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Biomedical subjects

P Weiss

Publications and source records attributed to P Weiss.

At least 19 recordsLinked to original sources

[Anti-arrhythmia treatment using L-carnitine in acute myocardial infarct].

Carnitine, a quaternary amine (3-hydroxy-4-N-trimethylaminobutyric acid), plays an important physiologic role in fatty acid transport and metabolism as well as in energy production of the myocardial cell. L-carnitine in high doses has been postulated to have an antiarrhythmic effect and this has also been clinically proven. We studied 20 patients with acute myocardial infarction (AMI), 4-12 hours after onset of pain. The patients were randomized and treated double-blind with 5 g L-carnitine (n = 12) or placebo (n = 8) at hours 0, 12, 24, 36, and with 2 x 3 g on days 3 to 7 by intravenous infusion over 2 hours. The two groups were similar for age, sex, infarct site, maximum CPK and conventional antiarrhythmic therapy. 24-hour Holter-ECG was performed on days 1, 2 and 7 and showed no significant difference between the two groups with respect to incidence of ventricular premature beats (VPB) per hour. On the second day following AMI, however, only 4 of 12 carnitine-treated patients showed high-grade VPB (Lown IVa and IVb), in comparison with 7 of 8 patients in the placebo group. The difference is significant: p = 0.028 (Fisher's Exact Test). Carnitine was well tolerated and the efficacy demonstrated on the second day following AMI must be interpreted with caution.

Aged

[Acute left heart insufficiency: possible leading symptom of a pheochromocytoma].

A 42-year-old patient with acute left-ventricular failure is described in whom pheochromocytoma was diagnosed only after prolonged and fruitless efforts. Pheochromocytoma may present without the typical features of paroxysmal or sustained hypertension, headache, increased sweating, and palpitations. Therefore, in cases of acute left-sided cardiac failure of primarily undetermined origin, pheochromocytoma should be considered in differential diagnosis.

Acute Disease

[Is it justifiable today to perform thrombolysis in only one fifth of the patients with myocardial infarct?].

The one year mortality data of 231 patients entering the hospital with acute myocardial infarction who did or did not undergo thrombolysis are presented. 49 patients (21.2%) received thrombolytic therapy. 31% were excluded from thrombolytic therapy because of age over 70 years, 29% because of the time lag since onset of symptoms (over 6 hours), 61% because of absent ECG criteria and 32% because of other contraindications. The one year mortality rate was significantly lower in patients undergoing thrombolysis (8.2%) versus patients without thrombolysis (20.3%, p less than 0.05). Mortality in patients without thrombolysis and age greater than 70 years was 23.6%, in patients with late entry 20.1%, in those excluded from thrombolytic therapy with missing ECG elevations 17.9% and in patients with contraindications 28%. If thrombolytic therapy was withheld due to age greater than 70 years or late entry only, mortality was high (33.3% and 38.5% respectively; p less than 0.02 versus lysis). This was not true for patients without significant ST elevation: to the contrary 12 of 42 patients without lysis (28.6%; p less than 0.02 versus lysed patients) and greater than or equal to 2 mm ST elevation irrespective of other exclusion criteria died. Since mortality in patients over 70 years of age or entering the hospital more than 6 hours after onset is of such magnitude (especially if there are ECG signs of ongoing ischemia), the risk-benefit ratio should be considered individually to ensure that these high-risk patients are not excluded a priori from thrombolytic therapy.

Adult

Regional cerebral glucose consumption measured by positron emission tomography in patients with Wilson's disease.

Using positron emission tomography (PET), the regional cerebral metabolic rate of glucose consumption (rCMRGlc) was measured in 14 patients with Wilson's disease (WD) and 23 normal subjects. In WD patients, cerebellar, striatal and--to a lesser extent--cortical and thalamic rCMRGlc were significantly decreased compared with controls. Striatal rCMRGlc was significantly reduced in those 4 patients who had recently started decoppering therapy as compared with striatal rCMRGlc measured in those 10 patients with longer duration of medication. Caudate rCMRGlc correlated significantly with various signs of extrapyramidal dysfunction. Cerebellar, thalamic and cortical rCMRGlc correlated significantly with the severity of pyramidal signs. These data indicate that the PET measurement of rCMRGlc may be a useful tool to evaluate cerebral involvement in WD and to monitor the response to treatment.

Adult

Possible risk for cardiac arrhythmia related to intravenous erythromycin.

OBJECTIVE: To evaluate the incidence of prolongation of the rate-corrected electrocardiographic QT interval (QTc) and of ventricular arrhythmia associated with intravenous administration of erythromycin lactobionate. DESIGN: A consecutive series of 7 critically ill patients treated with intravenous erythromycin for severe pneumonia. SETTING: A medical intensive care unit of a university hospital. MEASUREMENTS AND RESULTS: Registration of QTc duration before and after intravenous administration of erythromycin as a short infusion. Blood chemistry, hemodynamic variables, arrhythmias, and co-medications were recorded. Evaluation of at least 10 ECG intervals by 2 experienced investigators who were blinded as to the time of drug administration. If several measurements were performed in the same patient, only the mean value was used for further analysis. During 12 of 13 drug administrations studied in 7 patients QTc prolongation was observed. The extent of QTc prolongation was significantly correlated with the infusion rate (mg/min, r = 0.765, p = 0.05). In 3 patients ventricular arrhythmia occurred in close temporal relation to the erythromycin infusion; two of them developed ventricular fibrillation shortly after the first and second dose of erythromycin, respectively, and died within 3 h. CONCLUSION: In critically ill patients erythromycin-induced QTc prolongation is a frequent pharmacologic effect correlated with erythromycin infusion rate. To avoid changes in electrocardiographic intervals and thereby possibly potentially life-threatening ventricular arrhythmia administration with the lowest possible infusion rate and close cardiac rhythm monitoring are advisable in these patients.

Aged

[Steroid and protein hormone concentrations in serum and follicular fluid after stimulation for in vitro fertilization].

Sixty patients with tubal infertility were stimulated for IVF with a fixed schedule consisting of clomiphene and pure follicle stimulating hormone. They responded with an optimal estradiol increase and 2 to 4 embryos were transferred. Conception cycles (n = 17) could be differentiated from non-conception cycles (n = 43) by serum estradiol, serum progesterone, the serum progesterone/estradiol-ratio and serum LH concentrations. Testosterone, androstenedione and FSH in serum and follicular fluid showed no significant relation to a possible therapy outcome. We conclude from our findings, that, during the peri-implantation period, certain LH patterns followed by an optimal progesterone/estradiol-ratio in the serum support an embryo survival after transfer to the uterus.

Androstenedione

Absence of nitroglycerin-induced heparin resistance in healthy volunteers.

A previously described nitroglycerin-induced heparin resistance could not be verified by in-vitro experiments or in a randomized, double-blind, crossover trial in healthy volunteers. A clinically relevant attenuation of the anticoagulant effect of a heparin bolus (40 U.kg-1) by a concomitant infusion of nitroglycerin (100 micrograms.min-1) was absent. Activated partial thromboplastin time was not significantly different under nitroglycerin infusion as compared to placebo after heparin injection. Concentrations and activities of antithrombin III and heparin cofactor II remained unchanged during nitroglycerin infusion. An interaction of these two frequently combined drugs in patients with active thromboembolic disease or after a prolonged concomitant intravenous administration cannot be ruled out. Since this is of clinical importance, further studies must clarify a possible nitroglycerin-induced heparin resistance.

Adult

Doppler sonographic evaluation of mechanical and bioprosthetic mitral valve prostheses during exercise with a rate corrected pressure half time.

OBJECTIVE: To compare the effect of exercise on pressure half time in patients with mechanical or bioprosthetic mitral valves. A relative pressure half time (pressure half time as a percentage of RR interval) was used in an attempt to correct for the shortening of the diastolic time interval caused by the increase in heart rate during exercise and thus to uncover the effects of valve design on pressure half time during exercise. PATIENTS: Twenty clinically stable (New York Heart Association grade I-II) patients with mechanical (n = 12) or bioprosthetic (n = 8) mitral valves (median age 51) years. The median time since valve replacement was 42 months. METHODS: Continuous wave Doppler echocardiography from the apical view at rest and during moderate supine bicycle exercise (50 W). RESULTS: During exercise the mean (SD) heart rate increased from 79 (12) to 101 (12) beats per minute (95% confidence interval (95% CI) of difference, 15 to 29/min) and the peak pressure gradient from 11 (5) to 18 (6) mm Hg (95% CI of difference 5 to 9 mm Hg). The pressure half time decreased from 114 (30) to 78 (26) ms (95% CI of difference (30-42 ms). There was no difference between the valve types. The relative pressure half time remained unchanged in patients with mechanical valves during exercise (13 (4) rest and 13 (5)% exercise, respectively) and decreased in patients with bioprostheses (17 (3) and 12 (3)%, respectively (95% CI of difference 2 to 8%, p = 0.025). CONCLUSIONS: In patients with mechanical mitral valves the decrease in the pressure half time during exercise is probably mostly the result of the shortening of the diastolic time interval with increasing heart rate whereas in patients with bioprosthetic valves an increase in functional valve area may contribute to the shortening of pressure half time during exercise.

Adult

Rapid reversal of heart failure in a patient with phaeochromocytoma and catecholamine-induced cardiomyopathy who was treated with captopril.

A patient with a phaeochromocytoma and severe left ventricular heart failure caused by a catecholamine-induced cardiomyopathy is described. The clinical signs of congestive heart failure resolved rapidly on treatment with captopril and myocardial performance became normal within two weeks of medical treatment with captopril for one week and with captopril in combination with phenoxybenzamine for another week.

Acute Disease

Hyposialylated thyroglobulin in a patient with congenital goiter and hypothyroidism.

A large family (14 children) with congenital goiter whose parents are first cousins was studied. Thyroid tissue was obtained, after 125I in vivo labeling, from one of the siblings (JBM). Gel filtration of thyroid proteins indicated that thyroglobulin (Tg) eluted as a single symmetrical peak in the same position as authentic 19S Tg. Gel electrophoresis in a 7.5% sodium dodecyl sulfate-polyacrylamide gel revealed a major band with the same mobility and immunoreactivity as normal 19S Tg. Hydrolysis of the patient's Tg indicated that most of the radioactivity was mono- and diiodotyrosines. The yield of T4 from JBM Tg (26 pmol/mg protein) was 5-fold less than normal thyroid tissue (140 pmol/mg protein) and approximately half of that in thyroid tissue from endemic goiter (51 pmol/mg). Total T3 released from JBM Tg was similar to the other two tissues. When the carbohydrate content of normal and patient Tg was analyzed, there was no differences in glucosamine, galactose or mannose content. However, unlike normal and endemic-goiter Tg, that had a mean sialic acid content of 7.3 and 5.6 micrograms/mg protein, respectively, the sialic acid concentration of the patients Tg was only 0.3 microgram/mg. Sialyltransferase activity was readily demonstrated in homogenate from normal thyroid or endemic goiter, but no sialyltransferase activity was detectable in a homogenate of JBM-thyroid tissue. We conclude that the finding of severely hyposialylated Tg is linked to a defect in iodotyrosine coupling seen in this patient with a possibly abnormal migration of Tg into the follicular lumen.

Carbohydrate Sequence

Influence of different pressure gradients on late clinical outcome after aortic valve replacement.

Late outcome vs. hemodynamic parameters were assessed and compared in a series of 44 patients followed for 10-17 years after aortic valve replacement either with a Starr-Edwards A 1260 (SE) or a Bjork-Shiley 60 degrees (BS) prosthesis. The two groups, 22 patients each, were selected by computer from the data base SG as to be matched for age, sex, underlying lesion, date of implantation, valve size, left ventricular function, and concomitant coronary artery disease. There was no significant difference in mortality and complication rates. Clinical evaluation at a mean of 12.5 +/- 2.2 years postoperatively revealed identical findings of heart size on chest X-rays (CTR 0.50 +/- 0.04 SE vs. 0.50 +/- 0.05 BS) and nearly identical incidence of left ventricular hypertrophy on the ECG (2/22 SE and 1/22 BS). There was a statistically significant difference in Doppler ultrasonic peak pressure gradients between the two valve types (SE 32 +/- 15 mmHg, BS 23 +/- 9 mmHg; p = 0.047), and of fractional shortening on M-mode echocardiograms (SE 30 +/- 9%, BS 37 +/- 8%, p = 0.038), but this was not reflected by a difference in the symptomatic status of the two groups. It is concluded, that in two groups of patients surviving 10-17 years after isolated aortic valve replacement with SE or BS valves, the statistically significant nine mmHg difference in gradient across the two valve types had no effect on long-term clinical outcome.

Aortic Valve

Abbott IMx and serono MAIAclone assays compared for lutropin determinations in urine.

The urinary lutropin (luteinizing hormone; LH) profiles of 20 patients were determined in 10 consecutive urine samples (n = 200) with a manual technique (MAIAclone, Serono; y) and a fully automated (Abbott IMx; x) technique. For 132 single determinations within the range of detection, the regression line was y = 1.39 x - 0.07 (r = 0.85). Retrospective analysis of the LH profiles obtained by the IMx yielded the classification "not pregnant" (negative) in 14 cases, of which 13 were correctly classified; 6 profiles were classified as "pregnant" (positive), which correlated with the clinical findings in 4 cases. Nine of the LH profiles analyzed with the MAIAclone method were classified as negative, which was correct in seven cases. Retrospective analysis of 11 LH profiles established with the MAIAclone assay gave positive results, which agreed with the clinical outcome in three cases. The diagnostic sensitivity of the IMx and MAIAclone methods was 87% and 47%, respectively; diagnostic specificity was 80% and 60%, respectively. In smaller series (< or = 40 samples), the IMx method has considerable advantages over the MAIAclone method in cost and convenience, because standard curves can be stored and assays can be performed as single determinations.

Autoanalysis

[Hemodynamics of various heart valve prostheses].

Modern tilting disc and bileaflet prostheses, and bio-prostheses, perform similarly regarding pressure gradients, discharge coefficient and performance index; however, only bio-prostheses increase their opening area with increasing flow. Ball valve prostheses of the Starr-Edwards type perform less satisfactorily with higher pressure gradients and lower performance indices, which may result in less favorable long-term follow-up. Bio-prostheses show degenerative changes with increasing age which, over a period of 7-10 years, can lead to clinically relevant stenoses necessitating reoperation.

Bioprosthesis

[Are ECG criteria for indications for thrombolysis in acute myocardial infarct defined too narrowly?].

BACKGROUND: Despite the advantages of fibrinolytic therapy in acute myocardial infarction only about 20% of these patients receive this therapy. We studied patients excluded from fibrinolysis to identify subgroups with high mortality, which could derive benefit from more liberal interpretation of the indications for fibrinolytic therapy. METHODS: Retrospective chart review to identify patients with acute myocardial infarction in our coronary care unit 7/88-7/89. All patients received a questionnaire one year after this myocardial infarction. Patients not answering the questionnaire were contacted by phone or the information was sought from their physician. Indications for thrombolysis (with streptokinase or rTPA) were ST elevations of greater than or equal to 2 mm in greater than 2 adjacent leads and the absence of contraindications. RESULTS: In 231/242 (95%) of the identified patients a complete follow-up was obtained, 32% were age greater than 70 years, 30% were admitted greater than 6 h after the beginning of the symptoms, 64% did not fulfil the ECG criteria for thrombolysis, 21% (49/231) received thrombolytic therapy. The mortality after one year was 20.3% in patients not treated with thrombolysis and 8.2% in patients with thrombolysis (difference 12.1%, 95% confidence interval 2.9-21.3%, p = 0.048). Patients with preceding old infarctions (n = 58) fulfilled the ECG criteria for thrombolysis in a significantly smaller proportion (21% vs 41%, p = 0.004). Of all patients 12% were excluded from thrombolytic therapy due to a negative initial ECG and yet developed a Q ware infarction. The one year mortality of patients not given thrombolysis and with a Q wave infarction was 24% (22/93, p = 0.02 as compared to patients with thrombolysis), in patients with non Q wave infarction it was 13% (11/82, p = 0.41) and in patients with ambiguous ECG it was 57% (4/7, p = 0.006). The mortality in patients with a preceding infarction was 31% and significantly higher than in patients with a first infarction (16%, p = 0.049) and in patients receiving thrombolysis (8.2%, p = 0.005). CONCLUSIONS: By excluding patients with acute myocardial infarction from thrombolytic therapy a group with high first year mortality is selected. Most patients are excluded because of an initial ECG not showing enough ischemia to fulfil the criteria for thrombolytic therapy. A prospective study of thrombolytic therapy using less rigid ECG criteria in the subgroups with the highest mortality (patients with preceding myocardial infarction or ambiguous ECG) seems necessary.

Acute Disease

Sialic acid metabolism in sialuria fibroblasts.

Sialuria is a rare inborn error of metabolism caused by excessive synthesis of sialic acid (N-acetylneuraminic acid, NeuAc). Fibroblasts cultured from the three known cases of sialuria contained 70-200-fold increases in soluble sialic acid, but normal concentrations of bound sialic acid. The sialic acid appeared in the cytosolic fraction of the cells on differential centrifugation, and was susceptible to borohydride reduction, suggesting that accumulated sialic acid was in the form of NeuAc and not CMP-NeuAc. In biochemical studies, CMP-NeuAc (50 microM) inhibited the UDP-N-acetylglucosamine (UDP-GlcNAc) 2-epimerase of normal fibroblasts by 84-100%, but inhibited the epimerase from sialuria cells by only 19-31%. Feeding sialuria cells up to 5 mM D-glucosamine for 72 h increased free sialic acid content 20-60%, but normal cells were unaffected by this treatment. Cytidine feeding (5 mM, 72 h) reduced the NeuAc content of sialuria cells, initially 112, 104, and 266 nmol/mg protein, by 63-71 nmol/mg protein; CMP-NeuAc concentrations, initially 4, 2, and 5 nmol/mg protein, increased by 14-33 nmol/mg protein. Consequently, the total cellular content of soluble sialic acid (NeuAc + CMP-NeuAc) was lowered 14-46% by cytidine feeding. The inheritance pattern of sialuria has not been determined. However, cells from both parents of one sialuria patient contained normal concentrations of free sialic acid, and the parental epimerase activity also responded normally to CMP-NeuAc. We conclude that the basic biochemical defect in all known cases of sialuria is a failure of CMP-NeuAc to feedback-inhibit UDP-GlcNAc 2-epimerase and cytidine feeding can lower the intracellular soluble sialic acid concentration of sialuria cells.

Child, Preschool