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We assessed the effect of smooth muscle contraction and relaxation on airway lumen subtended by the internal perimeter (Ai) and total cross-sectional area (Ao) of human bronchial explants in the absence of the potential lung tethering forces of alveolar tissue to test the hypothesis that bronchoconstriction results in a comparable change of Ai and Ao. Luminal area (i.e., Ai) and Ao were measured by using computerized videomicrometry, and bronchial wall area was calculated accordingly. Images on videotape were captured; areas were outlined, and data were expressed as internal pixel number by using imaging software. Bronchial rings were dissected in 1.0- to 1.5-mm sections from macroscopically unaffected areas of lungs from patients undergoing resection for carcinoma, placed in microplate wells containing buffered saline, and allowed to equilibrate for 1 h. Baseline, Ao [5.21 +/- 0.354 (SE) mm2], and Ai (0.604 +/- 0.057 mm2) were measured before contraction of the airway smooth muscle (ASM) with carbachol. Mean Ai narrowed by 0.257 +/- 0.052 mm2 in response to 10 microM carbachol (P = 0.001 vs. baseline). Similarly, Ao narrowed by 0.272 +/- 0.110 mm2 in response to carbachol (P = 0.038 vs. baseline; P = 0.849 vs. change in Ai). Similar parallel changes in cross-sectional area for Ai and Ao were observed for relaxation of ASM from inherent tone of other bronchial rings in response to 10 microM isoproterenol. We demonstrate a unique characteristic of human ASM; i.e., both luminal and total cross-sectional area of human airways change similarly on contraction and relaxation in vitro, resulting in a conservation of bronchiolar wall area with bronchoconstriction and dilation.

We assessed the role of endogenously secreted tachykinins in mediating contraction caused by potassium chloride (KCl) in guinea pig tracheal smooth muscle (TSM) strips in vitro. Maximal isometric contraction was elicited with approximately 45 mM KCl and was 196 +/- 8% of the response to electrical field stimulation (% EFS) in the same tissues. Muscarinic receptor blockade with atropine modestly attenuated this contraction caused by KCl to 175 +/- 9 %EFS (P < 0.05), and treatment with a selective neurokinin subtype 1 (NK1) receptor antagonist, LY-297911, caused even greater inhibition of KCl-elicited contraction to 124 +/- 8 %EFS (P < 0.001). By contrast, SR-48968, a selective NK2 antagonist, had no effect on contraction caused by KCl (183 +/- 9 %EFS; P = NS vs. KCl alone). However, given together at the same concentration, SR-48968 augmented the inhibition of contraction caused by LY-297911 to 93 +/- 15 %EFS (P < 0.05 vs. LY-297911 alone). In contrast to the effect on KCl-induced contraction, LY-297911 caused only moderate inhibition of the contraction caused by capsaicin to 81 +/- 13 %EFS (P < 0.05 vs. control, 114 +/- 15 %EFS), whereas SR-48968 caused substantial attenuation of contraction caused by capsaicin to 23 +/- 5 %EFS (P < 0.005 vs. LY-297911). We demonstrate that a significant portion of the contraction caused by KCl, in addition to capsaicin, is elicited in guinea pig TSM through neurokinin secretion. However, NK1 receptors predominantly mediate contraction caused by KCl, and NK2 receptors predominantly mediate contraction elicited by capsaicin in guinea pig airway smooth muscle.

We assessed the effect of serotonergic inhibition by cyproheptadine on the responsiveness of tracheal smooth muscle (TSM) strips and epithelium-intact third-generation bronchial rings from immune-sensitized (Ascaris suum) cats after exposure to antigen. Cats were sensitized by IM administration of antigen and adjuvant twice over a 4-week period. Sensitization was confirmed in vivo by skin testing with antigen and by physiologic airway responses after exposure to nebulized antigen. Tissues were tethered isometrically to force transducers and were actively equilibrated by exposures to KCl-substituted perfusate. Maximal response after exposure to antigen (expressed as percentage of maximal contraction of each tissue to 63 mM KCl (%KCl) was 169 +/- 18% KCl for sensitized TSM and 43 +/- 18% KCl for sensitized TSM pretreated with cyproheptadine (P < 0.001). Similarly, maximal response to antigen was 81 +/- 27% KCl for sensitized bronchial rings, compared with 16 +/- 14% KCl for sensitized bronchial rings pretreated with cyproheptadine (P = 0.05 vs control). Blockade of leukotriene synthesis by 10(-6) to 10(-4) M A-64077, a selective 5-lipoxygenase inhibitor, had no significant effect on peak response for either TSM (193 +/- 13% KCl vs 169 +/- 18% KCl for sensitized untreated TSM) or bronchial rings (79 +/- 20% KCl vs 81 +/- 27% KCl for sensitized untreated bronchial rings). Release of serotonin from airway tissues was confirmed by the presence of serotonin in the perfusate of 8 sensitized TSM preparations after, but not before, antigen challenge.(ABSTRACT TRUNCATED AT 250 WORDS)

We assessed whether incubation with human serum from atopic individuals containing high concentrations of immunoglobulin E (IgE) causes augmentation of maximal contraction of human bronchial smooth muscle from non-atopic subjects in vitro. Bronchi were obtained from eight patients undergoing lung resection, and force-velocity relationships were determined for eight pairs of epithelium-intact bronchial rings of generations 6-7 using an electromagnetic lever system, which allowed isotonic shortening when load-clamps [from 0 to maximal isometric force (P0)] were applied at specific times after onset of contraction. Contractions were elicited by supramaximal electrical field stimulation (50 Hz, 10 s train duration, 25 V). Optimal length (Lo) for each tissue was determined during equilibration. After resection, tissues were sensitized passively with human sera containing high titers (> 1,000 U/ml) of IgE by incubation for 16 h at 20 degrees C. Maximal shortening velocity (Vmax) was increased for passively sensitized bronchi [0.1150 +/- 0.0240 1/2 circumferences/s (1/2Cir/s)] compared with sham-sensitized bronchi [0.0731 +/- 0.0152 1/2Cir/s, P = 0.038]. Similarly, maximal shortening (delta Lmax) was augmented in sensitized bronchial rings (11.27 +/- 1.80 %Lo) compared with sham-sensitized tissues (8.19 +/- 1.39 %Lo, P = 0.012). However, P0 did not differ between sensitized (122.5 +/- 24.4 mN/cm2) compared with sham-sensitized tissues (138.4 +/- 32.1 mN/cm2, P = 0.642). Our data are the first demonstration that Vmax and delta Lmax are augmented in sensitized but not challenged human bronchial rings after passive sensitization using human serum containing high concentrations of IgE.

We examined epithelial modulation of tracheal smooth muscle (TSM) responsiveness in vitro from guinea pigs receiving active immune sensitization in vivo. Initially, guinea pigs were either ovalbumin sensitized (by aerosol) or sham sensitized with normal saline; TSM responsiveness was assessed isometrically as active tension (AT) after equilibration by electrical field stimulation in vitro. For epithelium-intact (Epi+) tissues, sensitization caused an increase in baseline active spontaneous tone (1.89 +/- 0.20 g AT) vs. sham-sensitized tissues (1.18 +/- 0.28 g AT; P = 0.02). Spontaneous tone in sensitized TSM in which the epithelium was removed (Epi-) (1.01 +/- 0.14 g AT) was substantially less than from Epi+ tissues (P = 0.01) and did not differ from sham-sensitized epithelium-denuded tissues (0.82 +/- 0.24 g AT; P > 0.05). Indomethacin caused a reduction in spontaneous tone to comparable magnitude for all treatment paradigms. Immune sensitization caused physiological reduction in the ability to relax in response to isoproterenol; the concentration of isoproterenol eliciting 50% relaxation of spontaneous tone was 7.10 +/- 0.13 (-log M) for TSM from sensitized guinea pigs compared with 8.20 +/- 0.27 (-log M) for sham-sensitized tissues (P = 0.006). However, after precontraction with exogenous acetylcholine, relaxation caused by isoproterenol was not affected by either indomethacin or epithelial removal. Muscarinic responsiveness to acetylcholine was augmented by immune sensitization; however, the increase in response to acetylcholine was attenuated by epithelium removal or cyclooxygenase blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Recently, we demonstrated that chronic exposure to hyperoxia causes in vivo airway muscarinic receptor hyperresponsiveness in the developing rat [Am. J. Physiol. 262 (Lung Cell. Mol. Physiol. 6): L263-L269, 1992]. To test whether airway cholinergic hyperresponsiveness might result from intrinsic alterations in smooth muscle contractility, we measured the effect of in vivo hyperoxia on the contractile force elicited by acetylcholine (ACh) of isometrically mounted tracheal rings in vitro. Tracheal rings were obtained from 3-wk-old rats exposed to air or to > 95% O2 for 8 days. Muscarinic responses were determined by measuring the force elicited by exposure to increasing concentrations of ACh. Responses were normalized to the morphometrically determined tracheal smooth muscle cross-sectional area in a plane perpendicular to the axis of force generation. In vivo O2 exposure significantly increased maximal ACh-induced stress generation (response to 10(-3) M ACh: air, 15.92 +/- 1.37 g/mm2; O2, 21.78 +/- 1.52 g/mm2; P = 0.010). The ACh-induced stress generation of cylinders from hyperoxic rats was substantially reduced by both epithelial removal and treatment with the cyclooxygenase inhibitor indomethacin. We conclude that in vivo hyperoxic exposure increases tracheal smooth muscle contractile function in vitro and that epithelium-derived prostaglandin(s) contributes to the observed increase in maximal contractile responsiveness.

We studied the effect of either 1) immunogenic inflammation caused by aerosolized ovalbumin or 2) neurogenic inflammation caused by aerosolized capsaicin in vivo on guinea pig tracheal smooth muscle (TSM) contractility in vitro. Force-velocity relationships were determined for nine epithelium-intact TSM strips from ovalbumin-sensitized (OAS) vs. seven sham-sensitized controls and TSM strips for seven animals treated with capsaicin aerosol (Cap-Aer) vs. eight sham controls. Muscle strips were tethered to an electromagnetic lever system, which allowed isotonic shortening when load clamps [from 0 to maximal isometric force (Po)] were applied at specific times after onset of contraction. Contractions were elicited by supramaximal electrical field stimulation (60 Hz, 10-s duration, 18 V). Optimal length for each muscle was determined during equilibration. Maximal shortening velocity (Vmax) was increased in TSM from OAS (1.72 +/- 0.46 mm/s) compared with sham-sensitized animals (0.90 +/- 0.15 mm/s, P < 0.05); Vmax for TSM from Cap-Aer (0.88 +/- 0.11 mm/s) was not different from control TSM (1.13 +/- 0.08 mm/s, P = NS). Similarly, maximal shortening (delta max) was augmented in TSM from OAS (1.01 +/- 0.15 mm) compared with sham-sensitized animals (0.72 +/- 0.14 mm, P < 0.05); delta max for TSM from Cap-Aer animals (0.65 +/- 0.11 mm) was not different from saline aerosol controls (0.71 +/- 0.15 mm, P = NS). We demonstrate Vmax and delta max are augmented in TSM after ovalbumin sensitization; in contrast, neurogenic inflammation caused by capsaicin has no effect on isolated TSM contractility in vitro. These data suggest that airway hyperresponsiveness in vivo that occurs in association with immunogenic or neurogenic inflammation may result from different effects of these types of inflammation on airway smooth muscle.

We assessed the responsiveness of tracheobronchial lymphatic smooth muscle to mediators of inflammation to determine whether homogeneous responses to histamine and 5-hydroxytryptamine (5-HT) are demonstrated among species typically used in studies of lymph vessels. Fresh porcine and bovine tracheobronchial lymph vessels were suspended from force-displacement transducers in baths containing oxygenated Krebs solution. Concentration-response curves were generated by cumulative addition of histamine (10(-7) to 10(-3) M) or 5-HT (10(-7) to 3 x 10(-4) M). Active tension (AT) was expressed in milligrams and as a percentage of initial vessel ring response to 65mM KCl. Histamine elicited concentration-dependent contraction, yielding maximum AT in porcine rings of 1116 +/- 127 mg (n = 39; 129.1 +/- 10.5% of KCl response) and in bovine rings of 733 +/- 106 mg (n = 20; 65.8 +/- 12.9%; P = 0.0005 for percent responses). PD2 values (negative log10 of the concentration at half-maximum effect) were 4.49 +/- 0.08 and 4.82 +/- 0.08; (P = 0.0034). 5-HT elicited concentration-dependent contraction, yielding maximum AT of 560 +/- 50 mg in porcine rings (n = 15; 97.2 +/- 9.7%) and 2892 +/- 454 mg in bovine rings (n = 27; 159.0 +/- 29%; P < 0.0001 for percent responses). PD2 values were 6.25 +/- 0.05 and 5.28 +/- 0.04 (P < 0.0001). The data demonstrate a role for inflammatory mediators in the modulation of tracheobronchial lymphatic smooth muscle tone that is species- and mediator-specific, and support the potential for paracrine regulation of tracheobronchial lymph flow.

One theory of the relation between familiarity and the frequency of deception predicts that familiarity leads to the rarity of deception and another, that familiarity increases deception. We examined which theory applied to play by comparing familiar and unfamiliar partners during play between dogs (Canis familiaris) and humans (Homo sapiens). Deceptions by humans were based on directionality of movement and petting the dog and on the projects show object and throw object, which are specialized for play. Likewise, deceptions by dogs were based on directionality of movement and the project retrieve object (an analogue to show object). Deceptions based on directionality and petting were rare among familiars (and unfamiliars), whereas those based on show object, throw object, and retrieve object were more frequent. The findings suggest that, in play at least, deception may occur frequently.

DNA derived from chromosome band 3 of the cloned Giardia duodenalis line, WB-1B was used to construct a cloned library in E. coli. One of these clones, C3/23, has been identified as the 3' coding region of a G. duodenalis cysteine-rich variable surface protein (CRVSP) gene by homology with other published CRVSPs and also contains 720 bp of the 3' flanking region. The sequence of C3/23, was derived from genomic DNA independently of cDNA, or expression copies of the CRVSP genes. The 3' flanking region is not homologous to the 3' untranslated regions of published CRVSPs which probably reflects its genomic origin. Subclones of C3/23 were used to show that the 3' flanking region was conserved in all strains examined in this study and was repeated many times in the genome. The 3' flanking repeats were located on three chromosome bands and were not always associated with the coding sequence of C3/23 which was represented, although not equally, on all chromosome bands. The highly conserved nature of the 3' flanking region and its multiple representation in the genome emphasize the probable role of this sequence in the localization or regulation of expression of the CRVSPs in G. duodenalis.

We assessed the effect of immune sensitization on acetylcholine (ACh) release from parasympathetic nerve terminals in tracheal smooth muscle (TSM) strips from ragweed-sensitized (RWS) and sham-sensitized, littermate control (LMC) dogs. Strips of TSM were tethered to force transducers at optimal length in perfusion chambers containing [3H]choline and a fixed volume of physiological perfusate. Tissues were equilibrated for 1 h by electrical field stimulation (EFS) every 5 min to facilitate uptake of label into parasympathetic nerves as ACh. Fresh perfusate (containing 3 x 10(-8) M physostigmine) was collected at 5-min intervals for 1 h, and a rate coefficient of [3H]ACh release was determined. Tissues were exposed to agonists in the seventh collection period, and the increase in label release (ratio change where < or = 1.00 = baseline) and force production were determined. Ragweed antigen challenge stimulated [3H]ACh release and contraction in RWS but not LMC tissues. [3H]ACh release was 1.93 +/- 0.22 x baseline in RWS vs. 0.92 +/- 0.02 in control tissues (P < 0.01); contraction was 31.2 +/- 9.5% of that elicited by EFS (% EFS) in RWS vs. 0% EFS in LMC tissues (P < 0.01). Strips of TSM from RWS but not LMC dogs demonstrated concentration-dependent, augmented release of ACh caused by histamine. After 10(-4) M histamine, [3H]ACh release in RWS was 1.94 +/- 0.37 x baseline vs. 1.05 +/- 0.06 for LMC tissues (P < 0.05); histamine also caused greater contraction in RWS (106.5 +/- 5.9% EFS) vs. LMC (86.5 +/- 5.6% EFS; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

We studied the modulatory effect of airway epithelium on guinea pig tracheal smooth muscle (TSM) contraction. Isometric force was measured in vivo before and after removal of the tracheal epithelium. In parallel studies, TSM contraction was also measured isometrically in epithelium-intact and epithelium-denuded TSM strips in vitro. Epithelial removal in vivo did not alter the contractile response of TSM to acetylcholine (ACh) or serotonin. In nine guinea pigs, active tension (AT) caused by 3 x 10(-7) mol/kg of intravenous ACh was 0.74 +/- 0.14 g force per longitudinal length of the segment (g/cm) in the presence of epithelium versus 0.89 +/- 0.16 g/cm after removal of airway epithelium (confirmed histologically) (p NS). The threshold response to ACh was also unchanged (-8.0 +/- 0.3 log mol/kg control versus -8.3 +/- 0.3 log mol/kg after epithelial removal, p NS). In six guinea pigs, the AT caused by 3 x 10(-8) mol/kg of intravenous serotonin was 1.92 +/- 0.63 g/cm with an intact epithelium versus 2.15 +/- 0.70 g/cm after epithelial removal in vivo (p NS). Epithelial removal in vitro increased the sensitivity of TSM contraction to ACh when the data were expressed as the percentage maximal response to ACh. The concentration of ACh causing 50% of the maximal response (EC50) was -5.74 +/- 0.25 log M in eight epithelium-intact TSM strips versus -6.37 +/- 0.16 log M after epithelial removal in controls (n = 8) (p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Current information regarding the physiology of lymphatic smooth muscle is derived from experiments on mesenteric and thoracic duct lymph trunks. We hypothesized that tracheobronchial lymphatics share many of the same properties possessed by the mesenteric lymphatics, and examined the passive and active length-tension characteristics of the two. Fresh isolated lymph vessel rings were prepared from bovine mesenteric and tracheobronchial lymphatic collectors, mounted in organ baths, and connected to force-displacement transducers. Isometric contractions were induced by exposure to 65mM KCl-substituted perfusate after intermittent ring length changes. Active tension was calculated. Optimal vessel length was greater in tracheobronchial vessel rings, averaging 4.9 +/- 0.4mm vs 2.8 +/- 0.3mm in mesenteric rings (p < 0.001). Optimal resting tension and ATmax were similar for both truncal types, measuring 738 +/- 95mg and 2379 +/- 289mg in tracheobronchial vessel rings, and 625 +/- 108mg and 2501 +/- 320mg in mesenteric vessel rings, respectively. Stress developed at L(o) (optimal length) was similar for tracheobronchial (35.4 +/- 4.3mN mm-2) and mesenteric (26 +/- 4.3mN mm-2) lymphatics (P = N.S.). The data demonstrate that tracheobronchial lymph vessels are similar to mesenteric lymph vessels in their ability to generate significant stress, and suggest that these lymphatics participate in the regulation of lymph flow.

We studied the effect of pertussis toxin (PT) and partial muscarinic antagonism using pirenzepine (PIR) on beta-adrenergic relaxation of muscarinic contraction in 188 tracheal smooth muscle (TSM) preparations from 25 dogs in vitro. Strips of TSM were incubated for 4 h at 37 degrees C in Krebs-Henseleit (K-H) perfusate with or without 10 micrograms/ml of PT. In tissues contracted to target tension (TT; 50% of maximal response to 127 mM potassium-substituted K-H [KCl]) with acetylcholine (ACh), pretreatment with PT decreased the concentration of isoproterenol (ISO) causing 30% relaxation from TT (RC30) from 1.3 +/- 0.8 x 10(-7) M (control) to 2.8 +/- 0.7 x 10(-8) M (p = 0.013). Pretreatment with PT also augmented the maximal relaxation elicited by 10(-5) M ISO. In separate studies, strips of TSM were contracted with ACh; pretreatment with 10(-7) M PIR decreased the concentration of ISO causing 50% relaxation (RC50) from 3.4 +/- 0.6 x 10(-7) to 9.6 +/- 1.5 x 10(-8) M (p = 0.042). Pretreatment with PIR did not affect relaxation elicited by ISO for strips contracted equivalently with KCl. In addition, PIR increased both the potency and efficacy of ISO in relaxing muscarinic contraction in sham-incubated strips of TSM but had no effect after incubation with PT. Neither PT nor PIR affected beta-adrenergic relaxation of TSM contracted with KCl. Our data demonstrate that beta-adrenergic receptor relaxation of muscarinic contraction is augmented by (1) incubation with PT and (2) partial blockade of muscarinic receptors.

We examined the development of acetylcholinesterase (AChase) activity and tracheal smooth muscle (TSM) contraction elicited by acetylcholine (ACh) in a swine model of maturation and a dog model of allergic bronchospasm. Strips of TSM were tethered isometrically at optimal length and responses were expressed as a percentage of the maximum to KCl-substituted perfusate (% KCl). Maximal contraction (ATmax) to ACh in 2-week-old swine (168 +/- 8% KCl) was greater than in 10-week-old swine (142 +/- 2% KCl; p less than 0.02). The AChase inhibitor, physostigmine, augmented ACh-elicited ATmax in 10-week-old (27% increase; p less than 0.01) but not in 2-week-old swine (2% increase; p is NS) and caused a greater increase in sensitivity to muscarinic activation in 2 versus 10 week-old swine (p less than 0.02), thus demonstrating increased contraction of TSM in 2 versus 10-week-old swine, which results at least in part from reduced AChase activity in immature animals. In another study, TSM from ragweed-sensitized dogs demonstrated augmented efficacy to ACh-elicited contraction (180 +/- 6% KCl) compared with TSM from sham-sensitized, littermate controls (163 +/- 4% KCl; p less than 0.05). In the presence of physostigmine, ATmax was not different between ragweed-sensitized and control TSM.(ABSTRACT TRUNCATED AT 250 WORDS)

We examined the effect of maturation on force-velocity (F-V) parameters in porcine tracheal smooth muscle (TSM) to determine the relationship between maximal isometric contractile force (Po) and maximal velocity of shortening (Vmax). Strips of TSM excised from 1-day-old neonatal swine (neo; n = 8), 2-wk-old swine (2ws; n = 7), and 10-wk-old swine (10ws; n = 7) were tethered to an electromagnetic lever system for F-V analysis of contractility. TSM strips were activated by electrical field stimulation at optimal resting tension, voltage, and length (Lo) so that maximal reproducible contractile force (Po) was elicited. Velocities were measured at the early phase of isometric contraction (3.1 +/- 0.1 s for neo, 2.9 +/- 0.1 s for 2ws, and 3.1 +/- 0.1 s for 10ws; P = NS). Shortening velocity increased progressively with maturation; Vmax was 0.164 +/- 0.011 Lo/s for neo, 0.194 +/- 0.013 Lo/s for 2ws (P less than 0.05 vs. neo), and 0.260 +/- 0.024 Lo/s for 10ws (P less than 0.01 vs. neo; P less than 0.05 vs. 2ws). Maximal isometric force generation increased substantially during the first 2 wk of postnatal life and thereafter returned to neonatal levels; Po was 71.5 +/- 2.1 mN/mm2 for neo, 95.4 +/- 7.0 mN/mm2 for 2ws, and 74.7 +/- 6.2 mN/mm2 for 10ws (P less than 0.05, 2ws vs. neo and 10ws). In separate studies, we also determined whether differences in Vmax occurred during the normal cycling phase of the cross bridge (3 s) or during the slowly cycling phase of the latch bridge (8 s) in tissue from 12 additional animals.(ABSTRACT TRUNCATED AT 250 WORDS)

We studied the effect of maturation on potassium-induced parasympathetic activation and Ca2+ entry in tracheal smooth muscle (TSM) from fifteen 2-wk-old (2ws) and sixteen 10-wk-old (10ws) male domestic farm swine. Atropine (10(-7) M) caused inhibition of the maximal contraction elicited by potassium to 50.3 +/- 2.6% maximum of control response (P less than 0.001) in TSM from 2ws but had no significant effect in TSM from 10ws (94.6 +/- 4.2% maximum; P = NS vs. control). Verapamil (10(-7) M) plus 10(-7) M atropine reduced contraction elicited by potassium in both 2ws (23.7 +/- 5.8% maximum; P less than 0.001 vs. control) and 10ws (50.6 +/- 6.3% maximum; P less than 0.001 vs. control, P less than 0.05 vs. 2ws); 10(-6)M verapamil caused greater than 95% blockade of contraction caused by potassium in both 2ws and 10ws. In separate studies, atropine-treated strips were equilibrated with extracellular Ca2+ concentrations ([Ca2+]o) ranging from normal (1X [Ca2+]o) to four times normal (4x [Ca2+]o). Increasing [Ca2+]o increased maximal contractile response in atropine-treated TSM strips from 68.7 +/- 3.8% maximum for 1x [Ca2+]o to 100.8 +/- 4.8% maximum for 4x [Ca2+]o (P less than 0.001) in 2ws. Neither atropine nor [Ca2+]o affected maximal responses of TSM in 10ws (103.5 +/- 3.0% maximum for 1x [Ca2+]o; P = NS vs. control). However, in the presence of atropine and verapamil, 4x [Ca2+]o augmented KCl-elicited contraction of TSM from both 2ws (46.9 +/- 6.3% maximum; P less than 0.01 vs. control) and 10ws (78.6 +/- 2.3% maximum; P less than 0.005 vs. control).(ABSTRACT TRUNCATED AT 250 WORDS)

Previous investigations have demonstrated that cholinergic contraction of porcine tracheal smooth muscle (TSM) decreases between the second and tenth weeks of life. In this investigation, we hypothesized that the greater contractile response to acetylcholine (ACh) in TSM of 2-wk-old swine (2ws) vs. 10-wk-old swine (10ws) was the result of a relative decrease in activity of acetylcholinesterase (AChase). To examine this hypothesis, we assessed AChase activity directly in homogenates of TSM from eight 2ws and seven 10ws using a newly adapted method that measures the rate of cleavage of acetylthiocholine; enzyme activity was expressed as absorbance units per minute per milligram protein. The AChase from tissues of both age groups saturated at approximately 3 mM substrate. However, maximal AChase activity (Vmax) was significantly greater in 10ws than 2ws. Eadie-Hofstee analysis of enzyme kinetics revealed similar Michaelis-Menten constants for 2ws and 10ws. The concentration of physostigmine (PS), an inhibitor of cholinesterase, that elicited half-maximal inhibition of AChase activity also was similar for 2ws and 10ws. In separate studies, contraction of TSM strips was assessed in vitro at optimal resting length and expressed as a function of maximal force generation to potassium chloride. Strips of TSM from 2ws contracted with greater force than those of 10ws. After pretreatment with 10(-8) M PS, contractile forces were similar in 2ws and 10ws. We conclude that AChase activity measured directly in muscle homogenates is significantly reduced in TSM of 2ws vs. 10ws and that this may result in augmented contraction to ACh under conditions of zero-order kinetics.

Previous investigations have suggested that immune-sensitization increases airway smooth muscle responsiveness to cholinomimetic stimulation by reducing the rate of degradation of acetylcholine. To examine the hypothesis that increased cholinomimetic responsiveness of tracheal smooth muscle (TSM) caused by immune-sensitization results from inhibition of acetylcholinesterase (AChase) activity, we developed a method for direct measurement of AChase activity in homogenates of TSM obtained from mongrel dogs actively sensitized in vivo to ragweed pollen extract (n = 7) and sham-sensitized littermate controls (n = 7). For both sensitized and control specimens, saturation of AChase was obtained at approximately 3.12 mM substrate (acetylthiocholine); however, maximal enzyme activity in homogenates of ragweed-sensitized tissues was significantly less (0.862 +/- 0.088 absorbance units/min/mg protein [AU/min/mg]) compared to control homogenates (1.590 +/- 0.129 AU/min/mg; P less than 0.001). Kinetic analysis (Eadie-Hofstee plot) indicated similar Michaelis constants (Km) for AChase from ragweed-sensitized (0.360 +/- 0.063) and control (0.336 +/- 0.062) homogenates (P = NS). The concentration of physostigmine eliciting half-maximal inhibition (Ki) of AChase activity also was similar for tissues from sensitized (-7.92 +/- 0.032 log M) and control animals (-7.86 +/- 0.012 log M; P = NS). Pretreatment with selected mediators of anaphylaxis (10(-4) M histamine, 10(-6) M serotonin, 10(-5) M prostaglandin E2, 10(-6) M prostaglandin F2 alpha, and 10(-7) M leukotriene D4) did not affect AChase activity. Our data demonstrate reduced AChase activity in homogenates of canine TSM after active immune-sensitization in vivo. This corresponds to functional augmentation of cholinomimetic contraction in actively sensitized tissues.

We studied the relationship of airway morphometry, the content of myosin heavy-chain and isoform stoichiometry, and the distribution of bronchoconstrictor responses in the airways of maturing swine. Lungs were excised in 2-wk-old farm swine (2ws; n = 13) and 10-wk-old swine (10ws; n = 13), and tracheal smooth muscle strips and bronchial rings from generations 2-5 were fixed for in vitro isometric measurement of force generation. Split samples were placed in formaldehyde solution or glutaraldehyde for light- or electron-microscopic morphometry or frozen for analysis of tissue myosin content. The rank order of force generation elicited by both receptor- and nonreceptor-dependent mechanisms for both 2ws and 10ws was generation 4 greater than 3 greater than or equal to 2. For all matched airway generations, contractile force was 25-100% greater in 2ws than 10ws. Differences in force generation were not related to morphometric differences in smooth muscle mass content among airways. The relative cross-sectional area of smooth muscle derived by computerized morphometry was 5.5-7% for each airway generation and did not change with age. Electron-microscopic morphometry demonstrated comparable myocyte content within muscle bundles for all airways in both age groups. In generation 4 airways, myocyte size in 2ws (27.3 +/- 0.8 nuclei/2,500 microns2) hypertrophied approximately 15% in 10ws (20.4 +/- 0.6 nuclei/2,500 microns2; P less than 0.01). Tissue content of myosin measured by computerized laser densitometry of gel electrophoresis of homogenates was greater in trachea from 2ws than 10ws (135 +/- 10 vs. 90 +/- 4 micrograms/g tissue; P less than 0.01); homology of 200- and 205-kDa isoforms was confirmed by Western blot against polyclonal myosin antibody and Cleveland digest analysis of each band. Differences in contractile forces between generations in 2ws and 10ws were not correlated to functional myosin isoform content. We demonstrate a maturational downregulation of contractile forces in maturing swine. This response is independent of smooth muscle receptor distribution and is not related to morphological changes in airways muscle mass, cellularity, changes in content of nonmyocyte tissues, or tissue content of functional myosin isoform.

Five Giardia stocks collected from animals and man in Alberta, Canada, were compared by DNA fingerprinting. Although many DNA bands were common to all stocks, differences in the DNA banding patterns were seen. These same stocks had previously been shown to be identical by restriction enzyme cleavage of genomic DNA.

We evaluated the effect of preconditioning of the isometric contractile response of canine tracheal smooth muscle (TSM) in vitro. Strips of epithelium-free TSM (n = 90) were excised from 16 anesthetized dogs and fixed isometrically in tissue perfusion chambers. Experiments were performed using methods previously reported in which the following parameters were investigated: 1) quiescent equilibration time in the perfusion chamber (0-120 min); 2) effect of repeated exchange of perfusate; 3) method of determining the optimal resting length (Lmax) for presetting of resting tension (RT); 4) effect of precontraction during the equilibration phase on the contractile response to agonists administered subsequently; and 5) method of determining RT on the response to muscarinic stimulation. When other variables were uniform, neither equilibration time nor perfusate exchange affected potency or efficacy of the response generated subsequently to acetylcholine (ACh). However, both potency (range of EC50: -5.71 +/- 0.14 log M to -6.52 +/- 0.24 log M; P less than 0.02) and efficacy (range of maximal active tension: 1,143 +/- 268 g/cm2 to 2,878 +/- 151 g/cm2; P less than 0.001) of ACh were altered substantially as a result of the method used to estimate Lmax. Repeated precontraction by electrical field stimulation or with 127 mM KCl did not alter potency or efficacy of contraction elicited by ACh. Maximal active tension generated with 10(-3) M ACh was 2,878 +/- 151 g/cm2 after 12-15 tetanizing field stimulations and 2,696 +/- 198 g/cm2 after 5-7 contractions with 127 mM KCl (P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

We studied the effect of maturation on the topographic distribution of airway constriction in Generations 0 (trachea) through 6 in fourteen 2-wk-old swine (2ws) and sixteen 10-wk-old swine (10ws) in vivo and in excised airways from seven 2ws and seven 10ws in vitro. Animals were anesthetized with chloralose-urethane and received beta-adrenergic blockade and vagotomy prior to generation of random-order, dose-response curves with i.v. methacholine (MCh) and histamine (His) or serotonin (5HT) given intravenously. Lung resistance (RL) was measured, and airway diameter was assessed by tantalum bronchograms obtained at functional residual capacity for each dose of agonist. Baseline RL was substantially greater in 2ws (48 to 62 cm H2O/L/s) than in 10ws (9 to 11 cm H2O/L/s; p less than 0.001 for all groups). Intravenous infusion of 10(-6) mol/kg MCh caused a 416 +/- 110% increase in RL in 2 ws and a 314 +/- 32% increase in RL in 10 ws (p = NS); airway diameter (Daw) decreased by 10 +/- 1% (Generation 2) to 27 +/- 4% (Generation 6) in 2ws and from 8 +/- 2 (Generation 2) to 17 +/- 4% in 10ws. Intravenous infusion of 10(-6) mol/kg His caused a 513 +/- 85% increase in RL in 2ws and a 276 +/- 17% increase in RL in 10 ws (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

We studied the effect of endotoxin administration in vivo on arterial smooth muscle responses in vitro, testing the hypotheses that endotoxin augments adrenergic vasoconstriction and impairs endothelium-dependent vascular relaxation. Ten mongrel dogs were anesthetized and mechanically ventilated. Five received a bolus infusion of Escherichia coli endotoxin (5 mg/kg), and the remainder received a sham infusion. After 4 to 5 h, the anesthetized dogs were rapidly exsanguinated, and femoral, renal, and superior mesenteric arteries were removed. Arterial rings were mounted on force transducers in organ baths; contraction to phenylephrine or potassium-substituted Krebs-Henseleit solution (KCl), and relaxation to nitroprusside or acetylcholine were studied. Smooth muscle contractions to phenylephrine or KCl were similar between sham and endotoxin for each agonist. Also, nitroprusside-elicited relaxation from half-maximal phenylephrine-elicited contraction was similar. However, relaxation elicited by acetylcholine was markedly impaired in vessels from endotoxin-treated dogs. The negative log molar concentration of acetylcholine producing 50% relaxation for femoral arteries was 7.38 +/- 0.11 (endotoxin) versus 8.09 +/- 0.12 (control, p = 0.002), for renal arteries it was 6.71 +/- 0.33 (endotoxin) versus 7.81 +/- 0.18 (control, p = 0.019), and for mesenteric arteries it was 7.27 +/- 0.03 (endotoxin) versus 7.95 +/- 0.15 (control, p = 0.002). These results demonstrate that endotoxin treatment impairs endothelium-dependent relaxation of canine arteries in vitro. The data suggest that vascular changes in endotoxemia are accompanied by alteration in endothelial cell function, perhaps through altered endothelial production of vasodilatory mediators.

We examined postganglionic development of acetylcholinesterase (AChase) activity and tracheal smooth muscle (TSM) contraction elicited by cholinomimetic activation and electrical field depolarization in vitro. Epithelium-intact tracheal strips excised from 21 2-wk-old swine (2ws) and 19 10-wk-old swine (10ws) were tethered isometrically at optimal resting length, and responses were expressed as percent of the maximum to 63 mM potassium-chloride (%KCl). Cumulative concentration-response curves to KCl were equivalent for TSM from 2 and 10ws. However, maximal contraction to ACh in 2ws (168 +/- 8.4 %KCl) was greater than for 10ws (142 +/- 2.3 %KCl; P less than 0.02). Stimulus-response curves (field electrodes; AC source) demonstrated greater sensitivity for TSM in 10ws (stimulus causing 50% of the maximal response = 3.32 +/- 0.13 V in 2ws vs. 2.25 +/- 0.12 V in 10ws; P less than 0.001), indicating that the greater cholinomimetic responsiveness of 2ws did not result from augmented presynaptic nerve conduction. The AChase inhibitor, physostigmine, caused 1) greater sensitivity of responses elicited by electrical field stimulation in 2ws (P less than 0.05) but not in 10ws (P = NS), 2) augmentation of maximal responses to exogenous ACh in 10ws (27% increase; P less than 0.01) but not 2ws (2% increase; P = NS), and 3) a greater increase in sensitivity to cholinomimetic activation in 2ws compared with 10ws (P less than 0.02). These data demonstrate increased cholinergic contraction of TSM in 2 vs. 10ws that results at least in part from reduced AChase activity in the trachea of immature animals.

The catecholamine and cardiovascular responses to laryngoscopy and tracheal intubation were studied in 20 patients who underwent elective gynaecological surgery and who were allocated randomly to receive either practolol 10 mg or saline intravenously prior to induction of anaesthesia. Anaesthesia was induced with fentanyl and thiopentone; atracurium was administered and the lungs were ventilated artificially with 67% nitrous oxide in oxygen. Tracheal intubation was performed when muscle relaxation was adequate. Arterial pressure, heart rate, plasma noradrenaline and adrenaline concentrations were measured before and after tracheal intubation. A significant increase in catecholamine concentrations occurred in both groups in response to tracheal intubation but the magnitude of the increase in adrenaline was greater in the practolol group. There were no significant differences in arterial pressure or heart rate changes between the groups. We conclude that pretreatment with practolol is of no value in the attenuation of the hypertensive response to direct laryngoscopy and tracheal intubation in previously normotensive patients.

A case of primary hepatic pregnancy in which the presenting features were suggestive of ruptured ectopic pregnancy is described. The bleeding area on the liver was oversewn and the patient recovered uneventfully. Primary hepatic pregnancy is briefly discussed.

Amoxicillin in single oral doses of 2.0 g, 2.0 g plus 1.0 g probenecid, or 3.0 g was compared with ampicillin 3.5 g plus 1.0 g probenecid in the treatment of 203 males with uncomplicated acute gonococcal urethritis. Cure rates above 95% were produced by all treatments except the 2.0-g amoxicillin dose, which cured 89% of patients. Of 198 pretreatment gonococcus isolates tested by an agar dilution technique for susceptibility to penicillin G, ampicillin and amoxicillin, over 50% showed relative resistance (MIC > 0.06 mug/ml) to the antibiotics. However, amoxicillin was somewhat more active against isolates showing considerable resistance (MIC >/= 1.0 mug/ml) to penicillin G or ampicillin. Adverse effects of amoxicillin were few: two patients reported transient nausea and six noted short-lived diarrhea. No hypersensitivity reactions were observed.

The phenomenon of contractile agonist-dependent relaxation by isoproterenol (ISO) of active tension elicited by acetylcholine (ACh), histamine (HIS), serotonin (5-HT), and potassium chloride-substituted Krebs-Henseleit solution (KCl) was studied in 210 tracheal smooth muscle (TSM) strips from 28 mongrel dogs in vitro. All TSM strips were contracted to similar active tensions [target tension (TT) = 50% of the maximal active tension elicited by 127 mM KCl] with ACh, HIS, 5-HT, or KCl and relaxed with either ISO, forskolin (FSK), N6,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate (db-cAMP), or 3-isobutyl-1-methylxanthine (IMX). The concentrations of ISO causing 50% relaxation from TT (RC50) were ACh (2.9 +/- 1.1 x 10(-6) M) greater than 5-HT (8.4 +/- 1.5 x 10(-8) M) approximately KCl (8.1 +/- 2.1 x 10(-8) M) greater than HIS (1.6 +/- 0.2 x 10(-8) M). FSK and IMX relaxed TSM in the same rank order of potency as ISO. In contrast to the contractile agonist-dependent relaxation elicited by ISO, FSK, and IMX, db-cAMP was nearly equipotent in relaxing similarly contracted strips. These results are consistent with contractile agonist-specific interaction with cAMP production by ISO and FSK. These data demonstrate that the phenomenon of contractile agonist-dependent relaxation by ISO is not related specifically to the beta-adrenoceptor.

Previous reports from this laboratory of force-velocity relationships of canine tracheal smooth muscle (TSM) have presented maximum shortening velocities (Vmax) mathematically derived from the linearized transformation of the Hill equation (A. V. Hill, Proc. Roy. Soc. London, Ser. B., 126:136-195, 1938). Recent technical advances enable us to measure Vmax directly using an electromagnetic lever system that can instantaneously clamp to a zero load, thus we compared values of Vmax derived mathematically and those directly measured on the same TSM strips. Derived Vmax values from afterloaded isotonic shortening curves for loads greater than preload were 0.328 +/- 0.021 optimal length (lO)/s and were not significantly different from zero load-clamp measurements of 0.301 +/- 0.022 lO/s from the same (n = 15) muscles. These data indicate that Vmax values mathematically derived for TSM from conventional isotonic afterloaded force-velocity curves are valid estimates of zero load velocity, because they were not significantly different from values obtained by direct measurement using the zero load-clamp technique.

We compared isotonic shortening with isometric force generation as a function of external Ca2+ in 166 tracheal smooth muscle (TSM) strips from 27 mongrel dogs in vitro. Concentration-response curves were generated with muscarinic stimulation (acetylcholine, ACh), alpha-adrenergic receptor activation (norepinephrine after beta-adrenoceptor blockade, NE), serotonin (5-HT), and KCl-substituted Krebs-Henseleit solution. The concentrations of 5-HT causing half-maximal shortening (ECS50, 1.54 +/- 0.14 X 10(-7) M) and half-maximal active isometric tension (ECT50, 1.72 +/- 0.30 X 10(-7) M) were similar (P = NS). Likewise, ECS50 (21.9 +/- 0.7 mM) and ECT50, (22.0 +/- 0.9 mM) were similar for KCl. In contrast, facilitated isotonic shortening (i.e., greater isotonic shortening for comparable degrees of force generation) was elicited with ACh and NE for all levels of force generation between 15 and 85% of maximum and for all concentrations of ACh from 3 X 10(-8) to 3 X 10(-5) M (P less than 0.05 for all points). Facilitated isotonic shortening also was elicited for all concentrations of NE from 10(-8) to 10(-6) M (P less than 0.05 for all points). Removal of Ca2+ from the perfusate substantially reduced the potency of ACh (P less than 0.001) and abolished differences between ECS50 (2.23 +/- 0.28 X 10(-5) M) and ECT50 (2.50 +/- 0.46 X 10(-5) M, P = NS). We demonstrate that for comparable degrees of force generation, muscarinic and alpha-adrenergic receptor activation cause greater isotonic shortening than KCl or 5-HT and that this facilitated shortening is associated with the concentration of external Ca2+.

The present studies were undertaken to obtain histamine (HIST) dose-response curves for tracheal smooth muscle (TSM) from an actively ragweed-sensitized canine model of asthma and to compare these results with 1) HIST dose-response data from littermate control dogs, 2) initially nonsensitized TSM passively sensitized (in vitro) to ragweed and 3) the dose-response curve to an agonist that opens primarily voltage-sensitive calcium channels, i.e., K+. Actively ragweed-sensitized TSM was significantly hyperreactive (upward shift of the dose-response curve) to HIST (1.882 kg of force produced normalized to cross-sectional area-kg/cm2 +/- 0.087 S.E. vs. littermate controls 1.151 +/- 0.253) and hypersensitive as indicated by the leftward shift in the median effective dose or ED50 (1.86 X 10(-6) +/- 0.24 vs. 5.54 X 10(-6) +/- 1.35 M). Passively sensitized TSM (using serum from ragweed-sensitized dogs) also showed a hyperreactivity to HIST when compared to control TSM incubated with control serum (1.204 +/- 0.127 vs. 0.825 +/- 0.081 kg/cm2). No significant difference was found in the ED50 values, indicating similar sensitivities. Atropine (10(-7) M) reduced the hypersensitivity of actively sensitized TSM significantly toward control values; however, the hyperreactivity persisted. Atropine did not affect responses to HIST in control TSM. Ragweed actively sensitized TSMs were also hyperreactive and hypersensitive to K+ when compared to littermate control TSM. Atropine abolished both the hyperreactivity and hypersensitivity to K+ but had no effect on the dose-response curve of control TSM to K+.(ABSTRACT TRUNCATED AT 250 WORDS)

By means of telephone tracing 96% follow-up was achieved in men treated for gonococcal urethritis. A large proportion (34.8%) of patients required one or more calls before follow-up could be obtained. Frequency of sexual re-exposure, proportion with persistent gonorrhea or reinfection, and interval between initial therapy and follow-up were greater in those who required telephone contact for follow-up than in the group who returned for follow-up. Failure to reappear for follow-up does not imply either bacteriologic cure or disappearance of symptoms. Control of gonococcal infection still depends largely upon aggressive methods of case finding, appropriate therapy and careful follow-up.

Amoebic liver abscess is a rare complication of pregnancy. Two patients are described, one of whom was diagnosed at laparotomy at 28 weeks gestation, after which the pregnancy progressed normally to term. Diagnostic features and the importance of early treatment with metronidazole and aspiration or laparotomy are discussed.

A case of primary hepatocellular carcinoma (HCC) in a 17-year-old pregnant primigravida diagnosed during the 32nd week of pregnancy is presented. A live infant was delivered after induction of labour during the 33rd week. The mother, although still alive 3 months postpartum, had ongoing spread of the malignancy. Only 7 cases of primary liver cancer in pregnancy have been reported to date, with 100% maternal mortality and only 3 live infants. The literature and the diagnosis and management are discussed.

Tracheal smooth muscle (TSM) from an ovalbumin sensitized canine model of allergic asthma showed hypersensitivity and hyper-reactivity to histamine (H) when compared to that from littermate controls in vitro. Mepyramine abolished H responses in TSM of both groups; it also abolished the allergic response to obalbumin of TSM from sensitized dogs. The H2 receptor agonist, 4-methyl histamine (4-MH) caused small dose-related decreases in H contractures but had no effect on carbachol- or K+-induced tension. Metiamide, an H2 antagonist, did not enhance the H contracture, suggesting the 4-MH may not be exerting a relaxant effect since H2 receptors were absent. The maximum H-induced isometric tension was potentiated when the sensitized and control muscle strips were pre-equilibrated with 4-MH. These observations are consistent with the presence in canine TSM of H1 but not relaxant H2 receptors, the release of endogenous H to the tissue during the antigen-antibody reaction, and the competition of H and 4-MH for the H1 receptors. Experiments with specific blockers also indicated that in this model the only transmitter found in the ovalbumin-induced allergic bronchospasm was histamine.

Previous studies from our laboratory showed an atropine-sensitive component in the hyperresponsiveness of ragweed-sensitized canine tracheal smooth muscle (TSM) in vitro to histamine and potassium. The present studies were undertaken to elucidate the nature of the parasympathetic element in this hyperresponsiveness. TSM strips were dissected from ragweed-sensitized and littermate control dogs and their isometric force generation was measured in vitro. Mechanical responses of sensitized TSM were characterized by hyperreactivity (upward shift of the dose-response relationship) to acetylcholine (ACh), atropine-sensitive spontaneous base line activity and prolonged isometric force plateaus. Control TSM did not contract spontaneously and basal tone was maintained passively. However, eserine could produce spontaneous base-line activity and prolonged isometric force plateau in control TSM that mimicked that observed naturally in sensitized TSM. Sensitized TSM was supersensitive (leftward shift of the dose-response relationship) to ACh and electrical field stimulation, and showed a significant leftward shift of the threshold dose to carbamylcholine (carbachol). However, sensitized and control TSMs were equally reactive to carbachol at doses of 10(-8) M and greater. Also, ACh dose-response curves of sensitized and control TSMs in the presence of the cholinesterase inhibitor eserine (10(-8) M) showed no significant differences in sensitivity or reactivity. These results were consistent with a role for local parasympathetic mechanisms such as altered ACh release and/or breakdown in the hyperresponsiveness of ragweed-sensitized canine TSM.

Studies on oxidative phosphorylation revealed that, in frog skeletal muscle mitochondria (SKMM) from the thigh, the adenosine diphosphate/oxygen ratio (ADP/O) was 2.8 +/- 0.1 SE, and the respiratory control ratio was 9.5 +/- 0.9, with pyruvate/malate as the substrate. Oxygen uptake rate (Qo2) was 225 mumol O2 per minute per gram mitochondrial protein +/- 13; phosphorylation rate (ADP/O X Qo2 X 2) was 1,230 mumol ADP phosphorylation per minute per gram mitochondrial protein +/- 77; and the phosphorylation capacity (phosphorylation rate times tissue mitochondrial protein content) was 3.6 mumol ADP phosphorylated per gram wet weight of muscle +/- 0.2. Tissue mitochondrial protein content was determined by the measurement of nicotinamide adenine dinucleotide (NADH) oxidase activity. Electron microscopy (EM) revealed intact, isolated, energized twisted mitochondria of a condensed form. Frog sartorius muscle mitochondria gave similar oxidative phosphorylation parameters when investigated independently of the rest of the thigh. These values of SKMM respiration from the frog are similar to those values obtained from pigeon and rabbit heart and rat skeletal muscles. However, because of the low NADH-oxidase activity indicating reduced mitochondrial content (this was verified in low-magnification EM pictures), phosphorylation capacity was significantly reduced in frog skeletal muscle mitochondria.

Measurement were made of gastric pressure (GP), lower oesophageal sphincter pressure (LOSP) and barrier pressure (BrP) in the supine and lithotomy positions in 17 healthy women undergoing termination of pregnancy in the first trimester. Values in the supine position were similar to those seen in non-pregnant subjects, but there was a significant reduction in LOSP and BrP in the lithotomy position unrelated to any change in intragastric pressure. It is concluded that the lithotomy position is associated with increased risk of regurgitation in early pregnancy.

Males with acute gonococcal urethritis were treated at random with 2.4 million units aqueous procaine penicillin G intramuscularly plus 1.0 g. probenecid orally, 3.5 g. ampicillin orally plus 1.0 g. probenecid orally, or 2.0 g. spectinomycin intramuscularly. The overall follow-up was 97%. All treatments were of equal efficacy, eradication of gonococcal disease being observed in 93 to 97% of treated patients. Treatment failures occurred in each drug group and pre-treatment isolates recovered from these cases showed decreased susceptibility to the agent used. Aqueous procaine penicillin G plus probenecid remains the preferred therapy for gonorrhea. For patients hypersensitive to penicillin, spectinomycin is currently a reasonable alternative drug. This agent, unlike procaine penicillin-probenecid, is probably ineffective against concurrent incubating syphilis, and future development of bacterial resistance is a definite possibility.

Twenty women, undergoing lower abdominal surgery, were allocated randomly to receive a continuous extradural infusion of either 0.125% bupivacaine or placebo at a rate of 15 ml h-1. All had received an intra-operative extradural block. Pain scores were recorded at 30, 60, 90, 120, 150, 180, 240 and 360 min after surgery. From 150 min onwards there was a significant benefit for those receiving the active drug. Six of nine patients in this group had adequate analgesia over the 6-h study period, while all patients in the placebo group required further pain relief.

Endometrial biopsy (EB) specimens obtained from infertile women at Natalspruit Hospital are routinely subjected to histological examination, culture for tubercle bacilli and guinea-pig inoculation (GPI). A retrospective analysis of 103 EB specimens from Natalspruit Hospital and 255 specimens from private patients (in the Greater Johannesburg area) examined during January 1981 - August 1983 revealed a 1,96% overall incidence of endometrial tuberculosis (TB). The incidence of endometrial TB in infertile Black women attending Natalspruit Hospital during this period was 4,85%. Confirmed cases of endometrial TB yielded positive cultures in 57% of cases; GPIs were positive in 71% of cases and histological findings were positive in 42% of cases. Statistical comparison of culture and GPI was difficult because of the small number of cases involved. Cost analysis of culture and GPI suggested that culture of EB specimens as a routine screening procedure for infertile patients is more cost-effective and that GPI tests should be reserved for cases in which TB is highly probable. The literature on symptoms, pathology and diagnostic investigation of pelvic TB is briefly reviewed.