Development of a simple analytical method to determine the serum concentration of denopamine by high performance liquid chromatography with electrochemical detection and its clinical application

Denopamine (DP) is a new, orally active, selectively positive inotropic agent and used for the treatment of chronic cardiac insufficiency. The therapeutic effects of DP is highly related to its serum concentrations. A simple analytical method has been developed to determine the serum concentration of DP by use of high performance liquid chromatography (HPLC) with electrochemical detection (ECD). In order to extract the DP from the serum, a disposable solid extraction column (Sep-Pak cartridge, C-18) was used. The average recovery was 84.6 +/- 2.7%. The working electrode potential was fixed at 400 mV with a T1 cell, 600 mV with a T2 cell and 650 mV with a Guard cell in ECD. The analysis was performed on a Nova-Pak cartridge C-18 reverse-phase column (100 mm X 8 mm i.d., 4 microns). The mobile phase consisted of 0.1 M potassium phosphate buffer (pH 6.0) and acetonitrile (83: 17, v/v), and the flow rate was 1.0 ml/min. DP and internal standard phenolphthalein (PP) were eluted at 16.5 and 36.0 min, respectively. The peak-height ratio of DP to PP was linearly correlated (r = 0.9998) over a concentrations range between 1.25 and 15.0 ng/ml in the serum. The lowest detectable concentration was 1.0 ng/ml in the serum. The coefficient of variation of reproducibility in the assay was 6.0% By using the present method, serum concentration of DP was measured for four healthy volunteers after a single oral administration of 10 mg DP tablet after a overnight fast. From these DP concentration profiles, pharmacokinetic parameters were calculated.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of megestrol acetate on interleukin-1 activity.

The current study investigates the effect of megestrol acetate, a synthetic progestin, on the activity of interleukin-1. Murine thymocytes were suspended in vitro and stimulated with varying concentrations of interleukin-1. [3H]Thymidine uptake was observed as an index of thymocyte proliferation. A dose-dependent increase in [3H]thymidine uptake was observed with increasing concentrations of interleukin-1. When megestrol acetate was added to the solution, a marked suppressive effect was observed. Higher doses of megestrol acetate had a greater suppressive effect on thymocyte proliferation. Additional investigation is required to further delineate the potential systemic effects of megestrol acetate.     

Dual microcatheter and guidewire snare technique for retrieval of intravascular foreign body: technical note

A transjugular snare technique was used to retrieve a stretched, residual mechanical detachable coil which extended from the cavernous sinus to the femoral vein, obliterating the transpetrosal route for further embolisation. The coil was snared by a microguidewire. Our new technique is described in this paper. Received: 19 April 1995 Accepted: 31 July 1995     

A case of orbital apex syndrome caused by localized invasive aspergillosis successfully treated with voriconazole]

A 71-year-old man with left periorbital pain and diplopia was hospitalized for evaluation and treatment. He had a past history of untreated diabetes mellitus. Shortly after admission, the patient experienced rapid onset of visual loss in the left eye. MRI and CT showed a lesion expanding from the left orbital apex to the left pterygopalatine fossa. Invasive aspergillosis was diagnosed by open biopsy of intrasinus mucosa via the left maxillary sinus. The patient was treated with voriconazole, an antifungal agent, and marked improvements in left periorbital pain and eye movement were subsequently obtained, although visual acuity was not recovered. This is the first report documenting the clinical utility of voriconazole for sino-orbital invasive aspergillosis.     

Responses of resistance and capacitance vessels in human nasal mucosa to beta-receptor agonists

To investigate the responses of nasal vessels, divided into resistance and capacitance vessels, to a beta-receptor agonist in human, mucosal blood flow of the inferior turbinate and nasal airway resistance were measured when 1.5 mg terbutaline was applied topically. Mucosal blood flow was measured by the hydrogen clearance method just beneath the site where terbutaline in physiological saline (0.02 ml) was applied on an extremely localized area of the nasal mucosa. Nasal airway resistance of the ipsilateral and contralateral nasal cavities was measured separately by anterior rhinomanometry when terbutaline in normal saline (0.1 ml) was sprayed in the unilateral nasal cavity. Topical application of terbutaline elicited neither a significant increase of mucosal blood flow of the inferior turbinate nor an increase of nasal airway resistance. beta-Receptors seem not to be as densely distributed both in the resistance vessels and in the capacitance vessels as to cause vasodilatation by their activation in the nasal mucosa.     

Invasion of the skull base by carcinomas: histopathologically evidenced findings with CT and MRI

The depth and extent of the invasion of the skull base by a tumor are the most critical information for successful en bloc resection of the tumor. The only means available for the evaluation of these factors are CT or MRI images. In order to clarify the ability of these imaging modes to delineate the invasion of the skull base, preoperative images of ten patients who underwent en bloc resection of skull base tumors at Kobe University Hospital were compared with the histopathological findings of the resected specimens. CT proved to be superior to MRI for evaluating bone destruction of the skull base. On the other hand, MRI provided more useful information about intracranial invasion than CT. As a hypertrophic linear shadow on Gd-enhanced MRI represented dural invasion or thickened dura mater adjacent to the tumor, this technique should be taken into consideration to determine the dural resection. We concluded that preoperative evaluation of the depth of skull base invasion by both CT and Gd-enhanced MRI is essential for planning complete tumor resection.     

The anti-inflammatory effects of phenolic dental medicaments as determined by mouse ear edema assay

The anti-inflammatory effects of phenolic dental medicaments were evaluated by mouse ear edema assay. p-Chlorophenol (PCP) inhibited edema when applied topically in dosages of 0.2 and 0.5 mg per site at 15 min before or 1.0 and 2.0 mg per site at 60 min after the application of croton oil. The inhibitory effects were also noted with eugenol, guaiacol, o-cresol, phenol and orally administered indomethacin (10 mg/kg). The involvement of the effects on prostaglandin biosynthesis in the anti-inflammatory effects of these compounds is discussed.     

Local blood flow changes in malignant brain tumours under induced hypertension

Summary Changes in tumour blood flow under an induced hypertensive state were examined in malignant brain tumours to know if the precondition for the effectiveness of induced hypertensive chemotherapy — relative increase in tumour blood flow — are fulfilled. Tumour blood flow was measured under both a resting and an induced hypertensive state in 12 patients with various malignant brain tumours (6 gliomas, 6 metastatic brain tumours) using xenon-enhanced computed tomography. The blood pressure was elevated 40% above the systemic blood pressure of the resting state by the infusion of angiotensin II. Tumour blood flow increased 30% on average above the normal brain tissue blood flow after the induction of an induced hypertensive state (p < 0.05). The tumour blood flow increased in 11 cases of malignant tumours, but decreased in one case with massive brain oedema after induced hypertension. The increase in blood flow was higher in hypervascular tumours and less in hypovascular tumours. Therefore, induced hypertensive chemotherapy probably will be more effective in hypervascular malignant brain tumours with small mass effects.     

Charting of daily weight pattern reinforces maintenance of weight reduction in moderately obese patients.

To maintain reduced body weight by behavioral therapy in moderately obese patients, body weight was measured four times daily and charted in a weekly graph. Seventy-two female patients with simple obesity were divided into two groups: 55 patients with appliance of charting of weight pattern (group-I), and 17 patients without the charting (group-II). The percentage of patients followed for 2 years was different between group-I (87%) and group-II (65%) during 2 years after completion of weight reduction therapy interviews (p less than 0.05). Forty-eight of group-I patients succeeded in decreasing their weight by 15.2 +/- 1.5 (mean +/- SEM) kg during the 6.5 +/- 0.8 months of the therapy interviews. They were followed up for 3.8 years with no rebound weight gain. Eleven patients in group-II also succeeded in decreasing their weight by 16.8 +/- 1.9 kg during 7.8 +/- 1.3 months but their body weight rebounded by 9.0 kg during the 2-year followup period. Twelve of 15 male patients with weight charting maintained reduced weight during 4.3 years. It was easier and more effective for obese patients to maintain weight graphs for the longer period than to record no weight graphs. Obese patients could themselves monitor irregular weight patterns produced by overeating and correct the irregularities in food intake and daily lifestyles. This seems to explain why the illustration of daily fluctuations of weight measurements was useful for long-term maintenance of weight reduction.