The suicidality continuum in a large sample of obsessive-compulsive disorder (OCD) patients.

BACKGROUND: Obsessive-compulsive disorder (OCD) has a chronic course leading to huge impact in the patient's functioning. Suicidal thoughts and attempts are much more frequent in OCD subjects than once thought before. AIM: To empirically investigate whether the suicidal phenomena could be analyzed as a suicidality severity continuum and its association with obsessive-compulsive (OC) symptom dimensions and quality of life (QoL), in a large OCD sample. METHODS: Cross-sectional study with 548 patients diagnosed with OCD according to the DSM-IV criteria, interviewed in the Brazilian OCD Consortium (C-TOC) sites. Patients were evaluated by OCD experts using standardized instruments including: Yale-Brown Obsessive-Compulsive Scale (YBOCS); Dimensional Yale-Brown Obsessive-Compulsive Scale (DYBOCS); Beck Depression and Anxiety Inventories; Structured Clinical Interview for DSM-IV (SCID); and the SF-36 QoL Health Survey. RESULTS: There were extremely high correlations between all the suicidal phenomena. OCD patients with suicidality had significantly lower QoL, higher severity in the "sexual/religious", "aggression" and "symmetry/ordering" OC symptom dimensions, higher BDI and BA scores and a higher frequency of suicide attempts in a family member. In the regression analysis, the factors that most impacted suicidality were the sexual dimension severity, the SF-36 QoL Mental Health domain, the severity of depressive symptoms and a relative with an attempted suicide history. CONCLUSIONS: Suicidality could be analyzed as a severity continuum and patients should be carefully monitored since they present with suicidal ideation. Lower QoL scores, higher scores on the sexual dimension and a family history of suicide attempts should be considered as risk factors for suicidality among OCD patients.

Effects of angiotensin II, atrial natriuretic peptide and endothelin-1 on proliferation and steroidogenic output of bovine granulosa cells cultured in a chemically defined system.

The role of local factors in the modulation of granulosa cell (GC) proliferation and differentiation is well described in the literature. The present work used a long-term bovine GC culture, in chemically defined medium without gonadotropins, to study the effects of angiotensin II (Ang II), atrial natriuretic peptide (ANP) and endothelin-1 (EDN1) on the steroidogenesis and cellular proliferation. Small follicles (3-5mm in diameter) from ovaries obtained in the slaughterhouse were selected according to their vascularization and follicular fluid color in order to isolate GC. Granulosa cells were plated at a density of 5×10(4)cells/well in supplemented alpha-MEM containing 3 levels (0, 10(-8)M and 10(-7)M) of Ang II, ANP, and EDN1 for up to 96h. Proliferation was evaluated by tritiated thymidine incorporation. The results showed that Ang II, ANP, and EDN1 modulate the steroidogenic output and proliferation index of GCs depending on the dose and time of culture. The selected vasoactive peptides increased androstenedione (A4) consumption in parallel with increased estradiol (E2). Although the peptides also promoted a significant increase in pregnenolone (P5) and progesterone (P4) production, the E2:P4 ratio was maintained at a high at most of the tested doses. Taken together, our in vitro data suggest that these vasoactive factors may have a direct effect on physiological follicular deviation, favoring dominance of the selected follicle.

In vitro and in vivo analysis of fatty acid effects on metabolism of 17beta-estradiol and progesterone in dairy cows.

Some studies have reported improved reproductive performance with dietary fat supplementation. This study examined effects of fatty acids with different lengths, or desaturation, or both, on metabolism of estradiol (E2) and progesterone (P4) in bovine liver slice incubations (experiments 1 and 2) and in vivo (experiment 3). In experiment 1, effects of fatty acids C16:0 (palmitic acid), C16:1 (palmitoleic acid), C18:1 (oleic acid), and C18:3 (linolenic acid) were evaluated at 30, 100, and 300 microM on P4 and E2 metabolism in vitro. In experiment 2, stearic acid (C18:0) and C18:3 were evaluated in the same incubation conditions. In experiment 1, all of the fatty acids had some significant inhibitory effect on metabolism of P4, E2, or both (300 microM C16:0 on E2; 100 microM C16:1 on E2; 300 microM C16:1 on both P4 and E2; 300 microM C18:1 on P4; and 100 and 300 microM C18:3 on both P4 and E2). In experiment 2, C18:3 (100 and 300 microM) but not C18:0 decreased P4 and E2 metabolism. Overall, the most profound increase (approximately 60%) in half-life of P4 and E2 was observed with incubations of 300 microM C18:3 in both in vitro experiments. Based on these in vitro results, in experiment 3 linseed oil (rich in C18:3) was supplemented into the abomasum and acute effects on metabolism of E2 and P4 were evaluated. Cows (n=4) had endogenous E2 and P4 minimized (corpus luteum regressed, follicles aspirated) before receiving continuous intravenous infusion of E2 and P4 to analyze metabolic clearance rate for these hormones during abomasal infusion of saline (control) or 70 mL of linseed oil every 4h for 28h. Linseed oil infusion increased C18:3 in plasma by 46%; however, metabolic clearance rate for E2 and P4 were similar for control cows compared with linseed-treated cows. Thus, in vitro experiments indicated that E2 and P4 metabolism can be inhibited by high concentrations of C18:3. Nevertheless, in vivo, linseed oil did not acutely inhibit E2 and P4 metabolism, perhaps because insufficient C18:3 concentrations (increased to approximately 8 microM) were achieved. Further research is needed to determine the mechanism(s) of fatty acid inhibition of P4 and E2 metabolism and to discover practical methods to mimic this effect in vivo.

Use of alprostadil, a stable prostaglandin E1 analogue, for the attenuation of rat skeletal muscle ischemia and reperfusion injury.

AIM: Some stable prostaglandin analogues such as alprostadil have been used to attenuate the deleterious effects of ischemia and reperfusion injury. The aim of this paper was to test if alprostadil can decrease the ischemia- reperfusion injury in rat skeletal muscle using muscular enzymes as markers, such as aspartate aminotransferase (AST), creatine kinase (CPK), lactate dehydrogenase (LDH); degeneration products of cell membrane-malondialdehyde (MDA) and muscle glycogen storage. METHODS: Thirty male Wistar rats were used in a model of hind limb ischemia achieved by infrarenal aortic cross-clamping. The animals were randomized into three equal groups (N=10) submitted to 5 hours of ischemia followed by one hour of reperfusion. The first group (control) received continuous intravenous infusion of saline solution and the second group (preischemia, GPI) received continuous intravenous infusion of alprostadil throughout the experiment starting 20 minutes before the aortic cross-clamping. The third group, prereperfusion (GPR), received alprostadil only during the reperfusion period, with intravenous infusion being started 10 min before the clamp release. RESULTS: There was no difference in CPK, LDH, AST or tissue glycogen values between groups. However, a significant elevation in MDA was observed in the GPI and GPR groups compared to the control group, with no difference between the GPI and GPR. CONCLUSIONS: Under conditions of partial skeletal muscle ischemia, alprostadil did not reduce the release of muscular enzymes, the consumption of tissue glycogen or the effects of ischemia and reperfusion on the cell membrane, characterized by lipid peroxidation.

Metformin increases blood flow and forearm glucose uptake in a group of non-obese type 2 diabetes patients.

The present study was designed to determine the effects of metformin on the forearm glucose uptake and blood flow after an oral glucose challenge. Eleven normal subjects, and ten non-obese type 2 diabetes patients without medication of anti-hyperglycemic drug and with medication of metformin for four weeks, were studied after an overnight fast (12-14 h) and 3 hours after ingestion of 75 g of glucose. Peripheral glucose metabolism was analyzed by the forearm technique combined with indirect calorimetry. The forearm glucose uptake increased in diabetes patients taking metformin (63.5+/-9.1 VS. 39.1+/-5.3 mg/100 ml FA. 3 h). The increase of forearm glucose uptake was due to increase of blood flow. The glucose oxidation was greater in the group treated with metformin, compared to the same group without anti-hyperglycemic drug (19.3+/-2.6 VS. 7.7+/-2.6 mg/100 ml FA. 3 hrs). The free fatty acids were higher in diabetes patients, which normalized after taking metformin. In conclusion, it was found that in these participants metformin acts in insulin resistance; it increases glucose muscle uptake and blood flow. The enhancement of blood flow and lower free fatty acids, not described yet, could be direct effects of the drug or due to reduced glucose toxicity. These positive effects must be responsible for the improvement in vascular function.

Identification of polymorphisms in the 5'-untranslated region of the TAFI gene: relationship with plasma TAFI levels and risk of venous thrombosis.

BACKGROUND AND OBJECTIVES: Thrombin activatable fibrinolysis inhibitor (TAFI) plays an important role in hemostasis, functioning as a potent fibrinolysis inhibitor. TAFI gene variations may contribute to plasma TAFI levels and thrombotic risk. DESIGN AND METHODS: We sequenced a 2083-bp region of the 5'-regulatory region of the TAFI gene in 127 healthy subjects searching for variations, and correlated identified polymorphisms with plasma TAFI levels. TAFI polymorphisms were examined as risk factors for venous thrombosis by determining their prevalence in 388 patients with deep venous thrombosis (DVT) and in 388 controls. RESULTS: Seven novel polymorphisms were identified: -152 A/G, -438 A/G, -530 C/T, -1053 T/C, -1102 T/G, -1690 G/A, and -1925 T/C. -152 A/G, -530 C/T and -1925 T/C were found to be in strong linkage disequilibrium, as were the -438 A/G, -1053 T/C, -1102 T/G and -1690 G/A. Plasma TAFI levels were higher in -438GG/-1053CC/-1102GG/-1690AA homozygotes than in -438AG/-1053TC/-1102TG/-1690GA heterozygotes, and -438AA/-1053TT/-1102TT/-1690GG homozygotes had the lowest TAFI levels (p=0.0003). TAFI concentrations in -152AA/-530CC/-1925TT homozygotes were somewhat higher but not significantly different from levels observed for -152AG/-530CT/-1925TC heterozygotes. Taken in combination, -438AG/-1053TC/-1102TG/-1690GA and -438AA/-1053TT/-1102TT/-1690GG yielded an OR for DVT of 0.8 (95%CI: 0.6-1). In subjects aged <35 years the OR was 0.7 (95%CI: 0.5-1.1). The OR for -152AG/-530CT/-1925TC was 1 (95%CI: 0.5-2.2) in the whole group of patients and controls, whereas in subjects aged <35 years the OR was 0.1 (95%CI: 0.02-0.9). INTERPRETATION AND CONCLUSIONS: Polymorphisms in the TAFI promoter determine plasma antigen levels and may influence the risk of venous thrombophilia.

Indicators of oxidative injury and alterations of the cell membrane in the skeletal muscle of rats submitted to ischemia and reperfusion.

BACKGROUND: Oxygen free radicals are considered to be important components involved in the physiopathological tissue alterations observed during ischemia and reperfusion. The objective of the present study was to investigate oxidative stress based on indicators of oxygen free radical activity and on the changes in behavior of the lipoprotein membrane (O-phosphoserine) in the skeletal muscle of rats. MATERIAL AND METHODS: Twenty Wistar rats were divided into two groups of 10. One group was submitted to 3 h of total ischemia by applying a tourniquet to the hind limb and the contralateral hind limb was used as control. The second group was submitted to the same procedure and was reperfused for 45 min after 3 h of ischemia by removing the tourniquet, where the contralateral hind limb of the same animal was used as control. Muscle biopsies were taken after ischemia and reperfusion and the parameters indicating oxidative stress (reduced and oxidized glutathione, malondialdehyde, glutamine synthetase, protein carbonyl) and O-phosphoserine (OPS) alterations were analyzed. RESULTS: The following results display control versus experimental hindlimbs groups obtained from the same animal. The skeletal muscle of rats submitted to total ischemia of 3 h duration showed increased OPS release (2.69 +/- 4.52 vs 8.03 +/- 7.20; n = 10; P = 0.024) and no change in reduced and oxidized glutathione, glutamine synthetase, protein carbonyl, or malondialdehyde. After 45 min of reperfusion there was an increase in oxidized glutathione levels (0.30 +/- 0.06 vs 0.39 +/- 0.09; n = 8; P = 0.02) and malondialdehyde levels (154. 78 +/- 26.13 vs 206.30 +/- 47.30; n = 9; P = 0.008), a fall in glutamine synthetase (21.80 +/- 3.61 vs 13.52 +/- 6.78; n = 9; P = 0. 004), and a return of OPS to levels close to the initial ones. No changes in reduced glutathione or protein carbonyl were observed in the two groups studied. CONCLUSIONS: After a total ischemia duration of 3 h there were signs of damage to the phospholipid membrane of the rat skeletal muscle, as demonstrated by the elevation of OPS and the few or no oxidative changes in the cell. After 45 min of reperfusion, oxidative damage to the lipoprotein components of the cell membrane was observed, characterized by elevations of oxidized glutathione and malondialdehyde levels and a fall in glutamine synthetase levels.

Peripheral glucose metabolism in patients with essential hypertension.

The present study was designed to determine the effect of essential hypertension on peripheral glucose metabolism during the postabsorptive state and after an oral glucose challenge. Ten normal subjects and nine patients with essential hypertension were studied after an overnight fast (12-14 h) and for 3 h after the ingestion of 75 g of glucose. Peripheral glucose metabolism was analyzed by the forearm technique to estimate muscle exchange of substrate combined with indirect calorimetry. Decreased forearm glucose uptake was observed in hypertensive patients compared to normal subjects (4.9+/-0.6 vs. 8.6+/-0.5 mmol x 100 ml forearm(-1) x 3 h(-1)) with diminished nonoxidative glucose metabolism (2.7+/-0.5 vs. 6.9+/-0.6 mmol x 100 ml forearm(-1) x 3 h(-1)). Muscle glucose oxidation did not differ significantly between groups. Both serum free fatty acid levels and lipid oxidation rates were similar in the normal subjects and the hypertensive patients, and declined in a similar fashion after glucose ingestion. Basal serum insulin levels did not differ significantly between normal and hypertensive patients, whereas the insulinemic response to glucose load was greater among the patients with essential hypertension. These data show that insulin resistance occurring in patients with essential hypertension is accompanied by impaired muscle glucose uptake and nonoxidative metabolism.

Pseudoaneurysms of large arteries associated with AIDS.

BACKGROUND: Several vascular complications are known to occur in association with the acquired immunodeficiency syndrome (AIDS) and recent publications have called attention to the development of pseudoaneurysms of large arteries in patients with AIDS. CASE REPORT: We report on 2 patients with AIDS aged 23 and 31 years with pseudoaneurysms of the abdominal aorta and common iliac arteries. After clinical and radiological evaluation by arteriography and computed tomography, the patients were submitted to aneurysmectomy, with the placement of a patch of dacron in the first case and the interposition of a right aorto-iliac and left femoral prosthesis in the second. The second patient developed new aneurysms of the right subclavian and left popliteal arteries 2 months after surgery. Proximal ligation of the right subclavian artery was performed to treat the first aneurysm and resection and interposition of a reversed saphenous vein was carried out to treat the pseudoaneurysm of the popliteal artery. Histopathological examination of the popliteal artery revealed necrotizing arteritis.

Factor XIII Val34Leu is a genetic factor involved in the etiology of venous thrombosis.

A mutation in the factor XIII gene (FXIII Val34Leu) gene was recently reported to confer protection against myocardial infarction, but its relationship with venous thrombosis is unknown. In addition, a mutation in the 5'-untranslated region of the FXII gene (46 C->T) was identified which is associated with low plasma levels of the protein. Its prevalence in patients with venous thrombosis is also unknown. We investigated the frequency of the FXIII Val34Leu and FXII 46 C->T mutations in 189 patients with deep venous thrombosis and in 187 age-, gender- and race-matched controls. FXIII Val34Leu was detected in 38.6% of the patients and in 41.2% of the controls. Interestingly, homozygosity for the FXIII mutation was found in 1.6% of the patients and in 9.6% of the controls, yielding an odds ratio (OR) for venous thrombosis of 0.16 (95% CI: 0.05-0.5). The OR for heterozygotes was 1.1 (95% CI: 0.7-1.7). The FXII 46 C->T mutation was detected in 46.0% of the patients and in 48.6% of the controls. The OR for heterozygotes was 0.9 (95% CI: 0.6-1.4) and for homozygotes the OR was 0.8 (95% CI: 0.3-1.9). Our data indicate that the FXII 46 C->T mutation is unlikely to be a major risk factor for venous thrombotic disease. In contrast, the homozygous state for FXIII Val34Leu is a strong protective factor against venous thrombosis, which emerges as a novel genetic factor involved in the aetiology of thrombophilia.

A second mutation in the methylenetetrahydrofolate reductase gene and the risk of venous thrombotic disease.

We assessed the effect of a recently described mutation in the MTHFR gene (1298 A --> C) on the risk of deep venous thrombosis (DVT) by determining its prevalence in 190 patients with verified DVT and in age-, race- and gender-matched controls. MTHFR 1298 A --> C was found in 42.1% of patients and in 41.1% of controls. The OR for venous thrombosis was 1.07 (95% CI 0.70-1.65) for heterozygotes and 0.83 (95% CI 0.33-2.08) for homozygotes. The OR for the factor V Leiden (FVL) mutation was 3.40 (95% CI 1.22-9.48), for FII 20210 G --> A was 5.22 (95% CI 1.12-24.2) and for MTHFR 677 C --> T, 1.24 (95% CI 0.82-1.87). No significant increased risk for venous thrombosis was found when MTHFR 1298 A --> C was coinherited with FVL (OR 2.85, 95% CI 0.88-9.23), FII 20210 G --> A (OR 7.19, 95% CI 0.87-59.4) or MTHFR 677 C --> T (OR 1.44, 95% CI 0.71-2.92). These data do not support a critical role of MTHFR 1298 A --> C in the predisposition to DVT.

The frequency of 844ins68 mutation in the cystathionine beta-synthase gene is not increased in patients with venous thrombosis.

BACKGROUND AND OBJECTIVES: A frequent mutation in the cystathionine beta-synthase (CBS) gene (844ins68, a 68-bp insertion in the coding region of exon 8) was recently discovered. In the present study we investigated this mutation as a candidate risk factor for venous thrombosis. DESIGN AND METHODS: The prevalence of the 844ins68 CBS mutation was determined in 101 patients with objectively diagnosed deep venous thrombosis and in 101 healthy controls matched for age, sex and race. PCR amplification of a DNA fragment containing exon 8 of the CBS gene was employed to determine the genotypes. Additionally, Bsrl restriction enzyme digestion of the PCR products was performed in all samples from carriers of the insertion, to test for concurrent presence of a second mutation (T833C) in the CBS gene. RESULTS: The insertion was found in 21 out of 101 patients (20.8%; allele frequency 0.109) and in 20 out of 101 controls (19.8%; allele frequency 0.114), yielding a relative risk for venous thrombosis related to the 844ins68 CBS mutation close to 1.0. In addition, the T833C CBS mutation was detected in all alleles carrying the 844ins68 CBS insertion, confirming the co-inheritance of the two mutations. INTERPRETATION AND CONCLUSIONS: Our findings do not support the hypothesis that the 844ins68 mutation in the CBS gene is a genetic risk factor for venous thrombosis.

Factor V Arg306-->Thr (factor V Cambridge) and factor V Arg306-->Gly mutations in venous thrombotic disease.

We investigated the prevalence of two reported mutations of the factor V gene (factor V Arg306-->Thr, or factor V Cambridge, and factor V Arg306-->Gly) in 104 relatively young patients with verified venous thrombosis and in 208 age-, sex- and race-matched controls, in order to establish whether the two mutations are associated with increased predisposition for venous thrombosis. PCR amplification followed by BstNI and MspI digestion was employed to determine the genotypes, and each mutation was confirmed by DNA sequencing. Among the controls, one individual was found to be heterozygous for the factor V Arg306-->Thr mutation and one heterozygous for the factor VArg306-->Gly mutation; none of the patients carried either mutation. Our findings do not support factor V Cambridge and factor V Arg306-->Gly as risk factors for venous thrombosis.

Paracoccidioidomycotic aortitis with embolization to the lower limbs. Report of a case and review of the literature.

The authors report a clinical case of a 60-year-old Caucasian man, with two episodes of arterial embolization in the lower limbs. A microscope investigation of the emboli revealed that they originated from fungal aortitis caused by Paracoccidioides brasiliensis. A review of aortic infections showed only one similar report of this rare clinical expression of blastomycosis. The authors suggest a routine postoperative search for emboli followed by culture and histopathology.

Metabolic alterations of skeletal muscle during ischaemia and reperfusion.

Recent studies have demonstrated that skeletal muscle cells are resistant to prolonged periods of ischaemia, but damage is observed after reperfusion. Periods of time longer than three hours of normothermal ischaemia in skeletal muscle lead to irreversible lesions. In the present study muscle metabolism during ischaemia and reperfusion was studied. After three hours of ischaemia two experimental groups were produced depending on whether or not they were to be followed by two hours of reperfusion. Adult mongrel dogs were submitted to ischaemia of the gracilis muscle. In this tissue, energetic metabolism was evaluated by its mitochondrial function and by glycogen level measurement. In a second experimental group the same ischaemic period was followed by two hours of reperfusion. The contralateral muscle of the same animal was used as a control. No changes in mitochondrial function, analysed by respiratory control ratio (RCR) or in any of its components, basal (state IV respiration) or ADP-activated (state III respiration) was observed. Glycogen levels also remained unaffected during the three hour ischaemic period and after two hours of reperfusion. We conclude that in the present dog model of gracilis preparation the skeletal muscle displays great resistance to ischaemia and reperfusion.

Complicaçöes do cateterismo de veia umbilical em recém-nascidos com coto umbilical mumificado / Complications of umbilical vein catheterization in newborn infants with mummified umbilical cords

Os autores realizaram uma avaliação crítica e retrospectiva das complicaçöes com a cateterização de veia umbilical para ex-sanguíneo trasnfusão em recém-nascidos com coto mumificado no período de janeiro de 1983 a dezembro de 1992 no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto - USP. Estudaram 40 casos de recém-natos, no período assimilado; submetidos à cateterizaçãao de veia umbilical para ex-sanguíneo transfusão. Mantiveram-se os cateteres endovenosos, durante o procedimento de troca, em média 4 horas em 82,5 'por cento' dos casos, administrando-se por meio deles somente sangue e seus derivados. Analisou-se clinicamente o índice de complicaçöes precoces (infecçöes, tromboses) e tardias (hérnia incisional e hipertensão portal ) em 23 recém-nascidos sobreviventes. Revisaram-se as necrópsias de 15 a 17 crianças falecidas (todos falecidos em virtude da doença de base e não ligados ao procedimento) quanto à trombose da veia porta ou outra complicação ligada ao cateterismo. Contrariamente ao relato pela literatura, não foi observado nenhum caso de hérnia incisional ou sinais de hipertensão portal nas crianças sobreviventes e nenhum caso de trombose de veia porta nas autópsias dos recém-natos falecidos. Concluem que o cateterismo de veia umbilical pra o fim exclusivo de ex-sanguíneo transfusão é um procedimento simples, seguro e praticamente isento de complicaçöes.

Effect of hemodialysis on peripheral glucose metabolism of patients with chronic renal failure.

Glucose intolerance has been shown in patients with chronic renal failure (CRF), probably associated with insulin resistance in peripheral tissues. The present study was thus designed to investigate the effect of hemodialysis on peripheral muscle glucose metabolism of patients with CRF. Nine normal subjects and 6 patients with CRF were studied after an overnight fast (12-14 h) and during 3 h after ingestion of 75 g of glucose. Peripheral glucose metabolism was analyzed by the forearm technique to estimate the muscle exchange of substrates combined with indirect calorimetry. The CRF patients were studied before and after at least 1 month of hemodialysis treatment. Plasma glucose levels (arterial and venous) were higher in uremic patients before dialysis than in normal controls. After the dialysis therapy there was improvement in the glycemic profile of the CRF patients. Decreased forearm muscle glucose uptake was observed in the uremic patients before dialysis compared to the normal subjects (234 +/- 71 vs. 858 +/- 52 mumol/100 ml forearm . 3 h, p < 0.05) with diminished nonoxidative glucose metabolism (128 +/- 78 vs. 686 +/- 58 mumol/100 ml forearm . 3 h, p < 0.05). After the hemodialysis treatment of the CRF patients, the forearm glucose uptake and the nonoxidative glucose metabolism increased significantly to values of 527 +/- 64 and 384 +/- 87 mumol/100 ml forearm . 3 h, respectively. Muscle glucose oxidation did not differ significantly between normals and CRF patients before and after dialysis, as well as the serum insulin levels. These data demonstrate that insulin resistance in the presence of chronic uremia is accompanied by impaired muscle glucose uptake and nonoxidative glucose metabolism, which are significantly improved by the hemodialysis treatment.

Peripheral glucose metabolism in human hyperprolactinaemia.

OBJECTIVE: Prolactin has important biological actions in several species which include metabolic control and water/electrolyte balance. However, human PRL has generally been characterized as a mammotrophic hormone and it is unknown whether PRL has any important metabolic actions. This study was thus conducted to evaluate the effect of hyperprolactinaemia on peripheral muscle glucose metabolism. DESIGN: The study was designed to determine forearm muscle glucose uptake and utilization (oxidative and non-oxidative metabolism) in normal and hyperprolactinaemic subjects in the post-absorptive state and for 3 hours after the ingestion of 75 g of glucose. Peripheral glucose metabolism was analysed by the forearm technique to estimate muscle exchange of substrates combined with local indirect calorimetry. PATIENTS: Eight hyperprolactinaemic patients (HP group, 6 females and 2 males) and ten normal subjects (N group, 7 females and 3 males) were studied. The hyperprolactinaemic patients showed no clinical or laboratory evidence of acromegaly or hypothyroidism and were not using any PRL releasing drugs. MEASUREMENTS: Forearm blood flow was measured by capacitance plethysmography and arterial and venous blood samples were drawn simultaneously to determine plasma glucose, serum FFA, total blood CO2 and O2 and serum insulin in the post-absorptive state (0 time) and at 30, 60, 120 and 180 minutes after glucose ingestion. RESULTS: No significant difference in glucose uptake by the forearm muscle tissue was observed between the N and HP groups (823 +/- 103 vs 828 +/- 110 mumol/100 ml forearm 3 h, respectively), nor were any significant differences observed in the intracellular utilization of glucose (oxidative and non-oxidative metabolism). However, the serum insulin levels after glucose ingestion were significantly higher in hyperprolactinaemic patients than in normal subjects, especially at 30 (N 283 +/- 46 vs HP 581 +/- 133 pmol/l) and 60 minutes (N 291 +/- 37 vs HP 544 +/- 61 pmol/l). Furthermore, after glucose ingestion the suppression of serum FFA levels was smaller in the hyperprolactinaemic patients than in normal subjects. CONCLUSIONS: This study demonstrated that insulin resistance is associated with the presence of spontaneous human hyperprolactinaemia. The hyperinsulinaemia detected in the hyperprolactinaemic patients after the oral glucose stimulus did not determine a proportional increase in forearm glucose uptake and utilization, which were similar to the normal levels. The suppression of serum free fatty acid concentrations was also smaller in hyperprolactinaemic patients during the oral glucose challenge, suggesting an impaired antilipolytic effect of insulin.

Fístula aortoentérica primária / Primary aorto-enteric fistula

As fístulas aortoentéricas podem ser primárias ou secundárias. As últimas säo complicaçöes conhecidas de pacientes submetidos a cirurgias reconstrutivas da aorta. Enquanto estas säo relativamente comuns, as fístulas aortoentéricas primárias säo raras. Há cerca de 200 casos publicados na literatura mundial. Relata-se o caso de uma mulher de 71 anos com fístula aortoentérica primária que apresentava sangramento gatrointestinal de repetiçäo. O diagnóstico etiológico foi feito somente durante a cirurgi mediante o achado de um aneurisma aórtico comunicando-se com jejuno, apesar da exaustiva investigaçäo pré-operatória. Alguns aspectos clínicos e cirúrgicos dessa doença säo discutidos.

Peripheral glucose metabolism in patients with chronic renal failure.

The present study was designed to determine the effect of chronic renal failure on forearm muscle glucose uptake and oxidation during the postabsorptive state and after an oral glucose challenge. Twelve normal subjects and sixteen patients with chronic renal failure were studied after an overnight fast (12-14 h) and for 3 h after the ingestion of 75 g of glucose. Peripheral glucose metabolism was analyzed by the forearm technique to estimate muscle exchange of substrate combined with indirect calorimetry. Decreased forearm glucose uptake was observed in uremic patients compared to normal subjects (91.5 +/- 11.4 vs 154.8 +/- 7.8 mg 100 ml forearm-1 3 h-1) with diminished nonoxidative glucose metabolism (69.4 +/- 12.1 vs 117.2 +/- 12.8 mg 100 ml forearm-1 3 h-1). Muscle glucose oxidation did not differ significantly between groups. Both serum free fatty acid levels and lipid oxidation rates were similar in the normal subjects and the uremic patients, and declined in a similar fashion after glucose ingestion. Basal serum insulin levels did not differ significantly between normal and uremic patients, whereas the insulinemic response to glucose load was greater among the patients with chronic renal failure. These data show that insulin resistance occurring in patients with chronic renal failure is accompanied by impaired muscle glucose uptake and nonoxidative glucose metabolism.