Comparison of permanent cardiac pacing and cardiac pacing on demand in mixed carotid sinus syndrome. Acute- and medium-term follow-up study

The aim of the study was to evaluate the importance of atrial synchronism for pacing therapy of patients with mixed carotid sinus syndrome. On 23 patients (21 m, 2 f; mean age 69 +/- 8 years) affected by symptomatic mixed carotid sinus syndrome we performed: 1) the study of ventriculo-atrial conduction, 2) the evaluation of pacemaker effect and 3) the carotid sinus massage in standing position during VVI and DVI temporary pacing. All patients received a permanent DVI pacemaker and then underwent a two-month period single-blind, randomized, cross-over study on DVI vs VVI mode. During DVI period, no syncope occurred in any patients, minor symptoms persisted in 11 (48%) of them; during VVI period syncopes recurred in 3 patients, symptoms requiring the withdrawal of VVI pacing and premature DVI reprogramming in 8, minor symptoms were observed in 17 (74%). A comparison between 14 patients who preferred DVI period (Group A) and the remaining 9 patients who had no preference for DVI and VVI period (Group B) revealed that Group A patients had a greater pacemaker effect (-34 +/- 16 mmHg vs -16 +/- 14 mmHg; p less than 0.02) and a higher prevalence of ventriculo-atrial conduction (78% vs 44%; p = 0.1), while the entity of the systolic pressure fall caused by carotid sinus massage was similar in the two groups both during VVI mode (Group A -51 +/- 16 mmHg vs Group B -56 +/- 27 mmHg) and DVI mode (Group A -38 +/- 17 mmHg vs Group B -45 +/- 17 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)     

Autologous Unpurged Bone Marrow Transplantation for Acute Non Lymphoblastic Leukemia in First Remission

Forty consecutive adult patients under the age of 50 with acute non-lymphoblastic leukemia (ANLL) in first complete remission, underwent autologous bone marrow transplantation (ABMT) between March 1984 and April 1990. The conditioning regimen employed included cyclophosphamide and total body irradiation, followed by the administration of unpurged ABMT. The median time from diagnosis to transplant was 7 months (3-15 months), and the median time from complete remission to ABMT was 4 months (range 3-9 months). Twenty-two (51%) patients remain in complete remission 6-81 months (median 24 months) after ABMT.

The causes of death were, recurrent leukemia (11 patients), parenchymal toxicities such as acute respiratory distress syndrome and veno-occlusive disease (3 patients), hemorrhage (2 patients) and infection (2 patients). Eleven patients relapsed after 3-12 months (median 5 months). This study has produced survival data comparable to those of other institutions employing TBI for either allo or autotransplants.     

乳酸脱氢酶实验检测细胞新陈代谢的实验研究

目的 探索LDH实验检测细胞活力的可行性。方法 原代培养骨髓细胞和软骨细胞，用LDH实验测定上述两组细胞的活力，并与镜下活体观察到细胞的生长状况相比较。与目前比较成熟的测定细胞活力的MTS实验的测得的值相比较。结果 LDH实验对上述两组细胞的活力的测定结果与镜下活体观察到的结果相符合。与MTS实验的测得的结果经统计学处理无显著差异。结论 LDH实验可用于细胞活力的直接测定，而对活细胞的生存、繁殖无影响。     

Partial-solubility Parameters of Naproxen and Sodium Diclofenac

The expanded Hansen method was tested for determination of the solubility parameters of two non-steroidal anti-inflammatory drugs, naproxen and sodium diclofenac. This work describes for the first time the application of the method to the sodium salt of a drug. The original dependent variable of the expanded Hansen method, involving the activity coefficient of the drug, was compared with the direct use of the logarithm of the mole fraction solubility lnX₂ in the solubility models. The solubility of both drugs was measured in pure solvents of several chemical classes and the activity coefficient was obtained from the molar heat and the temperature of fusion. Differential scanning calorimetry was performed on the original powder and on the solid phase after equilibration with the pure solvents, enabling detection of possible changes of the thermal properties of the solid phase that might change the value of the activity coefficient. The molar heat and temperature of fusion of sodium diclofenac could not be determined because this drug decomposed near the fusion temperature. The best results for both drugs were obtained with the dependent variable lnX₂ in association with the four-parameter model which includes the acidic and basic partial-solubility parameters δ_a and δ_b instead of the Hansen hydrogen bonding parameter δ_h. Because the dispersion parameter does not vary greatly from one drug to another, the variation of solubility among solvents is largely a result of the dipolar and hydrogen-bonding parameters, a fact that is being consistently found for other drugs of small molecular weight. These results support earlier findings with citric acid and paracetamol that the expanded Hansen approach is suitable for determining partial-solubility parameters. The modification introduced in the expanded Hansen method, i.e. the use of lnX₂ as the dependent variable, provides better results than the activity coefficient used in the original method. This is advantageous for drugs such as sodium diclofenac for which the ideal solubility cannot be estimated. This paper shows for the first time that the method is suitable for determination of the partial-solubility parameters of a sodium salt of a drug, sodium diclofenac.     

Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism

Parathyroid hormone secretion is negatively regulated by a 7- transmembrane domain, G-protein coupled Ca(2+)-sensing receptor. We hypothesized that activating mutations in this receptor might cause autosomal dominant hypoparathyroidism (ADHP). Consistent with this hypothesis, we identified, in two families with ADHP, heterozygous missense mutations in the Ca(2+)-sensing receptor gene that cosegregated with the disorder. None of 50 normal controls had either mutation. We also identified a de novo, missense Ca(2+)-sensing receptor mutation in a child with severe sporadic hypoparathyroidism. The amino acid substitution in one ADHP family affected the N-terminal, extracellular domain of the receptor. The other mutations involved the transmembrane region. Unlike patients with acquired hypoparathyroidism, patients with these mutations had hypercalciuria even at low serum calcium concentrations. Their greater hypercalciuria presumably reflected activation of Ca(2+)-sensing receptors in kidney cells, where the receptor negatively regulates calcium reabsorption. This augmented hypercalciuria increases the risk of renal complications and thus has implications for the choice of therapy.      

A case-control study of risk factor for renal cell cancer in northern Italy

A hospital-based case-control study of renal cell cancer was conducted in northern Italy betwen 1986 and 1989, with 240 cases of renal cell cancer (150 males and 90 females), and 665 controls (445 males and 220 females) chosen on the basis of age, sex, and area of residence. No associations were found between renal cell cancer and: body mass index (BMI); number of cigarettes smoked; age at starting to smoke; years of smoking; consumption of wine, beer, spirits, coffee, decaffeinated coffee; tea; intake of animal protein, fruits, and vegetables; various resproductive factors; hormonal use; sexual habits; sexually transmitted diseases; or selected occupational exposures. The odds ratio (OR) was above unity in smokers (OR=1.34 for 15 cigarettes/day), but the trends in risk with dose or duration were not statistically significant. Significant positive associations were found between renal cell cancer and sources of fat intake, especially margarine (OR for highest vs lowest intake = 1.71), and oils (OR=1.89) whereas carrot intake showed a negative association (OR=0.62). Also, a history of nephrolithiasis and multiple episodes of cystitis showed weak positive associations (OR=2.00, 95 percent confidence interval (CI) 1.07–3.73; and OR=1.60, 95 percent CI 0.95–2.70, respectively).Address reprint requests to Dr Talamini. The work was conducted with the contribution of the Italian Association for Cancer Research, Milan, Italy and the CNR (Italian National Research Council) Applied Projects Oncology (Contract n. 85.02209.44).Drs Talamini, Barón, Barra, Bidoli, Serraino, and Franceschi are in the Epidemiology Unit, Aviano Cancer Center, Via Pedemontana Occ. 33081 Aviano (PN) Italy. At the time of this work, Dr Barón was a visiting biostatistician from the Department of Preventive Medicine and Biometrics, University of Colorado, Health Science Center, CO, funded by the National Cancer Institute (US) and the Italian National Research Council. Dr Franceschi is also chief of the Hormones and Sexual Factors and Cancer Working Group of the European Organization for Cooperation in Cancer Prevention Studies, Bruxelles, Belgium. Drs La Vecchia and Negri are in the Mario Negri Institute for Pharmacological Research, Milan, Italy. Dr La Vecchia is also in the Institute of Social and preventive Medicine, University of Lausanne, Switzerland.     

Original removing technique of the kidneys for transplantation. An experimental study (author's transl)]

The depicted procedure minimizes the hazards of aggressive manipulations, and excludes any possibility of so-called "warm ischaemia". The kidneys are flushed out in situ with cool pulsatile perfusion through an aortic cannula. Kidneys, aorta and inferior vena cava are then removed en-bloc without interrupting the perfusion, and preserved in Collins' solution at 4 degrees C. After a 6 to 19 hour storage time, one of the kidneys is transplanted on another dog, while the second one is submitted to histological examination. Nine transplantations were carried out, followed in 7 cases with a most satisfactory diuresis resuming, and with urinary ionic levels, as well as daily urea output, normalization within 48 hours. Histologic examination showed an unaffected glomerular apparatus, but some mild tubular lesions.     

Dibenzo[a,l]pyrene-induced DNA adduction, tumorigenicity, and Ki-ras oncogene mutations in strain A/J mouse lung

Dibenzo[a,l]pyrene (DB[a,l]P), an environmental polycyclic aromatic hydrocarbon, is the most potent carcinogen ever tested in mouse skin and rat mammary gland. In this study, DB[a,l]P was examined for DNA adduction, tumorigenicity, and induction of Ki-ras oncogene mutations in tumor DNA in strain A/J mouse lung. Groups of mice received a single i.p. injection of 0.3, 1.5, 3.0, or 6.0 mg/kg DB[a,l]P in tricaprylin. Following treatment, DNA adducts were measured at times between 1 and 28 days, while tumors were counted at 250 days and analyzed for the occurrence of point mutations in codons 12 and 61 of the Ki-ras oncogene. DB[a,l]P in strain A/J mouse lung induced six major and four minor DNA adducts. Maximal levels of adduction occurred between 5 and 10 days after injection followed by a gradual decrease. DB[a,l]P-DNA adducts in lung tissue were derived from both anti- and syn-11,12- dihydroxy-13,14-epoxy- 11,12,13,14-tetrahydrodibenzo[a,l]pyrene (DB[a,l]PDE) and both deoxyadenosine (dAdo) and deoxyguanosine (dGuo) residues in DNA as revealed by cochromatography. The major adduct was identified as a product of the reaction of an anti-DB[a,l]PDE with dAdo in DNA. DB[a,l]P induced significant numbers of lung adenomas in a dose- dependent manner, with the highest dose (6.0 mg/kg) yielding 16.1 adenomas/mouse. In tricaprylin-treated control animals, there were 0.67 adenomas/mouse. Based on the administered dose, DB[a,l]P was more active than other environmental carcinogens including benzo[a]pyrene. As a function of time-integrated DNA adduct levels, DB[a,l]P induced lung adenomas with about the same potency as other PAHs, suggesting that the adducts formed by DB[a,l]P are similar in carcinogenic potency to other PAHs in the strain A/J mouse lung model. Analysis of the Ki- ras mutation spectrum in DB[a,l]P-induced lung tumors revealed the predominant mutations to be G-->T transversions in the first base of codon 12, A-->G transitions in the second base of codon 12, and A-->T transversions in the second or third base of codon 61, concordant with the DNA adduct profile.