Use of cabergoline for oestrus induction in multiparous anoestrous Beagle bitches.

OBJECTIVE: The purpose of this study was to examine the efficacy of daily cabergoline administration on oestrus induction in bitches. METHODS AND RESULTS: Of 20 multiparous Beagle bitches, 15 were not mated with sires in their last oestrus and 5 bitches that had been mated whelped. All bitches were in early or mid-anoestrus and received 5 µg/kg/day cabergoline PO. Oestrus was induced in the mid-anoestrus bitches at a higher rate than in the early anoestrus bitches. Comparing the different histories of previous pregnancy among the mid-anoestrus bitches, the rate of oestrus induction in the non-pregnant bitches was higher than in the bitches that whelped. CONCLUSION: Cabergoline is effective for oestrus induction in mid-anoestrus bitches.

Effect of time for mating and gestation length on reproductive efficiency in dogs.

The purpose of this study was to examine the effect of time for mating and gestation length on reproductive efficiency in dogs. Groups of eight, six and six beagle bitches were mated with a total of three sires on days 3, 5 and 7, respectively, after the luteinizing hormone (LH) surge. All the bitches whelped successfully. The gestation lengths (the intervals from the LH surge to the whelping) were 65.1 +/- 1.9, 65.5 +/- 1.9 and 68.0 +/- 1.8 days, respectively. This length of mating 7 days after the LH surge was significantly longer than that of mating 3 and 5 days after the LH surge (p < 0.05). The litter sizes were 5.5 +/- 2.2, 6.2 +/- 1.9 and 4.8 +/- 2.1, respectively and there was no significant difference between any of the groups. In conclusion, mating 3-7 days after a bitch's LH surge results in a good reproductive efficiency and the intervals from the LH surge to the whelping of mating 7 days after the LH surge shows a longer day significantly in comparison with mating 3 and 5 days after the LH surge.

Effects of a synthetic progestogen, altrenogest, on oestrus synchronisation and fertility in miniature pigs.

Groups of six, six and eight miniature gilts, respectively, received 5, 10 or 15 mg/day of altrenogest for 18 days, and the numbers of corpora lutea and residual follicles were counted approximately 14 days after the treatment by an exploratory laparotomy. They were compared with the numbers in a control group of eight gilts which were examined six to eight days after oestrus. The interval between the last dose of altrenogest and the onset of oestrus increased with the dose of altrenogest, and was significantly longer after the treatments with 10 or 15 mg/day than after 5 mg/day (P < 0.01). Significantly more corpora lutea were observed in the gilts receiving 5 or 10 mg/day of altrenogest than in the control gilts (P < 0.1). Groups of six, seven and six miniature gilts that had respectively received 5, 10 or 15 mg/day of altrenogest were artificially inseminated; four, six and five of the gilts in these groups farrowed, and their mean (sd) litter sizes were 5.5 (2.4), 6.8 (1.2) and 5.0 (2.3), respectively. All six of a group of control gilts farrowed and their mean litter size was 5.8 (1.2).

[Two cases of alveolar hemorrhage due to inhalation of detergent aerosol].

We report on two cases of alveolar hemorrhage after inhalation of detergent aerosol. Case 1: A 54-year-old woman was referred to our hospital with a complaint of hemoptysis. She used a spray type detergent for ventilation fan cleaning, and recognized hemoptysis later for eight hours. She had mild anemia and severe hypoxemia, and chest radiographs and CT films infiltrative shadows were recognized predominantly in the right middle, left lingual lower lobes. Case 2: A 22-year-old woman was admitted to our hospital complaining of bloody sputum and dyspnea. She had used a spray-type detergent for bathroom cleaning intermittently for one week. Between the beginning of this activity and the seventh day, cough and dyspnea developed. Chest radiographs and CT films disclosed diffuse infiltrative shadows in both lung fields. In both cases, the condition was diagnosed by bronchoalveolar lavage as alveolar hemorrhage. In case 2, a transbronchial lung biopsy specimen revealed alveolitis without vasculitis or capillaritis. Both the clinical symptoms and the CT images were improved by steroid administration. The steroid dosage was decreased gradually and stopped, but there was no relapse of the hemoptysis. Neither patient was positive for antinuclear antibodies or antibodies against the cytoplasm of granulocytes. Urinalysis showed no pathological findings. Since the hemoptysis appeared after inhalation of a detergent aerosol, it was possible that inhalation was the cause of the hemorrhage.

Production of transgenic miniature pigs by pronuclear microinjection.

Miniature pig is an attractive animal for a wide range of research fields, such as medicine and pharmacology, because of its small size, the possibility of breeding it under minimum environmental controls and the physiology that is potentially similar to that of human. Although transgenic technology is useful for the analysis of gene function and for the development of model animals for various diseases, there have not yet been any reports on producing transgenic miniature pig. This study is the first successful report concerning the production of transgenic miniature pig by pronuclear microinjection. The huntingtin gene cloned from miniature pig, which is a homologue of candidate gene for Huntington's disease, connected with rat neuron-specific enolase promoter region, was injected into a pronucleus of fertilized eggs with micromanipulator. The eggs were transferred into the oviduct of recipient miniature pigs, whose estrus cycles were previously synchronized with a progesterone analogue. A total of 402 injected eggs from 171 donors were transferred to 23 synchronized recipients. Sixteen of them maintained pregnancy and delivered 65 young, and one resulted in abortion. Five of the 68 offspring (three of which were aborted) were determined to have transgene by PCR and Southern analysis. The overall rate of transgenic production was 1.24% (transgenic/injected eggs). This study provides the first success and useful information regarding production of transgenic miniature pig for biomedical research.

[Levofloxacin-induced eosinophilic pneumonia complicated by bronchial asthma].

A 76-year-old woman who had complained of cough and productive sputum since mid-January, 1999, was admitted to our hospital with fever and dyspnea on February 4, 1999. She had been treated with levofloxacin at an outpatient clinic. On admission, she had orthopnea, and auscultation revealed coarse crackles and wheeze in the bilateral lung fields. Chest x-ray and CT films showed non-segmental infiltration in bilateral lung fields. Laboratory data revealed eosinophilia in peripheral blood (= 24%) and sputum (= 10%), airflow limitation, hypoxemia (PaO2: 46 Torr), and increased airway responsiveness to methacholine (Dmin: 0.127 units). A bronchoalveolar lavage (BAL) fluid showed increased total cells and a 55% increase in eosinophils, and CD4/CD8 ratio was decreased to 0.8. In addition, IL-5 was increased in BAL fluid. Transbronchial lung biopsy specimens revealed infiltrations of eosinophils in the alveolar and interstitial compartments. Histological features of the bronchial biopsy specimens included increased eosinophils in the submucosa and goblet cell metaplasia. The woman was diagnosed with eosinophilic pneumonia complicated by bronchial asthma. She was given theophylline, pranlukast hydrate, and an inhaled beta 2 receptor agonist (procaterol hydrochloride), and pre-admission drugs including Levofloxacin were discontinued. Her symptoms were improved, peak expiratory flow rate and PaO2 increased, airway responsiveness to methacholine decreased (Dmin: 0.615 units), and radiographic abnormalities disappeared without steroid therapy. A leukocyte migration test for levofloxacin was weakly positive. An environmental provocation test in the patient's home gave negative results. A challenge test for levofloxacin was not performed due to a lack of informed consent. Based on these findings, we diagnosed this case as levofloxacin-induced lung injury manifesting as eosinophilic pneumonia complicated by bronchial asthma. Levofloxacin should be added to the list of agents that can produce eosinophilic pneumonia.

Induction of superovulation and recovery of fertilized oocytes in prepubertal miniature pigs after treatment with PG600.

The purpose of this study was to examine whether superovulation can be induced by hormonal treatment with PG600 (400 IU eCG and 200 IU hCG) at the prepubertal stage in miniature pigs. In Experiment 1, 14 prepubertal miniature pigs received 1, 1/2 or 1/4 vial of PG600, im on Day 0 (the first day of treatment). Presentation of estrus was monitored thereafter. On Days 10 to 13 (i.e., 6 to 8 d after estrus), the number of corpora lutea (CL) and residual follicles was counted by an exploratory laparotomy. Injection of 1/2 vial of PG600 effectively induced estrus and ovulation in the pigs. In Experiment 2, 15 prepubertal miniature pigs that received 1/2 vial of PG600 were artificially inseminated into the uterus by an exploratory laparotomy at 100 to 104 h after PG600 injection. Oocytes were recovered from the oviducts at 121 to 145 h after PG600 administration. The oocyte recovery rate was 66% (15 oocytes/pig, average), and 84% of these were at the 1-cell stage. In Experiment 3, 5 prepubertal miniature pigs that received 1/2 vial of PG600, followed by 100 IU hCG 70 h later, were artificially inseminated into the uterus. Oocytes were recovered synchronously at 120 to 122 h after PG600 treatment. The recovery rate was 80% (17 oocytes/pig, average) and 90% of the oocytes recovered were at the 1-cell stage. These results suggest that superovulation of prepubertal miniature pigs can be induced by 1/2 vial of PG600 injection, and by the combined treatment with PG600 and hCG injection, the fertilized ova can be synchronously recovered at around 120 h after PG600 injection. This procedure may provide a useful system for biomedical research using the miniature pigs, especially for producing transgenic animals for use in human disease models.

Paraneoplastic pemphigus associated with bronchiolitis obliterans.

Paraneoplastic pemphigus (PNP) is an autoantibody-mediated mucocutaneous blistering disease associated with underlying neoplasms. Autoantibodies of PNP bind to the plakin family of cytoplasmic proteins and desmogleins of cell-surface target antigens. We describe a 36-year-old female patient with PNP who had non-Hodgkin's lymphoma, and who developed bronchiolitis obliterans and died of respiratory failure. Autopsy findings confirmed luminal narrowing of bronchioles by scarring, which is a histopathologic features of bronchiolitis obliterans. After the onset of respiratory failure, the reaction of autoantibodies against the plakins detected by immunoprecipitation at the onset of PNP disappeared with negative immunofluorescence within the bronchial epithelium. It is thought that autoantibodies against some of these antigens play a role in causing acute inflammation of the respiratory epithelium. In treating PNP, the possibility of the patient developing the lethal complication bronchiolitis obliterans should be kept in mind. Furthermore, prevention of the initial autoantibody-mediated injury to the respiratory epithelium should be an important treatment goal.

[Pulmonary complications in adult measles].

The clinical features of pulmonary complications were evaluated in 15 patients with adult measles diagnosed by clinical and serologic investigations. Of those 15 patients, 12 were admitted because of high fever, sever anorexia and dyspnea. Almost all patients were found to have thrombocytopenia, elevations of LDH and aminotransferase. Pulmonary infiltrates were present in only 2 of the 12 patients (16.7%) on whom chest roentgenograms were performed, but hypoxemia (PaO2 < 70 Torr) were present in 8 of the 12 patients (66.7%). Pulmonary function tests in 8 patients showed mild decrease in VC, moderate decrease in FEV1 and severe decrease in V25. These findings suggest that hypoxemia in patients with normal chest radiographs may be largely caused by bronchiolitis. The observations of sequential peak flow rate measurement showed that severe pulmonary dysfunction continued for 4-5 days after the onset of the rash. To avoid the development of respiratory failure, patients with measles should be carefully monitored for bacterial superinfections of the respiratory tract especially within several days after the appearance of the rash.

[Pranoprofen-induced lung injury manifesting as acute eosinophilic pneumonia].

A 48-year-old man was admitted to our hospital complaining of fever, dyspnea, and cough. He had been treated with pranoprofen and antibiotics by an outpatient clinic for the preceding 4 days. Chest X-ray films revealed Kerley B lines, perivascular cuffing, and hilar haze with pleural effusion in both lungs. Chest computed tomographic films showed non-segmental patchy infiltrates, and thickening of bronchovascular bundles and interlobular septa. Laboratory data showed eosinophilia in peripheral blood (28%) and severe hypoxemia (PaO2:60 torr). Bronchoalveolar lavage fluid disclosed an increased total cell count, eosinophils (39%), and CD 4/CD 8 ratio (2.1). Microscopic examination of transbronchial lung biopsy specimens showed infiltration of eosinophils and mononuclear cells into alveolar wall's and spaces. Acute eosinophilic pneumonia was suspected on the basis of Allen's diagnostic criteria (N Engl J Med: 1989). After discontinuation of pranoprofen, the patient's clinical symptoms, laboratory data, and chest X-ray findings improved rapidly without steroid therapy. A leukocyte migration test (LMT) for pranoprofen was positive and a challenge test for smoking was negative. An environmental provocation test in the patient's home gave negative results. A challenge test for pranoprofen was not performed due to the lack of informed consent. Based on these findings, our diagnosis was pranoprofen-induced lung injury manifesting as acute eosinophilic pneumonia.

[Chronic eosinophilic pneumonia complicated by bronchial asthma and diabetes mellitus successfully treated with suplatast tosilate and high-dose inhaled corticosteroid therapy].

A 54-year-old woman complained of dyspnea, cough, and productive sputum. Auscultation detected a wheeze in the left and right lung fields. Chest x-ray and computed tomographic films showed non-segmental infiltration in the left upper lung field. Laboratory data revealed eosinophilia in peripheral blood and sputum, elevated levels of serum interleukin-5 (IL-5), airflow limitation, hypoxemia, and heightened airway sensitivity to methacholine (D min : 0.42 units). Bronchoalveolar lavage disclosed an increase in the total number of cells, a 32% increase in eosinophils, and a decreased CD 4/CD 8 ratio of 0.7. Transbronchial lung biopsy specimens revealed infiltrations of eosinophils in the alveolar and interstitial compartments. The histologic features of bronchial biopsy specimens included increased eosinophils in the submucosa and squamous metaplasia. In addition, blood glucose and HbA 1 c levels were elevated. Chronic eosinophilic pneumonia complicated by bronchial asthma and diabetes mellitus was diagnosed. Because the patient was diabetic, she was given suplatast tosilate to reduce the production of IL-5, and high-dose inhaled corticosteroid (beclometasone dipropionate, 1,600 mcg/day) instead of oral corticosteroid therapy. Her symptoms were relieved, peak expiratory flow rates increased, serum IL-5 levels became undetectable, airway sensitivity to methacholine decreased (D min : 4.64 units), and the radiographic abnormalities disappeared. Furthermore, treatment with beclomethasone dipropionate was progressively reduced to 1,200 mcg/day over the subsequent year without relapse. It was concluded that suplatast tosilate and high-dose inhaled corticosteroid therapy may be an effective alternative therapeutic approach to chronic eosinophilic pneumonia in some cases.

[A pilot phase II study of combination therapy with oxatomide, an antihistamine, plus dextromethoraphan and bakumondo-to, an herbal drug, in patients with postinfectious persistent cough].

Previously, we reported the effectiveness of treatment with oxatomide (O), an antihistamine, plus dextromethorphan (D), and that of Bakumondo-to (B), an herbal drug that inhibits the activation of C-fibers, in patients with persistent coughing after upper-airway infection. In this study, we evaluated the efficacy and side effects of combination therapy (O + D + B) in patients with postinfectious persistent cough. Patients who had been coughing for more than three weeks and had a history of upper-airway infection took part in the study. None had any history of nasal disease, gastroesophageal reflux, bronchial asthma, or other chronic pulmonary disease. All patients were non-smokers, and none used angiotensin converting enzyme (ACE) inhibitors. All had normal chest roentgenograms and normal pulmonary function. The following hematological data were obtained before treatment: peripheral eosinophil counts. CRP levels, serum IgE concentrations, and titers of cold agglutinins and antibodies to Mycoplasma pneumoniae. The effects of one week of treatment with O + D + B on the severity of coughing, as estimated with a cough diary, were examined. Thirty-six patients entered the study, but only 18 with normal hematological findings who satisfied the study criteria were eligible for efficacy and side-effect analyses. Cough scores decreased significantly from 5.1 +/- 2.4 (range, 2-9) to 1.2 +/- 1.9 (range, 0-6), and the rate of cough disappearance was 50%. Two patients reported slight drowsiness. Therapy with O + D + B reduced perception of coughing as estimated with a cough diary. These results suggest that this therapy (O + D + B) may be useful in patients with postinfectious persistent cough.

[Problems in noninvasive positive pressure ventilation of patients with acute-on-chronic hypercapnic respiratory failure].

In patients with acute exacerbations of chronic obstructive pulmonary disease non-invasive positive pressure ventilation (NPPV) has been used to avoid endotracheal intubation. The aim of this study was to identify factors that can prevent the success of this technique. We applied a BiPAP ventilatory assist device (Respironics, Inc., Murrysville, PA) via a nasal mask to 13 patients with acute exacerbation of chronic respiratory failure and analyzed their clinical and physiological status. Intubation was not needed in 11 of 14 episodes (78%). The mean pH, PaCO2, and heart rate before BiPAP in the three patients who required intubation differed significantly from those in the patients who did not require intubation (pH 7.19 vs. 7.31: p < 0.05, PaCO2 107.8 vs. 77.8 Torr: p < 0.05, heart rate 127 vs. 105/min; p < 0.05). In those who required intubation the mean pH improved during the first 12 hours of BiPAP but then worsened. In 5 episodes, the PaCO2 increased during the initial trial of BiPAP, but decreased after the amount of supplemental oxygen was reduced. We conclude that NPPV should be used soon after respiratory failure begins, and care should be taken not to supply too much oxygen.

[NO2 inhalation in two smokers and two non-smokers].

Four healthy men were exposed to an anti-rust substance in a stainless steel tank. Acute respiratory failure developed in two of them, both non-smokers. Their chest roentgenograms revealed marked infiltration, which suggested pulmonary edema due to the inhalation of NO2 and hydrogen fluoride. These two patients recovered from respiratory distress within several days. However, small airway disease was still evident one year later. The other two, who were smokers, had only mild respiratory symptoms. These cases indicate that smoking may reduce the sensitivity to NO2. Further study is needed to elucidate the relationship between smoking and the severity of responses to NO2 inhalation.

[A study of enhancing effects of monocyte culture supernatant on polymorphonuclear neutrophils-chemiluminescence--comparison between normal controls and collagen disease patients].

Priming effect of monocyte culture supernatant on polymorphonuclear neutrophils (PMN)-chemiluminescence (CL) was studied in patients with systemic lupus erythematosus (n = 11) and mixed connective tissue disease (n = 4). In normal controls, N-formyl-methionyl-leucyl-phenylalanine (FMLP) induced PMN-CL was enhanced when PMN were previously incubated for 15 minutes with monocyte culture supernatant (MS) or T lymphocyte culture supernatant (TS) or T lymphocyte culture supernatant (TS). The enhancing effect of MS on PMN-CL was greater than that of TS. This enhancing effect of MS was inhibited by adding of dexamethasone (1 microgram/ml) during the culture. Recombinant human TNF also enhanced PMN-CL as well as MS. When compared the enhancing effects of MS between patients and normal controls, that of patients under corticosteroid therapy (average prednisolone dose 39.5 mg/day) was reduced significantly. Thus, we concluded that the cytokines from monocyte contributed PMN phagocytosis of invading microorganisms, and that this monocyte-mediated PMN phagocytosis was suppressed partly by corticosteroids in collagen disease.

[Effects of disease activities and corticosteroid therapy on the chemiluminescence of peripheral polymorphonuclear leukocytes in patients with systemic lupus erythematosus].

To elucidate the phagocytic activity of polymorphonuclear leukocytes (PMN) in systemic lupus erythematosus (SLE), we assayed the luminol dependent chemiluminescence of PMN (PMN-CL) of 30 patients with SLE, and evaluated the effects of disease activities and corticosteroid (steroid) therapy on the PMN-CL. The PMN-CL of active SLE patients (n = 10) before steroid therapy increased significantly compared to normal controls when stimulated with phorbol myristate acetate (PMA) (p less than 0.05). On the contrary it decreased significantly when stimulated with opsonized zymosan (OZ) (p less than 0.01). The PMN-CL of SLE patients under steroid therapy (average prednisolone dose, 40.4 mg/day) revealed a tendency to decrease according to the increase of total steroid dose. It was correlated with the total steroid dose for the preceding 12 or 16 weeks, when stimulated with formyl-methionylleucyl-phenylalanine and PMA. However it was not related with the current steroid dose. Thus the increase of PMN-CL by PMA stimulation as well as the decrease by OZ stimulation seems to be a characteristic phenomenon in SLE. The PMN phagocytic activity in SLE will be suppressed after more than 12 weeks therapy of large doses of steroid.