Monoclonal antibody technology

The development, production, limitations, and uses of monoclonal antibody (MoAb) technology are presented. The first MoAbs were developed in 1975 using a process whereby the antibody-producing spleen cells of mice that had been immunized against sheep red blood cells were fused with the cells of a mouse myeloma cell line, producing hybridomas. These hybridoma cells are used to produce MoAbs, which are antibodies that will bind to only one specific target site on an antigen. Large quantities of MoAbs are grown, either in cell cultures or in the peritoneum of mice, and harvested. Although large quantities of MoAbs can be produced, these techniques are limited because of the potential for contamination by mouse viruses and the inability of the hybridomas to yield sufficient quantities of MoAbs. MoAbs are currently used in diagnostic techniques, including pregnancy tests and drug assays, as well as in tests for detecting viral and bacterial infections and cancer. MoAbs, coupled with dyes or radioactive isotopes, can be used in imaging techniques. Other possible applications of MoAbs include tissue typing, purification, therapy of cancer and autoimmune diseases, and treatment of drug toxicities. As the use of MoAbs in health care increases, pharmacists will need to have a good understanding of the functions and applications of these agents.     

The effects of reverse sequential anti-androgen therapy (cyproterone acetate and ethinyl estradiol) on hematological parameters

Hematological parameters were studied in female patients receiving reverse-sequential anti-androgen therapy for hirsutism and acne. A significant fall in hemoglobin, total red cell count and packed cell volume occurred after 3-month treatment in 30 patients during the 10-day cyproterone acetate and ethinyl estradiol phase; this change was sustained in 14 patients studied to 12 months. A fall in hemoglobin and packed cell volume alone occurred after 3 months in 31 patients in the ethinyl estradiol phase. Reverse-sequential therapy may influence hemopoiesis by its anti-androgenic action on erythropoiesis, although we found no relationship between changes in hematological parameters and total testosterone levels.     

大丁草中抗菌活性成分的研究Ⅳ

从秋季采收的菊科植物大丁草Gerbera anandria(L.)Sch Bip.全草中共分出十三种成分。本文报道其中三个新化合物的结构鉴定.它们分别是3,8-dihydroxy-4-methoxy-coumarin(ⅪⅩ),3,8-dihydroxy-4-methoxy-2-oxo-2 H-1-benzopyran-5-carboxylic acid(ⅩⅦ),和5,8-dihydroxy-7-(4-hydroxy-5-methyl-coumarin-3-)-coumarin(ⅩⅪ)。     

Results from the International Conference of Experts on Intra-abdominal Hypertension and Abdominal Compartment Syndrome. II. Recommendations

Objective Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) have been increasingly recognized in the critically ill over the past decade. In the absence of consensus definitions and treatment guidelines the diagnosis and management of IAH and ACS remains variable from institution to institution. Design An international consensus group of multidisciplinary critical care specialists convened at the second World Congress on Abdominal Compartment Syndrome to develop practice guidelines for the diagnosis, management, and prevention of IAH and ACS. Methods Prior to the conference the authors developed a blueprint for consensus definitions and treatment guidelines which were refined both during and after the conference. The present article is the second installment of the final report from the 2004 International ACS Consensus Definitions Conference and is endorsed by the World Society of the Abdominal Compartment Syndrome. Results The prevalence and etiological factors for IAH and ACS are reviewed. Evidence-based medicine treatment guidelines are presented to facilitate the diagnosis and management of IAH and ACS. Recommendations to guide future studies are proposed. Conclusions These definitions, guidelines, and recommendations, based upon current best evidence and expert opinion are proposed to assist clinicians in the management of IAH and ACS as well as serve as a reference for future clinical and basic science research.     

Total radical trapping antioxidant potential (TRAP) and exercise

The relationship between physical activity, physical fitness and total radical trapping antioxidant potential (TRAP) was examined in the Northern Ireland Health and Activity Survey. This was a cross-sectional population study (n = 1600) using a two-stage probability sample of the population. TRAP was calculated using the sum of the individual serum antioxidant concentrations (urate, protein thiols, ascorbate, alpha tocopherol and bilirubin) multiplied by their respective stoichiometric values. Physical fitness was determined by estimation of VO2max by extrapolation from submaximal oxygen uptake, and physical activity was recorded by computer-assisted interview. Mean serum TRAP concentrations were significantly higher in males (653 +/- 8.2 mumol/l, mean +/- SEM) compared to females (564 +/- 8.0 mumol/l) (p < 0.0001). Both male and female smokers had significantly lower TRAP values than non-smokers (males p < 0.0001, females p = 0.02). In females, there was a positive relationship of TRAP with age (p < 0.001) and body mass index (p < 0.001) but a negative relationship with physical fitness (p < 0.05). The known beneficial effects of exercise and activity do not appear to be directly mediated through increased antioxidant status.      

Intra-aortic balloon counterpulsation for cardiogenic shock due to cardiac contusion in an elderly trauma patient

Blunt thoracic trauma may cause cardiac contusion and cardiogenic shock resistant to inotropic support. The use of intra-aortic balloon counterpulsation (IABCP) as a mechanical means of augmenting cardiac function following cardiac contusion is rare with case reports largely limited to its use in young trauma patients. We describe the case of a frail, 80-year-old woman who suffered cardiac contusion in a motor vehicle crash. She developed cardiogenic shock with electrocardiograph changes, elevated troponin T and severe global dysfunction on echocardiography. She was successfully managed with invasive monitoring, inotropic support and IABCP. This case provides support for aggressive resuscitation even in the very elderly as recovery from severe cardiac contusion may be possible.     

Hyponatraemic states following 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') ingestion

BACKGROUND: Life-threatening and fatal hyponatraemic complications following ecstasy use have previously been documented. Aim: To define clinical features of hyponatraemia following the ingestion of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy'). DESIGN: Retrospective case series. METHODS: All enquiries to the London centre of the National Poisons Information Service (NPIS) between December 1993 and March 1996 were screened for cases of MDMA use associated with hyponatraemia (serum sodium <130 mmol/l). History of fluid consumption, presenting features and subsequent clinical course were recorded. RESULTS: Seventeen patients, aged 15-26 years, were identified. Serum sodium levels ranged between 107 mmol/l and 128 mmol/l. In six patients, biochemical results were consistent with inappropriate secretion of antidiuretic hormone (SIADH). Analytical confirmation of MDMA ingestion was obtained in 10 patients. Ten patients were known to have ingested a large amount of non-alcoholic or alcoholic fluid. The clinical pattern was remarkably uniform, with initial vomiting and disturbed behaviour, followed in 11 patients by seizures. Drowsiness, a mute state and disorientation were observed for up to 3 days. Two patients died; 14 made a complete recovery. DISCUSSION: MDMA can cause life-threatening hyponatraemic encephalopathy when accompanied by excessive fluid ingestion. The mechanism involves inappropriate secretion of antidiuretic hormone.     

Pattern of emphysema distribution in alpha1-antitrypsin deficiency influences lung function impairment

FEV(1) is fundamental to the diagnosis and staging of chronic obstructive pulmonary disease. In emphysema, airflow obstruction usually coexists with impairment of gas exchange, but discordance is not infrequent. We hypothesized that variations in the distribution of emphysema would be associated with functional differences and therefore account for discordant physiology. We used quantitative computed tomography to assess emphysema severity and distribution in 119 subjects with alpha1-antitrypsin deficiency (PiZ phenotype) and grouped them according to distribution pattern. In the 102 subjects with emphysema, 65 had a predominantly basal pattern ("basal"), but 37 (36%) had greater involvement of the upper regions ("apical"). Subjects from each group were matched for total volume of emphysema and age, and matched pairs analysis was used to relate emphysema distribution to clinical phenotype. Basal distribution was associated with greater impairment of FEV(1) (mean difference, 9.9% predicted; 95% confidence interval, 3.8 to 16.0; p = 0.002) but less impairment of gas exchange (Pa(O(2)) mean difference, 0.5 kPa, 0.03 to 0.1; p = 0.016) and alveolar-arterial oxygen gradient (mean difference, 0.7 kPa; 0.2 to 1.2; p = 0.007) than the apical distribution. Emphysema distribution correlated with physiologic discordance (r = -0.409, p < 0.001). The use of single physiologic parameters as a surrogate measure of emphysema severity may introduce systematic bias in the staging of subjects with emphysema.