EFFECT OF CHRONIC ETHANOL CONSUMPTION ON IN VIVO PROTEIN SYNTHESIS IN LIVERS FROM FEMALE AND MALE RATS FED TWO DIFFERENT DIET REGIMENS

Hepatic protein synthesis was studied in male and female ratsfed ethanol-supplemented diets for 6–7 weeks. In one group(group 1), male rats were fed an all-liquid diet with 36% ofthe energy as ethanol. The controls were pair-fed with carbohydratereplacing ethanol isoenergetically. The second group of malerats (group 2) was given a mixture of solid and liquid diets.The solid food was given ad libitum and was supplemented witheither an ethanol-containing liquid (20–30% of energyas ethanol) or isoenergetic amounts of lipid. Female rats (group3) received the same diet regimen as group 2. Rates of hepaticprotein synthesis were measured after a 12–18 hr fastby a 32 min continuous infusion of ³H-valine. Specific precursorradioactivity (valyl tRNA) was calculated from valine specificradioactivities and concentrations in intra- and extracellularwater at 12, 22 and 32 min. The rates of protein synthesis were lower in all three groupsof ethanol-treated rats than in controls. In group 1, ethanolfeeding resulted in protein accumulation, and the plasma proteinconcentration was significantly lower at 20 and 32 min. In conclusion,female and male rats fed various diets were susceptible to thesame inhibitory effect of chronic ethanol consumption on hepaticprotein synthesis.     

GM-CSF-induced acute eosinophilic pneumonia

Summary. There is increasing evidence that haemopoietic growth factors are effective in reversal of neutropenia associated with large granular lymphocytes (LGLs) proliferation. A 19-year-old woman with CD3⁺/TCRγδ⁺, CD4⁻, CD8⁻ LGL proliferation and severe neutropenia repeatedly developed blood eosinophilia, fever and dyspnoea after administration of GM-CSF. Acute eosinophilic pneumonia with a lobar lung infiltrate pleural effusion, and marked bronchoalveolar lavage fluid eosinophilia was diagnosed. Treatment with corticosteroids and discontinuation of GM-CSF lead to rapid improvement. In addition, haematological analysis revealed that H*1 Technicon, a widely-used automated cell counter, may misinterpret eosinophils erroneously as neutrophils, therefore examination of blood smears to prevent eosinophil-medlated toxicity during GM-CSF treatment is recommended.     

Arterial hypertension and sleep apnoea: effect of the angiotensin-converting enzyme (ACE) Inhibitor cilazapril on continuously measured blood pressure during sleep and wakefulness

SUMMARY  Male patients with arterial hypertension and obstructive sleep-related breathing disorders (mean age 50 y, Body Mass Index (BMI) 32.4 kg m^-2, Respiratory Disturbance Index (RDI) 47.2 and systolic/diastolic blood pressure (SBD/DBD) 162/103 mmHg) were examined before and after 8 days of treatment with the long-acting angiotensin-converting-enzyme (ACE) inhibitor cilazapril 2.5 mg vs. placebo in a double-blind design with parallel groups. Cardiorespiratory polysom-nography was carried out at night; during daytime wakefulness patients submitted to examinations of physical and mental exertion. Cilazapril reduced the mean pressure during the entire examination period (day and night) by 9.55 (SD±7.13) mmHg, compared to 4.57 (SD ±7.20) mmHg for placebo ( P < 0.006), independently from systematic changes of heart rate ( x = -3.3 and -3.5 bpm, respectively). During REM sleep, mean arterial pressure was significantly reduced by 8.63 (SD ±10.1) mmHg, compared to a reduction on placebo of 3.17 (SD 9.6) mmHg ( P = 0.023). Under psychometric strain, the mean arterial pressure was reduced by 15.31 (SD ±8.7) mmHg with cilazapril; under placebo medication by 6.19 (SD ±7.3) mmHg ( P < 0.0001). Heart rate was not significantly changed.     

Low-Energy Transvenous Cardioversion of Atrial Fibrillation Using a Single Atrial Lead System

Atrial Cardioversion Using a Single Atrial Lead System. Introduction: Clinical studies have shown that electrical conversion of atrial fibrillation (AF) is feasible with transvenous catheter electrodes at low energies. We developed a single atrial lead system that allows atrial pacing, sensing, and defibrillation to improve and facilitate this new therapeutic option. Methods and Results: The lead consists of a tripolar sensing, pacing, and defibrillation system. Two defibrillation coil electrodes are positioned on a stylet-guided lead. A ring electrode located between the two coils serves as the cathode for atrial sensing and pacing. We used this lead to cardiovert patients with acute or chronic AE. The distal coil was positioned in the coronary sinus, and the proximal coil and the ring electrode in the right atrium. R wave synchronized biphasic shocks were delivered between the two coils. Atrial signal detection and pacing were performed using the proximal coil and the ring electrode. Eight patients with acute AF (38 ± 9 min) and eight patients with chronic AF (6.6 ± 5 months) were included. The fluoroscopy time for lead placement was 3.5 ± 4.3 minutes. The atrial defibrillation threshold was 2.0 ± 1.4 J for patients with acute AE and 9.2 ± 5.9 J for patients with chronic AF (P < 0.01). The signal amplitude detected was 1.7 ± 1.1 mV during AF and 4.0 ± 2.9 mV after restoration of sinus rhythm (P < 0.001). Atrial pacing was feasible at a threshold of 4.4 ± 3.3 V (0.5-msec pulse width). Conclusions: Atrial signal detection, atrial pacing, and low-energy atrial defibrillation using this single atrial lead system is feasible in various clinical settings. Tbis system might lead to a simpler, less invasive approach for internal atrial cardioversion.     

THE ROLE OF GLUCOSE AND INSULIN IN THE EFFECT OF ETHANOL ON PROTEIN SYNTHESIS IN ISOLATED RAT HEPATOCYTES

The incorporation of ¹⁴C-valine into liver protein was studiedin isolated rat liver parenchymal cells. Various glucose levelsin the incubation media did not affect the rate of ¹⁴C-valineincorporation into proteins. The insulin stimulated incorporationof ¹⁴C-valine into proteins was also unaffected by the variousglucose levels. Ethanol decreased the incorporation of ¹⁴C-valineinto liver proteins, affecting stationary and export proteinsto the same extent. This inhibitory action of ethanol on valineincorporation was reversed by increasing exogenous glucose concentrations.The combination of insulin and high glucose level totally preventedthe ethanol inhibition.     

Intracardiac Emergency Defibrillation for Refractory Ventricular Fibrillation During Implantation of Cardioverter Defibrillators with Nonthoracotomy Lead Systems

Implantable cardioverter defibrillators (ICDs) are being implanted in increasing numbers. At inlraoperative defibrillation threshold tests refractory ventricular fibrillation (VF) requiring emergency open chest resuscitation is a major concern during impiantation of nonthoracotomy ICD lead systems. A new method of high energy endocardial/extrathoracic defibrillotion via the implanted ICD transvenous defibrillation electrode (TDE) was used to terminate refractory VF. During implantation of ICD with TDE in 20 patients refractory VF occurred in two patients. The arrhythmia was terminated with endocardial/extrathoracic defibrillation in both cases, and no complications were observed.     

THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS IN INFANTILE MALNUTRITION

We studied the circadian rhythm and the response of the hypothalamic-pituitary-adrenal (HPA) axis to ovine corticotrophin releasing hormone (oCRH) stimulation and dexamethasone suppression in 32 children with grade II-III marasmus. Children were studied prior to and after nutritional rehabilitation. Mean baseline plasma cortisol concentrations were elevated at admission and decreased significantly after nutritional rehabilitation. Mean +/- SEM plasma cortisol response to oCRH increased from a basal of 480 +/- 41 to a peak of 582 +/- 58 nmol/l at the time of admission, and from a basal of 234 +/- 27 to a peak of 532 +/- 41 nmol/l after caloric rehabilitation. Dexamethasone suppression in the malnourished group was associated with a decrease in the mean +/- SEM basal plasma cortisol concentration from 397 +/- 44 to 171 +/- 44 nmol/l. After caloric rehabilitation, basal cortisol levels decreased from 259 +/- 27 to 22 +/- 5 nmol/l following dexamethasone. Our results support the concept that malnutrition is associated with decreased responsiveness to oCRH and incomplete dexamethasone suppression, and that these abnormalities are restored after nutritional rehabilitation.     

PREVALENCE, MORPHOLOGY AND BIOLOGY OF RENAL CELL CARCINOMA IN VON HIPPEL-LINDAU DISEASE COMPARED TO SPORADIC RENAL CELL CARCINOMA

Purpose

Renal cell carcinoma occurs as a sporadic tumor but may be part of the autosomal dominant von Hippel-Lindau disease, characterized by retinal and central nervous system hemangioblastoma, pheochromocytoma, pancreatic cysts and renal cell carcinoma. We determine the prevalence of von Hippel-Lindau disease in a series of unselected renal cell carcinoma cases by molecular genetic analysis, and compare sporadic to von Hippel-Lindau renal cell carcinoma with respect to morphology and biology.

Materials and Methods

We established registers comprising 63 subjects with von Hippel-Lindau renal cell carcinoma, belonging to 30 distinct families (register A), and 460 unselected patients operated on for renal cell carcinoma in an 11-year period (register B). Molecular genetic analysis of the von Hippel-Lindau gene was performed for living patients of register A, representing 80% of von Hippel-Lindau families, and register B, 62% living patients, to identify von Hippel-Lindau germline mutations. In addition, register B was evaluated by a questionnaire (95% response) for familial occurrence of von Hippel-Lindau disease.

Results

The prevalence of von Hippel-Lindau renal cell carcinoma was 1.6% in 189 consenting unselected renal cell carcinoma patients. Risk factors for occult germline von Hippel-Lindau gene mutations in register B included familial renal cell carcinoma in 3 of 3 patients (100%), multifocal or bilateral renal cell carcinoma in 1 of 10 (10%) and age younger than 50 years at diagnosis in 1 of 33 (3%). Compared to sporadic von Hippel-Lindau renal cell carcinoma was characterized by an occurrence 25 years earlier, association with renal cysts, multifocal and bilateral tumors, cystic organization and low grade histology, and a better 10-year survival (p <0.001 each). In von Hippel-Lindau disease metastases occurred only in tumors larger than 7 cm.

Conclusions

Von Hippel-Lindau differs from sporadic renal cell carcinoma in morphology and biology. Our data provide arguments for planning surgery for von Hippel-Lindau renal cell carcinoma and should stimulate future investigations.