[Torsion of the middle lobe after right upper lobectomy of the lung; report of a case and the review of the Japanese literatures].

We report a case of torsion of the residual right middle lobe of the lung, following right upper lobectomy for lung cancer. A 71-year-old man who had medical treatment for emphysema was admitted with a lung tumor on chest computed tomography. The tumor was diagnosed as pulmonary adenocarcinoma by transbronchial biopsy. Right upper lobectomy with mediastinal lymph node dissection, and partial resection of the right lower lobe were performed. On the following day, chest X-ray showed an opacification in the right upper lung field, which gradually increased. Bronchoscopic examination revealed a stenotic middle lobe bronchus. Torsion of the middle lobe was suspected, and rethoracotomy was performed on the second postoperative day. The middle lobe was torsed 90-degree counterclockwise around its bronchovascular pedicle. A middle lobectomy was performed secondary to severe congestion. The patient was discharged in good condition on the 11th postoperative day. In reviewing the literatures including this case, 13 of 16 torsions occurred after right upper lobectomy of the lung. Thirteen patients had rethoracotomy, 10 of them underwent resection of the rotated lung. Simple detorsion was carried out in 3 patients, and 1 of them developed cerebral infarction. Lung torsion was reported to be potentially life-threatening. Therefore, fixation of a remaining lobe should be performed. Exploratory thoracotomy should be performed without delay, if lung torsion is suspected.

[Delayed rupture of a balloon reservoir in a disposable infusion pump].

We experienced delayed rupture of a balloon reservoir in a disposable infusion pump 3 hours after filling. The investigation revealed a sharp scratch in the reservoir. Furthermore, as we did not filtrate the drugs before filling, we speculate that ampule fragments could have provoked the rupture. When filling a disposable infusion pump with ampule solution, filtration against glass contamination is recommended.

Effects of the ester moiety on stereoselective hydrolysis of several propranolol prodrugs in rat tissues.

The stereochemical characteristics of the hydrolysis of several ester-type prodrugs of propranolol, O-acetyl, O-propionyl, O-butyryl, O-pivaloyl and succinyl esters, were studied in phosphate buffer (pH 7.4), rat plasma and rat tissue homogenates. In phosphate buffer, no differences were observed in the hydrolysis rate between the esters of (R)- and (S)-propranolol. The effects of the ester moieties on the hydrolysis rate in phosphate buffer were in the following order: acetate > propionate > butyrate > succinate > pivalate. In rat plasma and tissue homogenates, the hydrolysis of the esters was accelerated, and stereoselective hydrolysis was observed. In plasma, the hydrolysis of the (R)-isomer was faster than that of the (S)-isomer except for the succinate ester. On the other hand, in the liver and intestine homogenates, the (S)-isomer was hydrolyzed faster than the (R)-isomer except for the succinate and pivalate esters in the liver homogenate. Also, the ratio of the hydrolysis rates (S/R) changed with the type of prodrug. As the length of the alkyl chain of the ester increased, the S/R ratio approached unity in liver and intestine homogenates but stayed almost constant in plasma. For the pivalate ester, stereoselective hydrolysis was observed in plasma and intestine homogenate but not in liver homogenate. The stereoselective hydrolysis of the succinate ester was observed only in intestine homogenate, but the S/R ratio was almost 1 in plasma, liver and intestine homogenates. No interconversion between (R)- and (S)-isomer was observed during the hydrolysis of any of the ester prodrugs. These results indicate that hydrolysis of ester-type prodrugs of propranolol occurs stereoselectively in rat tissues, and that its selectivity is dependent on the kind of tissue and prodrug.

Percutaneous permeation of basic compounds through shed snake skin as a model membrane.

Relationships between the in-vitro permeability of basic compounds through shed snake skin as a suitable model membrane for human stratum corneum and their physiochemical properties were investigated. Compounds with low pKa values were selected to compare the permeabilities of non-ionized forms of the compounds. Steady-state penetration was achieved immediately without a lag time for all compounds. Flux rate and permeability coefficient were calculated from the steady-state penetration data and relationships between these parameters and the physicochemical properties were investigated. The results showed that permeability may be controlled by the lipophilicity and the molecular size of the compounds. Equations were developed to predict the permeability from the molecular weights and the partition coefficients of basic compounds.

Stereoselective hydrolysis of O-acetyl propranolol as prodrug in rat tissue homogenates.

The stereochemical characteristics of the hydrolysis of O-acetyl propranolol were studied using phosphate buffer (pH 7.4), rat plasma, and rat tissue homogenates. In the phosphate buffer, no difference was observed in the hydrolysis rate between the esters of (R)- and (S)-propranolol. In rat plasma and tissue homogenates, hydrolysis of the ester was both accelerated and stereoselective. Hydrolysis of O-acetyl (R)-propranolol was five times faster than that of the (S)-isomer in rat plasma. However, in the liver and intestine homogenates, the (S)-isomer was hydrolyzed faster than the (R)-isomer. Interconversion between the (R)- and (S)-isomers was not observed under the experimental conditions. The same stereoselective hydrolysis was also observed with racemic O-acetyl propranolol. However, observed rate constants for the hydrolysis were lower than those for the pure isomers. These results indicate that enzymatic hydrolysis of O-acetyl propranolol occurred stereoselectively and the selectivity of the plasma enzyme was different from those of liver and intestine enzymes.

[Changes of pupil size in brain death patients].

The representative criteria of brain death in Japan is Takeuchi Criteria (Koseisho Criteria), which is the definition of irreversible loss of brain function (functional brain death). The 3rd item of that criteria is "fixed pupil" and pupil size more than 4 mm. The 4th item is loss of the brain nerve reflexes including the light reflex. Three cases of brain death by whole brain destruction (organic brain death) who showed slow changes of pupil size were reported. Except fixed pupil, one case fulfilled Takeuchi Criteria. Other two cases fulfilled all items of Takeuchi Criteria, showing the same pupil size accidentally at the first and the second judgements. But, they changed their pupil size slowly and continuously after the examinations, showing tendencies toward mydriasis and/or miosis, repeatedly. They never decreased their pupil size less than 4 mm. The changes of pupil size were so slow that we could recognize them only after several hours or several days, and they were quite different from the light reflex. They did not receive any influences from turnover of day and night, darkness of the room, dopamine, etc. For the changes of pupil size were observed in the cases of organic brain death, it was elucidated that they were not due to the brain nerve activity. Then, it was considered that the changes of pupil size in the cases of functional brain death should be the same phenomena, because brain nerve function was lost.(ABSTRACT TRUNCATED AT 250 WORDS)

[Cryptosporidium diarrhea developing in two Japanese adults--one in AIDS and the other in a normal host. Research Group for Infectious Enteric Diseases, Japan].

Case I: A middle-age homosexual male developed AIDS with Pneumocystis carinii pneumonia (PCP) and esophageal candidiasis in 1986 during his stay in an European country about five months prior to transfer to Tokyo Metropolitan Komagome Hospital, Tokyo, in 1987. He was also diagnosed as having cryptosporidiosis presenting with mild diarrhea a month following the diagnosis of PCP. Diarrhea was successfully treated with spiramycin. On transfer to Tokyo Metropolitan Komagome Hospital, he was febrile but had no diarrhea. Serum HIV and TPHA were positive and his blood lymphocyte subset T4a was markedly decreased. On the 13th day after transfer to the hospital, watery diarrhea appeared. Cryptosporidium oocysts were detected from the feces taken on the 17th hospital day. The patient died of Escherichia coli septicemia on the 38th hospital day. Autopsy finding yielded Cryptosporidium infection widely spread over the stomach, ileum, bile and pancreatic ducts. Case II: A 31-year-old previously healthy female presented with abrupt onset of mucous stool five times daily. Mucous passage continued on the subsequent days despite administration of loperamide, and the passage increased to 20 times daily with mucous to watery diarrhea associated with mild abdominal cramps and nausea on the 4th day after onset of illness. On the 6th day of illness, she visited Tokyo Metropolitan Komagome Hospital. She denied close contact with pet animals or contact with any person presenting diarrhea. She had no recent history of travelling anywhere outside Tokyo. On examination she was an apparently healthy woman except for a slightly distended abdomen with localized tenderness in the right upper quadrant.(ABSTRACT TRUNCATED AT 250 WORDS)

In vitro percutaneous transport of sodium diclofenac and diclofenac from oleaginous vehicle.

The penetration enhancement of sodium diclofenac and diclofenac by alcohols with various alkyl chains (C8 to C14) was evaluated by the steady state flux of diclofenac through rat abdominal skin. Decanol showed the greatest effect in this series. A more remarkable enhancing effect of the alcohols was observed in sodium diclofenac than in diclofenac. Diclofenac can penetrate through the ethylene-vinyl acetate membrane as a lipoid model membrane, but sodium diclofenac can not. Decanol enhanced the penetration of phenol red being dependent on its concentration in the vehicle. Therefore, decanol may interact with lipoid components of the skin and increase the aqueous pathway in the skin. These results indicate that sodium diclofenac and diclofenac may be penetrated through partially different pathways.

In vitro transport of sodium diclofenac across rat abdominal skin: effect of selection of oleaginous component and the addition of alcohols to the vehicle.

The in vitro percutaneous transport of sodium diclofenac from various oil vehicles was examined using rat abdominal skin as a model skin membrane. The overall transport of diclofenac through the skin from the oleaginous vehicles was very poor because of a poor solubility of sodium diclofenac in nonpolar oils. To increase the solubility and the permeability of sodium diclofenac, ethanol and n-octanol were added to each oil (designated as the formulated vehicles). The addition of ethanol and n-octanol to the nonpolar vehicles resulted in an extreme increase in drug solubility in each vehicle, with a remarkable increase in the permeation of diclofenac. The effects of oil components in the formulated vehicle on the permeation of diclofenac across the skin were in the following order: squalane greater than or equal to squalene greater than liquid paraffin greater than middle chain triglyceride greater than olive oil greater than castor oil. In order to clarify the reason for the differences in permeation of diclofenac from these formulated vehicles, the release of diclofenac and n-octanol from these vehicles in vitro was studied. The release rates of n-octanol from the formulated vehicles were in the following order: liquid paraffin greater than squalene greater than or equal to squalane greater than middle chain triglyceride greater than or equal to olive oil greater than castor oil. On the other hand, a linear correlation was observed between the initial release rate of diclofenac from the formulated vehicle and the in vitro permeation of diclofenac through the vehicle to the skin.(ABSTRACT TRUNCATED AT 250 WORDS)

Stereoselective hydrolysis of O-acetyl propranolol as prodrug in human serum.

A direct high-performance liquid chromatographic method was developed for the assays of the enantiomers of O-acetyl propranolol. Using this procedure, the stereochemical characteristics on hydrolysis of racemic O-acetyl propranolol as a prodrug have been studied in phosphate buffer (pH 7.4) and in 90% human serum. In the phosphate buffer, no difference in the hydrolysis rate between the esters of (R)- and (S)-propranolol was observed. In 90% human serum, the hydrolysis of the esters was accelerated, and the hydrolysis rate of the ester of (R)-isomer was about three times faster than that of the ester of (S)-isomer. The interconversion between (R)- and (S)-isomer was not observed during the hydrolysis of prodrug in buffer and in human serum. These results indicated that hydrolysis of O-acetyl propranolol occurs stereoselectively in human serum.

[Trends in the study of AIDS].

The characteristics of the main route of HIV transmission today depends on life styles. But, in any country, it will be concentrated on the route of sexual intercourse and habitual intravenous injection of drug abusers, after education programs are in place. Epidemiological studies on HIV-II show that 21% of prostitutes in Cote d'Ivoire have antibody to HIV-II, and 0.3% of blood donors live in the high risk area in Paris. In the USA 4 AIDS patients with HIV-II infection were recognized by this February. Immunological cross reactions are seen between p26 from HIV-I and that from HIV-II, but, g140, p34 and p18 show different antigenicities. These antigens have being studied for developing vaccine. Recent studies show the usefulness of detecting antibody to accessory gene products, especially nef gene derived, for confirmation of HIV infection in the early clinical stage. HIV antigen shows the activity to control the function of plasmid which is introduced to the cell. That means HIV antigen works as a promoter in the infected cell. Anti-HIV agents have been studied from view points of inhibition of virus absorption to cell surface, activities of cell membrane, uncoating of virus in the infected cell, reading of virus gene and stage of virus maturation.

Detection of high levels of immunoreactive human beta-1 interferon in sera from HIV-infected patients.

We have examined human interferon beta-1 (HuIFN-beta 1) levels in the sera from patients with various diseases by using a newly developed highly sensitive enzyme-linked immunosorbent assay system (ELISA). High levels of HuIFN-beta 1 were detected in the sera from Human Immunodeficiency Virus-I (HIV-I) infected patients, especially of asymptomatic carriers. The serum level of HuIFN-beta 1 may be a good indicator of HIV-I infection and of other immunological disorders.

[In vitro studies on the activities of cephalothin against selected bacteria (author's transl)].

Cephalothin antimicrobial activities were studied against selected bacteria with special reference to the time of exposure of microbes to the drug assessed in broth medium. The minimal concentration of this drug producing 10(0)-10(1) reduction of colony forming unit (CFU) per ml after given exposure times -an approximation to the theoretical bacteriostatic concentration inhibiting increase or decrease of CFU- was designated as minimally reducing concentration (MRC). The concentration was determined after 6 h, 18 h and 42 h of incubation and designated as 6-h, 18-h and 42-h MRC, respectively. Conventional minimal inhibitory concentration (MIC) with 18 h exposure time was also studied. The minimal concentration of the drug yielding 99.9% reduction of CFU after an exposure to the drug was determined and designated as minimal lethal concentration (MLC). The determinations were made at 6 h, 18 h and 42 h of incubation and designated as 6-h, 18-h and 42-h MLC, respectively. The data indicated that the bacteriostatic concentration for Escherichia coli and Klebsiella sp. with brief exposure time (6-h MRC) was 2-4 times lower than the MIC. If the exposure time was prolonged (18-42 h), the bacteriostatic concentration increased and almost agreed with the MIC. A significant effect of inoculum size was observed on the MRC values for the Gram-negatives when the values were determined with the inoculum concentrations at 10(6)-10(7) CFU/ml and 10(3)-10(4) CFU/ml. In contrast to these Gram-negatives, the 6-h MRC for most strains of Staphylococcus aureus and Enterococcus roughly agreed with the MIC. If the ratio of bacteriostatic to bactericidal concentrations was used as the criterion, the mode of action of cephalothin appeared to be bactericidal for most of the Gram-negatives. This drug was bacteriostatic for a number of the Gram-positive strains, in particular to those of Enterococcus, especially when microbes were exposed to the drug over a brief period of time.