Decreased suppression of antibody-dependent cellular cytotoxicity by seminal plasma in unexplained infertility.

OBJECTIVE: To determine whether seminal plasma (SP) from unexplained infertile males has different suppressive activity on antibody-dependent cellular cytotoxicity (ADCC) than SP from fertile males or SP from males of couples with known infertility factor. DESIGN: Comparative clinical/experimental study. SETTING: In vitro fertilization program in a university hospital and a hospital research laboratory. PATIENT(S): A total of 245 SP samples from 174 infertile and 16 fertile couples were compared. INTERVENTION(S): SP suppression of ADCC was measured by using human 51chromium-labeled red blood cells (RBC), sensitized with IgG-rabbit-anti-human-RBC as targets and peripheral blood lymphocytes as effector cells. MAIN OUTCOME MEASURE(S): Suppressive activity of each sample was determined by calculating 51Cr-release in the presence and absence of SP. RESULT(S): When analyzed with respect to sperm number, motility, and morphology, suppressive activities of samples with normal semen analyses (n = 142) were significantly higher (x = 37% +/- 14%) than suppressive activities of abnormal samples (n = 103; x = 32% +/- 13%). There was no strong correlation of suppressive activity to other semen parameters. Within the andrologically normal males, SP from the unexplained infertile couples (n = 15) showed significantly lower suppressive activity (x = 24% +/- 11%) compared with the SP from fertile males (n = 16; x = 35% +/- 13%) and from couples with female infertility factor (n = 65; x = 39% +/- 14%). CONCLUSION(S): Loss of suppressive activity is associated with unexplained infertility, even in male patients who previously were considered normal by traditional methods of semen analysis.

The role of type-1 plasminogen activator inhibitor in failure of thrombolytic therapy with recombinant tissue plasminogen activator.

We investigated the possible role of type-1 plasminogen activator inhibitor (PAI-1) on success or failure of thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) in 10 responders and 10 non-responders with acute myocardial infarction and early initiation of therapy within 2 h of onset using the common infusion scheme (100 mg rt-PA over 3 h). We determined plasma levels of t-PA (activity and antigen) as well as PAI-1 (activity and antigen) in samples obtained before, during and after thrombolytic treatment and compared the course of each of those parameters between responders and non-responders to therapy. Success or failure of treatment was determined by a combination of noninvasive methods and proven by coronary angiography within 5 days of initiation of thrombolysis. Thirty, 60, 90, and 120 min after initiation of rt-PA infusion, specific t-PA activities in plasma of responders were 0.62, 0.63, 0.62, and 0.57 (IU/ng/ml), respectively, as compared to 0.42, 0.42, 0.40, and 0.32 (IU/ng/ml) in nonresponders (p < 0.001). Between 4 and 8 h after initiation of therapy, a time span known to be critical for thrombotic reocclusion, specific activities were still significantly elevated in responders as compared to non-responders (p < 0.01). PAI-1 activity levels, which were not detectable during rt-PA infusion in either group, recovered to pre-treatment values 2 h earlier in non-responders.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of cardiac output on peak t-PA plasma levels in patients receiving thrombolytic therapy with recombinant tissue-type plasminogen activator--correlation with patency rate.

We studied 35 consecutive patients with short onset of myocardial infarction who underwent thrombolytic therapy with rt-PA at a standard dosage regimen of 100 mg rt-PA total (10 mg given as a bolus followed by 50 mg, 20 mg and 20 mg per hour for 3 hours). These patients were monitored for t-PA antigen and t-PA activity and PAI-1 activity plasma levels during rt-PA infusion. Success or failure of thrombolytic therapy was evaluated by non-invasive criteria (early plasma creatine kinase peaks, early peak plasma myoglobin values, and electrocardiographic criteria) as well as by means of coronary angiography at the fourth day after thrombolytic treatment. In 24 (68.6%) of these patients a success of thrombolytic therapy could be established by these criteria, while 11 patients did not respond to thrombolytic therapy. Fifteen patients (14 responders and one non-responder) had to be excluded from the further evaluation because in these patients clinical laboratory data obtained upon admission before initiation of thrombolytic therapy were not complete. Therefore, 20 patients (10 responders and 10 non-responders) could further be analysed. The two groups of patients were not significantly different in body weight, body weight index, age, gender, liver or kidney functional parameters as determined before initiation of the thrombolytic therapy. Furthermore, PAI-1 plasma levels before initiation of thrombolytic therapy were not significantly different in the two groups, as were rt-PA dosage per body weight or body weight index.(ABSTRACT TRUNCATED AT 250 WORDS)

Parathyroid hormone and calcium behavior in advanced congestive heart failure.

Parathyroid hormone (PTH) regulates the content of calcium and thus exerts an effect on myocardial function. Abnormal secretion of PTH has been sporadically reported to be associated with depressed mechanical performance of the heart muscle. In the present study, we first measured PTH levels at baseline in 27 consecutive patients with advanced congestive heart failure (LVEF: 17 +/- 9%): five patients (18.5%) revealed elevated PTH levels, one case of hypoparathyroidism was discovered. Furthermore, nine unselected patients underwent symptom-limited exercise stress test leading to an increase in mean pulmonary artery pressure from 25.6 +/- 15 at baseline to 41.2 +/- 18 mm Hg at peak exercise. In contrast to observations in healthy subjects, in heart failure patients both mean PTH and blood calcium concentrations did not change significantly during peak exercise or recovery. Moreover, patients with the lowest left-ventricular ejection fraction showed a decrease in PTH during maximal stress. We conclude that abnormal baseline PTH secretion is common in patients with advanced congestive heart failure. More importantly, these studies show that PTH release is depressed under stress conditions, possibly indicating a dysfunction of the parathyroid gland in severe heart failure.

A decrease in plasminogen activator inhibitor-1 activity after successful percutaneous transluminal coronary angioplasty is associated with a significantly reduced risk for coronary restenosis.

To determine a possible relation of changes in plasma levels of plasminogen activator inhibitor 1 (PAI-1) and tissue plasminogen activator (t-PA) to the development of coronary restenosis after successful coronary angioplasty (PTCA), we followed 104 patients with a low grade residual stenosis after PTCA (less than 30%) for a period of 12 months. PAI-1 plasma levels (functional activity) and t-PA antigen were determined 1 day before PTCA and 3 days, 3 months and 6 months thereafter. Thirty-four patients (32.69%) developed angiographically proven coronary restenosis (group A) within a time range of 4-48 weeks (median 12.5 weeks) after PTCA while the remaining patients (group B) had neither clinical signs nor angiographic evidence of restenosis after 6 months. No significant differences could be demonstrated in t-PA antigen or PAI-1 activity (plasma levels between the two groups of patients the day before PTCA). During the whole observation period t-PA plasma levels were not significantly different between the two groups; however, PAI-1 plasma levels were significantly higher at 3 months and 6 months after PTCA in patients of group A (p less than 0.005). When the pattern of PAI-1 plasma levels over time (increase or decrease between two consecutive time points of blood collection) was used to discriminate between the two study groups only 3.5-18% of patients with a decrease in PAI-1 developed coronary restenosis within the following observation period in contrast to 25-58% of patients with an increase in PAI-1 plasma levels (p less than 0.05 to p less than 0.0005).

[Heart transplantation: indication, selection criteria and patient management]. / Herztransplantation: Indikation, Auswahlkriterien und Patientenmanagement.

Evaluation of potential candidates for cardiac transplantation is a difficult and wearisome process for both physician and patients. As long as we are confronted with the present situation of an increasing chronic donor unavailability, the importance of standardized, rational criteria for evaluation of heart transplantation candidates has to be emphasized, since the success of any organ transplantation depends on adequate selection of potential candidates.

Plasminogen activator inhibitor-1 levels in patients with chronic angina pectoris with or without angiographic evidence of coronary sclerosis.

Increased plasma levels of plasminogen activator inhibitor-1 (PAI-1) have been shown to exist in 40 to 60% of patients with stable coronary artery disease and have been suggested to be responsible for the development of coronary thrombotic complications. However, it is also discussed whether PAI-1 elevation might mainly be due to variables like increased age or to reactive mechanisms caused e.g. by the chest pain itself. To exclude age dependent or pain related influences, age-matched patients with stable angina pectoris (NHYA II) and angiographically proven coronary artery disease (CAD, n = 16) or without evidence for coronary sclerosis (variant angina, n = 10; angina-like syndrome with normal coronary angiogram, n = 5; non-CAD, n = 15) have been investigated for their plasma PAI-1 activity and t-PA antigen levels. The mean PAI activity in CAD patients (17.5 U/ml) was significantly higher than in non-CAD patients (9.6 U/ml) (p less than 0.0001). In the CAD patients no significant variation in plasma PAI-1 values could be demonstrated when related to the extent of the disease or to a history of previous myocardial infarction. t-PA antigen was also elevated in CAD patients as compared to the non-CAD group (p less than 0.02). The results suggest therefore a strong correlation between coronary artery disease itself and elevated levels of components of the plasma fibrinolytic system.

Heparin induced increase of t-PA antigen plasma levels in patients with unstable angina: no evidence for clinical benefit of heparinization during the initial phase of treatment.

Patients with unstable coronary artery disease were randomly treated either with a combination therapy consisting of nitrates and calcium-channel blockers without or with addition of clinical grade heparin administered subcutaneously; in order to evaluate the effect of heparin treatment on the fibrinolytic system, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) plasma levels were related to the clinical course of the disease. In heparinized patients thrombin time was prolonged more than 3-fold the normal range indicating effective heparin treatment. Heparinization led to a significant increase in t-PA antigen plasma levels (p less than 0.0001) within approximately four hours while PAI-1 activities remained unaltered. However, the measurable increase of the anticoagulant and pro-fibrinolytic activities of heparin did not result in a short-term benefit for the heparinized patients because the number of further ischemic attacks per patient during the observation period of three days was not different between the two study groups.

Circadian fluctuations of plasminogen activator inhibitor and tissue plasminogen activator levels in plasma of patients with unstable coronary artery disease and acute myocardial infarction.

A decrease in the fibrinolytic potential, mainly due to an elevation of plasminogen activator inhibitor (PAI), has been described in patients with stable coronary artery disease and a previous myocardial infarction. We investigated plasma levels of PAI and tissue plasminogen activator (t-PA) and their possible circadian variations in patients with unstable coronary artery disease (CAD). Sixty-three patients were studied for at least 2 consecutive days during their stay at the coronary care unit (CCU). Diurnal plasma fluctuations in PAI and t-PA and onset of further myocardial ischemic episodes were monitored. As controls we used 22 age-matched patients submitted to the clinic because of non cardiac chest pain or valvular disease who revealed no evidence of CAD. PAI levels were significantly elevated in patients with unstable CAD (p less than 0.0001) but were not influenced by the extent of underlying CAD, history of previous myocardial infarction, known risk factors for CAD, or by extent of myocardial damage. The circadian variation of PAI levels with peak values between midnight and 6 A.M. found in controls was still present in patients but at a higher level. Preservation of circadian pattern in PAI plasma levels despite myocardial ischemic attacks indicates that elevation of PAI is rather not caused by a reactive phenomenon. On the other hand, elevated PAI levels and episodes of severe myocardial ischemia exhibiting a median time of onset at 10 A.M. seem to be closely related.

Ketanserin combined with a beta-blocker or diuretic in essential hypertension. A multicentre study.

The antihypertensive effect of ketanserin 40 mg b.d. in combination with a beta-adrenergic blocking agent or a diuretic was assessed in an open study in 35 patients with essential hypertension, who had not responded to treatment with beta-blockers, diuretics or their combination. The ketanserin/beta-blocker combination decreased mean sitting systolic/diastolic blood pressure (SBP/DBP) from 169/107 mmHg to 156/91 mmHg at the end of the 12-week active treatment period. The decrease in systolic blood pressure was significant only at Week 8, while the decrease in diastolic blood pressure was highly significant at all times. A significant reduction in heart rate by 10 beats.min-1 was observed with the ketanserin + beta-blocker combination. The ketanserin/diuretic combination led to a significant reduction in mean SBP/DBP from 164/106 mmHg to 146/92 mmHg after 12 weeks, with no significant change in heart rate. Body weight slightly increased in both groups. There were significantly fewer adverse reactions with the ketanserin/diuretic combination than with the ketanserin/beta-blocker combination. The results indicate a potentially useful therapeutic role for ketanserin in combination with beta-blockers or diuretics.

R-wave amplitude changes during exercise stress testing: patients with dilative cardiomyopathy compared to patients with coronary artery disease.

R-wave amplitude (RWA) depends to a large extent on the left ventricular filling volume. Changes of RWA are attributed to the Brody-effect. Exercise has been shown to induce a decrease of RWA in a healthy population and an increase in patients with coronary artery disease (CAD). No clear data exist for cardiomyopathy (CMP). Controls (n = 12), patients with CMP (n = 32) and CAD (n = 58) were compared. Alterations of RWA (Wilson lead V5) were correlated with parameters of a bicycle exercise test including resting and exercise hemodynamics and parameters of LV-function including EF, LVEDV and LVEDP. CMP compared to CAD had smaller RWA at rest (0.78 +/- 0.47 vs 1.32 +/- 0.72 mV, P less than 0.01). During comparable levels of exercise CMP (EF 35 +/- 14%) showed no significant changes of RWA. CAD (EF 57 +/- 16%) presented an increase of RWA by +0.11 +/- 0.23 mV (P less than 0.01), while controls showed a straight decline of RWA (-0.31 +/- 0.24 mV). In patients with CAD delta RWA (RWA max exercise - RWA rest) was a more sensitive parameter for detection of disease (assuming delta RWA greater than or equal to +0.1 mV, 36/58 patients) than maximal ST-segment changes (ST-segment-depression in lead V5 greater than or equal to 0.2 mV at 0.08 sec after J-point, 22/58 patients). Precordial leads V2, V4, V5 and V6 showed similar changes. This paper supports the theory that changes of wall thickness or changes in the amount of air respective to the amount of fluid in the lungs are responsible for RWA changes. These changes are clearly dependent on the severity of the disease and on left ventricular function. Therefore measurement of RWA changes during exercise may offer additional information in patients with CAD as well as in patients with CMP.

[Value of long-term ECG in patients with syncope]. / Wertigkeit des Langzeit-EKG bei Patienten mit Synkopen.

In a prospective study 24 hour long-term ECG (LT-ECG) recordings under ambulatory conditions were performed in 126 patients with syncopes (SY) of unknown origin. LT-ECG revealed arrhythmias (AR) in 57%, whereas 43% had inconspicuous findings. One patient developed a SY during LT-ECG without any evidence for arrhythmias. In 40% of these patients AR not detected previously by other methods were discovered. In 36% AR detected by LT-ECG had to be considered as precursors of syncopes (i.e. bradycardia less than 40 b.p.m., tachycardia greater than 160 b.p.m., AV-block II/II and III, or ventricular arrhythmias Lown IV). LT-ECG increased the information about the cause of syncope in 35%, whereas in 65% LT-ECG did not produce any further information. Consequently LT-ECG led in 56% to drug therapy, in 8% to PM-implantation. During a mean follow-up of 22 months 22% of patients developed again a syncopal attack and 4% died suddenly. Despite LT-ECG recording an ECG-registration during a typical syncopal attack for the confirmation or exclusion of an arrhythmogenic genesis of the SY is achieved only by chance. Nevertheless further informations with regard to precursing AR can be obtained, which may lead to therapeutic consequences in some patients. Therefore, LT-ECG has to be recommended as an essential, non-invasive procedure in patients with SY of unknown origin.

[R spike potentials in ergometric stress: patients with dilated cardiomyopathy in comparison to coronary heart disease]. / R-Zackenpotentiale unter ergometrischer Belastung: Patienten mit dilatativer Kardiomyopathie im Vergleich mit koronarer Herzkrankheit.

R-wave amplitude changes during exercise were compared in patients with cardiomyopathy (n = 32), patients with coronary artery disease (n = 58) and controls (n = 12). Patients with cardiomyopathy (CMP) had a smaller R-wave amplitude (RWA) at rest than those with coronary artery disease (CAD). At comparable levels of exercise patients with CMP showed no change in RWA, while those with CAD demonstrated an increase in RWA. Controls showed a decline in RWA. In patients with CAD changes in RWA during exercise were more sensitive in the detection of disease than ST-segment changes. Left ventricular function was the major determinant of the direction and magnitude of RWA changes both in patients with CMP and CAD, with lesser changes in RWA in patients with more severely reduced left ventricular function.

[Hemofiltration and the neurohumoral system in patients with severe heart failure]. / Hämofiltration und neurohumorale Systeme bei Patienten mit schwerer Herzinsuffizienz.

6 fluid overloaded patients with congestive heart failure, NYHA classification IV, resistant to drug therapy, were treated by pump driven venovenous hemofiltration. The sympathetic nervous system measured by plasma norepinephrine concentration was stimulated in all patients. 4 of 6 patients had a markedly enhanced plasma renin activity. Between 7 and 20 l of fluid were removed by hemofiltration. The expected increase of plasma norepinephrine did not occur in 4 out of 6 patients. The improvement of cardiac pump function by hemofiltration could be an explanation for this apparent paradoxical regulation. Patients who had almost a normal plasma renin activity prior to hemofiltration showed a marked increase after the procedure. In patients with extremely high levels of plasma renin activity we noted a decrease after hemofiltration. Almost in every patient with a serum sodium concentration lower or equal 132 mmol/l the plasma renin activity was markedly elevated. Patients with normal serum sodium concentrations exhibited only slightly elevated plasma renin activity. Therefore, a hyponatremia in patients with heart failure can be used as a marker for high plasma renin activity. All patients had a significant improvement of the clinical state after hemofiltration. 3 patients, however, showed deterioration within a few weeks, due to the severity of the disease. Their plasma norepinephrine levels remained high or had a tendency to increase.

[Hemofiltration in chronic heart failure]. / Hämofiltration bei chronischer Herzinsuffizienz.

30 patients with severe congestive heart failure (NYHA IV) unresponsive to medical management were treated by continuous hemofiltration (CHF). 57% of patients received arteriovenous CHF and 43% of patients venovenous, machine assisted CHF over 95 +/- 31 hours. A reduction of body edemas was achieved. The removal of body fluid by CHF between 2 and 40 kg led to a reduction of body edemas and short-term clinical improvement. Furthermore CHF treatment induced hemodynamic improvement with a reduction of central venous pressure (18 +/- 6 cm H2O pre CHF vs 8 +/- 4 cm H2O post CHF p less than 0.01) and a reduction of left ventricular filling pressure (22 +/- 6 mm Hg vs 14 +/- 5 mm Hg, p less than 0.01), while the left ventricular ejection fraction remained unchanged. Patients with low serum sodium levels (less than 132 mval/l) benefited most. While 28/30 of patients has short-term clinical improvement between 2 and 8 weeks, 38% of patients had long-term benefits.

Diagnostic value of exercise testing versus long-term ECG in evaluation of arrhythmias in old age.

The usefulness of exercise testing (ET) in old age is so far undefined particularly for detection of arrhythmias. We compared the diagnostic value of ET with 24-h long-term ECG recording (LT-ECG) in patients older than 70 years that were evaluated because of symptoms possibly related to arrhythmias. In 37 patients (age 72.8 +/- 2.7 years) the incidence of ventricular arrhythmias (LOWN greater than or equal to 1) was greater during ET (67%) than during 24-h LT-ECG recording (48%, P less than 0.01). Complex ventricular arrhythmias were detected in 6/37 patients (16%) by ET, in 9/37 patients (24%) by LT-ECG, in one patient (3%) by both tests and in 14/37 patients (37%) by one of the two tests, while 23/37 patients (63%) had no significant complex arrhythmias recorded by either test. During ET 12 patients (32%) showed signs of myocardial ischaemia with ST-depression greater than or equal to 0.2 mV and/or increasing angina pectoris. In 42% of these patients complex ventricular arrhythmias LOWN greater than or equal to 3 occurred during ET. Thus both ET and LT-ECG are useful methods to uncover arrhythmias in symptomatic patients older than 70 years and have to be considered as complementary tools.

Reversible end-of-life indicator leading to erroneous pacemaker replacement-pitfalls of telemetry.

In several modern pacemakers, end-of-life (EOL) is indicated by a single-step rate drop, which is initiated by a voltage-sensitive electronic switch. This switch may also be activated by other causes, such as very short voltage drops, low temperatures, and electrocautery. We report a case in which a Cordis 233 F Sequicor II pulse generator was operating at 51.6 bpm in VOO mode at the time of implantation. As telemetry seemed to indicate that back-up pacing (the EOL indicator in this model) was "off," it was erroneously assumed that the pacemaker was not working properly. The unit was replaced by another impulse generator. At laboratory testing, the pacemaker was within specifications, when back-up pacing was separately programmed off. In conclusion, physicians should be aware of the new phenomenon of reversible EOL indicators, and that they may not rely on telemetry in this respect. Future pacemakers should incorporate a telemetry message which prevents similar misunderstandings.

Chylopericardium: a rare cause of pericardial effusion.

A 21 year old man presented with asymptomatic, isolated chylopericardium. Despite echocardiography, radionuclide-angiography, computer tomography, and chemical analysis of the chylous effusion, the etiology remained obscure. After patent blue dye infusion into peripheral soft tissues, the appearance of coloring material in the effusion at 4 hours suggested direct communication of the pericardium with an apparently large thoracic duct. Fifteen months later, cardiomegaly persists in site of medium-chain triglyceride dietary restriction.

[Value of ECG-telephone transmission in determining symptomatic heart-rhythm disorders]. / Wertigkeit der EKG-Telefon-Telemetrie in der Erfassung symptomatischer Herzrhythmus-Störungen.

The ECG-telephone-transmission (TTM) was used to record an ECG-strip during a typical symptomatic period in patients complaining of symptoms possibly caused by arrhythmias (palpitations, dizziness, paroxysm tachycardia, pulse irregularities; angina and dyspnea only if other reasons could be excluded). Patients complaining of syncope only were not admitted, because of the inability to make a telephone call successfully during such a symptomatic period. The ECG was transmitted to the CCU using a frequency modulation technique. In 60% of 196 patients an ECG-TTM could be achieved during a typical symptomatic period, whereas arrhythmias as cause for the symptoms could be excluded in 51 patients (26%). The remaining 66 patients (34%) demonstrated various arrhythmias ranging from simple SVPB and PVC to total AV-block and sustained VT. TTM, an easy-to-perform and cost-effective method allowed a successful ECG registration during a symptomatic period in almost two-thirds of symptomatic patients. In these patients arrhythmias could be verified or excluded as cause of the symptoms.