Detection of mycobacterial antigen in circulating immune complexes in patients with childhood tuberculosis

The presence of both components (antigen and antibody) in circulating immune complexes (CIC) were detected in tuberculosis in children. Fifty two patients with pulmonary and extrapulmonary tuberculosis showed the presence of either components or both. CIC--antigen was present in 92.3% (48/52) and CIC antibody in 88.96% (46,52). Out of these 52 patients, 20 were proved cases, CIC antigen (ag) and CIC--antibody (ab) were present in 100% (20/20). In the control group both CIC-ag and CIC-ab and CIC = ab can be taken as an additional marker in diagnosis of tuberculosis.     

Mutational analysis of the PTEN/MMAC1 gene in primary oesophageal squamous cell carcinomas.

AIM: To investigate whether PTEN/MMAC1 mutations play a role in the carcinogenesis of oesophageal squamous cell carcinoma. METHODS: A panel of 33 primary oesophageal squamous cell carcinoma tumour samples and 20 corresponding morphologically normal tissues was examined for mutations in all nine exons of the PTEN/MMAC1 gene by means of polymerase chain reaction single strand conformational polymorphism analysis (PCR-SSCP) and direct DNA sequencing methods. RESULTS: Only one of 33 oesophageal squamous cell carcinomas showed an aberrant SSCP band. Further sequencing analysis of this sample revealed an 802 -29 T-->C substitution in intron 7. PTEN/MMAC1 mutations were not found in the mutational "hot spot" in exon 5, even after direct sequencing of six oesophageal squamous cell carcinoma samples and three normal tissues. However, a deletion of one nucleotide T at position 492 +8 in intron 5 was seen in all samples. CONCLUSION: These results suggest that PTEN/MMAC1 mutations do not play a major role in the carcinogenesis of oesophageal squamous cell carcinoma.     

Myocardial infarction complicating gastrointestinal hemorrhage

OBJECTIVE: To determine the frequency of and risk factors for myocardial infarction (MI) in patients admitted to an intensive-care unit (ICU) with gastrointestinal (GI) hemorrhage and to ascertain the effects on mortality and lengths of stay. MATERIAL AND METHODS: Demographic, laboratory, and outcome data were determined for all patients admitted to a medical ICU with GI hemorrhage between April 1996 and January 1997. Serial creatine kinase with isoenzyme levels and electrocardiograms were interpreted blindly by a senior cardiologist. RESULTS: For 83 consecutive admissions to the ICU because of GI hemorrhage, the patients' mean (+/- standard error) age was 65.0 +/- 1.7 years and APACHE II (acute physiology and chronic health evaluation) score was 15.7 +/- 0.8. In-hospital death occurred in 16 patients (19%). Patients who did not survive had a lower admission systolic blood pressure (99.2 +/- 4.5 versus 115.0 +/- 4.0 mm Hg; P = 0.01) than did those who survived. Eleven of 83 patients (13%) fulfilled both enzymatic and electrocardiographic criteria for MI. Ten patients (12%) had electrocardiographic evidence of myocardial ischemia but did not meet criteria for MI. Patients with MI were older (74.4 +/- 4.0 versus 61.7 +/- 2.0 years; P < 0.05), had a higher acuity of illness (APACHE II score, 21.6 +/- 3.0 versus 14.6 +/- 0.7; P < 0.05), and had more coronary risk factors (2.3 +/- 0.3 versus 1.4 +/- 0.1; P < 0.05) in comparison with those without MI or ischemia. Patients with MI also had longer ICU (8.6 +/- 2.4 versus 3.3 +/- 0.4 days; P < 0.05) and hospital (16.3 +/- 3.4 versus 9.1 +/- 0.8 days; P < 0.05) lengths of stay. Patients older than 65 years had a threefold increased risk (risk ratio, 4.0; 95% confidence interval, 0.9 to 17.4) and those with two or more risk factors for coronary artery disease had a ninefold increased risk of MI (risk ratio, 10.2; 95% confidence interval, 1.4 to 76.1) in comparison with those who were younger or who had fewer coronary risk factors, respectively. MI complicating GI hemorrhage did not significantly affect the risk of in-hospital mortality (risk ratio, 1.5; 95% confidence interval, 0.5 to 4.4). CONCLUSION: MI occurs frequently in patients with GI hemorrhage admitted to an ICU. Age more than 65 years and two or more risk factors for coronary artery disease identify patients who are at greatest risk for occurrence of MI, which is associated with longer ICU and hospital stays.     

The oral bioavailability of pentosan polysulphate sodium in healthy volunteers

Objective: Pentosan polysulphate sodium (PPS), a heparin-like drug, is supposed to be orally applicable. The objective of the present study was to assess the oral bioavailability of PPS. However, since specific assays for PPS do not exist, this was done by using primary and secondary effect parameters. Methods: The study was carried out using a three-way randomized crossover design with 18 healthy young male volunteers. The subjects received three treatments: PPS i.v. (50 mg), PPS orally (1500 mg) and placebo (orally). Blood sampling was done for activated partial thromboplastin time (APTT), anti-Xa activity, hepatic triglyceride lipase, lipoprotein lipase, tissue plasminogen activator (t-PA) activity, fibrin plate lysis, total triglyceride, total cholesterol, HDL and LDL. Results: Intravenously administered PPS significantly increased APTT, anti-Xa activity, hepatic triglyceride lipase and lipoprotein lipase compared with placebo in a magnitude comparable to other i.v. heparin-like compounds. Orally administered PPS did not significantly influence any of the parameters when compared with placebo. Point estimates for the oral bioavailability of PPS were in the range of 0% with small confidence intervals (CIs). Conclusion: The oral bioavailability of PPS is negligible in young healthy males. Received: 8 June 1998 / Accepted in revised form: 19 October 1998     

Inhibition of deoxynucleotide-polymerizing enzyme activities of human leukemia lymphoblasts and simian sarcoma virus by tilorone and thirteen of its analogs.

Tilorone, which is 2,7-bis[2-(diethylamino)ethoxy]-9H-fluoren-9-one dihydrochloride, and 13 of its analogs inhibited human cellular DNA polymerases alpha and beta assayed with activated DNA as template and also cellular DNA polymerase gamma and DNA polymerase from simian sarcoma virus assayed with poly(A) (dT)12-18 as template. Terminal deoxynucleotidyltransferase (TdT), which has no template requirement, was not inhibited by any of the 14 compounds when d(A)12-18 or d(G)12-18 was used as initiator. Three compounds did not inhibit TdT assayed with activated DNA as initiator, but 11 compounds did, and these 11 compounds were generally less inhibitory to TdT than to the other DNA polymerases. The three compounds that did not inhibit TdT assayed with activated DNA but did inhibit the other DNA polymerases will be useful in the characterization of TdT activity. Modifications of the polycyclic ring structure of tilorone and the kinds of substituent groups attached to the ring structures influenced the degree of inhibition of all enzymes.     

Sensitivity and tolerance to nicotine in smokers and nonsmokers

We studied the responses of smokers and life-long non-smokers to transdermal nicotine patches over 24 h in three groups of subjects: non-smokers on a 15 mg patch (n=8), non-smokers on a 30 mg patch (n=8) and smokers on a 30 mg patch (n=8). Unexpectedly, the non-smokers appeared to absorb nicotine more rapidly. The increase in blood nicotine concentrations of non-smokers over the first 2 h of patch use was double that of the smokers, with mean increases of 4.5 (SD=3.7), 10.9 (SD=4.2) and 4.1 (SD=2.7) ng/ml in the three groups, respectively (P<0.005). The smokers had no pleasant or unpleasant effects from the 30 mg patch ( C_max 13.9 ng/ml, SD=4.9; T_max 8.75 h) but all eight non-smokers experienced mild nausea and lightheadedness (P<0.01) within the first hour, and seven dropped out (P<0.01) at 3–8 h due mainly to severe nausea, vomiting or headache ( C_max 18.4 ng/ml, SD=4.9; T_max 5.25 h). Only one non-smoker dropped out on the 15 mg patch, but five had transient nausea in the first hour ( C_max 7.9 ng/ml, SD=3.0; T_max 8.0). Our study provides evidence of chronic pharmacodynamic nicotine tolerance in smokers, but does not address whether this is acquired or innate. The higher rate of transdermal nicotine absorption in non-smokers is unexplained and requires replication.     

In vitro binding of gibberellin A(4) to extracts of cucumber measured by using DEAE-cellulose filters

A rapid method for assaying [³H]gibberellin A₄ bound to a soluble protein from cucumber hypocotyls by using DEAE-cellulose filter discs is described. The binding is saturable, reversible with unlabeled gibberellin A₄, and has a half-life of association under nonequilibrium conditions at 0-4°C of 6-7 min. By using this assay, the dissociation constant (K_d) was estimated to be 70 nM and the number of binding sites, 0.4 pmol mg^-1 of soluble protein or 0.69 pmol g^-1 (fresh weight) of hypocotyls. The speed and reliability of the assay make it invaluable for kinetic studies involving competitors. Thus, it has been possible to show that gibberellins that are biologically active in a cucumber bioassay compete for binding to the same protein and their calculated affinity constants bear a direct relationship to their known activities in the cucumber bioassay. Gibberellins that are inactive in this bioassay and other plant hormones, such as indoleacetic acid, abscisic acid, and kinetin, show a noncompetitive interaction.