Induction of Cytochrome P450 Isoenzymes after Toxicokinetic Interactions between 2,3,7,8-Tetrachlorodibenzo-p-dioxin and 2,2',4,4',5,5'-Hexachlorobiphenyl in the Liver of the Mouse

One group of male C57BL/6J mice received a single oral doseof 1 nmol 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)/kg. Sixother groups received single oral doses of 100, 300, or 1000µmol2,2',4,4',5,5'-hexachlorobiphenyl (HxCB)/kg, alone or in combinationwith 1 nmol/kg TCDD. Liver deposition of both compounds wasstudied at Day 3 after dosage. Hepatic CYP1A1 and CYP1A2 proteinlevels and related 7-ethoxyres-orufin-O-deethylation (EROD)and acetanilide 4-hydroxylation (ACOH) activities were alsostudied. A significant increase in the hepatic deposition ofTCDD was observed in all three mixed dose groups but TCDD didnot influence hepatic HxCB deposition. TCDD did increase bothCYP1A1 and CYP1A2 protein levels. In the HxCB-treated groups,CYP1A2 levels were also increased in a dose-dependent way butCYP1A1 levels were not increased. CYP1A2 activities (ACOH),but not protein levels, in the TCDD groups cotreated with HxCBwere higher than those in the group treated with TCDD alone.CYP1A1-dependent EROD activity and CYPlA2-dependent ACOH activitywere induced in all treated dose groups. It is concluded thatthe present results do not confirm a direct role of CYP1A2 inductionin the increase of hepatic TCDD levels by HxCB cotreatment inthe mixed HxCB/TCDD dose groups. However, in this aspect, thediscrepancy between CYP1A2 activities and protein levels remainsto be explained.     

Comparative Functional Effects of Chronic Ventricular Demand and Atrial Synchronous Ventricular Inhibited Pacing

We compared the effects of chronic ventricular inhibited (VVI) and atrial synchronous ventricular inhibited (VDD) pacing on functional capacity in 8 patients with complete atrioventricular heart block. Permanent VDD (Medtronic #2409, ASVIP) pacemakers were implanted in four men and four women (age range 27-76 years, mean 58.9 +/- 18.4 years), and randomly assigned to a three-month period of VDD or VVI pacing in this single blinded, crossover study. Functional capacity was assessed by questionnaire, graded treadmill exercise testing and radionuclide angiocardiography prior to pacemaker implant and following each pacing period. Following 3 months of pacing in each of VVI and VDD pacing modes, maximum heart rate (83.4 +/- 14 vs 134.9 +/- 16.4 beats/min, p less than 0.001) and double product (147.5 +/- 58.3 vs 218.9 +/- 52.7, p less than .001) were greater with VDD pacing. Although exercise duration on treadmill exercise testing (5.3 +/- 2.9 vs 6.9 +/- 3.1 minutes, p less than 0.1) was greater in the VDD mode, the difference was not significant. Similarly, there was no significant difference in functional capacity as measured by questionnaire scores (50.1 +/- 8.4 vs 46.9 +/- 8.9, p less than 0.1) or in left ventricular ejection fraction for the two pacing modes (.54 vs .55, p less than .5). Only one patient reported a subjective improvement with physiologic (VDD) pacing, whereas the remaining patients stated no preference. We conclude that VDD pacing offers improved maximal cardiac work during exercise compared to VVI pacing.(ABSTRACT TRUNCATED AT 250 WORDS)     

EXPRESSION OF BCL-2 PROTEIN IN HYPERPLASTIC POLYPS,ADENOMAS, AND CARCINOMAS OF THE COLON

The proto-oncogene Bcl-2 encodes a protein that protects cells from programmed cell death (apoptosis). The protein is expressed in the proliferative compartment of several normal tissues, including normal colonic crypts. The aim of this study was to test Bcl-2 expression in colorectal neoplasms, assuming that, as a regulator of apoptosis, it might be involved in the progression from adenoma to carcinoma. To this end, Bcl-2 reactivity was tested by immunohistochemistry in hyperplastic polyps, colonic adenomas, and carcinomas and its expression was compared with staining for the proliferation-associated Ki-67 antigen, using the MIB-1 antibody. Bcl-2 expression occurred in 2 out of 10 hyperplastic polyps and in 31 out of 35 (tubular, villous, and tubulovillous) adenomas, irrespective of their degree of dysplasia. Of ten carcinomas, only three were focally Bcl-2-positive, all moderately to well differentiated. In two of four carcinomas in Bcl-2-positive adenomas, no Bcl-2 staining was observed. High numbers of MIB-1-positive cells were found in all hyperplastic and neoplastic lesions, without apparent correlation between proliferation and Bcl-2 expression. These findings suggest that in the pathogenesis of hyperplastic polyps, increased crypt cell proliferation is primarily involved, but in some lesions decreased apoptosis may play a role. Furthermore, the increased Bcl-2 expression in adenomas but not in the majority of the carcinomas suggests either that decreased apoptosis is not usually involved in the pathogenesis of these lesions or that the regulation of apoptosis in colorectal epithelia involves additional regulatory factors.     

PENICILLINASE-PRODUCING NEISSERIA GONORRHOEA AS A CAUSE OF NEONATAL AND ADULT OPHTHALMIA

A retrospective analysis of 80 cases of gonococcal ophthalmia revealed six (7.5%) to be due to penicillinase-producing Neisseria gonorrhoeae (PPNG), five neonatal cases and one adult. All six cases were finally cured, but best results were obtained with topical chloramphenicol and single-dose spectinomycin (40 mg/kg) given intramuscularly. All gonococcal isolates should be tested promptly for penicillinase production, and if this is present systemic treatment, modified to spectinomycin or penicillinase-stable cephalosporin, should be given as single-dose treatment.     

A Quantitative Measurement of Spatial Orderin Ventricular Fibrillation

Quantifying Spatial Order in Fibrillation. Introduction: The degree of organization in ventricular fibrillation (V F) is not known. As an objective measurement of spatial order, spatial correlation functions and their characteristic lengths were estimated from epicardial electrograms of pigs in VF.
Methods and Results: VF was induced by premature stimulation in five pigs, EIectroj;raniswere simultaneously recorded with a 22 × 23 array of unipolar electrodes spaced 1.12 mmapart, Data were obtained by sampling the signals at 2000 Hz for 20 minutes immediately afterthe initiation of VF. Correlations between all pairs of signals were computed at various times.Correlation lengths were estimated from the decay of average correlation as a function of electrode separation. The correlation length of the VF in pigs was found to be approximately 4 to 10 mM. varying as fihrillation progressed. The degree of correlation decreased in the first 4 seconds after fibrillation then increased over the next minute.
Conclusion: The correlation length is much smaller than the scale of the heart, suggestingthat many independent regions of activity exist on the epicardium at any one time. On theother hand, the correlation length is 4 to 10 times the interelectrode spacing, indicating thatsome coherence is present. These results imply that the heart behaves during VF as a highdimensional, but not random, system involving many spatial degrees of freedom, which mayexplain the lack of convergence of fractal dimension estimates reported in the literature.Changes in the correlation length also suggest that VF reorganizes slightly in the first minuteafter an initial breakdown in structure.     

Operative tumour yield obviates preoperative pancreatic tumour localization in multiple endocrine neoplasia type 1

Abstract. The efficiency of pancreatic tumour localization was prospectively evaluated in 12 consecutive patients with multiple endocrine neoplasia type 1 (MEN1), who were subjected to extirpation of 56 islet cell neoplasms of 0.2–4 cm in diameter (mean 0.8 cm) during pancreatic resection and enucleation. Computed tomography, angiography of the coeliac trunc and superior mesenteric artery, and percutaneous ultrasound correctly localized 7–12% of the tumours and 21–37% of the 19 lesions measuring at least one centimetre in diameter. Transhepatic portal vein sampling correctly located tumour sites in the proximal or distal portions of the pancreas in four out of six patients, but demonstrated unsatisfactory specificity. Intra-operative ultrasound and bidigital palpation of the pancreas had overall sensitivities of 86 and 45%, respectively, and eight lesions below 0.3 cm in diameter remained undetected with intraoperative ultrasound. It is concluded that diagnosis of endocrine pancreatic neoplasms is biochemical in MEN1 and that broad screening of tumour markers efficiently reveals pancreatic involvement decades before the development of a clinically overt disease. Intra-operative ultrasound is a requisite for pancreatic endocrine surgery in MEN1, and it obviates the need for conventional pancreatic imaging unless a pre-operative search for metastatic disease and anatomical aberrations is considered important.