2155610##1990-02-28##Interleukin-1 beta analogues with markedly reduced pyrogenic activity can stimulate secretion of adrenocorticotropic hormone in rats.##We examined the adrenocorticotropic hormone-releasing activities of several human interleukin-1 beta analogues that have markedly reduced pyrogenic activities in rats. Among the analogues tested, [Gly4]-, [Leu93]- and [1-148]-interleukin-1 beta increased the plasma adrenocorticotropic hormone level to almost that induced by authentic human interleukin-1 beta. Modifications of the N-terminus of the authentic molecule, i.e., [7-153]- and [Des-Ala1, Asp4]-interleukin-1 beta, significantly reduced the hormone-releasing activity. These data suggest that the adrenocorticotropic hormone-releasing activity of human interleukin-1 beta resides in the N-terminal structure of the authentic peptide and can be separated from its pyrogenic activity.
2155021##1990-02-28##Regulation of cytoplasmic pH in resident and activated peritoneal macrophages.##Cytoplasmic pH (pHi) has been shown to be an important determinant of the activity of the NADPH oxidase in phagocytic cells. We hypothesized that a difference in pHi and/or its regulation existed between activated and resident macrophages (RES MOs) which might explain the increased NADPH oxidase activity observed in the former. The pHi of RES and lipopolysaccharide (LPS)-elicited MOs was examined using the fluorescent dye BCECF. Resting pHi did not differ between resident (RES) and elicited (ELI) MOs (7.16 +/- 0.05 and 7.20 +/- 0.05, respectively). pHi recovery after intracellular acid loading was partially dependent on the presence of Na+ in the extracellular medium, and was partially inhibited by the Na+/H+ antiport inhibitor, amiloride. At comparable pHi, the rate of acid extrusion during recovery was not different in RES and ELI MOs (1.48 +/- 0.12 and 1.53 +/- 0.06 mM/min, respectively). In both RES and ELI MOs, approx. 40% of total pHi recovery was insensitive to amiloride and independent of extracellular Na+. In both RES and ELI MOs, stimulation with TPA resulted in a biphasic pHi response: an initial acidification followed by a sustained alkalinization to a new steady-state pHi. This alkalinization was Na(+)-dependent and amiloride-sensitive, consistent with a TPA-induced increase in Na+/H+ antiport activity. The new steady-state pHi attained after TPA stimulation was equivalent in RES and ELI MOs (7.28 +/- 0.04 and 7.31 +/- 0.06, respectively), indicating comparable stimulated Na+/H+ antiport activity. However, the initial acidification induced by TPA was greater in ELI than in RES MOs (0.18 +/- 0.02 vs. 0.06 +/- 0.02 pH unit, respectively, P less than 0.05). The specific NADPH oxidase inhibitor diphenylene iodonium (DPI) completely inhibited the respiratory burst but reduced the magnitude of this pHi reduction by only about 50%. This suggested that the TPA-induced pHi reduction was due in part to acid produced via the respiratory burst, and in part to other acid-generating pathways stimulated by TPA.
2140313##1990-02-28##[Transluminal percutaneous angioplasty in renovascular hypertension caused by monolateral fibromuscular dysplasia]##The authors, following recent observation of two cases of renovascular hypertension, one related to single right renal artery stenosis and the other to fibromuscular dysplasia of the left renal artery, examine the value of the Captopril-Test and treatment with Percutaneous Transluminal Angioplasty (PTA), in the diagnosis and therapy of this form of hypertension. According to the latest experience, reported in the literature, the Captopril-Test yields valid information as regards the dependence of hypertension on the renin-angiotensin system, while PTA represents the primary procedure in the treatment of renovascular hypertension when some conditions are satisfied as in our cases.
2140311##1990-02-28##[Treatment with thymopentine of chronic bronchitis in elderly patients during seasonal prophylaxis]##The design of the present study permits to analyse the efficacy of thymopentin treatment in seasonal prophylaxis of chronic bronchitis in elderly patients. The immunologic and symptomatic responses were observed and evaluated. The elderly female patients, observed in the present study, were followed for six months after treatment with thymopentin.
2140310##1990-02-28##[The Ehlers-Danlos syndrome and its surgical implications]##The Ehlers-Danlos syndrome, type IV, i.e. the arterial and ecchymotic variety, has a severe prognosis and may represent a threat to life in that it predisposes to spontaneous rupture of the intestine and large vessels. The authors report a case in which spontaneous rupture of the colon and thoracic aorta occurred in short succession. Description of the syndrome and its many variants is preceded by a brief explanatory note on the formation and composition of collagen and its different types. The authors stress the important surgical implications of the syndrome the special risks deriving from elective surgery. Serious consequences may also derive from pregnancy trauma and from acts such as arteriography, endotracheal intubation, endoscopy and other invasive procedures. After examining the cases reported in literature (Sacks, Barabas, Beighton Sykes), they point out that, contrary to what is generally believed, the syndrome is not rare and cases, sporadic or familial, of recurrent episodes of spontaneous rupture of the intestine and large vessels or peripheral arteries are frequent. The authors come to the following conclusions: rupture of the aorta may occur spontaneously or after minimal trauma in subjects with EDS type IV and the cases complicated by spontaneous colon perforation would take advantage from definitive colostomy, considering the high incidence of recurrent perforations when intestinal continuity is restored.
2140309##1990-02-28##[Evaluation of the effectiveness of sodium piperacillin in the treatment of surgical infections in children]##A clinical trial has been carried out in 40 children (age ranging from 2 to 12 years) with postsurgical infections caused by aerobic, anaerobic and facultative bacteria. All have been treated by monotherapy with sodium piperacillin, with doses of 150-200 mg/kg daily in 3 administrations. The drug was administered for a mean period of 7 days, by intravenous infusion or intramuscular route. The causative organism was eradicated in all but 4 cases (90%). Side effects observed were all of mild intensity, and in no case it was necessary to discontinue the treatment with the drug. Both bacterial and clinical results indicate a high tolerability and a very rapid effectiveness of this antibiotic.
2138828##1990-02-28##[Prenatal ultrasonic diagnosis and Down's syndrome]##A total of 8,923 children were born at the Regional Hospital, Trondheim, Norway between 1 January 1986 and 30 June 1989 to mothers from surrounding municipalities. Among these children, 14 were diagnosed after birth as having Down's syndrome. A proportion of 85% of the pregnant women in these municipalities had had a routine examination with ultrasound in the 16th to 22nd weeks of gestation at the Ultrasound Laboratory at the Regional Hospital. Ten of the children/fetuses with Down's syndrome in the study population had been subjected to a routine scan. Five of the ten were suspected to have Down's syndrome after the routine scan, and the diagnosis was confirmed by prenatal chromosomal analysis. (All these five fetuses were examined in 1987-88, which means that five of seven were detected in 1987-88). Another two fetuses (out of three) were suspected to have Down's syndrome after an ultrasound scan later in pregnancy. The diagnoses were confirmed by chromosome analyses after birth. One fetus was diagnosed in a 38 year old woman by amniocentesis in the 15th week of gestation. Our study suggests that routine ultrasonic scans can detect a significant proportion of fetuses with Down's syndrome in the second trimester.
2129524##1990-02-28##Rat pancreatic colipase mRNA: nucleotide sequence of a cDNA clone and nutritional regulation by a lipidic diet.##A cDNA clone encoding rat pancreatic colipase was isolated using as a probe a synthetic deoxyoligonucleotide corresponding to a highly conserved amino acid sequence region in colipases from other species. The cloned messenger codes for a protein of 95 amino acids plus a signal peptide of 17 amino acids. The structure of the full-length cDNA was also determined and the corresponding amino acid sequence showed a high degree of homology with those of other known colipases. Quantification of the homologous mRNA in the pancreas of animals fed a high-lipid diet was consistent with a specific though moderate induction of colipase messenger by the nutritional manipulation.
2108517##1990-02-28##Long-term results with the Gn-RH analogue, buserelin, in metastatic prostate cancer.##LH-RH analogues have come into use to suppress the synthesis of testosterone by the testes and to induce palliation in advanced prostate cancer. Twenty-one patients were treated with buserelin (Hoe 766), and 19 were evaluable. Stages of disease were D1-D2. Seventeen patients responded to treatment, 3 patients are still in partial response, and 16 underwent progression. The median time to progression was 12 months (range, 3-36), and the median follow-up time was 10 months (mean, 25.4; range, 5-48).
2108516##1990-02-28##Open phase II with 5-fluorouracil, 4-epi-doxorubicin and mitomycin C (FEM) in advanced gastric cancer.##Forty-four patients with advanced gastric cancer were treated with a combination including 5-fluorouracil, 4-epi-doxorubicin and mitomycin C. 4-Epi-doxorubicin was substituted for adriamycin in MacDonald's original schedule. The combined treatment involved 600 mg/m2 i.v. of 5-fluorouracil on days 1, 8, 29 and 36; 80 mg/m2 i.v. of 4-epi-doxorubicin on days 1 and 29; and 10 g/m2 i.v. of mitomycin C on day 1. The cycle was repeated on day 57 after the start of treatment. Out of 44 patients, 39 were evaluable. Thirteen partial remissions (33%) were achieved. The average duration of remission was 7 months (range, 3-12 months). The average survival of the responders was 9 months, and that of nonresponders 3.5 months. Toxicity was moderate, well-tolerated and, as compared with the FAM schedule, less pronounced, particularly as regards myelotoxicity. Thus, the substitution of 4-epi-doxorubicin for adriamycin in the original schedule of MacDonald et al. (1980) did not improve treatment results, but the observed toxicity was less pronounced.