post exercise. Stroke rate (SR) and HR were measured during the first nine 100 m repetitions while rate of perceived exertion (RPE) was measured immediately after each 100 m. Significant diurnal variation was found at rest in To, HR, and VO2 on all three days and for VE and VCO2 on two of the days (P<0.05). During the training set no diurnal variation was evident in HR and SR responses or repetition times although RPE values were higher in morning trials compared to evening trials on two of the three days (P < 0.05). Post-exercise significant diurnal variation was found for To and blood glucose for two of the three days (P < 0.05). Therefore, although diurnal variation is evident at rest, there is no subsequent effect on physiological and kinematic responses during a sub-maximal training set following a standardised warm-up.

Adolescent↗

Hospital safety climate and its relationship with safe work practices and workplace exposure incidents.

BACKGROUND: In the industrial setting, employee perceptions regarding their organization's commitment to safety (i.e., safety climate) have been shown to be important correlates to both the adoption and maintenance of safe work practices and to workplace injury rates. However, safety climate measures specific to the hospital setting have rarely been evaluated. This study was designed to develop a short and effective tool to measure hospital safety climate with respect to institutional commitment to bloodborne pathogen risk management programs and to assess the relationship between hospital safety climate and (1) employee compliance with safe work practices and (2) incidents of workplace exposure to blood and other body fluids. METHODS: A questionnaire, which included 46 safety climate items, was developed and tested on a sample of 789 hospital-based health care workers at risk for bloodborne pathogen exposure incidents. RESULTS: A 20-item hospital safety climate scale that measures hospitals' commitment to bloodborne pathogen risk management programs was extracted through factor analysis from the 46 safety climate items. This new hospital safety climate scale subfactored into 6 different organizational dimensions: (1) senior management support for safety programs, (2) absence of workplace barriers to safe work practices, (3) cleanliness and orderliness of the work site, (4) minimal conflict and good communication among staff members, (5) frequent safety-related feedback/training by supervisors, and (6) availability of personal protective equipment and engineering controls. Of these, senior management support for safety programs, absence of workplace barriers to safe work practices, and cleanliness/orderliness of the work site were significantly related to compliance (P<.05). In addition, both senior management support for safety programs and frequent safety-related feedback/training were significantly related to workplace exposure incidents (P<.05). Thus the most significant finding in terms of enhancing compliance and reducing exposure incidents was the importance of the perception that senior management was supportive of the bloodborne pathogen safety program. CONCLUSIONS: Hospital safety climate with regards to bloodborne pathogens can be measured by using a short, 20-question scale that measures 6 separate dimensions. Whereas all 6 dimensions are essential elements of overall safety climate, 3 dimensions are significantly correlated with compliance, and 1 dimension (senior management support) is especially significant with regard to both compliance and exposure incidents. This short safety climate scale can be a useful tool for evaluating hospital employees' perceptions regarding their organization's bloodborne pathogens management program. In addition, because this scale measures specific dimensions of the safety climate, it can be used to target problem areas and guide the development of intervention strategies to reduce occupational exposure incidents to blood and other body fluids.

Adult↗

Psychological and physical health effects of sexual assaults and nonsexual traumas among male and female United States Army soldiers.

Lifetime trauma history was assessed in a health study of active duty United States Army soldiers. Five hundred fifty-five male and 573 female soldiers in the sample were asked whether they had ever experienced 14 different potentially traumatic experiences, including sexual assaults, violent stressors to self, and terrifying events that occurred to others and were secondarily traumatic through exposure by gaining information or as a witness to the event. Most soldiers had experienced multiple traumas, and premilitary exposure to events was much more common than exposure to events after entering the military. Global measures of current psychological distress and physical health symptoms were predicted by the lifetime number of sexual assaults and traumas to self. Social support from military unit leaders moderated the relationship between accumulated exposure to traumas and both health measures, whereas unit cohesion was directly associated with fewer mental health problems.

Adolescent↗