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Biomedical subjects

T Lynch

Publications and source records attributed to T Lynch.

At least 19 recordsLinked to original sources
PubMed2005

Sensory abnormalities in unaffected relatives in familial adult-onset dystonia.

Somatosensory abnormalities are found in adult-onset primary torsion dystonia (PTD). Therefore we assessed spatial discrimination thresholds (SDT), a measure of spatial acuity, in four multiplex families with adult-onset PTD. In family members aged 20 to 45 years vs controls (mean + 2.5 SD), abnormal SDTs were found in four of five affected with adult-onset PTD and in 12 of 49 unaffected relatives. Sensory abnormalities may be an endophenotype, possibly expressed later as adult-onset PTD.

Adult↗
PubMed2005

Clinicopathological features of the tauopathies.

Developments in molecular neuropathology have led to protein-based classification systems for neurodegenerative disorders. Key proteins include alpha-synuclein, amyloid and tau. Alternative mRNA splicing and post-translational change, induced by a bewildering variety of protein modifying processes such as phosphorylation and ubiquitination, have generated insights into new mechanisms of selective neuronal degeneration. The task now is to bring these developments in protein chemistry to the clinic, to try to determine whether this biochemical diversity can help in explaining the phenotypic variability that is so typical of neurodegeneration in general. In this review, we will explore the clinicopathological diversity of the tau-related disorders with specific reference to three of the most common tauopathies, frontotemporal dementia (familial and sporadic), progressive supranuclear palsy and corticobasal degeneration.

Brain↗
PubMed2005

Audit of an inpatient neurology consultation service in a tertiary referral centre: value of the consulting neurologist.

The Mater Misericordiae Hospital is a 575-bed tertiary referral centre with busy medical and surgical subspecialty services (including the national cardiac, cardiothoracic, spinal cord injury and pulmonary hypertension units). An audit of in-patient referrals to a neurology service was carried out over the twelve-month period of January to December 2002 inclusively. Five hundred and seventy seven inpatients were evaluated and managed in conjunction with the referring services. Consultation by the neurological service led to a significant contribution in the management of clinical cases in one of three ways: establishing a de novo diagnosis in patients admitted with active neurological symptoms where no working diagnosis exists (40.7% of referrals), significant alteration in diagnosis where the referring service have already established a specific working diagnosis (11.1% of referrals), or offering advice in the ongoing management of active neurological symptoms when the diagnosis is historically established and secure (48.2% of referrals). In order of frequency the most common reason for referral was stroke (131 cases (22.7%)), seizures unrelated to alcohol (59 cases (10.2%)), alcohol-related neurological problems (55 cases (9.5%)), movement disorders (41 cases (7.1%)), neuromuscular (40 cases (6.9%)), coma (35 cases (6%)), disorders of cognition (31 cases (5.3%)), acute headache (28 case (4.8%)) and functional neurological syndromes (26 cases (4.5%)). This audit highlights the value of a consulting neurology service in a multidisciplinary tertiary referral setting.

Adult↗
PubMed2004

Age at onset as a factor in determining the phenotype of primary torsion dystonia.

BACKGROUND: The genetic basis of most forms of primary torsion dystonia (PTD) is unknown; multiplex families are uncommon due to low penetrance. Intrafamilial, age-related, phenotypic heterogeneity was noted in 14 PTD families. The authors hypothesized that the clinical presentation of PTD was modulated by the age at onset of the dystonia, irrespective of the genotype. METHODS: This hypothesis was addressed in a study of 14 PTD families and a meta-analysis of 83 published series of PTD. RESULTS: In 12 families with adult-onset PTD, the index cases presented with cervical dystonia (CD); of the 22 affected relatives, 17 had CD, 2 had writer's cramp, 1 had blepharospasm, and 2 had spasmodic dysphonia. In the two other PTD families, the probands and all 10 symptomatic relatives had limb-onset dystonia at <20 years of age. There were differences between the median ages at onset of the different phenotypes (p = 0.0037). Analysis of 83 published series including 5,057 patients indicated significant differences in the mean age at onset of five phenotypes of PTD (mean age at onset; 95% CI): DYT1 dystonia (11.3 years; 10.3 to 12.2), writer's cramp (38.4; 36.9 to 39.9), CD (40.8; 40.3 to 41.3), spasmodic dysphonia (43.0; 42.2 to 43.9), and blepharospasm-oromandibular dystonia (55.7; 55.1 to 56.4). CONCLUSION: Phenotypic variation in PTD presentation is due to the effect of age at onset modulating the expression of a genetic disorder with a caudal-to-rostral change in the site of onset.

Adolescent↗
PubMed2004

PINK1 (PARK6) associated Parkinson disease in Ireland.

Mutations in the PINK1 gene have recently been shown to cause autosomal recessive Parkinson disease (PD). The authors assessed the prevalence of PINK1 gene mutations in 290 well-characterized early- and late-onset PD patients from Ireland. In a 51-year-old PD patient with a family history of PD, the authors identified a novel heterozygous mutation (R147H) in exon 2 of the PINK1 gene. Overall, these data indicate that PINK1 mutations are a rare cause of PD in Ireland.

Adolescent↗
PubMed2004

Fatal presentation of ornithine transcarbamylase deficiency in a 62-year-old man and family studies.

Ornithine transcarbamylase deficiency (OTCD) resulting from deficiency of the mitochondrial enzyme OTC shows extensive phenotypic heterogeneity influenced by allelic heterogeneity and modifying environmental influences such as protein intake. We report the fatal late-onset presentation of OTCD in a 62-year-old man with the V337L mutation, a previous presentation in his grandson and negative clinical and biochemical screening of the proband's three daughters.

Family Health↗
PubMed2003

Parkin-proven disease: common founders but divergent phenotypes.

OBJECTIVE: To compare and contrast clinical and genetic findings in six probands with parkinsonism with a parkin exon 3 438- to 477-bp deletion (Ex3Delta40) to search for evidence of a common founder. METHOD: Clinical review, parkin gene sequencing, dosage studies, and high-resolution genotype/haplotype analysis were performed. RESULTS: All subjects had two or more signs consistent with a diagnosis of possible or probable PD with age at onset younger than 45 years (mean +/- SD 29.3 +/- 10.2 years, range 16 to 42 years). Affected individuals were either homozygotes, compound heterozygotes, or Ex3Delta40 carriers with one normal parkin allele. Haplotype analysis revealed both Ex3Delta40 and Ex7 924 C-->T (R275W) mutations originated from common founders, the former most probably of Irish descent. Although three cases had Ex7 924 C-->T (R275W) and Ex3Delta40 mutations, their clinical presentation and mode of inheritance were variable. CONCLUSION: Parkin mutations on common parkin haplotypes provide testable hypotheses of parkin function in genetically defined parkinsonism.

Adult↗
PubMed2003

Deep vein thrombosis in a tiler wearing tight knee pads.

Venous compression is a rare but accepted cause of Deep Venous Thrombosis. We report a case of DVT caused by extrinsic compression of the popliteal vein by constricting elasticated knee pads. The knee pads were worn at work by a Tiler who did not have any hypercoagulability disorder.

Adult↗
PubMed2002

Evaluation of 50 probands with early-onset Parkinson's disease for Parkin mutations.

BACKGROUND: Early onset PD has been associated with different mutations in the Parkin gene, including exon deletions and duplications. METHODS: The authors performed an extensive mutational analysis on 50 probands with onset of PD at younger than 50 years of age. Thirteen probands were ascertained from a registry of familial PD and 37 probands by age at onset at younger than 50 years, blind to family history. Mutational analysis was undertaken on the probands and available family members and included conventional techniques (single strand conformation polymorphism analysis and sequencing) and a newly developed method of quantitative duplex PCR to detect alterations of gene dosage (exon deletions and duplications) in PARKIN: RESULTS: Using this new technique, the authors detected eight alterations of gene dosage in the probands, whereas 12 mutations were found by conventional methods among the probands and another different mutation in an affected family member. In total, the authors identified compound heterozygous mutations in 14%, heterozygous mutations in 12%, and no Parkin mutation in 74% of the 50 probands. We expanded the occurrence of Parkin mutations to another ethnic group (African-American). CONCLUSION: The authors systematically screened all 12 Parkin exons by quantitative PCR and conventional methods in 50 probands. Eight mutations were newly reported, 2 of which are localized in exon 1, and 38% of the mutations were gene dosage alterations. These results underline the need to screen all exons and to undertake gene dosage studies. Furthermore, this study reveals a frequency of heterozygous mutation carriers that may signify a unique mode of inheritance and expression of the Parkin gene.

Adult↗
PubMed2001

Early lumen loss after repeat coronary intervention for in-stent restenosis.

The purpose of this study was to compare the effects of balloon angioplasty versus repeat stenting on the early angiographic outcome in patients with in-stent restenosis. The treatment of in-stent restenosis using balloon angioplasty alone often yields excellent early results, but is associated with a high rate of late recurrence. In the SCRIPPS trial, patients with restenosis were treated either with balloon angioplasty alone or placement of additional stents to optimize angiographic results before randomization and exposure of the restenotic segment to gamma radiation or placebo. In patients undergoing repeat catheter based intervention for the treatment of in-stent restenosis, quantitative coronary angiography was used to compare the results of balloon angioplasty alone versus repeat stenting on early lumen loss. After a mean delay time interval of 71 min, the early loss was 0.35 +/- 0.34 mm in the balloon angioplasty alone group compared to 0.01 +/- 0.34 mm in the repeat-stenting group (P = 0.004). The early loss index in the balloon angioplasty alone group (12.8 +/- 12.9%) was significantly greater than in the repeat stenting group (0.7 +/- 12.1%; P = 0.003). Although balloon angioplasty for in-stent restenosis often provides excellent immediate angiographic results, luminal diameters are significantly reduced in the early time period after balloon dilatation. Repeat stenting nearly abolishes this early luminal loss.

Aged↗
PubMed2001

Pain and emotion: new research directions.

Recently, there has been growing interest in the relation between pain and emotion. Numerous recent studies have been conducted in this area. This article provides an introduction to this interesting area by highlighting selected research topics including studies on: stress and pain, negative emotional states and pain, catastrophizing and pain, the fear of pain, emotional regulation processes and pain, the effects of enhancing emotional regulation on pain, and the relation of emotional distress to treatment seeking in persons having pain. The article concludes with a discussion of important directions for future research in this area.

Chronic Disease↗
PubMed2001

Docetaxel (Taxotere) shows survival and quality-of-life benefits in the second-line treatment of non-small cell lung cancer: a review of two phase III trials.

The potential benefits of docetaxel (Taxotere; Aventis, Antony, France) to patients with previously-treated non-small cell lung cancer have been evaluated in two prospective randomized phase III trials. In one study, patients with stage IIIB/IV non-small cell lung cancer who had failed previous cisplatin-based chemotherapy were randomized to receive either docetaxel (100 or 75 mg/m2, once every 3 weeks) or best supportive care. Median survival was significantly longer for patients treated with docetaxel 75 mg/m2 (7.5 months v 4.6 months) as was 1-year survival (37% v 11%). A second trial, also in platinum-pretreated patients, randomized patients to docetaxel 100 mg/m2, docetaxel 75 mg/m2, or vinorelbine/ifosfamide. Median survival was similar across the three study groups. Thirty-two percent of patients assigned to docetaxel 75 mg/m2 and 21% to docetaxel 100 mg/m2, were alive at 1 year, versus 19% on the vinorelbine/ifosfamide arm. Docetaxel offers clinically meaningful benefits in the second-line setting. The recommended dose is 75 mg/m2 once every 3 weeks. The adverse events observed were predictable, tolerable, and manageable. These phase III trials showed that docetaxel provided clinical benefits to patients with non-small cell lung cancer.

Antineoplastic Agents, Phytogenic↗
PubMed2001

Absence of utrophin in intercalated discs of human cardiac muscle.

Utrophin is the autosomal homologue of dystrophin. In normal skeletal muscle it is localised only to neuromuscular and myotendinous junctions, nerves and vascular tissue. In Xp21 muscular dystrophies, utrophin is also detected on the sarcolemma of skeletal and cardiac muscle, while dystrophin is absent or reduced. In normal cardiac muscle, some reports have demonstrated utrophin at intercalated discs and T-tubules. We have re-examined the distribution of utrophin in normal human cardiac muscle using a panel of eight monoclonal antibodies against different epitopes in N- and C-terminal domains. In contrast to previous studies, utrophin was not detected at the intercalated discs or T-tubules, although labelling of blood vessels was strong. We conclude that the primary location of utrophin in normal heart is in the vascular system. In addition, our results show that the utrophin on cardiac blood vessels is full length, similar to that of skeletal muscle blood vessels.

Animals↗