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Biomedical subjects

C J Klein

Publications and source records attributed to C J Klein.

At least 19 recordsLinked to original sources
PubMed2006

Myelin protein zero mutation His39Pro: hereditary motor and sensory neuropathy with variable onset, hearing loss, restless legs and multiple sclerosis.

BACKGROUND: Mutations of myelin protein zero (MPZ) may cause inherited neuropathy with variable expression. OBJECTIVE: To report phenotypic variability in a large American kindred with MPZ mutation His39Pro. PATIENTS: Genetic testing was performed on 77 family members and 200 controls. Clinical and electrophysiological field study assessments were available for review in 47 family members. RESULTS: His39Pro was found in all 10 individuals prospectively identified with neuropathy. 200 normal controls were without mutation. Symptoms of neuropathy began in adulthood and were slowly progressive except for one acute-onset painful sensory neuropathy. Associated features included premature hearing loss (n = 7), nocturnal restless leg symptoms (n = 8) and multiple sclerosis in one. CONCLUSIONS: MPZ mutation His39Pro may be associated with acute-onset neuropathy, early-onset hearing loss and restless legs. The relationship with multiple sclerosis in the proband remains uncertain.

Adult↗
PubMed2005

SPTLC1 and RAB7 mutation analysis in dominantly inherited and idiopathic sensory neuropathies.

BACKGROUND: The variable clinical features of hereditary sensory and autonomic neuropathy (HSAN I) suggest heterogeneity. Some cases of idiopathic sensory neuropathy could be caused by missense mutations of SPTLC1 and RAB7 and not be recognised as familial. OBJECTIVE: To screen persons with dominantly inherited HSAN I and others with idiopathic sensory neuropathies for known mutations of SPTLC1 and RAB7. PATIENTS: DNA was examined from well characterised individuals of 25 kindreds with adult onset HSAN I for mutations of SPTLC1 and RAB7; 92 patients with idiopathic sensory neuropathy were also screened for known mutations of these genes. RESULTS: Of the 25 kindreds, only one had a mutation (SPTLC1 399T-->G). This kindred, and 10 without identified mutations, had prominent mutilating foot injuries with peroneal weakness. Of the remainder, 12 had foot insensitivity with injuries but no weakness, one had restless legs and burning feet, and one had dementia with hearing loss. No mutation of RAB7 was found in any of these. No known mutations of SPTLC1 or RAB7 were found in cases of idiopathic sensory neuropathy. CONCLUSIONS: Adult onset HSAN I is clinically and genetically heterogeneous and further work is required to identify additional genetic causes. Known SPTLC1or RAB7 mutations were not found in idiopathic sensory neuropathy.

Acyltransferases↗
PubMed2004

Chronic immune sensory polyradiculopathy: a possibly treatable sensory ataxia.

BACKGROUND: Chronic inflammatory neuropathies can present with a sensory ataxia due to involvement of dorsal root ganglia (DRG) or sensory nerves. Selective inflammatory involvement of sensory nerve roots proximal to the DRG has been postulated. METHODS: The authors identified 15 patients with a sensory syndrome and normal nerve conduction studies. Sensory nerve root involvement was suggested by either somatosensory evoked potential (SSEP) or imaging abnormalities. CNS disease was excluded. RESULTS: All patients had gait ataxia, large fiber sensory loss, and paresthesias, and nine had frequent falls. The disease course was chronic and progressive (median duration 5 years, range 3 months to 18 years). Sural sensory nerve action potential amplitudes were preserved and SSEP abnormalities were consistent with sensory nerve root involvement. Five patients had enlargement of lumbar nerve roots on MRI with enhancement in three. The CSF protein was elevated in 13 of 14 patients tested. Three patients had lumbar sensory rootlet biopsies that showed thickened rootlets, decreased density of large myelinated fibers, segmental demyelination, onion-bulb formation, and endoneurial inflammation. Six patients who required aids to walk were treated with immune modulating therapy and all had marked improvement with four returning to normal ambulation. CONCLUSION: Based on the described clinical features, normal nerve conduction studies, characteristic somatosensory evoked potential (SSEP) abnormality, enlarged nerve roots, elevated CSF protein, and inflammatory hypertrophic changes of sensory nerve rootlet tissue, we suggest the term chronic immune sensory polyradiculopathy (CISP) for this syndrome. This condition preferentially affects large myelinated fibers of the posterior roots, may respond favorably to treatment, and may be a restricted form of chronic inflammatory demyelinating polyradiculoneuropathy.

Adult↗
PubMed2003

The gene for HMSN2C maps to 12q23-24: a region of neuromuscular disorders.

BACKGROUND: Hereditary motor and sensory neuropathy type 2C (HMSN2C, Charcot-Marie-Tooth 2C [CMT2C]) is an autosomal dominant motor and sensory neuropathy involving limb, diaphragm, vocal cord, and intercostal muscles. OBJECTIVE: To identify the chromosome localization for this disorder in one large American family of English and Scottish ethnicity. METHODS: Variable clinical severity led the authors to combine several approaches to accurately identify affected patients. Genome-wide two-point linkage analysis, high-definition mapping, and multipoint and recombinant haplotype analyses were performed. Mutation analysis of the triplet repeat region of ataxin-2 was also carried out. RESULTS: The initial genome-wide scan identified a region at 12q24, and fine mapping provided a maximal lod score of 4.73 (D12S1645 and D12S1583 at theta = 0.01 and 0, respectively). With multipoint analysis, a higher lod score of 5.17 was obtained and localized to the same region at 119.0 cM. Haplotype analysis narrowed the region to approximately 5.0 cM between D12S1646,D12S1330 and D12S105,D12S1339 (12q23.3-24.21). Ataxin-2, the gene responsible for spinocerebellar ataxia type 2 (SCA2), localizes to this region, but no triplet repeat expansion or point mutations within the repeat were found. CONCLUSIONS: The gene for HMSN2C maps to 12q23-24. This region is associated with SCA2, scapuloperoneal spinal muscular atrophy, and congenital distal spinal muscular atrophy. Further studies are needed to demonstrate the specific gene alteration and its relationship with nearby genes.

Age of Onset↗
PubMed2003

Efficacy of NovoSeven during surgery on a haemophiliac with previous history of inhibitors.

Management of bleeding in haemophiliacs with a history of inhibitor remains problematic. With infusion of factor VIII (FVIII), development of an anamnestic response and possible appearance of high-titre inhibitor remains a valid concern. We report a case of a haemophiliac with a history of moderately high-titre FVIII inhibitor that had become undetectable. He had not received FVIII since 1997, when he became inhibitor negative. He had been managed during his bleeding episodes with prothrombin complex factor concentrates, which became less effective in controlling his bleeding. The patient had a history of recurrent, spontaneous shoulder joint dislocations with bleeding, pain and significant disability. Shoulder joint replacement surgery was suggested. Replacement therapy was discussed with the patient, who refused treatment with human FVIII because of his concern for possible anamnestic response and inhibitor rebound. Porcine FVIII was not acceptable due to his poor response when used once in the past, and his history of moderate allergic reaction. Therefore, recombinant factor VIIa (NovoSeven, Novo Nordisk, Princeton, NJ) was considered to be an acceptable option for the contemplated shoulder surgery. The patient underwent 2.5 h of surgery with NovoSeven infusion. The surgeons were impressed with the lack of bleeding in this traumatic surgery. Despite the continuously prolonged activated partial thromboplastin time and low FVIII levels, the patient maintained a remarkably dry surgical field. Effective haemostasis was achieved during and after this procedure. This case illustrates the usage of NovoSeven as an effective treatment modality in a haemophilia A patient with past history of inhibitor undergoing joint surgery.

Adult↗
PubMed2002

Inflammation and neuropathic attacks in hereditary brachial plexus neuropathy.

OBJECTIVE: To study the role of mechanical, infectious, and inflammatory factors inducing neuropathic attacks in hereditary brachial plexus neuropathy (HBPN), an autosomal dominant disorder characterised by attacks of pain and weakness, atrophy, and sensory alterations of the shoulder girdle and upper limb muscles. METHODS: Four patients from separate kindreds with HBPN were evaluated. Upper extremity nerve biopsies were obtained during attacks from a person of each kindred. In situ hybridisation for common viruses in nerve tissue and genetic testing for a hereditary tendency to pressure palsies (HNPP; tomaculous neuropathy) were undertaken. Two patients treated with intravenous methyl prednisolone had serial clinical and electrophysiological examinations. One patient was followed prospectively through pregnancy and during the development of a stereotypic attack after elective caesarean delivery. RESULTS: Upper extremity nerve biopsies in two patients showed prominent perivascular inflammatory infiltrates with vessel wall disruption. Nerve in situ hybridisation for viruses was negative. There were no tomaculous nerve changes. In two patients intravenous methyl prednisolone ameliorated symptoms (largely pain), but with tapering of steroid dose, signs and symptoms worsened. Elective caesarean delivery did not prevent a typical postpartum attack. CONCLUSIONS: Inflammation, probably immune, appears pathogenic for some if not all attacks of HBPN. Immune modulation may be useful in preventing or reducing the neuropathic attacks, although controlled trials are needed to establish efficacy, as correction of the mutant gene is still not possible. The genes involved in immune regulation may be candidates for causing HBPN disorders.

Adolescent↗
PubMed2001

Basal forebrain malformation with hyperhidrosis and hypothermia: variant of Shapiro's syndrome.

A 62-year-old woman presented with episodic sweating and shivering with reduced core temperature. Brain MRI demonstrated a basal forebrain malformation. Physiologic testing included EEG, SPECT, heat challenge, and autonomic testing. Glycopyrrolate aborted spells and raised core temperature. Hypothalamic dysregulation is likely the primary pathophysiology in the setting of other forebrain anomalies. These findings expand the structural abnormalities and treatment options within the temperature dysregulating conditions of Shapiro's syndrome and "diencephalic epilepsy."

Female↗
PubMed1999

Genetic variants in the tumor necrosis factor receptor 1 gene in patients with MS.

We scanned for all genetic variants in functionally important regions of the tumor necrosis factor receptor 1 gene (TNF-R1) in 100 to 111 MS patients from Olmsted County, MN, and analyzed selected variants for an association with disease course and severity. Ten genetic variants were uncovered. Only one variant, a silent substitution, was found in coding sequence. One intronic variant may generate a novel splice-junction sequence. We did not find an association between either this intronic variant or another common promoter variant and the course or severity of MS.

Chromosome Mapping↗
PubMed1999

Investigation of the impact of MIG1 and MIG2 on the physiology of Saccharomyces cerevisiae.

The gene functions of MIG1 and MIG2 are well known for their role in glucose control in Saccharomyces cerevisiae. A prototrophic mig1 disruptant (T468) and mig1mig2 double disruptant (T475) as well as their congenic wild-type strain (CEN.PK 113-7D) were analysed for changes in their peripheral metabolism (batch cultivations on sugar mixtures) and central metabolism (batch and continuous cultivations as well as acceleratostats). Sucrose metabolism was alleviated of glucose control in the mig1 disruptant, and even more so in the mig1mig2 disruptant compared with their wild-type strain. The lag phase in a batch cultivation grown on a glucose-galactose mixture was reduced by 50% in either disruptant, i.e. additional disruption of MIG2 in a mig1 background did not further alleviate galactose metabolism from glucose control. In contrast, both disruptants exhibited a more stringent glucose control of maltose metabolism compared with the wild-type strain. Growing on glucose, the mig1mig2 double disruptant exhibited a 12% higher specific growth rate than the wild-type strain, as well as a significantly higher respiratory capacity.

Culture Media↗
PubMed1999

Authorship: can you claim a byline?

Decisions about bylines, although seemingly straightforward, can "breed ill-will," "wreck friendships," and "even damage careers" if decisions are not in accord with professional guidelines and common sense. Editors have attempted to promote responsible authorship by creating Uniform Requirements. According to the International Committee of Medical Journal Editors, each author must have made a substantial contribution to all 3 of the following conditions to qualify for authorship: conceiving and designing the work represented by the article or analyzing and interpreting data; drafting the article or revising it critically for important intellectual content; and giving final approval of the version to be published. Despite these guidelines, bylines continue to include grafters and guests. Researchers believe guidelines for authorship are necessary but suggest the existing Uniform Requirements may be overly restrictive and easily misinterpreted. Editors will need to work with researchers to reach consensus on realistic and appropriate guidelines for authorship.

Authorship↗
PubMed1999

Central nervous system histoplasmosis mimicking a brain tumor: difficulties in diagnosis and treatment.

Neurologic involvement occurs in 10% to 20% of patients with disseminated histoplasmosis. We describe a 20-year-old woman who had headache and diplopia but no evidence of systemic infection. Magnetic resonance imaging showed an enhancing mass in the thalamomesencephalic and third ventricular region. After subtotal resection of what was presumed to be a glioma, the patient had symptoms and signs of meningitis. Subsequent pathological review demonstrated noncaseating granulomas, and serologic tests and cultures confirmed the diagnosis of histoplasmosis. Initiation of antifungal therapy and removal of an infected shunt system resulted in clinical improvement. Clinicians should maintain a high index of suspicion in patients who are from any area endemic for histoplasmosis.

Adult↗
PubMed1998

Overfeeding macronutrients to critically ill adults: metabolic complications.

Metabolic complications from overfeeding critically ill patients are serious and sometimes fatal. Nutrition care is best provided through repeated evaluation of patients' responses to feeding. Nutrition support may need to be modified over time to maintain metabolic stability and promote recovery. This article describes the etiology of 10 metabolic complications of overfeeding. Guidelines for recommending macronutrients are discussed, as are factors that could increase the risk of overfeeding. Patients who are very small, very large, or very old are particularly vulnerable to overfeeding. Overfeeding protein has led to azotemia, hypertonic dehydration, and metabolic acidosis. Excessive carbohydrate infusion has resulted in hyperglycemia, hypertriglyceridemia, and hepatic steatosis. High-fat infusions have caused hypertriglyceridemia and fat-overload syndrome. Hypercapnia and refeeding syndrome have also been caused by aggressive overfeeding. Dietitians can prevent or curtail the metabolic complications of overfeeding by identifying patients at risk, providing adequate assessment, coordinating interdisciplinary care plans, and delivering timely and appropriate monitoring and intervention. Dietitians need to document complications, interventions, and the outcomes of their clinical care to evaluate the appropriateness of existing nutrition guidelines.

Acidosis↗