Scaling of movement velocity: a measure of neuromotor retardation in individuals with psychopathology

The combination of ifosfamide, carboplatin and etoposide (modified ICE), was evaluated for its toxicity and activity in relapsed or refractory aggressive non-Hodgkin's lymphoma. Twenty patients, 14-69 years of age, with relapsed (19 cases) or refractory (one case) aggressive non-Hodgkin's lymphoma were treated with modified ICE therapy, consisting of ifosfamide 6 g/m2 (1.2 g/m2 day 1-5), carboplatin 400 mg/m2 (day 1) and etoposide 500 mg/m2 (100 mg/m2 day 1-5). The regimen was repeated at approximately 28-day intervals. All patients had undergone a doxorubicin-containing regimen before modified ICE therapy. Median total dose of previously received doxorubicin was 406 mg/m2 (range: 200-825 mg/m2). The median interval from diagnosis to modified ICE therapy was 9.4 months (range: 3.6-121 months). Two patients achieved CR and five achieved PR out of 16 patients with measurable lesions (response rate 43.8%; 95% confidence interval 19.0-68.6%). Median overall survival was 227 days (range: 41-552 days) from the start of modified ICE therapy. Myelosuppression was the most serious toxicity, namely 16 patients (80%) and 11 patients (55%) showed grade 4 neutropenia and grade 4 thrombocytopenia after the first course, respectively. Modified ICE therapy might be an active regimen with acceptable toxicity as a salvage chemotherapy in aggressive non-Hodgkin's lymphoma.     

Congenital epulis in the newborn

The authors report a case of congenital epulis in the lower gum of a new born female. This rare benign tumor of the newborn is histologically characterized by the granular aspect of its cells. It occurs more frequently in females than in males. Differential diagnosis mainly concerns Abrikossoff tumor whose histogenesis and evolution are different. The distinctive features of epulis are the presence of a fusiform cell component and the negativity of the granular cells for PS100.     

Assessment of the role of the renin-angiotensin system in cardiac contractility utilizing the renin inhibitor remikiren

1. The role of the renin-angiotensin system in the regulation of myocardial contractility is still debated. In order to investigate whether renin inhibition affects myocardial contractility and whether this action depends on intracardiac rather than circulating angiotensin II, the regional myocardial effects of systemic (i.v.) and intracoronary (i.c.) infusions of the renin inhibitor remikiren, were compared and related to the effects on systemic haemodynamics and circulating angiotensin II in open-chest anaesthetized pigs (25-30 kg). The specificity of the remikiren-induced effects was tested (1) by studying its i.c. effects after administration of the AT1-receptor antagonist L-158,809 and (2) by measuring its effects on contractile force of porcine isolated cardiac trabeculae. 2. Consecutive 10 min i.v. infusions of remikiren were given at 2, 5, 10 and 20 mg min-1. Mean arterial pressure (MAP), cardiac output (CO), heart rate (HR), systemic vascular resistance (SVR), myocardial oxygen consumption (MVO2) and left ventricular (LV) dP/dtmax were not affected by remikiren at 2 and 5 mg min-1, and were lowered at higher doses. At the highest dose, MAP decreased by 48%, CO by 13%, HR by 14%, SVR by 40%, MVO2 by 28% and LV dp/dtmax by 52% (mean values; P < 0.05 for difference from baseline, n = 5). The decrease in MVO2 was accompanied by a decrease in myocardial work (MAP x CO), but the larger decline in work (55% vs. 28%; P < 0.05) implies a reduced myocardial efficiency ((MAP x CO)/MVO2). 3. Consecutive 10 min i.c. infusions of remikiren were given at 0.2, 0.5, 1, 2, 5 and 10 mg min-1. MAP, CO, MVO2 and LV dP/dtmax were not affected by remikiren at 0.2, 0.5 and 1 mg min-1, and were reduced at higher doses. At the highest dose, MAP decreased by 31%, CO by 26%, MVO2 by 46% and LV dP/dtmax by 43% (mean values; P < 0.05 for difference from baseline, n = 6). HR and SVR did not change at any dose. 4. Thirty minutes after a 10 min i.v. infusion of the AT1 receptor antagonist, L-158,809 at 1 mg min-1, consecutive 10 min i.c. infusions (n = 5) of remikiren at 2, 5 and 10 mg min-1 no longer affected CO and MVO2, and decreased LV dP/dtmax by maximally 27% (P < 0.05) and MAP by 14% (P < 0.05), which was less than without AT1-receptor blockade (P < 0.05). HR and SVR remained unaffected. 5. Plasma renin activity and angiotensin I and II were reduced to levels at or below the detection limit at doses of remikiren that were not high enough to affect systemic haemodynamics or regional myocardial function, both after i.v. and i.c. infusion. 6. Remikiren (10(-10) to 10(-4) M) did not affect contractile force of porcine isolated cardiac trabeculae precontracted with noradrenaline. In trabeculae that were not precontracted no decrease in baseline contractility was observed with remikiren in concentrations up to 10(-5) M, whereas at 10(-4) M baseline contractility decreased by 19% (P < 0.05). 7. Results show that with remikiren i.v., at the doses we used, blood pressure was lowered primarily by vasodilation and with remikiren i.c. by cardiac depression. The blood levels of remikiren required for its vasodilator action are lower than the levels affecting cardiac contractile function. A decrease in circulating angiotensin II does not appear to be the sole explanation for these haemodynamic responses. Data support the contention that myocardial contractility is increased by renin-dependent angiotensin II formation in the heart.     

Par-4 is a mediator of neuronal degeneration associated with the pathogenesis of Alzheimer disease

Prostate apoptosis response-4 (Par-4) is a protein containing both a leucine zipper and a death domain that was isolated by differential screening for genes upregulated in prostate cancer cells undergoing apoptosis. Par-4 is expressed in the nervous system, where its function is unknown. In Alzheimer disease (AD), neurons may die by apoptosis, and amyloid beta-protein (A beta) may play a role in this. We report here that Par-4 expression is increased in vulnerable neurons in AD brain and is induced in cultured neurons undergoing apoptosis. Blockade of Par-4 expression or function prevented neuronal apoptosis induced by Ab and trophic factor withdrawal. Par-4 expression was enhanced, and mitochondrial dysfunction and apoptosis exacerbated, in cells expressing presenilin-1 mutations associated with early-onset inherited AD.     

Successful term pregnancy after Mustard operation for transposition of the great arteries

Transposition of the great arteries is a complex cardiac malformation with poor prognosis without surgical correction. Since the introduction of surgical procedures such as the intra-auricular reorientation of the venous return (Mustard procedure), an increasing number of patients may reach adulthood and experience pregnancy. Because long-term complications after the Mustard operation include systemic heart failure, arrhythmias, venous return stenosis and pulmonary edema, hemodynamic changes during pregnancy and delivery may potentially engender life-threatening complications in these patients. We report the case of a 24-year-old primigravida who underwent a Mustard procedure at the age of 2 years for transposition of the great vessels, and who carried out a full-term pregnancy. The pregnancy was uneventful until the 34th week, when the woman developed signs of moderate right ventricular failure and frequent episodes of accelerated junctional rhythm. Digitalisation improved symptoms and elicited return to normal sinus rhythm. The patient delivered at term by elective cesarean section, under close hemodynamic monitoring.     

Monitoring furosemide in racehorses participating in an EIPH program

We report a rare case of temporary and severe hypercalcemia: the patient, a 69-year-old woman, was admitted to Osaka City University Hospital on July 25, 1992, for severe hypercalcemia. The laboratory data on admission revealed severe hypercalcemia (14.9 mg/dl) and renal dysfunction with increased serum creatinine level (2.9 mg/dl). The urinary excretion of pyridinoline and deoxypyridinoline was increased, and serum levels of parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D were decreased. The data suggested that increased bone resorption was a probable main factor in the development of the hypercalcemia. The development of hypercalcemia seemed to be of acute onset because of (1) her severe symptoms caused by hypercalcemia and (2) impaired renal function which was improved after normalization of serum calcium level. Combination therapy with saline infusion and furosemide was administered, and there was a gradual decrease and subsequent normalization of serum calcium level along with serum creatinine. Even 8 months after discontinuation of the therapy for hypercalcemia, the serum calcium level remained within the normal range. The measured values of serum factors which are suspected to have a hypercalcemic effect, such as PTH, parathyroid hormone-related peptide and the cytokines (interleukin-1 alpha, interleukin-1 beta, interleukin-2, interleukin-6 and tumor necrosis factor-alpha) were all within the normal range. In summary, the hypercalcemia in this patient was regarded to be a type of disequilibrium hypercalcemia due to a combination of increased bone resorption and decreased renal capacity to excrete calcium. Furthermore, since it was temporary and did not recur even in the absence of treatment, the hypercalcemia was concluded to have developed due to an imbalance in calcium regulation rather than as a result of organic disease.