Use of Enzymatic Activity for Design of Orally Administered Enteric Dosing Forms

Abstract— Liquid and semi-solid enteric dosage forms were prepared by entrapping drug with an appropriate partition coefficient in a lipid base vehicle which would then be released by the action of intestinal enzymes. Lipid ester derivatives such as glyceryl monocaprylate and polysorbate 80 were used as vehicles. These vehicles readily dissolved the poorly water-soluble compounds used in the study, itazigrel, indomethacin and the dye, sudan II, and were digested by lipase and esterase, releasing the test drugs with time profiles similar to those observed in dissolution studies. The vehicles released little or only a small amount of the drugs into aqueous medium in the absence of an appropriate enzyme. The enzyme-sensitive enteric vehicles when containing sudan II did not release the dye in the stomach of rats after oral administration, but released significant amounts of the dye in the small intestine.     

A Case of Widely Split Double P Waves with Marked Intra-Atrial Conduction Delay

Widely Split Double P Wave. We report a 78-year-old man as the first documented case of double P waves separated by 400 msec on 12-lead ECG. These P waves had different polarities on lead V₁. The first P wave represented activation of the lateral wall of the right atrium, and the latter P wave represented activation of the nudial right atrium and the left atrium. Widely spaced double potentials were recorded craniocaudally along the line, presumably corresponding to the crista terminalis during sinus rhythm. For this to occur, conduction disturbance has to be present both in the upper and lower right atrium. Conduction disturbance in the upper right atrium would interrupt excitation from the sinus node to the medial wall, and conduction disturbance in the lower right atrium would interrupt excitation spreading from the lower lateral right atrium to the isthmus area where fragmented potentials were recorded. These multiple discrete lesions appear to constitute a unique electrical atriopathy in this patient.     

The Inhibitory Effects of Cephalosporin and Dipeptide on Ceftibuten Uptake by Human and Rat Intestinal Brush-border Membrane Vesicles

Abstract— The types of inhibitory effects caused by compound V (an analogue of ceftibuten) and alanylproline (dipeptide) on the uptake of ceftibuten by brush-border membrane vesicles (BBMV) prepared from human and rat small intestine were analysed. In the presence of an inward H⁺-gradient, the initial uptake rate of ceftibuten by both human and rat intestinal BBMV was concentration-dependent with apparent K_m and V_max values of 0·35 min and 2·052 nmol (mg protein)^?1 min^?1 for human BBMV, and 0·50 mm and 3·056 nmol (mg protein)^?1 min^?1 for rat BBMV, respectively. For both human and rat BBMV, kinetic analysis by Dixon and Lineweaver–Burk plots demonstrated that the uptake of ceftibuten was competitively inhibited by compound V, whereas inhibition by alanylproline was noncompetitive or partially competitive. These results suggest that there is a stereospecific transport system which is common to ceftibuten and compound V, and that this system is not identical to the carrier system for the dipeptide, alanylproline.     

A rupture of lung metastasis of hepatocellular carcinoma causing haemothorax

A 67 year old male with non-resectable hepatocellular carcinoma (HCC) in both lobes and liver cirrhosis was treated with transcatheter arterial embolization and regional chemotherapy. He was doing well for 18 months. He was readmitted for fever, chest pain and multiple pulmonary metastases. During interleukin-2 therapy, he suddenly developed dyspnoea and palpitation, and was in shock. Left-sided haemothorax was confirmed by draining 3 L of fresh blood. In spite of intensive care, he died within 36 h. Autopsy showed that the haemothorax was caused by rupture of one of the metastases in the upper lobe of the left lung, and that the primary HCC was totally necrotic. Survey of the literature failed to find a report of fatal bleeding from a lung metastasis of HCC.     

Electrostimulation of sympathetic nerve fibers during nerve-sparing laparoscopic retroperitoneal lymph node dissection in testicular tumor

A long-handled pair of electrodes with sufficient length to allow stimulation during laparoscopic retroperitoneal lymph node dissection (RPLND) was designed at our institute. We clinically utilized this electrode in the treatment of a 37-year-old patient with testicular tumor who underwent right orchidectomy and nerve-sparing laparoscopic RPLND. During laparoscopic RPLND, sympathetic nerve fibers relevant to ejaculation were electrically stimulated and changes in pressure at the bladder neck were observed. Nerve preservation was confirmed by increased pressure at the bladder neck and ejaculation immediately after the electrostimulation. The application of laparoscopic electrostimulation may become widespread, particularly since it meets the increasing demand for minimally invasive surgery.     

In Vivo and In Vitro Studies of a Chronic Oxygen Saturation Sensor

An oxygen saturation sensor, for the purpose of chronically controlling the heart rhythm produced by a pacemaker, should be specific to oxygen saturation and should be minimally affected by the harsh blood environment. For the sensor type we tested we found: (1) one sensor failure in 205.5 canine-months of chronic implantation (n = 11, range 4 to 50 months); (2) hematocrit-induced error of less than 5 percentage points of SvO2 over the range of 50% to 80% SvO2 and 15% to 45% hematocrit; (3) carboxyhemoglobin (HbCO)-induced error of less than 4 percentage points of SvO2 with HbCO up to 20%; (4) a fibrotic sheath-induced error of less than 3 percentage points of SvO2 in the range of 50% to 80% SvO2 due to fibrotic sheath thicknesses up to 0.22 mm; (5) no significant error induced by velocity variations local to the sensor; (6) no significant error due to temperature in the range of 30 degrees to 42 degrees C; and (7) that the sensor could be as close as 0.3mm to the ventricular wall and still only produce an error of 5% SvO2.     

Validity and reliability of the Japanese version of the Stress and Coping Inventory

Abstract We examined the validity and reliability of the Japanese version of the Stress and Coping Inventory (SCI) among 170 Japanese college students and 234 healthy subjects. The validity and reliability of this version of the SCI in the college student group were supported by significant test-retest correlations, relatively high internal consistency coefficients, and adequate correlations with the Coping Inventory for Stressful Situations (CISS). AS for the healthy subject group, the reliability was supported by relatively high internal consistency coefficients, although further analyses, such as test-retest, are required. The Japanese version of the SCI appears to be suitable for use among college students.     

Application of the relaxation technique in general hospital psychiatry

Abstract The present article demonstrates the clinical application and the efficacy of relaxation techniques in general hospital psychiatry in Japan. During April to December 1993, 20 patients were treated with progressive muscle relaxation and 'modified' autogenic training therapies. The targeted symptoms were anxiety attacks (or panic attacks), neurotic insomnia, hyperventilation syndrome, agoraphobia, chronic pain, and distress. Most patients (18/20) improved rapidly with the use of these techniques and their excellence encourages increased use in general hospital psychiatry for the following reasons. First, physically ill patients are likely to show unexpected reactions to psychotropic medications. Second, some patients prefer these treatment methods rather than medications because they feel that they are participating voluntarily in their own treatment and also because they are fearful of being addicted to tranquilizers. Third, these treatments have produced rapid improvement especially for patients with panic attacks and/or hyperventilation. This study strongly suggests that progressive muscle relaxation and 'modified' autogenic training are simple and useful methods which can be easily employed in the clinical practice of general hospital psychiatry.