Synthesis and antiviral activity of sulfonamidobenzophenone oximes and sulfonamidobenzamides

To find antiviral agents, various sulfonamidobenzophenone oximes (II) were synthesized from the appropriate m-sulfonamidobenzophenones by hydroxylamine reaction. The reaction products were generally obtained as syn/anti mixtures which were separable by fractional crystallization. The anti isomer had more potent antipoliovirus activity than the syn isomer. Various sulfonamidobenzamides (III) which were structurally related to II were synthesized by the reactions of amino-substituted benzamides with sulfuryl chloride or amines with (aminosulfonyl)benzoyl chloride. Antiviral activity was examined by the plaque-inhibition test. Compounds 5, 36, and 69 exhibited strong antipicornavirus activity. The structure-activity relationships are discussed.     

Experimental evaluation of respiratory assist and hemodynamic changes by veno-venous bypass

The veno-venous bypass (VVB) with a membrane lung is one of the effective procedures to provide respiratory assistance even in patients with a high mortality rate when assisted only with mechanical ventilation. The purpose of this experimental study was to reveal the efficacy of respiratory assistance and the hemodynamic changes by VVB in acute respiratory failure. VVB was carried out in 22 mongrel dogs with acute respiratory failure induced by intratracheal seawater infusion. The ventilation-perfusion ratio (V/Q) of a membrane lung was changed to 1.0, 2.0 and 3.0 for each of the bypass flow rates of 20%, 40%, 60% and 80% of pre-perfusion cardiac output. For each condition variables indicating blood gas status and hemodynamic parameters were measured. As the indicator evaluating the efficiency of CO2 removal by VVB, the index of VVBCO2R was used, indicating the blood CO2 tension differences between IVC and the pulmonary artery. Arterial oxygen saturation was increased with bypass flow rates greater than 60% compared with pre-VVB, but the change was not marked. VVB was considered to be inadequate as a method of oxygenation. Besides, oxygenation was not able to be controlled by changing V/Q. However, significant reduction of arterial CO2 tension (PaCO2) could be obtained even with a bypass flow rate of 20%. As the blood flow rate increased, PaCO2 was lowered. But no more significant reductions of PaCO2 were obtained even with the flow rate of 60% and 80%. VVBCO2R was increased by changing the bypass flow rate from 20% to 40%, while no further increases were observed even with changes from 40% to 60% and 80%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Analgesic dose-response relation in cervical epidural block

The relationship between the age and the spread of analgesia from different epidural anesthetic doses was examined by studying analgesic dose responses in cervical epidural analgesia. Two different anesthetic doses (5ml or 10ml) of 2% mepivacaine were injected into the cervical epidural space at a constant pressure (80mmHg) using an intravenous apparatus, and the spread of analgesia to pinprick was assessed. The significant correlation was found between the patients age and the number of spinal segments blocked (5ml:r = 0.8498, P < 0.01, 10ml:r = 0.5988, P < 0.01). The inverse linear relationship was found between the patients age and the segmental dose requirement (5ml:r = –0.6754, P < 0.01, 10ml:r = –0.5784, P < 0.01). Patients under 39 years of age showed a direct relationship between the dose injected and the number of spinal segments blocked, enabling prediction of the number of segments blocked with a given dose of local anesthetic. Doubling the epidural dose approximately doubled the number of spinal segments blocked. The analgesic dose-response relation in patients over 60 years of age differed from that in patients under 39 years of age and doubling the epidural dose did not double the number of spinal segments blocked. Progressively more extensive analgesia was obtained from a given dose of local anesthetic with advancing age. It was difficult to limit the extent of analgesia by injecting a smaller dose of local anaesthetic in the elderly.(Hirabayashi Y, Matsuda I, Inoue S et al.: Analgesic dose-response relation in cervical epidural block. J Anesth 2: 22–27, 1988)     

Evaluation of nicotine,cotinine, thiocyanate,carboxyhemoglobin, and expired carbon monoxide as biochemical tobacco smoke uptake parameters

Summary In a cross-sectional study on 236 individuals in Japan (174 males, 62 females; 149 smokers, 87 non-smokers) plasma nicotine (pnic), cotinine (pcot) and thiocyanate (pSCN), urinary creatinine ratios of nicotine (unic), cotinine (ucot) and thiocyanate (uSCN) as well as carboxyhemoglobin (COHb) and expired carbon monoxide (COex) were determined. All tobacco smoke uptake parameters (TSUP) were significantly elevated in smokers as compared to non-smokers. The discriminant power (smokers vs non-smokers) rank in the following order: ucot pcot unic > pSCN COHb pnic > COex uSCN. All parameters except for pnic are significantly correlated with the self-reported number of cigarettes smoked per day. The reason for the poor correlation of pnic with daily cigarette consumption is the short half-life of pnic coupled with the arbitrary time of blood drawing in relation to the last time of smoking.Dr. Muranaka, the chief author of this paper, was the director of our hospital. He died suddenly on 18 April 1986. This article is therefore the last monument to be planned and achieved under the late Dr. Muranaka's direction.     

HLA phenotype in patients with osteosarcoma

Nineteen patients with typical osteosarcoma were studied for evidence of association with human leukocyte antigen (HLA) phenotypes. HLA-A11 was detected in nine of 19 patients (47.4%) compared with 16.9% of 235 controls (chi 2 " 10.861, p less than 0.001), which yielded an odds ratio of 4.523. The positive rate of HLA-A11 was significantly increased in the patients. Interestingly, five of seven patients with poor prognosis had HLA-A11, compared with two of nine disease-free patients, 18 months after the initial treatment. These data suggest that major histocompatibility complex (MHC)-linked genes determines susceptibility to the occurrence of osteosarcoma and its prognosis.     

Clinical study on intracranial arachnoid cyst: with reference to the middle cranial fossa

Thirty-two cases of congenital arachnoid cyst (AC), 26 cases of supratentorial, and 6 cases of infratentorial cyst are reported. They were encountered over a period of 9 years. The 26 supratentorial cysts consisted of 21 cases located in the middle fossa, 2 in the frontal, and 3 in the suprasellar. Patients' ages ranged from 7 months to 67 years (mean: 19.3 years), with a male to female ratio of 23:9. The most common symptoms were headache, epileptic seizure, and cranial enlargement. Based on observations between neuroradiological examinations including analysis of the cyst content, and operation, typical AC might be defined as "duplicated arachnoid and its splitting", and it may be said that "there is continuous existence of cerebral structure such as cortex and white matter lying adjacent to AC on MRI". Out of 32 cases, 15 received surgical treatment because of mass effect of AC itself, abnormal dynamics of the AC fluid, and/or increasing sign of ICP. 13 cases had resection of AC outer membrane with craniotomy, and the remaining two had cystoperitoneal shunt. One of the shunting cases complicated subdural hematoma. Surgical treatment was discussed and radical craniotomy rather than a shunt procedure was preferred. Prognosis of all cases was favorable and uneventful.     

Transient induction of single GST-P positive hepatocytes by DEN

The single cells positive for placental glutathione S-transferase(GST-P), detectable in livers of rats soon after treatment withhepatocarcinogens, are possible ‘initiated cells’,the hypothesis tested in the present series of experiments.No low dose threshold was observed in male Sprague-Dawley ratsat different single doses of diethylnitrosamine (DEM) althougha plateau was reached between 160 and 200 mg/kg body weight.At the latter single dose 12 400 positive cells/cm³ were observedimmunohistochemically in rat livers after one week, the numbersthen decreasing to week 8 and thereafter rising again. In thenumbers then decreasing to week 8 and thereafter rising again.In the early stages single cells predominated but with timea gradual increase in mini-foci and larger lesions became evident.Application of selection pressure (feeding of diet containing0.02% 2-AAF plus partial hepatectomy) to rats 2–24 weeksafter single DEN-treatment resulted in the formation of largefoci positive for GST-P, especially in the early stages, thegrowth response being less pronounced with time. The numberof foci, on the other hand. was correlated with the number offoci, on the other hand, was correlated with the number ofsingle cells/mini-foci detected inhepatectomy tissue of thesame individuals. These results suggest that the early GST-Ppositive populations could be the precursor for preneoplasticfoci and nodules.