High-dose beta-blocker hypertrophic cardiomyopathy therapy in a patient with Friedreich ataxia.

Heart involvement in patients with Friedreich ataxia (FRDA) is a condition marked by inevitable progressive deterioration, with premature death. There is currently no specific treatment for FRDA. Recently, a therapy with idebenone, a short-chain coenzyme Q10 analogue, was reported to reduce left ventricular mass by 20% in about half of FRDA patients, but a double-blind placebo-controlled study did not fully confirm these results. In this case report, we present a 5-year follow-up of symmetrical concentric hypertrophic cardiomyopathy (HCM) in an FRDA patient treated with high-dose propranolol. The therapy resulted in a reduction in the thickness of the septal and posterior left ventricular walls and complete normalization of diffuse electrocardiographic repolarization abnormalities. To the best of our knowledge, this is the first such case to be reported in the literature, demonstrating the positive effects of high-dose beta-blocker treatment on heart involvement in patients with FRDA.

[Deletions in the dystrophin gene and its phenotype expression]. / Delecije u genu za distrofin i njihova fenotipska ekspresija.

About 60% of both Duchenne's muscular dystrophy (DMD) and Becker's muscular dystrophy (BMD) is due to deletions of dystrophin gene. For cases with deletion mutations the "reading frame" hypothesis predicts that deletions which result in disruption of the translation reading frame prevent production of stable protein and are associated with DMD. In contrast, intragenic deletions that involve exons encoding an integral number of triplet codons maintain proper reading frame. The resulting abnormal proteins are stable and partially functional, resulting in a milder and more variable BMD phenotype. To test the validity of this theory,we analyzed 40 patients-19 independent deletions at the DMD/BMD locus. Clinical/molecular correlations based on the altera-tions of the reading frame were valid in 69.2% of cases. After exclusion of: --2 patients with del 3-6 (with no consistent clinical expression); --1 DMD patient with large in-frame deletion; --2 patients that were too young to be classified; --4 patients in whom it was impossible to identify the extent of deletion (del 47 and del 44-45), the correlation between deletion and clinical severity was as predicted in 92.4% of cases. The present data should be useful in establishing the prognosis in individual patients even in sporadic cases with no affected relatives.

[Schimke immuno-osseous dysplasia]. / Simkeova imunsko-kostana displazija.

Schimke immuno-osseous dysplasia (OMIM *242900) is a rare autosomal recessive disorder that affects primarily the bone, the immune system, the kidneys, the skin and the vascular system. The patients have intrauterine growth retardation, short stature with short neck and trunk, peculiar clinical phenotype: triangular face, broad nasal bridge, bulbous nasal tip, small palpebral fissures, long upper lip and low hairline. The characteristic features include spondyloepiphyseal dysplasia, hyperpigmented maculae, proteinuria with progressive renal failure, lymphopenia with recurrent infections and cerebral ischaemia. We describe a girl, 5 years old, with short-trunk type of dwarfism (height 75 cm, below 3rd centile), short neck, accentuated lumbal lordosis and protruding abdomen. The patient had peculiar face with a broad, depressed nasal bridge, bulbous nasal tip, and slightly elongated upper lip. The hair was thin and sparse. Numerous pigmented spots resembling lentigines were visible on the trunk and abdomen. Radiographs showed spondyloepiphyseal dysplasia. At the age of 2 years laboratory analyses showed normal growth hormone secretion, normal thyroid function tests, normal female karyotype and no mucopolisachariduria. Since the age of 4 years, several episodes of transitory right-sided hemiparesis with spontaneous recovery, were observed. Seizures occurred at 5 years of age, when the MRI brain imaging showed multiple areas of ischaemia. She also experienced transient nephrotic syndrome, lymphopenia and low IgG accompanied by septicaemia.

[West syndrome--new therapeutic approach]. / Westov sindrom--novi terapijski pristup.

West syndrome (WS) is an age dependent epileptic syndrome caused by various brain disorders. WS has been frequently classified in two groups, cryptogenic and symptomatic. As symptomatic WS consists of patients with numerous types of brain lesions, the prognosis and evolutional changes may be different among the types of brain lesions. WS is resistant to treatment to most conventional antiepileptic drugs, and only valproic acid, benzodiazepines, adrenocorticotropic hormone (ACTH), corticosteroids and vigabatrin have been found efficacious. Benzodiazepine, notably nitrazepam, and less clonazepam had been effective in bringing spasms under control but emerging tolerance and significant side effects (hypotonia and drowsiness) precluded its wider use. ACTH has been the treatment of choice for infantile spasms ever since Sorel and Dusaucy-Bouloye described its effectiveness in 1958. Despite the empirical approach steroids were capable of controlling the spasms and normalizing EEG in about 60% of cases. Corticotropin (ACTH) was used in doses from 5 to 180 I.U. daily, prednizolone 2-10 mg/kg daily, hydrocortisone 5-10 mg/kg daily and dexamethason 0.3-0.5 mg/kg. However, poor consensus was defined regarding the best steroid molecule to use, the dosage, and the duration of treatment. Also frequent and sometimes serious side effects have occurred during ACTH therapy, notably serious infections and hypertension that promoted continuous search for alternative and safer drugs tolerated outpatient treatment, good tolerance and minor side effects. Recently a specific visual field loss has been reported in treated adults that raised concern about safety of vigabatrin. New reports in children claim that vigabatrin treatment of children and adolescents has a lower risk for visual field defect than in adults, because of reported reversibility. Vigabatrin paediatric advisory group recommend the trial of vigabatrin for 12-14 days as first treatment for WS and in the case of good clinical response continuation of therapy for six months. Other new antiepileptic drugs (lamotrigine, topiramate, felbamate and zonisamide) have shown significant efficacy in the treatment of resistant WS to previous medication. The current task is to determine risk/benefit ratios of these two drugs (vigabatine, ACTH) and to delineate the group of patients with WS where their use would be optimal.

Non-Hodgkin's lymphoma of the uterus and CNS.

We report a case of a non-Hodgkin's lymphoma of the uterus and central nervous system in an 8-year-old female. The neurologic signs included blurred vision, neck stiffness, and walking difficulties but no abdominal problems. She deteriorated further, and repeated lumbar punctures revealed the presence of malignant cells in the cerebrospinal fluid. A repeated ultrasound scan of the abdomen demonstrated a markedly enlarged uterus. Biopsy revealed B-cell non-Hodgkin's lymphoma. Treatment according to the Berlin-Frankfurt-Münster protocol was initiated, but she developed hyperventilation syndrome and required mechanical ventilation. Her condition improved after 1 week but then deteriorated again, and despite additional chemotherapy she developed myelosuppression and septicemia with multiresistant Klebsiella pneumoniae and eventually died 13 months after her first admission to the hospital. No clinical or laboratory signs of relapse were evident at the time of death.

Pulmonary blastoma presenting as a solitary lip metastasis: case report and review of the literature.

Pulmonary blastoma (PB) is an uncommon primary lung malignancy. This neoplasm was first described by Barrett and Barnard in 1945. The tumor is composed of immature epithelial and mesenchymal tissues which may recapitulate early embryological lung development. Under the microscope, the globular component resembles immature bronchus and connective tissue as seen in embryonic lung. More than one hundred cases have been reported in the literature. PB is more frequent in older people and in males and tends to affect blacks at younger ages. Symptomatology varies from asymptomatic to symptoms of a non-specific pulmonary disease. Cough, hemoptysis, dyspnea, chest pain, respiratory distress, fever, anorexia and weight loss are the most common presenting features. The most common roentgenologic pattern is a well-demarcated peripheral lesion, encapsulated by compression or atelectatic lung tissue, although in some cases there is a tendency to lobulation and cavitation. The size of the mass varies from a small peripheral nodule to a mass occupying the entire lobe or hemithorax. The treatment of choice has been surgical excision, radiation and, in selected cases, a combination of chemotherapy with radiation. The prognosis of this malignancy is poor; overall five-year survival is approximately 16 percent. No correlation has been established between histopathologic criteria and survival. The factors that indicate poor prognosis are tumor recurrence, metastasis at initial presentation, tumor size over 5 cm and lymph node metastasis. Liver, central nervous system and bones are the most frequent location of distant metastases. A rare case is presented of a pulmonary blastoma with an upper lip metastasis occurring in a paraplegic male. Diagnosis was confirmed by autopsy findings.(ABSTRACT TRUNCATED AT 250 WORDS)

[The Angelman's syndrome]. / Angelmanov sindrom.

Distinction of patients with Angelman's syndrome in a group of mentally retarded patients is important even though the syndrome was rarely reported since the original description in 1965. Before that time these patients were thought to suffer from neurologic sequelae of perinatal asphyxia, Lennox-Gastaut syndrome or mental retardation of unknown origin. Diagnosis is based on the following criteria: developmental delay from early age, absent speech (or speech limited to less than six words), jerky movements with an ataxic gait if the patient is walking, paroxysm of inappropriate laughing, dysmorphic craniofacial features (brachycephaly, mid-facial hypoplasia, deep set eyes, macrostomia, prominent mandible). About 60% of patients have deletion of chromozome 15q11-13. Cytogenetic studies suggest that de novo deletion of chromozome 15 is connected with the low recurrence risk and that families with several members with Angelman's syndrome belong to the group without identifiable deletion on citogenetic or molecular level. The article deals with the diagnostic criteria, clinical features and electroencephalographic changes (after several years of followup) in seven children with Angelman's syndrome (four girls and three boys).

Tumor debulking followed by immediate combination chemotherapy in advanced ovarian carcinoma. Phase II.

Fifty-one consecutive, previously untreated patients with FIGO stage III or IV epithelial ovarian carcinoma were enrolled in a prospective study over a period of 7 years (1981-1988). Significant improvement has been noted in patients with advanced ovarian cancer following the administration of modified PAC 1 (adriamycin, cytoxan and cyclophosphamide) immediately following primary debulking surgery (within 24 hours) and repeated for 11 monthly cycles. A second look operation was found as an important prognostic indicator. Thirty-one patients (all Stage III) completed the chemotherapy course and were eligible for second look operation. Of these, 21 patients (68%) showed negative second look. Of the patients with negative second look, 17 of 21 (81%) are alive with a mean survival of 61 months (range 19-103 months) after diagnosis. Among those with positive second look only 3 of 10 are alive with a mean of 41 months after diagnosis. The remaining 20 patients (13 stage III and 7 stage IV) did not undergo second look laparotomy. Only 2 of these 20 patients are alive with a mean of 35 months after diagnosis. Other factors of significant importance were: age and completion of chemotherapy course. Patients appeared to benefit from the combined regimen of optimal debulking surgery, completion of 12 courses of chemotherapy with the first course administered immediately after surgery and second look operation. Tumor type or histologic grade did not seem to influence results. The early use of chemotherapy was well tolerated and toxicity was minimal and acceptable.

The new International Federation of Gynecology and Obstetrics surgical staging and survival rates in early endometrial carcinoma.

The medical records of patients with clinical Stage I endometrial adenocarcinoma who were treated at the Maimonides Medical Center between October 1979 and October 1987 were reviewed. There was sufficient surgical-pathologic information to allow a reclassification based on the new International Federation of Gynecology and Obstetrics (FIGO) surgical staging in 93 patients. These are the subjects of analysis. Twenty-one patients (23%) were found surgically to have more than Stage I disease. The 5-year survival rate for the whole group (N = 93) was 90%. However, it was significantly better for patients with surgical Stage I disease (98%) than for patients with surgical Stage III disease (60%) (P less than 0.001). There was no significant statistical difference in survival among patients with different substages within surgical Stage I (i.e., IA, 100%; IB, 100%; and IC, 88%), whereas the distribution of adjuvant therapy among these substages was not statistically different (P = 0.17). Thus, survival was not significantly affected by depth of myometrial invasion in patients who had negative peritoneal washing and no involvement of lymph nodes or the peritoneal cavity.

Lymphvascular space involvement--a prognostic indicator in endometrial adenocarcinoma.

The present study evaluates the effects of various prognostic indicators on survival of patients with clinical Stage I endometrial carcinoma. Ninety-three patients who were treated for clinical Stage I endometrial adenocarcinoma at Maimonides Medical Center from October 1979 to October 1987 had sufficient surgical-pathological information for retrospective surgical staging according to the new FIGO classification. Histology was reviewed. A new grade and surgical stage was assigned to each patient in accordance with the recent FIGO guidelines for surgical staging of corpus cancer. Poor prognostic indicators, namely, tumor grade, depth of myometrial invasion, peritoneal cytology, lymph node metastases, and lymphvascular space (LVS) involvement, were correlated with 5-year survival rates. Survival rates were calculated by the life table method. Depth of myometrial invasion, lymph node involvement, and peritoneal cytology had significant statistical correlation with poor survival. Positive finding of each of the prognostic indicators, including LVS involvement, was significantly associated with poor survival (all P less than 0.001). The value of these prognostic indicators in early endometrial carcinoma is discussed.

Concomitant osteitis fibrosa cystica and ameloblastoma of the mandible.

A patient with a multiloculated cystic lesion of the mandible, and clinical as well as biological features of hyperparathyroidism is presented. This association suggesting the diagnosis of brown tumor was actually due to an ameloblastoma of the mandible. Such a concomitant association of an ameloblastoma with symptomatic hyperparathyroidism has never been reported to our knowledge.