Amyloid light-chain amyloidosis with primary involvement of the cardiorespiratory system--2 case reports

The authors describe the cases of two women suffering from AL amyloidosis with affection of the heart muscle in particular. In one of the patients there were also massive amyloid deposits in the lungs which is an exceptional finding. The observations confirm the adverse prognosis of amyloidosis, the rapid progression of the disease after the onset of symptoms of cardiac failure. The first cardial manifestation in both patients were palpitations. The first patient, but not the second one, had a myeloma confirmed on necropsy.     

Prevention of endometrial hyperplasia by progesterone during long-term estradiol replacement: influence of bleeding pattern and secretory changes

OBJECTIVE: To determine the relative influences of induction of withdrawal bleedings secretory transformation, and reduction of mitosis in glands on prevention of endometrial hyperplasia during long-term hormonal replacement therapy. DESIGN: Observational expanded clinical case report. SETTING: Reproductive Endocrine Department of Hospital Necker, Paris, France, and Pathology Department of Women's Hospital, Los Angeles County and University of Southern California Medical Center, Los Angeles, California. PATIENTS: Postmenopausal women seeking treatment for symptomatic menopause. INTERVENTIONS: Endometrial biopsy and/or ambulatory hysteroscopy. MAIN OUTCOME MEASURE: Endometrial histology including progestational maturation patterns and glandular epithelial mitosis rates. Macroscopic endometrial appearance. RESULTS: The use of larger doses of E2 and P induced more marked secretory changes and more frequent withdrawal bleeding than the lower doses. There was no evidence of endometrial hyperplasia after 5 years of E2/P replacement therapy independently of bleeding pattern or progestational maturation. Consistent reduction of mitosis rates in glandular epithelium was found after 9 or more days of P administration in each cycle. CONCLUSIONS: Control of endometrial growth is mainly related to control of mitosis in glands by a relatively low doses of P. Induction of withdrawal bleeding and endometrial secretory transformation, which require larger doses of Progesterone, do not provide additional benefit for prevention of hyperplasia. Induction of amenorrhea with a relatively low dose of P may be offered to women seeking hormone replacement therapy with similar levels of safety.     

A clinical study of the use of a combination of glucomannan with lactulose in the constipation of pregnancy

RATIONALE: Constipation is a problem frequently encountered during pregnancy as is excessive weight gain. Treatments of common use to control constipation are endowed with some drawbacks and they are not active in controlling weight increase. A preparation of lactulose and glucomannan in previous studies proved very effective and well tolerated in patients affected by stypsis and evidentiated also activity both in controlling excessive food intake and in correcting some metabolic imbalances regarding lipids and urea. MATERIAL AND METHODS: 50 pregnant females affected by constipation were treated with sachets containing a preparation of glucomannan (1.45 g) and lactulose (4.2 g) in a posology of 2 (1-4) sachets a day for 1-3 months. RESULTS: Treatment induced a return to normal frequency of weekly number of evacuations (4.9-5.8/week) and a parallel control of weight gain (within 20% of initial body weight). The latter finding seems to be related to hunger control induced by glucomannan at the gastric level which prevents an excessive food intake.     

A mammalian adaptor protein with conserved Src homology 2 and phosphotyrosine-binding domains is related to Shc and is specifically expressed in the brain

The Shc adaptor protein, hereafter referred to as ShcA, possesses two distinct phosphotyrosine-recognition modules, a C-terminal Src homology 2 (SH2) domain and an N-terminal phosphotyrosine-binding (PTB) domain, and is itself phosphorylated on tyrosine in response to many extracellular signals. Phosphorylation of human ShcA at Tyr-317 within its central (CH1) region induces binding to the Grb2 SH2 domain and is thereby implicated in activation of the Ras pathway. Two shc-related genes (shcB and shcC) have been identified in the mouse. shcB is closely related to human SCK, while shcC has not yet been found in other organisms. The ShcC protein is predicted to have a C-terminal SH2 domain, a CH1 region with a putative Grb2-binding site, and an N-terminal PTB domain. The ShcC and ShcB SH2 domains bind phosphotyrosine-containing peptides and receptors with a specificity related to, but distinct from, that of the ShcA SH2 domain. The ShcC PTB domain specifically associates in vitro with the autophosphorylated receptors for nerve growth factor and epidermal growth factor. These results indicate that ShcC has functional SH2 and PTB; domains. In contrast to shcA, which is widely expressed, shcC RNA and proteins are predominantly expressed in the adult brain. These results suggest that ShcC may mediate signaling from tyrosine kinases in the nervous system, such as receptors for neurotrophins.     

Impact of apolipoprotein E polymorphism on lipoproteins and risk of myocardial infarction. The ECTIM Study

Human apolipoprotein (apo) E, a polymorphic protein with three common alleles, epsilon 2, epsilon 3, and epsilon 4, plays an important role in lipoprotein metabolism. This article describes the association of this polymorphism with lipids, apolipoproteins, and lipoproteins with a particular regard to lipoprotein particles, as defined by their apolipoprotein content, as well as the risk of myocardial infarction in a multicenter population-based case-control study (ECTIM study). In the ECTIM study, 574 male patients aged 25 to 64 were examined 3 to 9 months after myocardial infarction in four regions participating in the World Health Organization MONICA project: Belfast (Northern Ireland) and Lille, Strasbourg, and Toulouse (France). Control subjects (n = 722) were randomly selected from the regional populations. The distribution of apoE phenotypes was significantly different across the four control samples (P = .04), with a higher frequency of the epsilon 4 allele in Belfast (14.3%) than in Toulouse (8.2%). The association of apoE polymorphism with biological measurements was studied in the control groups (n = 640) after men with coronary heart disease or those taking hypolipidemic drugs were omitted, with the apoE3/3 phenotype as a reference after adjustment for concomitant factors. Individuals carrying the epsilon 2 allele had lower levels of plasma cholesterol, low-density lipoprotein cholesterol (LDL-C), and apoB and higher levels of triglycerides, very-low-density lipoprotein cholesterol (VLDL-C), apoC-III, apoE, lipoprotein (Lp) C-III:B, and Lp E:B. However, the effect of the epsilon 2 allele on triglyceride, VLDL-C, apoE, and Lp E:B parameters was heterogeneous across the populations.(ABSTRACT TRUNCATED AT 250 WORDS)     

The role of squamous cell carcinoma antigen in the management of laryngeal and hypopharyngeal cancer

BACKGROUND: The efficacy of squamous cell carcinoma antigen (SCC-Ag) in laryngeal cancer to predict those patients who will relapse after primary treatment (surgery or radiotherapy) and its utility to detect relapses early and thereby increase salvage rates and cure were assessed. METHODS: Sixty healthy donors and 168 patients with laryngeal cancer were included in this prospective trial. Squamous cell carcinoma antigen was measured at diagnosis in all patients, 24 hours and 1 week after surgery in 113 patients and every 10 Gy of administered dose and 2 weeks after treatment in 49 patients primarily referred to radiotherapy. The marker was determined every 3-6 months during follow-up. All patients who relapsed had SCC-Ag studies before and after salvage treatment. RESULTS: The selected cut-off value was 1.5 ngr/ml (mean value in control group, 0.65 + 2 standard deviation [0.38]). Seventy-eight percent of patients with cancer had elevated SCC-Ag values at diagnosis. Squamous cell carcinoma antigen was statistically related to TNM categories (T, P < 0.04; N, P < 0.05; Stage, P < 0.01). Seventy-five percent of those patients with previously elevated pretreatment values normalized after treatment. Incomplete surgical resection (P < 0.0001) or persistence of the disease after radiotherapy (P < 0.01) were related to high posttreatment values. Squamous cell carcinoma antigen was elevated in 88% of the patients who relapsed. In 55% of the recurrences, SCC-Ag was elevated 3 months before pathologic confirmation of relapse. Salvage by surgery or radiotherapy was effective in 70% of the patients. Squamous cell carcinoma antigen posttreatment values were the most important factor in predicting disease free survival (DFS) (P < 0.0001) and overall survival (P < 0.03). CONCLUSIONS: Squamous cell carcinoma antigen is an excellent marker of residual disease after primary treatment that can lead to the addition of other therapeutic procedures (surgery and postoperative radiotherapy). The absence of posttreatment SCC-Ag is the best predictor of DFS, its presence detects recurrence in early stages, permitting salvage of an increased proportion of patients primarily referred for palliative treatment.     

Deep brain stimulation for essential tremor

We examined the effects and safety of deep brain stimulation (DBS) as a treatment for essential tremor (ET). Ten ET patients with disabling medication-refractory tremor underwent stereotactic implantation of a DBS lead in the left Vim thalamic nucleus and completed a 6-month follow-up. The Clinical Tremor Rating Scale and disability assessments were performed at baseline, 1-, 3-, and 6-month follow-up. There were significant improvements in dressing, drinking, eating, bathing, and handwriting as reported by the subjects. Tremor severity, writing, pouring, and spiral and line drawing were significantly improved as rated by the examiner. Improvements persisted through the 6-month follow-up period. Although global disability significantly lessened in the group as a whole, one subject with hand-finger tremor accentuated by writing had no change in disability status. In this 6-month open-label study, DBS was effective and safe in reducing tremor and functional disability in ET.     

Urinary stone proteins: an update

The discovery of an organic component in kidney stones dates back to 1684. More than 150 years elapsed before the incrustation of this organic component, which is now called the matrix, was proposed as the mechanism of stone formation. The composition of the matrix remained largely unknown until the development of electron microscopy and the advances in biochemistry combined in the 1950's to usher in the modern era of renal stone matrix investigation. Composed mainly of selectively incorporated proteins generally characterized by high glutamic and aspartic acid content and the frequent occurrence of gamma-carboxyglutamic acid, the matrix displays a variable and complex composition and shares a few proteins in many stones. The embryonic stone may first appear in the renal tubules where it can acquire the blood and cell membrane proteins recently found by analysis of stone protein extracts. The combination of supersaturation, an appropriate environment, the availability of calcium binding proteins which may be abnormal, and the incorporation of proteins extracted from leukocytes and cell wall membranes may induce stone formation.