[Laparoscopic adrenalectomy in adrenal carcinoma]. / Adrenalectomía laparoscópica por patología maligna.

There is general agreement on the suitability of the laparoscopic approach for benign adrenal lesions against open procedures because of the efficacy and less morbidity. For suspected adrenal malignancies laparoscopic use is controversial. We report our experience in 6 cases of laparoscopic adrenalectomy in patients with the suspicion of adrenal malignancy confined in the gland. In medium a follow up of 24 months (range 12 to 48 months) we observed no recurrences. We concluded that in a suspected adrenal malignancy organ confined laparoscopic adrenalectomy presents the advantage compared with open surgery of reduced morbidity and similar results in the follow up of the patient.

Comparative cytomorphology of maturing amphisbaenian (Amphisbaena alba) and snake (Waglerophis merremii) erythroid cells with regard to haemoglobin biosynthesis

A comparative ultrastructural study on organelles involved in haemoglobin (Hb) biosynthesis processing in the course of Amphisbaena alba (Amphisbaenia, Squamata, Reptilia) and Waglerophis merremii (Ophidia, Squamata, Reptilia) erythroid cells maturation, was accomplished; for this purpose, erythropoiesis was enhanced by phenylhydrazine hydrochloride and saponin, respectively. The fossorial amphisbaenians, which live in an hypoxic environment, denoted a lower metabolic rate than that of snakes; they presented a slow response to intoxication and to anaesthesia, and an apparently slow transformation of erythroid cell organelles for Hb biosynthesis. Iron uptake, probably via transferrin, results in accumulation in the form of siderosomes, which constitute iron sources for haeme biosynthesis. The inner compartment membrane of mitochondria differentiates to a lamellated body, from which a long doubly lamellated expansion arises for ferruginous compounds and globin polypeptides gathering; by folding upon itself the expansion compartmentalises all caught material into a prehaemosomal vesicle, which condenses and changes to a prohaemosome. This stage is followed by a haemosome, wherein haeme and globin assembly and the final Hb molecule formation take place. Basically, haemosomegenesis is very similar in the two squamates, as in other vertebrates, except that amphisbaenian erythroid cells exhibit haemosomes containing Hb molecules temporarily arranged in a transverse disposition, like steps within the organelle matrix.

Risperidone and reversible neutropenia: a negative rechallenge.

After 6 weeks of a risperidone rechallenge therapy (2-4 mg/day), no hematological abnormalities were observed in a 26-year-old schizophrenic woman. Two years previously after 9 days of risperidone therapy (2-6 mg/day), the same patient had developed a reversible neutropenia during a cold.

Hematological changes induced by Bothrops jararaca venom in dogs.

The mechanism of consumption coagulopathy observed in cases of human envenomation by Bothrops jararaca is well established. However, this mechanism may vary according to the animal species studied. In order to study both the clinical and laboratory aspects of bothropic envenomation in dogs, a sublethal defibrinating dose of venom (100 micrograms/kg) was given intravenously. A coagulopathy similar to that observed in humans - including fibrinogen depletion, consumption of factors II, X, V and antithrombin III, and moderate thrombocytopenia - was observed. The presence of circulating activated platelets was also noted. Neutrophilic leukocytosis, lymphopenia, and monocytosis occurred at different times. Erythrocytic values remained normal in dogs treated with B. jararaca venom compared with those treated with saline alone. The erythrocyte sedimentation rate fell rapidly after venom administration and this fall was correlated logarithmically with fibrinogen concentration. Since the effects of envenomation in dogs is similar to that in humans, it was concluded that the dog can be used as a good animal model for studying human venom-induced coagulopathy.

Hematological changes induced by Bothrops jararaca venom in dogs

The mechanism of consumption coagulopathy observed in cases of human envenomation by Bothrops jararaca is well established. However, this mechanism may vary according to the animal species studied. In order to study both the clinical and laboratory aspcts of bothropic envenomation in dogs, a sublethal defibrinating dose of venom (100 µg/kg) was given intravenously. A coagulopathy similar to that observed in humans - including fibronogen depletion, consumption of factors II, X, V and antithrombin III, and moderate thrombocytopenia -was observed. The presence of circulatin activated platelets was also noted. Neutrophilic leukocytosis, lymphopenia, and monocytosis occurred at different times. Erythrocytic values remained normal in dogs treated with B. jararaca venom compared with those treated with saline alone. The erythrocyte sedimentation rate fell rapidly after venom administration and this fall was correlated logarithmically with fibrinogen concentration. Since the effect of envenomation in dogs is similar to that in humans, it was concluded that the dog can be used as a good animal model for studying human venom-induced coagulopathy

Search of intravascular hemolysis in patients with the cutaneous form of loxoscelism.

Haptoglobin assay, a highly sensitive method to detect intravascular hemolysis was carried out in the sera of 19 patients referred to Hospital Vital Brazil with the cutaneous form of loxoscelism in order to investigate the occurrence of mild intravascular hemolysis. Data from this series did not show decreased levels haptoglobin, ruling out intravascular hemolysis in these patients with cutaneous form of loxoscelism.

Hemosomegenesis and hemoglobin biosynthesis in vertebrates.

1. Ultrastructural observations on maturing rabbit embryo erythroid cells led to the finding of hemoglobinized organelles distinguishable from mitochondria due to their highly dense matrix, two or three longitudinally arranged double lamellae, and smaller diameters. Intraorganellar 50-60 A particles identical to those contained in the hemoglobinized cytoplasm were found. 2. Their hemoglobin (Hb) content was demonstrated by electrophoresis of the concentrated supernatant from the isolated, washed, and osmotically lysed organellar fraction. We have proposed that these organelles are the sites for heme integration into the globin (G) polypeptide chains and subunits assembly. The term hemosome has been suggested for such entities. 3. This hypothesis has been sustained by several analytical and experimental works based on the postulation that hemosomes should be found at higher frequencies where the Hb biosynthesis rate is more intensive, or where the induction of this biosynthesis is always dependent on the formation of hemosomes. 4. Maturing erythroid cells of the circulating embryo blood contain hemosomes in higher frequency than in liver erythroid cells, coinciding with the higher Hb biosynthesis rate in peripheral blood than in the liver. In bleeding anemia, the decay of Hb concentration parallels the reduction of the mean number of hemosomes per reticulocyte, in comparison with normal reticulocytes. 5. In HeLa cells and epithelial cultured cells induced to synthesize Hb, it was shown that this biosynthesis is ever concomitant with the formation of hemosomes and depends on the presence of erythropoietin, as occurs in erythroid cells. 6. Studies on hemosomegenesis and Hb biosynthesis experimentally effected in epithelial cultured cells, allowed the interpretation of the sequence of events leading to hemosome formation in maturing erythroid cells. Simultaneously with iron uptake, mitochondria differentiate to lamellated bodies and, successively, expansions rise for ferruginous compounds and G polypeptides gathering, followed by prehemosome vesicles formation, which condense and change to prohemosomes that afterwards evolve to hemosomes. 7. These dynamics, and organellar Hb have been detected in immature erythrocytes of mammalians, including humans, avians, reptilians, amphibians and representative fish specimens. It appears that these events occur in the erythrocytary maturation of all vertebrate classes.

Studies on blood coagulation and fibrinolysis in patients bitten by Bothrops jararaca (jararaca).

The blood coagulation and the fibrinolytic systems of nine patients envenomed by Bothrops jararaca in São Paulo (Brazil) were studied. Five of the accidents were caused by young snakes (less than 50 cm). On admission, four patients had non-clotting and three partially-clotting blood. Fibrinogen levels were decreased due to the thrombin-like activity of the venom as expected. Consequent secondary activation of the fibrinolytic system was evident from the low levels of alpha-2-antiplasmin and the high titres of fibrin(ogen) degradation products. High titres of cross-linked fibrin fragment D (D-dimer) in seven patients together with decreased platelet counts and/or factor V, and/or factor VIII in some, suggests intrinsic thrombin formation as these factors are not consumed in the defibrinogenation induced by venom thrombin-like fractions such as Ancrod and Batroxobin. However, normal or increased levels of antithrombin III in all and normal levels of factor II in eight patients do not support this interpretation. The existence of variable concentrations of other proteins in the venom of B. jararaca such as botrocetin and thrombocytin isolated from B. jararaca and B. atrox or crotalocytin from Crotalus horridus venom should be considered. Such proteins are known to activate factors V, VIII, XIII, and platelets without affecting prothrombin (factor II) and antithrombin III. Slower recovery of the haemostatic disturbances after antivenom administration to patients bitten by young snakes suggests a more severe coagulopathy in such accidents. This is supported by clinical observations.

Methemoglobinemia associated with loxoscelism.

In twenty five patients who presented the cutaneous form of loxoscelism, serum haptoglobin and lactic dehydrogenase, erythrocyte glucose-6-phosphate dehydrogenase, glutathione reductase, glutathione peroxidase, methemoglobin, bilirubin and reticulocytes were investigated after bite. No hemolysis was detected but an increase in methemoglobin was found in 54% of the cases; in 7% it was between 1.1% and 2%, in 27% it ranged from 2.1% to 4%, and in 20% from 4.1% to 8%. Blood samples of a normal, blood group 0 individual and of a patient who exhibited methemoglobinemia after Loxosceles bite were incubated separately with antisera against Loxosceles gaucho, Crotalus terrificus, Bothrops jararaca, with Loxosceles gaucho venom and 0.3% phenol. No methemoglobin was found after 1, 4, 8 and 15 days in both sets of samples. At the 25th day all the samples, including the controls, exhibited similar methemoglobin reductase decrease. The data suggest that the methemoglobinemia which occurs in 50% of the patients probably arises from in vivo venom metabolism, inasmuch as the crude venom does not induce methemoglobinemia.

Comparative ultrastructure of maturing toad (Bufo ictericus) and rabbit (Oryctolagus cuniculus) erythroid cells with regard to hemoglobin biosynthesis.

1. Toad and rabbit maturing erythroid cells were comparatively analysed with regard to their ultrastructural modifications involved in hemoglobin (Hb) biosynthesis. 2. The mitochondrial inner membrane differentiates to a lamellated body that, successively, gives rise to prehemosomal vesicles, prohemosomes, and to hemoglobinized organelles called hemosomes. 3. The prehemosomal vesicle involves ferruginous inclusions, taken as iron sources for heme biosynthesis, as well as the polypeptide globin chains, assembling themselves in the course of volume reduction. 4. From the prohemosomal stage onwards, where possibly heme biosynthesis occurs, hemosomes are formed; these organelles are presumably sites where the final Hb biosynthesis could take place. 5. All development stages leading to hemosome formation are similar in toad and rabbit erythroid cells, except that, in the toad, the structural prohemosome characteristics persist in hemosomes. 6. Through toad erythroid cell fractionation and electrophoresis of the organelle lysate supernatant, a wide and a weak cytoplasmic Hb bands were obtained; the latter coincides with the intraorganellar Hb band.

The anticoagulant effect of Bothrops castelnaudi snake venom (Castelnaud's pit viper).

An inhibitory effect of Bothrops castelnaudi venom was observed on the following systems: prothrombin time, activated partial thromboplastin time, thrombin time, thromboplastin generation time, activation of factor X by Russell's viper venom and Russell's viper venom activated factor X (factor Xa). This effect did not require previous incubation and was prevented by the addition of Bothrops-antivenom. The prolonged activated partial thromboplastin time was not shortened by increased phospholipid concentration (0.5-10 mg/ml), suggesting that the inhibitory effect is not due to an anti-phospholipid activity. No significant fibrinogenolytic activity was detected upon incubation of human fibrinogen with the venom, since physiological levels of thrombin-clottable material were still present. Compared to Bothrops jararaca venom, the proteolytic activity on casein and on azocoll was very low. Thrombin-induced clots of human plasma and fibrinogen were not lysed by the venom within 24 hr. The results indicate that the anticoagulant effect of Bothrops castelnaudi venom is exerted at least at two levels of the blood coagulation mechanism: (1) before prothrombin activation, by inhibiting factor X-activation and factor Xa activity; (2) by direct action on thrombin.

The inactivating effect of Bothrops jararaca and Waglerophis merremii snake plasma on the coagulant activity of various snake venoms.

Plasmas of the poisonous snake Bothrops jararaca and of the non-poisonous snake Waglerophis merremii were not clotted by various snake venoms. These plasmas also inactivated venom clotting activity on human plasma. This effect was absent in snake serum and in heated snake plasma. The active fraction was isolated by gel chromatography from B. jararaca plasma and corresponded to the fibrinogen-containing fractions. It is suggested that the inactivation by snake plasma of the venom coagulant activity might be due to a fibrinogen-bound complex or to fibrinogen itself.