Polymorphisms in candidate genes for type 2 diabetes mellitus in a Mexican population with metabolic syndrome findings.

The metabolic or insulin resistance syndrome, characterized by hypertension, dyslipidemia, glucose intolerance and hyperinsulinemia, may have genetic determinants. The insulin gene (INS), insulin receptor gene (INSR) and insulin receptor substrate 1 gene (IRS1) have been proposed as candidate genes. We examined eight polymorphisms in these genes in 163 individuals from Yucatan, Mexico; this population has a high prevalence of obesity, type 2 diabetes mellitus and dyslipidemia. Subjects were evaluated for body mass index (BMI) and blood pressure. Blood samples were collected to determine glucose, insulin, triglycerides and cholesterol levels, as well as for DNA isolation. Restriction fragment length polymorphisms in INS, INSR and IRS1 were identified by polymerase chain reaction and digestion with selected restriction enzymes. Among the eight polymorphisms analyzed, the PstI polymorphism in INS was significantly associated with hypertriglyceridemia and with the presence of at least one abnormality related to the metabolic syndrome (P=0.007 and 0.004, respectively). The MaeIII polymorphism in INS was associated with fasting hyperinsulinemia (P=0.045). In multilocus analyses including both INS polymorphisms, significant associations were seen with hypertriglyceridemia (P=0.006), hypercholesterolemia (P=0.031) and with presence of at least one metabolic abnormality (P=0.009). None of the polymorphisms in INSR or IRS1 was associated with any of these traits. These findings suggest that the insulin gene may be an important determinant of metabolic syndrome, and particularly of dyslipidemia, in this population.

Cerebral tumor-like American trypanosomiasis in acquired immunodeficiency syndrome.

Cerebral tumor-like American trypanosomiasis (CTLAT) is an uncommon complication of Chagas' disease, observed only in immunosuppressed patients. We assessed 10 human immunodeficiency virus-positive patients with Chagas' disease who presented with CTLAT. All patients had neurological involvement and 6 developed intracranial hypertension. Neuroimaging studies showed supratentorial lesions in 9 patients, being single in 8. One case had infratentorial and supratentorial lesions. Low CD4+ cell counts were observed in all the cases and in 6 of them CTLAT was the first manifestation of acquired immunodeficiency syndrome. Serological tests for Chagas' disease were positive in 6 of 8 patients. Trypanosoma cruzi was identified in all brain specimens and in three cerebrospinal fluid samples. CTLAT should be considered in the differential diagnosis of intracranial mass lesions in human immunodeficiency virus-positive patients and should be added to the list of acquired immunodeficiency syndrome-defining illnesses.

[Hypopituitarism caused by colonic carcinoma metastasis associated with hypophysial aspergillosis]. / Hipopituitarismo originado por metástasis de carcinoma de colon asociado con aspergilosis hipofisaria.

Pituitary metastases constitute 1% to 8.3% of all metastatic brain tumors. The most frequent localization is in the posterior lobe and diabetes insipidus may be the only symptom of dysfunction. Cerebral aspergillosis is an unusual disease and it has been described complicating an underlying malignancy or following intracraneal surgery. We describe a case of hypopituitarism and hyperprolactinemia in a patient with pituitary metastases of a colon carcinoma and aspergillosis. Two years before a colon adenocarcinoma (Class C1 of Duke) had been resected. There were no clinical signs of hypopituitarism or galactorrea. The laboratory findings showed deficiency of cortocotropin (ACTH), luteinizing hormone (LH), follicle stimulating hormone (FSH) and slight hyperprolactinemia (PRL). Cerebral magnetic resonance image (MRI) revealed an intra and suprasellar mass which extended to the hypothalamus. Chest X-ray film and computed tomographic scanning (TC) confirmed a macronodular mass at the apical segment of the inferior left lung lobule with mediastinal hypertrophic lymph nodes. A non functional pituitary tumor was diagnosed and transphenoidal surgery was carried out. At microscopic examination a malignant proliferation was found suggesting colonic differentiation. Fragments of tumoral pituitary tissue showed hyphae of aspergillus in the form of abscess. Aspergillosis complicating neoplastic disease is more often present in leukemia and lymphoma than in solid tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Hipopituitarismo originado por metastasis de carcinoma de colon asociado con aspergilosis hipofisaria / Hypopituitarism originating to colonic carcinoma metastasis associated with hypophysial aspergillosis

Las metástasis hipofisiarias constituyen el 1 al 8,3 por ciento del total de tumores metastásicos cerebrales. La localización más frecuente es en el lóbulo posterior y la diabetes insípida puede ser el único síntoma de disfunción. La aspergilosis cerebral es una enfermedad inusual y ha sido descripta complicando una malignidad preexistente, o posteriormente a una cirugía intracraneal. Describimos un hipopituitarismo e hiperprolactinemia en una paciente quien presentó metástasis hipofisarias de un carcinoma de colon y aspergilosis coexistente. Dos años antes, se le había resecado un adenocarcinoma de colon (clase Cl de Duke). Ningún signo clínico de hipopituitarismo o galactorrea estaban presentes. Los hallazgos de laboratorio reflejan déficit de corticotrofina (ACTH), hormona luteinizante (LH), hormona folículo estimulante (FSH), y una leve hiperprolactinemia (PRL). Una resonancia magnética cerebral reveló una massa intra y supraselar la cual se extendía a hipotálamo. La radiografía de tórax y la tomografía computada confirmó una massa macronodular en el segmento apical del lóbulo pulmonar inferior izquierdo con nódulos hipertróficos meidastinales. Fue diagnosticado un tumor hipofisario no funcionante realizándose cirugía transfenoidal. El examen microscópico confirmó una proliferación maligna que sugería diferenciación colónica. Fragmentos de tejido ipofisário tumoral mostraron hifas de aspergilus formando abscesos. La aspergilosis como complicación de enfermedades neoplásicas, es mayor en leucemias y linfomas que en tumores sólidos. El diagnóstico de aspergilosis del SNC es dificultoso, siendo éste generalmente confirmado durante la necropsia. Esta localización puede aparecer como parte de una aspergilosis diseminada, o como una infección única del SNC, aunque la mayoría de los casos está asociada a una aspergilosis pulmonar. Hasta la fecha, no hemos encontrado publicada la asociación de hipopituitarismo y moderada hiperprolactinemia cuya etiología fue metástasis hipofisaria de carcinoma de colon y aspergilosis coexistente

Hipopituitarismo originado por metástasis de carcinoma de colon asociado con aspergilosis hipofisaria. / [Hypopituitarism caused by colonic carcinoma metastasis associated with hypophysial aspergillosis]

Pituitary metastases constitute 1

to 8.3

of all metastatic brain tumors. The most frequent localization is in the posterior lobe and diabetes insipidus may be the only symptom of dysfunction. Cerebral aspergillosis is an unusual disease and it has been described complicating an underlying malignancy or following intracraneal surgery. We describe a case of hypopituitarism and hyperprolactinemia in a patient with pituitary metastases of a colon carcinoma and aspergillosis. Two years before a colon adenocarcinoma (Class C1 of Duke) had been resected. There were no clinical signs of hypopituitarism or galactorrea. The laboratory findings showed deficiency of cortocotropin (ACTH), luteinizing hormone (LH), follicle stimulating hormone (FSH) and slight hyperprolactinemia (PRL). Cerebral magnetic resonance image (MRI) revealed an intra and suprasellar mass which extended to the hypothalamus. Chest X-ray film and computed tomographic scanning (TC) confirmed a macronodular mass at the apical segment of the inferior left lung lobule with mediastinal hypertrophic lymph nodes. A non functional pituitary tumor was diagnosed and transphenoidal surgery was carried out. At microscopic examination a malignant proliferation was found suggesting colonic differentiation. Fragments of tumoral pituitary tissue showed hyphae of aspergillus in the form of abscess. Aspergillosis complicating neoplastic disease is more often present in leukemia and lymphoma than in solid tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Hipopituitarismo originado por metastasis de carcinoma de colon asociado con aspergilosis hipofisaria / Hypopituitarism originating to colonic carcinoma metastasis associated with hypophysial aspergillosis

Las metástasis hipofisiarias constituyen el 1 al 8,3 por ciento del total de tumores metastásicos cerebrales. La localización más frecuente es en el lóbulo posterior y la diabetes insípida puede ser el único síntoma de disfunción. La aspergilosis cerebral es una enfermedad inusual y ha sido descripta complicando una malignidad preexistente, o posteriormente a una cirugía intracraneal. Describimos un hipopituitarismo e hiperprolactinemia en una paciente quien presentó metástasis hipofisarias de un carcinoma de colon y aspergilosis coexistente. Dos años antes, se le había resecado un adenocarcinoma de colon (clase Cl de Duke). Ningún signo clínico de hipopituitarismo o galactorrea estaban presentes. Los hallazgos de laboratorio reflejan déficit de corticotrofina (ACTH), hormona luteinizante (LH), hormona folículo estimulante (FSH), y una leve hiperprolactinemia (PRL). Una resonancia magnética cerebral reveló una massa intra y supraselar la cual se extendía a hipotálamo. La radiografía de tórax y la tomografía computada confirmó una massa macronodular en el segmento apical del lóbulo pulmonar inferior izquierdo con nódulos hipertróficos meidastinales. Fue diagnosticado un tumor hipofisario no funcionante realizándose cirugía transfenoidal. El examen microscópico confirmó una proliferación maligna que sugería diferenciación colónica. Fragmentos de tejido ipofisário tumoral mostraron hifas de aspergilus formando abscesos. La aspergilosis como complicación de enfermedades neoplásicas, es mayor en leucemias y linfomas que en tumores sólidos. El diagnóstico de aspergilosis del SNC es dificultoso, siendo éste generalmente confirmado durante la necropsia. Esta localización puede aparecer como parte de una aspergilosis diseminada, o como una infección única del SNC, aunque la mayoría de los casos está asociada a una aspergilosis pulmonar. Hasta la fecha, no hemos encontrado publicada la asociación de hipopituitarismo y moderada hiperprolactinemia cuya etiología fue metástasis hipofisaria de carcinoma de colon y aspergilosis coexistente (AU)

[Schwannomatosis: report of a new case]. / Schwannomatosis: presentacion de un nuevo caso.

Schwannomatosis is a rare disorder, still not quite well defined, seldom described in the literature. In this paper we report the case of male. Patient, 52 years old, who in the last 30 years developed five subcutaneous tumors within his limbs peripheral nerves, which histologically proved to be schwannomas. A brain computed tomography showed a partially calcified tumor in the left temporal lobe which most likely was a meningioma. A thorough clinical examination was unable to find signs of type I or type II neurofibromatosis. The present condition, probably a form of phacomatosis, has to be distinguished from neurofibromatosis and is considered as an independent clinical entity whose origin still awaits further detailed investigations.

[Chronic hexosaminidase A deficiency associated with pure sensory peripheral neuropathy]. / Deficiencia crónica de hexosaminidasa A asociada a neuropatía periférica sensitiva pura.

One patient with hexosaminidase A (Hx A) deficiency, which produces GM2 gangliosidosis, developed a complex progressive neurological syndrome, starting when he was 10 years old, which encompassed intellectual impairment, cerebellar involvement, features of upper and lower motoneurones compromise and sensory neuropathy without signs of motor fibre damage within the peripheral nerves. Sural nerve biopsy demonstrated loss of myelinated fibres, mainly of those of large and small diameters, clusters of small diameter fibres, fibres with abnormal thin myelin sheaths related to their axonal diameters, axonal degeneration, segmental and paranodal demyelination and remyelination. Electronmicroscopic examination showed small electrondense, non specific, bodies and concentric lamellar inclusions within the cytoplasm of the Schwann cells. These findings demonstrate that pure sensory peripheral neuropathy should be considered as part of the spectrum which may result from Hx A deficiency.

Deficiencia cronica de hexosaminidasa A asociada a neuropatia periferica sensitiva pura / Chronic hexosaminidase A deficiency associated to pure sensory peripheral neuropathy

Se presenta a un paciente con deficiencia de hexosaminidasa A (Hx A), que conduce a la gangliosidosis GM2, que desarrolla un cuadro neurológico progresivo cuyo comienzo pudo fijarse a los 10 años y que se caracterizó por deterioro intelectual, compromiso cerebeloso, alteración de neuromas motoras superior e inferior y neuropatía sensitiva sin aparente compromiso de las fibras motoras que integran el nervio mixto. La biopsia del nervio safeno externo mostró pérdida de fibras mielínicas, en especial de aquellas de mayor y menor diámetro, agrupamiento axonal, axones con cubiertas mielínicas anormalmente finas en relación con su diámetro, degeneración axonal, desmielinización segmentaria y paranodal y remielinización. La microscopia electrónica reveló cuerpos de inclusión electrodensos no específicos e incusiones laminares concéntricas dentro del citoplasma de las células de Schwann. Los hallazgos hechos señalan que la neuropatía sensitiva pura puede formar parte del espectroclínico de la deficiencia de HxA

Deficiencia crónica de hexosaminidasa A asociada a neuropatía periférica sensitiva pura. / [Chronic hexosaminidase A deficiency associated with pure sensory peripheral neuropathy]

One patient with hexosaminidase A (Hx A) deficiency, which produces GM2 gangliosidosis, developed a complex progressive neurological syndrome, starting when he was 10 years old, which encompassed intellectual impairment, cerebellar involvement, features of upper and lower motoneurones compromise and sensory neuropathy without signs of motor fibre damage within the peripheral nerves. Sural nerve biopsy demonstrated loss of myelinated fibres, mainly of those of large and small diameters, clusters of small diameter fibres, fibres with abnormal thin myelin sheaths related to their axonal diameters, axonal degeneration, segmental and paranodal demyelination and remyelination. Electronmicroscopic examination showed small electrondense, non specific, bodies and concentric lamellar inclusions within the cytoplasm of the Schwann cells. These findings demonstrate that pure sensory peripheral neuropathy should be considered as part of the spectrum which may result from Hx A deficiency.

Deficiencia crónica de hexosaminidasa A asociada a neuropatía periférica sensitiva pura. / [Chronic hexosaminidase A deficiency associated with pure sensory peripheral neuropathy]

One patient with hexosaminidase A (Hx A) deficiency, which produces GM2 gangliosidosis, developed a complex progressive neurological syndrome, starting when he was 10 years old, which encompassed intellectual impairment, cerebellar involvement, features of upper and lower motoneurones compromise and sensory neuropathy without signs of motor fibre damage within the peripheral nerves. Sural nerve biopsy demonstrated loss of myelinated fibres, mainly of those of large and small diameters, clusters of small diameter fibres, fibres with abnormal thin myelin sheaths related to their axonal diameters, axonal degeneration, segmental and paranodal demyelination and remyelination. Electronmicroscopic examination showed small electrondense, non specific, bodies and concentric lamellar inclusions within the cytoplasm of the Schwann cells. These findings demonstrate that pure sensory peripheral neuropathy should be considered as part of the spectrum which may result from Hx A deficiency.

Deficiencia cronica de hexosaminidasa A asociada a neuropatia periferica sensitiva pura / Chronic hexosaminidase A deficiency associated to pure sensory peripheral neuropathy

Se presenta a un paciente con deficiencia de hexosaminidasa A (Hx A), que conduce a la gangliosidosis GM2, que desarrolla un cuadro neurológico progresivo cuyo comienzo pudo fijarse a los 10 años y que se caracterizó por deterioro intelectual, compromiso cerebeloso, alteración de neuromas motoras superior e inferior y neuropatía sensitiva sin aparente compromiso de las fibras motoras que integran el nervio mixto. La biopsia del nervio safeno externo mostró pérdida de fibras mielínicas, en especial de aquellas de mayor y menor diámetro, agrupamiento axonal, axones con cubiertas mielínicas anormalmente finas en relación con su diámetro, degeneración axonal, desmielinización segmentaria y paranodal y remielinización. La microscopia electrónica reveló cuerpos de inclusión electrodensos no específicos e incusiones laminares concéntricas dentro del citoplasma de las células de Schwann. Los hallazgos hechos señalan que la neuropatía sensitiva pura puede formar parte del espectroclínico de la deficiencia de HxA (AU)

Type 2 neurofibromatosis with Lisch nodules.

We describe a patient who, throughout a period of 6 years, had several cranial tumors in different locations. Bilateral acoustic neuromas, frontal meningiomas and a brain stem schwannoma were found on clinical and CT scan examinations and were histologically confirmed after surgery. These findings were associated with cutaneous neurofibromas and large café au lait spots suggesting the diagnosis of neurofibromatosis (NF) type 2. However, the presence of Lisch nodules, which characterizes NF-1, makes this patient rather unique. Clinical findings in the patient's relatives suggested the existence of NF-1 within the family. That is, the patient combines features of both types of NF.

The role of prenylamine in the prevention of adriamycin-induced cardiotoxicity. A review of experimental and clinical findings.

Experimental and clinical trials to determine the potential of prenylamine in the prevention of adriamycin-related cardiotoxicity are reviewed. In mice given 4 mg/kg body weight adriamycin, the incidence of myocardial damage after 19 days' treatment was lower than in those given adriamycin and placebo. Rabbits were given adriamycin (total dose 10.8 mg/kg body weight), adriamycin plus prenylamine (1.5 mg/kg body weight), and adriamycin plus vitamins A (250 IU) and E (40 mg) for 9-11 weeks. Adriamycin-induced electrocardiogram changes were observed to a lesser extent in animals also receiving prenylamine. Heart homogenates from adriamycin-treated animals showed enhanced hydroperoxide-initiated chemiluminescence which was not affected by the simultaneous administration of prenylamine. The extent of adriamycin-induced myocytolysis and the degree of alterations observed on electron microscopy were markedly reduced by prenylamine. In a double-blind clinical trial with 26 oncological patients, no cardiomyopathy, arrhythmia or adverse reactions were observed in the group given adriamycin plus prenylamine. In those given adriamycin plus placebo, two patients developed congestive cardiopathy and another showed severe supraventricular arrhythmias together with hypotension and dyspnoea. The mechanisms of adriamycin-related cardiotoxicity, the effects of prenylamine and the benefit from combined treatment are discussed.

Histopathology of the heart conducting system in experimental Chagas disease in mice.

Although mice infected with Trypanosoma cruzi develop a wide variety of electrocardiographic (ECG) alterations, the typical isolated right bundle branch block or its association with the left anterior hemiblock patterns are not found in this model. This has been explained as related to topographic differences in the anatomy of the murine conducting system. However, there is no conclusive evidence that the murine conducting system differs from the human system. In this study, the anatomy of the murine conducting system is described, as well as its involvement in the chronic stages of experimental infection. 24 three-month-old C3H mice were infected with 50 bloodstream forms of T. cruzi, Tulahuén strain. Animals were killed after 3, 8 and 12 months. Whole frontal sections of the heart, including the conducting system, were serially studied. The sinoatrial node was located in the right atrial appendage, or in the junction between the superior vena cava and the right atrium, or "riding" on the interatrial septum. The atrioventricular (A-V) node and the His bundle showed a similar anatomic course to that in man. Therefore, there was no important anatomical difference that might have explained the lack of the ECG patterns observed in human chagasic myocardiopathy. The inflammatory involvement and the lesions of the conducting system were diverse and rarely severe. No significant difference was observed in animals killed at different times. The lesions in the working myocardium were similar to those observed in humans (chronic inflammatory infiltrates). Nevertheless, the topography of lesions was different: there was a selective involvement in the neighbourhood of the A-V groove.(ABSTRACT TRUNCATED AT 250 WORDS)

The neuromuscular pathology of experimental Chagas' disease.

In this work, we describe skeletal muscle, neuromuscular junction, nerve and spinal cord lesions in the mouse model system of Chagas' disease. Myositis was a common finding and Trypanosoma cruzi amastigote nests were frequently found in the muscle fibers. Angular atrophy, targetoid fibers, groups of atrophic fibers, fibrosis, myofiber necrosis and phagocytosis of cellular debris were also observed. The neuromuscular junction studies showed degeneration of intramuscular nerve fibers, swelling and distortion of nerve endings and multiple ramifications on the same muscle fiber. Collateral, terminal and ultraterminal axonal sprouts were also present. Inflammatory neuropathy was seen in all of the infected mice. Demyelination, axonal degeneration, remyelination and axonal regeneration were observed in the transverse sections. There was an average reduction of 29% in the total number of myelin fibers. The teasing of single myelin fibers showed segmental and paranodal demyelination and remyelination more frequently than axonal degeneration and regeneration. The lumbar spinal cords presented inflammatory cell infiltration associated with tissue destruction. Amastigote nests were found in 3 out of the 8 infected mice studied. There was a mean loss of 21% of the large cytoneurons of the anterior horn of the lumbar spinal cord.

Involvement of the peripheral sensory nervous system in human chronic Chagas disease

Veintitrés pacientes con el diagnóstico de enfermedad de Chagas, en estadio crónico, fueron estudiados electrofisiológicamente investigándose la velocidad de conducción sensitiva segmentaria y la amplitud del potencial sensitivo en el nervio mediano. También se exploró, con electrodos de aguja, el número de deflexiones que integraban el potencial sensitivo obtenido en los nervios mediano y safeno externo. Se observó disminución de la velocidad de conducción en el segmento distal del nervio mediano y reducción de la amplitud del potencial sensitivo a lo largo de todo el tronco nervioso en el grupo de pacientes. Por otra parte, el número de deflexiones que componían el potencial sensitivo estuvo significativamente reducido, tanto en el mediano como en el safeno externo, en el grupo enfermo. Como complemento de lo anterior se efectuó el estudio histológico del nervio safeno externo en cuatro pacientes hallándose pérdida axonal, desmielinización segmentaria y degeneración walleriana. Las observaciones hechas señalan que en la fase crónica de la enfermedad de Chagas humana puede producirse el compromiso de las fibras sensitivas que integran el nervio mixto, posiblemente debido a daño combinado del cuerpo de las neuronas del ganglio de la raíz dorsal y de los axones que de ellas emergen

Involvement of the peripheral sensory nervous system in human chronic Chagas disease

Veintitrés pacientes con el diagnóstico de enfermedad de Chagas, en estadio crónico, fueron estudiados electrofisiológicamente investigándose la velocidad de conducción sensitiva segmentaria y la amplitud del potencial sensitivo en el nervio mediano. También se exploró, con electrodos de aguja, el número de deflexiones que integraban el potencial sensitivo obtenido en los nervios mediano y safeno externo. Se observó disminución de la velocidad de conducción en el segmento distal del nervio mediano y reducción de la amplitud del potencial sensitivo a lo largo de todo el tronco nervioso en el grupo de pacientes. Por otra parte, el número de deflexiones que componían el potencial sensitivo estuvo significativamente reducido, tanto en el mediano como en el safeno externo, en el grupo enfermo. Como complemento de lo anterior se efectuó el estudio histológico del nervio safeno externo en cuatro pacientes hallándose pérdida axonal, desmielinización segmentaria y degeneración walleriana. Las observaciones hechas señalan que en la fase crónica de la enfermedad de Chagas humana puede producirse el compromiso de las fibras sensitivas que integran el nervio mixto, posiblemente debido a daño combinado del cuerpo de las neuronas del ganglio de la raíz dorsal y de los axones que de ellas emergen (AU)