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Biomedical subjects

S A Lynch

Publications and source records attributed to S A Lynch.

At least 19 recordsLinked to original sources
PubMed2006

Investigating the possible role of benthic macroinvertebrates and zooplankton in the life cycle of the haplosporidian Bonamia ostreae.

Bonamia ostreae is a protistan parasite of the European flat oyster, Ostrea edulis. Though direct transmission of the parasite can occur between oysters, it is unclear if this represents the complete life cycle of the parasite, and the role of a secondary or intermediate host or carrier species cannot be ruled out. In this preliminary study, benthic macroinvertebrates and zooplankton from a B. ostreae-endemic area were screened for the presence of parasite DNA, using polymerase chain reaction (PCR). Eight benthic macroinvertebrates and nineteen grouped zooplankton samples gave positive results. Certain species, found positive for the parasite DNA, were then used in laboratory transmission trials, to investigate if they could infect naïve oysters. Transmission of B. ostreae was effected to two naïve oysters cohabiting with the brittle star, Ophiothrix fragilis.

Animals↗
PubMed2005

Mutation screening in Borjeson-Forssman-Lehmann syndrome: identification of a novel de novo PHF6 mutation in a female patient.

BACKGROUND: Börjeson-Forssman-Lehmann syndrome (BFLS; MIM 301900) is an infrequently described X linked disorder caused by mutations in PHF6, a novel zinc finger gene of unknown function. OBJECTIVE: To present the results of mutation screening in individuals referred for PHF6 testing and discuss the value of prior X-inactivation testing in the mothers of these individuals. RESULTS: 25 unrelated individuals were screened (24 male, one female). Five PHF6 mutations were detected, two of which (c.940A-->G and c.27_28insA) were novel. One of these new mutations, c.27_28insA, was identified in a female BFLS patient. This was shown to be a de novo mutation arising on the paternal chromosome. This is the first report of a clinically diagnosed BFLS female with a confirmed PHF6 mutation. In addition, the X-inactivation status of the mothers of 19 males with suggested clinical diagnosis of BFLS was determined. Skewed (> or =70%) X-inactivation was present in five mothers, three of whom had sons in whom a PHF6 mutation was detected. The mutation positive female also showed skewing. CONCLUSIONS: The results indicate that the success of PHF6 screening in males suspected of having BFLS is markedly increased if there is a positive family history and/or skewed X-inactivation is found in the mother.

Abnormalities, Multiple↗
PubMed2005

Recurrence risk for psoriasis and psoriatic arthritis within sibships.

OBJECTIVE: To quantify the frequency of siblings of patients with psoriatic arthritis (PsA) having psoriasis and/or inflammatory arthritis. To describe the similarity or otherwise of patterns of arthritis in siblings. METHODS: Available and consenting index cases with PsA and one or more siblings living locally were assessed. Mean sibling concordance rates and Weinberg's segregation analysis were calculated. Heritability was also estimated. To assess whether the same type of arthritis occurred within the same sibship, the dually affected sibships were then classified for type of arthritis according to methods suggested by Moll, Helliwell, Veale and McGonagle. RESULTS: Eighty index cases and 112 siblings were assessed. The median age of index cases was 49 yr (range 24-80 yr) and for siblings 46 yr (range 18-79 yr). The concordance rate for all types of PsA was 14% (9% if enthesitis is excluded) and for psoriasis 21%. There was no difference in the two methods used to calculate concordance rates. Sixteen dually affected sib pairs were found. Four of the 16 sibships (25%) had the same pattern of joint involvement (Moll and Wright classification). The most frequent pattern seen was joint involvement identical to rheumatoid arthritis (3/5). The most common symptom in affected siblings was enthesitis (approximately 5%). When the dually affected sibships were analysed using the other classifications, the simpler the classification the greater the concordance for joint pattern. CONCLUSION: The concordance for psoriasis is greater than for PsA, but the concordance rate for PsA was similar to that in HLA identical siblings with rheumatoid arthritis. There was discordance in pattern of arthritis for most sib pairs. There is no support for the use of more complex classifications of PsA.

Adolescent↗
PubMed2004

NBCCS secondary to an interstitial chromosome 9q deletion.

Naevoid basal cell carcinoma syndrome (NBCCS) or Gorlin syndrome is a rare autosomal dominant cancer disorder. The Gorlin's gene, Patched 1 (PTCH1), maps to Chromosome 9q. Germline mutations of PTCH1 occur in patients with NBCCS. The subsequent loss of the remaining allele results in cancer formation. We present a patient with NBCCS and additional phenotypic features including severe developmental delay, short stature and hypotelorism who was found to have an interstitial chromosome 9q deletion. The NBCCS phenotype in our patient occurred as a result of PTCH1 deletion in contrast with an inherited mutation of this gene.

Adult↗
PubMed2004

Gene-gene interaction in folate-related genes and risk of neural tube defects in a UK population.

OBJECTIVE: To investigate the contribution of polymorphic variation in genes involved in the folate-dependent homocysteine pathway in the aetiology of neural tube defects (NTD). DESIGN: Case-control association study. SUBJECTS: A total of 530 individuals from families affected by NTD, 645 maternal controls, and 602 healthy newborn controls from the northern UK. MAIN OUTCOME MEASURES: Seven polymorphisms in six genes coding for proteins in the folate-dependent homocysteine pathway (MTHFR 677C-->T, MTHFR 1298A-->C, MTRR 66A-->G, SHMT 1420C-->T, CbetaS 844ins68, GCPII 1561C-->T, RFC-1 80G-->A). The impact of each polymorphism and the effect of gene-gene interactions (epistasis) upon risk of NTD were assessed using logistic regression analysis. RESULTS: The MTHFR 677C-->T polymorphism was shown to represent a risk factor in NTD cases (CC v CT+TT odds ratio (OR) 2.03 [95% confidence interval (CI) 1.09, 3.79] p = 0.025) and the MTRR 66A-->G polymorphism was shown to exert a protective effect in NTD cases (AA v AG+GG OR 0.31 [95% CI 0.10, 0.94] p = 0.04). When statistical tests for interaction were conducted, three genotype combinations in cases (MTRR/GCPII; MTHFR 677/CbetaS; MTHFR 677/MTRR) and one combination in case mothers (CbetaS/RFC-1) were shown to elevate NTD risk. Maternal-fetal interaction was also detected when offspring carried the MTHFR 677C-->T variant and mothers carried the MTRR 66A-->G variant, resulting in a significantly elevated risk of NTD. CONCLUSION: Both independent genetic effects and gene-gene interaction were observed in relation to NTD risk. Multi-locus rather than single locus analysis might be preferable to gain an accurate assessment of genetic susceptibility to NTD.

Case-Control Studies↗
PubMed2003

Genetic susceptibility to neural tube defect pregnancy varies with offspring phenotype.

Neural tube defects (NTDs) have a well-established genetic basis, although no single genetic factor has been identified as a major risk factor in NTD susceptibility. A large number of association studies have been conducted to investigate the possibility that NTD susceptibility is linked to polymorphic variation in genes involved in early embryonic development or in the absorption or metabolism of folate, a nutrient that has been clearly associated with a reduction in the risk of NTD pregnancy. A study of three candidate gene polymorphisms at loci implicated in folate absorption and metabolism has been conducted on a population of 211 mothers of a heterogeneous mix of NTD phenotypes: 59% spina bifida aperta (SBA), 20.3% spina bifida occulta (SBO), 17% anencephaly, and 3.7% other NTD. Allele and genotype frequencies were stratified according to offspring NTD phenotype, and variation in the level of NTD risk was associated with different phenotypes. All the three variants (MTHFR 677C > T, GCPII 1561C > T, and RFC-1 80G > A) were shown to significantly influence the risk of anencephalic pregnancy. In addition, the MTHFR 677C > T variant conferred a modest protective effect in SBO mothers and the total NTD mother group, but not in SBA mothers. The RFC-1 80G > A variant elevated the risk of SBO and anencephalic pregnancy. The findings of this study suggest that NTD phenotypic heterogeneity may help explain the mixed findings of previous association studies and that different polymorphisms may hold differing degrees of significance for the various NTD phenotypes.

Base Sequence↗
PubMed2002

Familial neurofibromatosis microdeletion syndrome complicated by rhabdomyosarcoma.

Neurofibromatosis type 1 with dysmorphism and developmental delay is reported in a mother and two children. The son required treatment for a prostatic rhabdomyosarcoma. His sister has an optic pathway glioma. Fluorescence in situ hybridisation confirmed a submicroscopic deletion at 17q11.2. New evidence suggests an increased malignancy frequency in microdeletion cases.

Adult↗
PubMed2002

Insulin resistance in adult rat offspring associated with maternal dietary fat and alcohol consumption.

Maternal diet during pregnancy has been reported to alter the offspring's ability to respond to a glucose challenge. The current studies report changes in basal and insulin-stimulated, in vitro glucose uptake in red (soleus) and white (extensor digitorum longus) muscle fiber types, as well as whole body insulin responsiveness of adult rat offspring associated with their mother's dietary fat and alcohol content during pregnancy. The offspring of Harlan-derived Sprague-Dawley female rats, dosed during pregnancy with ethanol (ETOH) via a liquid diet (35% of calories as ETOH) with either 12% or 35% of calories as fat, were compared with offspring from litters whose mothers were pair-fed an isocaloric amount of the liquid diet without ETOH. Maternal access to the liquid diets was terminated on day 20 of the pregnancies (sperm plug=day 0). The offspring were surrogate fostered within 48 h of birth to mothers which had consumed commercial chow throughout their pregnancy. Following weaning at 21 days of age, the offspring consumed only commercial rat chow and they were examined over the next 14 months for changes in glucose homeostasis as a consequence of in utero exposure to maternal dietary fat and/or alcohol. The 35% maternal fat diet resulted in both in vivo and in vitro decreases in insulin sensitivity. Thus, compared with adults whose mother's diet contained 12% fat, significant, in vitro muscle and in vivo whole body insulin resistance (measured by hyperinsulinemic-euglycemic clamping) was observed in adult rats whose mothers consumed 35% of dietary calories as fat. The addition of ethanol to the maternal 35% fat diet further reduced the offspring's red muscle tissues in vitro response to insulin, but did not affect whole body insulin sensitivity. Muscle basal and insulin-stimulated receptor tyrosine kinase activity were significantly decreased (approximately -50%) by the 35% fat maternal diet but there was no compensatory increase in serum insulin or glucose levels. Based upon both in vivo and in vitro data, these studies suggested that in utero exposure to 35% fat has a sustained effect on the adult offspring's glucose uptake/insulin sensitivity and that the effect is paralleled, at least in part, by decreased insulin receptor tyrosine kinase activity. In utero ETOH exposure resulted in the loss of basal and insulin-stimulated, in vitro glucose uptake in red muscle fibers but maternal dietary ETOH had no detectable effect on either in vivo insulin sensitivity or muscle tyrosine kinase activity.

Analysis of Variance↗
PubMed2001

Alcohol-induced modulation of the insulin-like growth factor system in early chick embryo cranial tissue.

BACKGROUND: Fetal alcohol exposure has been shown to reduce fetal/embryonic growth. The insulin-like growth factor (IGF) system plays a major role in normal growth and development of the embryo. The purpose of this study was to gain a better understanding of the effects of alcohol (ethanol, EtOH) exposure on the insulin-like growth factors, their binding proteins, and receptors during embryonic development. METHODS: After the administration of either alcohol or chick Ringer's solution to individual eggs at the start of incubation, type-1 IGF receptors, IGF-binding proteins (IGFBPs) as well as IGF-1 and IGF-2 levels were measured in chick embryo craniums on days 5, 6, 7, and 8 of incubation. RESULTS: Levels of the IGF-1 receptor protein were not significantly different between treatment groups on any day studied. In EtOH-treated embryos, the 30 kDa IGFBP levels were significantly higher than vehicle levels on days 5 and 6. On day 6, IGF-1 levels were significantly lower in the alcohol-treated embryos compared with levels in vehicle-treated embryos of the same age. By day 8 of incubation, IGF-1 levels were significantly higher and the 30 kDa IGFBP levels were significantly lower in the alcohol-treated group compared with vehicles. These results indicate an initial EtOH-associated reduction in the amount of IGF-1 available to bind to its receptor (bioavailability), followed by increased IGF-1 bioavailability by day 8. CONCLUSIONS: The elevated IGFBP levels and reduced IGF-1 levels on days 5 and 6 of incubation are congruent with an overall reduction in the bioavailability of IGF-1 during this period and correlate with the decreased embryo weight observed in the alcohol-treated embryos. An increased bioavailability of IGF-1 observed by day 8 may represent a rebound effect and is associated with increases in ornithine decarboxylase activity, a marker of increased growth.

Age Factors↗
PubMed2001

ARC syndrome: an expanding range of phenotypes.

AIM: To describe the clinical phenotype in infants with ARC syndrome, the association of arthrogryposis, renal tubular acidosis, and cholestasis. METHODS: The medical records for six patients with ARC syndrome were reviewed, presenting over 10 years to three paediatric referral centres. RESULTS: All patients had the typical pattern of arthrogryposis. Renal Fanconi syndrome was present in all but one patient, who presented with nephrogenic diabetes insipidus. Although all patients had severe cholestasis, serum gamma glutamyltransferase values were normal. Many of our patients showed dysmorphic features or ichthyosis. All had recurrent febrile illnesses, diarrhoea, and failed to thrive. Blood films revealed abnormally large platelets. CONCLUSIONS: ARC syndrome exhibits notable clinical variability and may not be as rare as previously thought. The association of Fanconi syndrome, ichthyosis, dysmorphism, jaundice, and diarrhoea has previously been reported as a separate syndrome: our observations indicate that it is part of the ARC spectrum.

Acidosis, Renal Tubular↗
PubMed2000

Mutation analysis and embryonic expression of the HLXB9 Currarino syndrome gene.

The HLXB9 homeobox gene was recently identified as a locus for autosomal dominant Currarino syndrome, also known as hereditary sacral agenesis (HSA). This gene specifies a 403-amino acid protein containing a homeodomain preceded by a very highly conserved 82-amino acid domain of unknown function; the remainder of the protein is not well conserved. Here we report an extensive mutation survey that has identified mutations in the HLXB9 gene in 20 of 21 patients tested with familial Currarino syndrome. Mutations were also detected in two of seven sporadic Currarino syndrome patients; the remainder could be explained by undetected mosaicism for an HLXB9 mutation or by genetic heterogeneity in the sporadic patients. Of the mutations identified in the 22 index patients, 19 were intragenic and included 11 mutations that could lead to the introduction of a premature termination codon. The other eight mutations were missense mutations that were significantly clustered in the homeodomain, resulting, in each patient, in nonconservative substitution of a highly conserved amino acid. All of the intragenic mutations were associated with comparable phenotypes. The only genotype-phenotype correlation appeared to be the occurrence of developmental delay in the case of three patients with microdeletions. HLXB9 expression was analyzed during early human development in a period spanning Carnegie stages 12-21. Signal was detected in the basal plate of the spinal cord and hindbrain and in the pharynx, esophagus, stomach, and pancreas. Significant spatial and temporal expression differences were evident when compared with expression of the mouse Hlxb9 gene, which may partly explain the significant human-mouse differences in mutant phenotype.

Abnormalities, Multiple↗
PubMed2000

Autosomal dominant sacral agenesis: Currarino syndrome.

Autosomal dominant sacral agenesis is characterised by a partial agenesis of the sacrum typically involving sacral vertebrae S2-S5 only. Associated features include anorectal malformation, a presacral mass, and urogenital malformation. Together, these features have been defined as the Currarino syndrome. Recently, HLXB9 has been identified as the major causative gene in Currarino syndrome allowing identification of asymptomatic heterozygotes. In this review, we have performed an analysis of medical publications, and our own additional cases, to identify the range of malformations and complications that occur. We have also estimated risks of malformation in heterozygotes by using Weinburg's proband method on families personally known to us in order to provide accurate genetic counselling information.

Anal Canal↗
PubMed1999

Repair of distal biceps tendon rupture with suture anchors.

We retrospectively evaluated six cases of distal biceps tendon rupture that were treated by a two-incision operative repair using suture anchor attachment to the radial tuberosity for clinical outcome and strength testing. All patients had repair performed by the same surgeon. The average age of the patients, all male, was 43 years (range, 32-57 years). Average time from injury to operative repair was 22 days (range, 9-54 days). Follow-up time averaged 24 months after definitive treatment (range, 11-46 months). At follow-up no patient had limitation of activity and all patients were able to return to their previous employment, although three noted some minor antecubital fossa discomfort. No patient developed a synostosis. Cybex (Medway, Mass.) isokinetic testing revealed elbow flexion strength return for peak torque, total work, and average power, of 107%, 103%, and 110% of the uninjured arm, respectively. Elbow flexion endurance was 2% less in the injured arm. Forearm supination strength measured by peak torque, total work, and average power, was 97%, 85%, and 88% of the uninjured arm, respectively. Forearm supination endurance was 10% less in the injured arm. Our results using suture anchor repair are similar to those previously reported in the literature from bone tunnel repair. Based on our data, we believe that a two-incision repair with suture anchor attachment is a safe and effective method for treatment of distal biceps tendon ruptures.

Adult↗
PubMed1999

Treatment of acute lateral ankle ligament rupture in the athlete. Conservative versus surgical treatment.

Acute lateral ankle ligament sprains are common in young athletes (15 to 35 years of age). Diagnostic and treatment protocols vary. Therapies range from cast immobilisation or acute surgical repair to functional rehabilitation. The lateral ligament complex includes 3 capsular ligaments: the anterior tibiofibular (ATFL), calcaneofibular (CFL) and posterior talofibular (PTFL) ligaments. Injuries typically occur during plantar flexion and inversion; the ATFL is most commonly torn. The CFL and the PTFL can also be injured and, after severe inversion, subtalar joint ligaments are also affected. Commonly, an athlete with a lateral ankle ligament sprain reports having 'rolled over' the outside of their ankle. The entire ankle and foot must be examined to ensure there are no other injuries. Clinical stability tests for ligamentous disruption include the anterior drawer test of ATFL function and inversion tilt test of both ATFL and CFL function. Radiographs may rule out treatable fractures in severe injuries or when pain or tenderness are not associated with lateral ligaments. Stress radiographs do not affect treatment. Ankle sprains are classified from grades I to III (mild, moderate or severe). Grade I and II injuries recover quickly with nonoperative management. A non-operative 'functional treatment' programme includes immediate use of RICE (rest, ice, compression, elevation), a short period of immobilisation and protection with a tape or bandage, and early range of motion, weight-bearing and neuromuscular training exercises. Proprioceptive training on a tilt board after 3 to 4 weeks helps improve balance and neuromuscular control of the ankle. Treatment for grade III injuries is more controversial. A comprehensive literature evaluation and meta-analysis showed that early functional treatment provided the fastest recovery of ankle mobility and earliest return to work and physical activity without affecting late mechanical stability. Functional treatment was complication-free, whereas surgery had serious, though infrequent, complications. Functional treatment produced no more sequelae than casting with or without surgical repair. Secondary surgical repair, even years after an injury, has results comparable to those of primary repair, so even competitive athletes can receive initial conservative treatment. Sequelae of lateral ligament injuries are common. After conservative or surgical treatment, 10 to 30% of patients have chronic symptoms, including persistent synovitis or tendinitis, ankle stiffness, swelling, pain, muscle weakness and 'giving-way'. Well-designed physical therapy programmes usually reduce instability. For individuals with chronic instability refractory to conservative measures, surgery may be needed. Subtalar instability should be carefully evaluated when considering surgery.

Acute Disease↗
PubMed1999

Groin injuries in sport: treatment strategies.

Groin pain in athletes is a common problem that can result in significant amounts of missed playing time. Many of the problems are related to the musculoskeletal system, but care must be taken not to overlook other more serious and potentially life threatening medical cases of pelvis and groin pain. Stress fractures of the bones of the pelvis occur, particularly after a sudden increase in the intensity of training. Most of these stress fractures will heal with rest, but femoral neck stress fractures can potentially lead to more serious problems, and require closer evaluation and sometimes surgical treatment. Avulsion fractures of the apophyses occur through the relatively weaker growth plate in adolescents. Most of these will heal with a graduated physical therapy programme and do not need surgery. Osteitis pubis is characterised by sclerosis and bony changes about the pubic symphysis. This is a self-limiting disease that can take several months to resolve. Corticosteroid injection can sometimes hasten the rehabilitation process. Sports hernias can cause prolonged groin pain, and provide a difficult diagnostic dilemma. In athletes with prolonged groin pain, with increased pain during valsalva manoeuvres and tenderness along the posterior inguinal wall and external canal, an insidious sports hernia should be considered. In cases of true sports hernia, treatment is by surgical reinforcement of the inguinal wall. Nerve compression can occur to the nerves supplying the groin. In cases that do not respond to desensitisation measures, neurolysis can relieve the pain. Adductor strains are common problems in kicking sports such as soccer. The majority of these are incomplete muscle tendon tears that occur just adjacent to, the musculotendinous junction. Most of these will respond to a graduated stretching and strengthening programme, but these can sometimes take a long time to completely heal. Patience is the key to obtain complete healing, because a return to sports too early can lead to chronic pain, which becomes increasingly difficult to treat. Management of groin injuries can be challenging, and diagnosis can be difficult because of the degree of overlap of symptoms between the different problems. By careful history and clinical examination, with judicious use of special tests and good team work, a correct diagnosis can be obtained.

Athletic Injuries↗