Nephrotoxic and Ototoxic Effects of Hydroxygentamicin in Cats

Nephrotoxic and Ototoxic Effects of Hydroxygentamicin in Cats.Slighter, R. G, FABIAN, R. J., DONIKIAN, M. R., RENCH, R. D.,NEIDL, M. J., AND BOSHART, C. R. (1984). Fundam. Appl. Toxicoi.4, 568–576. Hydroxygentamicin, an aminoglycoside antibiotic,was administered subcutaneously to cats in doses up to 160 mgbase/kg daily for 10 to 13 weeks. Gentamtcin and a vehide solutionwere tested as positive and negative control, respectively;in one test netilmicin was also included for comparative purposes.Several parameters, including serum urea nitrogen, serum creatinine,organ/body weight ratios, serum and tissue concentrations ofthe antibiotics, and renal pathology, were determined to ascertainthe nephrotoxic potential of the three ami-noglycosides. Inaddition, observations for the onset of ataxia and impairmentof righting reflex were made during the course of the studiesto compare the vestibular ototoxic effects of the three antibiotics.Although serum urea nitrogen and serum creatinine values increasedmarkedly in those cats which eventually died or were sacrificedmoribund, these parameters in survivors were slightly but notsignificantly higher than controls. -Serum concentrations ofthe drugs were proportional to the doses administered, but renalconcentrations were approximately two and five times as highfor netilmicin and gentamicin, respectively, as they were forequivalent doses of hydroxygentamicin. The morphological changesobserved in the kidney of cats given 60 mg base/kg of hydroxygentamicinwere slightly less than those seen in cats administered 10 mgbase/ kg of gentamicin; similarly, kidney changes in cats givennetilmicin were observed approximately twice as frequently asthey were in those receiving equivalent doses of hydroxygentamicin.The nephrotoxic effects of aminoglycoside antibiotics were directlyrelated to renal drug concentration and not to serum concentration,which was a function of dose. The reason for the lower incidenceof vestibular ototoxic effects with hydroxygentamicin than withgentamicin was not as readily apparent. Vestibular damage resultingfrom netilmicin administration was restricted to ataxia; thelack of righting reflex impairment in all five cats was notcharacteristic of the pattern of vestibular ototoxicity associatedwitn aminoglycoside therapy.     

Beta-mimetics in preterm labour: an overview of the randomized controlled trials

Summary. Controversy continues about the use of beta-mimetic drugs in preterm labour. One reason for this is that the adequately controlled trials of these drugs have all been small and have thus provided very imprecise estimates of their effects. We have therefore conducted a'meta-analysis' using data relating to 890 women who participated in the 16 methodologically acceptable controlled trials of these agents in the treatment of preterm labour. This analysis demonstrates an unequivocal effect of beta-mimetic tocolytic administration in delaying delivery, and this is reflected in a reduction in the frequency of preterm birth and low birthweight. However, no beneficial effect of this treatment on perinatal mortality or severe neonatal respiratory disorders could be detected.     

Neural Control Mechanisms and Vasovagal Syncope

Vasovagal Syncope, Patients with recurrent unexplained syncope may have cardioinhibitory and vasodepressor responses provokable with head-up tilt with or without exogenousbeta-adrenergic stimulation. Although these responses are believed to be neurally mediated, the neural mechanisms involved are pourly understood. Numerous studies have documentedperipheral vasodilation, hypotension, and bradycardia at the time of syncope and several casereports have shown sudden withdrawal of vasoconstrictor sympathetic neural outflow to skeletal muscle in human subjects. In cats and rats, a similar response can be provoked with hemorrhage and is prevented by interruption of cardiac vagal C-fiber afferents. In dogs, however, section of these fibers does not prevent the development of a vasodepressor response. Theprovocation of vasodepressor syncope during nitroprusside infusion in a heart transplantrecipient with presumed ventricular denervation also suggests that cardiac afferent nerves maynot be required for the development of vasodepressor responses in humans. Other potentialmechanisms include release of endogenous opioids or nitric oxide that may inhibit sympatheticnerve firing, and primary central nervous system activation (as in partial seizures) that triggerscardioinhibitory and vasodepressor responses. This article reviews our current understandingof the mechanisms involved in the development of neurally mediated syncope.     

The Relationship Between Intimal Tears During Coronary Angioplasty and Fibrinopeptide A

Arterial injury during routine percutaneous trans-luminal coronary angioplasty (PTCA) may stimulate clotting mechanisms. Excessive (i.e., angiographically visible) arterial trauma might accordingly predispose to a greater tendency for thrombosis. This study evaluates whether arterial trauma (i.e., angiographically visible intimal tears and arterial dissections) is related to evidence of active thrombosis. Fibrinopeptide A (FPA), a sensitive marker of thrombin activity, was measured in 79 patients undergoing elective PTCA immediately following angioplasty, as well as prior to hospital discharge (mean 2 days post-PTCA). Levels > 2.0 ng/mL were considered elevated. Intimal tears were visualized in 41 patients. Of these 41, 31 had elevated FPA levels (sensitivity = 0.76). This association between FPA elevation and intimal tears was significant (P = 0.033). Of the remaining 38 patients without intimal tears, 20 had elevated FPA levels (specificity = 0.47). Concomitant arterial dissection, as well as an intimal tear, was found in four patients with elevated FPA and in one patient with normal FPA. Conclusion. Arterial trauma during PTCA is accompanied by a greater degree of ongoing thrombosis. Although FPA elevation was not specific for intimal tears, a highly significant association with intimal tears was observed. Further study may yield even more specific hematologic parameters on ongoing early thrombosis following PTCA, particularly in patients with intimal tears. (J Interven Cardiol 1989:2:3)     

Trisomy 3 in marginal zone B-cell lymphoma: a study based on cytogenetic analysis and fluorescence in situ hybridization

Trisomy 3 represents the most frequent and consistent chromosomal abnormality characterizing the recently defined entity marginal zone B-cell lymphoma (MZBCL). By cytogenetic analysis and/or fluorescence in situ hybridization (FISH) on interphase nuclei we found an increased copy number of chromosome 3 in 22/36 (61%) successfully analysed cases, including 8/12 cases with extranodal MZBCL, 8/13 cases with nodal MZBCL, and 6/11 patients with splenic MZBCL. Sensitivity of interphase cytogenetics was somewhat higher than that of conventional cytogenetic investigation. Structural chromosomal changes involving at least one chromosome 3 were seen in 11/20 cases with an increased copy number of chromosome 3: +del(3)(p13) was demonstrated in three cases, and was the sole chromosomal abnormality in one of them; +i(3)(q10) was seen in two other patients; and rearrangements involving various breakpoints on the long arm of chromosome 3 were found in the remaining cases. FISH on metaphase spreads confirmed these structural abnormalities and additionally showed two unexpected translocations involving chromosome 3. We conclude that: (1) trisomy 3 occurs in a high proportion of extranodal, nodal and splenic MZBCL; (2) FISH on interphase nuclei is an additional and sensitive tool in detecting an increased copy number of chromosome 3 in MZBCL; (3) additional structural abnormalities involving the long arm of chromosome 3 are frequent but non-recurrent and are perhaps secondary changes; and (4) abnormalities such as +del(3)(p13) and +i(3)(q10) suggest that genes located on the long arm of chromosome 3 are of particular importance in the pathogenesis of MZBCL.     

Identification of a 94-kilodalton antigen on Leishmania promastigote forms and its specific recognition in human and canine visceral leishmaniasis

We have analysed by immunoblotting sera from humans and dogs with visceral leishmaniasis, from the Old World as well as the New. When lysates of promastigotes are used as antigens, antibodies against a 94 kDa Leishmania component are detected, regardless of the age and geographical origin of the patient, the serum antibody titre as measured by indirect immunofluorescence, and the number of arcs in counterimmunoelectrophoresis. Low dilutions of sera from patients with Old and New World cutaneous leishmaniasis did not react with the 94-kDa antigen, whatever the species of Leishmania used as antigens. Sera from patients with other infections than leishmaniases, or without infection, are negative, even at low dilution. Anti-94 kDa antibodies were detected in the sera of Leishmania-infected dogs from both the Old and the New World. When lysates of Leishmania mexicana axenic amastigotes are used as antigens, the 94-kDa antigen was little or none identified by sera from humans and dogs with visceral leishmaniasis, and never recognized by control sera. Thus, the specific recognition of the 94-kDa promastigote antigen in human and canine visceral leishmaniasis suggests that this antigen could be a potential candidate in the differential immunodiagnosis of the disease.     

Serial Lead Impedance Measurements Confirm Fixation of Helical Screw Electrodes During Pacemaker Implantation

The purpose of this study was to determine whether serial measurements of helical screw pacemaker lead impedance could reliably confirm electrode fixation in the right atrium and right ventricle. Fixation is generally assessed fluoroscopically, which can be misleading because the myocardium is radio lucent. Alternatively, because the electrical conductivity of blood is greater than that of myocardium, serial measurements of the lead impedance might be expected to show an impedance increase with appropriate fixation of the pacemaker electrode when the electrode becomes embedded in myocardial tissue. Impedance measurements were made during the placement of 23 atrial and 28 ventricular active fixation electrodes in 31 consecutive patients. Impedance measurements were recorded in unipolar and bipolar electrode configurations with the electrode free floating in the chamber, unfixed (with exposed screws) but touching the endocardial surface, and after fixation. No significant impedance differences were found between free-floating and unfixed electrode positions. With fixation, the lead impedance increased significantly in the ventricle (P = 0.0001, unipolar and bipolar) and the atrium (P = 0.0069 unipolar and 0.0052 bipolar). Typical increases, reflected by median values, were 197 ohms unipolar and 203 ohms bipolar in the ventricle and 47 ohms unipolar and 53 ohms bipolar in the atrium for electrodes with permanently exposed or retractable screw designs. Comparing serial measurements of lead impedance before and after electrode fixation is a valid electrical method of confirming appropriate fixation of helical screw electrodes.     

The Effects of Perfluorodecanoic Acid on Hepatic Stearoyl-Coenzyme A 1 Desaturase and Mixed Function Oxidase Activities in Rats

The Effects of Perfluorodecanoic Acid on Hepatic Stearoyl-CoenzymeA Desaturase and Mixed Function Oxidase Activities in Rats.VANRAFELGHAM, M. J., AND ANDERSON, M. E. (1988). Fundam. Appl.Toxicol. 11, 503-510. Perfluorodecanoic acid (PFDA) causes adioxin-lilce toxic syndrome and alters the hepatic oleate/stearateratio in rats. The acute toxic effects of a single ip dose (50mg/kg) of PFDA on hepatic stearoyl-CoA desaturase and mixedfunction oxidases were studied in male Fischer-344 rats, 14days after dosing. PFDA causes a marked decrease in food intakein rats, resulting in severe body weight loss with delayed lethality(2-3 weeks after dosing). To distinguish the effects of hypophagiafrom those caused by PFDA, pair-fed control rats were used inaddition to ad libitum-fed controls. Stearoyl-CoA desaturaseactivity, responsible for the conversion of stearoyl-CoA tooleoyl-CoA, was absent in both PFDA dosed rats and their pair-fedcontrols at Day 14. Electron transfer through the desaturasesystem was significantly reduced in PFDA-treated rats only,and in these rats there was a significant reduction in microsomalcytochrome an important component of this electron transfersystem. Pentobarbital sleeping times were significantly prolongedin both the PFDA-dosed and pairfed rats, as compared with thead libitumfed controls. This effect was more pronounced in PFDA-dosedrats. Waking plasma pentobarbital concentration was similarin all treatment groups. Hepatic microsomal cytochrome PASOcontent was unaffected. Aminopyrine N-de-methylase activitywas greatly reduced in PFDA-dosed rats. Although pairfed controlsalso had reduced demethylase activity, it was not as pronouncedas in PFDA-dosed rats, and was probably due to the fasted conditionof these animals. Although the mechanism of action of PFDA isnot known, it is possible that PFDA affects microsomal enzymesby altering the structure and/or function of the membranes inwhich they are located, through effects on lipid metabolism.