Sudden Death and Staged Therapy for Hemodynamic Stabilization in Patients Enrolled in a Heart Transplantation Program

To investigate the impact of staged therapy for advanced heart failure on therapeutic endpoints, 236 consecutive patients (coronary artery disease/dilated cardiomyopathy in 61/175 patients, left ventricular ejection fraction 14%± 5%, New York Heart Association Class IIl/IIIIV in 102/79/55 patients, respectively) with advanced heart failure were prospectively followed. One hundred thirtyseven patients enrolled from January 1989 to December 1991 were treated conventionally with digoxin, furosemide, and low dose angiotension converting enzyme (ACE) inhibition. Patients refractory to this therapy underwent urgent heart transplantation. Ninetynine patients enrolled from January 1992 to August 1993 underwent staged therapy: stage 1: maximal tolerated ACE inhibition; stage 2: therapy with PGE₁ for preand afterload reduction to achieve hemodynamic stabilization; or stage 3: refractory patients bridged to heart transplantation with continuous outpatient dobutamine. Sudden death was defined as death within 1 hour of symptoms if heart failure symptoms remained stable over the previous 7 days. Conventionally treated patients were followed for 10 ± 9 months; patients who underwent staged therapy for 9 ±5 months. In the group of patients that underwent standard therapy, 39 of 137 (28%) patients died: 5 (13%) deaths occurred suddenly, and death due to progressive pump failure occurred in the remaining 34 (87%) patients. In the group of patients that underwent staged therapy, 25 of 99 (25%) patients died: 13 (52%) deaths occurred suddenly, and 12 (48%) deaths occurred due to progressive pump failure. Thus, patients who underwent staged therapy were at increased risk for sudden death (P = 0.01, relative risk 3.4, 95% confidence interval 1.2–9.7) but were at lower risk for death from pump failure (P = 0.009, relative risk 0.44, 95% confidence interval 0.22–0.84). In patients who underwent therapy with continuous outpatient PGE₁ (n = 7) or dobutamine (n= 21), risk for sudden death (P = NS by log rank test) did not increase. In conclusion, staged therapy significantly reduced death from pump failure; however, patients who could be stabilized and considered too well for heart transplantation were at increased risk for sudden death. Thus, overall survival did not improve. Of note, outpatient dobutamine did not increase the risk for sudden death.     

Effects of Spascupreel versus hyoscine butylbromide for gastrointestinal cramps in children

BACKGROUND: Gastrointestinal spasms and cramps are common in children as well as in adults. Alternative medical practices such as chiropractice and homeopathy are becoming increasingly popular in Europe and the USA. The effectiveness and tolerability of the homeopathic preparation Spascupreel was compared with that of hyoscine butylbromide treatment in children <12 years of age. METHODS: An observational cohort study in 204 children <12 years was conducted over a 1 week treatment period. The efficacy of the respective therapies were evaluated on the effect on severity of spasms and clinical symptoms (pain/cramps, sleep disturbances, distress, eating or drinking difficulties and frequent crying). Compliance was evaluated on a four-point scale from 'very good' to 'low'. Evaluation was done by the practitioner based on information given by the patient or minder. RESULTS: The analysis showed comparative improvements with the homeopathic preparation and hyoscine butylbromide therapy on severity of spasms, pain/cramps, sleep disturbances, eating or drinking difficulties, and frequent crying, all as evaluated by the practitioner. Both treatments were very well tolerated. CONCLUSIONS: For patients opting for a homeopathic therapy, Spascupreel seems to be an effective and well tolerated alternative to conventional therapies in children suffering from gastrointestinal spasms.     

The impact of performance uncertainty on the postimperative negative variation

In a delayed matching-to-sample task, the impact of clear or ambiguous go versus clear no-go signals on the post-imperative negative variation (PINV) was examined in 11 patients with a chronic schizophrenic disorder (DSM-III-R) and in a control group of 13 healthy subjects matched to the patient sample by age, sex, and education. Size and spatial position of a visual S2 had to be matched to one of two visual patterns in the S1 presented 4 s earlier. In 96 trials, the S2 was identical in size with one of the two patterns of S1 (clear matching). These trials varied pseudorandomly, with 60 trials in which the S2 was of intermediate size. On a randomly interspersed additional 48 trials, an S2 differing in color and shape signaled no-go. The electroencephalogram was recorded from Fz, Cz, Pz, F3, F4, C3, C4, P3, and P4. Although groups did not differ in contingent negative variation amplitude the PINV was generally more pronounced in patients than in controls. In both groups, ambiguity of the to-be-matched S2 produced larger PINV amplitudes; the no-go signal elicited only a small PINV. Differential effects of ambiguity and no-go on PINV amplitude and its scalp distribution suggest that “performance” and “action” uncertainty contribute to PINV generation and that thresholds for both effects are reduced in schizophrenics.     

Heart rate increment analysis is not effective for sleep-disordered breathing screening in patients with chronic heart failure

Frequency domain analysis of heart rate variation has been suggested as an effective screening tool for sleep-disordered breathing (SDB) in the general population. The aim of this study was to assess this method in patients with chronic congestive heart failure (CHF). We included prospectively 84 patients with stable CHF, left ventricular ejection fraction (LVEF) <45% and sinus rhythm. The patients underwent polygraphy to measure the apnoea/hypopnoea index (AHI) and simultaneous Holter electrocardiogram monitoring to measure the power spectral density of the very low frequency component of the heart rate increment, expressed as the percentage of total power spectral density [% very low frequency increment (%VLFI)]. %VLFI could be determined in 54 patients (mean age, 52.8 ± 12.3 years; LVEF, 33.5 ± 9.8%). SDB defined as AHI ≥15 h⁻¹ was diagnosed in 57.4% of patients. Percent VLFI was not correlated with AHI ( r  =   0.12). Receiver-operating characteristic curves constructed using various AHI cut-offs (5–30 h⁻¹) failed to identify a %VLFI cut-off associated with SDB. The 2.4% VLFI cut-off recommended for the general population of patients with suspected SDB had low specificity (35%) and low positive and negative predictive values (35% and 54%, respectively). Heart rate increment analysis has several limitations in CHF patients and cannot be recommended as an SDB screening tool in the CHF population.     

EFFECTS OF FENTANYL-DIAZEPAM-NITRIOUS OXIDE ANAESTHESIA ON ARTERIAL BAROREFLEX CONTROL OF HEART RATE IN MAN

The effects of fentanyl 7.5 µg kg^–l (group I), 10.0µg kg^–1 (group Il) and 12.5 µg kg^–1(group lll) with diazepam 0.25 mg kg^–l and 70% nitrousoxide on baroreflex control of heart rate in humans were investigated.Phenylephrine (the pressor test), sodium nitroprusside (thedepressor test) and graded neck suction provoked baroreflexresponses. In group I the pressor, depressor and neck suctionbaroreflex slopes decreased during anaesthesia. In groups IIand III the depressor test slopes were also decreased duringanaesthesia. However, the slopes derived from the pressor andneck suction tests did not decrease. These data suggest thatbaroreflex control of heart rate is attenuated during low dosesof fentanyl (7.5 µg kg^–1). Baroreflex mediated tachycardiais decreased by higher doses of fentanyl (10.0 and 12.5 µgkg^–1). However, baroreflex-mediated bradycardia is maintainedduring the higher doses of fentanyl. We suggest this effectis the result of enhanced vagal efferent activity mediated byfentanyl.     

Effects of four orally administered analogues of prostaglandin E1 and E2 on glucose tolerance and on the secretion of pancreatic and gastrointestinal hormones in man

Oral glucose tolerance tests (75 g, 300 ml) were performed in 12 healthy volunteers, with prior administration of placebo, misoprostol (400 micrograms), rioprostil (300 micrograms), enprostil (70 micrograms), or nocloprost (200 micrograms), in a double-blind, randomized manner. None of the drugs significantly affected glucose tolerance, although with misoprostal some volunteers displayed an impaired glucose tolerance. Nocloprost was without effect on gastric inhibitory polypeptide (GIP) and did not influence insulin or C-peptide concentrations. Misoprostol and rioprostil reduced integrated incremental responses of GIP by 57% (P less than or equal to 0.001) and 45% (P less than or equal to 0.01), respectively, and both gave rise to an initial (approximately 10 min) delay of insulin and C-peptide responses, without a significant overall reduction in integrated incremental responses. Enprostil almost totally inhibited the GIP response (by 94%; P less than or equal to 0.001), delayed initial insulin and C-peptide responses, but reduced the integrated incremental C-peptide response (which corresponds to the overall release of insulin) by only 14% (P less than or equal to 0.05). Enprostil more substantially reduced the integrated incremental response of insulin by 36% (P less than or equal to 0.01), and also reduced the ratio of insulin and C-peptide incremental responses (P less than or equal to 0.001). In conclusion, prostaglandin E analogues which caused a reduction in GIP responses, and thereby disrupting the enteroinsular axis to varying degrees, delayed the time-course of insulin secretion without a significant impact on glucose tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sensitivity of Entamoeba histolytica and Entamoeba dispar patient isolates to human complement

Twenty-one Entamoeba histolytica and 56 Entamoeba dispar patient isolates were investigated for their sensitivity to the classical and alternative pathway of human complement. E. histolytica and E. dispar patient isolates were differentiated by polymerase chain reaction and hexokinase isoenzyme typing. It was found that 90.3% (±12.0%) of the trophozoites of E. histolytica were lysed after 30 min by the alternative pathway of complement in the presence of 50% human serum (19 isolates showed lysis rates higher than 80%), whereas E. dispar cells were less susceptible to the alternative pathway as 68.8% (±28.2%) of lysis occurred. However, 23 of the E. dispar isolates were lysed between 100 and 80% (90.9%±9.1%), demonstrating that about half of the tested E. dispar isolates were highly sensitive to complement lysis. Only 11 of the E. dispar isolates were proven to be 'resistant' to the alternative pathway of complement and were lysed less than 40%. These results are in conflict to earlier publications, describing resistance of E. dispar to complement lysis (Hamelmann et al. 1992, 1993).