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Biomedical subjects

A Forman

Publications and source records attributed to A Forman.

At least 55 records · Page 3Linked to original sources

Mechanical properties of isolated smooth muscle from human rectum and internal anal sphincter.

The passive and active length-tension relations of the circular smooth muscle layer of the human distal rectum and the proximal and distal internal anal sphincter were investigated. Muscle strips were prepared and mounted in organ baths for recording of isometric tension. Resting lengths (LR) were measured, and the preparations were elongated stepwise. At each length, the corresponding values for passive tension, spontaneous active resting tension, and the submaximal active tension were recorded. Elongations of 200-380% of LR were possible before a sharp increase in passive tension occurred. None of the mean tension values measured at length for maximal active tension (LO) differed significantly among the three muscle types. All strips developed active resting tension. This tension was myogenic and contributed 10 +/- 3, 23 +/- 6, and 27 +/- 6% to the total active performance of rectal and proximal and distal sphincter preparations, respectively. Collagen constituted approximately 50% of smooth muscle biopsies, with highest contents in distal internal anal sphincter. This study provides an acceptable method for assessing the optimal experimental length by stretching the strips in an inactive state to 200% of LR, followed by individual adjustment of the passive tension to 5 mN/mm2 measured at 200% of LR.

Adult↗

Acute tissue effects during transcervical endometrial resection.

The acute tissue effects of transcervical endometrial resection (TCRE) with a standard Iglesias resectoscope using glycine 1.5% for irrigation were studied in 8 women prior to hysterectomy. Combinations of 80 or 120 W cutting current with blend 1 or 2 were applied for endometrial resection, preceded by cornual endometrial coagulation with the roller ball electrode with a coagulation effect of 40 or 60 W. The temperature was measured at the uterine vessels, ovarian ligaments and serosal surface. The increase in temperature at the serosal surface was 2.0 degrees C during cornual coagulation and 0.3 degrees C during endometrial resection, independent of the current effect applied. The maximum depth of tissue damage was 1.7 mm. No change in temperature was found at the uterine vessels or ovarian ligaments. The tissue destruction and the increase in temperature of the uterine surface are minimal, and TCRE offers excellent histological material. Careful coagulation/resection in the cornual and isthmus regions is recommended.

Adult↗

Effects of vasoactive intestinal peptide, peptide histidine methionine, and neuropeptide Y on intracavernous pressure in the rabbit.

In anesthesized white rabbits blood was extracorporeally circulated from the left carotid artery into the penile corporeal bodies with a constant flow rate. Corpus cavernosum pressure (CCP) responses to intracavernous injections of drugs were recorded in animals with aortic nonocclusion and aortic occlusion, respectively. Vasoactive intestinal polypeptide (VIP, 1 microgram, 5 micrograms, and 20 micrograms), dissolved in 0.5 mL volumes, induced no significant increases in CCP compared with equivalent volumes of solvent, but the peptide increased the time interval until return of CCP to steady state level. Peptide histidine methionine induced a significant increase in the maximal CCP obtained in nonocclusion, and the time interval until return of CCP to steady state levels was increased in both aortic nonocclusion and occlusion. Neuropeptide Y produced an increase in the maximal CCP in animals with aortic occlusion, and a minor increase in the time interval until return of CCP values to steady state levels in both aortic nonocclusion and occlusion. Thus, all the peptides tested were capable of influencing the smooth muscle tissues involved in penile outflow regulation.

Animals↗

Electrically-induced, nerve-mediated relaxation of rabbit urethra involves nitric oxide.

Isolated smooth muscle preparations from the rabbit urethra precontracted with noradrenaline (10(-5) M), endothelin (10(-7) M), or arginine vasopressin (10(-7) M) responded to electrical field stimulation by frequency-dependent non-adrenergic, non-cholinergic relaxations, which could be blocked by tetrodotoxin (10(-6) M). Relaxation was more pronounced in preparations precontracted by endothelin than by noradrenaline or arginine vasopressin. The electrically induced relaxations were reduced in a concentration-dependent manner by pretreatment for 30 minutes with NG-nitro-L-arginine (10(-6) to 10(-4) M) and NG-monomethyl-L-arginine (10(-5) to 10(-4) M). At the highest concentration of NG-nitro-L-arginine used (10(-4) M), relaxation was abolished and/or changed into a contraction. The effect of NG-nitro-L-arginine was reversible. NG-nitro-D-arginine had no effect. Pretreatment for 30 minutes with L-arginine (10(-3) M) slightly, but significantly, enhanced the maximum relaxation to field stimulation in noradrenaline-precontracted preparations. L-arginine pretreatment also prevented the effects of low, but not high, concentrations of NG-nitro-L-arginine. In contrast, D-arginine had no effect. Electrically induced relaxations were not significantly affected by methylene blue (10(-5) M) or superoxide dismutase (20 U/ml). Addition of nitric oxide (present in acidified solution of NaNO2) caused transient and concentration-dependent relaxations in preparations precontracted by noradrenaline. At the maximum concentration used (10(-3) M), the relaxant response averaged 67% of the tension induced by noradrenaline. Nitric-oxide-induced relaxations were not affected by NG-nitro-L-arginine or L-arginine, but were significantly inhibited by methylene blue. In preliminary experiments, effects similar to those found in rabbit urethra were also observed in isolated urethral preparations obtained from three patients. It is suggested that in the urethra, nitric oxide is involved in the mediation of relaxation evoked by electrical stimulation of nerves.

Animals↗

Effects of thiopentone and chlormethiazole on human myometrial arteries from term pregnant women.

We have investigated the effects of thiopentone and chlormethiazole on maternal intramyometrial arteries dissected from myometrial biopsies taken during Caesarean section at term. Ring preparations were mounted in organ baths and isometric tension was recorded. Thiopentone 10(-4)-10(-3) mol litre-1 inhibited responses to K+ depolarization, noradrenaline and vasopressin. Chlormethiazole 3 x 10(-5)-3 x 10(-3) mol litre-1 inhibited responses to noradrenaline, while a concentration of 3 x 10(-3) mol litre-1 was required to attenuate responses to vasopressin and K+ depolarization. Neither of the two agents affected relaxant responses to prostacyclin. The results did not yield evidence that clinical use of thiopentone and chlormethiazole should impair uteroplacental vascular perfusion by a direct effect.

Arginine Vasopressin↗

Effects of prostanoids and indomethacin on isolated smooth muscle from the human lower oesophagus.

Smooth muscle strips representing the longitudinal and the circular muscle layers of the oesophageal body and the oesophagogastric junction of the human oesophagus were mounted in organ baths and isometric tension recorded. Transmural field stimulation was applied to strips from both layers of the oesophageal body and to strips from the longitudinal muscle layer of the oesophagogastric junction. This resulted in contractions after cessation of the stimulus train in circular muscle, and in contractions during stimulation in longitudinal muscle preparations. Indomethacin lowered active tension in strips from the circular muscle layer of the oesophagogastric junction, and decreased responses to transmural field stimulation in all strips from the longitudinal muscle layer. The response to transmural field stimulation was increased in strips from the circular muscle layer of the oesophageal body, suggesting an inhibitory function of endogenous prostanoids in this muscle layer. Prostaglandin (PG) F2 alpha and the thromboxane A2 mimic U-46619 increased the responses to transmural field stimulation in all muscle types and the active tension in circular muscle from the oesophagogastric junction. PGE1 and PGE2 increased the responses to transmural field stimulation strips from the longitudinal muscle layer. In circular muscle strips from the oesophageal body responses to transmural field stimulation were inhibited. PGE1 decreased active tension in circular muscle strips from the oesophagogastric junction, whereas PGE2 produced inconsistent effects. These results suggest a role of prostanoids in the regulation of neuromuscular function in the human lower oesophagus. Moreover, exogenous prostaglandins may modulate oesophageal motor function.

Adult↗

Mechanical effects of some prostanoids on isolated human oesophageal submucosal veins.

The effects of prostaglandins E1, E2, F2 alpha, prostacyclin, and the thromboxane A2-mimic U46619 were investigated on isolated human oesophageal submucosal veins from the oesophageal body and the oesophagogastric junction. U46619 most potently, but also PGF2 alpha produced venocontraction without differences between preparations from the oesophageal body and the oesophagogastric junction. PGE1 and prostacyclin caused relaxation of vessels precontracted with U46619 (10(-9) M). PGE2 induced either contraction or relaxation, but biphasic effects in the same vessel segment were not seen. Indomethacin 10(-6) M inhibited the contractile responses to both noradrenaline and K+ (124 mM), suggesting that the agonists induced synthesis or release of vasoconstrictor prostanoids. Prostanoids exert potent mechanical effects in submucosal oesophageal veins and may be of physiological importance.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Effects of the thromboxane-receptor antagonists AH 23848 and BM 13.177 on human uteroplacental arteries.

OBJECTIVE: We studied the effects of the thromboxane (Tx)A2-receptor antagonists AH 23848 and BM 13.177 in small isolated human uteroplacental arteries. METHODS: Fetal stem villous arteries and maternal intramyometrial arteries were dissected from placental specimens and from myometrial biopsies obtained at cesarean or from nonpregnant women after hysterectomy. Vascular ring preparations were prepared and mounted in organ baths, and isometric tension was recorded. RESULTS: AH 23848 produced competitive, concentration-dependent inhibition of responses to the TxA2-mimic U46619 in all vessel types tested. Mean (+/- standard error of the mean) pA2 values (the negative logarithm of the concentration of antagonist needed to double the half maximum response [EC50] value for U46619) were 8.69 +/- 0.16 in the stem villous arteries, 9.58 +/- 0.33 in intramyometrial arteries from term pregnant women, and 9.25 +/- 0.47 in intramyometrial arteries from nonpregnant women. In stem villous arteries, the pA2 value for BM 13.177 was 6.15 +/- 0.13, whereas these values in intramyometrial arteries could not be assessed. However, the concentrations needed to produce inhibition of U46619-induced contractions were considerably higher for BM 13.177 than for AH 23848. Both drugs inhibited responses to prostaglandin (PG)F2 alpha and PGE2 in stem villous arteries, while leaving responses to vasopressin in intramyometrial arteries unaffected. No differences in the effects of the two antagonists were found between intramyometrial arteries from nonpregnant and term pregnant women. CONCLUSIONS: Our results suggest that TxA2-receptor antagonists effectively inhibit responses to TxA2 in human uteroplacental arteries, and such drugs may represent an interesting therapeutic approach in preeclampsia.

Adult↗

Functional effects, binding sites and immunolocalization of endothelin-1 in isolated penile tissues from man and rabbit.

Functional effects of endothelin-1 (ET-1) were investigated in isolated preparations of human and rabbit corpus cavernosum (CC) and human penile circumflex veins (CV). In all preparations, ET-1 induced slowly developing, concentration-dependent contractions. The threshold concentration of ET-1 in CV was approximately 10 and 112 times lower than the threshold concentrations in human and rabbit CC, respectively. Furthermore, the contractions in CV reached a defined maximum at 10(-7) M ET-1 (-log EC50 = 9.12 +/- 0.17), whereas no maximum was obtained in CC preparations within the concentration range used (less than or equal to 3 x 10(-7) M). Pretreatment with the Ca++ channel blocker nimodipine partly reduced the ET-1-induced contractions in human and rabbit CC, but had no significant effect on CV preparations. In a Ca(++)-free medium containing the chelator ethyleneglycol-bis-(beta-aminoethylether)-N,N'-tetra-acetic acid, the contractions induced by ET-1 were reduced, but not abolished, in all preparations. The contractions induced by ET-1 are thus mediated mainly by influx of Ca++, although there seem to exist differences in the relative contribution of L-type Ca++ channels in CC and CV. Furthermore, additional mechanisms beside Ca++ influx are likely to be involved in both tissues. A high density of [125I]ET-1 binding sites was observed throughout the stroma and in the muscle layer of the deep penile artery in both human and rabbit CC. In the human CV, numerous binding sites were observed, but no clear difference between the various structures of the vessel wall could be detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Changes in serum electrolytes after transcervical resection of endometrium and submucous fibroids with use of glycine 1.5% for uterine irrigation.

OBJECTIVE: We evaluated the postoperative changes in serum electrolytes in relation to the amount of irrigating fluid absorption and the occurrence of nausea and vomiting after transcervical resection of endometrium and submucous fibroids. METHODS: From May 1989 to October 1991, 101 consecutive patients were operated on for menometrorrhagia with transcervical resection of endometrium and submucous fibroids using glycine 1.5% for uterine irrigation. The deficit of glycine was assessed during and at the end of the operation. During the postoperative course, attention was paid to the occurrence of cerebral confusion, nausea (defined by at least one incident of vomiting), and dyspnea. The serum levels of sodium, potassium, and chloride were assessed before the operation, at the end of the procedure, and after 4, 8, and 12 hours. RESULTS: No marked water intoxication or signs of volume overload were seen, but 33% of the patients had nausea and vomiting in the postoperative period. These patients showed a more pronounced postoperative decrease in serum sodium (P = .0001) and a larger glycine deficit (P = .004) than did patients without nausea. The postoperative decrease in serum sodium correlated significantly to the glycine deficit (R2 = 0.83, P less than .001). CONCLUSION: Postoperative hyponatremia after transcervical resection of the endometrium correlated with the deficit of irrigant fluid but not with the operation time or the total amount of irrigant fluid used. We recommend that serum sodium be controlled and corrected if necessary postoperatively in patients with nausea and vomiting.

Absorption↗

Phase I/II clinical trial of didemnin B in non-small-cell lung cancer: neuromuscular toxicity is dose-limiting.

Didemnin B (NSC 325,319), a cyclic depsipeptide isolated from a Caribbean tunicate, exhibits potent preclinical antitumor activity. In previous phase I studies, 3.47 mg/m2 was the maximally tolerated dose, with nausea and vomiting being the dose-limiting toxicity. The drug was given in a single bolus infusion over 30 min every 28 days. In the current study, 30 patients presenting with previously treated non-small-cell lung cancer (NSCLC) received 46 courses of the drug at doses ranging from 3.47 to 9.1 mg/m2. Neuromuscular toxicity was dose-limiting. Nausea and vomiting appeared to be correlated with dose levels and were ameliorated by a combination of antiemetics including dexamethasone. Other side effects included a mild rise in hepatic enzymes and an allergic reaction that was preventable by the addition of corticosteroids to the premedication regimen. In all, 2 minor responses were seen among 24 evaluable patients. Because neuromuscular toxicity is dose-limiting, we recommend that routine measurements of creatine kinase and aldolase, a careful neurologic evaluation, and electromyography and muscle biopsy (if indicated) be incorporated into phase II trials. The recommended dose for phase II studies using a single bolus schedule is 6.3 mg/m2, following the premedication of patients with antiemetics.

Adult↗

Effects of magnesium and terbutaline on contractility and K+ uptake in isolated human uterine muscle.

Mg++ (3 and 6 mmol/L), the beta 2-adrenergic agonist terbutaline (1 and 10 mumol/L), and dibutyryl cyclic adenosine 5'-monophosphate (0.1 and 1 mmol/L) suppressed spontaneous activity and the increase in contractile activity induced by ouabain or K(+)-free buffer in isolated human pregnant myometrium. The ouabain-suppressible rubidium 86 or potassium 42 uptake was unaffected by the presence of Mg++ (3 and 6 mmol/L), the beta 2-adrenergic agonist terbutaline (1 and 10 mumol/L), or dibutyryl cyclic adenosine 5'-monophosphate (1 mmol/L). However, loading of the strips with Na+ and incubation in high K+ induced a fivefold increase in rubidium 86 uptake. On the basis of these flux rates, our previous data on the total concentration of sodium-potassium pumps in the human myometrium, and an estimated maximum transport rate of the sodium-potassium pump of 8900 K+ ions per minute at 30 degrees C, it could be calculated that the sodium-potassium pump in the Na(+)-loaded strips reached around 80% of its maximal rate. Taken together, these results showed that the relaxant effects of Mg++, terbutaline, and dibutyryl cyclic adenosine 5'-monophosphate on human myometrium are not due to a stimulation of active sodium-potassium transport.

Biological Transport↗

Mechanical properties of isolated human oesophageal submucosal veins.

The mechanical properties of isolated human oesophageal submucosal veins were investigated. The veins were without tone or spontaneous activity and possessed a high compliance, tolerating a stretch of several hundred per cent of the length at which the vessels were first able to contract with only minor increases in passive tension. The veins were capable of producing active tension when the length exceeded 30% of L0 (the length at which maximum wall tension (T0) was developed when activated by 124 mM K(+)-solution). The veins from the oesophageal body (OB) had a higher L0 than the veins from the gastrooesophageal junction (GOJ) (1180 microns vs 820 microns) and T0 was correspondingly higher (1.1 mN/mm vs. 0.6 mN/mm). However, there was no significant difference in the calculated effective transmural pressure (P) at the two locations. Noradrenaline induced contractions in all preparations tested with a maximum response equivalent to the tension achieved after stimulation with 124 mM K(+)-solution, pD2 values for noradrenaline in vessels from the oesophageal body and the gastroesophageal junction were 7.03 +/- 0.28 (mean +/- SEM) and 7.15 +/- 0.20, respectively. The present model seems suitable for future studies of human oesophageal submucosal veins from the oesophageal body and the gastrooesophageal junction.

Adult↗

Nitric oxide mediating NANC inhibition in opossum lower esophageal sphincter.

Strips from opossum lower esophageal sphincter were prepared and mounted in organ baths for recording of isometric tension. Nonadrenergic, non-cholinergic (NANC) inhibitory responses were evoked by transmural field stimulation. The relaxant responses to field stimulation were inhibited in a concentration-dependent manner by N omega-nitro-L-arginine (L-NNA), a substance known to inhibit the formation of nitric oxide (NO). At a concentration at 10(-4) M of L-NNA, most preparations contracted during field stimulation, and this response was abolished by atropine (10(-6) M). L-Arginine (10(-5) M) shifted the concentration-response curve for L-NNA to the right. Relaxant responses to VIP (10(-9) to 10(-6)M) and sodium nitroprusside (10(-9) to 10(-5) M) were unaffected by preincubation with L-NNA (10(-5) to 10(-4) M) or L-arginine (10(-5) M). The inhibition of NANC-relaxation was apparently not due to an influence on release of a NANC transmitter different from NO, since L-NNA had no preserving effects on responses to field stimulation in preparations treated with scorpion venom. We conclude that involvement of a NO-generating process from L-arginine seems mandatory for NANC responses in the isolated lower esophageal sphincter.

Animals↗

Transcervical resection of endometrium and fibroids. Initial complications.

Transcervical resection of endometrium--and of submucous fibroids when present--seems to represent a new alternative to hysterectomy for patients with uncontrolled bleeding disorders. In the present study, we report our initial experience with the first 20 patients treated with a standard, rigid urological resectoscope. Resection of endometrium--and of fibroids when present--was carried out under general anesthesia. The uterine cavity was distended and irrigated with glycine 1.5%. Two perforations occurred, but damage to neighboring organs was not seen. In one patient, copious bleeding was encountered and hysterectomy became necessary the following day. Clinical signs of postoperative infection occurred in 3 patients. Otherwise, no major morbidity was seen during or after the procedure. In 2 patients with persistent metrorrhagia, re-resection was performed after 2-3 months and satisfactory bleeding control achieved. At the 3-month follow-up, 2 further patients complained of persistent bleeding and had an abdominal hysterectomy performed. In the remaining patients, satisfactory bleeding control was reported at the 6-month follow-up. Although large series are needed to assess the complications associated transcervical resection of the endometrium, the technique may be applied in departments with experience in routine hysteroscopy, and the approach seems to represent an attractive alternative to hysterectomy.

Adult↗

Mechanical properties of isolated smooth muscle from rabbit sphincter of Oddi and duodenum.

Isolated smooth muscle from rabbit sphincter of Oddi (SO) and duodenum were mounted in organ baths. The SO strips were obtained as transversal strips from the midsection of the SO. The duodenal strips were prepared as longitudinal (Dl) or circumferential (Dc) strips. Resting length was defined. Carbachol was used for activation of the contractile apparatus. By repeatedly increasing the length of the strips by 20% of the resting length and recording values of resting and active tension, length-tension relations for each muscle type were constructed. None of the strips developed active resting tension. Twelve of the Dl strips (75%) developed spontaneous contractions versus four of the Dc strips (10%) and one of the SO strips. The strips eventually reached a length (Lo) at which further elongation gave no additional increase in active tension development. The Lo from the Dc strips differed significantly from SO Lo (p greater than 0.02) and Dl Lo (p less than 0.02), indicating structural differences. SO Lo and Dl Lo did not differ significantly. Differential extension of these tissues should be applied in future experiments on smooth muscles from this area.

Animals↗

Effects of human relaxin on isolated rat and human myometrium and uteroplacental arteries.

We investigated the effects of synthetic human relaxin (hRLX-2) on isolated rat and human myometrium and on uteroplacental arteries from term pregnant women. The preparations were mounted in organ baths and isometric tension was recorded. In isolated myometrium from nonpregnant rats, hRLX-2 (10(-10)-10(-7) mol/L) produced concentration-dependent inhibition of contractile activity induced by vasopressin (10(-8) mol/L). In isolated human myometrium from the fundus or isthmus, hRLX-2 (10(-10)-10(-7) mol/L) did not influence spontaneous activity or contractions induced by oxytocin (10(-9) mol/L) and prostaglandin (PG) F2 alpha (10(-5) mol/L). Nor did it influence the tension induced in small intramyometrial arteries by U46619 (10(-7) mol/L), noradrenaline (10(-5) mol/L), and endothelin (10(-9) mol/L); or the tension induced in fetal stem villus arteries by U46619 (10(-7) mol/L), endothelin (10(-9) mol/L), and PGF2 alpha (10(-5) mol/L). The inhibitory effects of hRLX-2 in preparations of rat myometrium were not influenced by the presence of human myometrium in the organ bath or by pre-incubation of hRLX-2 with human myometrium. These results suggest that direct inhibitory effects of relaxin may be of minor importance for the regulation of myometrial activity and uteroplacental circulation in term human pregnancy.

Animals↗