Use of Single Lead VDD Pacing in Children

The development of transvenous ventricular pacing leads with proximal electrodes capable of atrial sensing and the recent availability of smaller generators has created the opportunity to treat children with complete AV block and normal sinus node function with a transvenous single lead VDD pacing system. Studies in adults have demonstrated this system to be efficacious with low complication rates. Transvenous single lead VDD pacemakers were implanted in ten children, aged 5–15 years, between December 1993 and April 1996, in our institution. The indications were complete AV block with severe bradycardia in 5 patients, second-degree or complete A V block following congenital heart surgery in 3, complete A V block with long QT syndrome in 1, and second-degree AV block and syncope in 1. There were no complications related to the procedure in any case. P and R wave amplitudes were measured and thresholds were determined intraoperatively on all patients. Amplitudes and thresholds were remeasured on seven patients with a mean follow-up of 17 months; Holter monitors were performed on seven patients with a mean follow-up of 16 months. P and H wave amplitudes were generally diminished at follow-up compared to initial values but remained within an acceptable range for all patients. Four patients required reprogramming after pacemaker insertion, 1 received an atrial lead for dual chamber pacing, 1 required repositioning for lead dislodgment. and 1 patient required a new lead for an inadequate ventricular pacing threshold. No patient had evidence of failure to sense or capture as evaluated by Halter monitoring at last follow-up. Single lead VDD pacing systems can be successfully used in properly selected children with high degree or complete AV block with normal sinus node function.     

Lesions of the Urinary Tract Produced in Fischer 344 Rats and B6C3F1 Mice After Chronic Administration of 11-Aminoundecanoic Acid

Lesions of the Urinary Tract Produced in Fischer 344 Rats andB6C3F₁ Mice After Chronic Administration of 11-AminoundecanoicAcid. Dunnick, J.K., Huff, James E., Haseman, J.K. and Boorman,G.A. (1983). Fundam. Appl. Toxicol. 3:614–618. 11-Aminoundecanoicacid, the monomer of nylon 11, was toxic to the urinary tractof both male and female B6C3F₁ mice and Fischer 344 rats, whenadministered in the diet at 7500 or 15 000 ppm for 103–104weeks. Dose-related effects included a decrease in mean bodyweight gain and in survival for male rats and for mice of eachsex; increased incidence of hyperplasia of the transitionalepithelium of the kidney in rats of each sex; increased incidenceof calcification of the kidney in the female rats; increasedincidence of hyperplasia of the urinary bladder in male rats;and mineralization of the kidney in mice of each sex. Transitionalcell carcinomas of the urinary bladder of the male rat occurredwith increased frequency in the high-dose group (control, 0/48;low-dose, 0/48; high-dose, 7/49). Additional evidence for carcinogenicityin the male rat was seen in the liver, where an increased frequencyof neoplastic nodules was found in the treated animals (controls,1/50; low-dose, 9/50; high-dose, 8/50). Therefore, under theconditions of these studies, 11-aminoundecanoic acid was carcinogenicfor male Fischer 344 rats, inducing transitional cell carcinomasin the urinary bladder and neoplastic nodules in the liver.The test chemical was not demonstrated to be carcinogenic forfemale Fischer 344 rats or for B6C3F₁ mice of either sex.     

Colorectal Cancer in Regional Ileitis

Six patients, with overt Crohn's disease of the small boweldeveloped colorectal cancer. Three distinct clinical patternswere observed. Three patients had advanced rectal adenocarcinomaand a relatively long duration of Crohn's disease, two patientshad an early adenocarcinoma and a short antecedent history,and a sixth patient had advanced cloacogenic cancer of the anorectum. The prognosis for a patient with carcinoma in association withregional enteritis was poor when there was advanced diseaseat the time of diagnosis. The late diagnosis of the cancer mayhave been the result of three erroneous assumptions. First,scepticism as to the association of Crohn's disease and cancerdespite the evidence to the contrary; second, misinterpretationof the intestinal symptoms of the carcinoma as those of theunderlying inflammatory bowel disease; and third, confusingthe clinical picture of colorectal cancer with that of benignperianal disease with stricture formation. Increased awareness of the association of cancer and Crohn'sdisease, particularly the development of cancer in apparentlynormal bowel, and careful evaluation of all new symptoms shouldimprove the prognosis of this potentially lethal complicationof inflammatory bowel disease.     

In-vivo Activity of Retinoid Esters in Skin is Related to In-vitro Hydrolysis Rate

BMS-181163 (4-acetamidophenyl retinoate, previously reported as BMY-30123), the acetamidophenyl ester of all-trans-retinoic acid (tRA), is topically active in various retinoid-sensitive animal models, but was recently shown to be ineffective for the treatment of acne in patients. To determine whether BMS-181163 functions as a prodrug of tRA in mice but not in man, the relative rates of ester hydrolysis in mouse and human skin homogenates were determined. In-vitro hydrolysis assays showed that BMS-181163 was substantially hydrolysed in mouse skin homogenates and minimally in human skin preparations. In addition, a series of phenyl esters of tRA and several known active synthetic retinoids (Ch-80: (E)-4-[3-oxo-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl] benzoic acid; CD-271: 6-[3-(1-adamantyl)-4-methyoxyphenyl]-2-naphthoic acid; and TTNPB: (E)-4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl] benzoic acid) was prepared and hydrolysis rates and in-vivo (rhino mouse utriculi reduction) activities were compared. The hydrolysis rates of the six test retinoid phenyl esters, ranging from 0·06 to 2·0 h^?1 were found to correlate with the in-vivo activity. Those esters (BMS-181163 and acetamidophenyl esters of Ch-80 and TTNPB) with a higher hydrolysis rate exhibited in-vivo activity only slightly lower than their parent free acid retinoids. In contrast, the three phenyl esters with a hydrolysis rate less than 0·3 h^?1 were inactive in-vivo. Data from both approaches suggest that the breakdown of the phenyl ester linkage in this series is essential for the respective in-vivo activity and that the active phenyl esters of retinoids function as prodrugs.     

Managing Drug Interactions With Oral Contraceptives

An increasing concern to nurses is the possibility of drug interactions involving oral contraceptives. Information regarding the mechanisms, significance, and management of drug interactions with oral contraceptives is provided. Approaches to counseling patients also are discussed.     

The Role of Methemoglobin in Acute Butyl Nitrite Toxicity in Mice

The Role of Methemoglobin in Acute Butyl Nitrite Toxicity inMice. McFadden, David P., Carlson, Gary P. and Maickel, RogerP. (1981). Fundam. Appl. Toxicol. 1:448–451. When micewere exposed to butyl nitrites in an inhalation chamber, a significantlevel of methemoglobinemia is produced. The potency order formethemoglobin production of the four butyl nitrites (n-, iso-,sec-, tert-) is the same as that of their lethal concentrations(LCSO values) and parallels the ability of the agents to causemethemoglobin formation in mouse erythrocytes in vitro. Pretreatmentwith a single dose of methylene blue prevents the methemoglobinformation and protects against the lethality of the butyl nitrites.