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Biomedical subjects

G Jakob

Publications and source records attributed to G Jakob.

At least 19 recordsLinked to original sources

Protection of reoxygenated cardiomyocytes against osmotic fragility by nitric oxide donors.

In ischemic-reperfused myocardium, myocardial cells are jeopardized not only by reoxygenation-induced hypercontracture but also by the development of a transsarcolemmal osmotic gradient. Here the question of whether osmotic fragility of cardiomyocytes can be reduced by interventions during reoxygenation was addressed. Isolated ventricular cardiomyocytes (from adult rats), exposed to 120 min of hypoxia and subsequent reoxygenation, were used as model. With reoxygenation, medium osmolarity was reduced from 270 to 80 mosM. Loss of sarcolemmal integrity was characterized by enzyme loss from cells (creatine kinase and lactate dehydrogenase). Cardiomyocytes reoxygenated after 120 min of hypoxia hypercontracted, but enhanced enzyme loss was observed only at 80 mosM. The nitric oxide (NO) donors 3-morpholinosydnonimine (10 mM), sodium nitroprusside (10 mM), S-nitroso-N-acetyl-DL-penicillamine (100 microM), and the antilipid peroxidant diphenylphenylenediamine (DPPD, 2.5 microM) reduced enzyme loss with hyposmolar reoxygenation. Agents activating guanosine 3',5'-cyclic monophosphate (cGMP)-dependent pathways [atrial natriuretic peptide (1 microM), urodilatin (1 microM), and 8-bromo-cGMP (10 mM)], the contractile inhibitor 2,3-butanedione monoxime (10 mM), and the SIN-1 metabolite SIN-1C (10 mM) did not protect cardiomyocytes against osmotic fragility. The results show that increased osmotic fragility of isolated adult rat cardiomyocytes can be prevented at the time of reoxygenation by NO donors and DPPD in a cGMP-independent way.

Animals

Ergometric exercise testing and sensitivity of cyclic guanosine 3',5'-monophosphate (cGMP) in diagnosing asymptomatic left ventricular dysfunction.

OBJECTIVE: Increased plasma concentrations of cyclic guanosine monophosphate (cGMP) have been reported in patients with manifest heart failure. At rest, however, cGMP concentrations in patients with asymptomatic left ventricular dysfunction or heart failure in New York Heart Association (NYHA) functional class I do not differ significantly from those of healthy subjects. The purpose of this study was to investigate whether graded exercise on an ergometer improves the sensitivity of cGMP in diagnosing asymptomatic left ventricular dysfunction. PATIENTS: Plasma cGMP concentrations were compared in 17 healthy controls and 98 patients with asymptomatic left ventricular dysfunction or congestive heart failure of different stages (asymptomatic left ventricular dysfunction or NYHA functional class I, 56 patients; NYHA class II, 31 patients; NYHA class III, 11 patients). RESULTS: Before exercise plasma cGMP concentrations in patients with clinical heart failure (NYHA functional classes II and III) were significantly higher than those in healthy controls. In patients with asymptomatic left ventricular dysfunction or heart failure of functional class I plasma cGMP concentrations were not significantly different from those in healthy subjects. Thirty minutes after exercise, however, cGMP concentrations in patients with asymptomatic left ventricular dysfunction or class I heart failure were significantly higher than those in healthy controls. CONCLUSION: Measurement of plasma cGMP concentrations 30 minutes after ergometric exercise testing allows better discrimination between healthy subjects and patients with symptomless left ventricular dysfunction or mild heart failure (NYHA class I) than measurement of such concentrations before exercise.

Adult

Different time courses of cardiac contractile proteins after acute myocardial infarction.

For the first time we have compared time courses of cardiac myosin light chain-1 (MLC-1), beta-type myosin heavy chain (MHC), troponin T (TnT), myoglobin, creatine kinase (CK) and CKMB in the same patients with acute myocardial infarction (AMI). Blood samples were serially collected in 23 patients with first-time AMI. All but 3 patients received intravenous thrombolytic treatment. TnT and MLC-1 time courses were biphasic in most patients and showed two distinct peaks in 13 and 8 patients, respectively. MHC time courses were usually monophasic. Only 1 patient showed a biphasic MHC time course with two distinct peak values. Although MHC and MLC were lower by about the fourth day after onset of AMI in early reperfused patients, reperfusion did not qualitatively alter MLC and MHC release (no significant influence on the first appearance in blood or on time to peak). MLC and MHC peaks correlated closely (r = 0.75, P = 0.0001), whereas TnT peaks were correlated less closely with MLC or MHC peaks (r = 0.58 each, P < 0.007). Peak values of all cardiac contractile proteins correlated closely and significantly with CKMB peaks (0.75 < or = r < or = 0.81, P < or = 0.0006). Myoglobin was the first marker to increase in blood after AMI and showed the earliest peaks, whereas MHC increased latest showing the latest peaks. TnT increased significantly (P = 0.0001) earlier than MLC and MHC. These results can be explained by the impact of the intracellular compartmentation of a cardiac protein on the rapidity with which it is released after AMI.

Adult

Clinical significance of urinary cyclic guanosine monophosphate in diagnosis of heart failure.

We measured concentrations of guanosine 3',5'-monophosphate (cGMP) in plasma and urine of healthy subjects and patients with congestive heart failure, renal impairment, neoplastic disease, and hepatic cirrhosis. There was no correlation between cGMP concentrations in urine and in plasma. In all patients except those with renal impairment, urinary cGMP concentrations were significantly higher than in healthy persons. Only patients with heart failure or renal impairment showed significantly increased plasma cGMP concentrations. In contrast, cGMP in urine does not relate to the clinically assessed severity of heart failure (New York Heart Association functional classes). Determination of cGMP in plasma results in higher sensitivity and specificity for diagnosing heart failure than measurement of cGMP in urine.

Adult

Release of cyclic guanosine monophosphate evaluated as a diagnostic tool in cardiac diseases.

Concentrations of atrial natriuretic peptide (ANP) are increased in plasma of patients with impaired cardiac and renal function. The second messenger of ANP, cyclic guanosine monophosphate (cGMP), is released into the plasma specifically upon stimulation of cells with ANP. Although nitrates can also activate intracellular cGMP synthesis, we detected no increase in plasma cGMP concentrations after infusions of glycerol trinitrate. Because immunoreactive ANP is highly susceptible to degradation and nonspecific influences in blood samples, determinations of ANP require immediate centrifugation and storage of plasma at -20 degrees C. In contrast, we found that cGMP is stable for five days in vitro in blood samples containing EDTA. In 147 healthy blood donors, the upper cutoff value for plasma cGMP was 6.60 nmol/L, not significantly different (P greater than 0.05) from that for 222 patients with disorders other than cardiovascular and renal. In 69 patients with manifest congestive heart failure (NYHA stages II-IV), 65 had increased cGMP values. Using the above cutoff value for cGMP gave diagnostic sensitivity of 94.2% and specificity of 93.7%. Plasma cGMP may thus provide an alternative for routine clinical measurements of ANP in cardiac diseases in the absence of renal disorders.

Adolescent

Famotidine versus ranitidine for the short-term treatment of duodenal ulcer.

One-hundred and eight-three patients with endoscopically proven duodenal ulcers, enrolled in this prospective, double-blind study, were randomly allocated to receive famotidine 40 mg once at night, 20 mg twice daily, 40 mg twice daily, or ranitidine 150 mg twice daily for 2-8 weeks. Pretreatment characteristics between the four groups were similar. After 4 weeks of treatment, among the famotidine-treated patients, 38 of 42 (90.5%) healed with the 40 mg once nightly regimen, 35 of 42 (83.3%) with 20 mg twice daily, and 37 of 41 (90.2%) with 40 mg twice daily. In the ranitidine group 40 of 43 patients (93.0%) healed. After 8 weeks of treatment, the respective data were: 97.6, 95.2, 100 and 93.0%. Different results between the famotidine groups and the ranitidine group were not statistically significant. All treatments were well tolerated and severe adverse events were rare. Famotidine 40 mg given once at night appears to be as safe and effective as conventional therapy with ranitidine, indicating the importance of overnight gastric acidity in the pathogenesis of duodenal ulcer disease.

Adolescent

[Famotidine versus ranitidine in the acute treatment of duodenal ulcer. A multicenter comparative study in Germany].

185 patients with endoscopically proven duodenal ulcers were randomly allocated to treatment with either famotidine 40 mg nocte, 20 mg bid, 40 mg bid or ranitidine 150 mg bid for 2-8 weeks in a prospective double-blind study. The four groups were similar with regard to age, sex, duration of ulcer disease, smoking habits etc. After 2 weeks treatment 28/42 patients (66.7%) healed on famotidine 40 mg nocte, 24/42 patients (57.1%) on famotidine 20 mg bid, 26/41 patients (63.4%) on famotidine 40 mg bid and 28/43 patients (65,1%) on ranitidine 150 mg bid. The corresponding healing rates after 4 weeks were 90.5%, 83.3%, 90.2% and 93%, respectively. After 8 weeks more than 93% of the patients had healed ulcers. At each time there was no statistical difference between the different famotidine regimens and the ranitidine group. All treatments were well tolerated and severe adverse events were rare. Famotidine 40 mg at night, therefore, appears to be as good as conventional ranitidine.

Adolescent

[The operative treatment of the spondylolisthesis with compression screws (author's transl)].

The author gives account of a direct osteosynthesis--joining the defect of the interarticular part--made in case of spondylolisthesis in his department. They carry out the operation having modified the method of Buck as they use A-O malleolar compression screw instead of all threaded screw. Applying compression screws the author can ensure a successful osteosynthesis in case of a greater vertebral displacement. This method widens the indication area of the operation. The adventage of the operation over other ones made in spondylolisthesis is the fact that after the wound-healing the patient can get up and the lumbar spine will not be limited in motion. The operation was made in 16 cases until now and operative complication was not observed. They propose to make this operation as early as possible in case of definite spondylolisthesis to prevent the development of further progression.

Adult

[Eosphagomanometric finding in man after intravenous administration of a new cholinolytic (pramiverine), atropine and scopolamine butylbromide].

The tone depressing effect on deglutition peristaltic processes in the esophagus by i.v. application of 4,4-diphenyl-N-isopropyl-cyclohexylamine hydrochloride (pramiverine, Sistalgin) (0.03 and 0.045 mg/kg body weight), atropine (0.5 mg) and hyoscine-N-butylbromide (scopolamine-butylbromide, SBB) (20 mg) was tested on trained subjects. During the first 30 min following the larger dose of pramiverine, the effect is not quite so pronounced as it is seen after the usual atropine dose; from the 30th to the 60th min, however, the tone depressing effect of pramiverine is superior to that of atropine, 1 h after application of pyramiverine the pressure amplitude is still reduced to 54.3% of the initial value, while after atropine the effect has returned to 70.9% of the initial value by this time. Neither atropine nor pramiverine were able to exert a tone depressing effect as pronounced as that of SSB. But 30 min after application of the effect of SBB was not statistically significant any longer and after 40 min it could not be measured at all. Following atropine and SBB, the side effect of tachycardia was correlated exactly to the main effect tested. Further side effects, such as dryness of mouth and disturbed accomodation, were most pronounced after atropine. With pramiverine at the effective doses of 0.03 and 0.045 mg/kg, the side effects were not appreciable; neither objective measuring nor subjective reports of the subjects indicated any conspicuous deviations.

Atropine