Combined oral positive inotropic and beta-blocker therapy for treatment of refractory class IV heart failure

OBJECTIVES: We sought to assess the effects of combined oral positive inotropic and beta-blocker therapy in patients with severe heart failure. BACKGROUND: Patients with severe, class IV heart failure who receive standard medical therapy exhibit a 1-year mortality rate >50%. Moreover, such patients generally do not tolerate beta-blockade, a promising new therapy for chronic heart failure. Positive inotropes, including phosphodiesterase inhibitors, are associated with increased mortality when administered over the long term in these patients. The addition of a beta-blocker to positive inotropic therapy might attenuate this adverse effect, although long-term oral inotropic therapy might serve as a bridge to beta-blockade. METHODS: Thirty patients with severe heart failure (left ventricular ejection fraction [LVEF] 17.2+/-1.2%, cardiac index 1.6+/-0.1 liter/min per m2) were treated with the combination of oral enoximone (a phosphodiesterase inhibitor) and oral metoprolol at two institutions. Enoximone was given at a dose of < or = 1 mg/kg body weight three times a day. After clinical stabilization, metoprolol was initiated at 6.25 mg twice a day and slowly titrated up to a target dose of 100 to 200 mg/day. RESULTS: Ninety-six percent of the patients tolerated enoximone, whereas 80% tolerated the addition of metoprolol. The mean duration of combination therapy was 9.4+/-1.8 months. The mean length of follow-up was 20.9+/-3.9 months. Of the 23 patients receiving the combination therapy, 48% were weaned off enoximone over the long term. The LVEF increased significantly, from 17.7+/-1.6% to 27.6+/-3.4% (p=0.01), whereas the New York Heart Association functional class improved from 4+/-0 to 2.8+/-0.1 (p=0.0001). The number of hospital admissions tended to decrease during therapy (p=0.06). The estimated probability of survival at 1 year was 81+/-9%. Heart transplantation was performed successfully in nine patients (30%). CONCLUSIONS: Combination therapy with a positive inotrope and a beta-blocker appears to be useful in the treatment of severe, class IV heart failure. It may be used as a palliative measure when transplantation is not an option or as a bridge to heart transplantation. Further study of this form of combined therapy is warranted.     

Unilateral phrenic nerve paralysis from cutting down a Christmas tree

Stretch injury to the phrenic nerve is an unusual cause of unilateral diaphragmatic paralysis. In this case the injury occurred while the patient was lying on the ground and cutting down a Christmas tree with a hand saw.     

Intraluminal duodenal diverticulum presenting as obstructive chronic pancreatitis

The presence of angiotensin II receptors was found on cells of three colorectal carcinoma cell lines. The binding assays with 125I-labelled angiotensin II and ligands specific for angiotensin AT1 or AT2 receptors showed that angiotensin receptors on colorectal cancer cells are mostly of the AT2 type. The binding capacity of tumor cells was not significantly changed by butyrate-induced differentiation.     

Copper/zinc superoxide dismutase transgenic brain accumulates hydrogen peroxide after perinatal hypoxia ischemia

OBJECTIVE: This study aims to evaluate the risk of esophagectomy in the elderly compared with younger patients and to determine whether results of esophagectomy in the elderly have improved in recent years. SUMMARY BACKGROUND DATA: An increased life expectancy has led to more elderly patients presenting with carcinoma of the esophagus in recent years. Esophagectomy for carcinoma of the esophagus is associated with significant morbidity and mortality, and advanced age is often considered a relative contraindication to esophagectomy despite advances in modern surgical practice. METHODS: The perioperative outcome and long-term survival of 167 elderly patients (70 years or more) with esophagectomy for carcinoma of the esophagus were compared with findings in 570 younger patients with esophagectomy in the period 1982 to 1996. Changes in perioperative outcome and survival between 1982 to 1989 and 1990 to 1996 were separately analyzed. RESULTS: The resection rate in the elderly was 48% (167/345), lower than the 65% (570/874) resection rate in younger patients (p < 0.001). There were significantly more preoperative risk factors and postoperative medical complications in the elderly, but no significant differences were observed in surgical complications. The 30-day mortality rate was higher in the elderly (7.2%) than in younger patients (3.0%) (p = 0.02), but the hospital mortality rate was not significantly different in the elderly (18.0%) and younger age groups (14.4%) (p = 0.27). The long-term survival after curative resection in elderly patients was worse than younger patients (p = 0.01). However, when deaths from unrelated medical conditions were excluded from analysis, survival was similar between the two age groups (p = 0.23). A comparison of data for the periods 1982 to 1989 and 1990 to 1996 revealed that the resection rate had increased from 44% to 54% in the elderly, with significantly fewer postoperative complications and lower 30-day and hospital mortality rates. Long-term survival has also improved, although this has not reached a statistically significant level. CONCLUSIONS: With current surgical management, esophagectomy for carcinoma of the esophagus can be carried out with acceptable risk in the elderly, but intensive perioperative support is required. The improved results of esophagectomy in the elderly in recent years are attributed to increased experience and better perioperative management. Long-term survival was similar to that of younger patients, excluding deaths caused by unrelated medical conditions.     

Hypocomplementemic autosomal recessive hemolytic uremic syndrome with decreased factor H

We describe the clinical course, complement components, and pathological findings of 10 infants with autosomal recessive hemolytic uremic syndrome (HUS). All patients were members of one extended highly inbred Bedouin kindred. The median age of presentation was 2 weeks (range 1-20 weeks). Eight patients died, 2 patients are alive, on dialysis. Renal biopsies revealed thrombotic microangiopathy with a predominant early arteriolar involvement and subsequent development of ischemic glomerular changes. Immunofluorescence was positive for C3 in glomeruli. All patients had low complement components levels during and between relapses, and in some this was evident soon after birth and prior to the onset of symptoms. This deficiency could not be normalized by repeated plasma transfusions. Biosynthetic labelling of patients' fibroblasts demonstrated normal rates of C3 protein synthesis. Serum factor H levels were greatly decreased or absent in 4 patients tested and moderately decreased in 15 of 23 healthy unaffected siblings and patients. This defect may cause complement activation and consumption, possibly at the endothelial cell level.     

The correlation between skin electrical conductance and the score of qi vacuity

In traditional Chinese medicine, the syndrome of qi vacuity means that the patient's body has a low level of energy to react to stress. Recently, we used a score, the QV score, by scaling the severity of symptoms and signs of qi vacuity in patients with tiredness. The aim of this study was to investigate the relationship between QV score and skin electrical conductance in patients with tiredness. One hundred and forty-three healthy controls and 103 patients with tiredness were involved. Each subject received a weak electrical stimulation with constant voltage (1.75 volt), and conductance was measured between two different limbs. The mean value of skin conductance among four limbs was calculated and expressed by a special unit, namely Chin. The correlation between the skin conductance and QV score was analyzed by a linear regression analysis. The results showed that skin electrical conductance of healthy controls was negatively correlated with age (r-coefficient = -0.51, P = 0.000). The skin conductance of patients with tiredness was significantly lower than that of healthy controls with matching age (P = 0.000 by Student's t-test). Moreover, there was a positive correlation between the decrease of skin conductance and the QV score in patients with tiredness (r-coefficient = +0.68, P = 0.000). These results suggest that a decrease in skin electrical conductance may be closely related to the severity of qi vacuity. The skin conductance test is a simple, reliable, and quantitative method for detection of syndrome of qi vacuity.     

Evidence for a heterozygote advantage in congenital adrenal hyperplasia due to 21-hydroxylase deficiency

21-Hydroxylase deficiency is one of the most common inherited disorders, with carrier frequencies of approximately 10% in all world populations studied to date. The high prevalence of the mutant gene is probably due to a flanking pseudogene serving as a reservoir for mutations. Despite the potential for a high rate of de novo mutations, a founder effect for specific gene conversions is observed in most populations. We hypothesized that there was a survival advantage to 21-hydroxylase heterozygotes, and here we report endocrinological and molecular investigations to test this hypothesis. We defined 28 carriers and 22 mutation-negative controls by molecular genotyping and determined ACTH-stimulated adrenal hormone responses. We found significantly elevated cortisol responses in the carriers compared to controls (30 min cortisol levels: normal, 24.2 +/- 4.6 micrograms/dL; carrier, 28.1 +/- 4.2 micrograms/dL; P < 0.005). Cortisol has a crucial role in maintaining homeostasis, influencing differentiation, suppressing inflammation, and effecting cross-talk among the immune, nervous, and endocrine systems. The brisk cortisol response we have documented in carriers of 21-hydroxylase may enable a rapid return to homeostasis in response to infectious, inflammatory, or other environmental stresses and may protect from inappropriate immune responses, such as autoimmune diseases.     

Salbutamol overcomes the effect of the noradrenergic neurotoxin DSP-4 on memory function in the day-old chick

These experiments investigated the effect of the relatively selective noradrenergic neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) on memory formation in day-old chicks trained on a discriminated passive avoidance task. A time course study showed that DSP-4 treatment resulted in amnesia as early as 20 min post-learning. In a second study, a series of alpha- and beta-adrenergic agonists (noradrenaline; the alpha 1 agonist phenylephrine; the beta 1 agonist dobutamine; and the beta 2 agonist salbutamol) were applied immediately after the training trial. Both noradrenaline and salbutamol were effective in ameliorating the memory deficits caused by DSP-4 treatment, and in consolidating weakly reinforced training. These studies support the notion that noradrenaline subserves a vital role in the consolidation of memory in the chick, and that the beta 2 receptor subtypes are principally involved in the intermediate phase of memory formation.