Metabolites as novel biomarkers for childhood obesity-related traits in Mexican-American children.

BACKGROUND/OBJECTIVES: Although newer approaches have identified several metabolites associated with obesity, there is paucity of such information in paediatric populations, especially among Mexican-Americans (MAs) who are at high risk of obesity. Therefore, we performed a global serum metabolite screening in MA children to identify biomarkers of childhood obesity. METHODS: We selected 15 normal-weight, 13 overweight and 14 obese MA children (6-17 years) and performed global serum metabolite screening using ultra-performance liquid chromatography/quadruple orthogonal acceleration time of flight tandem micro mass spectrometer. Metabolite values were analysed to assess mean differences among groups using one-way analysis of variance, to test for linear trend across groups and to examine Pearson's correlations between them and seven cardiometabolic traits (CMTs): body mass index, waist circumference, systolic blood pressure, diastolic blood pressure, homeostasis model of assessment-insulin resistance, triglycerides and high-density lipoprotein cholesterol. RESULTS: We identified 14 metabolites exhibiting differences between groups as well as linear trend across groups with nominal statistical significance. After adjustment for multiple testing, mean differences and linear trends across groups remained significant (P < 5.9 × 10(-5) ) for L-thyronine, bradykinin and naringenin. Of the examined metabolite-CMT trait pairs, all metabolites except for 2-methylbutyroylcarnitine were nominally associated with two or more CMTs, some exhibiting significance even after accounting for multiple testing (P < 3.6 × 10(-3) ). CONCLUSIONS: To our knowledge, this study - albeit pilot in nature - is the first study to identify these metabolites as novel biomarkers of childhood obesity and its correlates. These findings signify the need for future systematic investigations of metabolic pathways underlying childhood obesity.

Risks to Colombian amphibian fauna from cultivation of coca (Erythroxylum coca): a geographical analysis.

The Colombian amphibian fauna is among the richest known in the world, with about 20 species of salamanders (order Caudata), 35 of the limbless caecilians (order Gymnophiona), and more than 700 species of frogs and toads (order Anura) recorded from localities within the country. The potential effects of exposure to glyphosate on amphibians arising from production of illegal crops (coca) were examined. The analysis was based on (1) behavior and ecology of species and (2) proximities of actual museum records to localities in which illegal crops are being grown and the subset of those that have been sprayed with glyphosate. Based on data on the location of amphibians collected in Colombia, records were obtained for 193 species (28% of the national diversity) of frogs and toads found in localities within 10 km of areas where coca is grown. Further analyses with ARC MAP software allowed for measurement of the direct distance separating collection locations for frogs, known coca fields, and areas where aerial spraying was being conducted. Records in or near coca fields included data for 11 of 13 families of frogs and toads known to be present in Colombia. Only Ceratophryidae and Pipidae were not reported from these locations and appear not to be at risk. For eight species (Dendrobates truncatus, Craugastor raniformis, Pristimantis gaigeae, Smilisca phaeota, Elachistocleis ovale, Hypsiboas crepitans, Trachycephalus venulosus, and Pseudis paradoxa) selected to represent several habitat preferences and life-cycle strategies, large areas of their distributions lie outside coca production regions and their populations as a whole are at low risk. For a limited number of species that barely enter Colombian territory, the consequences of coca production may be more serious and may have placed several species of frogs at risk. These include Ameerega bilingua, Dendropsophus bifurcus, Pristimantis colomai, P. degener, P. diadematus, P. quaquaversus, P. variabilis, and Trachycephalus jordani. Other species may also be at risk but exact numbers are unknown since few investigations were undertaken in these areas during the past 30 yr. The main ranges for these species were assumed to be in Ecuador.

Effects of socioeconomic change from birth to early adulthood on height and overweight.

BACKGROUND: In this work we explored the association of height and overweight with change in socioeconomic position between birth and 19 years of age. METHODS: A birth cohort has been followed-up in Pelotas, Brazil, since 1982. All 5914 hospital births were enrolled in the study just after delivery. In 2001, 27% of the cohort subjects were sought, and 1031 (69% of the survivors) were interviewed. Weight and height were obtained for women; men had been examined 6 months earlier. Information on family income in 1982 and 2001 was used to classify the sample into tertiles, the lowest classified as 'poor' and the other two as 'non-poor'. Four trajectories resulted: always poor, never poor, poor at birth/non-poor at 19, and non-poor at birth/poor at 19-which were compared in terms of mean height and prevalence of overweight. RESULTS: Height showed a similar behaviour for men and women, with the never poor presenting the highest mean, followed by those who were non-poor at birth and later became poor. Those who were poor at birth, regardless of later status, were shortest. Overweight was approximately twice as common among men who were never poor in relation to the others. Among women, those who were always poor presented the highest prevalence of overweight. In this case, social determination seems to be complex and may involve aspects of lifestyle and behaviour acting differently for each gender. CONCLUSION: Socioeconomic trajectories affected both height and overweight, the effect on the latter being different for each gender.

Hereditary nonpolyposis colorectal cancer (Lynch syndrome II) in Uruguay.

PURPOSE: We updated an Uruguayan family with hereditary nonpolyposis colorectal cancer first described in 1977, incorporating knowledge of how the hMLH1 germline mutation has been established and shown to segregate in accord with the expected autosomal dominant mode of genetic transmission. METHODS: DNA-based molecular genetic testing was performed in conjunction with genetic counseling. Individuals were provided with their genetic test results, so that at-risk family members would be able to benefit from targeted management programs. RESULTS: We counseled 19 members of this kindred, 13 of whom were positive for the hMLH1 germline mutation. Specific recommendations for surveillance and management were provided. We were able to describe follow-up, including anecdotal cancer survival and pathology findings extending from the initial 1977 report of this family to the present. A remarkable sibship within this kindred was comprised of eight siblings, six of whom underwent resections for colorectal carcinoma between 1963 and 1971. Colon carcinomas before 1977 in this sibship were treated with classic hemicolectomies. Of those who had hemicolectomies for their first primary colorectal cancers, two had a second colon cancer primary, and two had a third colon cancer primary. CONCLUSIONS: Attention given to this extended family with hereditary nonpolyposis colorectal cancer has had a positive impact on the physician community in Uruguay, leading to the identification of additional families with hereditary nonpolyposis colorectal cancer.

Outcome of 337 intracranial aneurysms patients operated in a public hospital.

Many recent series of surgery for intracranial aneurysms have been based on experience of developed countries with great resources and a state of art health care. The purpose of the current study is to correlate the outcome of patients operated for intracranial aneurysms, reported from intensive high technology neurosurgical centers with the results of low technology, environment, where we practice. Between January 1986 and December 1996, 337 patients with intracranial aneurysms were operated on at the Servidores do Estado Hospital. We retrospectively reviewed the medical and radiologic records and compared the outcome of this group with other series derived from developed countries. The overall mortality of this series was 6.9%. Of the 313 good grades surgical patients, the mortality was 4.7% and the successful results were obtained in 88.8% individuals. We conclude that patients harboring intracranial aneurysms can be satisfactory handled in less developed nations, if a meticulous intraoperative technique is employed, even though sophisticated technology and equipment are not available.

[Intracranial cavernous angioma]. / Angioma cavernoso intracraniano.

Clinical, radiological and histopathological features of eight cases of symptomatic cavernous angioma are presented. Five patients were being evaluated for seizure, two for mass lesions and one for intracranial hemorrhage. CT and/or MRI detected the lesion in all cases, but there is not a characteristic image for cavernous angioma. Good results were obtained by microsurgical approach to these malformations in seven patients with only one patient suffering a worsening of neurological status after surgery.

Lipoprotein(a) and apolipoproteins B and A-1 in children and coronary vascular events in their grandparents.

Because premature coronary vascular disease in a first-degree relative increases risk of the disease and the mechanisms may include genetically determined abnormal levels of circulating apolipoproteins, we explored the relationships between schoolchildren's apolipoprotein levels and coronary events in their parents and grandparents. We measured capillary blood concentrations of lipoprotein(a) (Lp(a) and apolipoproteins (apo B and apo A-1) in dried blood spot samples obtained by finger prick from 2010 schoolchildren aged 8 to 12 years, and questioned parents about coronary vascular events in the children's parents and grandparents. Of the 2010 questionnaires sent, 1030 (51%) were returned fully completed. Twenty-three fathers, one mother, and 645 grandparents had had coronary vascular events. There were significant associations between increased Lp(a) levels in children and the numbers of grandparents with coronary vascular events and with increasing grandparent coronary history scores (p < 0.01). There were also positive associations for apo B (p < 0.01) but none for apo A-1. Discriminate analysis showed that the log-transformed Lp(a) level was the variable most predictive of event numbers and of history scores in grandparents (Wilks lambda value = 0.984; p = 0.026); the apo B level was also predictive (Wilks lambda value = 0.988; p = 0.041), but neither the apo A-1 level nor the apo B/A-1 ratio was. We conclude that high Lp(a) and apo B levels in children aged 8 to 12 years are associated with increased risk of coronary vascular disease in older family members, even with a generation gap. These apolipoproteins may largely account for the independent contribution of family history to disease risk. Measurements of Lp(a) and apo B in schoolchildren may help to identify children and their families at increased risk and may facilitate targeting of prevention.

[Lipomyelomeningocele: experience with 16 operated cases]. / Lipomielomeningoceles. Experiência com 16 casos operados.

Sixteen patients with lipomyelomeningoceles were operated by microsurgery technics from 1980 to 1991. Patients with lipomyelomeningoceles inappropriately treated or not submitted to treatment will develop significant neurological sequelae. In the authors' opinion, proper management of the patient with spinal lipoma requires early prophylactic resection of the lipoma and untethering of the spinal cord.

Unilateral pterional approach to bilateral cerebral aneurysms.

Between 1976 and 1991, we determined that 19 patients harboring bilateral supratentorial aneurysms should be approached in a single sitting through a unilateral pterional craniotomy. Using microsurgical techniques, the Sylvian cistern was opened widely to expose the aneurysms located ipsilateral to the craniotomy. These aneurysms were clipped in the usual fashion. Following clipping, a tunnel was developed over the contralateral anterior cerebral artery and over or under the contralateral optic nerve allowing access to the opposite carotid and middle cerebral arteries. The contralateral nonruptured aneurysms were clipped in a routine fashion. We were able to clip or wrap with muscle all bilateral aneurysms in 15 cases, and we have concluded that this approach can be safely employed in selected patients with bilateral supratentorial aneurysms, and thus a second craniotomy can be avoided.

[Multiple intracranial aneurysms]. / Aneurismas intracranianos múltiplos.

Thirty eight patients with multiple intracranial aneurysms were studied. They correspond to 19.4% of all aneurysms treated over a twelve year period in the Servidores do Estado Hospital. 89 aneurysms and 4 infundibuli were detected. In 71.0% of the patients, two aneurysms were found; in 18.4%, three aneurysms; and in 10.4%, 4 or 5 aneurysms were observed. Twenty-seven patients were women and 11 men, ranging in age from 16 to 72 (average 47 years old). Subarachnoid hemorrhage was found in 36 patients (86.8%). The operative mortality in this series was 3.5%. We concluded that patients with multiple intracranial aneurysms should have all aneurysms, that can bleed, clipped through standard micro-neurosurgery technics.

Conjunctive enhancement of enzymatic thrombolysis and prevention of thrombotic reocclusion with the selective factor Xa inhibitor, tick anticoagulant peptide. Comparison to hirudin and heparin in a canine model of acute coronary artery thrombosis.

BACKGROUND: Effective thrombolytic recanalization of an occluded coronary vessel is often limited by acute thrombotic reocclusion, which has galvanized the search for effective adjunctive or conjunctive antithrombotic agents. METHODS AND RESULTS: Recombinant versions of tick anticoagulant peptide (rTAP) and hirudin (rHIR) are highly selective and potent polypeptide inhibitors of factor Xa and thrombin, respectively. The comparative antithrombotic efficacies of rTAP, rHIR, and heparin, administered conjunctively with recombinant tissue-type plasminogen activator (rt-PA), on thrombolytic reperfusion and reocclusion, were determined in a canine model of occlusive coronary artery thrombosis with a superimposed critical stenosis. In this model, a platelet-rich occlusive thrombus was formed after damage to the intimal surface of the left circumflex coronary artery induced by electrolytic injury. Fifteen minutes after occlusion, the dogs received a systemic intravenous administration of either saline (control), heparin (200 units/kg bolus + 2 units/kg/min, heparin (HEP) 200 or 100 units/kg bolus + 1 unit/kg/min, HEP 100), rHIR (50 or 100 micrograms/kg/min, rHIR 50 or 100, respectively), or rTAP (100 micrograms/kg/min, rTAP 100) followed 15 minutes later by rt-PA (100 micrograms/kg bolus + 10 micrograms/kg/min over 90 minutes). Infusions of the conjunctive agents were discontinued 60 minutes after termination of rt-PA. The incidence and time (mean +/- SEM) to thrombolytic reperfusion were determined for control (five of 12; 68.0 +/- 7.8 minutes), HEP 100 (six of eight; 40.1 +/- 8.3 minutes), HEP 200 (six of eight; 39.8 +/- 9.5 minutes), rHIR 50 (six of eight; 51.7 +/- 14.6 minutes), rHIR 100 (eight of eight; 19.5 +/- 4.2 minutes), and rTAP 100 (eight of eight; 22.8 +/- 10.0 minutes). The incidence and time to reocclusion after rt-PA were determined for control (four of five; 45.7 +/- 12.5 minutes), HEP 100 (four of six; 18.2 +/- 10.7 minutes), HEP 200 (five of six; 26.2 +/- 20.7 minutes), rHIR 50 (four of six; 47.3 +/- 21.6 minutes), rHIR 100 (six of eight; 89.8 +/- 5.9 minutes), and rTAP 100 (three of eight; 54.0 +/- 16.3 minutes). All of the dogs that reoccluded in the rHIR 100 group did so after termination of the inhibitor infusion, whereas two of the three dogs in the rTAP 100 group that reoccluded did so during the inhibitor infusion. Coronary artery blood flow was characterized by intermittent periods of reocclusion and recanalization in all groups except rTAP 100. CONCLUSIONS: The potent antithrombotic effects of rTAP in this model directly implicate de novo thrombin formation as a major source of thrombin activity within the highly thrombogenic residual thrombus. These findings suggest that direct inhibition of prothrombinase activity may be an effective strategy in the development of a new class of conjunctive agents.

Negative lusitropic effect of DPI 201-106 and E4031. Possible role of prolonging action potential duration.

In open-chest anesthetized dogs, the time constant of isovolumic left ventricular pressure decay increased following the intravenous administration of either E4031, a class III antiarrhythmic agent which acts by K+ channel blockade, or DPI 201-106 (DPI), a cardiotonic agent which acts by delaying Na+ channel inactivation. In addition to prolonging cardiac refractoriness, both E4031 and DPI increased left ventricular +dP/dt but without significantly altering -dP/dt. Consequently, the value of the ratio (+dP/dt)/(-dP/dt) increased. There were no significant changes in heart rate, mean arterial pressure, or left ventricular end diastolic pressure. Since both E4031 and DPI prolonged the action potential duration (APD) and the refractory period, and slowed relaxation in vivo, the possibility of a causal link between these effects was further investigated under in vitro conditions. In isometrically contracting rabbit papillary muscles, E4031 and DPI increased peak developed tension (DT) and its maximal rate of rise (+T). Since the maximal rate of fall of DT (-T) did not increase by the same factor that +T increased, the value of the ratio +T/-T increased. Time to half relaxation increased, whereas time to peak tension was not significantly changed by either E4031 or DPI. These negative lusitropic effects produced by E4031 or DPI were not observed when equivalent increases in contractility were produced by increasing the extracellular Ca2+ concentration. The effective refractory period measured in the papillary muscles increased following superfusion with either of the two drugs, consistent with their known ability to increase APD. A causal link between the prolongation of APD and the negative lusitropic effects of E4031 and DPI is postulated as the possible mechanism.

Post-disaster epidemiological surveillance following Hurricane Hugo in Montserrat - abstract

Hurricane Hugo struck the island of Montserrat during the night of 17th September, 1989. Sustained winds of 130 mph were experienced for 8 hours with damage to 93 per cent of buildings; 50 per cent seriously and 20 per cent destroyed. The main hospital lost its roof and most health centres were severely affected. Two thousand five hundred persons were rendered homeless, of whom 1,000 were housed in shelters. Three days after, environmental health surveillance revealed unsatisfactory conditions in shelters with inadequate water supplies and faecal disposal. Water was trucked to shelters and a pit latrine programme commenced so that by the first week of October, all shelters had acceptable faecal disposal facilities. Island-wide, symptom-based daily reports of disease surveillance was introduced 9 days after the hurricane for respiratory infections and gastroenteritis. This allowed daily monitoring of disease occurrence by locality, targeting of health education and environmental health measures, and made it easier to dispel rumors which occurred after the hurricane. There was an increase in gastroenteritis 10 - 14 days after, but this subsided as potable water supplies were established. One month after, 30 cases of fever of unknown origin were detected. At first suspected to be dengue fever, it turned out to be influenza A (hl, N1) (AU)

[Chronic subdural hematoma: surgical treatment and results in 96 patients]. / Hematoma subdural crônico: tratamento cirúrgico e resultados em 96 pacientes operados.

Ninety-six patients with chronic subdural hematoma were treated surgically and their clinical features presented in detail. Carotid angiography gave the correct diagnosis in all patients. CT scan was performed in 38 and was diagnostic in 92.1% of the cases. The clots were removed through burr-holes or small trephines: 78 (81.3%) patients were cured, 6 (6.2%) had permanent disabilities and 12 (12.5%) died. Operative mortality was related to the degree of neurological impairment, advanced age and systemic diseases. Neurologic sequelae were mostly related to reoperations due to recurrence of the hematoma and bilateral clots, as well. Low intracranial pressure syndrome with brain collapse was seen in 3 cases and treated with lumbar injection of saline solution. The delay in diagnosis and operation as cause of bad outcome is stressed.

[Primary hematoma of the brain stem: considerations apropos of a case]. / Hematoma primário do tronco cerebral: considerações a propósito de um caso.

The case of a 48 year-old woman presenting with a primary pontine hematoma is reported. The clinical evolution simulated a brain stem tumor and the diagnosis of hematoma was not established before the operation. The preoperative neurological deficit improved except for a facial nerve palsy. These hematomas are thought to be due to rupture of "cryptic" arteriovenous malformations and should be differentiated from those secondary to systemic hypertension. The diagnosis of brain stem hematomas should be considered in any case of brain stem lesion, especially in young and normotensive patients.

[Xanthogranuloma of the choroid plexus: a case report]. / Xantogranuloma do plexo coróideo: relato de caso.

We report an unusual case of a 30-year-old man who presented blindness and raised intracranial pressure secondary to a huge lateral ventricle xanthogranuloma. Computed tomographic scanning showed a highly calcified hyperdense mass that did not enhance after contrast administration. The mass was subtotally resected via transcallosal approach. The pathogenesis of the choroid plexus xanthogranuloma is discussed.

[Intracerebral abscess: clinical treatment. Experience with a case]. / Abscesso intracerebral: tratamento clínico. Experiência com um caso.

A case of brain abscess treated non surgically is reported. Complete clinical and radiological resolution is demonstrated. The authors conclude that in selected patients conservative management of focal intracerebral infection may obviate the need for surgical intervention.