Complications following major abdominal surgery in cirrhotic patients

The morbidity and mortality associated with major abdominal surgical interventions in 34 histologically proven cirrhotic patients are analyzed by the authors. The surgical interventions were carried out as urgent, absolute and elective indications. Thirty-seven general and surgical complications were observed following major abdominal surgery in 34 cirrhotics. Seven out of 34 patients died, giving a mortality rate of 21%. Suture-line insufficiency, peritonitis, sepsis and other inflammatory processes turned out to be the most common complications. Statistical analysis showed that the Child criteria, prothrombin level and white blood cell count were useful prognostic factors.     

Interfering with the inhibitory mechanism of serpins: crystal structure of a complex formed between cleaved plasminogen activator inhibitor type 1 and a reactive-centre loop peptide

BACKGROUND: Plasminogen activator inhibitor type 1 (PAI-1) is an important endogenous regulator of the fibrinolytic system. Reduction of PAI-1 activity has been shown to enhance dissolution of blood clots. Like other serpins, PAI-1 binds covalently to a target serine protease, thereby irreversibly inactivating the enzyme. During this process the exposed reactive-centre loop of PAI-1 is believed to undergo a conformational change becoming inserted into beta sheet A of the serpin. Incubation with peptides from the reactive-centre loop transform serpins into a substrate for their target protease. It has been hypothesised that these peptides bind to beta sheet A, thereby hindering the conformational rearrangement leading to loop insertion and formation of the stable serpin-protease complex. RESULTS: We report here the 1.95 A X-ray crystal structure of a complex of a glycosylated mutant of PAI-1, PAI-1-ala335Glu, with two molecules of the inhibitory reactive-centre loop peptide N-Ac-TVASS-NH2. Both bound peptide molecules are located between beta strands 3A and 5A of the serpin. The binding kinetics of the peptide inhibitor to immobilised PAI-1-Ala335Glu, as monitored by surface plasmon resonance, is consistent with there being two different binding sites. CONCLUSIONS: This is the first reported crystal structure of a complex formed between a serpin and a serpin inhibitor. The localisation of the inhibitory peptide in the complex strongly supports the theory that molecules binding in the space between beta strands 3A and 5A of a serpin are able to prevent insertion of the reactive-centre loop into beta sheet A, thereby abolishing the ability of the serpin to irreversibly inactivate its target enzyme. The characterisation of the two binding sites for the peptide inhibitor provides a solid foundation for computer-aided design of novel, low molecular weight PAI-1 inhibitors.     

Reduced growth factor requirements and accelerated cell-cycle kinetics in adult human melanocytes transformed with SV40 large T antigen

Melanomas develop with high frequency in transgenic mice in which oncogenic sequences of the SV40 DNA tumor virus have been specifically targeted to melanocytes. To investigate the role of SV40 in melanomagenesis, cultured human melanocytes were transformed with a retroviral shuttle vector encoding the SV40 large T antigen and examined for changes in cell-cycle kinetics and growth-factor dependence. Colonies expressing the viral oncogene were morphologically indistinguishable from their non-T-antigen-transformed counterparts. Also like normal melanocytes, the infected cells remained anchorage dependent and non-tumorigenic in nude mice. However, T-antigen-positive cultures exhibited significantly accelerated population doubling times, increased saturation densities with highly confluent monolayers and a three- to fourfold extended life span. Most interestingly, cell-cycle analysis revealed a measurable shift from quiescent to cycling cells in T-antigen-expressing cultures and an acquired ability to progress more rapidly through G1. Moreover, T-antigen-positive melanocytes proliferated in the absence of PMA and required markedly reduced levels of exogenous bFGF. These studies indicate that the viral oncogen of simian virus 40 provides melanocytes with distinct growth advantages that may render these cells unusually susceptible to additional environmental challenges necessary for full expression of the malignant phenotype.     

Muscle strength in healthy people and in patients suffering from recent-onset inflammatory arthritis

Neuromuscular function was compared among 20 patients with relatively recent onset (symptomatic period 17 +/- 24 months) rheumatoid arthritis (RA) (experimental group; EG), and 20 age- and sex-matched healthy people (control group; CG). The comparison was repeated after a period of 6 months, when 16 patients had carried out progressive strength training. At baseline maximal grip strength and maximal dynamic unilateral strength of the knee extensors in the EG were significantly (P < 0.05) lower in comparison to the CG. The groups did not differ from each other in maximal isometric strength of the trunk flexors and extensors or the knee extensors. The 6-month dynamic strength training in the EG resulted in significant increases in maximal dynamic strength of the knee extensors (P < 0.001), in isometric grip strength (P < 0.001) and in isometric strength of the trunk flexors (P < 0.05) and extensors (P < 0.05) to the level of the healthy controls. Only minor changes took place in explosive strength and maximal isometric strength of the knee extensors. Erythrocyte sedimentation rate (P < 0.001), Ritchie's articular index (P < 0.01) and modified health assessment questionnaire (P < 0.01) improved significantly during the training period. The results suggest that inflammatory arthritis decreases dynamic and/or isometric muscle strength in selected muscle groups of the body already in the early stages of disease. However, progressive dynamic strength training rapidly increases the neuromuscular performance capacity of the patients even to the level of healthy people without detrimental effects on disease activity.     

Programs of early detection of breast cancer and access of mammography in Spain

BACKGROUND: We studied availability to mammography among Spanish women aged 40 to 70 years, variation in use of the mammography by autonomous community, and the situation and importance of breast cancer screening programs among other factors, in the access to mammography. SUBJECTS AND METHODS: A cross-sectional population survey was conducted in 1994 in a sample of 3,218 women. A questionnaire was used to collect data on the variable access (receipt of at least one mammogram in the last 2 years) as well as different access-related variables. Information on breast cancer screening programs was collected by contacting the responsible institutions. We considered that a program had total coverage if it included all the municipalities in the province and partial if it did not include all municipalities. RESULTS: Twenty-eight percent of women had performed a mammogram. This proportion varied among autonomous communities (AACC) from 11.5 to 73.8%. Breast cancer screening programs existed in 8 AACC. The multivariant analysis revealed an association between access to mammography and the existence of a screening program, especially when the later had total coverage (OR = 7.64; 95% CI = 5.24-11.10). An association was also found between access to mammography and physician-related factors, place of residence and attitudes of women toward mammography. CONCLUSIONS: Less than one third of women aged 40-70 have performed a mammography in the last 2 years, and this proportion varies among AACC. Gynecologist visits and the existence of breast cancer screening programs are fundamental factors in the access to mammography in Spain.     

Methotrexate and 6-mercaptopurine maintenance therapy for childhood acute lymphoblastic leukemia: dose adjustments by white cell counts or by pharmacokinetic parameters?

In a consecutive study of 14 boys and 17 girls with non-B-cell ALL who were > or = 1 year of age at diagnosis, the degree of myelosuppression during the last year of MTX/6MP maintenance therapy was analyzed in relation to the erythrocyte concentration of MTX polyglutamates and 6-thioguanine nucleotides (E-MTX and E-6TGN, the respective major cytotoxic metabolites of MTX and 6MP). For each patient, E-MTX and E-6TGN levels were measured 2-15 (median, 6) and 2-17 (median, 7) times, respectively. From these measurements, arithmetic means of E-MTX and E-6TGN were calculated (mE-MTX and mE-6TGN, respectively). Since MTX and 6MP probably work synergistically, the product of mE-MTX and mE-6TGN was calculated for each patient (mE-MTX x 6TGN). The degree of myelosuppression was registered as the mean WBC determined following cessation of the therapy minus the mean WBC measured during the therapy (mWBCshift). The mean WBCs measured on therapy (mWBC(on)) and off therapy were highly correlated (r = 0.48, P = 0.009). The median mWBCshift was 2.7 x 10(9)/l (range, 1.4-4.8 x 10(9)/l). In a multivariate regression analysis, the best-fit model to predict the mWBCshift included mE-MTX x 6TGN, age at drug withdrawal, and mWBC in the order given [mWBCshift = 4.3 + 0.00089 x (mE-MTX x 6TGN) - 0.097 x age - 0.41 x mWBC(on); global rs = 0.66, P = 0.0002]. Thus, the patients with higher mE-MTX x 6TGN values, the younger patients, and the patients with the lowest WBC during therapy had the most pronounced degree of myelosuppression as measured by mWBCshift. These results indicate that E-MTX and E-6TGN may give a better reflection of the treatment intensity than do the WBCs alone.     

Combined use of laparoscopic cholecystectomy and endoscopic retrograde cholangiography (ERC) and papillotomy (ERCP) in management of cholecysto-choledocholithiasis

In a review of 328 cases the combination of laparoscopic cholecystectomy with specific use of endoscopic retrograde cholangiography (pre- and postoperatively) proved to be a riskless, secure and time-saving procedure. In our opinion this is a minimal invasive method of treatment for patients with cholecysto-/choledocholithiasis.     

Cross sections of proton induced nuclear reactions on enriched 111Cd and 112Cd for the production of 111In for use in nuclear medicine

Proton induced nuclear reactions on enriched 111Cd and 112Cd have been studied up to 30 MeV in the context of routine production of the medically used isotope 111In with low and medium energy cyclotrons. The excitation functions of 111Cd(p,n)111m,gIn and 112Cd(p,2n)111m,gIn as production reactions and 111Cd(p,2n)110mIn, 111Cd(p,2n)110In, 111Cd(p,3n)109ml,m2,In, 112Cd(p,3n)110mIn, 112Cd(p,3n)110gIn as competing processes have been measured using the activation method involving the stacked-foil technique. The deduced thick target yields are compared with those obtained experimentally.