Diffuse alveolar damage in the horse

In a preliminary study the principles of standard gynaecological surgery, new operative laparoscopic techniques and mechanical elevation of the abdominal wall are combined. These early results indicate an advantage to both patient and hospitals from this approach. Further studies are required to verify our impressions that minilaparotomy combined with no insufflation laparoendoscopy will open up the concept of operative laparoscopic surgery to most gynaecologists.     

Potentiation of a three drug chemotherapy regimen by radiation

The combination of N-(phosphonacetyl)-L-aspartate, 6-methylmercaptopurine, and 6-aminonicotinamide has been shown to be an effective antineoplastic regimen and also to enhance the effects of other chemotherapeutic agents. The mechanism of action of this combination of drugs is not known definitively, but one possible mechanism is biochemical modulation of energy metabolism and inhibition of production of tumor ATP. Tumor-bearing mice were treated with N-(phosphonacetyl)-L-aspartate, followed 17 h later by 6-methylmercaptopurine and 6-aminonicotinamide. 31P nuclear magnetic resonance spectroscopic studies demonstrated a significant depletion of high energy phosphates at 10 h post-6-methylmercaptopurine and 6-aminonicotinamide. The addition of radiation at this time was shown to induce a significantly longer tumor growth delay and a greater number of regressions (including durable complete regressions) than either chemotherapy or radiation alone. The combination of chemotherapy and radiation was found to be supra-additive compared to the antineoplastic effects of either modality administered separately, without a measurable increase in host toxicity.     

Pharmacokinetics of a single dose of phenylpropanolamine following oral administration at two different times of the day

Pharmacokinetics of a single oral dose of phenylpropanolamine (CAS 154-41-6) was investigated by administering 50 mg of the drug at 10.00 and 22.00 h to 8 healthy male volunteers in a crossover design with a wash-out period of 10 days. Serum samples were analysed for phenylpropanolamine using high performance liquid chromatography. Pharmacokinetic parameters were calculated using model independent method. A significant (p < 0.05) elevation in Cmax (227.45 versus 181.98 micrograms/l) was observed following the drug administration at 22.00 h as compared to 10.00 h. These variations may be due to circadian changes in gastric pH contributing to the time dependent changes in the absorption of the drug.     

Outpatient chemotherapy of advanced breast cancer in a community setting: a five-drug regimen

Forty-two (37 evaluable) unselected women with advanced breast carcinoma were treated with a modified "Cooper regimen" in a community setting. After 12 weeks of induction therapy, the patients were evaluated for response and toxicity. The 74% overall response rate (78% in the evaluable group) compares favorably with that of other series. The median duration of remission was 13.7 months. The median survival was 17 months for the evaluable patients and 14 months for the entire group. Twenty-two percent of the patients required hospitalization during the induction phase, and 35% were treated exclusively as outpatients during all phases of therapy. There was only one drug-related death. It is concluded that a complex chemotherapeutic regimen can be managed adequately by physicians experienced in chemotherapy in a community setting with results comparable to those from cancer centers.     

Pregnancy following a single lung transplant

Successful pregnancy in a single lung transplant recipient has not been reported previously. The long term effect of pregnancy on graft function and management of deteriorating pulmonary function is not defined. This case describes the management, outcome, and problems encountered when a single lung transplant recipient developed a progressive deterioration in pulmonary function during pregnancy, attributed to accelerated obliterative bronchiolitis.     

Hepatic and renal metallothionein induction following single oral administration of gallium arsenide in rats

Metallothionein genes (MT) are inducible by a variety of agents, including heavy metals. We report the induction of MT expression by gallium arsenide (GaAs), a superior intermetallic semiconductor material at two time intervals following single oral exposure in rats. The data is also supplemented with two additional groups exposed to gallium (III) as gallium oxide and arsenic (III) as sodium arsenite to determine which of the two moieties in GaAs is responsible for any such possible effects. The results indicate that GaAs administration does significantly induces MT in hepatic tissues accompanied by an increase in cytosolic glutathione, arsenic, zinc and copper concentration. It thus proves that arsenic moiety is chiefly responsible for such an effect.     

Comparative bioavailability of aspirin and paracetamol following single dose administration of soluble and plain tablets

In this study, the bioavailability of aspirin and paracetamol was compared in plain and soluble combination formulations in fasting, healthy volunteers. Blood samples were taken and Cmax, Tmax and AUC measured at various times following administration of single doses of the two formulations in 12 subjects. The rapidity of uptake of aspirin following administration of a soluble formulation suggests significant absorption from the stomach. There was no significant difference in the pharmacokinetic parameters of paracetamol derived from a soluble or plain formulation. A comparison of the uptake of aspirin from the soluble aspirin formulation with paracetamol from either plain or soluble tablets showed that aspirin entered the plasma and achieved peak levels significantly more quickly. However, the half life of paracetamol was significantly longer than that of aspirin. These findings suggest that onset of analgesia should be more rapid following dosing with soluble aspirin, a conclusion supported by comparative efficacy studies conducted with differing formulations of aspirin.     

High Helicobacter pylori eradication rate with a 1-week regimen containing ranitidine bismuth citrate

HSR-903 is a newly synthesized quinolone antibacterial agent with low toxicity. The biliary and urinary excretion of unchanged HSR-903, its R-isomer, and their glucuronides was determined after iv bolus administration (5 mg/kg) to normal Sprague-Dawley rats (SDR) and Eisai hyperbilirubinemic mutant rats (EHBR). The values for the biliary excretion clearance of HSR-903 and its glucuronide in EHBR were decreased to approximately 40 and 2% of those in SDR, respectively, whereas the values for the urinary excretion clearance of HSR-903 and its glucuronide were comparable in SDR and EHBR. The biliary excretion clearance values for the R-isomer and its glucuronide were approximately 3 times greater than those for HSR-903. These results demonstrated that the enantiomers of HSR-903 and their conjugates were excreted into bile in a stereospecific manner. The hepatic uptake of [14C]HSR-903 in vivo was evaluated by means of integration plot analysis. The results indicated that the hepatic uptake of [14C]HSR-903 was very fast and was blood flow-limited. To clarify the mechanism of excretion of HSR-903 into bile, the uptake and efflux of [14C]HSR-903 were studied using isolated hepatocytes from SDR and EHBR. The initial uptake of HSR-903 by hepatocytes was temperature-dependent, saturable, and stereospecific. Unlabeled HSR-903 (S-isomer), the R-isomer, grepafloxacin, and sparfloxacin significantly inhibited the uptake of [14C]HSR-903. The efflux of [14C]HSR-903 from hepatocytes from EHBR was significantly slower than that from hepatocytes from SDR. The addition of sodium azide or bromosulfophthalein reduced the efflux of [14C]HSR-903. These results demonstrate that HSR-903 is actively excreted into bile via the canalicular multispecific organic anion transporter, which is deficient in EHBR.     

Hemopoietic stem cells and antitumoral drugs. 1. Variations of in vitro and in vivo colony forming cells following single dose administration of cyclophosphamide, vinblastine and azathioprine (author''s transl)

Disaggregated cell suspensions made from transplanted solid tumors, either chemically-induced fibrosarcomas, or spontaneous mammary carcinomas, can contain very high numbers of Fc receptor-bearing cells which are of host origin. Because most types of lymphoreticular cells have Fc receptors, and because T cells--most of which are Fc receptor-negative--appear to infiltrate such tumors only to a very limited degree, the possibility that Fc receptor cells could serve as a reliable and simple marker for host lymphoreticular cell infiltration of solid tumors was tested. This was accomplished by comparing the ratios of Fc rosetting cells to serologically detectable host cells in H2d or H2k haplotype tumor cell suspensions grown in (H2d X H2k)f1 hybrid mice, where host cells could be distinguished from tumor cells by treatment with the appropriate anti-H2 serum. Ratios of 0.8 to 1.08 were obtained for four different tumors including the SaD/2 fibrosarcoma, a CBA spontaneous fibrosarcoma, and the T1699 and CaD/2 mammary carcinomas. Analysis of the results showed that enumeration of Fc rosettes was a reliable host cell maker for at least three of the four tumors tested. The mean non-malignant host cell content of the various tumors, as assessed by anti-H2 cytotoxicity tests, ranged from 23% to 41%.     

Effects of a single administration of clozapine on mouse brain catecholamines

In acute experiments on cats anesthetized with nembutal and chloralose the projections of different parts of orbito-frontal cortex, basal temporal cortex and hippocampus to hypothalamic nuclei were studied by focal potential recording. It was found that the proreal gyrus has local projections into the latero-dorsal parts of the preoptical region, rostral parts of the forebrain medial bundle, lateral and posterior hypothalamus with mammilary bodies. The orbital gyrus is projected mainly into latero-dorsal parts of the forebrain medial bundle, latero-ventral part of the preoptical region, and the region of lateral and latero-dorsal hypothalamic nuclei. Projections from the orbital gyrus are of a relatively diffuse character. The basal temporal cortex has diffuse projections into the central part of the preoptical region, latero-ventral part of the forebrain medial bundle and lateral mammilary body. No pronounced foci were observed in the hypothalamic structures during stimulation of the hyppocampus, but diffuse projections were found into ventral parts of the preoptical region and ventral regions of the forebrain medial bundle as well as into lateral hypothalamus and lateral mammilary nucleus.     

Interstitial pregnancy and management with a single systemic administration of methotrexate

OBJECTIVE: To examine the effect of grapefruit juice on the disposition of oral administered itraconazole in healthy subjects. METHODS: Twenty-two healthy male subjects received a single 100 mg dose of itraconazole with either 350 ml grapefruit juice, orange juice or mineral water. Plasma concentrations of itraconazole were measured by HPLC, and pharmacokinetic parameters; Cmax, Tmax, T1/2, AUC, and AUC corrected by human body surface area: AUC/S, were calculated. RESULTS: Grapefruit juice had no effect on any pharmacokinetic parameter of itraconazole. However, T1/2, AUC, or AUC/S were significantly decreased in orange juice treatment group compared to those in mineral water group (average decrease 56%, p < 0.01, 41%, p < 0.05, and 43%, p < 0.05, respectively). CONCLUSION: Coadministration of grapefruit juice did not affect any pharmacokinetic parameter of itraconazole while that of orange juice decreased the parameters of T1/2, AUC, and AUC/S of the drug.     

Kinetics of chlorhexidine on intact skin following a single application

Residual chlorhexidine concentrations were measured after application of a single dose on the skin of 22 healthy volunteers. Dosage by high-pressure liquid chromatography in the skin cleansers revealed that the residual concentrations were higher than chlorhexidine MICs for most organisms of the resident skin flora and some responsible for hand-borne infections, even 24 h after application.     

Direct gas chromatographic determination of dechloroethylcyclophosphamide following microsomal incubation of cyclophosphamide

A method for the sensitive determination of dechloroethylcylclophosphamide (3-DCl) in microsomal incubation mixtures was developed. 3-DCl, a side-chain oxidation product of cyclophosphamide (CP), was isolated by extraction with acetic acid ethyl ester following solid-phase extraction on C8 cartridges. Quantification of the metabolite was performed by direct capillary gas chromatography with a nitrogen-phosphorus detector without prior derivatization. The method showed good sensitivity and reproducibility with a detection limit of 1 ng/ml and a limit of quantification of 5 ng/ml. The suitability of the method is shown for the quantification of 3-DCl following incubation of CP with human liver microsomes.     

Detection of amphetamine following administration of fenproporex

Drugs that are metabolized to amphetamine or methamphetamine are potentially significant concerns in the interpretation of amphetamine-positive drug testing results. A number of different compounds have been reported to produce amphetamine in the urine of users. One of these compounds, fenproporex, has been shown to produce amphetamine. Previous reports indicate that the parent compound can be detected only for a few hours following administration, whereas the amphetamine can be detected for several days. Administration of fenproporex to five healthy volunteers resulted in amphetamine being detected in the urine of all subjects. Peak concentrations of amphetamine were detected at approximately 6-20 h postdose and ranged from approximately 1200 to 2100 ng/mL amphetamine. Amphetamine could be detected (> 5 ng/mL) in the urine for up to 119 h. Analysis of the metabolically produced amphetamine showed the presence of both enantiomers, which can be helpful in the differentiation of some illicit amphetamine use from the use of this precursor drug. More significantly, all samples that contained amphetamine at a concentration of at least 500 ng/mL were shown to also contain measurable amounts of the parent compound.     

Diffuse cerebral artery vasospasm following total resection of posterior fossa meningioma: a case report]

Diffuse cerebral artery vasospasm following brain tumor resection is a rare complication. The authors reported a case of symptomatic diffuse cerebral artery vasospasm of early phase following resection of a left posterior fossa meningioma. A 50-year-old female patient was admitted to our hospital complaining of headache. No neurological deficits were detected at the time of admission. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a large mass in the left posterior fossa. Cerebral angiography demonstrated mildly diffuse stenosis of the bilateral internal carotid artery. The tumor was resected totally. CT after operation showed a small amount of subarachnoid hematoma in the superior aspect of the cerebellum. Pathological specimen of the tumor showed fibrous meningioma. One day after this radical operation, the patient was found to have weakness in her left leg. Then she developed left hemiparesis, weakness in the right leg and left homonymous hemianopsia. MRI showed ischemic lesions in the bilateral parietal and the occipital lobe. Angiography demonstrated diffuse severe vasospasm throughout the whole cerebral artery. Ten days after the operation, angiographical findings were improved. This case indicates that vasospasm may occur even after resection of brain tumors which are localized outside the suprasellar area.     

Cutaneous toxicity following the administration of dactinomycin

The author describes a patient who has a successful coronary artery bypass. Six weeks later, after a physical examination of the chest, she had unbearable sharp, stabbing pain around the incision which was not responding to nerve blocks, analgesics, nonsteroidal anti inflammatory agents, and epidural blocks. The pain was responsive to mexilitine and disappeared after three weeks of treatment.