Spinal cord injury and quality of life measures: a review of instrument psychometric quality.

INTRODUCTION: Quality of life (QOL) is often considered the primary endpoint in research, clinical medicine, and health promotion when impairments are incurable or insufficiently understood. For spinal cord injured (SCI) persons extended life spans and the need for life-long follow-up make it important to expand the outcome parameters of medical care and health services to include QOL measures. STUDY DESIGN: Review. OBJECTIVES: The aim of this study was to evaluate QOL research in SCI persons from the perspective of current criteria for instrument psychometric quality developed by Medical Outcomes Trust (MOT). METHODS: Relevant articles were extracted from the Medline, Cinahl, and PsycLit databases for approximately a recent 30-year period (1966 - 1999). The keyword 'spinal cord injuries' was cross-indexed with 'quality of life', 'personal satisfaction' and 'life satisfaction'. A total of 105 articles were identified and 46 met our inclusion criteria: (a) report of original research; (b) evaluation of QOL by self-report questionnaires or scales; and (c) publication in English. RESULTS: The quality of the research designs varied widely. Most of studies were cross-sectional with limited study populations. The number of instruments or different combinations of instruments nearly equalled the number of studies conducted. Most questionnaires were condition-specific and only used by the developers. The variety of instruments and the diversity of their core content made results difficult to compare, and evaluations and conclusions unpredictable and sometimes contradictory. The low psychometric standard of many instruments used further aggravates the interpretation of results. CONCLUSION: To improve future research in special populations such as the SCI, the MOT criteria for review of QOL instruments should be further disseminated and applied to reach desirable consensus of a limited number of standardised generic and condition-specific QOL measures.

Prognostic factors in resectable pancreatic cancer: p53 and bcl-2.

The p53 tumor suppressor gene and the Bcl-2 proto-oncogene regulate cell cycle progression and apoptosis. We evaluated the expression of these molecular markers with standard pathologic prognostic variables in patients who received multimodality therapy for resectable adenocarcinoma of the pancreas to study the effect of p53 and Bcl-2 on survival duration. Immunohistochemical staining of archival material was performed to determine levels of expression of p53 and Bcl-2 proteins in 70 patients with adenocarcinoma of pancreatic origin. All patients underwent a potentially curative pancreaticoduodenectomy and standardized pathologic analysis of resected specimens. Potential pathologic and molecular prognostic variables were assessed for their effect on survival duration. Nuclear staining for p53 was observed in 33 (47%) of 70 specimens. Immunostaining for Bcl-2 was observed in 23 specimens (33%). A trend toward improved survival duration was seen in patients whose tumors stained positive for either p53 or Bcl-2. Negative staining for both markers predicted short survival (P = 0.01). By univariate and multivariate analyses, no single pathologic factor was associated with survival duration. Immunohistochemical staging using both p53 and Bcl-2 significantly predicted survival duration by univariate and multivariate analysis; patients whose tumors stained positively for p53 and/or overexpressed Bcl-2 had a significantly longer survival than those whose tumors stained negative for both proteins.

Cancer vaccines. Part 2.

Cancer vaccines are being widely studied for the purpose of immune modulation and subsequent antitumor effects. This article cites only a few examples of the many studies underway. Many vaccines have shown efficacy in eliciting systemic responses with minimal toxicities. The use of vaccines as a modality of cancer therapy in combination with chemotherapy, surgery, and radiation therapy is also being investigated. Although the routine use of approved vaccines is still a goal for the future, instituting this fourth modality of cancer therapy is not too distant. Phase III trials with both melanoma and colon cancer vaccines have been completed. Synthetic carbohydrate antigen vaccines have shown efficacy in several tumor types during Phase II trials and are also generating enthusiasm. The potential impact of vaccine therapy on the profession of pharmacy may involve patient counseling regarding management of side effects and possibly also dispensing of vaccine therapy products to patients directly for home administration. As ambulatory sites open in conjunction with pharmacy services and pharmacists obtain prescribing authority, pharmacists' active involvement in vaccine counseling and administration seems likely.

Cancer vaccines (1).

Several cancer vaccines are in various phases of clinical research. As vaccine therapy evolves, this method of treating and/or preventing cancer will become more common. Part 2 of this column will describe some of the current vaccine studies and where vaccine therapy may be headed in the future.

Influence of bovine LH tracer quality on levels of LH in GnRH-treated cows.

Chromatography of 125I-bovine LH (LER-1716-2 and USDA-I-1) by means of anion exchange high performance liquid chromatography (HPLC) revealed two main peaks of radioactivity regardless as to whether or not the tracer was initially purified on cellulose CF11. The content of radioactivity in the first peak tended to increase as the storage time of the bLH preparation, either before or after iodination, increased. The first peak of radioactivity after HPLC fractionation either with or without cellulose adsorption consisted of material with low binding ability to bLH antiserum (6.9% +/- 0.5 and 13.0% +/- 1.0, respectively) and high binding ability to ovine LH alpha antiserum (51.0% +/- 2.7 and 35.2% +/- 3.6, respectively). The average ratio of alpha-subunit immuno-reactivity to 125I-bLH immunoreactivity in this material was 7.4 +/- 0.1 and 2.7 +/- 0.2, respectively (P less than 0.001). Peaks in 125I-bLH radioactivity and 125I-bLH immunoreactivity had different elution times. Radioimmunoassays with tracers obtained from fractions derived from the first radioactive peak after HPLC chromatography (i.e. 125I-bLH-LER-1716-2) both with and without cellulose adsorption, yielded significantly lower mean plasma LH levels in GnRH-treated cows compared with the control tracer routinely purified only on cellulose CF11 (e.g. 5.7 vs. 8.2 micrograms/; 4.6 vs. 8.2 micrograms/l). Plasma LH levels in GnRH-treated cows were significantly (P less than 0.001) lower as measured by radioimmunoassay utilizing 125I-USDA-blH-I-1 tracers than by radioimmunoassays utilizing 125I-blH-LER-1716-2 tracers (i.e. either Y = 0.17 + 0.75X or Y = 1.18 + 0.60X).

Human testis cytosol and ovarian follicular fluid contain high amounts of interleukin-1-like factor(s).

Human testicular cytosol and ovarian follicular fluid were analyzed for the presence of interleukin-1 (IL-1)-like factors. Both the follicular fluid and testis cytosol preparations exhibited significant IL-1-like activity as determined by the murine thymocyte proliferation bioassay. The dose-response lines obtained with the gonadal preparations were parallel to each other and to those obtained with monocyte-derived IL-1 and the activity of the gonadal IL-1 could be neutralized by specific IL-1 antibodies. After gel chromatography of human follicular fluid (hFF) and human testis cytosol (hTC) proteins, IL-1 activity was found in the molecular weight region between 30 and 50 kilodaltons (kDa). Chromatofocusing of IL-1 from hFF and hTC revealed that the major part of IL-1 in both cases exhibited similar charge properties (pI less than 6.0). However, two extra peaks (pI 7.0 and greater than 9.0, respectively) were observed in hFF preparations. After isoelectrofocusing (IEF), IL-1 activity of hFF was also found in two different pH regions; a broad area of activity was localized between pH 5.5 and 7.0, while a sharp peak was observed with an approximate pI value of 9.5. Re-chromatofocusing or IEF of alkaline IL-1-like activity resulted in a heterogeneous profile of IL-1-like activity suggesting that the alkaline material may represent either a precursor or an aggregated form of the acidic IL-1. None of the IL-1 peaks obtained from hFF or hTC exhibited IL-2 activity as assessed in a specific IL-2 bioassay. The results of the present study indicate that both gonads may produce high amounts of IL-1-like factor(s) which might play a regulatory role in normal gonadal function.

Characterization of a factor from human ovarian follicular fluid which stimulates Leydig cell testosterone production.

A factor from human ovarian follicular fluid (hFF) has been characterized which stimulates testosterone production of human, rat, mouse and hamster Leydig cells. hFF was obtained from women participating in an in vitro fertilization programme. Basal and hCG stimulated testosterone production of rat interstitial cells, and Percoll purified Leydig cells were significantly stimulated by hFF. The steroidogenic response of the cells was 3-5 fold higher than that obtained after stimulation with maximal doses of hCG. A serum pool from the same patients was found to be about 30 times less potent than hFF in stimulating steroidogenesis. The stimulatory activity was retained after precipitation with ammonium sulphate and dialysis. Precipitation with ethanol, ether and acetone resulted in a partial loss of activity, whereas extraction with charcoal or heating at 100 degrees C for 10 min resulted in significant loss of activity. When hFF was fractionated by gel chromatography, the stimulatory activity was eluted in a molecular weight region between 30 and 50 kD. The stimulatory factor was further purified by chromatofocusing and was eluted as a homogeneous peak with an isoelectric point between 8.8 and 9.5. The SDS-PAGE analysis of these fractions, however, revealed that the active substance was not homogeneous. The purified factor was immunologically distinct from hCG and hLH. These studies demonstrate for the first time the presence of a factor in the hFF which may potentiate the action of LH in the ovary.

Characterization of a thermostable LH-immunoreactive material from bovine pituitary gland.

A thermostable peptide, immunologically similar to the beta-subunit of ovine lutropin, was isolated from a heated extract of bovine pituitary glands. The relative molecular mass of the peptide as well as its amino acid composition differed significantly from the lutropin subunits. Antibodies were raised to a preparation of this peptide.

Evaluation of several strategies for preparing a bovine gonadotropin-like peptide using isotachophoresis, isoelectrofocusing and high-performance liquid chromatography.

Several strategies for preparing a gonadotropin-like, thermostable peptide from the bovine adenohypophysis were compared. Initially, we extracted bovine pituitaries, in the form of an acetone powder, with acetic acid and water. Using one strategy, we isolated the peptide from the crude extract by gel filtration, isotachophoresis, and isoelectrofocusing. The yield was ca. 50 micrograms of peptide from 100 pituitaries. Using another strategy, we isolated the peptide from the crude extract by precipitating the active material with ethanol followed by high-performance liquid chromatography (HPLC). The yield was ca. 500 micrograms of peptide from 100 pituitaries. Using analytical HPLC, we found that material obtained using the different strategies gave similar results. The HPLC route was, however, more efficient and faster than the other routes, and we recommend it for preparing this gonadotropin-like peptide.

Pattern of immunoreactivity after reverse-phase high performance liquid chromatography of ovine lutropin at different pH.

Unlabelled and radioiodinated ovine lutropin (oLH) was fractionated using reverse-phase high pressure liquid chromatography, employing a 5 micron Spherisorb C18 column. Following chromatography of unlabelled oLH at pH 3.3, 4.3 and 5.3, all eluted fractions were tested by radioimmunoassay of oLH, oLH alpha and oLH beta. Regardless of pH, the material corresponding to the first peak contained only alpha-subunit immunoreactivity. With increasing pH, the oLH alpha, oLH and oLH beta immunoreactivity separated into two groups of fractions. The retention times of the radioiodinated alpha- and beta-subunits of oLH corresponded to those of the first (descending part) and last peaks from unlabelled oLH, respectively. Following chromatography of radioiodinated oLH at pH 3.3, 5.3 and 6.5, all eluted fractions were analyzed using antiserum against either alpha- or beta-subunits of oLH. At pH 3.3 two radioactive peaks were detected: the first corresponded to the fraction with maximum binding to alpha-subunit antiserum, and the second corresponded to the fraction with maximum binding to beta-subunit antiserum. At pH 5.3 and 6.5, maximum radioactivity occurred in conjunction with maximum binding to both antisera. A free alpha-subunit in the radioiodinated oLH was even detected after chromatography at pH 6.5.

A gonadotropin-like thermostable peptide, prepared from bovine anterior pituitary, inducing spermiation in the frog Rana esculenta (L.) and binding to a rat ovarian FSH receptor.

A thermostable peptide, inducing sperm release in Rana esculenta L. and having immunological properties which resemble those of the gonadotropins but nonidentical with any one of the gonadotropins or their subunits, has been prepared from pars distalis of bovine anterior pituitaries by means of acetic acid extraction, heating, ethanol precipitation, and reverse-phase high-performance liquid chromatography (HPLC). During the purification, the biological activity was regularly followed by means of the potency of collected fractions to induce sperm release in frogs. Using HPLC (5 micron C18 silica), the activity was eluted with 38% of acetonitrile:water:trifluoroacetic acid (80:19.5:0.5) and 62% of 0.5% trifluoroacetic acid, pH 3.3. The active principle was also found to bind to a rat ovarian follitropin (FSH) receptor. In contrast, bovine FSH and LH treated identically to the peptide lost all such affinity, indicating that the peptide is not created from either of these during the purification procedure. Further, the peptide was, like FSH, also shown to stimulate aromatase activity in intact Sertoli cells from immature male rats in vitro.

Subunits of bovine lutropin. Hormonal and immunological activity after separation with reversed-phase high-performance liquid chromatography.

By means of reversed-phase high-performance liquid chromatography, we have fractionated bovine lutropin (LH) standard preparations. The highly purified NIAMDD-bLH-4 was fractionated into two components, while the less pure NIH-LH-B9 revealed three distinct peaks. The eluted material was further characterized by in vitro bioassay and by homologous radioimmunoassay for bovine LH, ovine LH-alpha and ovine LH-beta subunits. The material with the shortest retention time possessed almost no LH-activity and showed a displacement curve nearly identical with that of the ovine LH-alpha subunit. The material corresponding to the second peak exhibited 6% of the original LH-activity, and its immunoreactivity was equal to that of the ovine LH-beta subunit. Furthermore, the fractions supposed to contain the alpha and the beta subunits were rechromatographed and their aminoacid contents analyzed. The results show close similarities between the rechromatographed fractions and the pure subunits.