Radiofrequency ablation of accessory pathways in pre-excitation syndrome

Various parameters relating to the radio-frequency ablation of accessory pathways were studied in 53 patients (27 males, 26 females: mean age 38.5 [14-64] years) with a history of paroxysmal tachycardia (over 1 month to 50 years), shown to be caused by an accessory pathway (Wolff-Parkinson-White syndrome). In all patients the following values were obtained: (1) number of procedures necessary to achieve permanent blockage of the accessory pathway (1-4); (2) duration of each procedure (45-420 min); (3) duration of fluoroscopy (5-102 min); (4) number of necessary radio-frequency applications (1-48); and (5) cumulative energy per procedure. To ablate left-lateral pathways (n = 10) required fewer procedures, shorter duration per procedure, shorter fluoroscopy time, fewer current applications and less total energy than coagulation of right-sided pathways (n = 10). Those various parameters were greatest for ablation of septal and para-septal pathways (n = 9). Pathways which conducted only retrogradely (n = 15) were more difficult to ablate than those with anterograde conduction (n = 38). There were two complications. In one case a tension pneumothorax occurred after faulty puncture of the subclavian vein; in the other, the left ventricle was perforated causing an acute tamponade which required pericardiocentesis with subsequent suture closure of the perforation. It is concluded that, in principle, all accessory pathways, regardless of their conduction potential and site, can be ablated by a radio-frequency current.     

Severe atrioventricular block in 2 cases with pre-excitation syndrome

In two patients with WPW syndrome Type A suffering from syncopes and dizziness intermittent high degree A-V block was observed. The analysis of the surface Ecg revealed in the first case a complete A-V block within the normal conduction system at the level of the A-V node. In the second case there was a constant left bundle branch block with intermittent block in the right fascicle (intermittent trifascicular block). In both cases the preexcitation syndromes could be best explained by accessory tracts bypassing the normal nodal system left side. One-to-one conduction through the bypass occurred only at a distinct range of cycle lengths, at lower frequencies the accessory tracts were refractory and a IInd or IIIrd degree A-V block occurred. However, outside this frequency zone some P waves were conducted through the accessory tracts without changes in cycle lengths. The findings support the thesis of at least two functionally different atrioventricular pathways in patients with preexcitation syndrome.     

Multiple accessory pathways in patients with the pre-excitation syndrome

We have studied 135 patients with the pre-excitation syndrome and have demonstrated evidence of multiple accessory pathways in 20 patients. Five patients had two distinct accessory atrioventricular (A-V) connections, associated with enhanced A-V node conduction in one patient. Twelve patients had a single accessory A-V connection associated with enhanced A-V conduction. In one of these there was an additional fasciculo-ventricular connection. One patient had an accessory A-V connection associated with a nodoventricular bundle. Two patients had fasciculo-ventricular connections combined with enhanced A-V conduction. The latter two patients had electrocardiograms suggestive of a complete accessory A-V connection. Patients with enhanced A-V conduction had shorter cycle lengths during reciprocating tachycardia, primarily because of a short A-H during the dysrhythmia, than those without such conduction. In addition, patients with enhanced A-V conduction demonstrated more rapid conduction from atrium to His bundle during induced atrial fibrillation and two developed life-threatening ventricular responses during atrial fibrillation. A nodo-ventricular pathway was documented to participate in reciprocating tachycardia in one patient. Surgery was undertaken in 13 patients. In 11, the intraoperative mapping studies confirmed the preoperative predictions. In two patients, the presence of a second accessory A-V connection was documented after ablation of one.     

Cryosurgical ablation of accessory atrioventricular connections: a method for correction of the pre-excitation syndrome

Cryothermia, a new technique for definitive treatment of the pre-excitation syndrome, is described in two patients. The first patient presented with a normal P-R interval with a delta wave and reciprocating tachycardia. Preoperative electrophysiologic study suggested a free-wall atrioventricular connection on the left posterior atrioventricular (A-V) groove. At surgery, epicardial mapping confirmed the site of pre-excitation on the posterior left ventricular (LV) wall. An electrogram arising from the accessory pathway (AP) was recorded at the site of earliest ventricular activation. Interatrial delay combined with an apparently long accessory pathway to the ventricle caused the P-R interval to appear normal. Local pressure abolished pre-excitation. The site of early ventricular activation was cooled to -60 degrees C with a specially designed cryoprobe. All evidence of pre-excitation and arrhythmias disappeared. The second patient presented with a refractory reciprocating tachycardia and was found to have an AP in the septum capable of only retrograde conduction. Retrograde conduction was abolished by applying a temperature of 0 degrees C to the anulus at this site during tachycardia. Conduction over the AP and reciprocating tachycardia returned with rewarming. Ablation of the AP was obtained by applying a temperature of -60 degrees C for 90 seconds on two occasions to the same area. The His bundle was not injured.     

The familial chylomicronemia syndrome

The chylomicronemia syndrome is a disorder characterized by severe hypertriglyceridemia and fasting chylomicronemia. Genetic causes of the syndrome are rare and include deficiency of lipoprotein lipase (LPL), apolipoprotein C-II, and familial inhibitor of LPL. Patients with familial forms of hypertriglyceridemia in combination with secondary acquired disorders account for most individuals presenting with chylomicronemia. The clinical manifestations--lipid and other biochemical abnormalities--as well as treatment options for chylomicronemic patients are discussed.     

Diagnosis of familial Holt-Oram syndrome

Presented is one rare case in a family affected by a Holt- Oram-Syndrome. This syndrome is associated with an upper limb malformation and a congenital heart disease. In our case we found radiusaplasia on both sides, thenaraplasia on the left hand, a hypoplastic thumb on the right hand. The heart was malformed as a Fallot tetralogy, the left kidney was absent. Four additional affected members of the family are described. By routine ultrasound examination we could not find this malformation syndrome. In families with affected history ultrasound screening examination should be done on a center for prenatal diagnosis.     

Is there a familial carpal tunnel syndrome? An evaluation and literature review

We review the reports of families proposed to have the familial carpal tunnel syndrome (FCTS). The demographic features of sporadic carpal tunnel syndrome (CTS) differ from FCTS, where an earlier onset and increased bilateral involvement is seen. We also identify seven new potential FCTS pedigrees on the basis of their having four or more members with symptoms suggesting CTS. In all but two pedigrees an explanation other than FCTS was found. We conclude that the FCTS is a rare, but genetically distinct disorder.     

The nature, diagnosis and treatment of post-concussion syndrome

INTRODUCTION: The relationship between brief loss of consciousness, subsequent cognitive and emotional complaints, and impact on daily functioning continues to be hotly debated. DEVELOPMENT: In this paper the strong variability about prevalence of the postconcussional syndrome found in several studies is outstanding and the main issues of this disagreement are suggested. Recent neuroimaging techniques are discussed and some neuropsychological measures are suggested. CONCLUSIONS: Currents models (organic/psychogenic) of postconcussional symptoms are reviewed, and a multifactorial model which integrates biological factors with the relevance of neuropsychological deficits--attention, memory, speed of information processing--and coping process is proposed. Finally, according with this model, we conclude with some suggestions to improve neuropsychological intervention and medical treatment of these patients.     

Christian's spondylo-digital syndrome: second familial case

We studied a mother and daughter with skeletal dysplasia which was characterized clinically by proximal and distal flexion contractures in the phalanges, and by brachydactyly, clinodactyly and ulnar and radial subdislocations of the fingers. Radiologically, the 2nd metacarpal in the daughter was seen to be longer than the other metacarpals, with bone carpal fusion, and flexion contractures of the fingers in both hands. Thoraco-lumbar xyphorotoscoliosis and malformed vertebrae with dyssegmentation of L2-L3, T12 and L1 with cuneiform shape, asymmetry of the pelvic bones and exostotic lesions in the proximal third of the tibia and the distal third of the femur were also noted. The clinical and radiological characteristics were compatible with the syndrome described by Christian et al. in 1975 and called the second metatarsal syndrome. The purpose of this paper was to present a second corroborative familial case and to propose another name: Christian's spondylo-digital syndrome.     

Atypical familial microcytosis: a familial and genetic study

The characteristics of familiar atypical microcytosis studied during one year were evaluated. Out of 149 patients with microcytosis in whom iron deficiency was ruled out, a heterogenous beta-thalassemia was diagnosed in 72 cases, a heterozygous delta beta-thalassemia in 16 cases and a hemoglobinopathy in 3 cases. The microcytosis was related to an inflammatory anemia in 12 cases and to an hemopathy in 9 cases. An atypical microcytosis was detected in 37 patients. A familiar and molecular analysis was carried out to detect alpha-thalassemia in cases with atypical microcytosis. It was possible to complete the familiar and molecular analysis in 35 out of 37 cases, and an alpha-thalassemia was observed in 31 patients. Most cases proved to be heterozygous or homozygous-alpha 3.7-thalassemia. No patient with heterozygous alpha zero-thalassemia was found. Most cases of familiar atypical microcytosis in our country are due to -alpha 3.7-thalassemia. Bearing these findings in mind, this analysis should only be used in situations where a problem of prenatal diagnosis is present. Moreover, systematic molecular analysis of familiar atypical microcytosis could be justified if the MCV is lower than 75 fl.     

Genomic organization and mutational analysis of KVLQT1, a gene responsible for familial long QT syndrome

BACKGROUND: Turcot's Syndrome is the association of multiple adenomatous polyps of the colon with a primary tumor of the central nervous system. We present the first reported case of Turcot's Syndrome in a patient with malignant ependymomas. Recent advances in the elucidation of the genetic basis for the hereditary forms of colon cancer have provided a clearer understanding of the etiology of Turcot's Syndrome. This new information is relevant to the neurosurgical community and provides updated guidelines in the diagnosis and management of patients with this complex disease process. RESULTS: Turcot's Syndrome is related to two distinct genetic errors. The first involves a germ-line mutation in the adenomatous polyposis coli (APC) gene, which is postulated to act as a tumor suppressor gene. The second is a germ-line defect in one of a group of genes responsible for DNA nucleotide mismatch repair. CONCLUSION: The elucidation of the gene defects responsible for the hereditary forms of colon cancer has provided a clearer understanding of the molecular basis of Turcot's Syndrome. Patients with hereditary forms of colon cancer and neurologic symptoms require immediate and thorough investigation because of their significantly increased risk of developing CNS tumors. Previously healthy patients diagnosed with a CNS tumor with a family history of adenomatous polyposis coli should undergo screening and surveillance colonoscopy as the CNS lesion may precede colonic symptoms. CNS screening guidelines for asymptomatic patients with adenomatous polyposis coli requires further risk analysis studies. All patients diagnosed with Turcot's Syndrome should be tested for the gene defect, including the CNS tumor tissue to provide further data on the genetic relationship between Turcot's Syndrome and the hereditary forms of colon cancer.     

Secondary disorders of lipid metabolism, metabolic syndrome and familial combined hyperlipidemia

Secondary hyperlipoproteinemias are found in connection with other primary organic diseases. Typical examples are those seen with diabetes mellitus, liver and kidney diseases. In addition there are changes induced by hormonal dysfunctions such as hypothyroidism, by the use of oral contraceptives or in postmenopausal women. During pregnancy there is a physiological transient increase in lipoproteins. In addition to primary organic diseases there are a number of exogenous factors such as obesity, malnutrition and alcohol abuse causing hyperlipidemia. The relation between hypertension and hyperlipidemia described as familial dyslipidemic hypertension is less well known. Obesity, hypertension, dyslipidemia, hyperuricemia and impaired glucose tolerance are the basic conditions of the metabolic syndrome. Familial combined hyperlipidemia is a genetically determined, dyslipidemic syndrome with a high prevalence among patients with coronary artery disease and stroke. As there are some links between familial combined hyperlipidemia and secondary hyperlipoproteinemias, this disease entity is discussed together in this paper. Familial combined hyperlipidemia is metabolically, genetically and by this on a molecular level closely linked to familial dyslipidemic hypertension as well as the metabolic syndrome. The exact mechanism of this disease is currently unknown.     

A familial syndrome of cranial, facial, oral and limb anomalies

A family is described in which two male infants have microcephaly, abnormal ears, anti-mongoloid slant, small mouth, cleft palate, flexed overlapping fingers with syndactyly of digits three and four, syndactyly of the second to the fifth toes, and normal karyotype. This seems to be a new syndrome.     

Partial depletion and multiple deletions of muscle mtDNA in familial MNGIE syndrome

OBJECTIVE: To describe the unique combination of partial depletion and multiple deletions of mitochondrial DNA (mtDNA) on muscle DNA analysis of three siblings with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). BACKGROUND: MNGIE is a relatively homogeneous autosomal recessive disorder characterized by gastrointestinal dysmobility, ophthalmoparesis, peripheral neuropathy, mitochondrial myopathy, and altered white matter signal at brain imaging. Muscle multiple mtDNA deletions have been found in about half of the described cases. METHODS: We studied three affected siblings (two were monozygotic twins) born to nonconsanguineous parents. Muscle mtDNA was investigated by quantitative Southern and Slot blot techniques and by PCR analysis. Morphologic confirmation in the muscle tissue was achieved by using in situ hybridization with a mtDNA probe complementary to an undeleted region and by DNA immunohistochemistry. RESULTS: All three patients showed ragged red (RRF) and cytochrome c oxidase-negative fibers, as well as partial deficiency of complexes I and IV. Southern and Slot blot analyses showed mtDNA depletion in all patients. Multiple mtDNA deletions were also detected by PCR analysis. In situ hybridization demonstrated an overall signal weaker than controls, with a relatively higher signal in RRF. Antibodies against DNA showed a decreased cytoplasmic network. CONCLUSIONS: The muscle histopathology and respiratory chain enzyme defects may be accounted for by the decreased mtDNA amount and by the presence of mtDNA deleted molecules; however, relative levels of mtDNA seem to correlate with life span in these patients. The combination of partial depletion and multiple deletions of mtDNA might indicate the derangement of a common genetic mechanism controlling mtDNA copy number and integrity.     

The fish odour syndrome: biochemical, familial, and clinical aspects

OBJECTIVES: To study the biochemical, familial, and clinical features of the fish odour syndrome among subjects with suspected body malodour. DESIGN: Subjects who responded to a newspaper article were screened for the fish odour syndrome by interview and biochemical tests. Families of subjects with the syndrome were tested if possible. SETTING: St Mary's Hospital, London, and some interviews at subjects' homes. SUBJECTS: 187 subjects (28 males) with suspected body malodour, of whom 156 (19 males) underwent biochemical tests. Five families of six of the subjects with the fish odour syndrome agreed to further tests. MAIN OUTCOME MEASURES: Amounts of trimethylamine and trimethylamine N-oxide in urine collected over 24 hours under normal dietary conditions and for eight hours after oral challenge with 600 mg trimethylamine. RESULTS: The fish odour syndrome was diagnosed in 11 subjects: the percentage of total trimethylamine excreted in their urine samples that was oxidised to trimethylamine N-oxide was < 55% under normal dietary conditions and < 25% after oral challenge with trimethylamine (in normal subjects > 80% of trimethylamine was N-oxidised). Parents of six of the subjects with the syndrome were tested: all showed impaired N-oxidation of excreted trimethylamine (< 80%) after oral challenge, indicating that they were heterozygous carriers of the allele for the syndrome. The syndrome was associated with various psychosocial reactions including clinical depression. CONCLUSIONS: The fish odour syndrome can be inherited in an autosomal recessive fashion. It should be considered as a possible causative factor in patients complaining of body malodour.     

Hereditary arthro-ophthalmopathy (Stickler syndrome): a diagnosis to consider in familial premature osteoarthritis

A number of factors contribute to the pathogenesis of osteoarthritis. Genetic factors are predominant in some cases, including the syndrome of hereditary arthro-ophthalmopathy. The clinical features of the syndrome and the concept of genetic mutations in matrix components are discussed.