Comparison of two synthetic progesterones on ventilation in normal males: CMA vs. MPA.

We administered chlormadinone acetate (CMA), medroxyprogesterone acetate (MPA), and placebo to 16 normal male subjects using a randomized double-blind crossover study. After CMA administration, minute alveolar ventilation increased by +1.04 +/- 0.22 (SE) 1/min (P less than 0.05) accompanied by decrements of arterial PCO2 (-4.0 +/- 1.0 Torr) (P less than 0.01) and [HCO3-] (-2.1 +/- 0.05 mM/l) (P less than 0.01). On the other hand, in the MPA runs the corresponding changes of the above parameters were +0.71 +/- 0.21 l/min (P less than 0.05), -2.9 +/- 0.6 Torr (P less than 0.01), and -1.3 +/- 0.3 mM/l (P less than 0.01), respectively. The slopes of hypoxic ventilatory and occlusion pressure response lines remained unchanged in hypocapnia after CMA or MPA ingestion, but they increased when entidal PCO2 was adjusted to the predrug level. The hypercapnic ventilatory and occlusion pressure response lines merely shifted to the left without changing their slopes with these agents. No significant differences in all the above parameters were found between CMA and MPA runs. We concluded that in the normal males the effect of CMA on ventilation was similar to that of MPA, despite the fact that the luteinizing activity of CMA was reported to be approximately 10 times higher than the latter.

Afferent and cardiodynamic drives in the early phase of exercise hyperpnea in humans.

The ventilatory and cardiac responses to voluntary and passive exercise were studied in 20 healthy subjects. These responses to passive leg exercise were also studied in 23 patients with spinal cord transection at the level of T5-T12. In the normal subjects, minute ventilation (VE) increased abruptly from the first breath after the onset of the two types of exercise. In contrast, cardiac output (Q) increased gradually in voluntary exercise, exhibiting significant augmentation from the fifth breath. Q changed insignificantly in passive exercise. In the patients with spinal cord transection, neither VE nor Q changed with passive exercise. These results suggest that ventilatory responses at the onset of mild exercise are related to drives from the moving limbs. We could not detect any evidence to support cardiodynamic hyperpnea at the onset of exercise.

Ruthenium-catalysed asymmetric hydrosilylation of ketoximes using chiral oxazolinylferrocenylphosphines.

Chiral ruthenium(II) complexes, RuCl2(PPh3)(oxazolinylferrocenylphosphine), have been found to be effective catalysts for asymmetric hydrosilylation of ketoximes to give the corresponding primary amines in good yields with high enantioselectivities (up to 89% ee) after acid hydrolysis.

Intradural lumbar disc herniation. Report of three cases with a review of the literature.

Intradural lumbar disc herniation (ILDH) is rare. Three new cases of this condition are reported, adding to the 70 previously documented cases. An incidence of ILDH in between 0.04 and 0.33 percent of lumbar disc protrusions has been reported. More than one third of ILDH were observed at L1-2 to L3-4 levels, while only a tenth of cases occurred at L5-S1. The mechanism of ILDH is not known with certainty. Adhesions between the ventral wall of the dura and posterior longitudinal ligament could act as a preconditioning factor. A diagnosis of ILDH may be made with difficulty, and it is seldom suspected preoperatively. Prompt surgery is necessary because the neurologic prognosis appears to be closely linked with preoperative duration of neurologic symptoms.

Comparison of ventilatory response between dead space and CO2 breathing in humans.

Ventilatory response during external dead space (tube) breathing and CO2 inhalation for given increase in PETCO2 were compared at different levels of PETO2 (hyperoxia, normoxia, and hypoxia) in human subjects. At all the PETO2 levels studied, magnitude of increment in minute ventilation (VE) and tidal volume were larger in the dead space breathing than in the CO2 inhalation. The slope of CO2-ventilation response line was significantly steeper in the dead space breathing only in the hypoxic condition. There was no significant difference in frequency response to CO2 between the two methods. These results suggested that augmented ventilatory response to CO2 in the dead space breathing occurs in the condition of peripheral chemoreceptor activation.

Circulatory and respiratory responses to lower body negative pressure in man.

Circulatory and ventilatory responses to lower body negative pressure (LBNP) were simultaneously investigated in 8 healthy men before, during, and after the application of -20, -40, and -60 mmHg pressure. Minute ventilation (VE) decreased during LBNP due to a fall in respiratory frequency with sustained tidal volume. The cardiac output (Q) was reduced in proportion to the applied LBNP exposure, while VE decreased to almost the same level at all LBNP applications. In spite of decreased VE, end-tidal PO2 and PCO2 were increased and decreased, respectively, indicating a relative alveolar hyperventilation. The ventilation equivalent for O2 (VE/VO2) increased, while the cardiac output equivalent for O2 (Q/VO2) decreased. The relation between VE/VO2 and Q/VO2 showed a significant negative correlation (r = -0.93, p less than 0.01). The veno-arterial CO2 concentration difference (CvCO2--CaCO2) increased with LBNP, due to a fall in CaCO2 with constant CvCO2. The constant CvCO2 indicated a constant tissue acid-base balance. These observations suggest the existence of a ventilatory mechanism improving the efficiency of respiration in order to compensate for the sustained LBNP depression of Q at a given gas exchange.

Estimation of peripheral chemoreceptor contribution to exercise hyperpnea in man.

Nine normal male subjects were studied at three levels of exercise (0, 40, and 80 W). Single vital capacity breath test was applied at rest and during exercise (phases 2 and 3). Minimum minute ventilation found within 4 breaths following the test was compared to the control value. Significant depression in minute ventilation was invariably observed. The minute ventilation was depressed more and more with increasing intensity of exercise. A significant difference was found between exercise and rest. However, the relative contribution of chemoreceptor activity remained the same 10-20% at all exercise levels. The magnitude of ventilatory depression (delta V resp) in phase 2 was larger than that in phase 3, when work rate increased to 80 W, both relative and absolute. A significant part of the exercise hyperpnea is due to peripheral chemoreceptor activity. The peripheral chemoreceptor activity is greater in phase 2 than in phase 3 at work rates of light to moderate intensity.

Hypercapnic and hypoxic ventilatory responses during growth.

Cross-sectional studies on hypercapnic and hypoxic ventilatory chemosensitivities were performed in 71 children ranging in age from 7 to 18 yrs. The subjects were classified into 6 successive 2-year age groups. CO2 ventilatory response was measured by rebreathing 5% CO2 in O2, a slight modification of the method originally proposed by Read. The results were evaluated when the CO2-ventilation feedback control system was supposed to have attained the open-loop condition. Hypoxic ventilatory response was measured by the isocapnic progressive hypoxia test. To obtain good reproducibility in the ventilatory response, end-tidal PCO2 was maintained at 5 mmHg higher than the resting condition throughout the test. Normalized ventilatory responses to CO2 by body surface area (S/BSA) progressively decreased from the 7-8 through the 11-12 yr groups, and then tended to decrease further in a more gradual manner with increasing age. This trend was very similar to the normalized CO2 output (VCO2/BSA), but did not parallel so closely the normalized O2 intake (VO2/BSA). When ventilatory and metabolic parameters were normalized by body weight (BW), or the lean body mass (LBM), qualitatively similar relationships between CO2 sensitivities and metabolic parameters were also obtained. Contrary to the hypercapnic response, hypoxic ventilatory chemosensitivities were not significantly different among the 6 different age groups. We concluded that normalized hypercapnic chemosensitivity decreased during growth and corresponded well with decreased CO2 output per unit body mass.

Facial cold receptors and the survival reflex "diving bradycardia" in man.

We measured heart rate (HR), stroke volume (SV), systemic arterial blood pressure (BP), and mean arterial pressure (MAP) in 7 healthy volunteers in response to face immersion in water with concomitant breath-holding at different lung volumes. The subjects were at rest in the prone position. During breath-holding at total lung capacity (TLC), baseline HR (70 to 75 beats/min) fell by 10% within fractions of a second, both in the control preimmersion state when the head was surrounded by room air, and when it was immersed in water of 33 degrees C. This response was associated with rises in MAP and in SV. Immersion of the face in 10 degrees C water while breath-holding, was associated with a strong, negative chronotropic effect (22% fall in HR), which developed within 10 s. Breath-holding at functional residual capacity (FRC) reduced HR substantially only in 10 degrees C water, and in contrast to that at TLC, the response was slowly developing with a latency of 10-15 s. All these reductions in HR were significant and accompanied by increases in BP and MAP. The strong, negative chronotropic effect of cold water was typically linked to a rise in SV. The study identified two temporal components of HR reduction to face immersion: a fast parasympathetic response dependent on the input from the high pressure baroreceptors, and a late response mediated, in all likelihood, by sympathetic efferent activity. Facial receptors sensitive to cold seem to be vital in the largest responses observed. The fast response to breath-holding with the face in water of neutral temperature was equal to that in air. Thus "diving bradycardia" is in fact a basic survival response independent of water.

Contribution of chemical and non-chemical drives to breath-holding determined by visual analog scale (VAS).

Chemical and non-chemical contributions to breath-holding time (BHT) were directly determined by using a visual analog scale (VAS). These values were compared with those indirectly calculated from the method proposed by Godfrey and Campbell (1968). The magnitude of non-chemical factor at low PCO2 in our study was substantially less than the one obtained by the above investigators. We conclude that Godfrey and Campbell's model postulating linear augmentation of non-chemical sensation is inappropriate to explain dyspnea profile during breath-holding.

[Infant botulism was confirmed in Ehime Prefecture].

The third case of infant botulism in Japan is reported. A four-month-old baby boy suddenly had weakness of suckling force, constipation and generalized hypotonicity. He was the product of normal gestation, labor and delivery. Growth and development were normal until he was nineteen weeks old. He received fruit-juice and honey daily. By bacteriological examination, Clostridium botulism type A was isolated from his feces and the honey which he had received. Type A toxin was detected from his feces but not from his serum.

[Therapeutic effects of cefoxitin in the treatment of various infections in children (author's transl)].

In order to ascertain the therapeutic effects of cefoxitin (CFX), a new semisynthetic cephamycin antibiotic, it was administered to pediatric patients with several infections. There were 8 patients with acute respiratory disease (ARD), 3 with urinary tract infection (UTI), 2 with appendicitis complicated with peritonitis, 2 with scarlet fever, one each of left coxitis, infected medial cervical cyst, febrile illness after a V-P shunt operation, purulent parotitis and intractable diarrhea with fever, namely, a total of 20 patients aged from one month to 11 years 6 months. A CFX vial which contained 1 g of CFX was used in two ways, i.e., one shot intravenous injection and drip infusion. The dosage of the drug varied from 57 to 121 mg/kg/day and the administration was continued from 2 to 20 days. Clinical effects were evaluated as follows: when cardinal symptoms disappeared within 3 days it was considered to be 'excellent'; within 5 days 'good'; and no change of clinical symptoms within 5 days 'poor'. The bacteriological effect was expressed as 'eliminated', 'unchanged' and 'undetermined'. Clinical efficacy evaluated as 'excellent' occurred in 11 cases, 'good' in 8 cases and 'poor' in 1 case, the efficacy rate being 95.0%. When classified by the disease, the efficacy rate was as follows: 'good' to 'excellent' in 7 out of the 8 cases of ARD, 'excellent' in all of the 3 cases of UTI, 'good' and 'excellent' in the 2 cases of scarlet fever and in the 2 cases of peritonitis, 'excellent' in each case of left coxitis, purulent parotitis and intractable diarrhea with fever, 'good' in each case of infected medial cervical cyst and febrile illness with a V-P shunt operation. From the bacteriological point of view, 'eliminated' occurred in 5 cases, 'reduced' in 1 case and 'undetermined' in the 2 cases of ARD, 'eliminated' in all of the 3 cases of UTI, 'eliminated' in 1 case and 'undetermined' in the 1 case of peritonitis, 'undetermined' in the 2 cases of scarlet fever, 'eliminated' in each case of infected medial cervical cyst and purulent parotitis and 'undetermined' in the other cases. Antimicrobial efficacy measured by MIC was compared with CEZ and CET, and the results were as follows: CFX was inferior to the two cephalosporins for S. aureus, it was between CEZ and CET for H. influenzae and H. parainfluenzae, and CFX was superior to CEZ and CET for E. coli. All of the 3 antibiotics had poor antimicrobial efficacy for P. aeruginosa and S. faecalis. There were neither clinical side effects nor abnormal laboratory findings which were obviously attributable to CFX during and after administration of the drug.

[Clinical efficacy and safety of norfloxacin tablets in pediatrics].

We have evaluated norfloxacin (NFLX) tablets for therapeutic effectiveness and safety in children. The results are summarized as follows. 1. A clinical study was performed on 14 children with infections, including 12 with urinary tract infections and 2 with acute bronchitis. Doses ranging from 1.7 to 5.4 mg/kg body weight were given b.i.d. or t.i.d.. Lengths of treatment ranged from 3 to 15 days. The therapeutic responses were considered "excellent" in 8 and "good" in 5, with an efficacy rate of 93%. 2. Side effects were observed in 2 cases, one with light-headed feeling and one with vomiting. In clinical laboratory tests, eosinophilia was found in 2 cases and GOT was slightly elevated in 1 case. It has been concluded that NFLX is a usable drug for the treatment of bacterial infections in children.

[Therapeutic effects of cefmenoxime in the treatment of various infections on infants and children].

The therapeutic effects of cefmenoxime (CMX), a new synthetic cephalosporin antibiotic, were examined in the treatment of various pediatric infections. Patients treated were infants and children ranging from one-month-old to 13-year-old suffering from pharyngitis in 2 cases, bronchopneumonia in 3 cases, cervical lymphadenitis in 2 cases, urinary tract infections in 7 cases, tympanitis in 2 cases, suppurative meningitis, sepsis, subcutaneous apostem, acute enteritis, chest wall apostem, phlegmon, staphylococcal scalded skin syndrome in 1 case each, a total of 23 cases. As regards method of administration, CMX from a vial was dissolved in physiological saline or distilled water for injection, and the solution was administered by 3 to 5 minutes one short intravenous injection (14 cases), or CMX was diluted with large volume parenteral product and administered by 30 to 60 minutes drip infusion (9 cases). The dosage of the drug was 30 to 200 mg/kg/day; 103 mg/kg/day and under in 21 cases, 150 mg/kg/day and 200 mg/kg/day in 1 case each. The administration was continued for 3 to 27 days. As regards clinical efficacy, "good" or "excellent" results were obtained in all the cases except 2 cases, one was alpha-Streptococcus acute tympanitis supervening neuroblastoma, and the other was Pseudomonas urinary tract infection. The efficacy rate was 91.3% with excellent in 11 cases, good in 10 cases. As regards bacteriological effects, of 13 strains of Gram-positive bacteria, 10 strains were eliminated and 3 strains were not changed, while of 10 strains of Gram-negative bacteria, 8 strains were eliminated and 2 strains were reduced; thus CMX showed better results against Gram-negative bacteria rather than against Gram-positive ones. The antimicrobial activity of CMX against Gram-positive bacteria was inferior to those of CTM and CEZ, but CMX showed the highest antimicrobial activity against Gram-negative bacteria. No clinical side effects nor abnormal laboratory findings obviously attributable to CMX were observed.

Adhesion molecules in the lymphoid cell distribution in rheumatoid synovial membrane.

The staining pattern of a group of adhesion molecules on the immunoreactive cells in the lining layer of lymphocytic infiltrates of the rheumatoid synovial membrane was studied, using monoclonal antibodies by immunoperoxidase staining method against LFA-1, VLA-4, VLA-5, ELAM-1, and ICAM-1. The cells of the lining layer were strongly ICAM-1+ and VLA-5+, suggesting (1) that ICAM-1 may function to facilitate the adhesion of ICAM-1 bearing type A cells to type B cells, and (2) that the lining cells may utilize VLA-5 for anchorage to fibronectin at the surface of the synovial membrane. In the lymphocyte-rich and transitional area, the endothelial cells of the postcapillary venules were both ELAM-1+ and ICAM-1+. ICAM-1 staining of mononuclear cells was weak in lymphoid aggregates, but strong in the transitional area, indicating a paucity of ICAM-1 bearing cells in the lymphocyte-rich areas. On the other hand, LFA-1 staining was very strong in the lymphoid aggregates and only moderate in transitional areas. This suggests that the large numbers of T4 cells in the lymphocyte rich areas are sufficiently activated to express substantial levels of LFA-1, and also that the LFA-1 molecule is an important receptor for emigration from postcapillary venules. In germinal center-like areas in lymphoid aggregates, most of the cells stained strongly for ICAM-1 and VLA-4, suggesting that the proliferation of B lymphocytes may be facilitated by LFA-1 and VLA-4 dependent T and B cell interaction. The VLA molecules stained in the transitional areas may provide appropriate adhesion and anchorage for the achievement of the variety of immune reactions which occur in these areas.

Novel Catalytic Hydrogenolysis of Trimethylsilyl Enol Ethers by the Use of an Acidic Ruthenium Dihydrogen Complex.

The heterolytic cleavage of H(2) is the key to the novel catalytic hydrogenolysis of trimethylsilyl enol ethers catalyzed by [RuCl(eta(2)-H(2))(dppe)(2)]OTf (dppe = 1,2-bis(diphenylphosphanyl)ethane, OTf = trifluoromethanesulfonate), which results in the formation of a ketone and Me(3)SiH (see scheme). In addition, the stoichiometric, ruthenium-assisted protonation of a prochiral lithium enolate with H(2) gave a chiral ketone with high enantioselectivity (up to 75 % ee).

Formation of ammonia in the reactions of a tungsten dinitrogen with ruthenium dihydrogen complexes under mild reaction conditions.

Treatment of cis-[W(N2)2(PMe2Ph)4] (5) with an equilibrium mixture of trans-[RuCl(eta 2-H2)(dppp)2]X (3) with pKa = 4.4 and [RuCl(dppp)2]X (4) [X = PF6, BF4, or OTf; dppp = 1,3-bis(diphenylphosphino)propane] containing 10 equiv of the Ru atom based on tungsten in benzene-dichloroethane at 55 degrees C for 24 h under 1 atm of H2 gave NH3 in 45-55% total yields based on tungsten, together with the formation of trans-[RuHCl(dppp)2] (6). Free NH3 in 9-16% yields was observed in the reaction mixture, and further NH3 in 36-45% yields was released after base distillation. Detailed studies on the reaction of 5 with numerous Ru(eta 2-H2) complexes showed that the yield of NH3 produced critically depended upon the pKa value of the employed Ru(eta 2-H2) complexes. When 5 was treated with 10 equiv of trans-[RuCl(eta 2-H2)(dppe)2]X (8) with pKa = 6.0 [X = PF6, BF4, or OTf; dppe = 1,2-bis(diphenylphosphino)ethane] under 1 atm of H2, NH3 was formed in higher yields (up to 79% total yield) compared with the reaction with an equilibrium mixture of 3 and 4. If the pKa value of a Ru(eta 2-H2) complex was increased up to about 10, the yield of NH3 was remarkably decreased. In these reactions, heterolytic cleavage of H2 seems to occur at the Ru center via nucleophilic attack of the coordinated N2 on the coordinated H2 where a proton (H+) is used for the protonation of the coordinated N2 and a hydride (H-) remains at the Ru atom. Treatment of 5, trans-[W(N2)2(PMePh2)4] (14), or trans-[M(N2)2(dppe)2] [M = Mo (1), W (2)] with Ru(eta 2-H2) complexes at room temperature led to isolation of intermediate hydrazido(2-) complexes such as trans-[W(OTf)(NNH2)(PMe2Ph)4]OTf (19), trans-[W(OTf)(NNH2)(PMePh2)4]OTf (20), and trans-[WX(NNH2)(dppe)2]+ [X = OTf (15), F (16)]. The molecular structure of 19 was determined by X-ray analysis. Further ruthenium-assisted protonation of hydrazido(2-) intermediates such as 19 with H2 at 55 degrees C was considered to result in the formation of NH3, concurrent with the generation of W(VI) species. All of the electrons required for the reduction of N2 are provided by the zerovalent tungsten.

Bimetallic system for nitrogen fixation: ruthenium-assisted protonation of coordinated N2 on tungsten with H2

Treatment of the tungsten dinitrogen complex cis-[W(N2)2(PMe2Ph)4] (Me = methyl, Ph = phenyl) with an equilibrium mixture of [RuCl(dppp)2]X and trans-[RuCl(eta2-H2)(dppp)2]X [X = BF4, PF6, or OSO2CF3; dppp = 1,3-bis(diphenylphosphino)propane] under 1 atmosphere of dihydrogen at 55 degrees Celsius for 24 hours gave NH3 in moderate yield. The same reaction in the presence of acetone produced acetone azine in high yield. None of these reactions proceeded in the absence of dihydrogen.