Patient with unusual Hutchinson-Gilford syndrome (progeria)

A patient with unusual Hutchinson-Gilford syndrome (progeria) is reported. This 7-year-old boy had all the characteristics of progeria, except for coxa valga and the "horse-riding" stance. A previous cerebral infarction was detected in the right putamen on cranial magnetic resonance imaging. During treadmill exercise test electrocardiography, ST depression suggested the existence of arteriosclerotic lesions. Skin fibroblast culture exhibited 76% DNA-repair capacity compared to normal. He has not manifested endocrinologic abnormalities. From these findings it is concluded that this patient has an incomplete case of Hutchinson-Gilford syndrome and that a correlation may exist between the clinical features and the degree of DNA-repair capacity.     

Extragenital malignant mixed mesodermal tumor: case report and review of the literature

The hypothesis is presented that our life span is genetically programmed and that it is possible that a defect in produced proteins encoded by the 'longevity' gene is a cause of aging. A study of correlations between defective enzyme activity in two diseases characterized by premature aging (progeria and Werner's syndrome) could assist in elucidating the common mechanism for all aging processes.     

Aortic homograft and mitral valve repair in a patient with Werner's syndrome

We report the case of a 66-year-old man suffering from Werner's syndrome (adult progeria); he presented with several cardiac disorders, including coronary artery disease, aortic stenosis, and mitral regurgitation, mainly due to calcific deposits in the mitral annulus and the aortic cusps. Treatment consisted of mitral repair, homograft replacement of the aortic valve, and coronary artery bypass grafting. Avoidance of prosthetic material because of chronic infectious skin ulcers constituted the main goal of the operation.     

Surgical treatment for Scheie's syndrome (mucopolysaccharidosis type I-S): report of two cases

Scheie's syndrome (mucopolysaccharidosis type I-S) is a rare genetic lysosomal storage disease affecting mucopolysaccharide metabolism, and is known to include cardiovascular disease. Surgical treatment was carried out in 2 patients with Scheie's syndrome. Patient 1 was a 56-year-old man with triple-vessel coronary artery disease, who successfully underwent coronary artery bypass grafting. Patient 2 was a 52-year-old man with aortic and mitral valve stenosis, who successfully underwent combined aortic and mitral valve replacement. The literature on Scheie's syndrome associated with valvular and coronary artery disease is also reviewed.     

Changes of superoxide dismutase and lipid peroxide in lung tissue of rats after intratracheal injection of crocidolite and benzo(a) pyrene

Rambam-Hasharon syndrome (RHS) is a newly recognized autosomal recessive inborn error in fucose metabolism. Mental retardation, short stature, coarse facies, and recurrent infections are the main clinical findings. Several fucosilated proteoglycans are deficient in these patients. Leukocyte adhesion deficiency type 2 is associated with lack of the membrane glycoprotein sialyl-Lewisx (CD15s). In the red blood cells (RBCs), lack of the membrane glycoprotein H is manifested as a Bombay (Oh) blood type. Two consecutive pregnancies it risk for RHS were monitored during mid-trimester by cordocentesis. One fetus expressed H substance and her blood phenotype was O Rh+. The second fetus, a female, was 2 weeks smaller than expected by dates and had the Bombay blood type. The placenta of the affected fetus was small and irregular. This is the first prenatal diagnosis of this syndrome and the first case found in a female. The documentation of the syndrome in patients of both sexes and the parental consanguinity support an autosomal recessive inheritance. Two apparent recombinations between fucosyl-transferase 1 (FUT1, the H gene) and fucosyl-transferase 2 (secretor) are suggestive of non-allelic heterogeneity. We believe that the Bombay phenotype in this family is caused by a mutated gene, other than FUT1, which is causing multiple deficiencies of fucosilated proteoglycans.     

Severe hyperchloriduria-hyperkaliuria: a new congenital renal tubular abnormality?

A female infant, aged 5 weeks, had metabolic alkalosis associated with severe electrolyte disturbances. In addition to findings typically seen in patients with Bartter syndrome or hyperprostaglandin E syndrome, she had massive urinary excretion of prostaglandins E2 and E-M, normal calcium metabolism, hyperphosphaturia, and severe hyperchloriduria and hyperkaliuria with limited response to indomethacin. These findings may represent a new congenital renal tubular abnormality.     

The syndrome of inappropriate secretion of vasopressin (SIADH) (author's transl)

The syndrome of inappropriate ADH secretion ("SIADH") was first recognized 1935 by Roth et al. and described in detail 1957 by Schwartz et al. The clinical symptoms (hyponatremia, hypertonicity of urine and inability to excrete a water load) are caused by inadequately elevated ADH secretion under a variety of situations and diseases. Some recent work was focused on the pathogenesis of this syndrome and new clinical findings (low plasma levels of uric acid and potassium) as well as special forms ("SIADH" without elevated vasopressin levels in plasma) are thought to be of relevance. New therapeutical recommendations will be discussed.     

Antimicrobial effects of the macrocyclic Cu(II)-tetraanhydroaminobenzaldehyde complex

We report a case of a child with Noonan phenotype and incidental radiographic findings of mediastinal neuroblastoma. Recent studies have reported an increased association of Noonan syndrome with some malignancies, and the case we present here is the first reported case to our knowledge of an association of neuroblastoma with Noonan syndrome.     

Priapism following splenectomy in an unstable hemoglobin: hemoglobin Olmsted beta 141 (H19) Leu-->Arg

Approximately 10-20% of the reported patients with acute febrile neutrophilic dermatosis (Sweet's syndrome) have an associated neoplasm. Oral findings of Sweet's syndrome are rarely reported, and no cases in patients with oral cancer have been reported to date. This report describes the clinico- and histopathological findings of Sweet's syndrome in a patient with oral cancer, treated with radiotherapy. After 10 fractions of external beam radiotherapy, treatment was interrupted because of severe oral mucositis which extended beyond the radiation fields. Two days later the patient developed multiple tender skin lesions and the diagnosis Sweet's syndrome was made. Skin and oral lesions resolved without additional treatment and did not recur upon resuming radiotherapy. As suggested in previous case reports, tumour antigens might play a role in the development of Sweet's syndrome. In this case, irradiation therapy may also have been a trigger for this syndrome.     

Osteodysplasty (Melnick-Needles syndrome) (author's transl)

Authors report a new case of osteodisplasty (Melnick-Needles syndrome) and describe radiological findings that are typical of this entity: bony sclerosis of base structures, abnormal dental alignment, sclerosis and irregularity of clavicles and ribs, described as "band-like" deformity, cortical irregularity of tubular bones with metaphyseal flaring and diaphyseal bowing. Flat bones are broadened, particularly iliac crest and vertebral bones. Facial features described by the majority of authors in this entity are present in our patient in an incomplete form: craniofacial disproportion, micrognatia, depressed temples, exophthalmus (not in our patient) and broadened forehead. The paper is intended to gather clinical data of already reported cases in order to facilitate clinical research in the future from the immunological, genetical and biochemical points of view. Our patient has the same clinical history as the patient studied in the original paper. Dr. Melnick was kind enough to send us clinical data and autopsy findings.     

Polychlorinated biphenyls as a cause of sterility in women?

We report the ultrastructural and biochemical alterations of muscle mitochondria in two girls with Rett syndrome. Our findings suggest the presence of an energy metabolism impairment the primary or secondary role of which in the pathogenesis of this syndrome cannot be defined at present.     

Acute febrile neutrophilic dermatosis (Sweet's syndrome)

BACKGROUND: Sweet's syndrome is well recognized and not infrequently diagnosed in Spain; however, the range of clinical and pathologic expression may not have been fully realized. METHODS: We reviewed 30 consecutive Spanish cases of Sweet's syndrome diagnosed in our department from 1979 to 1990, with special attention to clinical and histopathologic findings. RESULTS: Distinctive clinical features in our series included oral mucosa lesions in four patients (13%), development of pathergy phenomenon in one case, concurrent nodular lesions resembling erythema nodosum on the limbs in nine cases (30%), and lung involvement in two patients. Infectious disease and drug treatment were recorded as possible triggering factors of Sweet's syndrome in eight and seven patients respectively. Associated underlying systemic disorders were present in 15 (50%) of our patients. The most frequent associations were hematologic neoplasia in four patients, solid neoplasia in two, and chronic idiopathic inflammatory bowel disease in three patients. Dressler's syndrome and sicca syndrome were found in one patient each. Histopathologic studies of skin biopsy specimens obtained at presentation disclosed typical features of Sweet's syndrome in all cases. Epidermal involvement, with variable degrees of spongiosis, exocytosis of polymorphonuclear leukocytes and keratinocyte necrosis, was a prominent feature in 83% of biopsy specimens. CONCLUSIONS: Further characterization of the clinicopathologic spectrum of Sweet's syndrome is necessary as the recognition of the full spectrum of this syndrome will improve our diagnostic abilities and provide a solid clinical basis for prospective studies that allow dissection of the intricate patho-mechanisms involved in this fascinating disorder.     

Report of a case of maxillo-nasal dysplasia (Binder syndrome)

The case of a girl with Binder syndrome (maxillonasal-dysplasia) is reported. The girl has a peculiar face due to severely depressed nasal bridge, the nasofrontal angle is absent and the nose is hypoplastic with flattened alae and nasal tip; the upper lip has a convex contour with poorly developed philtrum. The premaxillary is hypoplastic. Lateral and postero-anterior cephalometric findings are presented.     

Systematic growth studies, cocultivation, and cell hybridization studies of Werner syndrome cultured skin fibroblasts

The growth of 20 independently derived skin fibroblastlike (FL) cell strains from three individuals with Werner syndrome (adult progeria) was compared with the growth of ten FL cell strains from normal individuals. Population growth rates and total replicative life spans of Werner syndrome strains averaged 53% and 27%, respectively, of the growth rates and life spans of non-Werner strains. In the first few passages, four Werner syndrome strains demonstrated population growth rates in the low normal range, but the longest-lived Werner syndrome strain had only 75% of the total replicative potential of the shortest-lived normal strain. Exponential growth rates, cloning efficiencies, and saturation densities of Werner strains were also reduced, whereas cell attachment was normal. Viable cells (identified by dye exclusion) were maintained in post-replicative Werner syndrome and control cultures for periods of at least 10 months; there was no evidence of accelerated post-replicative senescence of cell death of Werner syndrome FL cells. Cocultivation of Werner syndrome and normal strains did not influence population growth rates of either strain. Two proliferating hybrid clones were obtained from fusions of normal and Werner syndrome FL cell strains and these hybrids displayed the reduced growth potential typical of Werner syndrome FL cells. These studies confirm that low growth rate and sharply reduced replicative life span are characteristic of cultured skin FL cells from patients with Werner syndrome, and they suggest that these characteristics are not affected by complementation with non-Werner FL cells.     

Syringomyelia in mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome): imaging findings following bone marrow transplantation

We present the imaging findings in a patient with mucopolysaccharidosis (MPS) type VI (Maroteaux-Lamy syndrome) who developed holocord syringomyelia. This represents the only reported case of syrinx formation in a child with MPS VI. Clinical, neurologic and spinal magnetic resonance imaging findings are presented. The patient has maintained a stable clinical and neurologic course over the period following allogeneic bone marrow transplant.     

A review of allergic granulomatous angitis (AGA) (Churg-Strauss syndrome)

We reported clinical features of 11 patients with Churg-Strauss syndrome (CSS). Subjects included 2 males and 9 females with a mean age of 56.3 year-old. The age of the onset of bronchial asthma was high, and most of the patients had been suffered from frequent and severe asthmatic attacks during the period preceding the vasculitis. At the onset of the disease, patients showed a variety of vasculitic symptoms, including fever and neuropathy. Peripheral blood eosinophilia was universally seen. Three patients died of heart failure or central nerve involvement. Vasculitis ameliorated in 8 cases following steroid treatment. Discontinuing maintenance therapy with low-dose steroid resulted in a relapse in only one case. The significance and indication for long-term maintenance therapy should be further clarified. Based on these findings and previous publications, the clinical characteristics of CSS in Japan are discussed.     

Anesthesia in Kearns-Sayre syndrome (mitochondrial myopathy)

We report the case of a 27-year-old woman with a history of Kearns-Sayre syndrome and a double mitral lesion who underwent surgery without complications. Anesthetic induction was achieved with propofol and fentanyl, and maintenance was with nitrous oxide and oxygen through a face mask. There were no instances of O2 desaturation or hemodynamic alterations. The postoperative period transpired without adverse events and the patient was released 24 h after surgery. The management of anesthesia in this rare mitochondrial disease is described, and anesthetic alternatives are discussed as depending on clinical findings that can occur in the context of these syndromes.     

Effects of isometric exercise (handgrip) on the respiratory system]

Sixteen consecutive adult cases of Parinaud's syndrome are reviewed. Ten of the sixteen cases were due to brain stem infarction while four patients were suspected of harboring tumors. Parinaud's syndrome alone did not favor a diagnosis of tumor in the pineal region in this series. Associated neuroophthalmic findings are discussed.     

Metabolism of the antiandrogenic drug (Flutamide) by human CYP1A2

The antiandrogenic drug, flutamide, is widely used in the treatment of carcinoma of the prostate. The present study examines the metabolism of flutamide by human liver microsomes and purified recombinant human cytochrome P450s (CYP), expressed as fusion proteins. These studies show the principal role of CYP1A2 in the metabolism of flutamide to 2-hydroxyflutamide. A minor metabolite is formed during the metabolism of flutamide by CYP3A4 in the presence of an excess of added purified NADPH-P450 reductase. The metabolism of flutamide is inhibited by low concentrations of alpha-naphthoflavone and ketoconazole. Other substrates of CYP1A2, such as phenacetin, imipramine, caffeine, and estradiol, are also inhibitors of flutamide metabolism by CYP1A2. Of interest is the inhibition of flutamide metabolism by its metabolite, 2-hydroxyflutamide, and the inhibition of the 2- and 4- hydroxylation of estradiol by flutamide. CV1 cells do not metabolize flutamide to 2-hydroxyflutamide. In assays performed using this cell line transfected with the cDNA for the androgen receptor, flutamide is a pure antagonist, and 2-hydroxyflutamide, while a more potent androgen receptor (AR) antagonist, activates the AR at higher concentrations. Stable expression of CYPIA2 in these CV1 cells causes flutamide to exhibit agonistic properties at higher concentrations, a behavior not exhibited by cells stably transfected only with the expression vector encoding the AR. These findings raise the possibility that increased conversion of flutamide to 2-hydroxyflutamide or accumulation of 2-hydroxyflutamide in cells may contribute to the anomalous responses to flutamide that are observed in some advanced prostate cancers.     

Additional post-mortem examination techniques to detect patho-morphological findings of nose and throat in cases of sudden infant death syndrome (SIDS) (author's transl)

To detect histopathological findings in nose and throat. These methods are especially advisable in cases of sudden infant death syndrome, as it could be proved, that in 25 of 30 in this manner examined cases there were inflammatory processes of different extent up to necrotic rhinitis. The morphological findings as well as the accompanying information of anamnesis and the bacteriological findings are discussed. We consider, it advisable, to make use of the described additional investigational methods.