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Benign prostatic hyperplasia occurs in the majority of men past middle age. Transurethral prostatectomy has stood the test of time, but it may not be suitable for some men by virtue of concurrent medical problems or because patients prefer to avoid the risks and complications associated with surgery. This article outlines some of the alternative therapeutic options that are available.

Functional data suggest that the kinetics of force production and relaxation are slowed in hypertrophied skeletal muscle because of chronic overload. The purpose of this study was to determine whether gene expression of the slow/cardiac isoform of the sarcoplasmic reticulum (SR) Ca(2+)-adenosinetriphosphatase (ATPase) pump is upregulated in overloaded fast-twitch plantaris muscles. Increased active muscle loading was induced in rat plantaris muscles bilaterally by surgical removal of gastrocnemius and soleus muscles. Mass of the plantaris muscle was 80% greater 5 wk after surgery than in age-matched unoperated control rats (P < 0.05). Expression of the slow pump mRNA was 135% greater in hypertrophied muscles, as determined from autoradiograms of Northern blots with use of a cDNA probe specific for the slow/cardiac isoform. A monoclonal antibody (7E6) was used to quantify slow Ca2+ pump in SR vesicles with use of Western blot analysis. Densitometry of blots showed that the relative expression of the slow pump protein was 130% greater in hypertrophied plantaris muscles. Expression of the fast SR Ca2+ pump protein isoform, assessed using monoclonal antibody A52, was 25% less in hypertrophied than in control muscles. The Ca2+ uptake rate and ATPase activity of SR vesicles was approximately 15% lower in hypertrophied plantaris muscles (P < 0.05). Differential phospholamban expression could not account for changes in SR Ca2+ handling, because it could not be detected in rat slow- or fast-twitch skeletal muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Aims: To evaluate the effect of microwave irradiation on the staining quality of a range of commonly used primary antibodies in archival, formalin fixed, paraffin wax embedded material, with emphasis on antibodies that have previously worked successfully only on frozen tissue., Methods: Immunocytochemistry (streptavidin-biotin complex technique) was performed on histological sections of a range of normal and pathological tissues, after varying treatment with microwave irradiation. The staining quality of each antibody was compared with that achieved without prior treatment of the sections or after enzyme predigestion., Results: Microwave irradiation permitted successful immunostaining with 20 antibodies that stained only frozen tissues before. The staining characteristics of 21 antibodies that were already known to stain formalin fixed, paraffin wax embedded material were improved. Another 39 antibodies did not show enhanced staining with microwave irradiation. The method preserves tissue morphology and produces more consistent staining than that achieved by enzyme predigestion with many antibodies. Microwave irradiation may also allow some primary antibodies to be used at higher working dilutions. The citrate buffer used in this study avoids the necessity of exposure to heavy metal salts., Conclusions: Microwave antigen retrieval represents an important technical advance within immunocytochemistry that will greatly increase the range of antibodies which can be used to study formalin fixed, paraffin wax embedded tissues.

We present a case in which significant gastric reflux of 99mTc-methoxy isobutylisonitrile (MIBI) was observed in a patient who underwent stress/rest 99mTc-MIBI SPECT myocardial perfusion imaging for suspected coronary artery disease. The intense gastric activity partially obscured myocardial uptake of 99mTc MIBI, particularly in the inferolateral wall of the left ventricle. The presence of significant gastric activity should be considered when performing SPECT myocardial imaging with 99mTc MIBI, and, where necessary, steps should be taken to minimize this activity prior to commencing acquisition.

Emphysematous cystitis in man and domestic animals is reviewed. A case of emphysematous cystitis occurring 5 d after standard therapy for urethral obstruction in a non-diabetic male Siamese-cross cat is described. Escherichia coli was isolated, and the cystitis resolved after antibiotic therapy.

At room temperature (23 degrees C-25 degrees C), the induction of long-term potentiation (LTP) in area CA1 of slices from young male Sprague-Dawley rats was depressed by preincubation with the nitric oxide synthase inhibitors NG-nitro-L-arginine (L-NA, 100 microM) and NG-nitro-L-arginine methyl ester (L-NAME, 100 microM). The D isomers were ineffective under the same conditions. Hemoglobin (20 microM) reduced but did not completely block LTP. Neither L-NA (at concentrations up to 1 mM) nor hemoglobin (20 microM) had any significant effect on LTP in slices from adult rats at room temperature, or in young rats at 29 degrees C-30 degrees C. These results suggest that nitric oxide is unlikely to play a role in the induction of LTP under physiological conditions.

Objectives: Our purpose was to determine whether the sequence of rotation disciplines taken can effect medical student examination scores on the National Board of Medical Examiners Subject Exam score for obstetrics and gynecology., Study Design: A retrospective study was conducted of 439 student files for the academic years 1987 through 1991. The final clerkship grades and subject examination scores for internal medicine, pediatrics, psychiatry, surgery, and obstetrics and gynecology were reviewed., Results: It was determined that completion of internal medicine or surgery before obstetrics and gynecology yielded higher scores in obstetrics and gynecology (p < 0.00001), with the largest improvement (from 533 to 586) observed when obstetrics and gynecology followed the internal medicine rotation., Conclusion: The sequence of rotation can affect scores on the National Board of Medical Examiners subject examination in obstetrics and gynecology. The largest improvement in student scores was observed when obstetrics and gynecology followed the internal medicine or surgery clerkships.

Prostaglandins may alter neuronal noradrenaline release or vascular responsiveness to sympathoexcitation. The purpose of this study was to determine if indomethacin, a prostaglandin synthesis inhibitor, influences the sympathetic and circulatory adjustments to a commonly utilized laboratory stressor in the clinical assessment of autonomic function, the cold pressor test. Venous plasma noradrenaline levels (n = 8), mean arterial pressure and heart rate (n = 10) were measured in healthy male subjects during immersion of the non-dominant hand in cold water (1 degree C) for 90 s. The subjects were given either placebo or indomethacin (100 mg) in a double-blind manner. The order of administration was counterbalanced and a 1 week period was given for systemic clearance of the drug. The absolute level of mean arterial pressure was elevated during the resting control period after indomethacin treatment (88 in placebo vs. 92 mmHg in indomethacin). Both heart rate and venous plasma noradrenaline levels were similar between trials during the resting control period. Mean arterial pressure and heart rate increased similarly during cold pressor testing in both indomethacin and placebo. Venous plasma noradrenaline levels increased during cold pressor testing 162 +/- 39 vs. 200 +/- 69 pg/ml in indomethacin vs. placebo (p > 0.05), respectively. In addition, perceived pain (peak level = 7 +/- 1 vs. 6 +/- 1 units; indomethacin vs. placebo, respectively) was not different between the trials. These results suggest that administration of indomethacin in a maximal single therapeutic dose, does not affect the sympathetic nervous system or circulatory responsiveness to cold pressor testing. It may not be necessary to discontinue indomethacin prior to autonomic function testing.

We have previously shown deficits in specific tension (N.cm-2) in whole hypertrophied skeletal muscle (18-30%). The purpose of the present study was to determine if this intrinsic deficit exists in chemically skinned, hypertrophied single fibers, and also to measure their Ca2+ sensitivity. One group of rats (N = 4) had bilateral surgical ablation of the gastrocnemius and soleus muscles, and another group (N = 4) had the gastrocnemius and plantaris muscles ablated to induce hypertrophy in the plantaris and soleus muscles, respectively. Thirty days after surgery five fibers were dissected and analyzed from each of eight muscles per group, including control muscles. In hypertrophied plantaris and soleus muscles, fiber cross-sectional area (CSA) was 20% and 29% greater, respectively, than control values. Maximal Ca2+ activated tension (Po, pCa 4.5) was 15% greater in hypertrophied plantaris fibers and 18% greater in hypertrophied soleus fibers compared with respective control values (P < 0.05). Therefore, Po expressed per fiber CSA was slightly depressed (3-8%) in both plantaris and soleus fibers (P < 0.05). Regarding Ca2+ sensitivity, the Ca2+ concentration to elicit 50% of Po (i.e., pCa50) was significantly lower in hypertrophied soleus (58%) and plantaris (29%) fibers. This leftward shift in the force-pCa curve reflects greater Ca2+ sensitivity in hypertrophied fibers. Since the single fiber Po/CSA was only slightly decreased, these data suggest that during tetanic stimulation of whole muscle Ca2+ delivery to the contractile apparatus may be impaired.(ABSTRACT TRUNCATED AT 250 WORDS)

The purpose of this investigation was to examine the Ca2+ and caffeine sensitivities of skinned skeletal muscle fibers after fatigue. Single frog semitendinosus fibers were chemically skinned in either a rested state or after tetanic contractions (80 Hz, 100 ms) evoked at 2 s-1 for 5 min. This protocol reduced tetanic force to 1.8 +/- 0.2% of control. Maximal Ca(2+)-activated force (F0, 20 degrees C) was not significantly different between rested and fatigued fibers. However, the concentration of Ca2+ required to evoke 50% of F0 was significantly lower in the fatigued fibers (1.80 +/- 0.18 vs. 1.33 +/- 0.16 microM; P < 0.05), an effect that persisted as the skinned fiber was allowed to incubate in the relaxing solution for > 90 min. The addition of caffeine (25 mM) after Ca2+ loading of the sarcoplasmic reticulum (SR) for periods of 5-30 s (0.25 microM free [Ca2+]) evoked smaller contractures in fatigued fibers than in rested fibers. However, when the loading period was prolonged (60-240 s), force developed after caffeine application was not significantly different between conditions. This suggests that the rate, but not the maximal capacity of Ca2+ loading by the SR, is reduced by fatigue. After Ca2+ loading (120 s), the minimal caffeine concentration required to evoke a contracture in fatigued fibers (5.7 +/- 0.3 mM) was significantly greater than that of control fibers (3.1 +/- 0.4 mM), an effect that persisted with prolonged incubation of the skinned fibers. In addition, the rate of force increase in response to 8 mM caffeine was reduced in fatigued fibers by 41%.(ABSTRACT TRUNCATED AT 250 WORDS)

The purpose of this study was to test the hypothesis that prostaglandins participate in metaboreceptor stimulation of the pressor response to sustained isometric handgrip contraction in humans. To accomplish this, mean arterial pressure, heart rate (n = 10), and plasma norepinephrine levels (n = 8) were measured in healthy male subjects during sustained isometric handgrip at 40% of maximal voluntary contraction force to exhaustion and during a period of postcontraction muscle ischemia. The subjects were given a double-blind and counterbalanced administration of placebo or a single 100-mg dose of indomethacin. A period of 1 wk was allowed for systemic clearance of the drug. Mean arterial pressure increased 25 +/- 5 vs. 22 +/- 4 mmHg during the final minute of isometric handgrip contraction and 26 +/- 2 vs. 21 +/- 5 during the last minute of postcontraction muscle ischemia in the placebo vs. the indomethacin trial (P > 0.05), respectively. Heart rate was increased 21 +/- 4 vs. 17 +/- 3 beats/min during the final minute of isometric handgrip contraction in the placebo vs. the indomethacin trial (P > 0.05), respectively, and returned to control values during postcontraction muscle ischemia. Plasma norepinephrine levels increased 343 +/- 89 vs. 289 +/- 89 pg/ml after isometric handgrip contraction and 675 +/- 132 vs. 632 +/- 132 pg/ml after postcontraction muscle ischemia (P > 0.05) in the placebo vs. the indomethacin trial, respectively. These results suggest that prostaglandin inhibition does not significantly modulate muscle contraction-induced stimulation of mean arterial pressure, heart rate, or plasma norepinephrine levels.

Besnoitiosis was confirmed in a pony which presented with inspiratory dyspnoea, scleroderma and ventral oedema. Numerous cysts were visible in the sclerae. Histological examination of the skin confirmed the presence of numerous cysts. The parasite could not be transmitted by subcutaneous injection of homogenised skin from the infected horse to rabbits and a horse. Ultrastructural morphology of the crescent-shaped bradyzoites was not compatable with Besnoitia besnoiti or B. jellisoni and it is proposed that the infection was caused by B. bennetti.

Bladder outflow tract obstruction was produced in immature female guinea-pigs. Obstruction caused an increase in voiding pressure and bladder weight and a decrease in bladder compliance. No change occurred in the sensitivity of obstructed detrusor strips to exogenous agonists, but the force of contraction and response to electrical stimulation of the intrinsic nerves were less than in the strips from controls. The response of strips from sham-operated animals to exogenous agonists and to electrical stimulation was greater than that from obstructed animals. The effects of length and tension could not account for the in vitro responses from obstructed animals. Histology after obstruction showed muscle hypertrophy, connective tissue infiltration and decrease in nerve density. Many of the changes resembled those seen in the obstructed human bladder.

When animals are preexposed to a stimulus without consequence they are subsequently slower to associate this stimulus with an important event, such as footshock. This retarding effect of stimulus preexposure is called latent inhibition and can be demonstrated in a variety of classical and instrumental paradigms and in a wide range of species, including man. Latent inhibition is disrupted in acute schizophrenics and by amphetamine treatment in both rat and man. The present study investigated the role of hippocampal 5HT terminals in latent inhibition using a conditioned suppression procedure with male Sprague-Dawley rats. Microinjections of 5,7-dihydroxytryptamine in the fornix-fimbria significantly reduced hippocampal indoleamine levels and attenuated latent inhibition of conditioned suppression. This finding supports the hypothesis that the destruction of mesolimbic 5-hydroxytryptamine terminals reduces latent inhibition. This result is discussed in terms of the possible involvement of reduced serotonergic function in schizophrenic attentional disorder. In addition to the predicted lesion effect, biochemical analyses indicated that experimental treatments in the latent inhibition procedure altered neurotransmitter turnover: utilization ratios for 5-hydroxytryptamine and/or dopamine were increased in preexposed relative to nonpreexposed animals in four of the six brain regions sampled.

Pulmonary vascular sequestration of leukocytes has been reported to increase in some models of lung injury, including that induced by gram-negative bacterial lipopolysaccharide (LPS). Neutrophils recruited to the lung likely participate in LPS-induced lung inflammation and associated injury, but the functional activities of these pulmonary vascular neutrophils have not been directly assessed. In the current study, cells were recovered by pulmonary vascular lavage (PVL) of isolated rat lungs, harvested 2 h after intravenous infusion of LPS (3 mg/kg) or saline in intact rats, at which time LPS-induced neutrophil recruitment to the lung could be appreciated histologically but not by airway lavage. Relative concentrations of leukocytes recovered from the pulmonary vasculature by PVL were compared with those present in circulating blood, normalizing for lavage dilution on the basis of erythrocyte counts. Excess neutrophils, lymphocytes, monocytes, and eosinophils were recovered from the pulmonary vasculature of controls, and LPS infusion increased recovery of neutrophils (most prominently), lymphocytes, and monocytes. Compared with cells recovered from controls, PVL neutrophils from LPS-infused animals were primed for increased zymosan-stimulated superoxide generation, determined by ferricytochrome C reduction, and were more adherent to nylon wool columns. Northern blots of extracted RNA demonstrated that LPS infusion also upregulated interleukin-1 beta (IL-1 beta) mRNA expression in PVL leukocyte samples, but not BAL or circulating blood samples. Ficoll-hypaque separation demonstrated that the LPS-induced IL-1 beta signal in PVL leukocytes was derived primarily from polymorphonuclear rather than mononuclear leukocytes. In conclusion, all circulating leukocyte populations are sequestered in rat lungs, and LPS increases pulmonary vascular sequestration of leukocytes, recruiting most prominently an activated pool of neutrophils that are more adherent, primed for increased oxygen radical production, and expressing increased IL-1 beta message. These findings suggest a more prominent role than previously appreciated for sequestered neutrophils in sepsis-induced lung inflammation.

Twenty subjects were randomly assigned to: 1) prophylactic ibuprofen (N = 5) [400 mg TID initiated 4 h before collection of baseline data and strenuous eccentric exercise bout], 2) therapeutic ibuprofen (N = 5) [400 mg TID initiated 24 h after baseline], 3) placebo (N = 5), or 4) control (N = 5). Muscle soreness perception, plasma creatine kinase, knee extensor torque, and EMG of the quadriceps were evaluated at baseline, 24, and 48 h. The prophylactic ibuprofen group had between 40 and 50% less muscle soreness perception and significantly less decline in isometric, concentric, and eccentric torque at 24 h compared with the other three groups (P < 0.05). At 48 h both prophylactic and therapeutic ibuprofen had significantly less muscle soreness perception and decline in torque than the placebo and control groups (P < 0.05). There was no difference between the amount of muscle damage between the four groups at 24 and 48 h. Vastus medialis and lateralis EMG magnitude decreased across time. Vastus lateralis EMG magnitude had significantly less decline from baseline for prophylactic ibuprofen compared with the other three treatments at 24 h, while both prophylactic and therapeutic ibuprofen had significantly less decline at 48 h. These data indicate that a prophylactic dosage of ibuprofen does not prevent CK release from muscle, but does decrease muscle soreness perception and may assist in restoring muscle function.

The use of quantitative 99Tcm-EHIDA imaging with cholecystokinin and the measurement of gall bladder ejection fraction in a prospective study of 89 patients with right upper quadrant pain is described. Correlation with surgical and histological findings and clinical follow-up suggests that gall bladder ejection fraction < or = 35% is a reliable and accurate indicator of acalculous gall bladder disease.

We performed an immunohistochemical analysis of frozen sections from testicular biopsies from 23 children with acute lymphoblastic leukemia. Eleven cases were infiltrated by leukemia. Tumor cells were immunostained by a panel of antibodies that identified CD10, CD43, CD19, CD3, CD7, and MHC class I and II. The immunoreactivity of normal testicular components was also studied. Normal testis showed no CD10 reactivity. Wide variation in the number of stromal macrophages identified by CD11c was found. Transferrin receptor (CD71) was expressed by some stromal macrophages, by seminiferous tubules, and by Leydig cells. B lymphocytes were absent from the testicular stroma but small numbers of T lymphocytes were consistently present. MHC class I and II were expressed by most stromal cells but not by seminiferous tubules.

The purpose of this paper is to describe a novel and practical technique for endobronchial catheter placement utilizing the flexible fiberoptic bronchoscope. Placement of endobronchial catheters via the flexible bronchoscope is limited by the small dimension of the bronchoscope's internal channel and frequently requires repeated manipulation to verify position endobronchially. We describe preliminary experience with a technique that we call the "bronchoscopic shuttle," which circumvents this limitation. The spectrum of possible clinical uses for this technique is discussed.

A university-based hospital serving mainly a developing community readily appreciated that its clientele was from a very different sociological and cultural background than that of the professional staff and that developed and developing communities and their pets exhibit different patterns in their health status, with most diseases being predominantly related to socio-economic predicament. The need for a community-orientated service was recognised. From 1987 to 1988, the small animal outpatient clinic was used for an informal, unstructured sociological observation and interview-based study of the clientele and their pets. During this period, an informal educational programme was implemented to teach basic pet health care, and the efficacy of this programme was empirically gauged by comparing the knowledge and attitudes of first-time clients with those of regular clients. Regular clients appeared to become increasingly concerned about the health and management of their pets and the condition of their animals appeared to improve, with a corresponding decline in the degree of parasitism. The majority of clients however, still regarded the main reason for keeping dogs as the provision of some form of security. It also appeared as if improved attitudes towards household pets paralleled improvements in socio-economic status.

These experiments sought to determine the influence of sarcolemmal Na(+)-Ca2+ exchange on halothane and on caffeine contractures of malignant hyperthermic (MH) skeletal muscle. Fiber bundles excised from MH susceptible pigs (Pietrain) were exposed to halothane (3%) and caffeine (0.5-8.0mM) while Na(+)-Ca2+ exchange was inhibited by reducing extracellular Na+ from 100% to 50, 25 and 0% of control. Halothane contracture magnitude was not altered by 50 or 25% Na+ whereas 0% Na+ increased the contractures by 51%. 0 and 25% Na+ increased the magnitude of caffeine contractures (2-8mM) by 53-176%. These results suggest that external Na+ and the Na(+)-Ca2+ exchange mechanism influences contractures of MH skeletal muscle.

A series of nine cases of localized amyloidosis of the lower genitourinary tract are reported. The patients comprised six males and three females with an age range of 50-79 years at initial presentation. Clinically and on cystoscopy, the lesions were often diagnosed as neoplasms. Histologically, seven cases had typical features of localized amyloid deposits, while two cases had an unusual appearance with a florid histiocytic and giant cell reaction. Using an immunoperoxidase staining method the deposits were non-reactive with antibodies to serum amyloid A protein, prealbumin and beta 2 microglobulin, while equivocal immunoreactivity was seen with anti-light chain antibodies.

The purpose of this investigation was to determine the effects of reduced pH on Ca(2+)-induced Ca2+ release (CICR) from skeletal muscle sarcoplasmic reticulum (SR). Frog semitendinosus fiber bundles (1-3/bundle) were chemically skinned via saponin treatment (50 micrograms/mL, 20 min), which removes the sarcolemma and leaves the SR functional. The SR was first depleted of Ca2+ then loaded for 2 min at pCa (log free Ca2+ concentration) 6.6. CICR was then evoked by exposing the fibers to pCa 5-7 for 5-60 s. CICR was evoked both in the absence of ATP and Mg2+ and in the presence of beta, gamma-methyleneadenosine-5'-triphosphate (AMPPCP, a nonhydrolyzable form of ATP) and Mg2+. Ca2+ remaining in the SR was then assayed via caffeine (25 mM) contracture. In all cases, CICR evoked at pH 6.5 resulted in larger caffeine contractures than that evoked at 7.0, suggesting that more Ca2+ was released during CICR at the higher pH. Accordingly, rate constants for CICR were significantly greater at pH 7.0 than at pH 6.5. These results indicate that reduced pH depresses CICR from skeletal muscle SR.

There exist numerous temperature-based techniques to calculate the early postmortem interval of human corpses. This paper presents eight commonly used time of death algorithms and describes how they were applied to eight corpses.

Objective: Intratracheal instillation of bleomycin in rats has been extensively used as an animal model of pulmonary fibrosis in humans, although it produces a patchy, airway based response. We proposed that the haemodynamic sequelae of the bleomycin model might be less severe than those associated with more diffuse lung injury., Methods: Pulmonary and systemic haemodynamic indices were examined in adult Sprague-Dawley rats (approximately 400 g, n = 10) both at rest and during submaximal exercise on a rodent treadmill, approximately 60 days after intratracheal bleomycin (6 units.kg-1), and the results compared to a control group (n = 6)., Results: Compared to controls, mean pulmonary artery pressure (PPA) was increased by intratracheal bleomycin (p = 0.02) both at rest [24.5 (SEM 2.6) v 18.2(0.9) mm Hg] and during exercise [34.7(3.0) v 26.7(0.7) mm Hg]. PPA-pulse product was also increased, with a similar trend in right ventricular work index, but cardiac index was not altered. Right ventricular hypertrophy was noted on necropsy examination. Consistent with pulmonary fibrosis, lung dry weight, total protein, and hydroxyproline were also raised, and these values correlated strongly with (mean) PPA at rest (r2 = 0.86, 0.81, 0.69, respectively) and during exercise (r2 = 0.81, 0.79, 0.65, respectively). Packed cell volume was increased by intratracheal bleomycin, at 49(1) v 45(1)%, p = 0.02. CaO2 tended to decrease with exercise in the bleomycin group, although this was not statistically significant, while systemic oxygen delivery and consumption were not altered., Conclusions: Pulmonary hypertension and right ventricular hypertrophy occur in this model of lung fibrosis, and correlate with the severity of fibrosis. However, these sequelae were less severe than those previously demonstrated in association with crotalaria ingestion. We suggest that the haemodynamic sequelae of the intratracheal bleomycin model are consistent with patchy, airway based fibrosis, but reflect less well the haemodynamic sequelae of more diffuse fibrotic injury associated with systemic processes.

The purpose of this study was to evaluate the pain alleviating effect of dexamethasone iontophoresis on delayed onset muscle soreness (DOMS) produced via an eccentric exercise bout, and to determine the effect on muscle function. Baseline data were collected on 18 female subjects for maximum isometric knee extension contraction (MVC), knee extension peak torque (PT), knee extension work (W), and muscle soreness perception (SP). All values were subsequently reassessed 24 and 48 hours after a 10-min bout of bench stepping. Immediately following the 24-hr reassessment, the experimental (E) (N = 6) and placebo (P) (N = 6) groups received iontophoresis treatment while the control (C) group (N = 6) received no treatment. Percent deviation from baseline of SP was significantly less at 48 hours (p less than 0.05) for the E group compared to P and C groups. However, MCV, PT, and W were no different between the three groups at 48 hours post muscle soreness bout.

1. In malignant hyperthermia susceptible muscle fibers, the calmodulin antagonist, W-7 (10 microM), evoked contractures and potentiated halothene (3%) induced contracture. No effect was seen at 0.1 or 1.0 microM) W-7. 2. Dantrolene sodium (6 microM) prevented and reversed W-7 induced contracture: nifedipine did not. 3. In chemically skinned fibers, 10 microM, 1.0 microM, and 0.1 microM W-7 released 100%, 30%, and 10% of stored calcium respectively, and the effect of 10 microM W-7 was irreversible in that the SR was unable to re-sequestor calcium after exposure to the drug. 4. The release of calcium by W-7 was not prevented by exogenously added calmodulin (3 microM), nor mimicked by mastoparan (10 microM). 5. Calcium release by W-7 appears to be independent of calmodulin inhibition.

This investigation examined the mechanical responses of malignant hyperthermic (MH) and normal porcine skeletal muscle to repetitive stimulation. Twitch and maximal tetanic tensions were not significantly different between muscle types. Tensions produced during stimulation at 20-80 Hz were significantly less in MH muscle than in normal muscle. In addition, MH muscle showed significantly greater force decline (tetanic fade) at the end of contractions evoked by 20-80 Hz stimulation. When stimulated to fatigue, both normal and MH muscle exhibited similar rates of tension decline during the initial minutes. Further stimulation caused additional decline in normal muscle, but a tension plateau in MH muscle. In all cases, normal muscle had greater magnitudes of fatigue than did MH muscle. Results show that there are marked differences between MH and normal muscle in the mechanical responses to repetitive stimulation. Due to its inability to properly regulate intracellular Ca2+ exchange, it is possible that MH muscle might be a useful tool for identifying the mechanisms of muscle fatigue in normal muscle.

It is well documented that repeated voluntary activity or electrical stimulation of skeletal muscle results in a decline in force production or power output. However, the precise physiological causes of "muscle fatigue" are not yet well understood. It is conceivable that the mechanism(s) may lie either in the conduction of action potentials in the central and peripheral nervous systems or in the transformation of the electrical event into mechanical force production by the muscle itself. In fact, none of the components of the electrical pathway from generation of impulses in the brain to their conduction over the neuron and the excitable membranes of the muscle can as yet be ruled out as potential contributors to the fatigue process. Relative to that on conduction failure, more information exists concerning the possibility that a defect in the excitation contraction coupling process in skeletal muscle, e.g., intracellular acidosis, inadequate supply of energy for contraction, or a disruption in Ca2+ homeostasis may also be significant in compromising force production following sustained activity. Despite this, the amount of conflicting data derived from these experiments has hindered the resolution of this question. In the future more attention must be given to such issues as the type of activity used to elicit fatigue and the fiber composition of the muscles studied. This is imperative as these factors clearly impact the nature of correlations between the biochemical and physiological events in muscle that are required to support prospective fatigue mechanisms.

The purpose of these experiments was to determine if the Ca2+ agonist BAY K 8644 and the Ca2+ antagonist nifedipine alter the mechanical responses of malignant hyperthermia-susceptible (MHS) skeletal muscle to halothane and caffeine. Muscle fiber bundles were dissected from MHS porcine skeletal muscle and exposed to BAY K 8644 (10 microM), nifedipine (1 microM), low-Ca2+ media [Ca2+ replaced by 1 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid], or diltiazem (30 microM) administered alone and with halothane (3%) or caffeine (0.5-0.8 mM). When administered alone, both halothane and BAY K 8644 evoked a significant change in resting tension (i.e., contracture) of 193.7 +/- 61.0 and 51.9 +/- 21.5 mN/cm2, respectively. When administered in combination, BAY K 8644 had no effect on the magnitude of the halothane contracture (195.2 +/- 58.6 mN/cm2) but reduced its onset time from 306.7 +/- 36.3 to 105.9 +/- 8.9 s. Nifedipine, low Ca2+, and diltiazem significantly reduced the halothane contracture (103.1 +/- 30.3, 123.1 +/- 20.6, and 112.6 +/- 16.2 mN/cm2, respectively) but had no effect on its onset time. In addition, low Ca2+ reduced the magnitude of the BAY K 8644 contracture (8.2 +/- 2.1 mN/cm2). BAY K 8644 also increased contractures induced by low caffeine concentrations (0.5-2.0 mM) but did not alter contractures induced by 4.0 and 8.0 mM caffeine, whereas nifedipine, low Ca2+, and diltiazem had no effect on these contractures. These results suggest that extracellular Ca2+ influx may have some influence on halothane but not on caffeine contractures of MHS skeletal muscle.

Caffeine is one of the most widely consumed drugs in the world. There is a strong belief that caffeine is an ergogenic aid to sports performance. Although much evidence suggests that caffeine may improve endurance exercise performance, questions still remain with regard to its effects on neuromuscular function and brief, high-intensity exercise performance. At the cellular level, caffeine stimulates the central nervous system (CNS), enhances neuromuscular transmission and improves skeletal muscle contractility. The former two effects seem to have facilitative effects on activities which require quick reactions and rapid movements. This is evident in that simple and choice reaction and movement times are reduced following ingestion of small quantities of caffeine. It appears, however, that the caffeine-induced increases in muscle contractility seen in vitro do not translate into improved strength, in vivo. Acute caffeine ingestion does not seem to increase maximal voluntary contractions or maximal power output nor delay fatigue. Thus use of caffeine to improve performance in activities requiring strength and short-term endurance seems unwarrented. Further research is needed before clear conclusions can be draw regarding caffeine's effects on neuromuscular function and high-intensity exercise performance.

The purpose of this investigation was to examine the effects of the Ca2+ agonist BAY K 8644 and the Ca2+ antagonist nifedipine on halothane- and caffeine-induced twitch potentiation of mammalian skeletal muscle. Muscle fiber bundles were taken from normal Landrace pigs and exposed to BAY K 8644 (10 microM), nifedipine (1 microM), and low Ca2+ media administered alone and in combination with halothane (3%) or with increasing concentrations of caffeine (0.5-8.0 mM). Both BAY K 8644 and halothane potentiated twitches by approximately 80%; when they were administered in combination, twitch potentiation was nearly double that caused by either drug alone. In the presence of nifedipine, halothane increased twitches by less than 30%. Low Ca2+ significantly depressed twitches by approximately 25% but also inhibited halothane's inotropic effect. BAY K 8644 augmented caffeine potentiation but only at low caffeine concentrations (0.5-2.0 mM). Nifedipine and low Ca2+ failed to inhibit caffeine's inotropic effects. These results suggest that halothane potentiates twitches via a mechanism that involves or is influenced by extracellular Ca2+.

Background and Methods: Pentoxifylline can inhibit blood leukocyte functions in vitro, and some inflammatory processes in the lung in vivo. Therefore, we examined the effects of pentoxifylline on alveolar macrophage functions in vitro. Alveolar macrophages were harvested from normal rat lungs by airway lavage. The dose-response relationship of varying concentrations of pentoxifylline and in vitro cell functions were examined. Macrophage functions studied included adherence to nylon wool, random (unstimulated) and zymosan-activated serum-stimulated migration through 5 microns millipore filters, and superoxide generation induced by zymosan-activated serum as assayed by cytochrome c reduction., Results: Pentoxifylline inhibited superoxide generation and stimulated migration (but not random migration or adherence) in a dose-dependent fashion. Statistically significant inhibition was demonstrated at 0.5 mM and 5.0 mM concentrations of pentoxifylline, respectively, for stimulated migration and superoxide generation., Conclusions: Pentoxifylline can inhibit some alveolar macrophage functions in vitro. These effects may inhibit some forms of inflammatory lung injury, particularly when iv infusion of high doses of pentoxifylline are utilized. However, potentially adverse effects on inflammatory defense mechanisms must be considered as well.

In an attempt to understand the pathogenesis of corneal changes and conjunctival scarring in trachoma, which are responsible for blindness in some 7 million people worldwide, the surface expression of major histocompatibility complex class II antigens on conjunctival epithelial cells was sought in patients with different clinical features of the disease. Class II expression was significantly associated with active (inflammatory) trachoma, but an independent association with corneal pannus or conjunctival scarring could not be shown. Longitudinal data suggest that class II expression may antedate clinically active disease and persist after it has resolved.

The Assessment of Living Skills and Resources (ALSAR), an innovative instrumental activities of daily living tool, systematically evaluates the accomplishment of 11 tasks by separately rating patient skill and resource levels for each task and combining these levels to determine risk. The ALSAR was administered to 75 elderly veterans in a home care program. It predicted change to more supportive living arrangements and a more structured living environment, nursing home placement, hospitalization, and death during the 6-month study period. The ALSAR has proven useful for interdisciplinary problem solving and treatment planning.

A computer based expert system for providing orthodontic advice for Class II Division 1 malocclusion has been developed and evaluated. Treatment plans produced by the system for 31 non-prior approval cases drawn from material provided by the Dental Practice Board were compared with the treatments actually carried out by the practitioners. The shortcomings of the system are discussed.

1. The purpose of this investigation was to determine if alterations in extracellular calcium (Ca2+) influx by the dihydropyridine derivatives Bay K 8644 and nifedipine affected skeletal muscle fatigue. 2. Tetanic contractions (80 Hz, 100 msec) of frog sartorius muscles were evoked every sec for 3 min. Muscles were fatigued in normal Ringer's solution (NR), in NR containing 1 microM nifedipine of 10 microM Bay K 8644 or in low Ca2+ Ringer's. 3. In each case, the experimental conditions increased the rate and magnitude of fatigue. Rate constants of fatigue obtained during Bay K 8644, nifedipine and low Ca2+ conditions (-.0122 +/- .0016, -.0397 +/- 0022 and 0.0169 +/- .0064 sec-1, respectively) were significantly greater than NR (-.0104 +/- .0006 sec-1, p less than .05). In addition, tetanic forces developed at the end of the stimulation period under the experimental conditions (3.90 +/- 0.81, 1.21 +/- 1.40 and 2.04 +/- 1.10% of initial) were significantly less than NR (7.18 +/- 1.27%, p less than .05). 4. Caffeine contracture forces (10 mM) evoked immediately after stimulation were not significantly different between conditions. 5. These results suggest that alterations in sarcolemmal Ca2+ exchange has some influence on the fatigue process.

1. The effects of the calcium agonist, Bay K 8644, on the mechanical output of skeletal muscle were studied in frog semitendinosus fiber bundles and in whole sartorius muscles. 2. Low concentrations of Bay K 8644 (less than or equal to 1 microM) had no significant influence on isometric twitches. Concentrations between 5-20 microM increased peak tension by 28.6 +/- 2.9% while higher concentrations (greater than or equal to 50 microM) initially increased then depressed twitches by 70 +/- 3.5%. 3. 10 microM Bay K 8644 also increased peak tension developed during low frequency stimulation (i.e. less than or equal to 40 Hz), slightly depressed high frequency contractions (i.e. greater than or equal to 80 Hz) but did not reduce maximal tetanic tension which occurred at about 60 Hz. 4. Potentiation of twitches and low frequency tetani and depression of high frequency tetani by Bay K 8644 were partially antagonized by nifedipine (10 microM), low extracellular calcium and D-600 (5 microM). These conditions did not, however, block the depressant actions of greater than or equal to 50 microM Bay K 8644. 5. In skinned fibers, 10 microM Bay K 8644 had no effect on resting or maximal Ca2+ activated tension. Also, 10 microM Bay K 8644 had no effect on caffeine contractures when added to the previous Ca2+ loading solution. 6. These results suggest that Bay K 8644 has both positive and negative inotropic actions on isolated skeletal muscle, which are dependent on drug concentration and muscle activation pattern.

In this study we report the numbers and metachromatic dye-staining characteristics of mast cells (MCs) in the conjunctiva of normal subjects and patients with seasonal allergic conjunctivitis caused by pollenosis. In addition, we have used a monoclonal antibody to the MC-specific enzyme, tryptase, to enumerate tryptase-positive cells immunohistochemically. Tarsal conjunctival MCs were found to be present in increased numbers in the allergic compared to the nonallergic subjects. Most of the MCs exhibited staining that was formaldehyde resistant, compatible with their identification as connective tissue MCs or basophils. The high positive staining for tryptase confirmed that the metachromatic cells stained with toluidine blue were MCs and not basophils, both in normal and allergic subjects.

Immunohistochemical staining of conjunctival biopsies from four normal subjects and five patients with atopic keratoconjunctivitis (AKC) was performed, using a monoclonal antibody to human mast cell tryptase. A massive hyperplasia of mast cells in the patients with AKC was demonstrated. The mean mast cell density in the normal patients was 55.6/mm2 and in the patients with AKC, 172/mm2. The appearance of large numbers of mast cells in the conjunctival epithelium of AKC patients was also demonstrated. The possible pathophysiological significance of these findings is discussed.

The effects of certain GABA-modulating drugs, fornicotomy, hippocampectomy and various septal lesions were analysed in a discrete-trial fixed ratio 5 (FR5) bar-press paradigm. Chlordiazepoxide, fornicotomy, hippocampectomy, electrolytic lateral septal lesions and ibotenic acid medial septal lesions facilitate extinction of the FR5 response. Some of these treatments (chlordiazepoxide, hippocampectomy, electrolytic lateral septal lesions) have previously been found to increase resistance to extinction of alley-running after continuously reinforced (CRF) acquisition training. The treatments which facilitated extinction in the discrete-trial FR5 paradigm have been found to reduce or abolish the partial reinforcement extinction effect in the alley. These results indicate that the discrete-trial FR5 paradigm is not analogous to a runway CRF schedule, but may be analogous to a runway partial reinforcement schedule.

A case of lead poisoning caused by ingestion of a lead roof-washer is described in a one-year-old, spayed Fox Terrier bitch, presented with nervous signs, and basophilic stippling of red blood cells. Blood concentrations of lead were in the low toxic range. Radiography of the abdomen revealed radio-dense objects in the stomach, which on gastrotomy included a lead roof-washer. Prior to removal of the foreign bodies, the dog showed remarkable improvement on non-specific symptomatic treatment alone, and recovered well after surgery, only to die unexpectedly several hours later. Concentrations of lead in the liver and kidneys were extremely high, and histology revealed typical intracellular inclusions and organ degeneration. In the light of these findings, it is suggested that all cases of suspected or confirmed lead poisoning be given specific chelation therapy.

The purpose of this investigation was to determine the effects of low extracellular calcium and calcium antagonists on skeletal muscle staircase and fatigue. Initial experiments revealed that, brief exposure (10 minutes) of single frog sartorius muscle to diltiazem, D-600 (5 and 30 microM) and low calcium Ringer's solution (LCR, calcium replaced by magnesium and EGTA) had little effect on isometric twitches evoked every 30 seconds. However, when stimulated at 1 per second for 15 minutes, the calcium antagonists significantly decreased the magnitude and time course of the staircase, whereas LCR decreased only the time course. Each experimental condition significantly increased the rate of fatigue while diltiazem and D-600 both increased the magnitude of fatigue. Following the stimulation period, caffeine (10 mM) elicited contractures from all muscles whereas high potassium (180 mM) elicited contractures from control muscles only. These results indicate that calcium channel antagonists depress the skeletal muscle staircase response. They also indicate that these compounds as well as LCR enhance the fatigue process. Extracellular calcium influx may therefore have some influence on skeletal muscle twitches during prolonged repetitive activity.

An intellectually delayed adult ingested and aspirated a large quantity of polyurethane foam, developing acute respiratory failure in association with partial airway obstruction. The foam was identified by flexible bronchoscopy and successfully removed from the bronchus intermedius and left mainstem bronchus with a retrieval basket. This facilitated normalization of blood gases and eventual recovery. However, the unobstructed right upper lobe became infiltrated radiographically, presumably resulting from regional hyperinflation and/or occult focal aspiration.

Microinjections of 5,7-dihydroxytryptamine (5,7-DHT) into the fornix-fimbria (FF) reduced dorsal hippocampal [3]5-HT uptake to 40% of control levels. The FF 5,7-DHT lesions increased nocturnal activity in photocell cages, but reduced central ambulation in diurnal open field tests. The lesions also disrupted both habituation of rearing across days in the open field and alternation in a Y-maze. Hence FF-derived hippocampal 5-HT terminals participate in controlling activity, but their role depends on the test apparatus and procedures.

An avidin-biotin enhanced immunoperoxidase procedure using monoclonal antibodies (AA1, AA3, and AA5) prepared against human mast cell tryptase resulted in intense staining of mast cells in paraffin-embedded tissue. The distribution of mast cells observed was similar to that seen when adjacent serial sections were stained using a standard procedure with toluidine blue, though the immunoperoxidase technique permitted the identification of significantly more mast cells. With monoclonal antibody AA1, immunostaining was entirely specific for mast cell granules, and there was negligible background staining in a range of tissues including lung, tonsil, colon, gastric mucosa, skin, and pituitary. There was no staining of antibody on basophils or on any other normal blood leukocyte. The technique was effective with tissue fixed in either Carnoy's or neutral buffered formalin, though the internal mast cell structure was better preserved with formaldehyde fixation. The immunoperoxidase staining procedure with monoclonal antibody AA1 is a highly specific and sensitive means for the detection of mast cells in routinely processed tissues.