[Flumazenil as an emergency management of patients with acute mental disorder]. From July 1, 1990 to June 30, 1991, 55 adult patients with acute alteration of mental status of unknown etiology were enrolled into this study in order to evaluate the diagnostic and therapeutic role of flumazenil in the management of this disorder. Patients who were pregnant or had severe head injury, hemodynamic instability or a provisional diagnosis of hypoglycemia, meningitis or acute cerebrovascular event were excluded. Flumazenil was injected intravenously first in a regimen of 0.3 mg followed by alternative 0.2 mg and 0.3 mg doses every minute until a total dose of 1 mg was given or until the patients responded. These patients were divided into 2 groups based on their response to flumazenil: Group 1, responders (N = 26) and Group 2, nonresponders (N = 29). Good response in Group 1 allowed the cancellation or discontinuation of brain CT scan in 18 patients; intubation and artificial ventilation in 2 and vasopressor infusion in one. The hospital stay was shortened significantly as compared with historical information in uncomplicated benzodiazepine intoxication patients who were admitted before flumazenil was introduced. The Group 2 patients who were with a great span of levels of severity in clinical courses, had higher admission and mortality rate than Group 1 (p < 0.01). We concluded that flumazenil may serve as a useful tool in the diagnosis and management of carefully selected patients. The use of flumazenil with our selective criteria will be cost effective, achieve rapid diagnosis and reduce laborious care in certain cases.


[Detection of the safety depth on human chest by computer tomographic scanning]. Knowledges of acupuncture has played a major role in the treatment of human diseases, and has been mentioned in ancient Chinese medical literature for thousands of years. The loci which are most commonly used as treatment sites are points on the Ren Channel, kidney Channel, Stomach Channel, Pericardium Channel, Lung Channel, Spleen Channel and Gallbladder Channel for those loci on the human chest, insertion depth beyond safety level, can create serious consequences other such as pneumothorax, internal organ bleeding or other damage. This study was designed to determine the real safety depth for each locus by using a current scientific approach. The study was carried out at Tri-Service General Hospital and Mackay General Hospital. The sample patient population was 120. According to their body weight and height, patients were divided into six groups with various body sizes, i.e. normal, over and under-weight adults, and by sex differences. After computer tomographic scanning chest, the relative acupuncture loci should be measured according to anatomical position, then the distance between surface of the chest and thoracic pleura can be defined as its safety depth. For each locus of the groups, the mean and its interval of confident can be found. The analysis of variance (ANOVA), t-test, and multiple regression were also calculated by computer. The results show that there are significant differences in body chest loci within the same sex but, for different body sizes, statistically significant differences for each locus appear, so the safety depth for each chest locus has actually been proved. Not only does his data provide useful information for clinical practices, but also the standard safety depth for each loci on the chest could this be established.


[Survey of heavy metals in traditional Chinese medicinal preparations]. Traditional Chinese medicinal preparations are still widely used by natives in Taiwan. Some traditional Chinese medicine prepared with ancient formulas have been found to contain some heavy metals. There has been an occasional pediatric case admitted with heavy metal intoxication. In the last two years, we collected 11 ancient formula drug samples from the families of the patients. We detected the heavy metals with an inductively-coupled plasma atomic emission spectrometry and a graphite furnace atomic absorption spectrometry. The final result of our report reveals the problem of heavy metals in traditional Chinese medicinal preparations as being very serious.


Percutaneous unroofing of renal cysts.

Percutaneous unroofing of renal cysts. Renal cyst is a common renal disease. It rarely produces symptoms, and thus rarely requires treatment. Treatment becomes necessary when the cyst is symptomatic or complicated. The possible approach includes surgical unroofing or cyst puncture without or with intracystic injection of sclerosing agents. This is a report on the percutaneous unroofing for the treatment of symptomatic or complicated renal cysts.


Imported kala-azar: a case report.

Imported kala-azar: a case report. A 77-year-old man returned from Honan Province, mainland China, and developed intermittent fever and loss of body weight. On physical examination there was evidence of chest infection but no lymphadenopathy or hepatosplenomegaly. Laboratory data suggested anemia, thrombocytopenia and polyclonal gammopathy. The diagnosis of Leishmaniasis was finally established by bone marrow aspiration which disclosed Leishman-Donovan bodies. Unfortunately, the patient expired soon after the diagnosis was made and a partial autopsy was performed. Kala-azar is a rare disease in Taiwan. However, it should be suspected in those patients who have visited the endemic areas, even though the clinical manifestations are atypical.


Suspected anaphylactoid shock to aminocaproic acid (plaslloid) during operation. Epsilon-aminocaproic acid (plaslloid) is one of the most common hemostatics used perioperatively. Although some minor untoward effects in association with its use are not uncommon, the incidence of anaphylactoid shock is extremely rare, especially in a patient under general anesthesia. Recently we came across a severe anaphylactoid reaction, possibly as a result of administration of plaslloid in a patient who was undergoing elective surgery for cervical carcinoma. It was manifested by profound hypotension, tachycardia, hypoxemia, skin-wheel eruption and conjunctival and labial edema. She was successfully resuscitated with prompt volume expansion and epinephrine injection. Our experience in the management of this patient is, hereunder, reported and discussed.


Pseudoaneurysm of the profundus femoris artery resulting from chronic injury of internal fixation screw. We present an unusual case of pseudoaneurysm of profundus femoris artery which formed after injury from internal fixation screw for intertrochanteric fracture 8 years before. The main clinical manifestation was progressively enlarged pulsating mass and mild intermittent claudication. We resected the pseudoaneurysm after ligating the vessel proximal and distal to the pseudoaneurysm and cut off the excessive tip of the screw. After operation, the recovery was uneventful and no problem of the limb viability was noted.


Intrathoracic schwannoma of vagus nerve. Intrathoracic neurogenic tumors are relatively common mediastinal tumors generally located in the posterior mediastinum. The most common origin is the intercostal nerve or the sympathetic chain. These tumors rarely arise from vagus nerve in the anterior mediastinum. The English literature demonstrates a total of 29 cases, which are more often on the left than the right. Here, we present another case: a 41-year-old man with a history of chronic cough for 10 years, whose chest radiograph showed a homogenous mass in the right anterosuperior mediastinum. The chest CT scan revealed a well-defined mass, 4-cm in diameter, located at the right side of trachea. Marked compression and lateral displacement of the R't innominate vein were noted. The mass was heterogenous with partial area of relative lower density and only mild enhancement was noted after contrast medium infusion. Sternotomy with tumor resection from the right vagus nerve was done. The histological diagnosis was schwannoma.


[Transcervical resection of endometrium and submucous myomas]. Transcervical resection of the endometrium and submucous myomas using an unmodified urologic resectoscope has recently been developed as a treatment for menorrhagia and/or infertility when conservative management proves unsatisfactory but the patient desires to preserve the fertility or wishes to avoid hysterectomy. Through June 1990, 7 patients were treated with this procedure including one for endometrial ablation and six for transcervical myomectomy alone. No significant complication was seen and the results were relatively satisfactory in an average 7 1/2 months follow up. This approach seems a safe, effective surgical procedure and represents an attractive alternative to hysterectomy or abdominal myomectomy.


HLA antibodies in multiple transfused patients. Totally 86 patients with multiple transfusions were followed up regularly for more than six months. Their sera were screened for HLA antibodies every two to four weeks. Subsequently 28 (33%) of them developed HLA antibodies. The specificities of identified antibodies were anti-A2, All, B16 and B60. However, most of the antibodies were either multiple or undetermined. The panel reactive activity (PRA) was correlated with the amount of blood components transfused. We concluded that about one third of the patients will develop HLA antibodies after multiple transfusions and the reactivity of the antibodies is correlated to the amount of blood components transfused.


Echocardiographic evaluation of thickened aortic valve and its relation to aortic stenosis and regurgitation. To elucidate the aging changes of human aortic valves and their relation to aortic regurgitation (AR) or stenosis (AS), consecutive echocardiographic examinations in 1601 subjects were carried out. These patients were prospectively divided into 5 groups: adolescence (< 20, N = 38); adulthood (20-39, N = 131); middle age (40-59, N-222); old age (60-79, N = 1194) and octogenarian (> = 80, N = 16). The incidence of thickened aortic valve (TAV), to be overall, was 29%. It was specifically 0% in the adolescence and adulthood, 15% in the middle age group, 35% in the elderly group and up to 69% in the octogenarian group. Among 307 subjects with TAV, the incidence of AR tended to increase with age, to be 31% in the 4th and 5th decades, 43% in the 6th and 7th decades and 62% in the 8th decades. The TAV existed more frequently over the noncoronary cusp (56%) than either left (22%) or right (22%) coronary cusp. In addition, the percentage of aortic stenosis and aortic regurgitation also tended to increase with age. In conclusion, TAV occurred more frequently at the noncoronary cusp than at the right or left coronary cusp. The incidence of TAV and the associated AS and AR tended to increase with age.


Radiological manifestations of cardiovocal syndrome. Cardiovocal syndrome is a rare clinical diagnosis that signifies vocal cord palsy associated with various cardiovascular diseases. The radiological manifestations of six cases of clinically diagnosed cardiovocal syndrome are reviewed retrospectively. The common clinical presentation of these six cases was hoarseness that was due to left vocal cord palsy. By means of chest X-rays (CXR) and cardioangiography, four cases were respectively diagnosed to have atrial septal defect (n = 1), ventricular septal defect (n = 1) and mitral stenosis (n = 2), all of which were associated with a common radiological finding of dilatation of pulmonary trunk. The other two cases were separately diagnosed to have proximal descending aortic saccular aneurysm (n = 1) by means of CXR and angiography, and fusiform ascending aortic aneurysm (n = 1) by computed tomography and magnetic resonance image. All these radiological presentations of either aortic aneurysm or dilated pulmonary trunk were associated with encroachment of aorticopulmonary window for which the left recurrent laryngeal nerve was presumably compressed with the result of left vocal cord palsy. Hoarseness that is caused by these underlying cardiovascular diseases is correctable after treatment of the underlying diseases. Hence, clinicians and radiologists should pay attention to the radiological manifestations of patients whose chief complaints are hoarseness and cardiovocal syndrome.


Postoperative radiotherapy for glioblastoma multiforme. Between July 1983 and December 1990, 39 patients with pathologically documented glioblastoma multiforme were treated with radiotherapy after biopsy (5 patients) or resection (34 patients). There were 30 males and 9 females ranging in age from 9 to 68 years (median 52). All but one of the 39 patients were treated with 10 MV photons. Whole brain irradiation was delivered through lateral parallel opposed fields for the first 40 Gy, followed by reduced portals to boost the tumor bearing area. The range of tumor dose was 58 to 70 Gy, with a median dose of 64 Gy (33 patients). Treatment was executed at 2 Gy per fraction, 5 days per week for all patients except 2 who received 1.8 Gy per fraction. Eight patients underwent reoperation at least once after radiotherapy due to suspicion of recurrence of the disease. No patients were lost to follow-up: 35 patients had died and 4 were still alive. The median survival time was 11.8 months. The 1- and 2-year survival rates were 49% and 12% respectively. A prognostic factor analysis shows that treatment response and the pre-irradiation Karnofsky status were statistically significant variables influencing survival. The median survival was 28.7 months for patients with complete response, compared with 9.8 months for those with partial response or stable disease (p = 0.002). The median survivals were 13.5 and 9.0 months in high (> or = 70%) and low Karnofsky performance scale (p = 0.04). Smaller tumors, a larger extent of resection, reoperation and younger age were favorable factors with borderline significance.(ABSTRACT TRUNCATED AT 250 WORDS)


[Blood lactate changes during incremental exercise in chronic obstructive pulmonary disease]. In order to evaluate whether the lactic acidosis is developed during incremental exercise test in COPD. 12 untrained subjects with COPD performed incremental maximal cycle ergometer tests. Ventilation (VE); O2 uptake (VO2), CO2 output (VCO2); and end-tidal CO2 fraction (FETCO2) were measured. Arterial lactate concentration and blood gas analysis were measured at rest, maximal exercise and recovery of exercise from an indwelling arterial catheter. of the degree of airway obstruction. (2) T40 and BEecf correlated well with lactate change (r = 0.83; 0.84, P < 0.05). (3) The change of VE, and RQ correlated with the lactate change (r = 0.81; 0.83, 0.72, P < 0.05), but not the VE/VO2, VE/VCO2, nor FETCO2, (r = 0.24; 0.06; 0.46, P > 0.05). We concluded that the blood lactate increased markedly in patients of COPD during increment exercise, and it was well corrected with the change of VE, VCO2 and RQ. The increased lactate could be indicated by the concomitant change of T40 and BEecf.


[Radiology of diffuse panbronchiolitis: experience in VGH-Taipei]. Eleven cases of diffuse panbronchiolitis (DPB) were reported. According to plain chest film (10 cases) and high-resolution computed tomography (HRCT) (11 cases) findings, all were grouped as x-ray type B or CT type II advanced stage. Among them, 4 cases were grouped between CT type II-III; 3, CT type III-IV. All 11 patients had history of chronic paranasal sinusitis (CPS). Three patients had HLA typing. 1 had positive HLA Bw54; 3, HLA Cw1. We suggested patient with CPS, positive HLA Bw54 and Cw1 typing and clinically suspected DPB, radiological study including HRCT should be done.


[Laparoscopic cholecystectomy: experience of VGH-Kaohsiung]. One hundred consecutive patients underwent laparoscopic cholecystectomy from May 1991 to February 1992 at Veterans General Hospital--Kaohsiung. Ninety-seven of them presented on an elective basis, including eight patients undergoing endoscopic sphincterotomy with extraction of common bile duct stone before laparoscopic cholecystectomy. The remaining 3 patients were operated during acute cholecystitis episode. Two patients with biliary injuries during laparoscopic cholecystectomy were converted to laparotomy, with a conversion rate of 2%. Intraoperative cystic cholangiogram was done selectively in 7 patients. Major complications occurred in 3 patients, including two biliary injuries and one residual CBD stone. Minor complications of wound infection were found in 7 patients. The overall morbidity rate was 10%. No operative mortality was found. Mean operation time was 112 minutes and mean blood loss was 90 ml. The mean hospital stay (3.1 days) and the mean time of returning to normal activity (14.7 days) were longer than those of Western series, but were shorter than those of open cholecystectomy. Laparoscopic cholecystectomy is a safe and effective procedure that can be performed with minimal risk. However, the importance of accurate preoperative screening and surgical experience should be emphasized for this new procedure. In patients with gall stone plus CBD stone, combined endoscopic sphincterotomy with extraction of CBD stone and laparoscopic cholecystectomy may offer a new therapeutic approach but the long term effect of endoscopic sphincterotomy needs further evaluation.


[Management of liver trauma in adults: the results of selective nonoperative management and operative treatment]. The liver trauma is still one of the major injury in thoracoabdominal trauma, with increasing numbers and incidence in Taiwan. There is a trend toward a more conservative approach in the treatment of liver trauma. Nonoperative management for the stable patients with blunt liver trauma has been advocated in literature recently. In Veterans General Hospital-Taipei, forty-five patients with liver trauma have been admitted to Emergency Department after accident in past four years. Eighty-three percent of the trauma mechanism was blunt injury, and seventeen percent penetrating. There were ten patients selected as nonoperative management, and eight of them succeeded without operation. Retrospective analyzing various factors including age, trauma score, revised trauma score, injury severity score, amount of hemoperitoneum, blood loss and transfusion, morbidity and hospitalization, there are no statistic significances between nonoperative and operative groups, except that nonoperative group are less amount of blood transfusion. We suggest that the decision to treat the patient without laparotomy is not based on the degree of hemoperitoneum or the grade of liver injury, but rather on the stability of the patient. And further evaluation is needed.


[Pituitary apoplexy: a study of eighteen cases]. Pituitary Apoplexy is a rare but sometimes life threatening condition which requires prompt recognition and timely medical intervention to avoid catastrophic consequences. From January 1979 to June 1989 and total of one hundred and ninety eight pituitary tumor patients were operated on our hospital. Eighteen cases (9.1%) were diagnosed "pituitary apoplexy" according to histopathological findings. The group consisted of twelve men and six women ranging in age from twenty two to sixty one years with a mean of forty. There were three cases of prolactin-secreting adenomas (16.7%), four growth-hormone secreting adenomas (22.2%), and eleven nonfunctional adenomas (61.1%) with an incidence of 6.1%, 8.3%, and 11.4% respectively (P > 0.05). Clinical manifestation occurred acutely in 66.7% and nonacutely in 33.3%. The patients presented with headaches (100%), visual impairment (83.3%), visual field defects (66%), disturbed consciousness (22%), fever and meningismus (11%). Radiological examinations able to demonstrate abnormalities included plain skull films (84%), computed tomography (84.6%), and angiography (93.8%). Various investigations of endocrine function pre and post operatively showed a deficient gonad axis (53%, 62.5%), adrenal axis (26.7%, 56.2%), and thyroid axis (20%, 43.8%). Sixteen cases received a transsphenoid operation and three cases underwent a transfrontal craniotomy. No case of mortality was reported. Postoperative radiotherapy was given to nine cases and nine cases were followed up on a regular basis. Therefore, our retrospective study suggests that pituitary apoplexy is not uncommon and has an acute clinical presentation. No particular tumor type was prone to occur. Various radiological examinations could define perisellar abnormalities. With a decreasing order of hormone deficiency, gonad, adrenal and thyroid axis were observed during the course of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)


Hydrochlorothiazide-induced pulmonary edema: a case report and literature review. A 67-year-old man developed non-cardiogenic pulmonary edema after taking a hydrochlorothiazide (HCTZ) tablet. The symptoms remitted following supportive treatment but recurred after rechallenge. Immunologic studies showed increased immunoglobulin E, negative lymphocyte transformation test when exposed to HCTZ, normal blood lymphocyte subpopulations and complement levels, and negative antinuclear antibodies. We reviewed 22 previous reported cases and emphasized that physicians should be aware of this rare but life-threatening reaction.


Pseudarthrosis and pseudopseudarthrosis of ankylosing spondylitis-report of 2 cases. Pseudarthrosis is a well known, late complication of ankylosing spondylitis associated with extensive discovertebral junction destruction and fracture of the posterior elements. In contrast, the term "Pseudopseudarthrosis" is published in the recent literature to portray similar roentgenologic findings of discovertebral destruction but without bony break of the posterior arch. In this article, each complication is presented by a single case using the demonstration of plain film and computed tomography studies to compare their differences in the posterior spinal elements.


[Multiple primary malignant neoplasms: a case report]. One individual with two or three malignant neoplasms is not uncommon. However, a patient with more than 5 primary malignancies is unusual. We present a 51-year-old female who developed 6 metachronous primary malignant neoplasms in a period of 10 years. The anatomic sites of neoplasms in this patient included the cervix, larynx, skin, left breast, bladder and right lung (middle lobe). All of the tumors were proven by pathologic examination, and each of these tumors was recognized as a distinct primary tumor. Aggressive surgical resection, post-operative irradiation and chemotherapy showed good response in this patient. This patient had no familial or hereditary tendencies but, definite impairment of the cellular immunity had been identified.


[Anaphylactic shock after readministration of rifampicin: a case report]. Many reports have shown that rifampicin could induce a variety of adverse effects. However, anaphylactic shock occurring after readministration of rifampicin, to our knowledge, has not been reported thoughtfully. Herein we present a case with anaphylactic shock after readministration of rifampicin. The possible mechanism may be the interaction between IgE antibody and mast cell or basophils. Compared with continuous regimen, intermittent rifampicin regimen has longer interval to accumulate more rifampicin-induced antibodies, and more immunogenic side effects are the sequelae when re-encountered with rifampicin.


[Double aortic arch-three cases report and operative treatment]. This report is on three double aortic arch cases. They were diagnosed in our department between 1982 and 1992. The first case was complicated by dilated cardiomyopathy whose diagnosis was delayed due to a lack of clinical experience. Corrective surgery relieved the airway obstruction and his breathing improved postoperatively. The patient finally died of heart failure due to concurrent progressive dilated cardiomyopathy one and half years later. The second and third cases were diagnosed on the day of admission by a barium esophagogram and echocardiogram. MRI (Magnetic resonance image) of the cardiovascular system on these two patients revealed no other associated abnormalities. No angiography was done on the third case. They underwent surgery with excellent results. In any infant younger than 3 months with dyspnea and dysphagia, double aortic arch should be suspected. The esophagogram can show extrinsic compression. An echocardiogram can reveal two aortic arches. Both procedures can be performed easily and safely at the bedside. We recommend that these to be considered as routine examinations in such patients.


[Successful treatment of congenital anaplastic astrocytoma by combining vinblastine, cisplatin and etoposide: a case report]. Congenital brain tumor is a rare disease in the neonatal period. According to the literatures, they comprise only about 1% of childhood brain tumors. Among the congenital brain tumors, 10%-25% are astrocytomas. Anaplastic astrocytoma is one of the malignant glioma. The prognosis is usually not good in the childhood or adult stage. We report one case of congenital anaplastic astrocytoma who received combination chemotherapy, including vinblastine, cisplatin and etoposide following subtotal resection of tumor. After chemotherapy, he got a favorable outcome. And now, he is still no evidence of tumor recurrence for two years.


[Changes in the calcium channel of the sarcoplasmic reticulum (the ryanodine receptor) during myocardial ischemia]. We determined 3H-ryanodine binding in isolated rat hearts subjected to aerobic perfusion or to global normothermic ischemia (10-30 min). Ischemia produced a significant reduction in the number of ryanodine binding sites, while the dissociation constant of the binding reaction was unaffected.


[Variations in the functionality of cardiac adenyl cyclase as a function of age]. The metabolic and functional activity of the heart closely depends on cAMP and therefore on the integrity of adenylate cyclase (AC) system. Alterations of this signal transduction system might be co-responsible for the impairment of cardiac performance observed with aging. Evidence is here provided that basal activity of cardiac membrane-bound (48,000 x g) AC significantly declines with the age of the rat (1, 12, 24 month-old). This is accompanied with the decrease of cAMP content, which leads to the fall of cAMP/cGMP molar ratio a possible final determinant of cardiac performance. Kinetic analyses indicate that aging is associated with a net increase of the Km of a cardiac AC, while the Vmax is unaffected. Besides, the response in vitro of AC from 24-month-old heart to the inhibitor spermine or a different stimulants, such as Gpp (NH) p, isoproterenol, PGE1 or forskolin, is significantly lower than that of AC from 1 month-old one. The suggestion is made that aging causes an impairment in the capability of the catalytic moiety of cardiac AC to make functional complexes with activated guanine nucleotide binding proteins.


Naloxone potentiates the inotropic effects of isoproterenol in vitro by a nonopiate receptor mechanism. Naloxone potentiates the effects of adrenergic agonists when administered to hypovolemic dogs, and it has been assumed that this effect is due to naloxone's action at opiate receptors. To help determine the site and mechanism of this interaction, we administered naloxone and its "d" stereo-isomer (which does not bind to opiate receptors) to guinea pig papillary muscles in the presence and absence of pharmacologic (isoproterenol) and physiologic (treppe) inotropic stimulation. In control muscles and in rapidly paced muscles, naloxone was without significant inotropic effect. In the presence of isoproterenol, d- and l-naloxone exerted significant positive inotropic effects that were dose dependent. We conclude that, since both d- and l-naloxone potentiated the inotropic effects of isoproterenol and this was seen in the absence of opioids, naloxone may increase contractility by a nonopiate receptor-mediated mechanism.


Effect of endotoxic shock on basal and insulin-mediated Na+/K(+)-pump activity in rat soleus muscle. This study evaluated basal and insulin-mediated Na+/K+ transport in skeletal muscle during endotoxic shock. Fasted male Holtzman rats (80-100 g) were killed 5 hr after the i.v. injection of saline (control) or 20 mg/kg Salmonella enteritidis endotoxin. 86Rb+ uptake into the cellular compartment of soleus muscle was determined in the presence and absence of 100 mU/ml insulin. The rate coefficient and rate of 22Na+ efflux and muscle intracellular 22Na+ content (in percentage of total muscle 22Na+) were determined in the presence and absence of 1 mM ouabain. The rate of basal cellular 86Rb+ uptake (cpm x 10(3).g wet weight-1.min-1) was not significantly different between control (77.7 +/- 2.9) and endotoxic soleus muscles (76.1 +/- 3.9). Insulin increased the rate of cellular 86Rb+ uptake by 19% in control (92.4 +/- 3.7) and 23% in endotoxic soleus muscles (93.8 +/- 4.1). Cellular 22Na+ content was 40% greater in endotoxic muscle (16.8 +/- 1.4) as compared to control muscles (12.0 +/- 0.9). The rate coefficient for ouabain-sensitive 22Na+ efflux in endotoxic muscles (0.028 min-1) was 1.7-fold greater than that in control muscles (0.017 min-1). The rate of ouabain-sensitive 22Na+ efflux was more than doubled in endotoxic muscles (0.470%/min) compared with control muscles (0.204%/min). Endotoxic shock did not alter insulin's ability to stimulate Na+/K+ transport in muscle. An increase in the electrogenicity of the Na+/K+ pump is consistent with an increased rate coefficient for 22Na+ efflux, with no change in the rate of 86Rb+ uptake in endotoxic soleus muscle.(ABSTRACT TRUNCATED AT 250 WORDS)


Oxygen radical generation during ischemia-reperfusion in the isolated perfused rat liver monitored by enhanced chemiluminescence. Using luminol- and lucigenin-enhanced chemiluminescence (Lm-CL and Lg-CL), we monitored oxygen radical generation during ischemia-reperfusion in the isolated perfused rat liver. Both enhanced chemiluminescence levels decreased during 30 min of ischemia and increased markedly at the onset of reperfusion. When the liver was subjected to another 30 min of ischemia, reperfusion caused a progressive increase in both types of enhanced chemiluminescence. Administration of superoxide dismutase (SOD) into the perfusate strongly attenuated Lm-CL, but had a limited effect on Lg-CL. Catalase (CAT) and allupurionol (ALP) failed to attenuate both types of enhanced chemiluminescence. Thus the predominant oxygen radicals in the liver during reperfusion is superoxide and the lack of effect of ALP on oxygen radical generation indicates that hypoxanthine-xanthine oxidase reaction is unlikely to be a primary source of oxygen radicals. The different response to SOD in Lm-CL and Lg-CL is considered to be based on the diffusion space of luminol and lucigenin in the tissue. The relationship between oxygen radical levels and tissue damage, and the site of oxygen radical detection are discussed.


[The value of using serum specific antibody in differential diagnosis of periodontitis]. In the present study, serum anti-Bacteroides gingivalis (Bg) and anti-Actinobacillus actinomycetemcomitans (Aa) antibody titers in RPP, AP patients and healthy subjects were determined by ELISA. Discriminant analysis for differential diagnosis of RPP, AP and healthy subjects was performed using clinical measurements (PD, AL, PII, BI) and serum antibody levels as combined parameters. The results showed significantly different serum antibody levels among the three examined groups. The results also suggested that the combined use of clinical parameters and serum specific antibody titers may be a valuable measure in differential diagnosis of periodontal diseases.


Susceptibility of recent clinical isolates to temafloxacin (A-63004) and other antimicrobial agents. In vitro susceptibility of 1008 strains of recent clinical isolates was determined against the new aryl fluoroquinolone temafloxacin (T-167, A-63004) ciprofloxacin, norfloxacin, ampicillin, piperacillin, cephalothin, cefoxitin, ceftazidime, gentamicin, amikacin, oxacillin and vancomycin. The minimum inhibitory concentrations (MICs) of temafloxacin in micrograms/ml required for > or = 90% isolates were 0.13-0.5 for enterobacter, 0.03-0.25 for Escherichia coli, 0.12-0.5 for Klebsiella, 0.5-1.0 for Proteus mirabilis, 0.12-0.5 for Morganella morganii, 0.03-0.12 for Salmonella, 0.25-1.0 for Serratia marcescens, 0.03-0.12 for Shigella, 0.06-4.0 for Pseudomonas aeruginosa, 0.06-0.12 for Aeromonas hydrophila, 0.12-0.5 for Staphylococcus aureus, 0.12-1.0 for coagulase negative staphylococci and 4.0-8.0 for enterococci. The antibacterial activity of temafloxacin was comparable or superior to other drugs tested against most organisms. However, Xanthomonas malthophilia was relatively more susceptible to ciprofloxacin and norfloxacin, and temafloxacin had significantly high antibacterial activity against enterococci as compared to other fluoroquinolones.


Gastric secretory function in the developing human stomach. Little data exists regarding the activity of gastric parietal cells in the very immature infant. Therefore we have examined the developing human stomach for the presence and location of parietal cells, using both standard histological methods and antibodies to the H+/K+ ATPase (proton pump) and intrinsic factor, in 35 fetuses (ranging from 13-28 weeks) and in five infants (2-21 weeks). Parietal cell activity was noted in the body, antrum and pyloric regions in all the fetal specimens examined. However, this activity was much more limited in the infant specimens. We have noted that from the end of the first trimester parietal cells are present in a mature, functional form with the potential to secrete both gastric acid and intrinsic factor.


Identification of tyrosylprotein sulfotransferase in rat gastric mucosa. An enzyme activity which catalyzes the transfer of the sulfate group from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to poly-Glu6,Ala3,Tyr1 (EAY; M(r) 47,000) has been demonstrated in the antral and body mucosa of the rat stomach. The distribution of this tyrosylprotein sulfotransferase was similar to that of the Golgi marker enzyme, glycoprotein sulfotransferase, and its activity from body mucosa was 23% higher than that from the antrum. The optimum for tyrosylprotein sulfotransferase activity was obtained at pH 6.8, in the presence of 0.5% Triton X-100, 20 mmol/l MnCl2, 50 mmol/l NaF, 2 mmol/l 5'-AMP, and 1 mmol/l DTT, whereas Ca2+, Mg2+, Cu2+, Zn2+, EDTA, NEM, NaCl and Na2SO4 were inhibitory. The apparent Km of the sulfotransferase for EAY was 1.5 x 10(-6) mol/l and for PAPS 0.75 x 10(-6) mol/l. The enzyme was 28 times less susceptible to 2,6-dichloro-4-nitrophenol inhibition as compared to that required for phenol sulfotransferase inhibition. The tyrosine sulfation by the tyrosylprotein sulfotransferase was independent of the sulfation of carbohydrate residues in mucous glycoproteins and glycolipids, thus indicating that the identified sulfotransferase is specific for sulfation of the tyrosyl residues in the peptide core.


Characterization of multiple forms of carbonyl reductase from chicken liver. Three enzyme forms (CR1, CR2 and CR3) of carbonyl reductase were purified from chicken liver with using 4-benzoylpyridine as a substrate. CR1 was a dimeric enzyme composed of two identical 25-kD subunits. CR2 and CR3 were monomeric enzymes whose molecular weights were both 32 kD. CR1 exhibited 17 beta-hydroxysteroid dehydrogenase activity as well as carbonyl reductase activity in the presence of both NADP(H) and NAD(H). CR2 and CR3 had similar properties with regard to substrate specificity and inhibitor sensitivity. They could exhibit the activity only with NADPH and had no hydroxysteroid dehydrogenase activity. CR2 and CR3 cross-reacted with anti-chicken kidney carbonyl reductase antibody, though CR1 did not. The results suggest that CR1 is a hydroxysteroid dehydrogenase, and CR2 and CR3 are similar to each other and to the kidney enzymes.


Protective action of iron-chelating agents (catechol, mimosine, deferoxamine, and kojic acid) against ischemia-reperfusion injury of isolated neonatal rabbit hearts. Iron is suggested to play an important role in free radical generation during ischemia reperfusion. In the present study, the protective action of 4 iron-chelating agents, with different iron affinities, against reperfusion injury was examined in Langendorff-perfused hearts of neonatal rabbits. The chelators and their iron-binding constants (log Km) were as follows: catechol (43), mimosine (36), deferoxamine (31) and kojic acid (27). Following cardiac arrest, the hearts were subjected to global ischemia for 45 min at 37 degrees C, and then reperfused with modified Krebs-Henseleit solution for 30 min. In control, the left ventricular developed pressures (LVDP) after 30 min reperfusion recovered to 50.5 %/- 3.0% (mean +/- SEM; n = 5) of the preischemic level. In the hearts treated with catechol (30 microM), mimosine (30 microM) or deferoxamine (30 microM), the LVDP recovery was significantly improved up to 84.9 +/- 1.3, 88.2 +/- 2.9 or 87.4 +/- 1.5%, respectively (p < 0.01 vs. control). Creatine phosphokinase (CPK) leakage during the initial 5 min of reperfusion was significantly decreased to about half of control in the hearts treated with catechol, mimosine, or deferoxamine. However, the treatment with kojic acid (30 microM) showed no improvement in the LVDP recovery and CPK leakage. Free radical generation was measured with an electron spin resonance using a spin-trapping agent, 5,5-dimethyl-pyrroline-N-oxide (DMPO). The treatment with catechol, mimosine, or deferoxamine reduced the maximum intensity of DMPO-OH signal to about one third of control. However, the maximum intensity in the hearts treated with kojic acid showed a similar level to control.(ABSTRACT TRUNCATED AT 250 WORDS)


Superoxide production by liver macrophages in a septic rat model--relation to arterial ketone body ratio. The relationship between superoxide production by liver macrophages and arterial ketone body ratio (AKBR), which reflects the oxidation-reduction state in the mitochondrial compartment of hepatocytes, was studied in rats with lethal and sublethal septicemia induced by intravenous injection of live Escherichia coli 014. In the sublethal model, AKBR decreased transiently (p < 0.01) and superoxide production by isolated liver macrophages increased significantly after opsonized zymosan (OZ) stimulation (p < 0.05). On the other hand, in the lethal model, AKBR decreased markedly (p < 0.01) to below 0.4 without recovery, and superoxide production was not activated by OZ stimulation. Thus, when AKBR decreases to an irreversible level, below about 0.4, superoxide production by liver macrophages is impaired, while as long as AKBR remains reversible, more than about 0.4, it is enhanced. It is suggested that superoxide production by the Kupffer cells is related to the intrahepatic oxidation-reduction state in the septic model.


Interaction of diltiazem with single L-type calcium channels in guinea-pig ventricular myocytes. The effects of diltiazem on cardiac L-type calcium channels were studied at the single channel level, using Ba2+ ions as the charge carrier. Patch clamp experiments were performed on enzymatically isolated guinea-pig ventricular myocytes. It was shown in cell-attached configuration on multichannel patches that diltiazem, when applied to the bath, can approach the calcium channel under the pipette after diffusion through the membrane phase. The time constant of the onset of the effect was 60 s. The rate of recovery seemed to be of the same order. Diltiazem had most prominent effect on calcium channel open state probability by reducing the frequency of openings, and by increasing the frequency of records without channel opening (nulls). The effect on mean open time was found to be insignificant at 1 kHz resolution. Diltiazem had no effect on the amplitude of unitary currents. These data are consistent with the assumption that diltiazem interacts mainly with the inactivated state (although interaction with the closed states was not ruled out), and does not bind to the open state of the calcium channel.


Modulation of high affinity phenylalkylamine binding sites on cultured human embryonal vascular smooth muscle cells. Two phenylalkylamine Ca2+ channel ligands, (+/-)-[3H]verapamil ((+/-)-[3H]V) (-)-[3H]desmethoxyverapamil ((-)-[3H]DV), were employed in whole cell binding assays to characterize the specific high affinity binding sites on Ca2+ channels, their cooperativity and modulations induced on cultured human embryonal vascular smooth muscle preparation (VSM) by: 1) Beta-adrenergic stimulation of the cell, 2) exposure to high K+ concentration, 3) exposure to high concentration of Mg2+ ions, 4) the presence of a benzothiazepine Ca2+ channel antagonist and modulator d-cis-diltiazem, and 5) guanylylimidodiphosphate. The total amounts of specific (+/-)-[3H]V and (-)-[3H]DV binding sites present on VSM cells increased significantly after beta-adrenergic receptor activation, following cell membrane depolarization induced by high concentrations of K+, in the presence of Ca2+ chelator Na3EDTA, and after incubation of VSM cells with a benzothiazine-type Ca2+ channel blocker d-cis-diltiazem. A marked reduction of (-)-[3H]DV binding was observed after permanent G-protein activation by a nonhydrolyzable analog of guanylylimidodiphosphate, after incubation of the cells with norepinephrine, and after incubation of VSM cells with millimolar concentration of Mg2+. The results suggest the existence of multiple modulations of specific (-)-[3H]DV binding sites on Ca2+ channel corresponding to the way of activation of the cell and also to the immediate "state" of the membrane bound Ca2+ channels present on VSM cells, the positive heterotropic interaction after beta-adrenergic stimulation, the homotropic positive allosteric interaction induced by d-cis-diltiazem and pure noncompetitive inhibition induced by guanylylimidodiphosphate. The presence of high concentrations of Mg2+ inhibited whereas the presence of Ca2+ chelator, of ethylenediamine-tetraacetic acid sodium salt, significantly increased the total number of specific high affinity (-)-[3H]DV binding sites on VSM cells.


Effects of dimethyl sulfoxide and polycationic neomycin on stimulation of purified plasma membrane Ca(2+)-pump by negatively charged phospholipids. At least two reaction steps are involved in the activation of purified plasma membrane Ca(2+)-transport ATPase by negatively charged phospholipids depending on the type of phospholipids (Lehotský et al. 1992). The effect of negatively charged phospholipids on Ca(2+)-stimulated ATPase (cycling activity) was compared with that of p-nitrophenylphosphatase (E2-form activity) catalyzed by Ca(2+)-pump. PIP like PS, activated Ca(2+)-ATPase activity by modifying ATP activation curve with increasing Vmax of the high affinity site. Ca(2+)-ATPase activity reconstituted in PC was stimulated by DMSO(10%) by a factor of 1.36. The activity stimulation by DMSO was only weak in PS and activity was inhibited in PIP. Also, phosphatase activity catalyzed by Ca(2+)-pump was strongly stimulated by DMSO and was differentially affected by phospholipid head group. Positively charged neomycin (5 mmol/l) had no effect on Ca(2+)-ATPase activity reactivated in PC or PS, but the stimulatory action of PIP was suppressed. Relative stimulation of phosphatase activity by PS was not influenced. Both hydrolytic activities catalyzed by Ca(2+)-transport ATPase were differentially affected by organic solvents and polycations with respect to the kind of the phospholipid.


Cleavage by restriction enzymes of DNA modified with the antitumour drug cis-diamminedichloroplatinum(II). The effect of binding of an antitumour drug cis-diamminedichloroplatinum(II) (cis-[Pt(NH3)2Cl2]) to DNA on cutting effectiveness of BamHI, EcoRI, and SalI restriction endonucleases was quantitatively determined. The platinum complex inhibits the cleavage of plasmid pHC624 DNA linearized by BglI restrictase. From the present results we conclude that the yield of restriction endonuclease cleavage is also lowered if the platinum complex is bound outside the recognition DNA sequence of these enzymes. We propose that the origin of platinum adducts on DNA outside the recognition sequence can decrease the yield of restriction enzyme cleavage via inducing a conformational perturbation in the recognition DNA sequence of these enzymes and also via inhibition of the linear diffusion of these enzymes on DNA.


Sensitivity of the brain synaptosomal membrane Mg(2+)-ATPase activity to arachidonic acid is under control of the Na+,K(+)-ATPase state. Evidence is presented for the sensitivity of the synaptosomal plasma membrane Mg(2+)-ATPase activity to arachidonic acid being dependent on the functional state of Na+,K(+)-ATPase. An "Inversion effect" was observed at arachidonic acid concentrations exceeding 80 mumol/l when the Mg(2+)-ATPase activity (after ouabain addition) is higher than the total ATPase activity (without ouabain). The "Inversion effect" is reduced by cyclooxygenase inhibitor indomethacin or acetylsalicylic acid and restored by prostaglandin PGA2 or PGD2.


Activation of guinea pig eosinophil respiratory burst by leukotriene B4: role of protein kinase C. Leukotriene B4 (LTB4) and the protein kinase C activator, 4-beta-phorbol dibutyrate (PDBu), both induced a pronounced and concentration-dependent stimulation of hydrogen peroxide (H2O2) generation by purified guinea pig peritoneal eosinophils in the concentration range 1 nM-1 microM. The LTB4 response was inhibited competitively by the specific LTB4 receptor antagonist, U-75302, with a KB of 25 nM, while the concentration-response curves for both stimuli were shifted rightwards (3.8-fold and 2.8-fold for LTB4 and PDBu, respectively) by the competitive protein kinase C inhibitor, 1-O-hexadecyl-2-O-methylglycerol at a concentration of 300 microM. LTB4 appears, therefore, to induce respiratory burst in eosinophils via a receptor-mediated mechanism involving protein kinase C.


Diurnal variations in plasma ACTH, cortisol and beta-endorphin levels in cocaine addicts. In order to establish possible alterations in the hypothalamic pituitary-adrenal axis and in ACTH-related opioids in cocaine addicts, plasma ACTH, cortisol and beta-endorphin levels were measured throughout the day in 9 cocaine addicts [age: 27 +/- 5 years (mean +/- SE); weight: 72 +/- 6.1 kg, duration of cocaine addiction: at least 2 years] on the day of their admission to a recovery community for drug abusers (first test) and after 15 days of abstinence (second test). Nine normal controls (age: 28 +/- 6 years; weight: 73 +/- 3.2 kg) were tested only once in a similar manner. Blood samples were taken at 06:00, 08:00, 10:00, 12:00, 18:00 and 20:00 h and served for hormonal assays. Urine samples were taken from cocaine addicts at 08:00 h on the experimental day and on the following day. Results of both urine assays were positive for cocaine catabolites, indicating cocaine administration during the day before the experimental test. From the day of their admission in the community (1st experimental day), the patients were forbidden to use cocaine. For 4 days after admission, they were treated with symptomatics to attenuate withdrawal symptoms. Thereafter, the patients underwent a washout period of pharmacological treatments for 10 days before being retested (second test). Urine samples taken at 08:00 h on this second experimental day and on the next day were negative for the presence of drug catabolites. During the first test, cocaine addicts showed higher plasma ACTH, cortisol and beta-endorphin levels than normal controls at all examined time points.(ABSTRACT TRUNCATED AT 250 WORDS)


Aniridia--Wilms' tumour association--a case with 11p 13-14.1 deletion and ventricular septal defect. A two year old female child with bilateral wilms tumor (WT) along with multiple congenital anomalies like bilateral aniridia with congenital cataracts and nystagmus, microcephaly, mental retardation and ventricular septal defect has been described. The karyotype analysis revealed 46 xx, del 11p 13-14.1. Association of ventricular septal defect with the classical features of 'Aniridia-Wilms' tumor association' is an unusual feature in this case.


Anxiogenic effects of the intraamygdala injection of flumazenil, a benzodiazepine receptor antagonist. The effects of bilateral intraamygdala microinjection of flumazenil, a benzodiazepine receptor (BZD-R) antagonist, on the exploratory activity in an elevated plus maze were examined in chronically implanted rats. This compound induced a significant decrease in the time spent in the open arms, which is consistent with an anxiogenic action. No effect was observed after intrastriatal injections of flumazenil. Naive rats exposed to the elevated plus maze showed a rapid and selective decline in the content of BZD-like molecules in amygdala (-68%) but not in striatum and hippocampus. These data suggest that the anxiogenic effects of the intraamygdala injection of flumazenil is probably due to the blockade of BZD-like molecules released during the performance.


Excitatory amino acids and neuronal plasticity: modulation of AMPA receptors as a novel substrate for the action of nootropic drugs. The nootropic drug, aniracetam, behaves as a positive modulator of AMPA-sensitive glutamate receptors in a variety of systems, including intact brain tissue, amphibian oocytes injected with rat brain mRNA, and cultured neurons. In electrophysiological studies, aniracetam both increases the peak amplitude and reduces the rate of decay of the ion current generated by AMPA or quisqualate. In cultured neurons, aniracetam (as well as oxiracetam and piracetam) enhances the stimulation of 45Ca2+ influx produced by AMPA but not that produced by kainate or NMDA. In addition, aniracetam (as other nootropic drugs) increases the maximal density of low affinity binding sites for [3H]AMPA in crude synaptic membranes. Positive modulation of AMPA receptors by aniracetam provides a novel molecular substrate which explains the clinical efficacy of nootropic drugs as memory and cognition enhancers.


The pathophysiology of chronic fatigue syndrome: confirmations, contradictions, and conjectures. To examine published data regarding patient cohorts with the recently defined chronic fatigue syndrome. Review of thirty-two peer-assessed research publications that included full disclosure of the methodology employed; classification of the findings as confirmed, contradictory, or non-duplicated. Research studies have confirmed that the majority of patients with the chronic fatigue syndrome: 1) are white middle-aged women, 2) have a high prevalence of current major depression and somatization disorder, 3) have abnormal personality traits, 4) believe that their fatigue has a physical cause, and 5) show mild abnormalities of humoral immunity. Contradictory data have been presented with regard to: 1) the time of onset of depressive disorders, 2) the etiologic role of herpetic and enteroviral infections, 3) the presence of abnormal cellular immunity, and 4) the clinical utility of immunoglobulin therapy. Non-duplicated research has indicated 1) hypothalamic-pituitary-adrenal axis dysfunction, 2) abnormalities on magnetic resonance images of the brain, 3) altered cytokine production, and 4) the possibility of retroviral infection. As presently defined, the chronic fatigue syndrome has many of the clinical and biological features associated with depressive and somatoform disorders. A specific etiologic role for infections or immune dysfunction has not been confirmed.


Scrapie-associated tubulofilamentous particles in scrapie hamsters. Examination of thin sections from the cerebral cortex of scrapie-infected hamster brains revealed characteristic circular 26-30 nm diameter tubulofilamentous particles, identical to those previously described in both experimentally induced scrapie in mice, hamsters and natural scrapie of sheep, bovine spongiform encephalopathy and human Creutzfeldt-Jakob disease and mice and chimpanzees infected with Creutzfeldt-Jakob disease. Longitudinal forms of tubulofilamentous particles were also observed in dendrites and myelinated axons. Both transverse and longitudinally cut particles were readily distinguished from microtubules and synaptic vesicles, thus there appears to be no relationship between tubulofilamentous particles, and microtubules or synaptic vesicles.


Oncogenic transformation by cellular DNA isolated from human cytomegalovirus-infected cells. Delayed replication of human cytomegalovirus (CMV) was initiated in human embryonic fibroblasts using partially ultraviolet light-inactivated virus stock. Cellular [high molecular weight (HMW)] DNA extracted from CMV-infected cell cultures demonstrated a substantial increase in transforming activity after introduction into hamster embryo fibroblasts relative to HMW DNA extracted from mock-infected cells. The transforming activity of HMW DNA varied between 0.01 and 0.25 foci/micrograms DNA. HMW DNA isolated from CMV-infected cells after initiation of viral DNA synthesis demonstrated a significant decrease in the induction of morphologically transformed foci. The transforming activity of HMW DNA was unaffected by HindIII or XbaI endonuclease digestion, but it was sensitive to sonication and EcoRI endonuclease and DNase treatment. Six cell lines were established from the foci of morphologically altered cells. Cells of these lines demonstrated loss of contact inhibition, replication in semisolid agarose or in medium containing low serum, a high saturation density, and tumorigenicity when implanted into hamsters. Histopathological examination of the tumors identified the tissues as fibrosarcomas. In situ hybridization of cells isolated from foci of morphologically altered cells or Southern blot analysis of DNA isolated from either the cell lines or tumors did not demonstrate the presence of sequences with homology to viral DNA using the transforming region or the entire viral DNA as a probe. The lack of viral DNA sequences as well as the similar phenotypic characteristics of cell lines and tumors suggest that alteration(s) induced by CMV may occur in specific region(s) of cellular DNA.


A sequence-specific DNA-binding protein recognising a GA-rich element cooperates with Oct-1 at the herpes simplex virus type 1 IE3 promoter. Herpes simplex virus immediate early (IE) gene transcription is regulated via the upstream TAATGARAT motif and involves the recruitment of the ubiquitous octamer-binding protein Oct-1 and a component of the virion Vmw65 into a multiprotein complex termed the immediate early complex (IEC). An upstream GA-rich element (GA-RE) has been postulated to mediate a response to Vmw65 independent of TAATGARAT. We have studied IEC formation in gel shift assays using DNA fragments containing these sequence elements from the HSV-1 IE gene 3 promoter in different combinations. The results show that a factor which footprints to the GA-RE cooperates with Oct-1 to increase IEC levels on a TAATGARAT motif located 5 bp 5' to the GA-RE. The factor alone is unable to promote IEC formation. We were unable to demonstrate any effect of this factor on a TAATGARAT motif located 16 bp from the GA-RE, suggesting that this effect is not universal for all TAATGARAT motifs.


Stable expression of functional human cytomegalovirus immediate-early proteins IE1 and IE2 in HeLa cells. The major immediate-early (IE) genes 1 and 2 of human cytomegalovirus (HCMV) encode proteins that regulate the expression of HCMV genes as well as some other viral and cellular genes. In order to study the expression and function of these IE gene products, we established several HeLa cell lines that stably expressed the 68-kD IE1 protein, the 82-kD IE2 protein, or both proteins. The IE proteins expressed in these cell lines were biologically active, as shown by transient chloramphenicol acetyltransferase assays. Transcription from the major IE promoter was augmented in the IE1-expressing cells, while transcription from the HCMV early gene UL84 promoter was activated in the IE2-expressing cells. In addition, we found that the IE2-expressing cells established colonies in soft agarose more efficiently than the parental HeLa and the IE1-expressing cells. Furthermore, expression of both the IE1 and IE2 proteins was increased by treatment of these cell lines with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate. Thus, our cell lines provide a useful system to study the regulation of IE gene expression in human cells as well as to study transaction by HCMV IE proteins on various viral and cellular genes.


Modulation of sodium channel activity in frog ventricular cells by guanidyl-side armed cyclam. The mechanism underlying the Na channel blocking action of guanidyl-side armed cyclam (G-cyclam) was studied using conventional patch-clamp methods. G-cyclam applied to the cytoplasmic surface of the membrane reduced the amplitude of single Na channel currents without inducing a flickering block. This effect was enhanced by depolarization and was fully reversible upon washout of the drug. The relationship between the concentration of G-cyclam and the reduction of unitary current could be expressed mathematically assuming one-to-one stoichiometry. During maximal suppression of the single channel current by G-cyclam approximately 40% of the current remained. Low concentration of G-cyclam (3 x 10(-4) M) prolonged, while higher concentration (3 x 10(-3) M) shortened the mean open time suggesting the involvement of two processes in the Na channel blocking action of this agent. It appears that low concentration of G-cyclam induce rapid and frequent transition between open and less conductive state resulting in a reduced current, and higher concentration make the channel nonconductive with slower single channel kinetics.


Occurrence and expression of human papillomavirus type 16 genes in uterine cervical carcinomas. The detection of human papillomavirus (HPV) type 16 early genes: E7, E5, and the late gene: L1 was attempted in 42 uterine cervical neoplasia (35 cervical carcinomas and 7 cervical dysplasias) using the polymerase chain reaction (PCR) method. Consequently, E7 gene was detected in 19 (54.3%) of 35 carcinomas and in 5 (71.4%) of 7 dysplasias, E5 gene was detected in 7 (20.0%) of 35 carcinomas and in 5 (71.4%) of 7 dysplasias, L1 gene was detected in 18 (51.4%) of 35 carcinomas and in 5 (71.4%) of 7 dysplasias, respectively. In order to elucidate the transcriptional pattern of HPV type 16 in each of the clinical stages, the expression of mRNA for E7, E5 and L1 genes was examined in HPV DNA positive cases using the reverse transcriptase polymerase chain reaction (RT-PCR) method. E7 gene mRNA was detected in 18 (94.7%) of 19 cervical carcinomas, whereas E5 and L1 genes mRNAs were detected in only 4 (57.1%) of 7 and in one (5.6%) of 18 carcinomas respectively. In cervical dysplasias, E7, E5 and L1 genes mRNA were detected in all cases. E7, E5 and L1 genes were transcriptionally active in all dysplasias, whereas E5 and L1 genes were not always transcriptionally active in carcinomas. These results suggest that the HPV type 16 early gene E7 is present preferentially as integrated form and transcriptionally active in the carcinoma cell, and plays an important role in the development of malignancy. On the other hand, E5 and L1 genes are present and transcribed in the dysplasia cell but their transcriptional activity is less frequent in the carcinoma cell.


Genetically defined lysosomal acetylesterase EC 3.1.1.6 in the cauda epididymidis of mouse, rat, and man. After inhibition by bis-p-nitrophenyl phosphate and subsequent staining for esterase using naphthol AS-D acetate as the substrate, a strong lysosomal esterase was demonstrated in the cauda epididymidis of mouse, rat, and man. Owing to its behaviour towards the classifying inhibitors eserine, diisopropyl fluorophosphate, bis-p-nitrophenyl phosphate, and p-chloromercuriphenylsulphonate, this lysosomal esterase was shown to be an acetylesterase (EC 3.1.1.6). Control experiments involving isoelectric focusing revealed that this acetylesterase was identical with the genetically defined homologues ES-17, ES-6, and ES-A4 in mouse, rat, and man, respectively.


Epidermodysplasia verruciformis.

Epidermodysplasia verruciformis. Epidermodysplasia verruciformis is a rare skin disease characterized by the disseminated, flat, wart-like lesions caused by human papillomavirus and a high frequency of various skin cancers. The clinical aspects, histological findings, genetic and immunological factors, and human papillomavirus types found in the disease and their roles in skin cancers are reviewed.


Treatment of Nippostrongylus brasiliensis in normal and SPF rats using tetramisole loaded into zeolite. Administration to rats of tetramisole loaded into zeolite was more successful in killing adults of Nippostrongylus brasiliensis than the administration of tetramisole alone. The most successful treatment occurred in SPF (Specific Pathogen Free) rats dosed with tetramisole loaded into zeolite and no worms were present in this group at autopsy eight days post-infection. It is concluded that the slow release of drug from the zeolite matrix improved its efficacy, especially in removing worms from low-grade infections.


Detection of human papillomavirus DNA in skin warts from immunocompromised patients but not in semen from men whose wives have abnormal cervical cytology. The epidemiology of human papillomaviruses (HPV) was studied in 61 immunocompromised patients (e.g. renal and cardiac transplants; Bowen's disease; genital cancer) undergoing therapy at the University Hospital of Wales at Cardiff U.K. Warts from various sites of these patients were studied for the presence of HPV types 6, 11, 16 and 18 using the dot-blot DNA hybridization technique. Four HPV-16 and one HPV-11 was detected. The presence of HPV-16 in our study is quite significant since it suggests the potential occurrence of genital HPV types in skin warts in immunocompromised patients and hence the need for screening such patients against HPV types. HPV, mainly types 16 and 18 are usually associated with genital cancer, cervical malignancies and cervical intraepithelial neoplasia. The semen of the husband of 30 women with cervical abnormalities and the semen of 30 husbands (control) of wives with normal cervix were tested for HPV-6, 11, 16 and 18. No HPV-DNA could be detected in all of the 60 specimen. This suggests that specimens were either truly negative for any of those types or because virus DNA could present in a small amount less than 5 pg/microliters in some patients. Whether semen plays a role in transmitting HPV is still controversial.


Measurement of human sperm intracellular water volume by electron spin resonance. An electron spin resonance technique using the spin label tempone and the broadening agent potassium chromium oxalate was used to measure the water volume of human sperm. The toxicity of tempone (5 mmol/L) and potassium chromium oxalate (50 mmol/L) to sperm was measured over a time span of 120 minutes using computer-assisted semen analysis. Tempone had no effect on any computer-assisted semen analysis parameters, including motility. Potassium chromium oxalate reduced sperm motility by an average of 24% during the first 30 minutes of exposure. After selection by swim-up and correction for the presence of dead cells and cytoplasmic droplets, a water volume of 20.0 +/- 2.9 microns3 was obtained. This yields a total volume of 33.9 microns3 if a water compartment of 59% by volume is assumed. These results are consistent with other shape-independent techniques for measuring volume, but larger than the generally accepted optical and electronic particle counter sizes.


The human sperm acrosome reaction does not depend on arachidonic acid metabolism via the cyclooxygenase and lipoxygenase pathways. The objective of this study was to determine whether the metabolism of arachidonic acid via the cyclooxygenase pathway, the lipoxygenase pathway, or both has a pivotal role in the human sperm acrosome reaction. To do so, the stimulatory effect of arachidonic acid and a number of its metabolites, as well as the inhibitory effect of cyclooxygenase and lipoxygenase inhibitors on the acrosome reaction, was evaluated. Arachidonic acid, prostaglandin E2, and prostacyclin (PGI2) induced the acrosome reaction when added to 3-hour preincubated (capacitated) spermatozoa. The arachidonic acid-induced acrosome reaction was dependent upon extracellular calcium. Leukotriene B4 and 15-HPETE only induced the acrosome reaction when present throughout the preincubation period, indicating that they may enhance the capacitation process rather than the acrosome reaction. Thromboxane did not affect the acrosome reaction under any of the conditions tested. Inhibitors of cyclooxygenase (indomethacin, phenylbutazone) and lipoxygenase (phenidone, nordihydroguiaretic acid) or FPL 55712 (a leukotriene antagonist) did not prevent the arachidonic acid-stimulated acrosome reaction. Furthermore, 5, 8, 11, 14-eicosatetraynoic acid (ETYA), the acetylenic analog of arachidonic acid that inhibits arachidonic acid metabolism, induced an acrosome reaction equivalent to that of arachidonic acid. These results strongly suggest that the acrosome reaction induced by exogenous arachidonic acid is not mediated via either the cyclooxygenase pathway or the lipoxygenase pathway.(ABSTRACT TRUNCATED AT 250 WORDS)


Platelet aggregation in spontaneous hypertension: genetic determination and correlation analysis. Hyper-responsive platelets are often found in essential hypertension. It has also been suggested that in hypertensive patients platelets may serve as an easily accessible indicator of abnormalities in contractile cell function. To test these suggestions, we analysed the relationship between platelet aggregation and genetic hypertension in the rat. Linear regression analysis of mean values of recombinant inbred strains was used to evaluate the relationship between blood pressure and ADP-induced platelet aggregation. ADP-induced platelet aggregation in platelet-rich plasma in spontaneously hypertensive rats (SHR) was significantly decreased compared with in normotensive Brown Norway (BN) rats. However, in recombinant inbred strains, derived from (SHR x BN) F2 hybrids, correlation analysis revealed that platelet aggregation and blood pressure are independent traits. The present results suggest strongly that spontaneous hypertension and platelet hypo-aggregability in SHR were linked together by chance due to drift during selective inbreeding. The absence of a correlation between the two traits also indicates that alterations in platelet function in essential hypertension, often found in population-based studies, may have to be reaffirmed in genetically better-defined situations, e.g. by pedigree analysis.


Effect of stress and food restriction on blood pressure and lifespan of Dahl salt-sensitive rats. To evaluate the long-term consequences of stress in rats with genetic hypertension. Rapp-Dahl salt-sensitive rats, maintained on a low-salt diet, were stressed periodically over 8 weeks during which time their blood pressures were measured. In experiment 1 both stressed and unstressed control rats were given ad libitum access to food. Because of significant differences in body weights, in experiment 2 the unstressed controls were pair-fed to maintain their food intake at a level similar to that of the stressed rats. Rats were subjected to 2-h sessions of supine immobilization stress 5 days a week every other week for 8 weeks. Blood pressures were measured during non-stress weeks, at least 4 days after the last exposure to the stressor and at monthly intervals thereafter. Survival curves were also established. In experiment 1 stressed rats developed hypertension at a slower rate than controls and lived significantly longer, but also weighted significantly less than controls, presumably because of diminished food intake. In experiment 2, in which food intake was controlled, body weights were similar in the two groups of rats, and hypertension developed at the same rate in both groups. Survival curves were not significantly different. Food restriction extended life compared with free feeding. Stress need not have long-term, deleterious health consequences in rats with genetically inherited hypertension, whereas caloric restriction is protective.


Angiotensin II increases proto-oncogene expression and phosphoinositide turnover in vascular smooth muscle cells via the angiotensin II AT1 receptor. The aim of this study was to determine which angiotensin II receptor (AT receptor) mediates proto-oncogene expression and phosphoinositide metabolism in vascular smooth muscle cells in vitro. The AT receptor antagonists DuP753 (losartan), an AT1 antagonist, and PD 123319, an AT2 antagonist, were used to characterize AT receptors on cultured vascular smooth muscle cells derived from the rat mesenteric artery and to identify which receptor subtype mediates the angiotensin II-induced increase in proto-oncogene expression and phosphoinositide metabolism. Rat mesenteric artery vascular smooth muscle cells were grown using standard cell culture methods. Proto-oncogene induction was measured using Northern blotting. Phosphoinositide breakdown was assessed by measuring [3H]-inositol phosphates released from prelabelled cells. Receptor-binding studies revealed that the AT1 receptor predominated on vascular smooth muscle cells. Incubation of quiescent cells with 0.1 mumol/l angiotensin II resulted in a 65% increase in total [3H]-inositol phosphates released compared with unstimulated cells and in a rapid accumulation of c-fos messenger RNA (mRNA). Pre-incubation of the cells with 10(-5) mol/l PD 123319 had no effect on either total inositol phosphates release or c-fos mRNA induction. Both responses, however, were totally abolished by pre-incubation of the cells with 10(-5) mol/l losartan or saralasin. Angiotensin II acts through the AT1 receptor to increase c-fos expression and phosphoinositide turnover in vascular smooth muscle cells. These mechanisms may be important in angiotensin II-induced smooth muscle hypertrophy.


Differential effects of captopril and nicardipine on baroreflex control of sympathetic nerve activity and heart rate in renal hypertension. To test the hypothesis that an angiotensin I converting enzyme inhibitor and a calcium channel blocker have different effects on the arterial baroreflex in renal hypertension. We examined the baroreflex control of renal sympathetic nerve activity and heart rate before and after blood pressure was reduced by a similar magnitude (11 +/- 1 mmHg) with intravenous captopril or nicardipine in two-kidney, one clip hypertensive (mean arterial pressure 92 +/- 2 mmHg, n = 12) and normotensive rabbits (mean arterial pressure 75 +/- 1 mmHg, n = 9) in the conscious state. Data obtained during activation and deactivation of baroreceptors were analysed with logistic function curves, and the maximum slope of the curve was taken as the sensitivity of the baroreflex. The maximum slopes of the curves relating mean arterial pressure to renal sympathetic nerve activity and to the heart rate in hypertensive rabbits were significantly smaller than the maximum slopes in normotensive rabbits. In renal hypertensive rabbits, the maximum slope of the mean arterial pressure-renal sympathetic nerve activity curve was increased with captopril compared with that with vehicle. In contrast, the maximum slope of the mean arterial pressure-heart rate curve was increased with nicardipine compared with that with vehicle. Our data indicating that the baroreflex control of renal sympathetic nerve activity was improved by captopril and that baroreflex control of the heart rate was potentiated by nicardipine suggest that these classes of antihypertensive agents had differential effects in conscious hypertensive rabbits.


Platelet aggregation and dense granule secretion in a colony of dogs with spontaneous hypertension. Since canine hereditary essential hypertension has been previously reported in a colony of Siberian husky dogs, we tested the suitability of this model for use in studies on the platelet defect identified in humans with essential hypertension. Platelet aggregation and dense granule ATP secretion were measured in dogs with essential hypertension and normotensive control dogs. The platelets from the hypertensive group showed significantly increased aggregation and secretion in response to stimulation with ADP. There was no significant increase in aggregation or secretion when platelets from hypertensive dogs were stimulated by platelet-activating factor, thrombin, calcium ionophore A23187 or phorbol myristate acetate. The increased aggregation and secretion responses in platelets from the hypertensive dogs suggest that a defect similar to that reported in humans with essential hypertension exists and that further investigation is warranted.


Plasma calcitonin gene-related peptide levels in patients with various hypertensive diseases. To clarify the pathophysiological role of calcitonin gene-related peptide (CGRP) in hypertensive diseases. Using a sensitive radioimmunoassay established in our laboratory, plasma CGRP levels were evaluated in control subjects and in patients with essential hypertension, phaeochromocytoma or primary aldosteronism. The CGRP levels in the three hypertensive groups were significantly higher than in normal controls, but no statistically significant difference was observed among CGRP levels in the three hypertensive groups. In the three cases of secondary hypertensives (one patient with phaeochromocytoma and two with primary aldosteronism), a significant decrease in plasma CGRP levels and a marked reduction in blood pressure were observed after adrenalectomy. These results suggest that increased plasma CGRP levels in hypertensive patients could be a compensatory reaction to elevated blood pressure.


Regulation of proliferation by vasopressin in aortic smooth muscle cells: function of protein kinase C. To investigate the effect of arginine vasopressin-stimulated prostaglandin synthesis and the activation of protein kinase C on DNA synthesis in rat aortic smooth muscle cells. The effects of arginine vasopressin on the release of arachidonic acid and the synthesis of prostaglandin (PG) E2 and prostacyclin (PGI2) were determined. The effects of 12-o-tetradecanoylphorbol-13-acetate (TPA), a protein kinase C-activating phorbol ester, and of 1-oleoyl-2-acetylglycerol, a specific activator of protein kinase C, were evaluated in cultured rat aortic smooth muscle cells. The effects of arginine vasopressin and prostaglandins on the progression from the late G1 to the S phase of the cell cycle were evaluated by measuring the DNA synthesis, and the effects of TPA on them were evaluated. Arginine vasopressin dose-dependently stimulated arachidonic acid release. TPA and 1-oleoyl-2-acetylglycerol dose-dependently increased the vasopressin-induced arachidonic acid release. Vasopressin stimulated the synthesis of both PGE2 and PGI2. TPA increased the vasopressin-stimulated prostaglandin synthesis as well as the arachidonic acid release. Vasopressin, added at the G0/G1 phase of the cell cycle, stimulated DNA synthesis of aortic smooth muscle cells. Exogenous PGE2 and PGI2 inhibited the DNA synthesis and showed maximum inhibition when added at the late G1 phase. TPA alone, added at the late G1 phase, reduced the DNA synthesis stimulated by vasopressin at the G0/G1 phase to about 45%, but vasopressin alone, added at the late G1 phase, had little effect. However, with TPA pretreatment, vasopressin significantly suppressed the DNA synthesis by about 70%. Staurosporine, a protein kinase C inhibitor, reduced the suppression by TPA alone or by vasopressin with TPA pretreatment almost to the control level. Indomethacin, a cyclo-oxygenase inhibitor, reduced the suppression by vasopressin with TPA pretreatment almost to the level of TPA alone. These results suggest that arginine vasopressin has a suppressive effect on DNA synthesis in rat aortic smooth muscle cells by inhibiting progression from the late G1 into the S phase of the cell cycle through the synthesis of PGE2 and PGI2, and that protein kinase C acts as an amplifier of this mechanism.


Regression of left ventricular hypertrophy in previously untreated essential hypertension: different effects of enalapril and hydrochlorothiazide. Primarily to investigate the long-term effects of antihypertensive therapy on left ventricular morphology in non-malignant essential hypertension and in particular to compare an angiotensin converting enzyme inhibitor and a diuretic in this respect. Previously untreated males aged 20-65 years with diastolic blood pressure > or = 95 mmHg during a 4- to 6-week placebo period were randomly assigned to double-blind treatment with enalapril or hydrochlorothiazide. Indirect and intra-arterial blood pressure, echocardiography, apex cardiography, carotid pulse tracing and phonocardiography. Left ventricular mass (LVM) was significantly correlated with intra-arterial blood pressure at baseline. During long-term treatment (14-18 months) blood pressure decreased significantly in both treatment groups (indirectly and intra-arterially), at rest and during dynamic exercise. No significant differences in blood pressure response were seen between the two therapeutic alternatives. LVM decreased progressively and significantly on enalapril after 18 months of monotherapy and decreased non-significantly on hydrochlorothiazide after 14 months of monotherapy. The difference in effect between treatments was significant in a stepwise regression analysis taking change in blood pressure into account. The relationship between the reductions in LVM and blood pressure were significant for enalapril but not for hydrochlorothiazide. Neither therapy affected left ventricular diastolic or systolic diameters significantly, but enalapril reduced posterior wall thickness and interventricular septal thickness significantly, and improved left ventricular distensibility significantly. Neither therapy had any negative effects on systolic function, although hydrochlorothiazide decreased left ventricular ejection time index significantly. Enalapril was significantly more effective than hydrochlorothiazide in reversing left ventricular hypertrophy without negatively affecting left ventricular function.


Antihypertensive efficacy and side effects of three beta-blockers and a diuretic in elderly hypertensives: a report from the STOP-Hypertension study. To compare the blood pressure-lowering efficacy, the frequency of side effects and changes in laboratory values of three beta-blockers and a potassium-sparing diuretic combination in elderly hypertensive patients. The Swedish Trial in Old Patients with Hypertension (STOP-Hypertension) was a prospective, randomized, double-blind, multicentre trial comparing active antihypertensive treatment with placebo in patients aged 70-84 years. The study group consisted of 1627 elderly hypertensive patients (mean +/- SD age 75.7 +/- 3.7 years; 37% males, 63% females). Supine and standing blood pressure, heart rate and side effects were recorded at each visit. Blood was drawn for routine analysis. The mean length of follow-up was 25 months (range 6-65). No patient was lost to follow-up. After 2-months' single-drug therapy, all four active drugs were found to be equally effective in reducing diastolic blood pressure (DBP). However, there were differences in their efficacy in reducing systolic blood pressure (SBP); the diuretic was significantly more effective than the beta-receptor blockers. The results of a series of multiple linear regression analyses showed that the observed differences in effect on SBP could not be explained by the different effects of the drugs on heart rate. More than two-thirds of the patients were given supplementary treatment, most of them already by the 2-month visit, after which there was no significant difference in blood pressure among the treatment regimens. The changes in laboratory values and in the prevalence of symptoms were minor for all four regimens. Metoprolol (controlled release), atenolol, pindolol and the combination hydrochlorothiazide + amiloride were equally effective as single drugs in reducing DBP. There were differences in their efficacy in reducing SBP, the diuretic being more effective than the beta-blockers. After addition of supplementary treatment (beta-blocker to diuretic, or vice versa) there were no significant differences in blood pressure reduction among the groups. The changes in laboratory values and in the prevalence of symptoms were minor for all active treatment regimens. Thus, the satisfactory effect on cardiovascular morbidity and mortality was not impaired by low tolerability of the drugs.


Limited reproducibility of hourly blood pressure values obtained by ambulatory blood pressure monitoring: implications for studies on antihypertensive drugs. To assess the reproducibility of average hourly blood pressure values obtained by 24-h non-invasive ambulatory monitoring. Fifteen outpatients with essential hypertension. In all subjects antihypertensive treatment was withdrawn for 4 weeks before and during the 4 weeks of the study. The 24-h blood pressure was monitored by a SpaceLabs 5300 device (four readings per hour during the day and three readings per hour during the night) twice, at a 4-week interval. Systolic (SBP) and diastolic blood pressure (DBP) were averaged for each hour and for the whole 24-h period, and hourly and 24-h reproducibility was quantified by the standard deviation of the mean difference (SDD) between the values obtained in the two recordings. The SDD of hourly SBP and DBP was much greater than that of the 24-h values and ranged widely between the hours of recording. The SDD of hourly SBP and DBP were also variably greater than the SDD of the 24-h value in another 14 untreated essential hypertensives in whom 24-h ambulatory blood pressure was monitored intra-arterially twice at a 4-week interval to calculate hourly average blood pressure on thousands rather than on three or four values per hour. Reproducibility is less for hourly than for 24-h average blood pressure. This feature (which probably depends on behavioural differences between two recordings) suggests that ambulatory blood pressure measurement partly loses its advantages for reproducibility and reduction in trial size if the results are analysed over hourly periods.


[Clinical varicella-zoster virus reinfection observed in two advanced-age persons]. We observed two mild varicella cases of an advanced-age man and woman, although varicella in the adult generally presents a more severe course than in the child. The cases had been exposed to his great-grandchild and her grandchild with varicella in their home. They did not experience neuralgia as is typical from herpes zoster. Serological examinations revealed that they had high IgG-antibodies (Ab) against varicella-zoster virus (VZV), but low anti-VZV IgM-Ab. They were also found to have a high level of Ab against VZV soluble antigens (Ag) which are generally low in primary VZV infection. Immunoblotting analysis of anti-VZV IgG-Abs using sera from case 1 or 2 showed that their reaction patterns resembled those of sera children who contracted mild varicella after immunization with varicella vaccine and a herpes zoster-patient rather than those of sera from an immunocompetent adult with varicella. These results of serological examinations and their clinical course indicated that the cases had contracted varicella in the past and were again exposed to VZV resulting in clinically overt but mild varicella.


[Detection and serotyping of HRVs collected from children with acute gastroenteritis in winter of 1986 to 1991]. Fecal samples from sporadic acute gastroenteritis patients who visited at a pediatrician during five consecutive winter seasons in Kurume City located at north part of Kyushu district. Fecal samples were subjected to detection of rotavirus and other viruses and study of yearly changes in serotype of rotavirus. The rate of group A rotavirus positives in third winter and other consecutive winters were 12.5%, 40 to 65%, respectively. 60% specimens were successfully serotyped: 58% was serotype 1.22% was serotype 3.6% was serotype 2, and 14% was serotype 4. The dominant serotype in first, fourth and fifth winter was type 1. However in second winter each serotype of rotavirus was almost equally detected. During five consecutive winters six patients visited at the same pediatrician twice more than two months interval. They all had acute gastrointestinal symptoms. In six patients rotavirus was detective just once.


[Dose finding study of sparfloxacin in single-dose therapy for female acute uncomplicated cystitis]. Sparfloxacin (SPFX) is a new quinolone compound with a long half-life of 16 hours and a potent antibacterial activity (MIC90: < or = 0.025 micrograms/ml against Escherichia coli), suggesting that the agent can be effectively used in single-dose therapy for acute uncomplicated cystitis in female patients. To find the optimum dose, the present dose-finding study was conducted. A dose of either 100 mg or 200 mg of SPFX was selected by the double-blind method, and was administered only once (single dose therapy). The clinical efficacy was judged on day 3, 7 and 14 after administration. On day 3, of the 49 pts. in the 100 mg-group, the efficacy rate was 95.9% (excellent rate: 79.6%), and of the 42 pts. in the 200 mg-group, it was 100% (excellent rate: 88.1%). On day 7, of 38 pts. in the 100 mg-group, it was 94.7% (excellent rate: 78.9%), and of 28 pts. in the 200 mg-group, it was 100% (excellent rate: 92.9%). On day 14, of 27 pts. in the 100 mg-group, it was 92.6% (excellent rate: 66.7%), and of 26 in the 200 mg-group, it was 96.2% (excellent rate: 84.6%). Recurrence was observed in 4.8% (1/21) in the 200 mg-group. Therefore, there was no significant difference in the efficacy rate between the two groups, but the rate of excellent responses was higher in the 200 mg-group. Otherwise, the efficacy was estimated to be insufficient in 3 pts. and recurrent in 1 pt. they were examined the findings of detailed urological intractableness. Among 2 pts. in whom the external genitalia and urethra were closely examined, a urethral caruncle was noted in 1 pt. The results of our study indicate that 200 mg of SPFX is recommended as a single dose therapy for acute uncomplicated cystitis in females.


[Cytomegalovirus pneumonia treated with ganciclovir and intravenous CMV-hyperimmune globulin: case report]. A 60-year-old male with adult T-cell leukemia (ATL) complained of fever, cough and dyspnea, after anti-leukemic chemotherapy. Chest X-ray film showed a diffuse interstitial shadow, and cytomegalic inclusions and cytomegalovirus (CMV) antigen were detected in the bronchoalveolar lavage specimen and sputum. The diagnosis of CMV pneumonia was made, then ganciclovir and intravenous CMV-hyperimmune globin was administered. Although CMV pneumonia was improved with the treatment, the patient died of ATL. There was no cytomegalic inclusions in the lung but in the adrenal at autopsy. The combination therapy of ganciclovir and intravenous CMV-hyperimmune globulin is considered to be effective for CMV pneumonia.


Gross and histological abnormalities of the foregut in familial adenomatous polyposis: a study from a South East Asian Registry. Polyps in the stomach and duodenum are frequently found in familial adenomatous polyposis. Cancer arising from some of these polyps may be an important cause of death in patients who have had large bowel resections. This study aims to determine the nature and distribution of foregut polyps in Chinese patients. Twenty-five patients with familial adenomatous polyposis were gastroscoped by a single operator using the end viewing video-endoscopy system. Representative biopsies of normal mucosa or polyps where appropriate were taken from the gastric fundus, antrum and the duodenum. Twenty-five patients were studied. Male = 17, female = 8. Median age was 32 years (range = 17-63 yrs). Nineteen patients were found to have macroscopically visible polyps in the foregut. Ten patients had gastric polyps alone, three patients had duodenal polyps alone whilst six patients had both gastric and duodenal polyps. Twelve, one and three patients had more than 20 polyps in the gastric fundus, antrum and duodenum respectively. Only one patient had polyps which were larger than 10 mm. The commonest polyp in the gastric fundus was the fundic gland polyp whilst hyperplastic and adenomatous polyps were the commonest polyps in the gastric antrum and duodenum respectively. Five patients had adenomatous polyps of which four had duodenal adenomas alone whilst one patient had adenomas in the duodenum, gastric antrum and fundus. Seventy-six per cent of our patients with familial adenomatous polyposis had foregut polyposis. Adenomatous polyps were found in 56% of patients with duodenal polyps or 20% of patients with foregut polyps but hyperplastic and hamartomatous polyps occur commonly in patients with familial adenomatous polyposis as well.


Abdominal rectopexy with sigmoidectomy vs. rectopexy alone for rectal prolapse: a prospective, randomized study. A prospective, randomized study comparing abdominal rectopexy and sigmoid resection (Group I; n = 15) with polyglycolic acid mesh rectopexy without sigmoidectomy (Group II; n = 15) for complete rectal prolapse was carried out. One patient in Group I died of myocardial infarction, one patient in Group II had a small bowel obstruction and two patients in Group I an asymptomatic stricture of the anastomosis. Otherwise a safe and efficient control of the prolapse was achieved in both groups. Eleven (73%) patients in Group I and 12 (80%) patients in Group II were more or less incontinent before surgery. After correction of prolapse incontinence improved in eight and ten patients in Groups I and II, but became slightly worse in one patient in Group II. A similar rise in anal pressures was measured in both groups after surgery. Constipation disappeared in three and seven patients in Groups I and II six months after surgery, but five additional patients in Group II became severely constipated and colectomy had to be performed in one of them. Surgery caused no significant change in colonic transit times even though increased transit times were measured in each group six months postoperatively. Sigmoid resection in conjunction with rectopexy does not seem to increase operative morbidity but tends to diminish postoperative constipation possibly by causing less outlet obstruction.


Human papilloma virus infection in cervical cytology study. The prevalence of HPV infection detected by cytology examination in this study (1990) was 2.26 per cent, in which 50.18 per cent of them were HPV infection alone and 49.82 per cent were HPV infection coexisted with abnormal Pap smears. This viral infection was detected in all age groups but was highest in the age, between 40 to 44 years, and lowest in the age group older than 65 years. It was also noted that, 25.98 per cent of CIN (252 out of 970) and 4.56 percent of carcinoma (19 out of 417) showing morphologic cell changes due to HPV infection with the average number of cell changes indicating this viral infection in 19.54 per cent of all abnormal Pap smears (271 from 1,387).


Electron microscopic study on the development of herpesviruses. This review is concerned with comparative electron microscopic observations of in vitro cultured cells infected with twelve kinds of herpesviruses including six human herpesviruses. Morphological differences in intranuclear particles with cores of low density among these viruses mainly due to inherent differences in the ultrastructure of particular viruses, the morphological variety of intranuclear particles of herpes simplex virus due to their different developmental stages, and unusual structures observed in cells infected with some herpesviruses are described. Viral envelopment relevant to the final step of maturation of herpesviruses and their egress from infected cells are discussed.


Receptive field organization of retinal ganglion cells in the spastic mutant mouse. 1. We examined the receptive field properties of retinal ganglion cells in the isolated, superfused retinae of spastic mutant mice (B6C3Fe-spa/spa) that did not have the retinal degeneration (rd) phenotype. Glycine receptor density in the spastic mutant is greatly reduced in all areas of the CNS that have been examined. Phenotypically normal litter-mates were used as controls. Radial sections from the retinae of both spastic and normal animals were examined with light and electron microscopy and no differences were observed. The planimetric density of the cell bodies in the inner nuclear layer did not differ between the normal and mutant animals, about 400 cm-2. The absolute dark-adapted sensitivity of spastic ganglion cells was greater (271 +/- 69.0 impulses quanta-1 rod-1) than that of normal ganglion cells (47.7 +/- 10.4 impulses quanta-1 rod-1; P < 0.01). 2. Extracellular recordings of retinal ganglion cell responses to circular and annular stimuli, centred on the receptive field, were used to construct peri-stimulus-time histograms. In normal retinae, an annular stimulus elicited a response that was characteristic of the surround response mechanism of receptive fields with antagonistic centre-surround organization. In the mutant retina, annular stimuli did not elicit a surround-type response; instead, a centre-type response was recorded. 3. Illumination of the receptive field periphery attenuated centre-type responses in ganglion cells from both spastic and normal retinae. Centred circular stimuli of various areas (14, 35, 78, 122, 235, 783 deg2) were presented to the receptive fields. For mutant and normal ganglion cells, the response to the largest stimulus was smaller than that to an intermediate-sized stimulus. 4. The effect of strychnine, a glycine receptor antagonist, on the response to circular stimuli was examined. Very low concentrations of strychnine attenuated the light response in mutant retinae (apparent inhibitory binding constant KI = 8.1 x 10(-13) M). In normal animals, the light response was also attenuated by strychnine, but the apparent KI was much higher (apparent KI = 1 x 10(-7) M). 5. In normal ganglion cells, the sustained component of the light response was much more attenuated by strychnine than was the transient component. Interestingly, ganglion cells from spastic retinae did not exhibit a sustained component, even at stimulus luminances that evoked responses near threshold.(ABSTRACT TRUNCATED AT 400 WORDS)


Mechanisms of caffeine-induced contraction and relaxation of rat aortic smooth muscle. 1. Using front-surface fluorimetry and Fura-2, we determined the effects of caffeine on cytosolic calcium concentration ([Ca2+]i) and on tension of strips of the rat thoracic aorta. We also determined the effects of caffeine on 45Ca2+ influx into the strips. The objective was to elucidate the mechanism of contraction and relaxation in vascular smooth muscle, as induced by caffeine. 2. In normal physiological salt solution (PSS), caffeine induced a transient tension development, while it induced a biphasic change in [Ca2+]i. The initial transient peak in [Ca2+]i which coincided with tension development was followed by a sustained increase. Thus, changes in tension did not follow changes in [Ca2+]i. In Ca(2+)-free PSS, both the caffeine-induced contraction and the increase in [Ca2+]i were transient. It was suggested that in both the presence and absence of extracellular Ca2+, the transient increase in [Ca2+]i was due to the release of Ca2+ from the intracellular store. Although the sustained increase in [Ca2+]i depended on extracellular Ca2+, it was not affected by diltiazem, a Ca2+ antagonist. 3. Caffeine inhibited the increase in [Ca2+]i and tension development during 118 mM-K+ depolarization, in a concentration-dependent manner. The extent of reduction in tension (relaxation) was greater than that expected from the reduction in [Ca2+]i based on the [Ca2+]i-tension relationship observed with K+ depolarization. Pretreatment of the strips with ryanodine did not alter the inhibitory effects of caffeine. 4. Caffeine inhibited the increased [Ca2+]i and developed tension during stimulation by 10(-5) M-noradrenaline, in a concentration-dependent manner. 5. Dibutyryl cAMP (10(-4) M) inhibited both high K(+)-induced and noradrenaline-induced tension development. Inhibition of an increase in [Ca2+]i in relation to the inhibition of tension during noradrenaline stimulation was much greater than that in 118 mM-K+ depolarization. 6. Although caffeine per se had no effect on 45Ca2+ influx in the strips in normal PSS, caffeine did inhibit the increase in 45Ca2+ influx stimulated by 118 mM-K+ or by 10(-5) M-noradrenaline, to a similar extent and with similar IC50 values. 7. The characteristic features of the effects of caffeine on vascular smooth muscle, i.e. the transient nature of contraction and the relaxation of precontracted strips could be explained as follows: caffeine is able to reduce [Ca2+]i after releasing Ca2+ from intracellular stores; however, this may play a minor role. Independent of the [Ca2+]i reduction, the second messenger, cAMP, might directly influence the [Ca2+]i-tension relationship, and if so, would play a major role.