Journal of International Medical Research

Moxifloxacin, a new 8-methoxyfluoroquinolone, was evaluated in a large community-based study involving 16 007 patients over a 9-month period. This study was designed as a large post-marketing observational study of the speed, efficacy and tolerability of moxifloxacin when used in clinical practice for the treatment of community-acquired bacterial pneumonia, or acute exacerbations of chronic bronchitis. Physicians and patients were specifically questioned about overall efficacy and safety as well as symptom relief. According to physicians' assessments 96.3% of patients were cured or improved after moxifloxacin treatment. Symptom relief (‘feeling better’) occurred in almost 70% of patients by day 3 and only 2.3% reported an adverse drug reaction. No individual adverse drug reaction was reported at a frequency above 1%. Among the 209 events considered as serious, only 34 were regarded as possibly or probably related to therapy. There were no moxifloxacin-related clinically relevant cases of phototoxicity, hepatotoxicity or cardiotoxicity. Overall, 92.1% of patients considered moxifloxacin to have been beneficial.

The clinical success of a 5-day course of oral moxifloxacin (administered once daily at a dose of 400 mg) was evaluated in 328 patients with acute exacerbations of chronic bronchitis (Anthonisen type 1) in a non-comparative study conducted by chest physicians in private practice. Results were assessed on the basis of clinical parameters and, for the first time in a trial involving oral moxifloxacin, by the surrogate marker of patient satisfaction. Improvement in (and severity of) cough, dyspnoea, chest pain and sputum were scored daily by patients. Cough, chest pain and purulent sputum production improved rapidly within the first 5 days of treatment. At least 90% of patients were satisfied with the antibiotic. The clinical success rate (cure and improvement) for all patients involved (intent-to-treat analysis) was 90.5%. The most commonly experienced adverse events were gastrointestinal related, with diarrhoea the most frequent of these (2.7% of all patients)

Moxifloxacin, a new respiratory quinolone, was compared with the macrolides azithromycin, clarithromycin and roxithromycin in a cohort study to assess clinical, safety and health-related outcomes of these antimicrobials in general practice settings. In total 332 patients with acute exacerbations of chronic bronchitis (AECB) each received one of the antimicrobial agents for a standard short course of therapy. Random allocation of therapeutic agents occurred by centre, not individuals, and the drugs were prescribed in an open manner. In addition to clinical evaluation by their physicians, all patients kept daily diaries to assess AECB symptoms over the study period, therapy received and quality of life. The overall clinical response rate was 96% and all four regimens were well tolerated. After 14 days there were no significant differences between the study groups, but analyses of patients' daily evaluations of certain AECB specific symptoms showed a faster response rate in the moxifloxacin group

Recombinant human granulocyte colony-stimulating factor (rHuG-CSF) may have a significant impact on preventing infections associated with chemotherapy-induced neutropenia, as well as shortening time to tree lineage engraftment following high-dose chemotherapy and progenitor transplantation. However, the scientific literature documenting evidence-based practice is insufficient and often misinterpreted. This review presents data and discusses the evidence for actual clinical practice in the use of rHuG-CSF in conventional cyclic chemotherapy, either prophylactic or therapeutic, and high-dose therapy, either in priming for mobilization or post-transplantation. In the past decade, many reports have based their conclusions on surrogate markers, and it is time to move towards evaluation of clinically relevant factors. Data must be generated prospectively based on current clinical practice, and several issues must be considered and evaluated to define the true clinical benefit of rHuG-CSF with or without stem-cell support. Evaluation should include complications and needs for resources as well as impact on toxicity and efficacy of conventional or high-dose chemotherapy.

This multicentre, randomized, double-blind study compared the anti-hypertensive efficacy and safety of oral once-daily imidapril 5–20 mg and hydrochlorothiazide 12.5–50 mg in elderly patients with mild-to-moderate essential hypertension. After 24 weeks of treatment, there was a significant reduction in mean sitting diastolic blood pressure from 102.5 mmHg to 87.2 mmHg in the imidapril group (n = 226) and from 102.7 mmHg to 87.4 mmHg in the hydrochlorothiazide group (n = 123) (intent-to-treat population). There were corresponding reductions in sitting systolic blood pressure and standing blood pressure. At least one adverse event was reported by 46% of patients in the imidapril group and 53% of patients in the hydrochlorothiazide group. Imidapril 5–20 mg is as effective and well tolerated as hydrochlorothiazide in the treatment of mild-to-moderate hypertension in elderly patients.

We measured leptin concentrations in patients with acute myocardial infarction (AMI, n = 21) and in 15 age-matched controls, and compared leptin concentrations with levels of other myocardial enzymes and indicators of AMI. Blood was sampled immediately after hospital admission and at 1 h, 2 h, 3 h, 6 h and 9 h, then every 12 h until 5 days post-admission. Patients were stratified into three groups according to peak leptin concentrations: hypoleptinaemia (< 3 ng/ml); normoleptinaemia (≥ 3 – < 15 ng/ml) and hyperleptinaemia (≥ 15 ng/ml). Hypoleptinaemic AMI patients had significantly increased concentrations of plasma lactate dehydrogenase compared with normoleptinaemic patients. No significant differences in other serum markers were noted between hyperleptinaemic and normoleptinaemic AMI patients. A significant negative correlation was found between the peak concentrations of leptin and interleukin 6. Leptin may play a role in the regulation of the development of cardiac damage in patients with AMI.

To investigate the possible involvement of protein phosphatase (PP)1 and PP2A in the process of erythropoiesis, we assessed the effect of PP1 and PP2A inhibitors on erythroid colony formation using an in vitro colony formation assay. Okadaic acid (OKA), calyculin A (Cal-A) and tautomycin suppressed colony formation but 1-nor-okadaone did not. These results suggest that PP1 and PP2A both play an important role in erythropoiesis. Furthermore, higher concentrations of tautomycin were needed to suppress colony formation compared to concentrations of OKA and Cal-A. The target enzyme of inhibitors in erythropoiesis may be PP2A.

The aim of this study was to investigate the ability of portovenously administered donor antigens to induce immune hyporesponsiveness. Lewis (LEW, RT-1^l) rats received Brown Norway (BN, RT-1ⁿ) rat donor splenocytes, via either the portal vein (PV group) or the peripheral vein (IV group). The immune responses of LEW rats, treated with either donor BN or third party Wistar King A (WKA, RT-1^k) splenocytes were established by the persistence of donor dendritic cells (DCs) in the host liver measured using fluorescence microscopy and flow cytometry and by the mixed lymphocyte reaction (MLR). The effect of intravenous gadolinium chloride (GDCl₃) on the blockade of Kupffer cell function prior to portovenous administration of splenocytes was also assessed. The MLR response was strongly inhibited in a BN-restricted manner after portovenous administration of donor BN splenocytes, but not by venous nor by portovenous administration of WKA splenocytes. Immunosuppression was blocked by pretreatment with GDCl₃. The percentage of donor DCs in hepatic non-parenchymal cells (NPCs) was significantly higher in the PV group compared with the IV group. Treatment with GDCl₃ decreased the percentage of donor DCs. In addition, cytotoxic T lymphocyte antigen 4 (CTLA4/CD152), which may function as an immune attenuator, was strongly stained, and B7 was weakly stained in recipient liver in the PV group compared with the IV group. These results suggest that both donor DCs and recipient Kupffer cells (self DCs) are involved in the induction of immune hyporesponsiveness by donor cells. This occurs via portovenous administration, in which a signal of the CTLA4–B7 pathway played an important part in inhibiting the interaction of CD28 and its B7 ligands.

The present study investigated the effects of telmisartan, a selective AT₁ receptor antagonist, on renal function in dogs. Conscious female dogs were treated with (i) vehicle (controls) and three doses of telmisartan (0.03 mg/kg, 0.1 mg/kg and 0.3 mg/kg) administered intravenously; (ii) vehicle and three doses of telmisartan (0.3 mg/kg, 1.0 mg/kg and 3.0 mg/kg) administered orally; or (iii) 1.0 mg/kg per day telmisartan orally for 12 days. Eight dogs were used for each experiment. Each of the four treatments in (i) and (ii) was administered 7 days apart. During the 6 h after intravenous administration, urine volume was significantly higher in dogs treated with telmisartan 0.1 mg/kg (8.5 ± 1.6 ml/kg) and 0.3 mg/kg (7.0 ± 0.9 ml/kg) than controls (2.7 ± 0.3 ml/kg; P < 0.05), and renal sodium excretion was increased significantly with telmisartan 0.03 mg/kg (803 ± 124 μmol/kg), 0.1 mg/kg (1039 ± 213 μmol/kg) and 0.3 mg/kg (966 ± 161 μmol/kg) versus controls (159 ± 21 μmol/kg; P < 0.05). Oral telmisartan at doses of 1.0 mg/kg and 3.0 mg/kg also produced significant increases in urine volume (7.2 ± 1.1 ml/kg and 6.6 ± 1.2 ml/kg, respectively) and renal sodium excretion (599 ± 146 μmol/kg and 555 ± 131 μmol/kg, respectively) compared with controls (2.8 ± 0.5 ml/kg and 80 ± 33 μmol/kg; P < 0.05) over the 6-h post-dose period. Telmisartan at all intravenous doses and at 3.0 mg/kg orally increased the urinary excretion of chloride significantly over the 6-h post-dose period compared with vehicle alone. The excretion of potassium and creatinine were unchanged by any treatment. Telmisartan 1.0 mg/kg administered orally for 12 days produced similar results. In conclusion, acute intravenous or oral as well as subchronic oral administration of telmisartan to conscious dogs promotes diuresis and natriuresis without affecting potassium or creatinine excretion.

A 62-year-old female was admitted to our hospital with suspected acute leukaemia and after investigation we diagnosed acute myeloblastic leukaemia (AML-M1). The patient's blood type was found to be the very rare Bombay type and surveillance of her relatives showed the same blood type in her male cousin on her mother's side. Alongside chemotherapy the patient received 4000 ml of frozen Bombay-type red cells, 1400 ml of concentrated red cells in manitol adenine phosphate solutions and 360 units of type O concentrated platelets without marked effects. The anti-H antibody was initially at 128 dilution but for unknown reasons increased to 2048 dilution after remission of AML-M1. About 3 months after hospitalization the patient died of Cryptococcus neoformans pneumonia despite strict precautions against infection. Although AML-M1 is a common adult leukaemia and is chemosensitive to anti-leukaemic drugs, neither AML-M1 in a patient with Bombay-type red cells nor its treatment with chemotherapy and transfusion with type Oh frozen red cells have previously been reported.