Randomised clinical trial: herbal extract HMPL-004 in active ulcerative colitis - a double-blind comparison with sustained release mesalazine.

BACKGROUND: Andrographis paniculata is an herbal mixture used to treat inflammatory diseases. An extract of the herb, HMPL-004, inhibits TNF-α and IL-1ß, and prevents colitis in animal models. AIM: To determine the efficacy and safety of HMPL-004 in patients with mild-to-moderate ulcerative colitis. METHODS: A randomised, double-blind, multicentre, 8-week parallel group study was conducted using HMPL-004 1200 mg/day compared with 4500 mg/day of slow release mesalazine (mesalamine) granules in patients with mild-to-moderately active ulcerative colitis. Disease activity was assessed at baseline and every 2 weeks for clinical response, and at baseline and 8 weeks by colonoscopy. RESULTS: One hundred and twenty patients at five centres in China were randomised and dosed. Clinical remission and response were seen in 21% and 76% of HMPL-004-treated patients, and 16% and 82% of mesalazine-treated patients. By colonoscopy, remission and response were seen in 28% and 74% of HMPL-004-treated patients and 24% and 71% of mesalazine-treated patients, respectively. There was no significant difference between the two treatment groups. CONCLUSION: HMPL-004 may be an efficacious alternative to mesalazine in ulcerative colitis.

Characterization of mitogen-stimulated porcine lymphocytes using a stable fluorescent dye (PKH2) and multicolor flow cytometry.

Stimulation of lymphocyte proliferation using mitogens or specific antigens is a method that is used frequently to assess immune responsiveness. While useful, lymphocyte blastogenesis, or [3H]-thymidine incorporation, provides little information regarding the response of specific subsets to the stimulant. Here, we report that the fluorescent cell membrane probe, PKH2, is a useful tool for measuring the proliferation of porcine lymphocyte subpopulations by utilizing multicolor flow cytometry. For this study, mitogen-induced proliferation of porcine peripheral blood mononuclear cells (PBMCs) was measured using [3H]-thymidine incorporation as well as a flow cytometric-based proliferation assay. From the [3H]-thymidine incorporation data alone, it was observed that PBMC stimulated with either concanavalin A (Con A), phytohemagglutinin (PHA) or pokeweed mitogen (PWM) demonstrated greater proliferation on day 3 than on day 5 of culture. Using the PKH dye and flow cytometric analysis, the responsiveness of specific lymphocyte subsets to mitogen stimulation was detected. The predominant subsets of porcine lymphocytes responding to Con A or PHA stimulation were CD4(+)CD8(+), CD4(-)CD8alpha(hi), CD4(-)CD8alpha(lo) and gammadelta TCR(+) cells. PWM stimulation induced responses by CD4(+)CD8(+), CD4CD8alpha(hi) but not by CD4(-)CD8alpha(lo) or gammadelta TCR(+) cells. Con A stimulation resulted in a sustained proliferation of CD8alpha(hi) cells over the 5-day period while PHA stimulation resulted in proliferation that peaked within the first 3 days. Little or no proliferative responses were detected within the IgM(+) population (e.g. B cells). This is the first study to define the contribution of individual lymphocyte subsets to mitogen-induced proliferation of porcine PBMCs.

Primary care outcomes and provider practice styles.

The purpose of this study was to evaluate change in patient outcomes as a function of practice styles of primary care providers. A prospective, repeated-measures, correlational design was used. Data were collected about (1) providers' self-ratings of practice styles, inclusive of practice model, confidence, autonomy, collaboration, information giving, and job satisfaction, and (2) primary care patients' self-ratings of health status, functional status, information seeking, and satisfaction. When severity and comorbidity were controlled, physicians, nurse practitioners, and physician assistants produced equivalent outcomes; neither practice style nor provider type resulted in differences in health outcomes of primary care patients. Practice style did affect patient satisfaction. Patients were least satisfied with providers who scored high on collaboration and most satisfied with providers who scored low on the practice model. Neither provider type nor interpersonal attributes had an effect on health outcomes; sicker patients got better and healthy patients stayed that way.

Measurement of murine IgE antibody responses to dust mite allergens by in vitro assay.

In an analysis of murine immune responses to the dust mite allergen Der p 1, treatment with purified allergen induced a significant increase in the level of circulating IgE immunoglobulin (from less than 100 ng/ml in normal mice to 1,350 ng/ml in mice receiving the allergen). Even so, specific IgE antibodies binding to purified Der p 1 were not detected in a conventional ELISA, and the major response appeared to be the induction of high titre IgG antibodies. Specific circulating murine IgE antibodies were however detected using the following assay format: murine IgE was captured to anti-murine IgE antibody coated wells; Der p 1 was added and bound by immobilized anti-Der p 1 IgE antibodies; the captured Der p 1 was then detected by the addition of monoclonal IgG antibodies against Der p 1 and these antibodies were measured by the addition of anti-murine IgG antibody-enzyme conjugate with which colour development is produced after substrate addition. This assay establishes a procedure to measure circulating anti-Der p 1 IgE antibodies which are present together with competing high titre IgG anti-Der p 1 antibodies.

Provider satisfaction in army primary care clinics.

The job satisfaction of physicians, nurse practitioners, and physician assistants was assessed during the course of a multicenter study of Army primary care clinics. All providers in nine clinics at three medical centers who were engaged in adult or family care were invited to participate in the study. Questionnaires on job satisfaction and other practice style variables were completed by 26 physicians, 19 nurse practitioners, and 13 physician assistants (46, 76, and 41% of eligible providers, respectively). Analysis revealed a broad range of job satisfaction in the sample. However, average levels of job satisfaction were not significantly different across the three groups of primary care providers. Autonomy and collaboration were significant predictors of job satisfaction. It is clear that changes in health care systems that reduce, or appear to reduce, the primary care provider's autonomy in clinical matters are likely to reduce provider satisfaction as well.

Regulation of the contact sensitivity response to urushiol with anti-urushiol monoclonal antibody ALG 991.

The objective of the studies was to demonstrate that the contact sensitivity (CS) response to poison ivy/oak could be downregulated following treatment with a monoclonal antibody (mAb) reacting with the allergen urushiol. Conjugation of urushiol and its synthetic analogue 3-n-pentadecylcatechol (PDC) to N-acetylcysteine yielded hydrosoluble derivatives which induced humoral immune responses in BALB/c mice. Hybridomas secreting monoclonal antibodies (mAbs) reacting with urushiol and PDC were generated by fusion of B lymphocytes from immunized mice with mouse myeloma P3NS0 cells. The specificity of mAb ALG 991 (IgM isotype) was defined by inhibition of antibody binding by PDC analogues. This demonstrated that mAb ALG 991 reacted with the catechol moiety of urushiol, the region of the allergen being critically important in the induction of contact dermatitis. The CS response to urushiol in BALB/c mice was suppressed by stimulation with mAb ALG 991 and the role of sensitized T cells, including suppressor T cells, has been considered. Suppression of CS was most effective with low doses (1 microg) of mAb incorporated into a vaccine with Freund's adjuvant. This treatment suppressed CS responses in BALB/c mice already sensitized to urushiol.

The relationship between premorbid life-style and wandering behaviors in institutionalized people with dementia.

Forty-nine ambulatory residents participated in a study conducted to determine the relationship between premorbid life-style, work, and ways of handling stress, and wandering in dementia units. The sample consisted of 23 males and 26 females with a mean age of 79. Family members responded to open-ended questionnaires that asked about premorbid leisure activities, hobbies, exercise, stress management, type of employment and social interactions. Activities were ranked according to energy expended on the Metabolic Cost of Activities (MET) Scale. No activity equaled Inactive (0); 1.5-2 METS equaled Mildly Active (1), 2-3 METS equaled Moderately Active (2), and 3-4 METS equaled Very Active (3). Subjects were observed three times for one-hour intervals on each of three shifts (day, evening, night) at randomly selected times to assess wandering behavior. Behavior was logged every five minutes. The subjects' most frequent conditions were awake (21%), alone (20%), and in their own rooms (17%). Twenty-four (50%) of the subjects were observed pacing, and 16 (33%) were agitated/restless at some point in time. Statistical analyses showed no significant correlations between premorbid life-style variable rankings and the amount of time spent standing, walking and pacing. The findings suggest that wandering behavior is not influenced by premorbid life-styles.

Overview of the data collection process.

The data collection plan is a series of well-thought-out strategies to implement the data collection process. The details of the plan are written out on paper. Once the research proposal is approved the data collection plan is implemented. This implementation is the action or doing phase of the study. The aim of this phase is to collect the evidence or data. During implementation, the researcher can experience problems related to people, researcher, institution and events. The data collection process is a time that is very challenging and requires the researcher to use mental and interpersonal skills.

Importance of health and family variables related to quality of life in individuals with uncontrolled seizures.

Approximately 2.5 million Americans are epileptic, and nearly 150,000 new cases are diagnosed in the United States each year. While seizures are the most common physical symptom of epilepsy, treatment must include far more than medical intervention for seizure control. Virtually all aspects of life are affected by the disorder including personal relationships, employment, perception of self and overall quality of life. A literature review indicates that, while progress is being made in identifying variables which impact quality of life, little consensus exists regarding their nature. No two patients are necessarily alike, nor are their methods of dealing with the disorder necessarily the same. Arguments have been posed which state that age of onset is a factor, as is the degree to which seizures can be controlled. This is not to say, however, that effective interventions cannot be developed to assist patients in dealing not only with the physical manifestations of epilepsy but other common related factors as well. The purpose of this study was to identify those variables which impact quality of life for persons with epilepsy, and in light of the findings, to make recommendations for nursing interventions.

A phase II study of effect of addition of trichosanthin to zidovudine in patients with HIV disease and failing antiretroviral agents.

Patients infected with HIV, including those with AIDS-related complex and AIDS, and failing treatment with antiretroviral agents such as zidovudine, have been evaluated following addition of trichosanthin to the antiretroviral agent regimen. This ribosomal inhibitory protein is specifically cytotoxic for HIV-infected macrophages and lymphocytes. Ninety-three patients were treated with trichosanthin, using a schedule of weekly, then monthly, intravenous injections of 1.2 mg of drug in combination with antiretroviral agents, usually zidovudine. Side effects included myalgias, fevers, mild elevation in liver function tests, and mild-moderate anaphylactic reactions, which respond well to therapy with steroids and/or benedryl. Reversible mental status changes were noted in two patients, both receiving concomitant therapy with ddI. Clinical responses to trichosanthin treatment were monitored primarily by changes in laboratory parameters, particularly levels of CD4+ T lymphocytes. In the total population evaluated for efficacy (85 patients) there was a significant increase in CD4+ cell levels after initiation of trichosanthin therapy. A second analysis performed on 72 patients measured the rate of change of CD4+ cells during therapy, using an "area under the curve" analysis. During therapy there was a median increase of 1.2 cells/mm3/month. In patients in the top 25th percentile, this increase was greater than 8.4 cells/mm3/month. In 59 of the 72 patients, responses could also be monitored by comparing the rate of loss of CD4+ cell levels on antiretroviral agents (zidovudine or ddI) alone, during the year prior to initiation of trichosanthin, to the rate of change when trichosanthin was added to the treatment regimen. During the period before trichosanthin treatment (311 +/- 11.7 days) the median loss of CD4+ cells was 6.91 cells/mm3/month. Addition of trichosanthin to the treatment regimen resulted in a median gain of 1.1 CD4+ cells/mm3/month.

Novel antiepileptic drugs: nursing implications.

It has been 14 years since the last AED was placed on the drug market in the United States. This article reviews four novel AEDs that hold promise for treating epilepsy. One drug, felbamate, has recently been released, while the other three are expected to be available within 5 years. Since nurses play a critical role in AED therapy, nursing intervention related to assessment, teaching and emotional support is important in the management of epilepsy.

Suppression of antibody responses to ricin A chain (RTA) by monoclonal anti-RTA antibodies.

Balb/c mice treated with an immunotoxin constructed by conjugation of murine monoclonal antibody 791T/36 via a disulfide linker to ricin A chain generate a pronounced antibody response to peptide epitopes on ricin A chain. Monoclonal anti-RTA antibodies which recognize peptide epitopes have been developed and these have been used to down-regulate anti-RTA antibody responses in 791T/36-RTA immunotoxin-treated Balb/c mice. Of the five MAB tests, two (608/7 and 596/134) proved most effective, inhibiting anti-RTA antibody formation by up to 73%. MAB treatment was effective when initiated up to 3 days after immunotoxin treatment. Pharmacokinetic studies with 791T/36-RTA have shown that the immunotoxin is rapidly eliminated from the circulation, with no more than 4% remaining in blood after 24 hr. It is proposed that the down-regulation of anti-RTA antibodies is effected by MAB interfering with antigen processing.

Neurological reactions in HIV-infected patients treated with trichosanthin.

Trichosanthin is a ribosome-inactivating protein that is being studied as a possible treatment for patients infected with human immunodeficiency virus (HIV). We report the clinical and pathological features in two patients who experienced neurological reactions to trichosanthin. Both patients were neurologically asymptomatic prior to treatment but developed coma and multifocal neurological deficits after treatment. Neuropathological examination revealed regions of severe, multifocal necrosis with histiocytic infiltrates. These reactions to trichosanthin may be mediated by soluble factors released by HIV-infected macrophages.

Effects of an anti-CD5 immunoconjugate (CD5-plus) in recent onset type I diabetes mellitus: a preliminary investigation. The CD5 Diabetes Project Team.

Type-I (insulin-dependent) diabetes mellitus is an immunologically mediated disease that results in destruction of the insulin secreting beta cells of the pancreas. T cells have been implicated in the pathogenesis of this disease. One novel form of anti-T-cell therapy is the immunoconjugate CD5-Plus. This agent is composed of the murine IgG1 monoclonal antibody H65, which is directed toward the CD5+ antigen; and ricin A chain, a ribosomal inhibitor protein. We performed a pilot study to evaluate the safety of the immunoconjugate in subjects with type-I diabetes mellitus. We conducted a dose-escalation study using CD5-Plus given as an intravenous infusion for 5 consecutive days. Fifteen subjects (12 men and 3 women) with a mean age of 26 years, a mean duration of diabetes of 4.8 months, and a minimum stimulated C peptide of 0.3 pmol/mL were entered. Six subjects each were treated at the 0.1 and 0.2 mg/kg/day dosage levels, and three subjects were treated at the 0.33 mg/kg/day dose. Glycemic control was determined monthly by recording the glycohemoglobin, total daily insulin requirements, and fasting blood glucoses. Beta-cell function was measured by determining the C-peptide response to a mixed formula meal (Sustacal) at baseline and at 1,3,6,9, and 12 months after treatment. The area under the curve (AUC) of the C-peptide response was calculated and, to reduce variability, related to that of the same subject at baseline. An analysis of subjects who retained at least 80% of their baseline beta-cell function as measured by the AUC was performed.(ABSTRACT TRUNCATED AT 250 WORDS)

Multiple chemical sensitivities: a practicing clinician's point of view. Clinical and immunologic research findings.

The multiple chemical sensitivities syndrome is a symptom complex characterized by emotional depression, short-term memory loss, acquired intolerance to environmental agents such as aerosolized petrochemicals and foods, and alteration in metabolic rate associated with increased body mass. This syndrome can be caused by multiple etiologic agents. With careful evaluation, it is rare that a causal agent can not be identified in this syndrome. Our treatment regimens include combinations of diet and environment control as well as antiviral, antifungal, and immune modulator therapy. We find that the majority of patients can, through time and appropriate treatment, be restored to a normal and productive lives.

Impact of epilepsy on quality of life.

Epilepsy is a chronic condition with a profound effect on the quality of life. Health, family life, social, community and civic activities, economics and personal development are the major variables associated with quality of life for the person with epilepsy. In this article, a model describing the relationship between these variables and quality of life is presented. This model organizes a comprehensive nursing approach to the patient with epilepsy. A case study analysis approach is used to help further illustrate interactions among the variables. Nursing interventions based upon analysis of the model are suggested.

Phase I trial of H65-RTA immunoconjugate in patients with cutaneous T-cell lymphoma.

H65-RTA is an immunoconjugate that consists of the A chain of ricin (RTA), a ribosomal-inhibiting protein, coupled to a murine monoclonal antibody (H65) directed against the pan-T-cell antigen CD5. The CD5 antigen is heterogeneously expressed on cutaneous T-cell lymphoma tumor cells, but is not expressed on normal cells except lymphocytes. A phase I trial was therefore conducted in which 14 patients with cutaneous T-cell lymphoma progressive on other therapies were treated with up to three cycles of H65-RTA. The maximal tolerated dose (MTD) of H65-RTA was 0.33 mg/kg/d administered intravenously for 10 days as defined by dyspnea at rest at higher doses. Other reversible side effects included myalgia, mild hypoalbuminemia with weight gain, pedal edema, fatigue, fevers, and chills. Six patients received more than one cycle of H65-RTA without increased side effects compared with the first cycle. Pharmacokinetic analysis showed that peak serum drug levels were dose-dependent, and ranged from 1.13 to 5.56 micrograms/mL, with a terminal half-life ranging from 1.0 to 2.9 hours. The development of antibodies against the immunoconjugate was associated with a lower peak drug level, but not with enhanced side effects. Partial responses lasting from 3 to 8 months were documented in four patients. Three of the responding patients received more than one cycle of H65-RTA in the presence of anti-immunoconjugate antibodies. The results from this phase I trial suggest that H65-RTA is an active drug in the treatment of cutaneous T-cell lymphoma. The immunoconjugate may be safely administered repeatedly, even in the presence of anti-immunoconjugate antibodies, with responses noted. Additional studies at the MTD are needed to define the response rate in this disease.