C-reactive protein mediates the solubilization of nuclear DNA by complement in vitro.

We have studied the interaction of C-reactive protein (CRP)-chromatin complexes with serum. The amount of chromatin solubilized by serum is directly proportional to the amount of CRP present. Serum minus C3 did not appreciably solubilize chromatin within the time allowed in these experiments regardless of the amount of CRP present. This indicates that, in addition to CRP, complement is critical to the solubilization process. Studies using genetically C2-deficient serum and purified C2 indicate that the classical complement pathway is primarily involved in the solubilization, however, there may be minor involvement by the alternative pathway. We used an enzyme-linked immunosorbent assay to determine the amounts of CRP in plasma from eight patients with systemic lupus erythematosus; two of the eight had levels of CRP far lower than previously reported for normal individuals, and an additional sample had antibodies reactive with CRP. Together, these results suggest that one of the functions of CRP is to mediate the removal of exposed nuclear DNA by complement-dependent solubilization of chromatin. A defect in this mechanism could (a) facilitate the production of antibodies against chromatin components exposed due to tissue damage or (b) contribute to immune complexes containing the chromatin components released from damaged tissue because they are not rapidly cleared.

Vasostatin, a calreticulin fragment, inhibits angiogenesis and suppresses tumor growth.

An endothelial cell inhibitor was purified from supernatant of an Epstein-Barr virus-immortalized cell line and identified as fragments of calreticulin. The purified recombinant NH2-terminal domain of calreticulin (amino acids 1-180) inhibited the proliferation of endothelial cells, but not cells of other lineages, and suppressed angiogenesis in vivo. We have named this NH2-terminal domain of calreticulin vasostatin. When inoculated into athymic mice, vasostatin significantly reduced growth of human Burkitt lymphoma and human colon carcinoma. Compared with other inhibitors of angiogenesis, vasostatin is a small, soluble, and stable molecule that is easy to produce and deliver. As an angiogenesis inhibitor that specifically targets proliferating endothelial cells, vasostatin has a unique potential for cancer treatment.

Communication of adenomyosis with the endometrial cavity: visualization with saline contrast sonohysterography.

We report four cases of a finding of communication between the endometrial cavity and adenomyotic lesions observed during saline contrast sonohysterography. In each case there was a saline-filled defect extending from the endometrial cavity into the myometrium in the region of previously suspected adenomyosis. We believe this finding represents the sonohysterographic correlate of endometrium invading the myometrium, as has been described histologically.

Monocyte-derived human B-cell growth factor identified as interferon-beta 2 (BSF-2, IL-6).

Soluble products of either Epstein-Barr virus (EBV)-infected B cells or activated monocytes promote the proliferation of EBV-infected B cells and permit their growth at low cell densities. This suggests that growth factors are important for B-cell immortalization by EBV. In this study, a monocyte-derived factor that promotes the growth of EBV-infected b cells was purified and identified as interferon-beta 2 (IFN-beta 2), which is also known as 26-kilodalton protein, B-cell differentiation factor (BSF-2), and interleukin-6 (IL-6). The purified protein has a specific activity of approximately 4 X 10(7) units per milligram of protein in assays of B-cell growth. Thus, IFN-beta 2/BSF-2 is a B-cell growth factor that promotes the proliferation of human B cells infected with EBV.

Meta-analysis using individual patient data from randomised trials to assess the effectiveness of laparoscopic uterosacral nerve ablation in the treatment of chronic pelvic pain: a proposed protocol.

BACKGROUND: Currently, there are a number of clinical trials, but no international collaboration for collating research on effectiveness of laparoscopic uterosacral nerve ablation (LUNA) for alleviating chronic pelvic pain. OBJECTIVE: Meta-analysis was used by collecting individual patient data (IPD) from the existing trials, to provide a comprehensive assessment of the effectiveness of LUNA that will be generalisable in various clinical contexts. METHODS: IPD will be sought and collected from all relevant (both already finished and continuing) randomised trials identified through previous systematic reviews. After obtaining raw data and cleaning the database, analysis will be of all patients ever randomised based on the intention-to-treat principle using endpoints measured at 12 months following randomisation. PROPOSAL: We will update searches, contact all authors, obtain data in whatever form it can be provided, build a single database, produce results for individual studies, have them verified by original authors, explore of any heterogeneity and reasons behind it and finally pool all raw data in to a meta-analysis using appropriate statistical methods. The project will test the effectiveness of LUNA for women with chronic pelvic pain. It will also motivate collaborating primary investigators to undertake new primary studies to corroborate or improve upon the conclusions derived from the retrospective analysis.

Obstipation as a paraneoplastic presentation of small cell lung cancer: case report and literature review.

Paraneoplastic symptoms caused by abnormal gastrointestinal motility may be the initial manifestation of small cell lung cancer (SCLC). We report a case of a 63-year-old woman who presented with progressive constipation culminating in obstipation, and associated symptoms of more widespread dysmotility. A paraneoplastic syndrome was suspected. The only abnormality on chest computed tomography was a minimally enlarged paratracheal lymph node. Positron emission tomography demonstrated increased activity in the lymph node. The antinuclear neuronal antibody titer was elevated. Bronchoscopy with transtracheal biopsy confirmed the diagnosis of SCLC. One year after diagnosis, the patient had progressive symptoms of intestinal obstruction, and ultimately feculent vomiting. On abdominal radiography, colonic sitz markers ingested a year earlier were in virtually the same positions as after ingestion. Palliative colectomy with ileostomy was performed. The myenteric plexus in the terminal ileum and colon showed infiltration by a mixture of B-cell and T-cell lymphocytes and plasma cells, and no gross neuronal abnormalities. We review the clinical and pathologic features, clinical course, and management of paraneoplastic pseudoobstruction.

Evidence for a role of haloperidol-sensitive sigma-'opiate' receptors in the motor effects of antipsychotic drugs.

Haloperidol exhibits a high affinity for a subclass of sigma- "opiate" binding sites which have a unique anatomic distribution and a unique drug selectivity pattern. These binding sites differ from phencyclidine-sensitive sigma-receptors and are found in many brain areas involved in the control of movement. 1,3-Di-o-tolylguanidine (DTG), a highly selective ligand for the haloperidol-sensitive sigma-receptor, produced marked dystonia in rats after microinjection into the red nucleus, a motor area rich in this receptor. Haloperidol and another sigma-ligand [(+)-SKF 10,047] produced similar effects. On the other hand, clozapine, an antipsychotic drug which fails to bind to sigma-receptors and fails to induce movement disorders in humans, failed to induce these dystonic reactions in rats. Phencyclidine was also without effect, as were injections of the active compounds in sites distant to the red nucleus. Microinjections of DTG in the substantia nigra produced vigorous contralateral circling behavior at extremely low doses. These findings suggest that sigma-binding sites represent biologically functional receptors that are active in the neural control of movement. Since haloperidol (and many other antipsychotic drugs) exhibit an affinity for sigma-receptors which is at least equal to its affinity for dopamine receptors, these data raise the further possibility that sigma-receptors are involved in the motor side effects of antipsychotic drugs.

Cybernetic model of the growth dynamics of Saccharomyces cerevisiae in batch and continuous cultures.

Growth of Saccharomyces cerevisiae on glucose in aerobic batch culture follows the well-documented diauxic pattern of completely fermenting glucose to ethanol during the first exponential growth phase, followed by an intermediate lag phase and a second exponential growth phase consuming ethanol. In continuous cultures over a range of intermediate dilution rates, the yeast bioreactor exhibits sustained oscillations in all the measured concentrations, such as cell mass, glucose, ethanol, and dissolved oxygen, the amounts of intracellular storage carbohydrates, such as glycogen and trehalose, the fraction of budded cells as well as the culture pH. We present here a structured, unsegregated model for the yeast growth dynamics developed from the 'cybernetic' modeling framework, to simulate the dynamic competition between all the available metabolic pathways. This cybernetic model accurately predicts all the key experimentally observed aspects: (i) in batch cultures, duration of the intermediate lag phase, sequential production and consumption of ethanol, and the dynamics of the gaseous exchange rates of oxygen and carbon dioxide; and (ii) in continuous cultures, the spontaneous generation of oscillations as well as the variations in period and amplitude of oscillations when the dilution rate or agitatin rate are changed.

Laser laparoscopy for endometriosis and endometriotic cysts.

BACKGROUND: Endometriosis is a common and debilitating condition involving women during their reproductive years. It is characterized by the occurrence of endometrial glands and stroma outside the uterine cavity. Presenting symptoms include chronic nonmenstrual pelvic pain, dysmenorrhea, dyspareunia, and subfertility. The condition is diagnosed at laparoscopy, and operative laparoscopic surgery for endometriosis is also possible. METHODS: This article critically evaluates the evidence for the laparoscopic management of endometriosis and endometriotic cysts. It focuses on laser laparoscopy and reviews the contribution made by the Minimal Access Therapy Training Unit, Guildford, UK, to the treatment of this condition. RESULTS: Few randomized controlled trials have been undertaken to evaluate the surgical management of endometriosis. The studies that have been done show that laparoscopic surgery, including laser laparoscopy, is effective in the management of painful symptoms and subfertility and preventing cyst recurrence. Several of the landmark studies in this area have been carried out in Guildford. CONCLUSION: Laparoscopic surgery is the treatment of choice for patients with endometriosis and endometriotic cysts.

Interpretation of biopsy findings in the transplant liver.

With several thousand liver transplants being performed each year and many patients being managed in their local medical centers, much of the interpretation of transplant liver biopsy specimens has moved from the transplant hospital to the community setting. This article discusses both typical and more peculiar changes that occur in the transplant liver biopsy specimen. Accurate interpretation requires clear knowledge of these possible changes as well as knowledge of clinical data, such as time elapsed since transplantation and the patient's primary disease.

Dyspareunia: three case reports.

Dyspareunia, a symptom rather than a diagnosis, is defined as pain experienced by a woman during intercourse. This article discusses how to elicit an accurate sexual history and lists 12 common causes of dyspareunia. Three case reports from the authors' practices will be used to describe the diagnosis and treatment of women with vulvar vestibulitis, hymenal strands, and vaginismus.

Long-term follow-up of a controlled trial of laser laparoscopy for pelvic pain.

BACKGROUND AND OBJECTIVES: The purpose of this study was to assess the long-term efficacy of laparoscopic laser surgery in the treatment of painful pelvic endometriosis. METHODS: We conducted a long-term follow-up of 56 patients who had participated in a randomized, double-blind controlled study at a tertiary referral center for the laparoscopic treatment of endometriosis. The patients had pelvic pain, minimal-to-moderate endometriosis, and underwent laser laparoscopy. We asked patients whether they had now achieved satisfactory symptom relief or whether they had received any further medical intervention for their endometriosis. The main outcome measure was continued symptom relief after treatment and subsequent medical history. RESULTS: Of the original 56 patients, we were able to contact 38 (67.9%). The mean (range) time since operation was 73 months. Painful symptoms had recurred in 28/38 (73.7%) patients at some point since their operation. The median (range) time for recurrence was 19.7 (5-60) months. At the time of follow-up, satisfactory symptom relief was reported in 21/38 (55.3%) patients. The remaining 17/38 (44.7%) patients continued to experience painful symptoms, and eight eventually had a hysterectomy. CONCLUSIONS: This study suggests that operative laparoscopy can have long-term benefits for the majority of women with pelvic pain due to endometriosis, but because of the small numbers, this study lacks the power to demonstrate this conclusively.

Expanding the praxis debate: contributions to clinical inquiry.

Nursing science continues to debate the adequacy of various philosophic paradigms for their ability to forward the discipline. Nursing must embrace multiple paradigms, methodologies, and their philosophic assumptions to adequately address the complex and multifaceted human phenomena that is the focus of clinical inquiry in nursing. This article examines the differences in interpretive and critical approaches to clinical inquiry relative to praxis, expanding how praxis can be used to inform nursing practice. Differences in the nature of knowledge, goals of inquiry, and claims to praxis between the interpretive and critical traditions are discussed. Praxis, realized through clinical inquiry in both the interpretive and the critical paradigms, may contribute important pieces of the puzzle to improve the human condition. Expanding the praxis debate challenges nurses to consider the emancipatory possibilities of clinical inquiry within both interpretive and clinical paradigms.

Selecting doctoral programs in nursing: resources for students and faculty.

Sixty-nine doctoral programs in nursing are currently offered at 75 universities in the United States. Resources to assist prospective doctoral students in making decisions concerning successfully pursuing doctoral education are collected and organized by a variety of nursing organizations. Nurses in academic settings access these lists and specialty publications through their deans' offices and professional affiliations. Prospective students, on the other hand, are largely employed in clinical settings and are often unaware of the existence of this information, which could assist them in their decisions. The purpose of this article is to provide prospective doctoral students and the faculty that may advise them with a current information to use in selecting a doctoral program in nursing.

Vulvodynia: diagnostic techniques and treatment modalities.

Vulvodynia is a chronic vulvar discomfort often characterized by the patient's complaint of burning, stinging, irritation, or rawness. Vulvodynia has been recorded for centuries. Successful diagnostic techniques and treatment modalities, however, have come about only in the last decade. An accurate diagnosis is based on an exhaustive history and detailed physical examination. Highly technical and costly diagnostics provide little supplemental information. Differential diagnosis, previously called subsets of vulvodynia, includes infections (Candida, human papillomavirus, and herpes simplex virus), dermatoses (lichen sclerosus and inflammatory dermatoses), vulvar vestibulitis, iatrogenic causes, and dysesthesias (pudendal neuralgia and reflex sympathetic dystrophy). Primary care providers are fully capable of accurately diagnosing and managing vulvodynia patients, relying on subspecialty referral only for surgical intervention in selected cases.

Individual patient data meta-analysis of randomized evidence to assess the effectiveness of laparoscopic uterosacral nerve ablation in chronic pelvic pain.

BACKGROUND: There have been conflicting results in randomized trials of the effects of laparoscopic uterosacral nerve ablation (LUNA) in chronic pelvic pain. Our objective was to perform a meta-analysis using individual patient data (IPD) to provide the most comprehensive and reliable assessment of the effectiveness of LUNA. METHODS: Electronic searches were conducted in the Medline, Embase, PsycInfo and Cochrane Library databases from database inception to August 2009. The reference lists of known relevant papers were searched for any further articles. Randomized trials comparing LUNA with no additional intervention were selected and authors contacted for IPD. Raw data were available from 862 women randomized into five trials. Pain scores were calibrated to a 10-point scale and were analysed using a multilevel model allowing for repeated measures. RESULTS: There was no significant difference between LUNA and No LUNA for the worst pain recorded over a 12 month time period (mean difference 0.25 points in favour of No LUNA on a 0-10 point scale, 95% confidence interval: -0.08 to 0.58; P = 0.1). CONCLUSIONS: LUNA does not result in improved chronic pelvic pain.