Heart failure accompanied by sick euthyroid syndrome and exercise training.

Sick euthyroid syndrome is defined as the decrease of serum free triiodothyronine with normal free L-thyroxin and thyrotropin. Its appearance in patients with chronic heart failure is an indicator of severity. Exercise training through a wide variety of mechanisms reverses sick euthyroid syndrome (normalization of free triiodothyronine levels) and improves the ability to exercise. There is a connection during exercise among dyspnea, hyperventilation, fatigue, catecholamines, a decrease in the number and function of beta-blocker receptors, and elevation of serum free triiodothyronine. It is not known whether sick euthyroid syndrome contributes to the development of heart failure or is only an attendant syndrome.

Risk factors of ischaemic heart disease and long-term outcome after coronary bypass surgery.

BACKGROUND: To investigate the effect of ischaemic heart disease (IHD) risk factors on the long-term course of patients who undergo coronary artery bypass graft (CABG) surgery, was the aim of our study. METHODS: We studied a total of 128 people, who were classified into 4 groups. Control Group A consisted of 24 healthy adults, Group B of 23 patients who underwent CABG for 3-vessel disease and had no complications in the first two postoperative years, Group C of 41 patients who were hospitalized for acute myocardial infarction (AMI) during the first or second post-CABG year and Group D of 40 patients who were hospitalized for AMI without previous CABG. All subjects were investigated for IHD risk factors (blood glucose, serum lipids, lipoprotein-a) with concurrent assays of coagulation-fibrinolysis factors (fibrinogen, antithrombin-III, PAI-1 and t-PA). RESULTS: We found that: 1. Patients with previous CABG represented 50.6% of the total number of patients admitted with AMI in our department during one year. Compared to Groups A (controls) and B (CABG with good course), these patients (Group C) had significant increases in Lp (a), fibrinogen, LDL-ch, PAI-1 and t-PA and decreased HDL-ch and AT-III. 2. There were no significant differences in these factors in patients with AMI, regardless of whether they had had previous CABG. CONCLUSIONS: It is concluded that the accumulation of IHD risk factors and coagulation-fibrinolysis abnormalities play a significant role in the postoperative course of patients undergoing CABG, regardless of the use of anti-angina medication. It is imperative that such factors be corrected.

Effect of pyrazinamide and probenecid on peritoneal urate transport kinetics during continuous ambulatory peritoneal dialysis.

OBJECTIVE: We administered pyrazinamide (PZA) and probenecid (PB) --two well-known modulators of urate transport via the proximal tubules - to evaluate their impact on urate transport through the peritoneal membrane and to clarify mechanisms affecting peritoneal transport. SETTING: A continuous ambulatory peritoneal dialysis (CAPD) unit in 2nd Hospital of IKA (Social Services Institute), Greece. PATIENTS: In 20 stable CAPD patients, on the study day, a 4-hour, 2-L, 1.36% glucose exchange was performed (control exchange). Pyrazinamide 3 g was given orally and another identical exchange was performed (study exchange). The same protocol was repeated with 2 g PB. KtN, peritoneal clearances of urea, creatinine, and urate for each exchange, and mass transfer area coefficients (MTAC) for the three solutes and their dialysate-to-plasma concentration (D/P) ratios were used to estimate peritoneal transport. RESULTS: Administration of PZA resulted in decreased clearances and MTAC values for the three solutes. The D/P ratio decreased significantly only for urate, indicating a more intense influence of PZA on urate. After PB administration, clearances of urea, creatinine, and urate were increased. MTAC and DIP ratio increased significantly only for urate (p < 0.05), demonstrating an action similar to that exerted on renal tubules. CONCLUSIONS: These findings provide evidence that unrestricted diffusion is not the only transport mechanism in the case of urate, and demonstrate the existence of an active mechanism in peritoneal urate transport with a reabsorptive and, probably, a secretive component that resembles that of renal tubule urate transport. Attention should be given in the case of CAPD patients undergoing antituberculous (PZA) treatment: it might have a negative impact on urea, creatinine, and urate peritoneal transport rates.

Antigenic stimulation in T-cell cultures in cardiomyopathies: differences in cytokine profiles.

Immune-mediated mechanisms are involved in the pathogenesis of cardiomyopathies. In this study, we investigate which pattern of immune response (Th1 or Th2) lies behind these diseases by analysing the basic cytokines secreted from PHA-cultured T lymphocytes and determining what differences, if any, exist between dilated cardiomyopathy (DMC) and hypertrophic cardiomyopathy (HCM). Two groups of patients were studied: 10 patients with DCM and 10 patients with HCM. Age- and sex-matched healthy individuals were used as controls. PHA-cultured T lymphocytes in the presence or absence of different myocardial antigen (MA) concentrations were measured. Interleukine-2 (IL-2), Interleukine-6 (IL-6) and Interferon-gamma (IFN-gamma) levels were measured in culture supernatants by an ELISA method. At the same time, delayed-type hyperactivity (DTH) against the same antigenic preparation was measured by the leukocyte migration inhibitory index technique. Patients were subdivided into DTH-positive and DTH-negative and re-examined for IL-2 cytokine expression. IL-6 levels were found to increase both in the presence and in the absence of MA in the patient groups compared to the controls. IL-2 levels were decreased in both groups, in an antigen dose-related manner. Anergic patients showed a further reduction in IL-2 levels for both groups of patients. IFN-gamma remained unaffected in the patient groups. Almost half of the patients exhibited anergy to the DTH reaction against MA. We conclude that, upon antigenic stimulation, the initially mounted immune response (increased IL-6) is somehow blocked/switched off in patients, resulting in an immunologic tolerance/unresponsiveness to MA (IL-2 decreased, IFN-gamma unchanged). Finally, increased IL-6 could lead to a perpetuation of immunologic injury through the release of oxygen-free radicals with a cytotoxic effect on the myocardium. We hypothesize an antigen-related, defective macrophage-Th1 cell reaction, which accounts for the differences in the IL-2 profile between the DCM and HCM groups, that might cause local immune responses to lead to immunosuppression (immune tolerance effect), thus contributing to the pathogenesis of cardiomyopathies.

In vivo effect of granulocyte-macrophage colony-stimulating factor and interferon combination on monocyte-macrophage and T-lymphocyte functions in chronic hepatitis B leukocytopenic patients.

BACKGROUND/AIMS: Both rhGM-CSF and IFN-gamma have antiviral and immunoregulatory effects. Furthermore, GM-CSF has the advantage of increasing WBC in leukocytopenic patients. METHODOLOGY: We investigated a) the antiviral effects of rhGM-CSF and INF-alpha combination treatment in 12 chronic hepatitis B patients with leukocytopenia as a result or not of previous interferon therapy, b) the in vivo effects of these agents on monocyte-macrophage and T-lymphocyte functions and, c) their correlation to HBV infection outcome. RESULTS: Combination therapy caused a significant fall in HBV-DNA levels (p<0.0002), accompanied by significant reductions in transaminase levels and in histological activity index (p<0.0001, in each case). In parallel, rhGM-CSF induced a 2.7- to 5-fold weekly increment in WBC. Moreover, treatment caused a significant increase in all monocyte-macrophage parameters (p<0.0001 for random, directed migration and phagocytosis index) and in peripheral blood lymphocyte parameters (p<0.0001 for IL-2r and HLA-DR expression) studied. A similar picture was also obtained from cytokine levels (IL-2 and GM-CSF) in the supernatants from PHA-cultured T-lymphocytes (p<0.0003, <0.001, respectively). CONCLUSIONS: The combined therapy achieves the initial treatment aim of increasing WBC and exerting an antiviral effect. In addition, the observed changes in immunological parameters probably reflect a Th1 pattern of immune response that could be responsible for the fate of HBV infection. Finally, cytokine levels (IL-2 and GM-CSF) in the supernatants might serve to monitor viral activity and outcome of the HBV infection.

The effect of mannitol and secretin on the biliary transport of urate in humans.

No evidence is available on the transport of biliary urate and the possible role of choleretic agents in the regulation of biliary urate elimination in humans. To test this hypothesis we studied the following: (1) 45 cholecystomized patients to determine urate levels in hepatic bile and gallbladder bile, and (2) 13 cholecystomized patients fitted with T-tubes to determine the effects of secretin injection (either 70 U of porcine secretin or 0.02 mg.kg-1 of synthetic human secretin, as a single dose) and/or mannitol infusion (5 cm3.min-1 for 90 minutes) on biliary urate excretion. In the latter group, samples of bile and serum were analyzed for urate under basal state and after the administration of both agents. In our first approach, results showed that urate concentrations present in hepatic as well as in gallbladder bile were much lower than the corresponding values in serum (P < .001). The mean gallbladder bile urate concentration was not significantly increased over the concentration in hepatic bile. When compared with basal state values, procine and synthetic secretin induced a significant increase in mean urate clearance (P < .001) because of a significant increase in mean bile flow (P < .001), whereas the mean biliary urate concentration significantly decreased (P < .001) with a concomitant decrease in the mean serum urate concentration (P < .02). Mannitol also induced a significant increase in the mean urate clearance (P < .002) because of a significant increase in the mean biliary urate concentration (P < .01) with a concomitant decrease in the mean serum urate concentration (P < .01) and without changes in the mean bile flow (P > .05). Therefore, it appears that a substantial amount of urate is eliminated by biliary route. The load of biliary urate excreted may be modified by mannitol and secretin and possibly other factors, a finding that could have an application in some pathological conditions associated with decreased renal urate excretion.

Interferon-A 2a administration in chronic anergic brucellosis.

Two cases with chronic anergic brucellosis are described. Both patients suffered repeated disease relapses and responded poorly to conventional treatment. The immunologic research revealed that both patients were anergic to brucella antigens and immunocompromised. In an effort to restore patients' defective immune responses, we administered Interferon-A 2a during a six month treatment period as follows: a) loading dose- 3MU SC 3 days/week for an 8 week trial, followed by, b) maintenance period- 3MU SC three times/week. Our results showed that IFN administration induced clinical remission in both patients by the end of the 4th month of treatment. Additionally, Coombs' agglutination titers decreased gradually, the leucocyte migration index and the skin tests developed "energy" to antigens and the monocyte macrophage function tests were restored to normal. We concluded that IFN treatment can be beneficial in chronic anergic brucellosis by restoring defective immune responses, promoting therefore a sufficient inflammatory response against brucella infection.

Recombinant a2 interferon (a-IFN) with chemo-hormonal therapy in patients with hepatocellular carcinoma (HCC).

Recent studies on HCC treatment reveal a tendency to use combined immuno-chemo-therapy. Additionally, new agents have been suggested in this field. We therefore studied 7 patients with proven inoperable HCC who were treated in accordance with the following protocol, and 5 untreated patients used as controls. Therapeutic trial: 1) 1FNa (Roferon): 6 MU x 7 days consecutively every 3 weeks, 2) Adriamycin (doxorubicin): 60 mg/m2 i. v. once every 3 weeks (500 mg total dose), 3) Tamoxifen: 10 mg p.o. twice daily continuously 4) Desferrioxamine (DFO): 500 mg i.m. daily x 7 days consecutively every 3 weeks, 5) ascorbic acid: 300 mg p.o. daily 1 hour after DFO administration x 7 days consecutively every 3 weeks. Follow-up studies were performed monthly and comprised clinical, biochemical, radiological and immunological (T-cell subsets, NK cells, monocyte-macrophage function, IL-2r expression, HLA-DR expression) parameters. Compared with the control group, the treated group had a longer survival rate (p < 0.001), increased tumor regression and less progressive disease. Immunologically, the treated patients with the maintenance of a sufficient immune status were associated with a prolonged survival rate. No serious side effects of the regimen were observed. In conclusion, IFNa combined with chemohormonal therapy appears to be beneficial in HCC patients. In addition, a prolonged survival rate might correlate with the maintenance of an adequate immune status in the patients.

Intravenous administration of diltiazem in the treatment of supraventricular tachyarrhythmias.

UNLABELLED: The aim of the study was to investigate the efficacy of diltiazem bolus intravenous administration, compared to disopyramide, in the treatment of various types of paroxysmal supraventricular tachyarrhythmias. METHOD: Fifty patients (23 males, 27 females, mean age 47.7 +/- 15.2 years) with paroxysmal supraventricular tachyarrhythmia (20 with paroxysmal atrial tachycardia, 23 with paroxysmal atrial fibrillation and rapid ventricular response and 7 with atrial fluttering) were studied. Diltiazem at a dose of 0.25-0.30 mg/kg BW or disopyramide at a dose of 50 mg were given bolus IV. If conversion of the arrhythmia to sinus rhythm could not be achieved with the initial drug, the alternate was given. The order of administration of the drugs was random, independent of the type of the arrhythmia. Before and during drug administration detailed clinical examination and frequent blood pressure (BP) measurements were performed. Twenty-four hour Holter monitoring was done in all patients, starting with the administration of the antiarrhythmic drug. RESULTS: 1) Paroxysmal atrial tachycardia: diltiazem administration converted the arrhythmia to sinus rhythm in all patients while disopyramide in only 1 of 9 patients who received this drug. 2) Paroxysmal atrial fibrillation: disopyramide converted the arrhythmia in 5 patients without significant change in ventricular response in the others. Diltiazem did not convert the arrhythmia though it caused significant decrease in ventricular response (< 100 bpm) and in 1 patient an important bradycardia (45 bpm). 3) Atrial fluttering: disopyramide converted the arrhythmia to sinus rhythm in 1 patient without significant change in the ventricular response in the others. Diltiazem caused significant decrease in the ventricular response without conversion to sinus rhythm. During conversion to sinus rhythm an AV junctional rhythm of short duration (< 1 min) was noticed in 5 patients and a short pause (< 2 sec) with or without an initial premature contraction in the remaining 21. Disopyramide administration was not associated with side effects. Diltiazem administration cause small (< 20 mm Hg), transient (< 30 min) decrease of BP without symptoms with the exception of the patient with bradycardia in whom the BP decrease was significant (90/60 from 160/80 mm Hg) followed by intense symptoms which lasted for six hours. CONCLUSIONS: Diltiazem administration is extremely effective in conversion of paroxysmal atrial tachycardia to sinus rhythm. In addition it retards ventricular response in patients with atrial fibrillation and fluttering. Compared to disopyramide these effects of diltiazem are more pronounced and clinically pertinent.

The predictive value of troponin T in patients who underwent an extracardiac surgery operation.

UNLABELLED: Purpose of the study is the research of the diagnostic value of the determination of Troponin T in relation with the other cardiac enzymes in patients who underwent extracardiac surgery operation. METHODS: 42 pts (M = 24, F = 18, mean age 51.7 +/- 17 years) who underwent a surgery operation were studies. For all pts serum enzyme CPK, CPK MB, SGOT and Troponin T was determined 24 hours before and after the operation. RESULTS: increased value of CPK was observed in all patients. In 14.3% of pts was found abnormal value of CPK. In 1 pt CPK MB was found increased. In no one of the above pts was observed an increased value of Tr-T. No one of the pts had ECG changes and clinical symptoms indicative of ischemic heart disease. CONCLUSIONS: these results suggest that the determination of Tr-T in serum is more useful diagnostic index for myocardial cell injury in pts who underwent an extracardiac surgery because is not detected in skeletal muscle injury.

In vivo effect of omeprazole on HLA-DR expression and the monocyte-macrophage function in patients with duodenal ulcer disease.

It is not known if omeprazole possesses any action on immune system. Therefore, we examined the effect of omeprazole on parameters of cellular immunity [T-cell subsets-CD3+, CD4+, CD(8+)- and HLA-DR expression on peripheral blood lymphocytes (PBLs)] and on function of peripheral blood monocyte-macrophages (PBMMs) [random migration (RM), directed migration (DM), phagocytosis index (P-I) and HLA-DR expression] in 13 duodenal ulcer patients before and during 3-mo omeprazole treatment. The number of T-cell subsets varied at pretreatment values (p > 0.05), whereas the percentage of HLA-DR positive PBLs increased significantly after 3-mo therapy (p < 0.001). On the other hand, all studied parameters concerning PBMMs (RM, DM, P-I and HLA-DR expression) increased significantly after 3-mo therapy (p < 0.001, p < 0.001, p < 0.003, p < 0.001, respectively vs. baseline values). In conclusion, omeprazole exerts an immunopotentiating effect on functions of PBMMs and may also influence T-cell function. These effects can be considered as an advantage of omeprazole in long-term treated patients with peptic ulcer disease.

The diagnostic value of the determination of troponin T in the diagnosis of unstable angina.

UNLABELLED: The purpose of the study is the predictive value of determination of Tr-T in diagnosis of unstable angina. METHODS: 35 pts (24 male, 11 female, mean age 53.4 +/- 5 years) were studied. Group A: 20 pts (15 male, 5 female, mean age 50 +/- 6 years) with unstable angina. Group B: 15 pts (9 male, 6 female, mean age 56.4 +/- 4 years) with stable angina RESULTS: pts with stable angina (group B) had normal value of CPK-MB, SGOT, LDH, Tr-T. Eight pts with unstable angina (group A) had increased value of Tr-T with normal value of CPK-MB, SGOT, LDH. In conclusion the determination of Tr-T is helpful in diagnosis of unstable angina and it may be useful in the prognosis of these pts.

Value of ascitic fluid ferritin in the differential diagnosis of malignant ascites.

The ascitic fluid ferritin concentrations were compared with serum-ascites albumin gradient (SAAG), in their diagnostic ability for detection of malignancy in 60 patients with ascites: 29 with chronic liver disease alone (CLD) and 31 patients with various neoplasms. Of the patients with malignancy, 12 had liver metastases, 9 had no evidence of liver involvement, and 10 had hepatocellular carcinoma (HCC) with or without coexisting liver cirrhosis. Analysis of our data confirms that the ascitic ferritin is a more accurate indicator of malignant ascites (MA) than the SAAG. This new parameter is particularly helpful in distinguishing MA associated with HCC and/or metastatic liver disease from nonmalignant ascites due to CLD alone.

Single kidney function: early and late changes in urate transport after nephrectomy.

Renal urate transport was studied by means of pyrazinamide (PZA) and probenecid (PB): (a) before and at 2, 6, 24 weeks (24 patients), (b) 1 to 30 years after uninephrectomy in 27 and 12 patients with Ccr greater than 80 and 30 to 70 ml/min, respectively. Uninephrectomy was followed by important tubular urate transport modifications during at least two weeks, which lead to a marked uricosuria as indicated by significant increase in FEur (mean value +/- SD, 0.228 +/- 0.059 vs. 0.097 +/- 0.014 and 0.099 +/- 0.019 in normals and chronically diseased solitary kidneys). Reduced response to PZA and PB suggests a diminished reabsorptive capacity for urate mainly at the presecretory site which persisted after FENa normalization. Tubular compensations were presumably complete at six weeks, since pattern of urate transport returned to normal with an almost complete reabsorption of filtered urate load (99%) and a percentage of postsecretory reabsorption (80%) very close to those seen in normal subjects with a pair of kidneys. The adjustment in urate excretion in solitary kidneys was achieved by a significant increase of secreted urate as compared with 50% of pre-uninephrectomy values. Thus, increased urate secretion by the remaining intact organ is sufficient to maintain urate balance with a normal serum level.

Cholangiocarcinoma and severe renal hypouricemia: a study of the renal mechanisms.

Hypouricemia in malignant neoplasms is rarely reported. We present a previously unreported case of cholangiocarcinoma associated with severe persistent hypouricemia (serum uric acid levels ranged from 0.07 to 0.08 mmol/L [1.16 to 1.40 mg/100 mL], and increased urate clearance (50.90 to 57.33 mL/min v a mean value in 20 normal subjects of 9.75 +/- 1.65 mL/min). High fractional urate clearance (Cus/Ccr = 0.50 to 0.58 v 0.09 +/- 0.01 in normals) was suppressed only slightly following pyrazinamide (PZA), to 0.29 versus 0.007, and was surprisingly enhanced by probenecid (PB) to 1.78 versus 0.63 in normals. No other renal tubular or metabolic abnormalities were detected. This previously unreported association of a high PZA-nonsuppressible urate excretion with a postprobenecid urate clearance exceeding glomerular filtration rate suggests that a combined renal tubular defect is responsible for hypouricemia. The patient described here provides evidence to support the presence of a presecretory reabsorptive defect in association with a "relatively high" urate secretion by the renal tubule. This report adds to the list of hypouricemic conditions and presents an important clue to elucidate urate handling mechanisms in man.

Insulin-dependent diabetes and renal hypouricemia.

We studied 14 patients (11 women and 3 men) from 18 to 33 years old, suffering from type I diabetes mellitus with normal renal function (creatinine clearance 106.91 +/- 28.73 ml/min) and serum uric acid below 2.5 mg/dl (2.34 +/- 0.11 mg/dl) as well as a high uric acid clearance (23.04 +/- 5.92 ml/min) and fractional urate excretion (21.4 +/- 2.6) versus urate clearance 9.82 ml/min and fractional urate excretion 8.80 +/- 1.3 in 14 normal control subjects. The study of the uricosuric mechanisms was conducted by the combination of probenecid (PB) test which inhibits the reabsorption of secreted urate, and pyrazinamide (PZA) test, which inhibits its tubular secretion. The results of studies indicate that the increase in urate clearance was accounted for by increased PZA-nonsuppressible urate suggesting a decreased reabsorption of filtered urate. Increased PZA-suppressible urate excretion combined with impaired response to a uricosuric drug is consistent with impaired reabsorption of secreted urate. According to our findings, increased urate excretion in diabetic patients may be attributed to the inhibition of both filtered and secreted reabsorption. This reabsorptive tubular abnormality is consistent with the view of an interference of tubular reabsorption of glucose with the tubular capacity for uric acid reabsorption.

Psittacosis and arthritis.

Recent findings justify the opinion that Chlamydia psittaci is the reappearance of a forgotten pathogen. The clinical manifestation and the course of psittacosis are extremely variable, whereas the clinical spectrum of the infection with the different strains of C. psittaci is not known. Reactive arthritis during the course of psittacosis has been rarely described in humans. However, it has been stated that C. psittaci could be added to the list of infectious agents able to induce reactive arthritis. We describe a patient who presented with clinical signs consistent with reactive arthritis during the course of psittacosis, and we emphasize the good therapeutical results with ceftriaxone in the treatment of psittacosis.

Value of serum protective activity against acid precipitation of poly (U) in the differentiation between cirrhotic patients with and without hepatocellular carcinoma.

The serum protective activity against acid precipitation of poly (U) and a-fetoprotein levels were compared in 39 cirrhotic patients with hepatocellular carcinoma (HCC) and in 33 patients with chronic liver disease (CLD) alone, in order to differentiate malignant and nonmalignant chronic liver disease. All but one (97.4%) patients with HCC were found to have serum protective activity levels of greater than or equal to 21 micrograms/ml, whereas all but one (97%) patients with CLD had serum protective activity levels of less than or equal to 20 micrograms/ml. Mean serum protective activity levels were significantly higher in the HCC group than in those with CLD (p less than 0.0001). Serum a-fetoprotein concentrations of over 500 ng/ml, suggesting malignancy, were observed in 54% of patients with HCC and in 15% of patients with CLD. Application of the best discriminating values for protective activity (greater than 21 micrograms/ml) and for a-fetoprotein (greater than 500 ng/ml) to 72 patients with or without HCC revealed an efficiency of 97.2% for protective activity and only 68.1% for a-fetoprotein.

Monocyte locomotion in anergic chronic brucellosis patients: the in vivo effect of ascorbic acid.

In 14 patients suffering from relapsing chronic brucellosis who were anergic to brucella antigens, we have studied peripheral blood monocyte random migration and chemotaxis against non-specific and specific leukoattractants, as well as plasma and monocyte ascorbic acid levels. We found that all parameters studied, were significantly beneath normal, when compared to normal subjects. After the oral administration of ascorbic acid at a daily dose of 1gr for 15 consequetive days, random and directed migration against a non-specific stimulus (casein) returned to normal. Directed migration against disease associated leukoattractants (brucella melitensis and brucella abortus) antigens improved significantly, without reaching normal values. We concluded that ascorbic acid supplementation might partially restore peripheral, monocyte function and help the monocyte-macrophage system to mount an effective immune response against chronicity of brucella infection.

Rhabdomyolysis and acute renal failure associated with pyloric stenosis.

Rhabdomyolysis and acute tubular necrosis (ATN) are described in a patient with pyloric stenosis in whom severe hypokalemia developed due to repetitive vomiting. Furthermore, the importance of hypokalemia in the development of acute renal failure is emphasized.