Convulsant action of a benzodiazepine receptor agonist/inverse agonist Ro 19-4603 in developing rats

An inverse benzodiazepine receptor agonist Ro 19-4603, administered intraperitoneally, was found to induce two types of motor seizures, i.e. minimal, predominantly clonic and major, generalized tonic-clonic, in rats at all developmental stages studied (7, 12, 18 and 25 days old). The developmental profile of the two types of seizure was different. Minimal seizures could be induced easily in the two youngest groups, whereas there were no marked differences in the induction of major seizures between the age groups. A lethal outcome was more common in 18- and 25-day-old rats than in younger animals. The convulsant action of the benzodiazepine agonist/inverse agonist Ro 19-4603 shows only quantitative changes during post-natal development in the rat.Abbreviations DPPC Diplamitoylphosphat     

Incidence of IDDM during 1988–1992 in Zagreb,Croatia

Summary The objective of this study was to determine the incidence of insulin-dependent diabetes mellitus (IDDM) in the population of Zagreb, Croatia, during 1988–1992. A centralized diabetes registry was the primary source of data, while secondary sources were used to assess ascertainment. A total of 282 new cases of IDDM were diagnosed in the study period, the primary and secondary sources identifying annually 93–100% of the cases. The annual incidence rate ranged from 5.6 per 100,000 to 6.6 per 100,000. Early fatality in persons older than 50 years was the major cause of underascertainment. The incidence peaked in the 10–14 years age group (12.4 per 100,000), and remained stable after age 24 years. Males had a significantly higher incidence in the 5–9 and 24–44 years age groups. In the 45–54 years age group, females had a significantly higher incidence. No seasonality was observed. Despite the war conditions in Croatia, the low overall IDDM incidence rates did not change significantly during the study period.Abbreviations IDDM Insulin-dependent diabetes mellitus - DKA diabetic ketoacidosis     

Incidence and mechanisms of aminoglycoside resistance inPseudomonas aeruginosa serotype O11 isolates

Summary Mechanisms of resistance to five aminoglycoside antibiotics: gentamicin (G), tobramycin (T), netilmicin (N), amikacin (A) and isepamicin (I), were assessed in 16 clinical isolates ofPseudomonas aeruginosa serotype O11, originating from five hospitals in Bratislava. All isolates werein vitro highly resistant to all mentioned aminoglycoside antibiotics (MIC>32 mg/l). Thirteen isolates produced three aminoglycoside-modifying enzymes (AGME), responsible for resistance to the respective aminoglycosides: AAC(6)-I (T, N, A); APH (2) (G, T); APH (3)-VI (I). In addition to this, in four isolates a production of AAC(3)-II (G, T, N) was observed. In three isolates no production of AGME was observed. The strains studied were isolated mainly from urine. Several isolates were able to transfer aminoglycoside resistance by bacterial conjugation toP. aeruginosa 1008 rif^r recipient. The transconjugants from these transfers expressed the same resistance pattern and nearly the same mechanisms of resistance as the donor strains.

---

Inzidenz und Mechanismus der Aminoglykosid-Resistenz beiPseudomonas aeruginosa O11-Isolaten

Zusammenfassung Bei 16 klinischen Isolaten vonPseudomonas aeruginosa Serotyp O11 aus fünf Krankenhäusern in Bratislava wurde der Mechanismus der Resistenz gegen fünf Aminoglykosid-Antibiotika untersucht; Gentamicin (G), Tobramycin (T), Netilmicin (N), Amikacin (A) und Isepamicin (I). Alle Isolate warenin vitro hochresistent gegen alle genannten Aminoglykosid-Antibiotika (MHK-Werte >32 mg/l). 13 der Isolate bildeten drei Aminoglykosid-modifizierende Enzyme (AGME), die für die Resistenz gegenüber den entsprechenden Aminoglykosiden verantwortlich waren: AAC(6)-I (TNA): APH (2) (G, T): APH (3)-VI (I). Zusätzlich wurde bei drei Isolaten die Produktion von AAC(3)-II (G, T. N) beobachtet. In drei Isolaten fand sich keine Produktion von AGME. Die untersuchten Stämme waren überwiegend aus Urin isoliert worden. Mehrere der Isolate waren fähig, die Aminoglykosid-Resistenz durch bakterielle Konjugation auf denP. aeruginosa 1008 rif^r Rezipienten zu übertragen. Die Transkonjugate von diesen Übertragungen exprimierten dasselbe Resistenzmuster und wiesen nahezu denselben Resistenzmechanismus auf wie die Spenderstämme.

     

Urinary excretion of adenosine deaminase binding protein in neonates treated with tobramycin

The potential tubulotoxicity of tobramycin and cefotaxim were assessed in neonates by measuring the urinary level of adenosine deaminase binding protein (ABP) and urinary ₁-microglobulin and ₂-microglobulin. In a prospective study, 33 neonates who received tobramycin and cefotaxim for suspected neonatal sepsis were compared with 48 untreated newborns during the first 10 days of life. The urinary concentrations of ABP and its excretion rates, corrected for body weight and body surface area, were significantly increased from the 1st day of treatment. Urinary ₁-microglobulin and ₂-microglobulin were not elevated under tobramycin and cefotaxim during the first 2 days of treatment. We conclude that ABP may be a sensitive marker for the detection of proximal renal tubular injury during tobramycin and cefotaxim treatments of neonates. The increase in urinary ABP which occurs before an elevation of urinary ₁-microglobulin and ₂-microglobulin may reflect earlier structural than functional alterations. However, since none of the treated infants had signs of electrolyte disorders or glomerular dysfunction, the clinical relevance of ABP measurement should be reevaluated.     

TTAGG Telomeric Repeats in Chromosomes of Some Insects and Other Arthropods

We studied the occurrence of the TTAGG telomere repeats by fluorescence in-situ hybridization (FISH) and Southern hybridization in ten insect species and two other arthropods. (TTAGG)_n-containing telomeres were found in three Lepidoptera species, the silkworm Bombyx mori (in which the telomeric sequence was recently discovered), the flour moth Ephestia kuehniella, and the wax moth Galleria mellonella, in one species of Hymenoptera, the honey bee Apis mellifera, in one species of Coleoptera, the bark beetle Ips typographus, in one species of Orthoptera, the locust Locusta migratoria, and in a crustacean, the amphipod Gammarus pulex. They were absent in another species of Coleoptera, the mealworm Tenebrio molitor, two representatives of Diptera, Drosophila melanogaster and Megaselia scalaris, a species of Heteroptera, the bug Pyrrhocoris apterus and a spider, Tegenaria ferruginea. Our results, which confirm and extend earlier observations, suggest that (TTAGG)_n was a phylogenetically ancestral telomere motif in the insect lineage but was lost independently in different groups, being replaced probably by other telomere motifs. In the Coleoptera this must have happened rather recently as even members of the same family, Curculionidae, differ with respect to the telomeric DNA.     

Idiopathic interstitial pneumonitis presenting with Wells grade III. Can imaging methods help predict further progression of disease?

PURPOSE: Three different grades of idiopathic pulmonary fibrosis can be identified by HRCT pattern. Patients with predominant ground-glass opacity (grade I) usually improve after treatment and may have a better prognosis. The subjects with a predominant reticular pattern and honeycombing (grade III) have irreversible fibrosis and usually do not improve after immunosuppressive therapy. Nevertheless, these patients may worsen even in the absence of HRCT features of the so-called alveolitis. We investigated the predictive role of some noninvasive imaging methods (HRCT with visual score of disease extent; Gallium scintigraphy; DTPA scintigraphy) in patients with idiopathic fibrosis and a prevalent macroscopic fibrosis at HRCT study. MATERIAL AND METHODS: Fourteen former smokers with grade III idiopathic fibrosis were examined. None of the patients had been treated. They were all submitted to HRCT, lung function studies, Gallium and DTPA scintigraphy, both at presentation (T0) and follow-up sessions (T1: mean one year post-diagnosis). The HRCT extent of disease was evaluated by means of the visual score as the fraction of the total lung volume. The patients were divided into two groups, using a cut-off value of 50%. All the patients underwent a Gallium scintiscan (using a fixation index of 160 as cut-off) and a ventilatory scintigraphy with DTPA-aerosol, with radionuclide clearance assessment. The lung function tests considered were vital capacity (VC), arterial blood oxygen partial pressure (PaO2) and the diffusing lung capacity for carbon monoxide (DLCO). RESULTS: After one year of follow-up, the HRCT extent score increased (from 46.6% to 50%) and lung function worsened (VC from 66.8% to 63.4% of predicted; DLCO from 37.6% to 27.1%; PaO2 from 77 to 71 mmHg). The patients presenting with HRCT extension score > 50% had a worse lung function at T0 and showed a significant deterioration of PaO2 and HRCT at T1. On the other hand, VC and DLCO significantly worsened in the subjects with HRCT score < 50% at presentation. The patients with a Gallium fixation index > 160 significantly deteriorated in HRCT score, VC and DLCO. Those with Gallium index < 160 had major worsening only for diffusing lung capacity for carbon monoxide. Thirteen of 14 patients had an abnormal value of DTPA clearance at presentation. No variation was observed at T1. DISCUSSION AND CONCLUSIONS: The majority of patients with idiopathic fibrosis are grade III at presentation. They can further deteriorate both in HRCT extent of disease and lung function impairment. After one year of follow-up HRCT extent score increased in 64% of the patients, with a mean increase of 5%. HRCT worsening was more apparent in the patients with a HRCT score > 50% at presentation. In the remaining patients, the worsening of lung function tests was more apparent than the anatomoradiological changes. DTPA clearance had no predictive value in this series. Gallium scintigraphy was a useful prognostic index. The patients with Gallium fixation index > 160 had better lung function and lower HRCT extent score at T0 but significantly deteriorated at T1. A positive Gallium scan at presentation could be considered a useful index of persisting active "alveolitis" in patients with grade III disease, not visible at HRCT study, due to overwhelming fibrosis. These patients, who were untreated, exhibit quicker radiological and functional worsening.     

The concordance and discordance of cardiovascular risk factors in a group of twin children

The cross-sectional study of epidemiological screening type has permitted to evaluate some cardiovascular risk factors in two groups of monozygotic (MZ) and dizygotic (DZ) twins born between 1975-1990, in the town of Ia?i. In the 89 MZ pairs and 112 DZ pairs, certain constitutional and behavioural cardiovascular risk factors have presented values of prevalence with statistical signification (p < 0.05) in terms of their age, sex, the urbanisation time and the educational level of their parents. In risk factors existence or absence to both of the twins have put into evidence, to the MZ, most enhanced values of concordance as regards: overweight (66.6%), excessive consumption of salt (56.9%), food with atherogenic risk (50.9%). The concordance values have been less in DZ compared to MZ concerning all the risk factors excepting compartmental type A (77.7%). By analysing the concordance variants, an preponderant influence of the environment has been noted in the studied MZ and heredity and environment influence in DZ. By measuring the arterial blood pressure values at the twins and the twins parents, a prevalence of the essential arterial hypertension is noticed to both of the twins, 6.2% in MZ pairs and 6.9% in DZ ones.     

Prospective Evaluation of Prostate Specific Antigen (PSA), PSA Density,Free-to-Total PSA Ratio and a New Formula (Prostate Malignancy Index) for Detecting Prostate Cancer and Preventing Negative Biopsies in Patients with Normal Rectal Examinations and Intermediate PSA Levels

Objective: To improve the specificity and sensitivity of prostatic cancer detection, we prospectively evaluated total prostate specific antigen (PSA) level, PSA density, free-to-total PSA ratio and a new formula called prostate malignancy index (PMI) as a discriminator of prostate cancer in patients with intermediate PSA levels and normal digital rectal examinations. Materials and methods: Between November 1995 and October 1997, 95 patients who had serum PSA levels of 4.0 to 10.0 ng/ml with normal digital rectal examinations were prospectively evaluated. All patients underwent one or two times transrectal ultrasound guided prostate biopsies. Based on age specific reference range of PSA, PSA density and % free PSA ratio, PMI was calculated for each patient. The free and total serum PSA concentrations were determined by an Immulite assay system. (Diagnostic Product Corp., Los Angeles, California). Results: Overall 20 of 95 (21%) patients had prostate cancer. There were no significant differences in patient mean age and mean total PSA between those with benign and those with malignant biopsies (p>0.05). However, there were significant differences in mean PSAD, mean free-to-total PSA ratio and mean PMI (p<0.01, p<0.05, p<0.01, respectively). Benign condition specificities for PM index, percent free PSA, PSA density and total PSA at a 90% sensitivity for prostate cancer were 48%, 10.6%, 8% and 4%, respectively. Of 95 patients, 27 (28.4%) had a PMI of equal or more than 3.1, including 12 of 75 (16%) with negative biopsy and 15 of 20 (75%) with positive biopsy. Furthermore a cutoff MI 0.86 P correctly identified 24% of benign cases without missing any prostate cancer cases. The comparison of receiver operating characteristic (ROC) curve areas showed that PMI was better than total PSA (p<0.01). Although, the area under the ROC curve of % free PSA and PSAD were higher than the area of total PSA, these differences were not statistically significant (p>0.05). Conclusions: We concluded that the prostate malignancy index could be utilized to differentiate benign conditions from prostate cancer in patients with intermediate PSA levels and normal digital rectal examination. Also significant numbers of negative biopsies can be prevented in these patients.