Comparison of flomoxef with latamoxef in the treatment of sepsis and/or Gram-negative bacteremia in adult patients

The safety and efficacy of flomoxef and latamoxef were compared in the treatment of hospitalized patients with sepsis and/or Gram-negative bacteremia in a prospective, open-labelled clinical trial. Patients were randomized to receive 1 to 2 g intravenous doses of either flomoxef every 6 to 12 h, or latamoxef every 8 to 12 h. Data from 21 patients given flomoxef and 23 patients given latamoxef were included in the evaluation of efficacy. Flomoxef produced clinical cure and satisfactory microbiological responses in 85.7% and 100% of patients, respectively. These results were similar to those obtained with latamoxef (87% and 100%, respectively). In addition, no significant difference was found in mean age, sex, severity of infection, distribution of pathogens and focus of infection between the two groups. However, the flomoxef group included more patients with ultimately fatal diseases. Six patients given flomoxef and two patients given latamoxef developed superinfections caused by yeast, enterococci and Pseudomonas aeruginosa in the urinary tract. Mild and reversible adverse reactions probably related to flomoxef and latamoxef were noted in 14.3% and 13% of patients, respectively. The results of this study demonstrated that flomoxef is a safe and effective antimicrobial agent in the treatment of patients with sepsis and/or Gram-negative bacteremia.     

Is male gender a risk factor for conversion of laparoscopic into open cholecystectomy?

Background: Based on a clinical observation that the conversion rate of laparoscopic cholecystectomy (LC) to open cholecystectomy (OC) is higher in males, we decided to review our records and to verify whether a significant difference in conversion rates exists between sexes. Methods: A retrospective study on conversion rates of elective laparoscopic cholecystectomy (LC) into open cholecystectomy (LC) in relation to gender was carried out in 329 patients: 267 females and 62 males. Results: Our data revealed that the probability of conversion is fivefold greater in males than females, 21% vs 4.5%, respectively (p=0.0001). We attribute this striking difference to significantly more adhesions (p=0.0002) and anatomical difficulties (p=0.003) in males during LC, leading to conversion. Conclusions: We conclude that conversion of LC to OC is more prevalent among males and is probably attributable to a greater incidence of anatomical difficulties.     

Cytokines predict coronary aneurysm formation in Kawasaki disease patients

In this study, we measured serially the serum levels of cytokines including interleukin-6 (IL-6), IL-8, soluble IL-2 receptor (sIL-2R) and tumour necrosis factor (TNF-) in 60 patients with Kawasaki disease (KD) and evaluated the clinical significance of these cytokines in predicting coronary aneurysm formation. Of the 60 patients, 12 were complicated with coronary aneurysm. Blood samples were collected within the 1st week after onset of fever, then once a week for the 1st month, and once a month for another 5 months. The serum levels of IL-6, IL-8, sIL-2R and TNF were measured using an ELISA or RIA method. Our results show that the changes in serum IL-6 and IL-8 were faster than those of sIL-2R and TNF. Within the 1st week, the serum levels of IL-6 and IL-8 were significantly higher in the patients with than in those without coronary aneurysm (P<0.001). In addition, the serum levels of IL-6 and IL-8 obtained in the 1st week were highly correlated (P<0.001) with those of C-reactive protein and erythrocyte sedimentation rate, and the serum levels of sIL-2R and TNF were also increased at the 1st week reaching the highest level in the 2nd week. In the 2nd week, the serum levels of sIL-2R and TNF were significantly higher in the patients with than in those without coronary aneurysm (P<0.05). These findings suggest that the serum levels of IL-6 and IL-8 obtained in the 1st week may serve as useful parameters in predicting coronary aneurysm formation in KD patients.     

Accuracy of a rapid 10-minute carbon-14 urea breath test for the diagnosis of Helicobacter pylori-associated peptic ulcer disease

Urease in the human gastric mucosa is a marker for infection with Helicobacter pylori (HP), an organism which is associated with peptic ulcer disease. To detect gastric urease, we examined 184 patients (144 males, 40 females; mean age: 49.8±15.6 years) with suspected peptic ulcer disease. Fasting patients were given orally 5 Ci of carbon-14 labelled urea. From each patient only one breath sample was collected in hyamine at 10 min. The amount of ¹⁴C collected at 10 min was expressed as follows: [(DPM/mmol CO₂ collected)/(DPM administered)] × 100 × body weight (kg). The presence of HP colonization was determined by examination of multiple endoscopic prepyloric antral biopsy specimens subjected to culture or a rapid urease test. For the purpose of this study, HP-positive patients were defined as those with characteristic bacteria as indicated by a positive result of either the culture or the rapid urease test; HP-negative patients were defined as those with negative findings on both the culture and the rapid urease test. Of the 184 cases, 99 (53.8%) were positive for HP infection, and 85 (46.2%), negative. The sensitivity and specificity of the rapid 10 min ¹⁴C-urea breath test for the diagnosis of HP-associated peptic ulcer disease were evaluated by a receiver operating characteristic (ROC) curve with a variable cut-off value from 1.5 to 4.5. When a cut-off value of 1.5 was selected, the sensitivity was 100% and the specificity, 83.5%; when a cut-off value of 4.5 was selected, the sensitivity was 54.5% and the specificity, 97.6%. Correspondence to: Chia-Hung Kao     

Activation of striatal dopamine receptors induces pain inhibition in rats

Summary In the rat, elevating dopamine content in corpus striatum with electrical stimulation of substantia nigra or direct administration of apomorphine (50–200g) into the lateral cerebral ventricle or apomorphine (2–10g) into the caudate-putamen complex decreased pain sensitivity (as shown by an increase in the latency to hind-paw lick in the hot plate test). Furthermore, the decreased pain sensitivity after the central administration of apomorphine was antagonized by pretreatment with haloperidol (a dopamine antagonist). On the other hand, lowering dopamine content in corpus striatum with electrolytic destruction of substantia nigra and 6-hydroxydopamine lesions to the substantia nigra, as well as direct injection of haloperidol into the lateral cerebral ventricle or caudate-putamen complex increased pain sensitivity. The data indicate that activation of striatal dopamine receptors in rat brain induces pain inhibition.     

Effects of adenosine 3′, 5′-cyclic monophosphate on thermoregulation in both rats and rabbits

Summary The effects of intraventricular administration of dibutyryl adenosine 3, 5-cyclic monophosphate (db cyclic AMP) on the thermoregulatory responses of unanesthetized rats and rabbits to different ambient temperatures (T_a) were assessed. Administration of db cyclic AMP (10–60 mM) produced dose-dependent hypothermia in both rats and rabbits at T_a 2–22 °C. The hypothermia in response to db cyclic AMP was due to decreased metabolic heat production and cutaneous vasodilatation. There was no change in respiratory evaporative heat loss. In contrast, in the heat (30–32 °C), db cyclic AMP administration produced dose-dependent hyperthermia in these animals. The hyperthermia was due to increased metabolism (due to muscular shivering) and decreased heat losses. The reduction in heat losses was shown by a decrease in both cutaneous circulation and respiratory evaporative heat loss. The data demonstrate that the thermoregulatory responses induced by central administration of db cyclic AMP are T_a-dependent.     

Development of a new controlled-release formulation of chlorpheniramine maleate using in vitro/in vivo correlations

Development of a controlled-released formulation of chlorpheniramine maleate is described, using in vitro/in vivo correlates, according to a process that has been termed "biorelevant dissolution". The process begins with simulations using several possible input rates combined with known disposition parameters of chlorpheniramine maleate. Based on desired plasma concentrations, an input rate is selected for further development which consists of a combination of clinical bioequivalence studies and further in vitro testing and simulations. The method is designed to reduce the requirements for trial and error clinical bioequivalence testing of a new controlled-release formulation.     

兴山五味子的质量研究

兴山五味子;;襄五脂素;;主要药理作用     

Synovial activation of chondrocytes: Evidence for complex cytokine interactions

Synoviocytes secrete factors which induce the synthesis of neutral metalloproteinases (NMP) and prostaglandin E₂ (PGE₂) by chondrocytes in a response called chondrocyte activation. We analyzed synovial chondrocyte activating factors (CAF) for the presence of cytokines which modulated the NMP production by articular chondrocytes. These studies suggested the presence of several other cytokines in addition to interleukin-1 (IL-1). Both resting and activated synoviocytes contained mRNA for basic fibroblast growth factor (bFGF) which is a synergist for IL-1 induced NMP production, and secreted bFGF into their culture media. They also expressed mRNA for transforming growth factor (TGF) which inhibits IL-1 induced NMP production. These cells also produce tumor necrosis factor (TNF) and trace amounts of interleukin-6 (IL-6). In addition to these there is evidence for a synovial activator of chondrocytes which is distinct from IL-1. Since a number of recombinant cytokines including TNF, IL-6 and bFGF failed to activate chondrocytes, this could be a novel cytokine.