Massive renal angiomyolipoma in tuberous sclerosis

Endoscopic surgery has been used as a new procedure to simplify different surgical processes. The goal of this study was to evaluate the benefits of endoscopic retroperitoneal surgery for lumbar sympathectomies. Between February 93 and November 95 we performed 35 lumbar sympathectomies using this technique. All patients were arteritic. The results were as follows: for 25% of the patients, conversion classical open technique was required; 6% complications (septic); 3% of the patients died. In comparing the various techniques of sympathectomy and sympatholysis, it would appear that the endoscopic technique produces fewer complications. However we believe that a learning period is necessary before this technique can be fully mastered.     

Incorporation of conscience objectors in Insalud

Patients often request laser therapy or other dramatic measures for treatment of nongenital warts. Because some popular interventions may be painful and costly and lead to scarring, it is wise to make sure a procedure's merits outweigh its side effects before commencing.     

Can retrograde perfusion mitigate cerebral injury after particulate embolization? A study in a chronic porcine model

OBJECTIVE: We assessed the impact on histologic and behavioral outcome of an interval of retrograde cerebral perfusion after arterial embolization, comparing retrograde cerebral perfusion with and without inferior vena caval occlusion with continued antegrade perfusion. METHODS: Sixty Yorkshire pigs (27 to 30 kg) were randomly assigned to the following groups: antegrade cerebral perfusion control; antegrade cerebral perfusion after embolization; retrograde cerebral perfusion control; retrograde cerebral perfusion after embolization; retrograde cerebral perfusion with inferior vena cava occlusion, retrograde cerebral perfusion with inferior vena cava occlusion control, and retrograde cerebral perfusion with inferior vena cava occlusion after embolization. After cooling to 20 degrees C, a bolus of 200 mg of polystyrene microspheres 250 to 750 (microm diameter (or saline solution) was injected into the isolated aortic arch. After 5 minutes of antegrade cerebral perfusion, 25 minutes of antegrade cerebral perfusion, retrograde cerebral perfusion, or retrograde cerebral perfusion with inferior vena cava occlusion was instituted. After the operation, all animals underwent daily assessment of neurologic status until the time of death on day 7. RESULTS: Aortic arch return, cerebral vascular resistance, and oxygen extraction data during retrograde cerebral perfusion showed differences, suggesting that more effective flow occurs during retrograde cerebral perfusion with inferior vena cava occlusion, which also resulted in more pronounced fluid sequestration. Microsphere recovery from the brain revealed significantly fewer emboli after retrograde cerebral perfusion with inferior vena cava occlusion. Behavioral scores showed full recovery in all but one control animal (after retrograde cerebral perfusion with inferior vena cava occlusion) by day 7 but were considerably lower after embolization, with no significant differences between groups. The extent of histopathologic injury was not significantly different among embolized groups. Although no histopathologic lesions were present in either the antegrade cerebral perfusion control group or the retrograde cerebral perfusion control group, mild significant ischemic damage occurred after retrograde cerebral perfusion with inferior vena cava occlusion even in control animals. CONCLUSIONS: Although effective washout of particulate emboli from the brain can be achieved with retrograde cerebral perfusion with inferior vena cava occlusion, no advantage of retrograde cerebral perfusion with inferior vena cava occlusion after embolization is seen from behavioral scores, electroencephalographic recovery, or histopathologic examination; retrograde cerebral perfusion with inferior vena cava occlusion results in greater fluid sequestration and mild histopathologic injury even in control animals. Retrograde cerebral perfusion with inferior vena cava occlusion shows clear promise in the management of embolization, but further refinements must be sought to address its still worrisome potential for harm.     

Enhanced specificity of truncated transmembrane protein for serologic confirmation of human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2 infections by western blot (immunoblot) assay containing recombinant envelope glycoproteins

Immunoassays based on the highly immunogenic transmembrane protein of human T-cell lymphotropic virus type 1 (HTLV-1) (protein 21c) are capable of detecting antibodies in all individuals infected with HTLV-1 and HTLV-2. However, because of antigenic mimicry with other cellular and viral proteins, such assays also have a large proportion of false-positive reactions. We have recently identified an immunodominant epitope, designated GD21-I located within amino acids 361 to 404 of the transmembrane protein, that appears to eliminate such false positivity. This recombinant GD21-I protein was used in conjunction with additional recombinant HTLV type-specific proteins and a whole virus lysate to develop a modified Western blot (immunoblot) assay (HTLV WB 2.4). The sensitivity and specificity of this assay were evaluated with 352 specimens whose infection status was determined by PCR assay for the presence or absence of HTLV-1/2 proviral sequences. All HTLV-1-positive (n = 102) and HTLV-2-positive (n = 107) specimens reacted with GD21-1 in the HTLV WB 2.4 assay, yielding a test sensitivity of 100%. Furthermore, all specimens derived from individuals infected with different viral subtypes of HTLV-1 (Cosmopolitan, Japanese, and Melanesian) and HTLV-2 (IIa0, a3, a4, IIb1, b4, and b5) reacted with GD21-I in the HTLV WB 2.4 assay. More importantly, HTLV WB 2.4 analysis of 81 PCR-negative specimens, all of which reacted to recombinant protein 21e in the presence or absence of p24 and p19 reactivity in the standard WB assay, showed that only two specimens retained reactivity to GD21-I, yielding an improved test specificity for the transmembrane protein of 97.5%. None of 41 specimens with gag reactivity only or 21 HTLV-negative specimens demonstrated reactivity to GD21-I. In an analysis of additional specimens (n = 169) from different geographic areas for which PCR results were not available, a substantial increase in the specificity of GD21-I detection was demonstrated, with no effect on the sensitivity of GD21-I detection among specimens from seropositive donors. Thus, the highly sensitive, GD21-I-based HTLV WB 2.4 assay eliminates the majority of false-positive transmembrane results, thereby increasing the specificity for serologic confirmation of HTLV-1 and HTLV-2 infections.     

Studies of 5-fluorodeoxyuridine 5'-monophosphate binding to carboxypeptidase A-inactivated thymidylate synthase from Lactobacillus casei

The binding of 5-fluorodeoxyuridylate (FdUMP) to carboxypeptidase-inactivated thymidylate synthase obtained from methotrexate-resistant Lactobacillus casei was investigated using [3H]FdUMP in a trichloroacetic acid precipitation assay and by 19F nuclear magnetic resonance spectroscopy. The cleavage of 1 valine residue from the carboxyl terminus of one of the identical subunits of the enzyme dimer correlates with complete loss of thymidylate synthesis (Aull, J. L., Loeble, R. B., and Dunlap, R. B. (1974) J. Biol. Chem. 249, 1167-1172). We have further investigated the phenomenon of carboxypeptidase A-dependent inactivation of thymidylate synthase by employing immobilized carboxypeptidase A in order to facilitate the isolation and characterization of the inactivated enzyme. The time course of carboxypeptidase treatment of thymidylate synthase has been profiled by the spectrophotometric assay, tritium release assay, trichloroacetic acid precipitation assay (covalent adduct analysis), 19F nuclear magnetic resonance spectroscopy, and amino acid analysis. The techniques utilized in this study yielded results which showed that the completely inactivated enzyme (failure to catalyze thymidylate formation) continued to catalyze both covalent FdUMP-enzyme interactions and the formation of the covalent inhibitory ternary complex with the cofactor, 5,1O-methylenetetrahydrofolate, although to a reduced extent, thus effectively uncoupling these processes from thymidylate synthesis activity.     

Feasibility of dose-intensive continuous 5-fluorouracil, doxorubicin, and cyclophosphamide as adjuvant therapy for breast cancer

BACKGROUND: Several studies support the belief that the efficacy of adjuvant chemotherapy in breast cancer is related to the dose intensity of the chemotherapy used (expressed in milligrams per square meter per week). Retrospective analyses indicate that the actual delivered dose intensity may correlate more strongly with efficacy than the intended dose delivery. METHODS: A doxorubicin-based adjuvant regimen was studied for breast cancer. It was modeled on the Southwest Oncology Group's regimen of cyclophosphamide, methotrexate, and 5-fluorouracil in that daily oral cyclophosphamide and weekly intravenous 5-fluorouracil were used, but weekly doxorubicin was substituted for methotrexate and administered in both the adjuvant and neoadjuvant setting to 29 patients. RESULTS: The actual dose delivery was 1.21-1.24-fold that calculated for the delivered dose in the two other adjuvant regimens using the same three drugs (5-fluorouracil, doxorubicin, and cyclophosphamide) for which this could be determined. This regimen was tolerated well. Toxicity was minimal and consisted largely of expected neutropenia. CONCLUSIONS: Whether improved dose intensity can be increased further with the use of growth factors or actually confers improved outcomes awaits the results of larger future trials.     

Survival and functional demonstration of interregional pathways in fore/midbrain slice explant cultures

An important general question in neurobiology concerns the development and expression of the rich context of neuronal phenotypes, especially in relation to the diverse patterns of connectivity. Organotypic cultures of brain slices may offer distinct advantages for such studies if such a preparation survives, maintains a wide diversity of neuronal phenotypes and displays appropriate synaptic connections between regions. To address these requirements, we utilized long-term organotypic cultures of intact horizontal slices of rat forebrain and midbrain and assessed a variety of markers of phenotype in combination with functional tests of connectivity. This explant preparation displayed a distinct viability requirement such that the greatest explant survival was seen in slices taken from pups of less than postnatal day 7 and was independent of N-methyl-D-aspartate channel blockade. The anatomical features of the major brain regions (e.g., neocortex, striatum, septum, hippocampus, diencephalon and midbrain) were observed in their normal boundaries. The presence of cholinergic and catecholaminergic neurons was demonstrated with acetylcholinesterase histochemistry and tyrosine hydroxylase immunohistochemistry. Labelled neurons displayed multiple, regionally-appropriate cytoarchitectures and, in some cases, could be seen to project to brain regions in a manner quite similar to that seen in vivo. Finally, the direct demonstration of spontaneous and evoked interregional excitatory synaptic transmission was made using whole-cell patch-clamp recordings from striatal neurons which revealed an intact glutamate-using corticostriatal pathway. This simple explant preparation appears to contain a rich diversity of neuronal types and synaptic organization. Therefore, this preparation appears to have several distinct advantages for basic neurobiologic research since it combines long-term culture viability and many features of mature brain including complex interregional neuronal systems.