ECT in the treatment of recurrent psychotic depression.

Two cases of recurrent psychotic depression are reported in which ECT (electroconvulsive therapy) was administered with good results for previous episodes of depression, but treatment of the current episode with combined drug therapy (antidepressant and antipsychotic drugs) in one case and antidepressant chemotherapy in the other resulted in failure to improve. The patients were transferred to another facility, and improved when ECT was administered. Pertinent literature on ECT and drug treatment of depression is reviewed, and the conditions for which ECT is probably the treatment of choice are enumerated.     

Immunological approaches as therapy for Alzheimer's disease

The pathology of Alzheimer's disease (AD) shows a significant correlation between beta-amyloid peptide (AbetaP) conformation and the clinical severity of dementia. For many years, efforts have been focused on the development of inhibitors of beta-amyloid (Abeta) formation and its related neurotoxic effects. The author has developed a new concept showing that site-directed antibodies may modulate formation of Abeta. The performance of anti-Abeta antibodies in transgenic mice models of AD showed that they are delivered to the central nervous system (CNS), preventing in vivo formation of Abeta. Moreover, these antibodies dissolve Abeta plaques and protect the mice from learning difficulties and age-related memory deficits. Experimental active immunisation with Abeta (1-42) in humans has been stopped in Phase II of their clinical trials. However, several new preparations, able to provide antibodies against Abeta by either active or passive routes, have been formulated and at least one of these is likely to reach clinical testing. These data support the hypothesis that AbetaP plays a central role in AD and antibodies which modulate Abeta conformation may lead to immunotherapy of the disease.     

A molecular basis for nonsecretory myeloma

The biosynthesis of aberrant immunoglobulin polypeptides by monoclonal plasma cells has been implicated in the pathogenesis of nonsecretory myeloma. Our studies of a patient with this disorder indeed have demonstrated the presence of abnormal kappa light chains that resulted from a frameshift mutation in nucleotides encoding the constant region of the molecule. As a consequence of a 2-base deletion in codon 187 and loss of the normal stop codon, this portion of the kappa chain was composed of 128 amino acids (rather than the expected 106), with a completely anomalous sequence after position 187 that included absence of the cysteines required for intrachain and interchain disulfide bonds. The unusual primary structure of this component was confirmed by mass spectrometric and amino acid sequence analyses of cytoplasmic protein extracts. Our studies provide the first evidence that human nonsecretory myeloma may result from an alteration in the light-chain constant region.     

Thyrotoxicosis presenting as hypogonadism: a case of central hyperthyroidism

Herein, we present a case of central thyrotoxicosis with well-documented serial therapeutic interventions. Thyroid-stimulating hormone (TSH)-secreting pituitary tumors represent a rare cause of hyperthyroidism. It is being diagnosed more frequently with the third-generation TSH assay. Many conditions can produce normal or elevated TSH levels in combination with elevated thyroid hormone levels. The differential diagnosis includes resistance to thyroid hormone (RTH, Refetoff's syndrome), assay interference from anti-T4/T3 and heterophile antibodies, elevated or altered binding proteins, drugs affecting peripheral metabolism, and noncompliance with thyroid replacement therapy. In contrast to RTH, our patient presented had high alpha-subunit-to-TSH molar ratio, failed TSH response to thyrotropin-releasing hormone stimulation, and a large pituitary mass. Normal or high TSH in the presence of elevated T4 or T3 is a fairly common clinical scenario with many etiologic possibilities. This TSH-producing adenoma represents an unusual initial clinical presentation, as hypogonadism appeared before features of thyrotoxicosis were appreciated. This case represents the most modern therapeutic approach to the management of this rare disease. Our patient has done well on octreotide with control of thyrotoxicosis and an additional 30% shrinkage of his tumor mass.     

Long-term results of anterior resection using the double-stapling technique

PURPOSE: This study was designed to determine the anastomotic leak rate, local recurrence rate, and survival of patients undergoing anterior resection with the double-stapling technique for rectal cancer. METHODS: Between 1981 and 1992, 189 patients underwent a curative (166) or palliative (23) anterior resection using the double-stapling technique. A chart review was performed, and follow-up information was obtained from the patient or family physician. Follow-up was complete in 186 patients (98 percent). RESULTS: There were five (2.6 percent) stapler-related complications, of which two patients required a defunctioning colostomy. Postoperative mortality was 1.6 percent, and clinical leak rate was 7.3 percent. Clinical leak rate was significantly higher in patients with lesions in the lower third (20 percent) compared with those in the middle and upper thirds (9 and 1 percent, respectively;P <0.05). After a mean follow-up of 32±29 months, local recurrence rate was 9.1 percent but was significantly higher in patients more than 65 years old (14 vs.1 percent;P <0.005) and in patients with resection margins less than 2.0 cm (17 vs.5.5 percent;P <0.05). Five-year survival was 78 percent. CONCLUSIONS: Anterior resection performed with the double-stapling technique has an acceptable clinical leak rate, local recurrence rate, and survival rate. However, the clinical leak rate appears to be increased in patients with low tumors and, therefore, a defunctioning colostomy should be considered. Resection margins of more than 2 cm are necessary.Read at the meeting of the Royal College of Physicians and Surgeons of Canada, Vancouver, British Columbia, Canada, September 10 to 13, 1993, and the Tripartite Colorectal Meeting, Sydney, Australia, October 17 to 20, 1993.     

Soluble ST2 and Risk of Arrhythmias,Heart Failure,or Death in Patients with Mildly Symptomatic Heart Failure: Results from MADIT-CRT

Soluble ST2 is an established biomarker of heart failure (HF) progression. Data about its prognostic implications in patients with mildly symptomatic HF eligible to receive cardiac resynchronization therapy defibrillators (CRT-D) are limited. In a cohort of 684 patients enrolled in Multicenter Automated Defibrillator Implantation Trial (MADIT)-CRT, levels of soluble ST2 (sST2) were serially assessed at baseline and 1 year (n?=?410). In multivariable-adjusted models, elevated baseline sST2 was associated with an increased risk of death, death or HF, and death or ventricular arrhythmia (VA) even when adjusting for baseline brain natriuretic protein (BNP) levels. In addition, patients with lower baseline sST2 levels had greater risk reduction with CRT-D (p?=?0.006). Serial assessment revealed increased risk of VA and death or VA (HR per 10 % increase in sST2 1.11 (1.04–1.20), p?=?0.004). Among patients with mildly symptomatic HF and eligibility for CRT-D, baseline and serial assessments sST2 may provide important information for risk stratification.     

Usefulness of four echocardiographic risk assessments in predicting 30-day outcome in acute myocardial infarction

One thousand fifty-one consecutive patients who had acute myocardial infarction were classified into 3 risk groups by 4 echocardiographic risk assessments: left ventricular ejection fraction, left ventricular filling pattern, estimated systolic pulmonary artery pressure, and mitral regurgitation, with 30-day mortality rates of 13.7%, 3.8%, and 1%, respectively (p <0.001). Independent echocardiographic and clinical predictors of 30-day mortality included age (10 years, hazard ratio [HR] 1.30, 95% confidence interval [CI] 0.91 to 1.89), female gender (HR 2.12, 95% CI 0.94 to 4.74), Killip's class > or =II on admission (HR 3.09, 95% CI 1.38 to 7.11), group 2 (moderate) risk (HR 2.89, 95% CI 1.07 to 8.56), and group 1 (high) risk (HR 8.16, 95% CI 2.95 to 25.23).     

RACK1 binds to inositol 1,4,5-trisphosphate receptors and mediates Ca2+ release

RACK1 is not a G protein but closely resembles the heterotrimeric Gbeta-subunit. RACK1 serves as a scaffold, linking protein kinase C to its substrates. We demonstrate that RACK1 physiologically binds inositol 1,4,5-trisphosphate receptors and regulates Ca2+ release by enhancing inositol 1,4,5-trisphosphate receptor binding affinity for inositol 1,4,5-trisphosphate. Overexpression of RACK1 or depletion of RACK1 by interference RNA markedly augments or diminishes Ca2+ release, respectively, without affecting Ca2+ entry. These findings establish RACK1 as a physiologic mediator of agonist-induced Ca2+ release.