Minactivin expression in human monocyte and macrophage populations

Adherent monolayer cultures of human blood monocytes, peritoneal macrophages, bone marrow macrophages, and colonic mucosa macrophages were examined for their ability to produce and secrete minactivin, a specific inactivator of urokinase-type plasminogen activator. All except colonic mucosa macrophages produced and secreted appreciable amounts of minactivin, but only blood monocytes were stimulated by muramyl dipeptide (adjuvant peptide) to increase production. The minactivin from each of these populations could be shown to preferentially inhibit urokinase-type plasminogen activator and not trypsin, plasmin, or "tissue"-type plasminogen activator (HPA66). A plasminogen-activating enzyme present in monocyte cultures appeared unaffected by the presence of minactivin and could be shown to be regulated independently by dexamethasone.     

Androgen inhibition of follicle-stimulating hormone-stimulated luteinizing hormone receptor formation in cultured rat granulosa cells

Since LH receptors are decreased in atretic follicles known to contain high androgen levels, we have studied the androgen modulation of LH receptor formation in vitro. Granulosa cells from hypophysectomized, diethylstilbestrol-treated rats were cultured for 3 days with FSH in the presence or absence of nonaromatizable androgens, dihydrotestosterone and 5 alpha-androstane-3 alpha, 17 beta-diol, or a synthetic androgen, R1881 (17 beta-hydroxy-17 alpha-methyl-4,9,11-estratrien-3-one). FSH increased LH receptor content in granulosa cells, while concomitant androgen treatment decreased LH receptor content in a dose- and time-dependent manner, without changing the equilibrium dissociation constant (Kd) for human CG. R1881 (10(-7) M), dihydrotestosterone (10(-6) M), and 5 alpha-androstane-3 alpha, 17 beta-diol (10(-6) M) inhibited LH receptor content by 68%, 65%, and 65%, respectively. Similar to earlier findings, these androgens enhanced FSH-stimulated progesterone biosynthesis and aromatase activity in the same cells. To study their LH responsiveness, androgen-treated cells were washed and reincubated for 2 more days with or without LH. Although basal progesterone production was elevated by R1881 pretreatment, the androgen-pretreated cells were less responsive to LH. Treatment with cyanoketone, an inhibitor of 3 beta-hydroxysteroid dehydrogenase, did not alter the inhibitory effects of R1881 on LH receptors, indicating that the androgen action is not mediated by endogenous progestins. Furthermore, R1881 inhibited the stimulation of LH receptor formation by forskolin, cholera toxin, and 8-bromo-cAMP, suggesting that androgens may inhibit LH receptor induction by affecting post-cAMP events. Estrogen treatment enhanced the FSH induction of LH receptor content, while concomitant addition of R1881 also suppressed the estrogen action. Thus, androgens inhibit FSH-induced functional LH receptors in cultured rat granulosa cells. The androgen effect is exerted, at least partially, at post-cAMP sites and is independent of changes in progestin biosynthesis.     

In vitro susceptibilities of Escherichia coli isolated from patients with intra-abdominal infections worldwide in 2002-2004: results from SMART (Study for Monitoring Antimicrobial Resistance Trends)

BACKGROUND: Since 2002, the worldwide Study for Monitoring Antimicrobial Resistance Trends (SMART) has tracked resistance patterns among aerobic and facultative gram-negative bacilli isolated from patients with intra-abdominal infections. Escherichia coli has been by far the most frequently isolated species. METHODS: Antimicrobial susceptibilities for consecutive non-duplicate isolates of aerobic and facultative gram-negative bacilli recovered from intra-abdominal infections were determined by standard broth microdilution techniques. A subanalysis was performed for E. coli isolates from the first three years of the study. RESULTS: A total of 7,002 E. coli isolates were recovered, most commonly from the peritoneal cavity followed by the biliary tract. Susceptibility rates to the 12 antimicrobial agents tested differed among geographic regions, with isolates from Asia/Pacific generally having the highest resistance rates. Overall, extended-spectrum beta-lactamase (ESBL)-producers had a more antibiotic-resistant profile than non-ESBL-producers but usually were susceptible to the carbapenems and amikacin. Community-acquired E. coli strains comprised slightly more than one-half of the isolates and were susceptible to the agents tested more frequently than were hospital-acquired E. coli. CONCLUSIONS: The prevalence of antimicrobial resistance among E. coli isolated from intraabdominal infections is not inconsequential, especially in the Asia/Pacific region. The carbapenems and amikacin were consistently active in vitro against E. coli isolates worldwide, including ESBL-producers.     

Clinics in diagnostic imaging (165)

Oesophageal rupture is a life-threatening complication of balloon tamponade for bleeding oesophageal varices. We herein describe the clinical course and imaging findings in a 33-year-old Indian man who had a Sengstaken-Blakemore (SB) tube inserted for uncontrolled haematemesis, which was unfortunately complicated by malposition of the gastric balloon with resultant oesophageal rupture. The inflated SB tube gastric balloon was visualised within the right hemithorax on chest radiography after the SB tube insertion. Further evaluation of the thorax on computed tomography confirmed the diagnosis of oesophageal rupture associated with right-sided haemopneumothorax. It is crucial for both the referring clinician and reporting radiologist to recognise early the imaging features of an incorrectly positioned SB tube gastric balloon, so as to ensure prompt intervention and a reduction in patient morbidity and mortality.     

恶性肿瘤靶向给药的临床应用

恶性肿瘤靶向给药是指利用具有一定肿瘤靶向性的导向分子（载体）携带治疗肿瘤的药物,在肿瘤局部选择性杀伤肿瘤细胞（及转移的肿瘤细胞）,以避免药物的全身毒副作用,提高疗效的一种治疗方法．由于抗癌药物在杀伤肿瘤细胞的同时也杀伤正常细胞,增加了全身的毒副作用．因此,近几年来,对恶性肿瘤靶向治疗的研究突飞猛进,发展了人源性抗HER-2mAb、依西美坦、放射性核素、     

Effectiveness of diclofenac versus paracetamol in knee osteoarthritis: a randomised controlled trial in primary care

Background

The effectiveness of diclofenac versus paracetamol in primary care patients with pain caused by knee osteoarthritis is unclear.

Aim

To assess the effectiveness of diclofenac compared with paracetamol over a period of 2, 4, and 12 weeks in patients with knee osteoarthritis.

Design and setting

Randomised controlled trial in general practice.

Method

There were 104 patients included in the study, they were aged ≥45 years consulting their GP with knee pain caused by knee osteoarthritis. Patients were randomly allocated to diclofenac (n = 52) or paracetamol (n = 52) for at least 2 weeks. Primary outcomes were daily knee pain severity, and knee pain and function measured with the Knee Injury and Osteoarthritis Outcome Score (KOOS).

Results

Over a period of 2- and 4-weeks follow-up, no significant difference in daily knee pain was found between the patient groups: estimated differences of 0.5 (95% CI = −0.2 to 1.3) and −0.2 (95% CI = −1.0 to 0.7), respectively. Over the 12-weeks follow-up, no significant differences were found between both groups for KOOS pain: estimated difference of −2.8 (95% CI = −10.7 to 5.1) and KOOS function of −2.7 (−10.6 to 5.0).

Conclusion

Over a period of 2- and 4-weeks follow-up no significant difference in daily measured knee pain severity was found between primary care patients with knee osteoarthritis taking paracetamol or diclofenac. Also, over a period of 12-weeks follow-up no significant differences were found regarding KOOS pain and KOOS function between both groups. Patients more frequently reported minor adverse events after taking diclofenac (64%) than paracetamol (46%).     

Stage-dependent role of growth differentiation factor-9 in ovarian follicle development

GDF-9 was shown to be essential for follicle progression and is the only factor secreted by the oocyte shown to increase the number of primordial and primary follicles in vivo. Furthermore, GDF-9 is a major growth factor involved in the oocyte control of granulosa cell differentiation. A concentration gradient of the paracrine factor GDF-9 established by the oocyte could provide the basis to explain the stratification of granulosa cells in antral and preovulatory follicles. The stimulatory effects of GDF-9 on early follicle development provide a basis for the use of GDF-9 in the treatment of infertility.     

Severe community-acquired pneumonia due to Acinetobacter baumannii

STUDY OBJECTIVES: To investigate the clinical, epidemiologic, and microbiological characteristics of community-acquired pneumonia (CAP) due to Acinetobacter baumannii. METHODS: Retrospective chart and radiographic reviews of all patients who were admitted to National Taiwan University Hospital from January 1993 to August 1999, fulfilled the criteria for CAP, and had an isolate of A. baumannii from blood or pleural fluid at hospital admission. RESULTS: Thirteen patients (9 men and 4 women; age range, 37 to 85 years) met the criteria. Conditions associated with the infection included male gender, old age, alcoholism, malignancy, cerebrovascular disease, diabetes mellitus, renal disease, and liver cirrhosis. Eleven patients (85%) acquired the infection during the warmer months of April to October. Twelve patients (92%) had a fulminant course presenting with septic shock and respiratory failure, and 11 patients (85%) needed ventilator support and were treated in an ICU. Six patients (46%) had leukopenia. Lobar consolidations were found in 12 patients (92%), and pleural effusions were present in 4 patients (31%). All patients had positive blood culture results, two patients (15%) had positive pleural effusion culture findings, and nine patients (69%) positive sputum culture results. All the isolates were susceptible to imipenem, and most were susceptible to aminoglycosides, ceftazidime, ciprofloxacin, and extended-spectrum penicillins. Eight patients (62%) died. Four of the five survivors were initially treated with combination of a third-generation cephalosporin and an aminoglycoside. CONCLUSION: A. baumannii should be considered as a possible etiologic agent in community-acquired lobar pneumonia when (1) patients with a fulminant course present during the warmer and more humid months of the year, and (2) patients are younger alcoholics. A good sputum smear, defined as a Gram stain smear of an adequate sputum specimen that comes from the lower respiratory tract and contains > 25 leukocytes per high-power (100x) field on microscopic examination, can help early diagnosis and treatment. A combination of a third-generation cephalosporin and an aminoglycoside may be appropriate empirical therapy.     

Familial factors in the antihypertensive response to lisinopril

BACKGROUND: Although it is widely recognized that there are familial elements in the pathogenesis of hypertension, remarkably little is known about the influence of family history on response to specific antihypertensive agents. METHODS: This study was designed to address that issue by comparing the depressor response to lisinopril in a dose range of 10 to 40 mg in 74 patients enrolled as sibling pairs. Because all patients were treated with lisinopril, ambulatory blood pressure monitoring (ABPM), an objective measure not influenced by the investigators, was used to assess the primary blood pressure (BP) outcome variable. RESULTS: Diastolic BP was highly correlated between sibling pairs at baseline (r = 0.476; P < .03) and on treatment (r = 0.524; P = .0021). Ethnicity/race had a striking influence on lisinopril dose and response rate. Among African American patients, 23 of 28 reached the top dose of 40 mg/day, whereas only 14 of 36 Caucasian patients reached that dose level. Among Caucasians, 92% responded, and only 48% of African Americans. Responders were characterized by being younger and heavier, having significantly lower microalbuminuria at baseline, higher baseline renal plasma flow (RPF), and higher urinary kallikrein. CONCLUSION: Among Caucasians, the presence of a hypertensive sibling predicts a striking therapeutic response to angiotensin converting enzyme inhibition.