Effects of cavotricuspid isthmus catheter ablation on paroxysmal atrial fibrillation.

It has been demonstrated that successful cavotricuspid isthmus ablation of typical atrial flutter combined with atrial fibrillation (AF) sometimes influences the preablation history of paroxysmal AF. However, the effectiveness of only isthmus ablation on AF itself is unclear. Endocardial catheter mapping during induced AF was performed around the tricuspid annulus using duodecapolar clectrode catheters in 39 patients with drug-refractory paroxysmal AF. Isthmus ablation was performed in 16 patients (41%) in whom catheter mapping during AF showed an organized activation pattern around the tricuspid annulus. During a mean follow-up of 12.3 months, isthmus ablation was successful in preventing AF in 12 (75%) patients, 8 without medication and 4 with a previously ineffective drug. This success group had a significantly higher F wave amplitude in lead V1 (0.29+/-0.10 vs 0. 15+/-0.04 mV, p < 0.01), a higher left ventricular ejection fraction (74+/-9 vs 58+/-2%, p < 0.05), and a smaller left atrial dimension (35+/-6 vs 43+/-4 mm, p < 0.05) than the failure group. Isthmus ablation may be effective in preventing paroxysmal AF with an organized activation pattern around the tricuspid annulus. F wave amplitude, left ventricular ejection fraction, and left atrial dimension were significant predictors of success.

Purpura fulminans induced by disseminated intravascular coagulation following infection in 2 unrelated children with double heterozygosity for factor V Leiden and protein S deficiency.

Purpura fulminans is associated with homozygous protein C and homozygous protein S deficiency or may follow bacterial or viral infections. We present 2 children from 2 unrelated Arab families with purpura fulminans who were double heterozygotes for factor V Leiden inherited from their fathers and protein S deficiency inherited from their mothers. No previous thrombotic events have occurred in either patient or their respective family members. In one patient sepsis accompanied by disseminated intravascular coagulation appeared to be the trigger of purpura fulminans. In the other patient varicella infection preceded purpura fulminans and was also associated with disseminated intravascular coagulation. This report emphasizes the need for evaluation of hereditary defects in the inhibitory mechanisms of blood coagulation in patients with purpura fulminans at any age.

Disturbed patterns of globin chain synthesis in childhood monosomy 7 myeloproliferative syndrome.

Two children with typical clinical and haematological features of monosomy 7 myeloproliferative syndrome are presented. Both children displayed decreased production of beta-globin chains and unbalanced high alpha/non-alpha synthetic ratios similar to those characteristic of homozygous beta-thalassaemia. These provide further evidence for the involvement of the erythroid line as part of the malignant clone, indicating neoplastic transformation of a pluripotential stem cell in this disease.

Muscle fiber type transformation in nemaline myopathy and congenital fiber type disproportion.

In a morphometric study on biopsied muscles from 5 patients with nemaline myopathy (NM) and 5 with congenital fiber type disproportion (CFTD), the common findings were relative type 1 fiber smallness, type 1 fiber predominance and occasional hypertrophic type 2 fibers. In NM, the relatively larger type 1 fibers increased in number with age in parallel with a decrease in the number of normal to hypertrophic type 2 fibers, reflecting active fiber type transformation from type 2 to type 1, which resulted in striking type 1 fiber predominance. The presence of scattered non-atrophic type 2C fibers also reflected active fiber type transformation because the fibers during the maturational or degenerating process are known to show the type 2C reaction on ATPase staining. On the other hand, the type 1 fibers in CFTD were small in caliber and showed minimal variation in size, suggesting practically no fiber type transformation from hypertrophic type 2 to type 1.

The interaction of hemoglobin O Arab with Hb S and beta+ thalassemia among Israeli Arabs.

We have studied 105 individuals in the village of Jasser El Zarka in the Northern Coast of Israel of whom 59% had at least one abnormal hemoglobin. Of the individuals studied 41% were AA, 13.3% AS, 28.6% AOArab, 10.5% SOArab, 0.9% SS, 38% OArab-beta + Thal, and 1.9% beta Thal trait. The SOArab double heterozygotes were characterized by a normal mean corpuscular volume (MCV) and mean corpuscular hemoglobin concentration (MCHC), and an increase of Hb F (11.7 +/- 4.3%) and 2,3-diphosphoglycerate levels (27.8 microns/g Hb). The increase of Hb F is higher than the one seen among OArabs of other ethnic backgrounds. Their clinical course was moderately severe and osteoporosis was quite frequent. The interactions of Hb OArab and Hb S were studied in vitro and it was confirmed the Hb OArab lowers the minimal gelling concentration of mixtures with Hb S (as compared to mixtures of Hb S and Hb A), but that this effect is ionic-strength dependent. Our data are in conflict with previous claims that Hb OArab mixtures with Hb S polymerized almost as much as pure S. Oxygen association curves show a significant displacement of the p50 to the right, but the effect of oxygen dissociation is less apparent. The displacement was not nearly as significant as with SS cells, confirming our gelation data. Blood group determinations establish that these Arab populations had black African admixture. The Hb OArab/beta + Thal double heterozygotes exhibit moderate anemia (10.3 g% of Hb) and the percentage of Hb A was 17.2 +/- 1.8%. The fetal Hb was 5.4 +/- 2.1% and the 2,3-diphosphoglycerate level in two cases was 17.4 mumol/g Hb. The only case of a homozygote SS had moderate anemia (10.3g Hb%), 25.7% of Hb F, and a very benign course.

An electron microscopical study of the T-system in biopsied muscles from Fukuyama type congenital muscular dystrophy.

The behavior of the tubular system in muscles from six patients with Fukuyama type congenital muscular dystrophy (FCMD) was examined by electron microscopy using a lanthanum nitrate stain for a comparison with that in Duchenne muscular dystrophy (DMD). In FCMD, many fibers showed morphological changes of the T-system as follows: aggregated tubular components forming honeycomb-like structures, focal dilatation of T-tubules with tangle formation, and numerous longitudinally projecting tubules, which were quite similar to those found in cases with DMD. The fibers with abnormal T-systems occasionally showed ultrastructural characteristics of regenerating fibers, including excessive ribosome particles, immaturely organized myofibrils, and an increased number of internal nuclei and satellite cells. The present results suggested that there was no qualitative difference in the behavior of the T-system between FCMD and DMD, and the morphological changes of the T-system in dystrophic muscles were not primary lesions initiating myonecrosis but reflected the behavior of sarcotubular formation in the process of muscle regeneration.

Behavior of sarcotubular system formation in experimentally induced regeneration of muscle fibers.

To examine the behavior of transverse (T)-tubule formation in experimentally-induced regenerating fibers, a local anesthetic, bupivacaine hydrochloride, was injected directly into the rat soleus muscle to cause myonecrosis. The regenerating fibers following necrosis were then examined by electron microscopy using lanthanum nitrate which clearly demonstrated the sarcotubular system. In the early stage of regeneration within 7 days after muscle necrosis, the T-tubules seemed to be composed of markedly proliferated subsarcolemmal caveolae with occasional honeycomb structure formation. Around 10 days, the T-tubules in regenerating fibers were tortuously and irregularly arranged with focal dilatation in diameter, and extended longitudinally along the axis of well organized myofibrils. As the regenerating fibers matured, the sarcotubular system, irregular in course and in shape, gradually became organized into a regular transverse position against the myofibrils, along with a marked decrease in longitudinally arranged tubular components. These morphological findings of the early T-tubule formation seen in the present study were similar to those found in early myogenesis, and in biopsied muscles from cases of polymyositis and progressive muscular dystrophy.

Auditory nerve-brainstem evoked responses in hyperbilirubinemic neonates.

On the basis of the known predilection of the auditory brainstem pathway for bilirubin toxicity, we have examined auditory brainstem responses of neonates during the period of hyperbilirubinemia. The auditory brainstem responses of 24 infants with serum bilirubin values between 15 to 25 mg/dL were compared with the responses of 19 infants without hyperbilirubinemia, who had similar gestational and postnatal ages. Wave IV-V complex was absent in at least one recording of 10/24 jaundiced infants, whereas wave complex IV-V was consistently present in all of the 19 infants without hyperbilirubinemia (P less than .001). Jaundiced infants also had prolonged brainstem transmission time (P less than .01) which reflected increased latency at both lower and upper brainstem levels. The above changes were rapidly reversed in the majority of instances. Neonatal jaundice was associated with significant transient aberrations of auditory brainstem responses, suggestive of a transient brainstem encephalopathy. This evidence of bilirubin entry to the brain at conventionally acceptable serum concentrations raises questions about current concepts of the mechanism of transfer of bilirubin across the blood-brain barrier.

Longitudinal changes in selenium content of breast milk.

The selenium (Se) contents of human milk, serum and hair obtained from 22 lactating mothers were measured by fluorometric analysis. The Se contents in 41 milk samples from different stages of lactation were obtained longitudinally from 10 mothers. They showed a large variance of individual samples at any stage of studies. The highest Se level was found in colostrum (median 80 ng/ml); subsequently, Se content declined significantly during the first month of lactation and then came to a plateau level (median 17-18 ng/ml). No positive correlation of Se content was found between the serum and the milk samples at three months of lactation. No positive correlation of Se content was found between the hair and the milk samples obtained from lactating mothers.

Intracytoplasmic inclusions in the atrophic muscle fibers in Werdnig-Hoffmann disease.

In the biopsied muscle from a male infant having clinical and pathological characteristics of Werdnig-Hoffmann disease, unusual intracytoplasmic inclusions measuring from 1.5-7 micron in dimension were observed in approximately 3% of the atrophic fibers. Although the ultrastructural characteristics of the inclusion were almost identical to that of "cytoplasmic body" seen in various neuromuscular disorders, which showed somewhat different histochemical reactions. This unusual structure was assumed to have originated from degenerated myofibrils and possibly from mitochondria, while the significance of the body formation still remains to be solved.

A fluorescent microscopy study of biopsied muscles from infantile neuromuscular disorders.

The Acridine Orange (AO) stain for muscle biopsies is particularly useful to identify regenerating and ongoing hypertrophic muscle fibers under fluorescent microscopy. This method was applied to muscle biopsies from 65 patients who suffered from various childhood neuromuscular disorders. While normal fibers showed dull green cytoplasm with small green-yellow nuclei, striking fluorescent fibers were observed in eight cases of congenital muscular dystrophy (CMD) and 12 cases of Duchenne muscular dystrophy (DMD); these fibers were characterized as follows: (1) small fibers with big oval or spherical nuclei which fluoresced strongly with a bright orange color; (2) fibers of various sizes and different degrees of orange fluorescence; and (3) opaque fibers with bright yellow cytoplasm. The small diameter fibers in Werdnig-Hoffmann (WH) disease, nemaline myopathy, and congenital fiber type disproportion failed to show apparent AO-RNA fluorescence. Although all the atrophic fibers in Kugelberg-Welander (KW) disease showed a vague orange fluorescent color, this was obviously different from that of regenerating fibers seen in CMD and DMD. In addition to these findings, the hypertrophic fibers in a case of unclassified myopathy also showed moderate orange fluorescence around the entire periphery of the cytoplasm.

Subacute sclerosing panencephalitis. An autopsy case with impaired cellular immunity.

An autopsy case of subacute sclerosing panencephalitis (SSPE) in a 5-year-old boy, with rapid progression to a comatose state in 2 weeks after the onset of right hemiplegia, is described. The levels of antibody to measles virus in the serum and the cerebrospinal fluid were increased, and high levels of IgG in the latter were found. A characteristic pattern of electroencephalogram (EEG) showing periodic suppression of high voltage complexes was also found during the course of the disease. Microscopical examination revealed perivascular cuffing, numerous hypertrophied astrocytes with a diffuse gliosis and sporadic intranuclear inclusions in the brain. In addition to these typical findings of SSPE, impaired cellular immunity was recognized by delayed skin test in vivo, and pathologically severe atrophy of thymus, and follicular atrophy of spleen with amyloid deposition in the wall of the sheathed arteries were found.

Infantile glycogen storage myopathy in a girl with phosphorylase kinase deficiency.

A 19-month-old girl with moderate hypotonia was studied. Histochemical and electronmicroscopic findings revealed that many skeletal muscle fibers contained an excess amount of glycogen. The phosphorylase reaction was normalized only after activation with 5' AMP. Biochemical studies showed an increased glycogen content and decreased activities of phosphorylase "a" and an active form of phosphorylase kinase, whereas activities of total phosphorylase, total phosphorylase kinase, and cyclic AMP-dependent protein kinase were all in the normal range. Thus, phosphorylase kinase in the patient's muscle seemed to be a variant form, which was activated partially under the physiologic condition. This condition may be inherited as an X-linked recessive trait.

Xanthine oxidase inhibitor in Duchenne muscular dystrophy.

The treatment with xanthine oxidase inhibitor, allopurinol, was evaluated in 17 patients with Duchenne muscular dystrophy (aged 2 years 9 months to 13 years 9 months) using the double blind technique. The total observed period was 27 months. The results of 100-point scale of graded functional abilities revealed that an improvement, unchange and progression of dysfunction were found in 2, 2 and 6 patients, respectively, in allopurinol group and in 0, 2 and 5 patients, respectively in placebo group. The patients' age and stage of the disease seemed to be related to the effectiveness or allopurinol treatment.

An acute variant of subacute sclerosing panencephalitis: an autopsy case report.

An acute variant of subacute sclerosing panencephalitis (SSPE) was described in a 5-year-old boy who showed rapid progression of coma within 14 days of right hemiplegia. He had measles at 3 years of age. The diagnosis of SSPE was based on the following findings: high anti-measles antibody titer in the serum and in the spinal fluid, periodic complex of EEG, and typical pathological changes of the brain. Treatment with transfer factor failed to improve the worsening clinical course. It is suggested that SSPE should be considered in the differential diagnosis of acute fulminating encephalitides or intracranial vascular lesions.

Serum vitamin E concentration in patients with severe multiple handicaps treated with anticonvulsants.

Serum vitamin E concentrations were measured in 47 severely handicapped patients, aged from 4 to 23 years, and in 22 controls. Thirty-three of the handicapped patients with seizures were treated with phenytoin and phenobarbital; the remaining 14 patients were not treated. The serum vitamin E levels were lower in the handicapped than in controls. Among the handicapped, those treated with anticonvulsants showed much lower levels of serum vitamin E than those untreated. Ten patients under anticonvulsant therapy were selected to receive d-1-alpha tocopherol acetate, 100 mg/day, based on their low serum vitamin E levels (range of 0.27 to 0.61 mg/100 ml). After one month of tocopherol treatment, both their serum vitamin E levels and hemolysis tests returned to normal. During a three-month tocopherol treatment period, both the frequencies of seizure attacks and the electroencephalogram (EEG) patterns remained unchanged. Supplementation with vitamin E is recommended in some patients under anticonvulsant therapy.

Mitochondrial fraction of serum glutamic-oxaloacetic transaminase in Duchenne muscular dystrophy.

The mitochondrial fraction of serum glutamic-oxaloacetic transaminase was measured in the serum of 50 patients with Duchenne muscular dystrophy by an immunoadsorbent method. The enzyme activities in patients in the early, midstage, and late stages of the disease and controls were 21.8 +/- 7.4 (N=9), 12.2 +/- 3.7 (N=38), 6.4 +/- 1.2 (N=3) and 4.2 +/1 1.2 units/ml (N=15), respectively. The enzyme level in the early stage was significantly elevated (p less than 0.01, vs. control, p less than 0.05 vs. mid stage). As the disease progressed, the levels gradually declined, but mid-stage values were still higher than the late stage (p less than 0.01) or control values (p less than 0.01). In the late stage, enzyme activity was within the control range.