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Biomedical subjects

I M Lang

Publications and source records attributed to I M Lang.

At least 55 records · Page 3Linked to original sources
PubMed1996

Initiation of esophageal secondary peristalsis by slow fluid infusion in the opossum: effect of hydrochloric acid.

We investigated the mechanisms of slow fluid infusion-induced secondary peristalsis and the effects of hydrochloric acid on this response. In 13 chronically esophagostomized opossum, acidic and neutral barium sulfate were infused into the distal esophagus at a rate of 1.1 ml/min, while recording the esophageal dimension by videofluoroscopy and esophageal intraluminal pressure concurrently. The effects of atropine, tetrodotoxin, capsaicin, and bilateral cervical vagotomy on the response to slow fluid infusion were examined. Acidic barium initiated secondary peristalsis more frequently and at shorter latency with less increase of preperistaltic intraesophageal pressure than neutral barium (P < 0.05). Atropine abolished secondary peristalsis initiated by neutral barium. For acidic barium, atropine decreased the incidence of secondary peristalsis, increased the latency for initiation of secondary peristalsis, and initiated secondary peristalsis more distally (P < 0.05). Tetrodotoxin or vagotomy and capsaicin abolished activation of secondary peristalsis. We concluded that secondary peristalsis can be stimulated in response to slow distension by minute amounts of fluid. This peristalsis is atropine and capsaicin sensitive and vagally mediated. The presence of acid significantly lowers the threshold for stimulation of secondary peristalsis induced by slow fluid distension. This effect seems to be atropine resistant.

Animals↗
PubMed1996

Medical management of primary pulmonary hypertension.

Primary pulmonary hypertension (PPH) is a poorly understood, progressive disease that is characterized by elevation of pulmonary artery pressure and vascular resistance, leading to right ventricular failure and death within 2-3 yrs after diagnosis. Based upon the concept that vasoconstriction and thrombotic occlusion of resistance vessels precipitate this process, vasodilator therapy and anticoagulation have become the main strategies for improving survival in these patients. Whereas, a few years ago, medical therapy of primary pulmonary hypertension was perceived as a bridging therapy to lung or heart lung transplantation, modes of therapy are being clinically tested at this time to offer an alternative to the surgical treatment of this disease. However, no selective pulmonary vasodilator is yet available. Therefore, and because of the potential hazards of vasodilator treatment, standardized haemodynamic testing is performed prior to initiation of vasodilator treatment. In this update, the currently available compounds both for haemodynamic testing and chronic therapy, their mode of action, method of administration and efficacy are reviewed.

Anticoagulants↗
PubMed1996

Vascular endothelial growth factor production in normal epidermis and in benign and malignant epithelial skin tumors.

Vascular endothellal growth factor (VEGF) increases vascular permeability and acts as a mitogen for endothelial cells in vivo and in vitro. We and others recently demonstrated that cultured human keratinocytes constitutively secrete VEGF. In the present study, we examined the expression of this growth factor in various epithelial skin tumors and in normal skin. Using in situ hybridization, we detected strong VEGF mRNA expression in all of 10 squamous cell carcinomas, 13 common warts, 11 seborrheic keratoses, and in 7 of 8 keratoacanthomas studied. By contrast, we found no VEGF mRNA in 9 of 14 basal cell carcinomas. VEGF mRNA was readily detectable within the epidermis adjacent to the tumors as well as in tumor cells and in the epidermis of normal human skin. Northern hybridization of RNA derived from normal human epidermis identified VEGF transcripts of 3.7 and 1.8 kb, and reverse transcriptase polymerase chain reaction confirmed that epidermal cells, like keratinocytes in vitro, express the three major splice forms of VEGF. Immunohistochemical staining with monoclonal antibodies confirmed that expression of VEGF mRNA was accompanied by the presence of VEGF protein. Our data demonstrate that VEGF production by tumor cells in situ does not distinguish malignant from benign epithelial tumors of the skin because it is present in both. The constitutive expression of VEGF by normal keratinocytes in situ suggests that this angiotropic cytokine is important for the regulation of vessel function under physiologic conditions.

Blotting, Northern↗
PubMed1995

MR imaging appearances of cervical epidural abscess.

Epidural abscess of the cervical spine is an uncommon disorder. The presentation is often non-specific and the diagnosis unsuspected. Magnetic resonance (MR) imaging is now considered the imaging investigation of choice. We report six patients with cervical epidural abscess diagnosed on MR imaging. The MR imaging showed the abscess to have a variable appearance and enhancement characteristics. Follow-up MR examinations confirmed resolution of the abscess and, in five cases, allowed conservative management.

Abscess↗
PubMed1994

Effect of aging on the deglutitive oral, pharyngeal, and esophageal motor function.

Aging affects some members of the swallowing orchestra and spares the others. It seems that changes in the pharynx of the elderly are more of a positive nature than a negative one and reflect an adaptation to age-induced structural changes of the upper esophageal sphincter. In the esophagus, the positive change in deglutitive peristaltic amplitude and duration seem to revert to a negative one over the age of 90 years. In the upper esophageal sphincter, it appears that aging reduces the resting pressure, but spares its response to various stimuli. Considering the increasing elderly population and their medical needs, further normalcy data about various manometric aspects of deglutition is needed for physiologic studies as well as diagnostic and therapeutic purposes.

Adult↗
PubMed1994

An update on the physiology of the components of the upper esophageal sphincter.

The upper esophageal sphincter is composed of both opening and closing muscles. The opening muscles include the thyrohyoideus and the geniohyoideus, and the closing muscles include the cricopharyngeus, thyropharyngeus, and cervical esophagus. The relative contribution of each muscle to the opening and closing of the UES varies with the physiologic state. Although the cricopharyngeus may be the primary muscle of the UES, it cannot account for all of the observed functions of the UES.

Arousal↗
PubMed1994

Case report: an unusual association of a rectovaginal fistula with the Currarino triad.

Currarino et al. in 1981 described an association between an anterior sacral defect, congenital anorectal stenosis or another type of low anorectal malformation and a presacral mass. We are only aware of one previous report in the English literature of the association of a rectovaginal fistula with this triad and to our knowledge the association has not been described in the radiological literature.

Female↗
PubMed1994

Characterization and quantification of a pharyngo-UES contractile reflex in cats.

We characterized and quantified a reflex from the pharyngeal mucosa to the upper esophageal sphincter (UES). Seventeen cats were decerebrated, and the pharynx was exposed by opening the cricothyroid ligament. UES motor activity was assessed by recording electromyographic (EMG) activity from the pharyngeal constrictors, i.e., the thyropharyngeus (TP) and cricopharyngeus (CP). The pharyngeal mucosa was stimulated by touch or pressure. Both stimuli activated contraction of the CP primarily when applied to the naso-, laryngo-, or hypopharynx, but pressure was more effective. The anteromedial portion of the hypopharynx was the most sensitive zone, but there was no strong stimulus-response relationship. The reflex response to a 1-s stimulus occurred at a delay of 0.46 +/- 0.06 s and lasted 4.5 +/- 0.5 s. This pharyngo-UES reflex was blocked by anesthesia of the mucosa or transection of the glossopharyngeal or pharyngoesophageal nerves but not the vagus nerves. In contrast, the esophago-UES contractile reflex was not blocked by anesthesia of the pharyngeal mucosa or transection of the glossopharyngeal nerves but was blocked by transection of either the vagus or pharyngoesophageal nerves. We concluded that the pharyngo-UES contractile reflex was activated by pharyngeal mucosal mechanoreceptors whose afferent limb was the glossopharyngeal nerve and whose efferent limb was the pharyngoesophageal branch of the vagus nerve.

Animals↗
PubMed1994

Expression of type 1 plasminogen activator inhibitor in chronic pulmonary thromboemboli.

BACKGROUND: Chronic thromboembolic pulmonary hypertension is the result of nonresolving pulmonary emboli that lead to chronic obstruction of the central pulmonary arteries. METHODS AND RESULTS: To determine if the failure to lyse pulmonary thromboemboli is caused by the local expression of the primary inhibitor of tissue-type plasminogen activator (type 1 plasminogen activator inhibitor, PAI-1), levels of PAI-1 antigen and mRNA were analyzed by immunohistochemistry and in situ hybridization in specimens harvested from a series of patients during pulmonary thromboendarterectomies. Red, fibrin-rich thrombi within the thromboendarterectomy specimens were lined with a single layer of endothelial cells exhibiting high levels of PAI-1 antigen. Quantitation of the in situ hybridization signal revealed that a significant increase in PAI-1 mRNA was present in the endothelial cells lining the fresh thrombi in comparison to the signal present in the endothelial cells from noninvolved areas of patients' pulmonary arteries (n = 16, P < .001). In contrast, tissue-type plasminogen activator antigen levels were low in all samples. Yellowish-white thrombi were composed of smooth muscle cells and endothelial cells in numerous vessels that stained prominently for PAI-1 antigen. Both types of cells within the highly organized tissues also exhibited elevated PAI-1 mRNA levels in comparison to patient pulmonary artery specimens that were free of thrombus (n = 16, P < .02). CONCLUSIONS: The prevalence of PAI-1 expression within pulmonary thromboemboli suggests that this inhibitory may play a role in the stabilization of vascular thrombi.

Adult↗
PubMed1994

Parallel analysis of tissue-type plasminogen activator and type 1 plasminogen activator inhibitor in plasma and endothelial cells derived from patients with chronic pulmonary thromboemboli.

BACKGROUND: Chronic thromboembolic pulmonary hypertension is the result of nonresolving pulmonary emboli that lead to chronic obstruction of the central pulmonary arteries. METHODS AND RESULTS: To determine if the failure to lyse pulmonary thromboemboli is caused by an abnormality in the endothelial cell (EC)-associated fibrinolytic system, conditions were established to culture ECs from patient main pulmonary arteries during surgical pulmonary thromboendarterectomies and to analyze the conditioned media for levels of tissue-type plasminogen activator (TPA) and type 1 plasminogen activator inhibitor (PAI-1). Our data indicate that the levels of TPA antigen and PAI-1 activity in media conditioned by primary ECs harvested from areas free of thrombus were not significantly different between patients with chronic thromboemboli and organ donors. In 13 consecutive patients, no correlation was obtained in either the TPA antigen or PAI-1 activity level in a patient's plasma and the respective levels in media conditioned by the patient's pulmonary ECs. Moreover, patient pulmonary arterial ECs were observed to increase the secretion of TPA and PAI-1 in response to thrombin in a fashion similar to donor pulmonary artery ECs. CONCLUSIONS: The data suggest that an inherent EC-mediated fibrinolytic imbalance is not a generalized phenomenon observed in pulmonary arteries of patients with chronic pulmonary thromboemboli.

Adult↗
PubMed1994

Suppression of thrombolysis in a canine model of pulmonary embolism.

BACKGROUND: The brisk fibrinolytic response of canines has impaired efforts to develop a canine model of chronic thromboembolic pulmonary hypertension. Difficulties in retaining chronic embolic residuals were partially overcome by administration of tranexamic acid (TXA) (Circulation. 1991;83:1272-1279.). In this study, we used type 1 plasminogen activator inhibitor (PAI-1), a major inhibitor of the endogenous fibrinolytic system, to determine its efficacy in the suppression of thrombolysis in canines. METHODS AND RESULTS: Thrombus was induced in the inferior vena cava of anesthetized mongrel dogs with thrombin and a special double-balloon catheter; 2 hours later, the thrombus was embolized. In one group of dogs, activated type 1 plasminogen activator inhibitor (PAI-1) (130 micrograms) was delivered directly into the forming thrombus; in another, TXA (110 mg/kg) was given intravenously before thrombus formation; in controls, thrombus was induced without inhibitors. Cross-linked fibrin degradation product (D-dimer) appeared in the blood of control animals within 1 hour of thrombus induction (176 +/- 62.5 versus 1.02 +/- 0.39 ng/mL baseline; mean +/- SEM), was maximal by 4 hours (413 +/- 110 ng/mL) and remained elevated at 24 hours (90.8 +/- 19.5 ng/mL). Compared with controls, PAI-1 and TXA suppressed D-dimer release by 80% and 85%, respectively, over the first 24 hours. One week later, animals were killed, and residual emboli were harvested. Perfusion scan defects persisted in all animals at this time, but there were no scan defect differences among groups. However, emboli recovered from animals receiving PAI-1 still harbored immunoreactive PAI-1 and were, on average, more than twofold greater in mass (393 +/- 56 mg) than emboli recovered from either controls (183 +/- 76 mg) or animals receiving TXA (180 +/- 80 mg). CONCLUSIONS: Intravenous TXA and intrathrombus PAI-1 effectively suppress thrombolysis for 24 hours in canines. Thromboemboli enriched with PAI-1 appear to resist lysis for longer periods of time (up to 1 week). These findings are consistent with the hypothesis that PAI-1 remains associated with the embolus, where it continues to inhibit lysis, whereas TXA eventually diffuses out of the embolus, allowing lysis to ensue.

Animals↗
PubMed1993

Pharyngeal, esophageal, and proximal gastric responses associated with vomiting.

The motor activities of the pharynx, esophagus, and proximal stomach associated with vomiting were characterized and quantified in 25 awake chronically instrumented dogs. These motor events were correlated temporally with motor responses of the gastrointestinal and respiratory tracts. Vomiting was stimulated by apomorphine or UK-14304, and motor activities of striated and smooth muscles were recorded by electromyography and strain-gauge transducers, respectively. We found responses that began 1) before retching: increased swallow frequency, relaxation of the lower esophageal sphincter (LES) and proximal stomach, and tonic contraction of the cricopharyngeus and cervical esophagus; 2) during retching: rhythmic relaxation and contraction of the pharynx and cervical esophagus 180 degrees out of phase with retching; and 3) during vomitus expulsion: relaxation of the pharynx and cervical esophagus but strong contraction of the geniohyoideus and a retrograde contraction of the cervical esophagus and pharynx. The increased pharyngoesophageal tone occurred in an all-or-none fashion independent of vomiting or the gastrointestinal correlates of vomiting. Cervical vagal blockade increased swallow frequency but did not alter the other pharyngoesophageal responses associated with vomiting. We concluded that the motor events of the pharynx and esophagus play a significant role in gastrooral evacuation during vomiting and that these motor events (except LES relaxation) are not controlled by subnodose vagal pathways.

Adrenergic alpha-Agonists↗
PubMed1993

Factors contributing to increased vascular fibrinolytic activity in mongrel dogs.

BACKGROUND: Numerous investigators have observed that pulmonary emboli are rapidly lysed in a canine model system. This study was undertaken to delineate the unique mechanism that accounts for the rapid dissolution of pulmonary emboli in mongrel dogs. METHODS AND RESULTS: Canine plasminogen activator (PA) activity (2.6 +/- 1.1 IU/mL acidified platelet-poor plasma [PPP], < 0.3 IU/mL acidified whole blood serum [WBS], mean +/- SD; n = 6) and PA inhibitor activity (6.1 +/- 2.6 U/mL PPP, 35.4 +/- 7.8 U/mL WBS; n = 6) were determined in standard plasminogen-based chromogenic assays. Analysis of canine PPP, WBS, platelet lysates, and primary canine endothelial cell (EC) cultures by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fibrin autography revealed a plasminogen-dependent lytic zone at 45-kd relative molecular mass that was shown to be related to urokinase-type PA (u-PA) by its selective inhibition through amiloride. Analysis of canine platelets on standard 125I fibrin plate assays revealed a net fibrinolytic activity. In a clot lysis assay system, canine platelets were able to stimulate fibrinolysis when layered on the outside of fibrin clots containing autologous PPP. Moreover, net fibrinolytic activity of primary canine pulmonary artery endothelial cells was higher than the activities expressed by canine aortic or carotid artery endothelial cells. CONCLUSIONS: Rapid lysis of pulmonary emboli in mongrel dogs appears to be a result of 1) the high u-PA activity in canine PPP and 2) the predominant association of u-PA activity with canine platelets and canine pulmonary artery endothelial cells.

Animals↗
PubMed1993

Gallbladder function after endoscopic sphincterotomy--a dynamic ultrasound assessment.

There is controversy regarding the function of the gallbladder following endoscopic sphincterotomy (ES) for the treatment of gallstones. Using ultrasound to assess gallbladder volume, we evaluated gallbladder contractility in 34 patients (18 male, 16 female), mean age 73 years, who had ES and common bile duct (CBD) clearance a mean of 18 months earlier. In 16 patients gallbladder function could not be measured, either because the fasting gallbladder was small and contracted or because it contained gas. The remaining 18 patients (53%) had "normal" gallbladder contraction with a mean initial fasting volume of 30.3 ml and mean post fatty meal volume of 13.8 ml. 14 of these 18 patients had a repeat fasting volume which showed refilling in all except one. Those with a functioning gallbladder had had significantly smaller stones extracted from the CBD at the time of ES. A smaller or incomplete sphincterotomy may have been performed in these patients, therefore allowing some residual sphincter of Oddi function.

Adult↗
PubMed1992

Presence of active and latent type 1 plasminogen activator inhibitor associated with porcine platelets.

Data from a number of laboratories indicate that human platelets contain type I plasminogen activator inhibitor (PAI-1) primarily in a latent form; however, one report (Biochemistry 28:5773, 1989) indicated that it is predominantly the active form of PAI-1 that is present in and can be purified from an ammonium sulfate precipitate of porcine platelets. To clarify this situation, we investigated and compared the status of PAI-1 in porcine and human platelets. Immunologic analysis of the ability of PAI-1 to form complexes with immobilized t-PA indicated that porcine and human platelets contained 3.7 +/- 0.4 and 1.7 +/- 0.3 U of PAI activity per 10(8) platelets (n = 6; +/- SD), respectively; sodium dodecyl sulfate (SDS)-activation of the lysates increased PAI-1 activity to 10.8 +/- 3.0 and 3.8 +/- 0.5 U per 10(8) platelets. Platelet lysates were also treated with an excess of soluble t-PA, which formed complexes with active PAI-1, whereas the latent form was detected by SDS-polyacrylamide gel electrophoresis and reverse fibrin autography. Furthermore, immobilized t-PA was able to deplete active PAI-1 from the platelet extracts, and the latent form remaining in the absorbed extract could be quantitated by activation with 4 mol/L guanidine. To investigate the differences between our observations and the published data, porcine platelets were extracted, and PAI-1 was partially purified as described in the literature. For quantitative analysis, porcine platelet PAI-1 was also purified to homogeneity using standard chromatographic procedures optimized in our laboratory for endothelial PAI-1, and the purified protein was used to develop an enzyme-linked immunoabsorbent assay for porcine PAI-1 antigen. Our results indicate that: (1) latent PAI-1 in concentrated ammonium sulfate precipitates of porcine platelet lysates cannot be detected unless the precipitates are diluted before treatment with denaturants; and (2) active and latent porcine platelet PAI-1 can be separated by gel filtration over molecular sieving columns. In summary, this report documents that PAI-1 in porcine platelets is present in both an active and a latent form.

Animals↗
PubMed1992

Endogenous fibrinolytic system in chronic large-vessel thromboembolic pulmonary hypertension.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a disorder characterized by pulmonary arterial hypertension as a consequence of organized thrombotic material in the central pulmonary arteries. Incomplete resolution of acute pulmonary emboli is believed to be pathogenically important; however, the mechanism for poor thrombus dissolution remains to be explained. We undertook this study to assess the major determinants of plasma fibrinolysis in patients with CTEPH (n = 32). METHODS AND RESULTS: Immunological and functional levels of tissue-type plasminogen activator (t-PA) and type 1 plasminogen activator inhibitor (PAI-1) were quantified in platelet-poor plasma (PPP) from patients with CTEPH as well as age-matched controls. Although basal PPP t-PA antigen levels (CTEPH mean, 29.5 ng/ml; control mean, 2.7 ng/ml) and PAI-1 antigen levels (CTEPH mean, 55.8 ng/ml; control mean, 21.0 ng/ml) were higher in the CTEPH group, no between-group differences were detected in the enzymatic activities of these two molecules. The CTEPH group demonstrated a greater rise in t-PA antigen (CTEPH mean rise, 53.0 ng/ml; control mean rise, 5.6 ng/ml) and PA activity (CTEPH mean rise, 10.5 IU/ml; control mean rise, 1.2 IU/ml) than controls in response to an experimentally induced venous occlusion. Immunoprecipitation and fibrin autography of PPP from two patients with markedly elevated basal t-PA antigen levels demonstrate that the t-PA antigen was present in PPP primarily in complex with PAI-1. CONCLUSIONS: Although abnormalities of the fibrinolytic system were detected, neither a high resting plasma PAI-1 activity nor a blunted response of t-PA to venous occlusion can be invoked as an etiology for CTEPH:

Adolescent↗
PubMed1992

The role of adrenergic receptors in the initiation of vomiting and its gastrointestinal motor correlates.

We investigated the role of adrenergic receptors in the mechanisms of initiation of vomiting and its gastrointestinal (GI) motor correlates. The effects of clonidine, UK-14304, St-91, naphazoline, phenylephrine and isoproterenol were examined for their ability to initiate vomiting and its GI motor correlates. Only the alpha-2 adrenoceptor agonists UK-14304, clonidine, St-91 and naphazoline activated vomiting and its GI motor correlates. Tolerance of vomiting, but not its GI motor correlates, readily developed to all alpha-2 adrenergic receptor agonists but St-91. The responses to UK-14304 or clonidine were blocked by idazoxan, yohimbine, clonidine tolerance or high doses of phenoxybenzamine, but not by propranolol or prazosin. The responses to UK-14304 or clonidine were also blocked by fentanyl, 1-(1-naphthyl) piperazine, methysergide, SCH 22390 or scopolamine, but not by haloperidol, sulpiride, domperidone or naloxone. Adrenoceptor antagonists, clonidine tolerance or sympathetic blockade did not block vomiting or its GI motor correlates activated by apomorphine, CuSO4 or cholecystokinin-octapeptide. We concluded that alpha-2 adrenergic receptors of the chemoreceptive trigger zone can initiate vomiting and its GI motor correlates, but these receptors do not mediate vomiting induced by another chemoreceptive trigger zone stimulant, apomorphine, or stimulation of the GI tract using CuSO4. However, 5-hydroxytryptamine-2 serotonergic, muscarinic cholinergic and opiate receptors within the central nervous system participate in controlling emesis activated by alpha-2 adrenergic agonists. Peripheral adrenergic receptors do not mediate the GI motor correlates of vomiting.

Adrenergic alpha-Agonists↗