Chronic lymphatic leukemia. Peroral cladribine as primary treatment

Ten patients with newly diagnosed B-chronic lymphocytic leukaemia were treated with cladribin orally for five days every four weeks with a median of four series. This is the first reported clinical study where a purine analogue is administered orally. The tumour reducing effect was fast. Eight out of 10 patients responded with a partial or clinical complete remission. Two of these were in molecular biological complete remission. With an observation time of 22 months we have seen no serious side effects so far. A randomized study (including a long term follow up) between chlorambucil, fludarabin and cladribin is needed to clarify the future role of cladribin in B-CLL treatment.     

Separation of bacterial capsular and lipopolysaccharides by preparative electrophoresis

Preparative gel electrophoresis was used to separate and purify extracellular, capsular and lipopolysaccharides (EPSs, CPSs, and LPSs, respectively) from crude bacterial extracts. The procedure effectively separates CPS from LPSs. In addition discreet size ranges of these various polysaccharides can be isolated. The 'rough' (R-type), 'smooth' (S-type), and 'semi-smooth' LPSs were separated from one another. In addition different size classes of 'semi-smooth', or S-type LPS, can be separated. This procedure was demonstrated for diverse bacterial species, including the soil bacteria Rhizobium fredii, and the enteric bacterial species, Salmonella enteritidis and Proteus mirabilis. In the latter case, it was also possible to separate capsular polysaccharide from its lipid-bound form.     

Quantitative relations in the retinal ganglion cell layer of the rat: neurons, glia and capillaries before and after optic nerve section

The severity of pulmonary fibrosis is the main prognostic factor for survival of patients with interstitial lung diseases (ILD). Unfortunately, lung biopsy, which is the best method to assess fibrosis quantitatively, is done only once during the evolution of the disease. In this study we analyzed the relationship between the degree of fibrosis and the exponential constant k, derived from the lung pressure-volume curve (LPVC) in 33 patients with chronic ILD, 19 with pigeon breeder's disease (PBD), and 14 with idiopathic pulmonary fibrosis (IPF). Pulmonary function tests, including the LPVC, were obtained before biopsy. A semiquantitative histologic assessment of the severity of fibrosis was performed on lung tissues. All patients showed a decrease of total lung capacity, residual volume, compliance, and Pao2. The mean value of the constant k was 0.08 +/- 0.06. When expressed as a percent of normal values, 25 patients exhibited values of k lower than 70% of predicted; of the remaining 8 patients whose values were above 70% of predicted, 7 had PBD and only one IPF. On morphologic analysis, 19 patients displayed more than 50% fibrosis. No significant correlations were found between the extent of the lesion or severity of lung fibrosis and the conventional pulmonary function tests. By contrast, a moderate but significant correlation was found between k and the severity of lung fibrosis (r = -0.38, p < 0.05). These findings show that the shape of the LPVC, represented by the constant k, predicts the degree of lung fibrosis and could be useful in the clinical assessment and follow-up of patients with ILD.     

Molecular characterization of Borrelia burgdorferi sensu lato from Slovenia revealing significant differences between tick and human isolates

The aim of the study was to evaluate the morphological and functional status of the liver in acute, oral cholinesterase inhibitors poisoning using static scintigraphy, hepatography and measurements of chosen enzymes activity. Considering the different clinical picture of cholinesterase inhibitors poisonings in people, it was necessary to estimate the poisoning severity and its dependence on the frequency and intensification of the liver lesion. Under examination there were 37 cholinesterase inhibitors orally poisoned patients, treated at the Department of Toxicology in the years 1992-1995. The examined group comprised 7 women (19%) and 30 men (81%). Organophosphate compounds poisoning was noted in 14 patients, and carbamates poisonings in 23 patients. The reference group comprised 30 healthy men aged 24 to 59 years not exposed to hepatotoxic agents. More than 90% of patients were classified as severe poisoned. Any fatal case was not noted. A differently intensified pathological changes of the liver dependent on age and poisoning severity were found in 97.2% of patients and their frequency was significantly higher than in the control group. Hepatographic picture revealed in 96.6% of cases the liver lesion. Hepatographic picture of the liver was also dependent on poisoning severity. The higher activity of AST, ALT, AP and higher bilirubin concentration in blood were noted in poisoned men compared to the control group. Control scintigraphic examination revealed a considerable improvement in the intensification of the liver scintigraphic picture in 40% of the patients and a higher intensification in 13% of the subjects. In 46.6% of the patients the intensification of scintigraphic changes remained at the same level. Considering arbitrary criteria for the degree of the liver lesion, the improvement in the intensification of hepatographic changes was noted in 42.8% of the patients; the intensification of the liver lesion was not noted even in one case. Analyzing the percentage of the liver lesion for each individual patient, improvement was noted in 92.8% of the examined patients, and the changes with the same level of intensification in 7.2%. Deterioration was not noted at all. Conclusion: The liver scintigraphy and hepatography combined with biochemical analysis allows to assess the liver condition in acute cholinesterase inhibitors poisoning.     

In vitro effect of ketones and hyperglycemia on feline hemoglobin oxidation and D- and L-lactate production

Postoperative nausea and vomiting (PONV) are unpleasant, often underestimated side effects of anaesthesia and surgery, not devoid of medical complications. Prevention with antiemetics is only partially effective. Propofol has been shown recently to possess antiemetic properties in several situations. In this prospective, randomized, controlled trial, we have compared the antiemetic efficacy of subhypnotic doses of propofol, with Intralipid as placebo, after thyroidectomy. We studied 64 patients of both sexes, aged 22-71 yr, ASA I or II, undergoing thyroidectomy. After premedication with a benzodiazepine, balanced anaesthesia was produced with isoflurane and nitrous oxide in oxygen, and supplementary analgesia with fentanyl i.v. as required. Postoperative analgesia was provided with non-opioids, and piritramide 0.25 mg kg-1 i.m. on demand. Patients were allocated randomly and blindly to receive a 20-h infusion of either propofol or 10% Intralipid 0.1 ml kg-1 h-1. Intralipid, the excipient of propofol, was chosen as placebo as it is devoid of antiemetic effects. Sedation scores, respiratory and cardiovascular variables, and incidence of PONV were assessed every 4 h for 24 h. Pulse oximetry and ECG were monitored continuously. Both groups were comparable in characteristics, surgical and anaesthesia procedures, amount of opioids given during and after operation, and total amount of the study drug infused after operation. Occurrence of PONV was similar before the start (propofol 41%, Intralipid 50%) and after completion (propofol 0.64%, Intralipid 1.6%) of infusion and decreased with time in both groups during the infusion. However, symptoms were reduced to nil with propofol but persisted and were more severe with Intralipid during infusion (P < or = 0.01). The overall incidence of PONV during infusion was 10% (three of 32 patients) in the propofol group and 65% (21 of 32 patients) in the Intralipid group. Cardiovascular and respiratory variables, and SpO2 were unaltered, and sedation decreased similarly with time in both groups. We conclude that propofol, given at subhypnotic doses, effectively reduced the incidence of PONV without untoward sedative or cardiovascular effects.     

Using focus groups to identify psychosocial issues of urban black individuals with diabetes

BACKGROUND: Human serum represents an important barrier to the entry of most mucosal organisms into tissues and to the systemic circulation. If at all present, Helicobacter pylori within gastric tissue is rare, and bacteremia for this organism has been described only once. METHODS: To assess the susceptibility of H. pylori to the bactericidal activity present in normal human serum (NHS), we examined 13 H. pylori isolates. To assess the contributions of the classical and alternative complement pathways to killing, we added either C2-deficient or factor B-deficient serum, respectively, to heat-inactivated NHS. Also we assessed the ability of the strains to bind 125I-C3. RESULTS: After incubation for 60 minutes at 37 degrees C, all 13 H. pylori strains were killed by NHS; heating to 56 degrees C for 30 minutes ablated killing, indicating complement dependence for this phenomenon. In the absence of an antibody source, there was no killing when either an alternative or classical complement pathway source was used. Adding B-deficient serum to heat-inactivated normal human serum did not restore killing, but adding C2-deficient serum permitted partial killing. All of the 13 strains bound 125I-C3. Although the kinetics varied from strain to strain, C3 bound was significantly correlated (r = 0.61, p = 0.03) with serum susceptibility. CONCLUSIONS: H. pylori are susceptible to complement, alternative pathway activation appears critical, and C3 binding is a major locus of variability.     

Contribution of plasminogen activators and their inhibitors to the survival prognosis of patients with Dukes' stage B and C colorectal cancer

Despite the advances in pre-, peri- and post-operative medical care of colorectal carcinoma patients, the prognosis has improved only marginally over recent decades. Thus, additional prognostic indicators would be of great clinical value to select patients for adjuvant therapy. In previous studies we found that colorectal carcinomas have a marked increase of the urokinase-type of plasminogen activator (u-PA), and the inhibitors PAI-1 and PAI-2, whereas the tissue-type plasminogen activator (t-PA) is found to be decreased in comparison with adjacent normal mucosa. In the present study we evaluated the prognostic value of several plasminogen activation parameters, determined in both normal and carcinomatous tissue from colorectal resection specimens, for overall survival of 136 Dukes' stage B and C colorectal cancer patients, in relation to major clinicopathological parameters. Uni- and multivariate analyses indicated that a high PAI-2 antigen level in carcinoma, a low t-PA activity and antigen level and a high u-PA/t-PA antigen ratio in adjacent normal mucosa are significantly associated with a poor overall survival. A high ratio of u-PA antigen in the carcinomas and t-PA antigen in normal mucosa, i.e. u-PA(C)/t-PA(N), was found to be predictive of a poor overall survival as well. All these parameters were found to be prognostically independent of the clinicopathological parameters. Multivariate analysis of combinations of these prognostically significant plasminogen activation parameters revealed that they are important independent prognostic indicators and have in fact a better prognostic value than their separate components. Based on these combined parameters, subgroups of patients with Dukes' stage B and C colorectal cancer could be identified as having either a high or a low risk regarding overall survival. In conclusion, these findings emphasize the relevance of the intestinal plasminogen activation system for survival prognosis of patients with colorectal cancer and, in the future, might constitute a patient selection criterion for adjuvant therapy.