A comparative evaluation of the action of depressant and stimulant drugs on human derformance

Summary The effects of orally administered alcohol (10 and 20 cm³), alcohol (10 cm) together with distraction, of pentobarbital (150mg), of amphetamine (7.5 mg) and of caffeine (100 and 200 mg) on performance of motor and intellectual tasks by intelligent human subjects was studied.Pentobarbital depressed all of these tests, whereas the other drugs showed differential actions: alcohol prominently increased errors in the addition test at doses not affecting other intellectual tasks or motor performance. Amphetamine and caffeine decreased errors on mental tasks while not affecting the motor tasks. Distraction acted in these individuals as a stimulant, decreasing errors apparently by raising the level of alertness, and it also counteracted the deleterious effect s of alcohol on these tasks.     

Wavelet analysis of cutaneous blood flow in melanocytic skin lesions

Laser Doppler flowmetry (LDF) is frequently used to study the microcirculation. Usually LDF time series are analyzed by conventional linear methods, mainly Fourier analysis. The aim of this study was to observe dynamic blood perfusion of the skin in malignant and benign melanocytic skin lesions. Wavelet transformation was performed on each LDF time series in order to calculate a vasomotion field. First, the differences in vasomotion between healthy and pigmented skin were evaluated visually on six different time scales of the vasomotion field. In order to quantify the findings, vasomotion scale variance (VSV) was calculated for each scale plane of the vasomotion field. These VSV were compared using contrast DeltaVSV to determine the difference between healthy skin and a pigmented skin lesion in the same patient. After the measurements, the skin lesions were excised and examined histologically. We found that wavelet analysis of LDF time series is a specific, sensitive method for the in vivo identification of malignant melanoma. It is a non-invasive procedure and takes minimal time to be carried out.     

Detecting and monitoring leprosy neuropathy: which test to chose?]

The purpose of the study is to propose a simple and reproducible test for assessing nerve damage in leprosy. It is applied to the sensory branch of the radial nerve of leprosy patients, prior to any treatment. Skin sensitivity is measured by means of a needle, a drop of ether and some calibrated filaments. These three tests are collated and compared with the results of electromyographic examination of the nerve. The filament calibrated to 0.2 grams gives optimum sensitivity (0.79) and excellent specificity (0.95) in relation to the electromyographic test. Its routine use in the field is simple and reproducible and should result in a greater number of patients receiving the treatment they need.     

Synthesis,antitumor activity,distribution and toxicity of 4-[4-[Bis(2-chloroethyl)amino]phenyl]-1-hydroxybutane-1 1-bisphosphonic acid (BAD), a new lost derivative with increased accumulation in rat osteosarcoma

The aim of this study was to investigate whether the newly synthesized bisphosphonic acid-linked N-Lost derivative BAD retains bone-seeking and cytostatic properties. The paper describes experiments on mutagenicity in vitro and on toxicity in vivo. BAD is characterized by very low mutagenic activity toward histidine auxotrophic Salmonella typhimurium strains. Cytotoxic effects were tested in rat osteosarcoma and in Walker carcinosarcoma 256B. The LD50 of i.v. injected BAD was 146 mg/kg. Acute toxicity is probably caused by calcium complexing of the bisphosphonate part of the molecule. Labeling experiments showed moderate accumulation in bone and osteosarcoma, as well as in lung metastases. BAD effected high tumor growth inhibition in osteosarcoma and Walker carcinosarcoma-bearing rats and marked prolongation of survival; histologic and radiographic examination revealed rapid calcification of osteosarcoma and lung metastases. BAD-pretreatment produced protective effects against osteolysis induced by intratibially implanted Walker carcinosarcoma ascites cells. The cytostatic efficacy of equitoxic doses of BAD in rat osteosarcoma is comparable to that of dacarbazine and in Walker carcinosarcoma to that of melphalan.     

Varicella zoster infection and pulmonary complications

A 34-year-old immunocompetent man with varicella zoster (VZ) infection developed deep vein thrombosis and pulmonary embolism after suffering severe pneumonitis. He recovered after treatment with acyclovir, high-dose steroids, and ventilatory support. The endothelial damage could be a direct link between VZ pneumonitis and pulmonary emboli.     

Hepatitis B reactivation during ruxolitinib treatment

Annals of Hematology -     

Protein intake and kidney function in humans: its effect on 'normal aging'

The effect of dietary protein on kidney function expressed by creatinine clearance was studied in healthy subjects following a "normal" unrestricted protein diet and compared with a group of vegetarians maintained on a long-term low-protein diet. Both groups had similar kidney function and displayed the same rate of progressive deterioration in renal function with age. These results suggest that, in contrast with the important therapeutic effect of low-protein intake on the progressive deterioration of kidney function in diseased kidneys, such a diet does not significantly affect kidney function with "normal aging" in healthy subjects.     

Gene therapy of hepatocellular carcinoma in vitro and in vivo in nude mice by adenoviral transfer of the Escherichia coli purine nucleoside phosphorylase gene

Expression of viral or bacterial enzymes in tumor cells to convert nontoxic prodrugs into highly toxic metabolites is an attractive gene-therapeutic approach for the treatment of hepatocellular carcinoma (HCC). The Escherichia coli purine nucleoside phosphorylase (PNP) converts purine analogs into freely diffusible metabolites, which are highly toxic to dividing and nondividing cells. We investigated the antitumor effects of PNP in the human HCC cell lines, HepG2, Hep3B, and HuH-7, and performed a comparison with herpes simplex thymidine kinase (TK). The genes for PNP, TK, and enhanced green fluorescent protein (EGFP) were delivered to HCC cells by identical adenoviral vectors. Fludarabine and ganciclovir (GCV) served as prodrugs for PNP and TK, respectively. Expression of PNP highly sensitized HCC cells to fludarabine treatment. Fludarabine concentrations between 0.5 and 1 microg/mL killed 100% of the cells expressing PNP with no detectable toxicity in control cells expressing EGFP. Expression of PNP in as few as 10% of HCC cells induced efficient killing of most bystander cells. Expression of TK followed by GCV treatment produced a potent growth inhibition but failed to kill all TK-expressing HCC cells. More importantly, the TK system exhibited a lower degree of bystander effect. Adenoviral delivery of PNP followed by fludarabine administration prevented subcutaneous and intrahepatic tumor formation in nude mice and was also effective for the treatment of established tumors. These results demonstrate the potential of the PNP/fludarabine system for the treatment of HCC.     

Identification of an oncogenic form of the thrombopoietin receptor MPL using retrovirus-mediated gene transfer

Thrombopoietin and its receptor (MPL) are important regulators of megakaryopoiesis. We have identified an activating mutation of MPL using a combination of a retrovirus-mediated gene transfer and polymerase chain reaction-driven random mutagenesis. This point mutation causes a single amino acid substitution from Ser498 to Asn498 in the transmembrane region and abrogates factor-dependency of all interleukin-3-dependent cell lines tested. Murine interleukin-3- dependent Ba/F3 cells expressing the mutated but not the normal form of MPL were tumorigenic when transduced into syngeneic mice. Analysis of intracellular signaling pathways indicated that the mutant MPL protein constitutively activated two distinct signaling pathways, SHC-Raf-MAPK and JAK2-STAT3/STAT5.