The use of natural interferon alpha conjugated to a monoclonal antibody anti mammary epithelial mucin (Mc5) for the treatment of human breast cancer xenografts

Summary An immunoconjugate composed of natural interferon (nIFN) bound in a noncleavable fashion to a monoclonal antibody (MoAb) recognizing a breast epithelial membrane mucin (Mc5) was used to treat xenografts of a human mammary carcinoma cell line (MCF-7) growing in nude mice. The immunoconjugate (nIFN/Mc5) was administered as 20 intralesional (i.l.) injections to 1 of 2 xenografts in each animal. It was found that nIFN/Mc5 produced a significant enhancement of the growth inhibitory actions of nIFN on the injected tumors. Further enhancement was obtained when nIFN or nIFN together with Mc5 (at a dose 10 times larger than that present in nIFN/Mc5) were added to the immunoconjugate. Biodistribution experiments showed that the uptake of¹²⁵I-nIFN/Mc5 by the tumors was greater and its elimination slower than for¹²⁵I-nIFN alone or conjugated to irrelevant mouse IgG₁. In addition, the immunoconjugate up-regulated the antigenic expression of a breast epithelial membrane mucin by the carcinoma cells, an up-regulation which was not significantly different from that produced by nIFN alone. The contralateral noninjected tumors exposed to systemic levels of the immunoconjugate showed an enhancement of antitumor effects, but to a lesser extent than the injected tumors. These findings suggest that the enhancement of the growth inhibitory action of the immunoconjugate was related to the specific binding of Mc5 which targeted the IFN to the carcinoma cells and impeded its elimination. It is likely that the targeting was favored by the IFN-mediated up-regulation of antigenic expression by the carcinoma cells, thereby producing a cascade of interrelated effects. The results of this study point out the feasibility and potential usefulness of IFN treatment by means of immunoconjugates as well as the worth of pursuing and improving this form of therapy.     

Energy intake, not energy output, is a determinant of body size in infants

BACKGROUND: It has been proposed that the primary determinants of body weight at 1 y of age are genetic background, as represented by parental obesity, and low total energy expenditure. OBJECTIVE: The objective was to determine the relative contributions of genetic background and energy intake and expenditure as determinants of body weight at 1 y of age. DESIGN: Forty infants of obese and 38 infants of lean mothers, half boys and half girls, were assessed at 3 mo of age for 10 risk factors for obesity: sex, risk group (obese or nonobese mothers), maternal and paternal body mass index, body weight, feeding mode (breast, bottle, or both), 3-d energy intake, nutritive sucking behavior during a test meal, total energy expenditure, sleeping energy expenditure, and interactions among them. RESULTS: The only difference between risk groups at baseline was that the high-risk group sucked more vigorously during the test meal. Four measures accounted for 62% of the variability in weight at 12 mo: 3-mo weight (41%, P = 0.0001), nutritive sucking behavior (9%, P = 0.0002), 3-d food intake (8%, P = 0.0002), and male sex (3%, P = 0.05). Food intake and sucking behavior at 3 mo accounted for similar amounts of variability in weight-for-length, body fat, fat-free mass, and skinfold thickness at 12 mo. Contrary to expectations, neither total nor sleeping energy expenditure at 3 mo nor maternal obesity contributed to measures of body size at 12 mo. CONCLUSIONS: Energy intake contributes significantly to measures of body weight and composition at 1 y of age; parental obesity and energy expenditure do not.     

The marketing audit: a tool for health service organizations

Recent articles have explained the philosophy of marketing health services. Highlighted here are the important concerns in the "hands-on" development and implementation of a marketing plan.     

Blood-retinal barrier breakdown investigated by real-time magnetic resonance imaging after gadolinium-diethylenetriaminepentaacetic acid injection

Recent magnetic resonance imaging (MRI) studies show that gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) entry into the vitreous space can be used as a qualitative marker of blood-retinal barrier (BRB) disruption. To determine if a more quantitative measurement of BRB breakdown could be obtained, the utility of acquiring real-time, T1-weighted proton images was studied after Gd-DTPA injection. Two days before the MRI experiment, panretinal photocoagulation was done. The mean signal intensity over selected regions-of-interest (ROI) in the vitreous and anterior chamber was followed before and after (0, 10, 20, 30, 45, and 60 min) Gd-DTPA injection (1.0 mmol/kg, intravenously). At every laser power setting used in this study (0, 200, 400, 600, and 800 mW), the change in the mean signal intensity could be approximated by a simple exponential equation. However, the time constants determined for these curves were too imprecise to be useful as correlates between laser power and BRB breakdown. The slope of the line fit to the data in the first 20 min postinjection (ie, an initial-rate analysis) was a more precise correlate between BRB breakdown and laser power. This slope represented the rate of change in mean signal intensity in the ROI as a result of the entry of Gd-DTPA, and it was called the "leakiness" parameter. The leakiness parameter reflected changes in the permeability surface area product of the BRB if the blood flow and the Gd-DTPA arterial concentration immediately after injection were approximately the same between animals.     

Sexual assault tracking study: who gets lost to follow-up?

OBJECTIVES: To determine whether loss to follow-up can be predicted in patients who present to an emergency sexual assault assessment service and to generate hypotheses regarding the prediction of loss to follow-up on the basis of patient characteristics, assault characteristics and the services provided. DESIGN: Prospective, exploratory study. SETTING: Emergency department functioning as a regional sexual assault centre in a tertiary care hospital. PATIENTS: All 294 women over the age of 16 years who presented to the emergency department with a complaint of sexual assault and consented to be followed up. INTERVENTIONS: Telephone interviews at 24 to 48 hours and 1 month after presentation; face-to-face interviews after 1 week, 3 months and 6 months. MAIN OUTCOME MEASURES: Follow-up status (tracked versus lost to follow-up), State-Trait Anxiety Inventory (STAI-Y), Beck Depression Scale (Beck) and Rape Trauma Symptom Rating Scale (RTSRS). RESULTS: At 24 to 48 hours 136 (46%) of the patients could not be reached. Only 61 (21%) were still tracked at 6 months. Loss to follow-up at 1 month accurately predicted loss to follow-up at 6 months in 209 (98%) of 214 patients. For tracked patients the STAI-Y and Beck scores improved over 6 months. These scores at 1 week did not predict follow-up status at 6 months, but the numbers were small. Subjects with a higher RTSRS score at 24 to 48 hours were most likely to remain tracked throughout the 6 months. CONCLUSIONS: Decisions regarding how vigorously to track patients with a complaint of sexual assault can tentatively be based on the characteristics of the victim and of the assault. We hypothesize that the characteristics predicting loss to follow-up include denial and avoidance behaviour, lack of a telephone number or forwarding address, history of a psychiatric condition, a disability (e.g., deafness), characterization as a "street person," a high degree of violence or injury in the assault, and threat by the assailant. Although a predictive model requires further data, crisis intervention services in an emergency department are essential, given the large number of patients lost to follow-up.     

Haptoglobin-alpha subunit as potential serum biomarker in ovarian cancer: identification and characterization using proteomic profiling and mass spectrometry.

PURPOSE: The objective of this study was to identify and characterize new serum biomarkers in ovarian cancer patients using mass spectrometric protein profiling and specific immunological assays. Experimental Design: Serum samples from 80 cancer patients and 91 healthy women were analyzed by surface enhanced laser desorption and ionization-mass spectrometry (MS) profiling. A candidate biomarker was purified by affinity chromatography, and its sequence was determined by liquid chromatography-tandem MS. An antibody was generated from the synthesized peptide for quantitative validation in the cases and controls. CA125 was determined and compared with the same set of specimens. RESULTS: Using surface enhanced laser desorption and ionization, we found a serum biomarker at approximately 11700 Da, which had peak intensity significantly higher in cases (1.366) compared with controls (0.208, P = 0.002), and subsequently identified this as the alpha chain of haptoglobin. ELISA indicated that Hp-alpha was 相似文献