QRS Amplitudes,QTc Intervals and ECG Abnormalities in Pheochromocytoma Patients before,during and after Treatment

ABSTRACT QRS amplitudes (S₁ + R₅), Minnesota Code ECG abnormalities and QT_c intervals were analyzed in ECGs from 31 pheochromocytoma patients on admission to hospital, after 17±7.2 (SD) days of preoperative phenoxybenzamine therapy in a dosage of 148± 45.0 (SD) mg/day and after a mean postoperative follow-up of 6 years. QRS voltage decreased significantly from 3.37± 1.48 on admission, to 2.26±0.69 mV at postoperative follow-up (p<0.001). The prevalence of total Minnesota Code changes increased or was unchanged on the different occasions. Severe to moderate changes, however, became less prevalent, while mild changes increased. The QT_c interval was 0.44±0.04 s on admission and 0.41±0.02 s at follow-up (p<0.01). No significant differences were observed during treatment with phenoxybenzamine. Pathological ECGs are common findings in patients with pheochromocytoma and significant improvements occur after surgery. Significant effects of phenoxybenzamine therapy were only found in patients with sustained hypertension.     

Comments on adequacy, nutrition and survival with peritoneal dialysis and haemodialysis

Summary: This paper summarizes the status of the worldwide peritoneal dialysis population at the end of 1994. Relative mortality risks on peritoneal dialysis and haemodialysis are compared. Clearance targets for continuous ambulatory peritoneal dialysis are discussed.     

Tissue Distribution and Toxicokinetics of 2,3,7,8-Tetrachlorodibenzo-p-dioxin in Rats after Intravenous Injection

Tissue Distribution and Toxicokinetics of 2,3,7,8-Tetrachlorodibenzo-p-dioxinin Rats after Intravenous Injection. WEBER, L. W. D., ERNST,S. W., STAHL, B. U., AND ROZMAN, K. (1993). Fundam. Appl. Toxicol.21, 523–534. Male Sprague-Dawley rats (240–290 g) received intravenouslya nonlethal (9.25 µg/kg) or a lethal (72.7 µg/kg)dose of ¹⁴C-labeled 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)administered as an emulsion. Animals were euthanized between5 min and 16 days (lethal dose) or 32 days (nonlethal dose)after treatment. Tissue distribution was considered completeafter 24 hr, as by this time radioactivity levels in white adiposetissue had reached a maximum. The highest levels of radioactivitywere found in liver (5% of dose/g tissue), followed by whitefat (1% of dose/g tissue); serum was lowest at 0.01% of dose/mlserum. Relatively high levels of radioactivity were also detectedin most known target organs of TCDD toxicity, e.g., brown fat,adrenals, and thyroid. The pattern of organ distribution ofTCDD was essentially the same after the lethal and the nonlethaldose, but did not follow a simple lipophilicity relationship,as levels in liver were higher than those in white fat, andthose in brain were extremely low. A pool of TCDD in liposomesinitially trapped in lung and spleen was redistributed within24 hr mainly to liver and adipose tissue. Affinity of TCDD tostorage fat seemed to play a more important role as a drivingforce for redistribution than did induction of cytochrome P4501A2. The terminal slope of elimination of TCDD from tissuesindicated a half-life of 16 days after the nonlethal dose. Afterthe lethal dose radioactivity declined in all tissues for 2to 8 days and then increased again, reflecting shrinking tissuevolumes as well as remobilization of TCDD caused by the processof body mass wasting. Distribution data for 17 tissues and serumwere subjected to regression analysis and resulted in up totwo uptake phases and up to three elimination phases for a giventissue. After the nonlethal dose TCDD was mainly excreted viafeces; combined urinary and fecal excretions occurred with abiological half-life of 16.3 ± 3.0 days. Much longerhalf-lives were detected in white fat and skin. After the lethaldose, the fecal excretion of TCDD-derived radioactivity decreasedafter 8 days, and urinary excretion increased starting 12 daysafter dosing. Radioactivity in liver and white fat and the extractableportion in feces was mainly unchanged TCDD, as determined bythin-layer chromatography. Radioactivity in urine indicatedthe presence of a metabolite(s) of TCDD only.     

Increased plasma levels of atrial natriuretic peptide in patients with congestive heart failure

Atrial natriuretic peptide (ANP) is a recently discovered hormone,originating from atrial myocardium. The peptide (or family ofpeptides) induces potent diuretic/natiuretic, vasorelaxing andaldosterone inhibitory effects. We have investigated plasmaconcentrations of immunoreactive ANP in 10 patients with congestiveheart failure (CHF). Mean plasma ANP concentrations were morethan three times higher in CHF patients than in a matched controlgroup. High plasma ANP concentrations in pathophysiologicalconditions with a high preload combined with salt and waterretention is consistent with a physiological role of this hormoneto correct hypervolemia by causing natriuresis and diuresis.It is concluded that ANP homeostasis is altered in patientswith CHF and that this hormone may be of importance in the pathophysiologyof CHF.     

Increased Neurotoxicity Following Concurrent Exposure to Pyridostigmine Bromide, DEET, and Chlorpyrifos

The operating environment of the service personnel during thePersian Gulf War involved psychological, biological, and chemicalelements including exposure to pesticides such as the insectrepellent DEET (N,N-diethyl-m-toluamide) and the insecticidechlorpyrifos (O,O-diethyl O-3,5,6-trichloropyridinyl phosphorothioate)and to pyridostigmine bromide (PB, 3-dimethylaminocarbonyloxy-N-methylpyridiniumbromide) that was administered as a prophylactic agent againstpossible nerve gas attack. The present study was designed todetermine the toxicity produced by individual or coexposureof hens 5 days/week for 2 months to 5 mg PB/kg/day in water,by gavage; 500 mg DEET/kg/day, neat, sc; and 10 mg chlorpyrifoskg/day in corn oil, sc. Coexposure to various binary treatmentsproduced greater neurotoxicity than that caused by individualexposures and was characterized by severe neurologic deficitand neuropathological alterations. Also, neurotoxicity was furtherenhanced following concurrent administration of the three chemicals.Severe inhibition of plasma butyrylcholinesterase (BuChE) activitywas produced in hens treated with PB (activity 17% of control)compared to those treated with chlorpyrifos (activity 51% ofcontrol) or DEET (activity 83% of control). BuChE inhibitionwas further increased in binary and tertiary treatment groupscompared to individual treatment groups. In contrast, a significantinhibition of brain acetylcholinesterase (AChE) was producedin hens administered chlorpyrifos alone (activity 67% of control),while those given chlorpyrifos in combination with other compoundsexhibited a significant inhibition of brain AChE activity rangingfrom 43 to 76%. Brain neurotoxicity target esterase (NTE) wasnot inhibited in any of the individual treatment groups or PBIDEET,but was significantly inhibited and had activity expressed asa percentage of control in groups administered combined chlorpyrifoswith PB of 73% or DEET of 74% and in the tertiary treatmentgroup of 71%. We hypothesize that test compounds may competefor xenobiotic metabolizing enzymes in the liver and blood andmay also compromise the integrity of the blood-brain barrier,leading to an increase in their "effective con centrations"in the nervous system to levels equivalent to the toxic dosesof individual compounds. This is consistent with the presentobservation of increases in (1) the inhibition of brain AChEand NTE, (2) the extent of neurologic dysfunction, and (3) theseverity and frequency of neuropathologic lesions in the combinedtreat ment groups compared to those administered individualcompounds.     

Corticosterone Modulates Acute Toxicity of 2,3,7,8-Tetrachlorodibenzo-p-1 dioxin (TCDD) in Male Sprague--Dawley Rats

Corticosterone Modulates Acute Toxicity of 2,3,7,8-Tetrachlorodibenzo-p-dioxin(TCDD) in Male Sprague-Dawley Rats.GORSKI, J. R., ROZMAN, T.,GREIM, H., AND ROXMAN, K. (1988). Fundam Appl. Toxicol 11, 494-502.Bilateral adrenalectomy or adrenal demedullation was performedon male Sprague-Dawley rats by established surgical techniques.Subsequently, the dose-response (mortality and mean time todeath) to TCDD was determined in adrenalecto-mized (10, 20,40 µg/kg TCDD ip in 95:5 corn oil: acetone) or demedullated(15, 30, 60 µg/kg TCDD) rats. Adrenalectomy drasticallyincreased mortality and greatly shortened mean time to deathafter dosing with TCDD. More importantly, adrenalectomized TCDD-treatedrats died 3 of hypoglycemic shock without losing much body weightConversely, adrenal demedullation had no effect on mortalityor mean time to death caused by TCDD when compared to non-demedullatedTCDD-treated controls. Thus, it was concluded that the factors)modulating the acute toxicity of TCDD resides in the adrenalcortex and not in the medulla. Administration of corticosterone(25 ngjµl in drinking water) to adrenalectomized ratsreturned the toxicity of TCDD to levels seen in nonadrenalectomizedrats suggesting that this hormone is another key 3 factor (inaddition to the thyroid hormones) in the modulation of the acutetoxicity of TCDD. Corticosterone supplementation (25, 50, or100 µg/) to nonadrenalectomized rats, or to thy- roidectomized-adrenalectomizedrats (25 µg/ml), resulted in no additional beneficialeffect indicating that a factoids) other than thyroid hormonesand corticosterone is also involved in the 14 acute toxicityof TCDD     

Target Tissue Morphology and Serum Biochemistry following 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) Exposure in a TCDD-Susceptible and a TCDD-Resistant Rat Strain

Target Tissue Morphology and Serum Biochemistry following 2,3,7,8-Tetrachlorodibenzo-p-dioxin(TCDD) Exposure in a TCDD-Susceptible and a TCDD-Resistant RatStrain. POHJANVIRTA, R., KULJU, T., MORSELT, A. F. W., TUOMINEN,R., JUVONEN, R., ROZMAN, K.,MÄNNISTÖ, P., COLLAN,Y., SAINIO, E.-L., AND TUOMISTO, J. (1989). Fundam. Appl. Toxicol.12, 698–712. The mode of action of the highly toxic environmentalcontaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is unknown.It was recently discovered that two strains of rat, Long-Evans(L-E) and Han/Wistar (H/W), differ widely in susceptibilityto TCDD. Employing this strain divergence as a probe, the presentstudy set out to assess the role of various biochemical andmorphological effects in TCDD lethality. In the main experiment,the rats were treated once ip with 0, 5, 50, or (H/W) 500 µg/kgTCDD and killed 1 to 16 days postexposure. Several target organswere evaluated by light microscopy and a number of serum lipidand carbohydrate parameters as well as a few major regulatoryhormones were analyzed. The results demonstrated that most alterationscaused by TCDD were essentially similar in both strains. TCDDreduced circulating thyroxine to a slightly greater extent andmore permanently in the sensitive L-E strain. Moreover, a highlysignificant interaction on thyroid-stimulating hormone was foundamong strain, dose. and time. Serum concentrations of corticosteroneand free fatty acids were increased only in the L-E rats given50 µg/kg TCDD, i.e., at an apparent LDl00 dose level forthis strain. Yet, the most striking interstrain difference wasseen in the liver which was distinctly affected after Day 4in L-E rats given 50 µg/kg TCDD but only marginally affectedin rats from any H/W group. The lesion, while showing no necroticcell changes, was suggestive of plasma membrane damage, possiblyreflecting the production of free radicals. The relation ofthe findings to possible mechanisms of TCDD action is discussed.     

Cryoballoon Pulmonary Vein Isolation with Real-Time Recordings from the Pulmonary Veins

Introduction: Cryoballoon (CB) ablation represents a novel technology for pulmonary vein isolation (PVI). We investigated feasibility and safety of CB-PVI, utilizing a novel spiral catheter (SC), thereby obtaining real-time PV potential registration.
Methods: Following double transseptal puncture, a Lasso catheter (Biosense Webster, Diamond Bar, CA, USA) and the 28 mm CB were positioned within the left atrium. A novel SC (Promap, ProRhythm Inc., Ronkonkoma, NY, USA) was inserted through the lumen of the CB allowing PV signal registration during treatment. Time to PV conduction block was analyzed. If no stable balloon position was obtained, the SC was exchanged for a regular guide wire and PV conduction was assessed after treatment by Lasso catheter.
Results: In 18 patients, 39 of 72 PVs (54%) were successfully isolated using the SC. The remaining 33 PVs were isolated switching to the regular guide wire. Time to PV conduction block was significantly shorter in PVs in which sustained PVI was achieved as compared to PVs in which PV conduction recovered within 30 minutes (33 ± 21 seconds vs 99 ± 65 seconds). In 40 PVs, time to PV conduction block was not obtained because of: (1) PVI not being achieved during initial treatment; (2) a distal position of the SC; or (3) isolation with regular guide wire. No procedural complications occurred.
Conclusion: Visualization of real-time PV conduction during CB PVI is safe, feasible, and allows accurate timing of PVI onset in a subset of PVs. Time to PV conduction block predicts sustained PVI. However, mechanical properties of the SC need to be improved to further simplify CB PVI.