Preliminary evidence for a role of apolipoprotein E alleles in identifying haemodialysis patients at high vascular risk

Conventional risk factors have very low predictive power in identifying haemodialysis patients at high risk of vascular accidents. A role for apolipoprotein E isotypes was looked for in a small, but rigorously defined, cohort of longterm haemodialysis patients. In individuals with high vascular risk, as identified by higher common carotid intima/media thickness, we found an excess of apolipoprotein E4 alleles. This preliminary result requires confirmation in large patient cohorts.      

Experience with the P.A.S.-PORT Venous Access Device in Patients with Gynecologic Malignancies

Experience with the P.A.S.-PORT, a peripherally implanted central venous access device, is evaluated in a retrospective review of 154 patients from July 1991 to June 1994. Blood could not be aspirated from six patients. Complications included temporary minor thrombophlebitis in seven patients (4.5%), symptomatic axillary or subclavian vein thrombosis in five patients (3.2%), clotted port in two patients (1.2%), port pocket cellulitis in two patients (1.2%), and fungal sepsis in two patients (1.2%). In six patients (3.8%) the P.A.S.-PORT had to be removed because of complications. The P.A.S.-PORT facilitated delivery of chemotherapy, parenteral nutrition, blood products, antibiotics, hydration, and blood sampling. It was demonstrated that the P.A.S.-PORT may be inserted and used with a low incidence of complications in gynecologic cancer patients.     

Nonprogression of subclinical beta-cell dysfunction among first-degree relatives of IDDM patients. 5-yr follow-up of the Seattle Family Study

It is unknown among first-degree relatives of individuals with insulin-dependent diabetes mellitus (IDDM) whether the disease process occurs in relatively few but always progresses to clinical IDDM or whether subclinical disease is more common but remains nonprogressive in many cases. Islet cell antibodies (ICAs) were found in 21 of 724 (2.9%) first-degree relatives during screening in the greater Seattle area between 1983 and 1988. Measures of beta-cell function (glucose disappearance rate [Kg], fasting insulin, acute insulin response to intravenous arginine [AIRarg], acute insulin response to intravenous glucose [AIRgluc], slope of glucose potentiation of AIRarg) and insulin sensitivity were obtained. Twenty individuals, 9 ICA+ relatives and 11 ICA- relatives, were evaluated prospectively. When expressed in relation to the expected AIRgluc based on each subject's sensitivity index, AIRgluc in 18 of 20 relatives fell below 100%, indicating inappropriately low insulin secretion (subclinical beta-cell dysfunction). After a median follow-up of 42 mo, 10 of 11 ICA- relatives remained ICA-. None showed deteriorating beta-cell dysfunction, and none developed diabetes. Five ICA+ relatives showed persistent immunologic positivity. beta-Cell function remained remarkably stable in all except 2 relatives. One was a 15-yr-old boy who developed IDDM shortly after screening and before evaluation of beta-cell function could be carried out. The other was an 18-yr-old monozygotic twin who developed IDDM after 27 mo. Both of these individuals had ICAs of 80 Juvenile Diabetes Foundation U and had been discordant for less than 5 yr.(ABSTRACT TRUNCATED AT 250 WORDS)     

Human peripheral monocytes express putative receptors for neuroexcitatory amino acids.

Human peripheral mononuclear cells responded chemotactically to 4-carboxyl-L-glutamic acid. The maximal chemotactic response occurred at 0.1 nM. No chemotactic response was found with neutrophils or fetal bovine fibroblasts. Glutamic acid, a neuroexcitatory dicarboxylic amino acid and the parent compound of 4-carboxyglutamic acid, did not stimulate chemotaxis in any of the cells tested. However, it functioned as an antagonist to 4-carboxyglutamic acid (ED50 approximately 2 pM; ED100 approximately 10 pM). In contrast to the lack of response to glutamic acid, its dicarboxylic cyclic analogue, kainic acid, excited a chemotactic response in mononuclear cells. The data suggest that mononuclear phagocytes have receptors for dicarboxylic neuroexcitatory amino acids, and we speculate that 4-carboxyglutamic acid, a tricarboxylic acid, may have a previously unrecognized role as a neuroexcitatory amino acid.     

Radiation and thermal sensitivities of murine tumor (FSa-II) cells recurrent after a heavy irradiation.

Radiation and thermal sensitivities, and cell doubling times (Tds) of C3Hf/Sed mouse FSa-II cells recurring after a heavy irradiation were examined in vitro. Tumors in the leg were irradiated with gamma-rays and observed for late recurrence (in vivo clones), or removed immediately after irradiation and single cell suspensions were plated for colony formation (in vitro clones). Five subclones were selected from original cells in vitro. Survival curves were fitted to the multi-target and linear quadratic models. Surviving fractions at 2 (SF2) and 10 Gy (SF10) irradiations, and those at 30 and 60 min heatings at 44 degrees C (SF30 and SF60), were obtained for each clone. Although, Tds of subclones were slightly longer than those of the parental cells, those of recurrent clones were prolonged substantially with an exception of one cell line. Radiosensitivities of FSa-II parental cells tested in vitro and in vivo were equally radioresistant. Thermal sensitivities of parental cells tested in vitro and in vivo were also identical. All subclones were more radiosensitive compared to the parental cells. The in vitro recurrent clones showed smaller D0 (radiation dose to reduce survival from S to S/e in the exponential portion of survival curve) than the D0 of the parental cells. The SF2 values of four in vitro recurrent clones were greater than that of the parental cells whereas those of two lines were smaller. It was of interest that the in vivo recurrent tumor cells showed a wide variation in the radiation sensitivity. Among 9 tumor cell lines examined, 4 lines were more sensitive and 4 were more resistant compared to the original. FSa-II subclones as well as both in vitro and in vivo recurrent clones showed a wide variation in thermal sensitivity. No consistent changes in the shoulder or in the slope were found. The SF30 or SF60 showed that 5 out of 9 in vivo recurrent clones and 4 out of 9 in vitro clones were more resistant compared to the original cells. No correlation was observed between thermal and radiation sensitivities. The Td was not related with radiation or thermal sensitivity.     

A comparison of problems reported by persons with cancer and their same sex siblings

Problem reporting rates of 180 persons with cancer (PWC) were compared with those of their closest in age same sex cancer-free siblings living outside their households for the same time periods. PWC had significantly higher reporting rates for physical, activities of daily living, nutrition, and emotional problems and a significantly lower rate for family problems. Sibling problem reporting rates, which indicate the likelihood that PWC would have experienced similar problems without a diagnosis of cancer, were highest for physical, emotional, employment, and family problems suggesting that noncancer factors are especially likely to play a role in those types of problems. Regression analyses showed that female and younger PWCs tended to report more problems than their siblings suggesting that they were more affected by cancer and its treatments than were other types of PWC.