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PubMed2004

Liver dysfunction induced by bile duct ligation and galactosamine injection alters cardiac protein synthesis.

Liver disease has been shown to affect the cardiovascular system and may influence cardiac protein metabolism. This hypothesis was tested by measuring rates of cardiac protein synthesis in 2 models of liver disease in rats. The study consisted of 5 groups--group 1: control, injected with saline and fed ad libitum; group 2: acute liver injury, by dosage with 400 mg/kg galactosamine; group 3: injected with saline and pair-fed to group 2; group 4: chronic liver disease, using bile duct ligation; and group 5: sham-operated and pair-fed to group 4. Rates of cardiac protein synthesis were measured using the flooding dose technique. After 1 week, galactosamine injection caused the following cardiac changes, i.e. group (2) versus (3): an increased RNA content, RNA/DNA ratio, and RNA/protein ratio. However, there was no change in DNA or protein content, or protein/DNA ratio. There was an increase in the fractional rate of protein synthesis, and the absolute synthesis rate. Cellular efficiency was increased, but RNA activity remained unchanged. Comparison of groups 4 and 5 showed that bile duct ligation caused no change in any parameters measured. Although comparison of the ad libitum-fed group 1 with the bile duct ligation group 4 showed reduced cardiac weight, protein, and RNA content, with decreased right ventricular absolute synthesis rates; this was also seen in the pair-fed group 5, suggesting that these effects were due solely to reduced oral intake. Thus, although galactosamine-induced acute liver injury caused marked changes in cardiac biochemistry, bile duct ligation per se did not. This study also illustrates the importance of including a pair-fed group.

Algorithms↗
PubMed2005

Experiments with nitric oxide synthase inhibitors in spinal nerve ligated rats provide no evidence of a role for nitric oxide in neuropathic mechanical allodynia.

We have investigated the effect of treatment with N(omega)-nitro-l-arginine methylester (l-NAME), a non-selective nitric oxide synthase inhibitor (NOS), both before and after the induction of mechanical allodynia by tight ligation of the left L5 and L6 spinal nerves in rats (SNL rats). The degree of mechanical allodynia was measured by tactile threshold for paw flinching with von Frey filaments. Intraperitoneal (i.p.) administration of l-NAME (3-30 mg/kg) 1 week after the spinal nerve ligation produced a dose-dependent reduction of the behavioral signs of mechanical allodynia, but the effect was not reversed by pretreatment with l-arginine (300 mg/kg). N(omega)-Nitro-l-arginine (l-NNA, i.p., 30 mg/kg), aminoguanidine (AG, i.p., 30 mg/kg) and a potent neuronal NOS inhibitor (LY457963, i.p., 30 mg/kg) did not reduce mechanical sensitivity in the SNL rats. Furthermore, using an ex vivo NOS activity assay, l-NAME partially inhibited the spinal NOS activity, whereas LY457963 almost completely inhibited the spinal NOS activity. Prior administration of l-NAME (i.p., 30 mg/kg) or of MK-801 (0.5 mg/kg), an NMDA antagonist, 30 min before the spinal nerve ligation significantly prevented the development of mechanical allodynia after spinal nerve ligation for an extended period of time. High doses of l-arginine (100 mg/kg or 300 mg/kg, i.p.), however, did not reverse the preemptive effect of l-NAME. These results suggest that neither the anti-allodynic nor the preemptive effects of l-NAME are mediated by NOS inhibition.

Animals↗
PubMed2006

Loose ligation of the sciatic nerve in rats elicits transient up-regulation of Homer1a gene expression in the spinal dorsal horn.

Changes in the expression of many genes underlie injury-elicited plasticity in the spinal dorsal horn. Homer1 is a recently identified gene that appears to play a critical role in the expression of synaptic plasticity in several brain regions, including the hippocampus. In this study we investigated the early consequences of chronic constriction injury of the sciatic nerve on Homer1 gene expression in the spinal dorsal horn. Significant increases in Homer1a mRNA levels in the ipsilateral dorsal horn were detected at 4h post-ligation, and these levels remained elevated at 8h before returning to baseline values by 24h after the ligation. In contrast, the levels of Homer1b/c mRNA did not change at any of these selected post-ligation times. The ligation-associated induction of Homer1a was dependent on activation of NMDA receptors and the extracellular signal-regulated kinase 1 and 2 (ERK1/2) pathway. The non-competitive NMDA-receptor antagonist, MK-801, and a specific inhibitor of the ERK1/2 pathway, U0126, significantly attenuated the injury-elicited increases in Homer1a mRNA when compared to saline-treated animals. These data provide the first evidence for a potential role of Homer1a in peripheral nerve injury-elicited plasticity in the spinal dorsal horn. These data also imply that the early and transient up-regulation of Homer1a gene expression may be an important contributor to the eventual development of neuropathic pain.

Animals↗
PubMed2004

Plasticity of spinal nicotinic acetylcholine receptors following spinal nerve ligation.

The nicotinic cholinergic system is known to be important in the processing of nociceptive information. In the spinal cord, nicotinic receptors are expressed on primary afferent terminals, inhibitory interneurons and descending noradrenergic and serotoninergic fibers. Following peripheral nerve injury, the expression of numerous receptors involved in nociceptive processing is altered in the superficial dorsal horn of the spinal cord. However, the expression of nicotinic acetylcholine receptor subunits in the lumbar spinal cord following peripheral nerve injury has not been investigated. We examined the expression of the alpha3, alpha4, alpha5, alpha7, beta2, beta3 and beta4 nicotinic subunits in the spinal cord of normal and spinal nerve ligated rats using immunocytochemistry. Two nicotinic subunits were found to have an increased expression following spinal nerve ligation. The number of cells expressing the alpha3 subunit in the dorsal horn increased bilaterally following spinal nerve injury. Also, the number of alpha5 immunoreactive fibers increased significantly ipsilateral to ligation. The expression of the alpha4, alpha7, beta2, beta3 and beta4 subunits was unchanged. We propose that the increased expression of the alpha3 and alpha5 nicotinic subunits may contribute to the mechanical hypersensitivity observed following spinal nerve ligation.

Animals↗
PubMed2005

Unilateral spinal nerve ligation leads to an asymmetrical distribution of mast cells in the thalamus of female but not male mice.

Mast cells are restricted to the leptomeninges and thalamus of healthy mice. These populations are increased by stress and highly sensitive to reproductive hormones. To examine the influence of nociception, a form of stress, on thalamic mast cells, we ligated the left fifth lumbar spinal nerve of male and female mice to induce hyperalgesia. Two, 7 and 14 days later, mice were killed and thalami examined histologically using toluidine blue stain. The total number of thalamic mast cells was not influenced by ligation of the spinal nerve compared to sham-operation in either female or male mice. However, in females, the percent of thalamic mast cells located on the side of the thalamus contralateral to the ligation was greater on days 2 and 7, coincident with mechanical hyperalgesia. At these times, areas in which mast cells were most dense contralateral to nerve-injury included the posterior (Po) and lateral geniculate (LG) nuclei compared to their symmetrical distribution in sham-operated mice. These data suggest that local nociceptive signals to each side of the thalamus rather than stress hormones influence the location of mast cells during the development of allodynia and hyperalgesia. In addition, both hyperalgesia and mast cell distribution induced by nerve-ligation differ in females compared to males, reflecting a novel neuroimmune response to pain within the CNS.

Animals↗
PubMed2006

Testicular blood flow measurements and mean resistive index values after microsurgical and high ligation varicocelectomy.

OBJECTIVES: To compare the effects of the two most commonly used surgical methods in the management of varicocele disease, namely, microsurgery and high-ligation varicocelectomy, on testicular blood flow changes and mean residual index values in a prospective randomized study. METHODS: A total of 56 patients clinically diagnosed with varicocele were randomized into two groups: 28 were selected for high-ligation surgery and 28 for microsurgery. The testicular blood flow was evaluated in all patients before and 7 days after surgery, and the maximal flow velocity (Vmax), minimal flow velocity, and resistive index were measured. The data assessment was performed using the paired t test, and independent t test was used in comparison of the two groups. RESULTS: No significant difference was detected between the preoperative resistive index, Vmax, and minimal flow velocity of the two groups. The values of the same parameters measured 7 days postoperatively were also not significantly different. The preoperative and postoperative comparison of the three parameters within the microsurgery group revealed no difference, although the postoperative Vmax was significantly lower than the preoperative Vmax in the high-ligation group. CONCLUSIONS: Our data have shown that no significant impairment in testicular circulation results after low microsurgical varicocele repair compared with high ligation.

Adult↗
PubMed1997

Chlamydia trachomatis and febrile complications of postpartum tubal ligation.

OBJECTIVE: Our goal was to determine whether chlamydia-infected women have a higher rate of febrile complications after postpartum tubal ligation. STUDY DESIGN: Cross-sectional analysis of 1447 women tested for chlamydial infection within 2 weeks of delivery and who underwent postpartum tubal ligation was performed. Subjects were identified with the Regenstrief Institute for Health Care database. Infected subjects were compared with uninfected subjects for incidence of fever not explained by nongynecologic sources. RESULTS: Women infected with Chlamydia trachomatis at delivery were more likely to experience febrile postoperative complications after tubal ligation (p < 0.0001, relative risk 9.5, 95% confidence interval 4.5 to 20.1). CONCLUSION: Women undergoing postpartum tuba ligation may benefit from prompt diagnosis and preoperative treatment of chlamydial infection.

Adult↗
PubMed1998

Is thigh saphenectomy a necessary adjunct to high ligation and stab avulsion phlebectomy?

BACKGROUND: Controversy still exists as to whether the thigh saphenous vein should be stripped concomitant with high ligation and phlebectomy. METHOD: A total of 218 procedures were retrospectively grouped into three groups: group 1, 10 limbs with visible, duplex scan-confirmed varicose veins of the thigh saphenous vein; group 2, 13 saphenous veins with varices that were not clinically evident; group 3, 195 limbs with incompetent saphenous veins without thigh saphenous varices. RESULTS: Five limbs in group 1 were treated by high ligation, phlebectomy, and thigh saphenectomy. All did well. Five had high ligation and phlebectomy only. Two developed painful phlebitis, and two had residual varices in the saphenous vein. Group 2 and group 3 were treated by high ligation and phlebectomy. One group 2 limb developed saphenous phlebitis. Five limbs in group 3 developed recurrent veins that were removed in the office. CONCLUSION: Thigh saphenectomy is only required when there are visible, duplex scan-confirmed varices of the thigh saphenous itself, or when the procedure is performed for severely symptomatic patients or those with advanced stasis changes.

Adolescent↗
PubMed1995

A comparison of conservative therapy and early selective ligation in the treatment of lymphatic complications following vascular procedures.

BACKGROUND: Lymphatic leakage is a relatively uncommon but serious complication following vascular procedures. A conservative approach consisting of bed rest, leg elevation, prophylactic antibiotics, compressive dressings, and intermittent aspiration is the most commonly used treatment. Because of the long time it takes to cure this condition and the potential for infections, a more aggressive approach consisting of wound exploration and ligation of the leaking lymphatic has been proposed. We review our experience of the past 3 years treating 17 of these complications by using 1 of these 2 approaches. PATIENTS AND METHODS: Seventeen groin complications were seen over a period of 3 years. Ten (59%) patients were treated by selective ligation assisted with isosulfan blue dye injection, and the remaining 7 (41%) were treated conservatively. RESULTS: Mean hospital stay was 2.4 days (range 1 to 4) for the operative group versus 19 days (range 14 to 42) for the conservative group. One complication was seen in the operative group, whereas 4 (57%) patients developed groin infections following conservative therapy. One (10%) patient developed a recurrence following ligation that was treated successfully by reoperation. CONCLUSION: Our experience with the use of surgical ligation of leaking lymphatic assisted by isosulfan blue, when compared with conservative treatment, has led to a decrease in hospital stay, lower complication rates, and fewer recurrences. In our view, this approach represents the best form of treatment for postoperative groin lymphatic complications.

Adult↗
PubMed2002

[Surgery technique: preventive ligation of the thoracic duct during esophagectomy for cancer].

Chylothorax is a rare but life-threatening complication of esophagectomy for cancer. Elective ligation of the thoracic duct above the diaphragm does not suppress completely the risk of chylothorax due to possible trauma of the thoracic duct wall at the level of ligation, or incomplete ligation in case of anatomic variation. This study describes a technique of preventive ligation "en block" with surrounding tissues in order to minimize the risk of chylothorax following oesophagectomy, whatever performed transthoracically or through transhiatal approach.

Carcinoma↗
PubMed1981

Supradiaphragmatic ligation of the thoracic duct in intractable chylous fistula.

Spontaneous closure of a chylous fistula is usual, but the rare intractable fistula may lead to disastrous nutritional and immunological consequences. We report the surgical management of 5 patients with intractable fistulas with daily drainage averaging 2,060 ml. Conservative therapy failing, the 5 patients underwent 6 ligations of the thoracic duct. A limited posterolateral thoracotomy was used in 3, full right thoracotomy in 2, and left thoracotomy in 1. Ligations were carried out immediately above the diaphragm, and not at the fistula site, by a mass ligature technique encircling all tissue between the azygos vein and aorta. The ligation achieved immediate cessation of drainage in four of five initial procedures and in the fifth patient, at a second operation. High-output thoracic duct fistulas may be handled by supradiphragmatic ligation of the thoracic duct. Identification of the fistula site or the dissection of the thoracic duct itself is avoided by this technique.

Aged↗
PubMed1986

C-terminal PTH (70-84) after biliary ligation in rats: implications for the diagnostic importance in hepatobiliary disease.

The pathogenesis of hepatic osteodystrophy is still poorly understood. To date, there is no convincing evidence for the involvement of one of the vitamin D metabolites. Recent observations provided evidence for an disturbed hepatic metabolism of intact PTH in patients with primary biliary cirrhosis and children with biliary atresia. To confirm these data experimentally, the extrahepatic bile-duct was ligated and dissected in rats. As expected GOT and AP activity increased in ligated group, calcium and mid-C-PTH remained constant for the first 44 days post-ligation. Similar to the data in the respective groups of patients, C-terminal PTH immunoreactivity increased after biliary ligation. The radioimmunological discrimination between intact PTH and the bone-seaking N-terminal PTH peptide is still impossible without further chromatographic procedures. Therefore, C-PTH may represent an important laboratory parameter for the evaluation of the hepatic metabolism of PTH which seems to be disturbed during severe longstanding cholestasis.

Alkaline Phosphatase↗
PubMed2001

Sympathetic sprouting in the dorsal root ganglion after spinal nerve ligation: evidence of regenerative collateral sprouting.

It is well documented that there is an increase in the number of sympathetic fibers within the dorsal root ganglion (DRG) after a peripheral nerve injury. The present study examined the numbers and distribution of sympathetic fibers in the DRG and their sprouting routes by utilizing various surgical manipulations and retrograde tracing and immunohistochemical staining methods in spinal nerve-ligated neuropathic rats. The appearance of many double immunostained fibers with antibodies to tyrosine hydroxylase (TH) and growth associated protein-43 (GAP-43) in the L5 DRG 1 week after L5 spinal nerve ligation, indicated sprouting of sympathetic fibers. The confined location of early sprouting sympathetic fibers in the distal half of the L5 DRG confirmed that sprouting fibers come primarily from the injured spinal nerve. A second cut proximal to the previously ligated L5 spinal nerve -- a process which would transect the regenerating sympathetic fibers extending from the injury site -- did not change the density of sympathetic fibers in the L5 DRG. When retrograde tracers (fast blue and diamidino yellow) were injected into the L5 spinal nerve and DRG, respectively, the number of double-labeled sympathetic postganglionic neurons was greatly increased after spinal nerve ligation, suggesting the increased number of sympathetic neurons projecting to both the spinal nerve and DRG. All these results indicate that many sympathetic fibers in the DRG are regenerating branches that are sprouting from the proximal part of the injured spinal nerve (regenerative collateral sprouting).

Animals↗
PubMed2003

Decreased L5 spinal nerve ligation nociceptive behavior following L4 spinal nerve transection.

This study used the escape/avoidance paradigm to explore the role of the L4 spinal nerve in L5 ligation nociception. Unlike L5-ligated controls, L5-ligated/L4-transected animals had normal mechanical withdrawal threshold and did not escape/avoid mechanical stimulation of the afflicted paw. The result from the escape/avoidance paradigm, which does not rely on a reflexive withdrawal response, directly supports the hypothesis that the L4 spinal nerve contributes to L5 ligation neuropathic pain.

Animals↗
PubMed2000

Involvement of spinal protein kinase C in thermal hyperalgesia evoked by partial sciatic nerve ligation, but not by inflammation in the mouse.

Activation of several protein kinases contributes to the development of hyperalgesia evoked by injuries. The present study was designed to investigate the role of protein kinase C in the spinal cord in thermal hyperalgesia evoked by sciatic nerve ligation or by intraplantar injection of complete Freund's adjuvant. The paw withdrawal latency on the ipsilateral side, but not on the contralateral side, was markedly decreased after sciatic nerve ligation. Intraplantar injection of complete Freund's adjuvant also caused markedly decreases of the paw withdrawal latency. Intrathecal pretreatment with protein kinase C inhibitor calphostin C (100 and 250 ng) attenuated the decrease of the paw withdrawal latency evoked by sciatic nerve ligation. In contrast, the decrease of the paw withdrawal latency evoked by inflammation was only slightly attenuated by intrathecal pretreatment with calphostin C. The results indicate that protein kinase C in the spinal cord is involved in the development of the thermal hyperalgesia evoked by nerve ligation and is much less involved in the thermal hyperalgesia by complete Freund's adjuvant's-induced inflammation.

Animals↗
PubMed1997

Effect of sodium tauroursodeoxycholate (UR-906) on liver dysfunction in bile duct-ligated rats.

We investigated the effect of sodium tauroursodeoxycholate (UR-906) on cholestasis in common bile duct-ligated rats in comparison with the effect of dehydrocholic acid. UR-906 (30-180 mumol/kg) and dehydrocholic acid (180 mumol/kg) were intravenously given once daily for consecutive 20 days in rats and the common bile duct was ligated for the last 10 days. On the next day after the last test drug administration, serum biochemical and plasma hemostatic variables were determined. UR-906 significantly ameliorated the elevation of serum cholesterol, phospholipid, bilirubin and bile acid concentrations in bile duct-ligated rats. UR-906 significantly suppressed the prolongation of plasma prothrombin time and activated partial thromboplastin time. Furthermore, UR-906 significantly suppressed the decreases in plasma coagulation factor II and X activities. However, dehydrocholic acid did not cause significant changes in any of the variables examined in this model. These results suggest that UR-906 has a beneficial effect against cholestasis induced by bile duct ligation in rats and that this drug may be useful in the treatment of clinical cholestatic disorders.

Animals↗
PubMed1981

Endometriosis and the development of tuboperitoneal fistulas after tubal ligation.

The present study details gross and histologic findings of 79 previously ligated fallopian tubes from 3 groups of patients. Of 20 oviducts removed after documented sterilization failure (group I), 6 revealed a process compatible with endometriosis. Four of nine previously ligated fallopian tubes removed at the Johns Hopkins Hospital (group II) were successfully injected with India ink. In two patients histologic examination demonstrated the India ink in epithelium-lined spaces that lay beyond the muscle of the tubal wall extending from the tubal lumen to the serosal surface. Fifty oviducts were studied in twenty-five patients requesting reversal of their sterilizations (group III). A higher percentage of fistulas was demonstrated in patients with less than 4 cm of remaining proximal tubal segment. Furthermore, most of these fistulas were demonstrated in patients for whom 3 years had elapsed since the original sterilization procedure. Patients sterilzed by laparoscopic cautery methods were observed to have a higher percentage of fistula formation and histologic documentation of endometriosis at the sterilization site as compared with patients sterilized by other methods. Our observations suggest that ligation of the oviduct within 4 cm of the uterine cornu may predispose to the development of endometriosis and subsequent fistula formation in the tip of the ligated oviduct.

Endometriosis↗
PubMed1999

Are sperm motion parameters influenced by varicocele ligation?

OBJECTIVE: To document objectively, improvements in sperm motion parameters in subfertile men after varicocele ligation with the use of computer-aided sperm analysis. DESIGN: Retrospective chart review. SETTING: An academic clinical environment. PATIENT(S): Thirty-four men with varicocele as the primary cause of infertility who underwent a physical examination, hormonal profile, and Doppler ultrasound evaluation. INTERVENTION(S): Computer-aided sperm analysis was performed before and after either subinguinal or laparoscopic varicocele ligation. MAIN OUTCOME MEASURE(S): Patients were followed up for 3-18 months after operation, and average computer-aided sperm analysis values were obtained before and after operation. Computer-aided sperm analysis values were analyzed by paired Student's t-test, with special reference to motility and sperm motion parameters. RESULT(S): After varicocele ligation, patients demonstrated increases in mean sperm density and in the overall distribution of sperm with rapid velocity, although the increases were not statistically significant. Mean measures of straightness, linearity, and track speed also were increased after operation, but only progressive sperm velocity was increased to a statistically significant level. CONCLUSION(S): Because progressive velocity has been a primary computer-aided sperm analysis parameter predictive of male fertility and the success of assisted reproductive techniques, we conclude that varicocele ligation results in improvements in semen parameters, especially the key parameter of progressive sperm velocity.

Adult↗