Experimental Evaluation of the Dialdehyde Starch Preserved Bovine Internal Mammary Artery as a Small Diameter Arterial Substitute

A canine femoral artery model was used for evaluation of a dialdehyde starch preserved bovine internal mammary artery (BIMA) (3 and 4 mm internal diameter) in comparison to a polytetrafluoroethylene (PTFE) graft. The study comprised three groups for a 2-hour (n = 7, 3 mm), 3-month (n = 10, 4 mm), and 6-month (n = 10, 4 mm) follow-up. The thrombogenicity of the grafts was measured after 2 hours and 3 months using chromium 51 labeled autologous platelets. In addition, compliance studies were done. To control the wall stability of the xenografts, the collagen content before implantation and after explantation was examined together with the diameter of the grafts. Healing characteristics were studied using appropriate histologic methods. The acute platelet adhesion rate (2 hours) of the BIMA graft was 181 +/- 69 x 10(4) platelets/mm2 as compared to 57 +/- 43 x 10(4) for PTFE (p less than 0.05, t-test). However, after 3 months the thrombogenicity of the biograft had decreased whereas the platelet count at the PTFE graft had increased (BIMA: 79 +/- 48 x 10(4); PTFE: 179 +/- 102 x 10(4), p less than 0.05). At implantation, the compliance of the BIMA graft was 0.028% +/- 0.009% per mmHg as compared to 0.06% +/- 0.0025% of the femoral artery. The PTFE graft was uncompliant (0.008 +/- 0.005). After 6 months, the compliance of the femoral artery had decreased to 0.039% +/- 0.013% per mmHg, which was now well matched to the nearly unchanged compliance of the biograft (0.0027 +/- 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)     

Carvedilol Versus Metoprolol in Patients Undergoing Direct Percutaneous Coronary Interventions for Myocardial Infarction: Effects on QT Dynamicity

Beta-adrenergic blockers exert significant antiarrhythmic activity during ischemia and reperfusion. To further explore the beneficial effects conferred by alpha-1-adrenoceptor blockade on ventricular repolarization dynamicity in the acute phase of myocardial infarction (AMI), we compared carvedilol with metoprolol in the setting of primary percutaneous coronary intervention (PCI). In a prospective study, 100 consecutive patients undergoing primary PCI for AMI were randomized to metoprolol 200 mg/day versus carvedilol 25 mg/day. The first oral dose of study drug was administered and a 24-hour ambulatory electrocardiogram recorded upon hospital admission. Slopes of the linear QT/RR regression were determined before and after reperfusion. A total of 38 recordings of patients treated with metoprolol and 34 recordings of patients with carvedilol were eligible for analysis of QT/RR slopes. The two study groups were similar with respect to age, gender, TIMI perfusion grades, ventricular function, duration of ischemia, and site and size of infarction. Mean RR- and QT-intervals were similar to the metoprolol and carvedilol groups, before and after PCI. Likewise, there was no significant difference in QT/RR slopes between the metoprolol and carvedilol groups before PCI. In contrast, after PCI, there was a trend toward lower QT/RR slopes in the metoprolol group (from 0.18 ± 0.07 to 0.17 ± 0.08), and a significant decrease in QT/RR slopes in the carvedilol group (from 0.17 ± 0.07 to 0.14 ± 0.09). In patients undergoing successful direct PCI for AMI, treatment with carvedilol, in contrast to metoprolol, was associated with a significant decrease in QT–RR slopes, suggesting greater cardiac electrical stability.     

Early Afterdepolarizations Produced by d,1-Sotalol and Clofilium

EAD Formation by Class III Drugs. Introduction: The roles for L-type calcium current and Na-Ca exchange in early afterdepolarizations (EADs) attending d, l-sotalol and clofilium were examined in canine Purkinje fibers and in enzymatically dispersed myocytes from canine subepicardium. Methods and Results: Spontaneous EADs were compared to EAD formation potentiated by stimulation of Na-Ca exchange and facilitation of I_Ca-L (Bay K8644). Bay K8644 (10^-8 M) and stimulation of Na-Ca exchange potentiated bradycardia-dependent EADs. Stimulation of Na-Ca exchange in Pnrkinje fibers pretreated with d, l-sotalol (10^-5 M) and clofilium (10^-7 M) induced EADs at takeoff potentials negative (-63 ± 4 and -62 ± 4 mV, respectively) to EADs potentiated by Bay K8644 (10^-8 M) (-33 ± 2 and -34 ± 2 mV, respectively, P < 0.05), or EADs induced by Bay K8644 alone (10^-6 M) (-31 ± 5 mV). In myocytes, Bay K8644 (10^-8 M) potentiated EADs in d, l-sotalol- (10^-6 to 10^-4M) or clofilium-treated (10^-9 to 10^-7 M) cells at reduced potentials (-10 ± 3 and -10 ± 4 mV, respectively) compared to EADs elicited by clofilium or d, l-sotalol alone (-25 ± 3 and -24 ± 3 mV, respectively), or stimulation of Na-Ca exchange in the presence of d, l-sotalol or clofilium (-26 ± 4 and -26 ± 4 mV, respectively). Spontaneous EADs or EADs elicited by stimulation of Na-Ca exchange coincident with drug treatment were suppressed by increasing Ca_o²⁺ but were not suppressed by nifedipine (10^-7 M). Conclusion: EADs elicited by d, l-sotalol and clolllium in canine Purkinje tissue and epicardial myocytes are dependent upon Na-Ca excbange rather than I_Ca-L“window current.”     

New optical technologies for earlier endoscopic diagnosis of premalignant gastrointestinal lesions

Gastrointestinal malignancies continue to be the second leading cause of cancer-related deaths in the developed world. The early detection and treatment of gastrointestinal preneoplasms has been demonstrated to significantly improve patient survival. Conventional screening tools include standard white light endoscopy (WLE) and frequent surveillance with biopsy. Well-defined endoscopic surveillance biopsy protocols aimed at early detection of dysplasia and malignancy have been undertaken for groups at high risk. Unfortunately, the poor sensitivity associated with WLE is a significant limitation. In this regard, major efforts continue in the development and evaluation of alternative diagnostic techniques. This review will focus on notable developments made at the forefront of research in modern gastrointestinal endoscopy based on novel optical endoscopic modalities, which rely on the interactions of light with tissues. Here we present the 'state - of - the - art' in fluorescence endoscopic imaging and spectroscopy, Raman spectroscopy, optical coherence tomography, light scattering spectroscopy, chromoendoscopy, confocal fluorescence endoscopy, and immunofluorescence endoscopy. These new developments may offer significant improvements in the diagnosis of early lesions by allowing for targeted mucosal excisional biopsies, and perhaps may even provide 'optical biopsies' of equivalent histological accuracy. This enhancement of the endoscopist's ability to detect subtle preneoplastic changes in the gastrointestional mucosa in real time and improved staging of lesions could lead to curative endoscopic ablation of these lesions and, in the long term, improve patient survival and quality of life.     

A Dose-Response Analysis of Methoxychlor-Induced Alterations of Reproductive Development and Function in the Rat

A Dose-Response Analysis of Methoxychlor-Induced Alterationsof Reproductive Development and Function in the Rat. GRAY, L.E., JR., OSTBY, J., FERRELL, J., REHNBERG, G., LINDER, R., COOPER,R., GOLDMAN, J., SLOTT, V., AND LASKEY, J. (1989). Fundam. Appl.Toxicol12, 92–108. In the present study rats were dosed fromweaning, through puberty and gestation, to Day 15 of lactationwith methoxychlor at 25, 50, 100, or 200 mg/kg/day. Morphologicallandmarks of puberty were measured, including the ages at vaginalopening, first estrus, and first estrous cycle in females andat preputial separation in males. In the female, estrous cyclicity,fertility, litter size, number of implantation sites, organweights, and ovarian and uterine histology were also measured.The viability of the offspring (F1) and their fertility wereevaluated using a continuous breeding protocol. Males were necropsiedafter breeding, the reproductive organs were weighed, and thecauda epididymal sperm counts were determined. One testis wasused for histopathology, while the other was used to quantifyinterstitial fluid (IF) content, IF testosterone concentration,and testicular sperm production. Testosterone and an drogen-bindingprotein were measured in the caput epididymis, and sperm motilityand morphology were evaluated from a caudal sample. The serumand pituitary were saved for hormonal determinations. Methoxychloraccelerated the age at vaginal opening and first estrus, andthe vaginal smears were cornified. Growth was retarded at 100and 200 mg/kg/day and fertility was reduced when the femaleswere bred with untreated or similarly treated males. In thehighest- dose group, the mated females went from constant estrusinto pseudopregnancy following mating, but they had no implants.In males, methoxychlor treatment markedly reduced growth, seminalvesicle weight, cauda epididymal weight, caudal sperm content,and pituitary weight. Puberty was delayed in the two highest-dosagegroups. Testicular sperm measures were much less affected thancaudal measures. Testis weight and histology were slightly affected,and testicular sperm production, sperm morphology, and motilitywere unaffected. Endocrine function of the testes and pituitarywas altered by methoxychlor administration. Leydig cell testosteroneproduction, in response to human chorionic gonadotropin challenge,was reduced and pituitary levels of prolactin, thyroid-stimulatinghormone (TSH), and follicle-stimulating hormone (FSH) were altered.In contrast, serum levels of prolactin, FSH, and luteinizinghormone were unaffected. Serum TSH was reduced by 50% of controlat 100 and 200 mg/kg/day, while pituitary levels were increased.Gonadotropin-releasing hormone concentration in the mediobasalhypothalamus was also elevated. In spite of the many reproductivealterations, the fertility of treated males was not reducedwhen they were mated with untreated females. Growth and viabilityof the offspring (F1) from the 50 mg/kg/day treatment groupwere normal, but in the females, vaginal opening was accelerated,estrous cyclicity was abnormal in the rats during middle age,and fecundity was reduced.     

Comparison of Two Antitachycardia Pacing Modes in Supraventricular Tachycardia

The comparative efficacy of two different antitachycardia pacing techniques was evaluated in 22 consecutive patients who received the pacemaker Intertach® with an atrial electrode for drug refractory, recurrent Supraventricular tachycardia (SVT). The Intertach® has two consecutive programmable primary and secondary termination modes. The termination programs investigated were adaptive autodecremental burst pacing and adaptive decremental scanning. Atrioventricular nodal reentrant tachycardia was present in 15 patients and atrioventricular reentrant tachycardia due to Wolff-Parkinson-White syndrome in seven patients. The prospective comparison was arranged in a randomized, cross-over study over a period of 12 months. To assess long-term efficacy, diagnostic data of the pacemakers were obtained in intervals of 3 months. In addition, noninvasive programmed stimulation was performed to compare the incidence of pacing-induced atrial fibrillation with both termination programs. During a follow-up of 12 months the overall success rate of autodecremental burst pacing and decremental scanning was 80% and 95%, respectively. Decremental scanning was more effective in 12 patients and less successful in two patients than autodecremental burst pacing. During noninvasive electrophysiological studies, pacing induced atrial fibrillation could be documented in three often patients (30%) using autodecremental burst pacing, compared to one often patients (10%) using decremental scanning. These data suggest that decremental scanning proved to be more successful in the long-term management of patients with recurrent S VT than autodecremental burst pacing. Furthermore, the occurrence of pacing-induced atrial fibrillation could be documented more frequently with autodecremental burst pacing compared to decremental scanning.     

Immunotoxicologic Assessment of Subacute Exposure of Rats to Carbon Tetrachloride with Comparison to Hepatotoxicity and Nephrotoxicity

Immunotoxicologic Assessment of Subacute Exposure of Rats toCarbon Tetrachloride with Comparison to Hepatotoxicity and Nephrotoxicity.SMIALOWICZ, R.J., SIMMONS, J. E., LUEBKE, R. W., AND ALLIS,J. W. (1991). Fundam. Appl. Toxicol 17, 186-196. The immunotoxicity,hepatotoxicity, and nephrotoxicity of subacute exposure to carbontetrachloride (CCI4) were evaluated in young adult (8-9 weeksold) male Fischer 344 rats dosed by gavage with CCI4 for 10consecutive days at 0, 5, 10, 20 or 40 mg/kg/day. Two days followingthe last treatment rats were evaluated for alterations in immunefunction by monitoring the following; body and lymphoid organweights; mitogen and mixed leukocyte reaction lymphoproliferativeresponses; natural killer cell activity; and cytotoxic T lymphocyteresponses. A separate group of similarly dosed rats was immunizedwith sheep red blood cells (SRBQ on Day 9 of dosing, and theprimary antibody response was assessed 4 days later. Hepaticand renal toxicity were assessed 2 days after the last treatmentby monitoring organ weights, serum indicators of hepatic andrenal damage, and hepatic cytochrome P450 levels, as well asby histological evaluation. Significant increases in relativeliver weights were observed in rats dosed at 40 mg/kg/day. Histologically,these livers displayed mild to moderate vacuolar degenerationand minimal to mild hepatocellular necrosis. In addition, serumlevels of aspartate aminotransferase and alanine aminotransferasewere elevated at this dosage, as well as at 20 mg/kg/day. Therewere no renal effects observed at these dosages of CCU. In addition,no consistent alterations were observed in the immune parametersexamined in these same animals nor in the rats immunized withSRBC. Furthermore, there was no difference in the antibody responseto SRBC in another set of rats dosed at 40, 80, or 160 mg/kg/dayCCI⁴. These results indicate that CCU is not immunotoxic inthe rat at dosages that produce overt hepatotoxicity.     

Endoscopic treatment of sphenoid sinusitis

Juxtaposed between the posterior nasal cavity and skull base, the diseased sphenoid sinus presents unique challenges when surgical drainage is required. Endoscopic techniques have gained widespread popularity for the treatment of sphenoid sinusitis, yet the efficacy of such treatment remains largely unknown. Thirty-four patients who underwent endoscopic sphenoidotomy were monitored over a period of 6 months to 5 years. Surgery was performed with the superior turbinate used as the key landmark for identification and enlargement of the natural sphenoid ostium. Surgical access was through either a transnasal or transethmoid approach, depending on whether disease was limited to the sphenoid sinus. Prospective analysis of 26 patients with established outcome measures demonstrated a significant reduction in facial pain, nasal drainage, and congestion 6 months after surgery (p < 0.0001). Medication use was also reduced but to a lesser extent (p < 0.05). Endoscopic sphenoidotomy appears to be a safe technique that effectively reduces patient morbidity associated with sphenoid sinusitis. (Otolaryngol Head Neck Surg 1996;114:736-44.)