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Biomedical subjects

A Forman

Publications and source records attributed to A Forman.

At least 73 records · Page 4Linked to original sources

Effects of vasodilators on isolated human uteroplacental arteries.

The effects of the vasodilator drugs hydralazine, labetalol, prazosin, and nitrendipine were studied on responses to K+ (124 mmol/L), noradrenaline, vasopressin, and angiotensin II in small human maternal intramyometrial arteries and on responses to K+, prostaglandin (PG) F2 alpha, and angiotensin II in fetal stem villous arteries. The vessels were dissected from biopsy specimens obtained during term cesareans and mounted in organ baths. Hydralazine failed to inhibit responses to any of the agonists tested in the fetal and maternal arteries. Labetalol and prazosin decreased responses to noradrenaline but did not affect contractions induced by the other agonists in maternal arteries. In fetal arteries, which did not respond to noradrenaline, no effects of labetalol and prazosin were found. Nitrendipine inhibited responses to all the agonists tested in maternal arteries. In fetal preparations, the drug decreased responses to K+ and PGF2 alpha but did not affect contractions induced by angiotensin II. Vasodilator drugs applied for treatment of pregnancy-induced hypertension show differential effects on human maternal and fetal uteroplacental arteries, depending on their mode of action and the agonists responsible for the contractile activation in these vessels.

Angiotensin II↗

In vitro analysis of muscular contractile ability and passive biomechanical properties of uterine cervical samples from nonpregnant women.

We assessed the maximal muscular contractile ability, the passive biomechanical properties, and the hydroxyproline concentration in uterine cervical tissue samples from 28 nonpregnant women. Circular cervical tissue strips were mounted in organ baths and isometric tension was recorded. The mean (+/- SEM) maximal mechanical responses induced at the length of optimal mechanical performance by K+ (124 mmol/L) equaled 0.16 +/- 0.05 mN/mm2 in the distal cervix and 0.84 +/- 0.47 mN/mm2 in the proximal cervix, as compared with 4.85 +/- 1.0 mN/mm2 in tissues from the isthmus and 6.50 +/- 1.4 mN/mm2 in the fundus. The passive biomechanical properties were analyzed by a materials-testing machine. No significant differences were found between tissues from the distal and proximal cervix or between circular and longitudinal preparations. Tensile strength equaled 1.5-1.7 N/mm2, ie, 10(4)-fold the maximal muscular contractile ability. The extensibility was 0.63-0.76 and the stress-relaxation was 41-48%. The hydroxyproline concentration was 22.5 micrograms/mg wet weight in the distal cervix and 21.6 micrograms/mg in the proximal cervix, as compared with 16.6 micrograms/mg in the isthmus and 12.6 micrograms/mg in the fundus. A method for analysis of the biomechanical properties of the human cervix was designed, and from the measurements obtained it may be concluded that the passive biomechanical strength of the cervix markedly exceeds the active muscular contractile ability. This may be explained by a high collagen concentration and a low content of smooth muscle in the cervical tissue.

Adult↗

[Surgical pulmonary embolectomy and thrombolytic therapy].

Acute, massive pulmonary embolism is life-threatening and must be treated immediately. Since the early 1970's when thrombolytic therapy was shown to hasten resolution of pulmonary emboli, there has been a debate in the literature as to new indications for surgical pulmonary embolectomy. Some authors believed that there are no longer any indications for embolectomy, while others justify surgery for certain indications. Although the debate is still on, this operation is very rarely performed today. We present a patient who developed massive pulmonary embolism, with continuing extreme hemodynamic and respiratory disturbances despite full thrombolytic treatment. Embolectomy was successfully performed.

Female↗

Effects of magnesium and isradipine on contractile activation induced by the thromboxane A2 analog U46619 in human uteroplacental arteries in term pregnancy.

The effects of Mg++ and the dihydropyridine calcium channel blocker isradipine on contractions induced by the thromboxane A2 mimetic U46619 were studied in isolated human uteroplacental arteries. In all preparations investigated U46619 10(-10) to 10(-6) mol/L induced concentration-related contractile responses. In maternal vessels U46619 produced a biphasic concentration-response curve, whereas the compound in fetal vessels produced a sigmoid concentration-response curve parallel to that of prostaglandin F2 alpha. Mg++ (1.0 to 6.0 mmol/L) and isradipine (10(-10) to 10(-5) mol/L) both relaxed U46619-induced contractions by up to about 40%. In preparations precontracted by U46619 and exposed to isradipine 10(-6) mol/L, addition of Mg++ 6.0 mmol/L consistently produced a further small relaxation. Removal of the endothelium or pretreatment with indomethacin 10(-6) mol/L or digoxin 10(-6) mol/L did not influence the inhibition produced by Mg++ or isradipine. In vessels pretreated in Ca(++)-free medium Mg++ 6.0 mmol/L depressed and isradipine abolished responses to Ca++ (0.01 to 4.0 mmol/L) after depolarization with K+ 124 mmol/L. In maternal and fetal arteries stimulated with U46619, however, Mg++ 6.0 mmol/L and isradipine 10(-6) mol/L produced a similar, partial inhibition of responses to Ca++ (0.01 to 4.0 mmol/L). Mg++ seems to inhibit transmembrane Ca++ influx, although less efficiently than the dihydropyridine calcium antagonist isradipine. In addition, Mg++ may interfere with Ca++ at intracellular binding sites. Provided that preeclampsia comprises enhanced vascular actions of thromboxane A2, the present results support the established use of Mg++ in the treatment of this condition and suggest that calcium antagonists are of potential benefit.

Antihypertensive Agents↗

Regional differences in vascular responses in the human uterus.

Tissue specimens from the fundus, isthmus and distal cervix were obtained from 14 women at hysterectomy at various phases of the menstrual cycle. Ring preparations of small intramyometrial and intracervical arteries were dissected and mounted in organ baths; isometric tension was recorded and responses to contractile agents were studied. The amplitude of responses to K+ (124 mmol/l) of the vessel preparations ranked fundus greater than or equal to isthmus greater than cervix. While similar pD2 values for noradrenaline (NA) were found, the Emax values ranked cervix greater than or equal to isthmus greater than or equal to fundus (cervix greater than fundus). The pD2 values for arginine-vasopressin (AVP) showed minor differences, while the Emax values for this peptide ranked fundus greater than or equal to isthmus greater than or equal to cervix (fundus greater than cervix). Arteries from the fundus and isthmus displayed weak, inconsistent contractile responses to prostaglandin F2 alpha, but more pronounced contractions were induced by this prostanoid in arterial preparations from the distal cervix. The results suggest regional differences in vascular mechanical responses to endogenous vasoactive agents in the human uterus.

Adult↗

The actions of some beta-receptor agonists and xanthines on isolated muscle strips from the human oesophago-gastric junction.

Isolated preparations from the circular muscle layer of the human oesophago-gastric junction were mounted in organ baths and isometric tension recorded. During an equilibration period, active resting tension developed suggesting that the preparations were representing the lower oesophageal sphincter. Active tension was abolished by exposing the preparations to Ca(++)-free medium. The two xanthines theophylline and enprofylline almost equipotently relaxed the preparations in a concentration-dependent manner (10(-7)-10(-3) M). Within therapeutic concentrations, theophylline inhibited active resting tension by 30-60%, while enprofylline lowered tension by less than 20%. Inhibitory actions of adenosine were demonstrated, and this suggests that adenosine antagonism is not the mechanism of action for xanthines in the oesophagus. Non-selective beta-receptor stimulation with isoprenaline inhibited active tension by 70% (10(-7) M), while beta 2-receptor stimulation with terbutaline inhibited tension by 47% (10(-5) M). Dobutamine, believed to preferentially stimulate beta 1-receptors, inhibited active tension in a concentration-dependent manner (10(-7)-10(-4) M). Metoprolol (10(-6) M), a selective beta 1-receptor antagonist, shifted the concentration-response curve for isoprenaline to the right, but left the maximal response unchanged. It is concluded that xanthines and beta-receptor agonists have inhibitory actions on circular muscle from the human oesophagogastric junction. The experimental data suggest the presence of beta 1- as well as beta 2-receptors, both mediating inhibition of active resting tension.

Adenosine↗

Effects of magnesium on isolated human fetal and maternal uteroplacental vessels.

The effects of Mg2+ were studied in human umbilical arteries, stem villous arteries and maternal intramyometrial arteries. The vessels were dissected and mounted in organ baths, and isometric tension was recorded. In all fetal preparations investigated, Mg2+ (0.5-6.0 mM) in a concentration-related way decreased pD2 values for prostaglandin F2 alpha responses. The maximum response to prostaglandin F2 alpha was depressed in umbilical arteries, but remained unaffected in stem villous artery preparations. In stem villous arteries pretreated in Ca2(+)-free medium, increasing concentrations of Mg2+ markedly depressed the response to Ca2+ after stimulation with K+ or prostaglandin F2 alpha, suggesting that Mg2+ inhibited transmembrane calcium influx and interfered with intracellular calcium effects. In both stem villous and intramyometrial arteries, increasing concentrations of Mg2+ increased EC50 values for responses to K+, whereas Emax values were unaffected. Mg2+ produced relaxation of agonist-induced contractions by up to 60% in stem villous arteries and up to 40% in intramyometrial artery preparations. The relaxant effect of Mg2+ did not seem to be mediated through the endothelium or through changes in the synthesis of prostanoids, since endothelial disruption and treatment with indomethacin left the responses to Mg2+ unaffected. Relaxation of vessels important for resistance regulation in the human uteroplacental vascular bed may be of benefit when uteroplacental blood flow is impaired, and the present results support the established use of magnesium sulphate in the treatment of pre-eclampsia.

Arteries↗

Effects of postganglionic nerve stimulation in oesophageal achalasia: an in vitro study.

The functional postganglionic innervation of isolated smooth muscle strips from the oesophagogastric junction was examined in specimens taken from six achalasia patients and seven controls. Muscle strips representing either the longitudinal or the circular layer were prepared and mounted in organ baths and isometric tension was recorded. Electrical field stimulation, selectively exciting nerves, was applied. Strips from the circular layer from controls relaxed during field stimulation, an effect that was the result of stimulation of noncholinergic, non-adrenergic, inhibitory nerves. Circular muscle strips from achalasia patients contracted during field stimulation, an effect that was caused by muscarinic receptor activation. In one patient, atropine reversed the contraction to a relaxation. Longitudinal muscle strips contracted in response to stimulation in both controls and achalasia patients. This response was abolished by atropine. In conclusion the function of postganglionic inhibitory nerve fibres to the circular layer of the oesophagogastric junction is severely impaired in achalasia, while there is a conspicuous, functional cholinergic innervation.

Adolescent↗

Mechanical properties of isolated human esophageal smooth muscle.

Isolated smooth muscle strips from the human esophagus representing both the longitudinal and circular layers of the esophagogastric junction and the esophageal body were prepared. The strips were mounted in organ baths, and resting length was defined. By repeatedly increasing the length of the strips with 20% of resting length and recording values of resting and active tensions, length-tension relations for each muscle type were constructed. Only circular strips from the esophagogastric junction developed active, resting tension, disclosed by replacing the normal Ca2(+)-containing Krebs solution with Ca2(+)-free medium. Carbachol (10(-6) M) was used for submaximal activation of the contractile apparatus. At lengths between 180 and 260% of resting length, all strips reached optimum length (LO) where further elongation gave no further increase in active tension development. Repeated stimulations with carbachol was possible at a length of 200% of LO without affecting reproducibility. Determination of different collagen components revealed no differences between muscle types.

Calcium↗

Effects of transmural field stimulation in isolated muscle strips from human esophagus.

Smooth muscle strips representing longitudinal and circular muscle layers of the esophagogastric junction (EGJ) and esophageal body (EB) of the human esophagus were prepared. The strips were mounted in organ baths and isometric tension was recorded. Square wave stimulation was applied through platinum electrodes. Only responses abolished by tetrodotoxin (TTX) were considered neurogenic. Strips taken from longitudinal muscle layers of the EB and EGJ contracted during field stimulation. The responses evoked were abolished by atropine, and optimal frequency of stimulation was 40 Hz. In strips taken from the circular muscle layer of the EB, a contraction occurred after cessation of the stimulus. Atropine inhibited 90% of this response; the optimal stimulation frequency was 40 Hz. When a tone was induced in strips from this layer, a TTX-sensitive relaxation was seen during field stimulation. During stimulation of strips from the EGJ circular muscle layer, which was the only preparation developing spontaneous active tone, a relaxation was seen. A small contraction followed after termination of the stimulus. The relaxation, which was nonadrenergic, noncholinergic, reached maximum at 10 Hz. Atropine inhibited 40% of the contraction. The results suggest that in the longitudinal muscle layer of the human lower esophagus field stimulation causes postganglionic nerves to release transmitter(s) acting on muscarinic receptors. The responses of circular muscle layers seem to be mediated through release of at least two transmitters.

Atropine↗

Peripheral neuropathy in cancer patients: clinical types, etiology, and presentation. Part 2.

Peripheral neuropathies in cancer patients may be caused by compression due to tumor invasion, by radiation injury, or by chemotherapy. Plexopathy may also be caused by non-oncologic conditions such as diabetes mellitus, trauma, and aneurysms, thus adding to the diagnostic difficulty. The most common iatrogenic neuropathies are those caused by vincristine and cisplatin. Vincristine, while causing the least myelosuppression of all the vinca alkaloids, is the most neurotoxic. Cisplatin neuropathy often limits the use of this agent, even in patients whose tumors are responsive to it. Part 1 of this article appeared in January.

Cisplatin↗

Peripheral neuropathy in cancer patients: incidence, features, and pathophysiology.

Peripheral nerve disorders are a common problem in cancer patients. Clinical severity may range from mild acroparesthesia to ataxia so severe it makes patients bed-bound to muscle wasting so extensive it compromises respiratory function. Treatment-related neuropathies add to the patient's suffering and may even be a dose-limiting factor. While symptoms of neuropathic disease may be diverse, certain general patterns can be recognized. The author discusses clinical features and the latest methods of evaluation, including single fiber electromyography.

Humans↗

Alpha-adrenoceptor function in isolated penile circumflex veins from potent and impotent men.

Alpha-adrenoceptor functions were investigated in isolated human penile circumflex veins from six potent and four impotent men. Contractions elicited by noradrenaline and phenylephrine were inhibited by prazosin, yohimbine, phentolamine and papaverine. No differences were found between vessels from potent and impotent men. The results suggest that alpha-adrenoceptors in penile circumflex veins are of both alpha 1- and alpha 2-type, and that no changes in alpha-adrenoceptor function occur in impotence associated with an increased penile venous outflow.

Adult↗

Effect of endogenous vasoconstrictors on maternal intramyometrial and fetal stem villous arteries in pre-eclampsia.

The contractile responses to various endogenous vasoactive agents were investigated in isolated human uteroplacental arteries from normotensive (NT) patients and patients with pre-eclampsia (PE) undergoing caesarian section. Tissue samples were obtained from the uterine incision and from macroscopically normal cotyledons. Vascular ring preparations of intramyometrial and stem villous arteries (length 1.0-1.3 mm, outer diameter 400-600 microns) were dissected and mounted in organ baths and isometric tension was recorded. Concentration-response relationships for vasopressin (VP), oxytocin (OX), angiotensin II (Ang II), noradrenaline (NA), 5-hydroxytryptamine (5-HT), prostaglandin F2 alpha (PGF2 alpha) and prostaglandin E2 (PGE2) were assessed. For each compound, the mean maximum contractile effect (Emax) and the drug concentration producing half-maximal response (EC50) were determined. In intramyometrial arteries from NT and PE patients, VP, Ang II, NA, 5-HT and PGF2 alpha induced contraction while OX and PGE2 produced weak or no responses. Preparations from PE patients showed higher Emax values, while no differences in EC50 were found between the two groups. In fetal stem villous arteries, Ang II, 5-HT, PGF2 alpha and PGE2 induced contractions, while VP, NA and OX produced weak responses. No differences in Emax or EC50 values were found between the fetal vessels of PE and NT patients. No qualitative differences were demonstrated in response to the agents tested between the vessels (fetal and maternal) from NT women at term and PE patients. However, the results may reflect quantitative differences, suggesting increased contractility of maternal uteroplacental arteries from women with PE.

Amines↗

Neuropeptide Y in the human female genital tract: localization and biological action.

The distribution, localization, and smooth muscle effects of neuropeptide Y (NPY) were studied in the human female genital tract. High concentrations of NPY immunoreactivity were demonstrated in the uterine artery, the ovary, the fallopian tube, cervix, and the vagina. The NPY immunoreactivity was confined to nerve fibers. The highest density of nerve fibers was observed in relation to blood vessels, although some NPY-immunoreactive nerves were also seen close to nonvascular smooth muscle. The NPY-immunoreactive material throughout the genital tract was identical to synthetic amidated human NPY with regard to size, hydrophobicity, and charge as evaluated by gel filtration, high-performance liquid chromatography, and isoelectric focusing. NPY (10(-10) to 10(-6) M) exerted a direct vasoconstrictory effect on small arteries dissected from the cervix and an additive effect of NPY and norepinephrine responses was observed. Exogenous NPY did not have a direct effect on nonvascular smooth muscle specimens from the fallopian tube or the myometrium. The close relation between NPY-immunoreactive nerves and blood vessels, the presence of NPY-immunoreactive material identical to amidated synthetic human NPY, and the vasoconstrictory effects of NPY indicate that NPY is involved in the regulation of the blood flow in the human female genital tract.

Antibodies↗

Effects of indomethacin on human placental stem villous arteries.

Ring preparations of human stem villous arteries were prepared by microtechnique from placentae born after normal-term vaginal delivery. Isometric tension was recorded in organ baths. Indomethacin 10(-8)-10(-5) M left responses to K+ depolarization and contractions produced by prostaglandin F2 alpha (PGF2 alpha) unaffected, while indomethacin 10(-4) M slightly decreased K+-induced contractions and inhibited responses to PGF2 alpha. In contrast, nitrendipine 10(-9)-10(-6) M markedly decreased responses to K+ while nitrendipine 10(-8)-10(-6) M inhibited PGF2 alpha-induced responses. Relaxant responses to vasointestinal polypeptide 10(-8)-10(-7)M were left unaffected by pretreatment with indomethacin 5 X 10(-5) M. Indomethacin affects contractile activation in human stem villous arteries only in high concentrations, and the effects differ in profile from those of calcium entry blockers like nitrendipine. The results do not leave evidence for increased placental arterial tone during indomethacin treatment in pregnancy.

Arteries↗