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The analysis of methadone in nail clippings from patients in a methadone-maintenance program.

This study offers an analytical scheme for methadone in fingernail clippings. Nail specimens (0.18-16.33 mg) were collected from 30 consenting adults participating in a methadone-maintenance program along with questionnaires regarding their drug-use histories. The nail clippings were stored in plastic bags and transferred to the laboratory for analysis. They were decontaminated by sonication for 15-min intervals successively in 0.1% sodium dodecyl sulfate, water (three times), and methanol (three times). The methanolic washes were collected and screened for methadone by enzyme immunoassay (EIA). Three washes were found sufficient to provide EIA negative results. The decontaminated nail clippings were hydrolyzed in 1M NaOH. Aliquots of the hydrolysates were screened for methadone by EIA and confirmed by gas chromatography-mass spectrometry (GC-MS). The mean methadone concentrations in fingernail clippings determined by EIA and GC-MS were 32.8 and 26.9 ng/mg, respectively. Hydrolysates of the equivalent of 10 mg of blank nail clippings were spiked with known concentrations of methadone and analyzed by the developed procedures in order to determine extraction recoveries and limits of detection of the two techniques. Based on our results, fingernails appear to be a potentially useful biological specimen for the analysis of methadone and the monitoring of patient compliance to methadone-maintenance programs.

Adult↗

Deposition characteristics of methamphetamine and amphetamine in fingernail clippings and hair sections.

Fingernail clippings collected from 97 consenting females, who admitted amphetamines and/or opiates use and are currently under treatment, were quantitatively analyzed for the presence of methamphetamine and amphetamine. Sixty-two subjects were found positive for methamphetamine/amphetamine. Paired nail-hair specimens were collected from 6 of these subjects for a 12-week period and analyzed to determine the duration of detectability and deposition characteristics of amphetamines in fingernails; whether data derived from the analysis of nail clippings and hair sections are reflective of drug use patterns; and whether there is a relationship between the analytical data derived from the paired nail-hair specimens. Typical sample pre-treatment procedures and GC-MS protocols were evaluated to establish the validity of various analytical parameters and to ensure that the resulting data can be properly interpreted. Major findings include 1. Methamphetamine was found in the nails of 62 subjects collected in Week 0. The distribution of methamphetamine concentrations (ng/mg) in these nail samples are range, 0.46-61.50; mean, 9.96; and standard deviation: 13.33. The corresponding data for amphetamine are < 0.20-5.42, 0.93, and 1.01, respectively. 2. Sectional analyses of hair samples collected from 6 subjects in Week 0 show methamphetamine concentrations peak at different distances from the root. 3. The concentrations of methamphetamine and amphetamine in nail clippings are generally lower than the first 1.5-cm section of hair samples collected at the same time from the same individual. 4. Amphetamine/ methamphetamine concentration ratios in nail clippings and hair samples are comparable. 5. Methamphetamine concentration in the nail clippings collected at Weeks 0, 4, 8, and 12 decreases in a pattern similar to that exhibited by the first 1.5-cm sections of the hair samples collected at the same time.

Adult↗

Renal expression of aminopeptidase A in rats with two-kidney, one-clip hypertension.

BACKGROUND: Angiotensin II (ANG II) is a major factor involved in the progression of chronic renal disease. Although the generation of this vasoactive peptide has been investigated in great detail, only a few studies have hitherto addressed the metabolism of ANG II into fragments such as angiotensin III and IV (ANG III, IV) which may exert physiological effects independent of ANG II. Aminopeptidase A (APA) is the major enzyme degrading ANG II. The aim of the current study was to evaluate glomerular APA expression in rats with two-kidney, one-clip hypertension. METHODS: The left renal artery was restricted with a 0.2-mm silver clip. Kidneys were harvested 1 and 4 weeks after surgery. APA enzyme and protein expression was evaluated in kidney sections. Total APA enzyme activity and mRNA expression was assessed in isolated glomeruli. Degradation of exogenous ANG II by isolated glomeruli was measured with reverse-phase high-performance liquid chromatography. RESULTS: APA enzyme activity, protein, and mRNA expression were stimulated in the clipped kidney 1 week after surgery compared with the contralateral kidney or normal controls. In contrast, 4 weeks after clipping APA activity and expression was higher in the contralateral kidney. In parallel to these findings, degradation of ANG II was greatest in isolated glomeruli obtained from the clipped kidney after 1 week. However, preparations from the contralateral kidney 4 weeks after surgery were more active in the metabolism of exogenous ANG II. CONCLUSION: The present study provides evidence that APA is complexly regulated in in vivo situations with an activated local renin-ANG II system. ANG II appears to play a direct role in this regulation. However, since conversion of ANG II to ANG III by APA is the initial step leading to the formation of ANG IV which may exert detrimental effects not mediated through classical ANG II receptors, a local increase in APA activity may contribute to the progression of chronic renal disease even during complete AT(1)-receptor blockade.

Aminopeptidases↗

The inferior vena cava clip. The percutaneous approach.

Pulmonary embolism in high-risk patients may be minimized by surgical inferior vena cava (IVC) clipping or by the insertion of caval filters. A percutaneous clipping technique was developed that narrows the cava while allowing caval patency. The caval clip is inserted through a percutaneous translumbar approach under fluoroscopic control. Nine dogs underwent percutaneous translumbar caval clip placement without complications. Three of four dogs, followed-up for 5 to 19 weeks by angiography and caval pressure measurements, showed caval patency. This technique eliminates the risks of surgical IVC clip placement and risks from the insertion of intravascular foreign bodies such as filters.

Angiography↗

Two-kidney, one clip renal hypertension in the marmoset.

The purpose of this study was to assess whether two-kidney, one clip (2K1C) renal hypertension can be induced in the marmoset. During the first 3-5 weeks after renal arterial clipping, blood pressure (BP) and plasma renin activity (PRA) increased in approximately one-third of the operated marmosets. However, within 10 weeks after clipping, BP and PRA had returned to control values. There was a significant positive correlation between BP and log PRA 3 and 5 weeks after the operation, but no correlation was observed at 10 weeks. In a selected group of marmosets with the highest values of BP (greater than 140 mmHg; n = 4), the converting enzyme inhibitor, enalapril (2 mg/kg s.c.) lowered BP by 58 +/- 7 (s.e.m.) mmHg when given 3 weeks after clipping. At 18 weeks the response to enalapril was only -17 +/- 6 mmHg. These results demonstrate that unilateral renal arterial clipping in marmosets results in a transient renin-dependent hypertension. Marmosets in this initial hypertensive phase could be useful for investigating the antihypertensive effects of inhibitors of human renin.

Angiotensin-Converting Enzyme Inhibitors↗

Renal angiotensin II receptor regulation and renin-angiotensin system inhibition in one-kidney, one clip hypertensive rats.

OBJECTIVE: To characterize glomerular and preglomerular vascular angiotensin II receptors during the acute phase of nonrenin-dependent one-kidney, one clip hypertension in rats, using the angiotensin II antagonists losartan and PD 123319, and to investigate their regulation after renin-angiotensin system blockade with either an angiotensin converting enzyme inhibitor, captopril, or an angiotensin II receptor antagonist, TCV-116. MATERIALS AND METHODS: One-kidney, one clip hypertension was produced in male Sprague-Dawley rats by placing a silver clip (internal diameter 0.2 mm) on the left renal artery and removing the contralateral kidney. After 1, 2 or 4 weeks, the rats were killed, and their glomerular and preglomerular vascular membranes were purified. Competitive binding studies were performed using specific angiotensin II antagonists. Similarly, one-kidney, one clip hypertension was allowed to develop for 2 weeks before treatment with captopril or TCV-116 for 2 weeks. RESULTS: Competitive binding studies showed that only the angiotensin II type 1 (AT1) receptor was detected on both glomeruli and preglomerular vessels of all groups. The vascular AT1 receptor density was significantly higher in the 1 and 2 week one-kidney, one clip groups, but the glomerular receptor density was not different in these rats compared with age-matched uninephrectomized controls. The glomerular receptor density was significantly higher in captopril-treated rats and significantly lower in TCV-116-treated rats compared with untreated and control rats, but no significant changes were detected in any groups in vascular AT1 receptor density. CONCLUSIONS: Angiotensin II receptors on preglomerular vessels and glomeruli are differentially regulated during the early phase of hypertension and after renin-angiotensin system blockade. Vascular angiotensin II receptors are upregulated in the early phase of hypertension whereas glomerular angiotensin II receptors are not However, after renin-angiotensin system blockade, glomerular but not vascular angiotensin II receptors were differentially regulated according to the type of blockade.

Angiotensin Receptor Antagonists↗

Arterial repair with synthetic patch by using titanium clips.

BACKGROUND: Vascular closure staple (VCS) clips made of titanium were originally developed for microvascular anastomoses. There is limited experience with their applicability to vascular reconstruction in larger vessels. This study compares VCS clips to standard sutures in arterial repair using a synthetic patch. METHODS: In an experimental study with pigs, two sequential 10-mm abdominal aortotomies were allocated randomly to synthetic patch (polytetrafluoroethylene) repair with VCS clips or continuous 6-0 polypropylene sutures. Angiographic, macroscopic, and microscopic results were assessed after 2 months. RESULTS: There were no significant differences in the patency rate, vessel diameter at the repair site, or healing indices. The mean (SD) clamp time was 8.7 (3.0) minutes for clip repair and 14.3 (7.4) minutes for suture repair (p = 0.04), and the times required for the vessel reconstruction were 5.3 (1.3) and 9.3 (3.0) minutes, respectively (p = 0.009). CONCLUSION: Patched arterial repair with VCS clips is faster than sutured reconstruction with comparable results after 2 months of follow up.

Animals↗

Dural closure with nonpenetrating clips prevents meningoneural adhesions: an experimental study in dogs.

OBJECTIVE: Meningospinal and cranial dural adhesions were compared in a canine model, after duraplasty using nonpenetrating clips or penetrating needles and sutures. METHODS: Fourteen dogs underwent bilateral craniotomies and duraplasties, with implantation of dural prostheses (DuraGuard; Biovascular Corp., Minneapolis, MN), using either 6-0 silk sutures or titanium clips (DuraClose; Surgical Dynamics, Norwalk, CT). Fourteen other dogs underwent L3-L4 laminectomies; three longitudinal dural incisions were closed with 6-0 silk sutures, 6-0 polyglactin 910 (Vicryl) sutures, or clips. Groups of eight dogs (four cranially treated and four spinally treated) were killed 6, 12, 24, and 52 weeks after surgery, and specimens were collected for study after perfusion and fixation (two cranial and two spinal dural reconstructions at 52 wk). Evaluations included assessment of the appearance of approximated dural margins and responses to clips, sutures, and dural prostheses (inflammation, foreign body reaction, fibrosis, and severity of meningospinal/meningocerebral adhesions). Data were evaluated using the Wilcoxon signed-rank and McNemar tests. RESULTS: Duraplasties with clips displayed significantly less extensive acute and chronic inflammation, foreign body reaction, and meningoneural adhesions than did repairs with needles and sutures. CONCLUSION: This report is the first long-term experimental study comparing two fundamentally different methods for dural repair in a relevant animal model.

Animals↗

Repair of a tear at the base of a blister-like aneurysm with suturing and an encircling clip: technical note.

OBJECTIVE: An aneurysm can produce large defects in the parent vessel if the aneurysm tears at the neck of the vessel. The authors present a technique to repair a tear at the base of a blister-like aneurysm encountered during microsurgical clipping of an anterior wall aneurysm of the internal carotid artery. METHODS: The repair technique involved suturing and covering the aneurysm with an encircling aneurysm clip. A large tear had destroyed the vessel's tubular structure, and repair was not sufficient using an encircling clip alone. Two microsuture stitches were placed on the tear, so that a split artery re-formed a tubular structure. The lesion was then covered with Surgicel (Ethicon, Inc., Somerville, NJ) and fibrin glue. When the Surgicel and fibrin glue were applied, the temporary clip on the distal internal carotid artery was removed for a moment, allowing retrograde blood flow to provide the counterforce necessary to maintain the vessel's tubular structure. An encircling clip was then applied to cover the entire circumference of the lesion. RESULTS: This method required only a short occlusion time for arterial repair, thus helping avoid ischemic complications. The patient awoke with transient hemiparesis, but recovery was prompt. CONCLUSION: This technique is useful for repairing an aneurysmal tear at its base, especially if the tear is large.

Aneurysm, Ruptured↗

Use of the vascular closure staple clip applier for microvascular anastomosis in free-flap surgery.

We report our initial experience using the vascular closure staple clip applier (a nonpenetrating titanium clip applied in an interrupted, everting fashion) for microvascular anastomosis in free-flap surgery. In total, 153 anastomoses were performed in 87 free flaps (174 potential anastomoses) using the vascular closure stapler between October of 1997 and June of 1999. In 66 flaps, both the arterial and venous anastomosis were performed with the clip applier, whereas in 21 flaps only the venous anastomosis was performed using the clips. A total of 146 anastomoses were performed in an end-to-end fashion, and seven were performed end-to-side. Of the 87 flaps there were 53 TRAM flaps, seven bilateral TRAM, five latissimus dorsi, four gastrocnemius, three rectus abdominis, two radial forearm fibula, and four Rubens fat-pad flaps. Seventy flaps were used for breast reconstruction, seven flaps for lower limb reconstruction, four flaps for head and neck reconstruction, and six flaps for chest wall/trunk reconstruction. There were no postoperative anastomotic complications of bleeding, thrombosis, or need for revision (100 percent patency rate), with a significantly reduced time for completion of anastomoses. The clip applier is a safe, reliable method for performing microvascular anastomoses, allowing reduced operating time and possible cost savings in free-flap surgery.

Anastomosis, Surgical↗

Changes of endothelin and calcitonin gene-related peptide during desflurane anesthesia in patients undergoing intracranial aneurysm clipping.

The purpose of this study was to explore whether the changes of plasma concentrations of endothelin (ET) and calcitonin gene-related peptide (CGRP) were possibly involved during desflurane anesthesia in patients undergoing intracranial aneurysm clipping. Forty-five consecutive patients scheduled for selective craniotomy and aneurysm clipping were anesthetized with desflurane in oxygen. Radial arterial catheter was inserted for blood sampling before anesthesia. Serial plasma concentrations of ET and CGRP were measured with radioimmunoassay prior to induction, after dura incision, after clipping of the aneurysm, and 30 minutes after clipping the aneurysm, respectively. Plasma concentrations of ET decreased significantly during the anesthesia and surgery compared with the baseline. An observed decrease in mean CGRP during anesthesia and surgery was not statistically significant. Considering the well-recognized vasoconstrictive effect of ET, it is possible that a decrease in its plasma concentration plays a role in the prevention of the acute cerebral vasospasm during desflurane anesthesia in patients undergoing intracranial aneurysm clipping.

Adolescent↗

Migration of intracranial hemostatic clip into the lumbar spinal canal causing sacral radiculopathy: a case report.

STUDY DESIGN: A case report. OBJECTIVES: A case of spontaneous migration of intracranial hemostatic clip into the lumbar spinal canal causing a sacral radiculopathy and severe low back pain was presented. SUMMARY OF BACKGROUND DATA: Only five cases have been reported in the literature. The first report was described by Oyesiku in 1986; thereafter, four cases have been reported. This serves as the first report clearly describing the relationship between the migrated site of a foreign body and neurologic symptom, as well as achieving a remission of symptom after surgical extirpation. METHODS: A patient who had received hemostatic clips to the aqueductal stenosis 31 years ago presented with low back pain and sacral radiculopathy. Plain radiography, myelography, and subsequent CT revealed that a metal foreign body was located in the subarachnoid space at L4 level. Laminectomy of L4 and extirpation of the foreign body were performed. RESULTS: The foreign body was a hemostatic clip made of cobalt-based alloy that had been applied during the previous intracranial surgery. The clip irritated the adjoined intrathecal nerve root and possibly caused the adhesive arachnoiditis. All symptoms completely disappeared after the extirpation. CONCLUSIONS: An uncommon case of an intracranial hemostatic clip migrating into the lumbar subarachnoid space as well as causing sacral radiculopathy was reported. The surgical extirpation provided an excellent clinical outcome.

Foreign-Body Migration↗

CLIP score as a prognostic indicator for hepatocellular carcinoma: experience with patients in the Middle East.

OBJECTIVE: To assess the prognostic ability of the Cancer of the Liver Italian Programme (CLIP) score and compare it with the Okuda system in patients with hepatocellular carcinoma from the Middle East, where the majority (70%) present with intermediate or advanced stages of the disease and do not receive any tumour-specific treatment. METHODS: The medical records of 145 patients (113 males; mean age, 58.8 +/- 12.2 years) diagnosed with hepatocellular carcinoma over a 6-year period were reviewed and the disease was staged according to the CLIP and Okuda systems. The survival was compared by Kaplan-Meier curves and Cox regression analysis. RESULTS: The overall median survival of patients with hepatocellular carcinoma was 8.3 months (95% confidence interval, 6.6-9.4). The median survivals for CLIP score 0, 1, 2, 3 and 4-6 were 35, 29, 9, 6, and 2 months, respectively; for Okuda stages I, II and III, they were 24, 9 and 4 months, respectively. The CLIP system was judged to be statistically more efficient and consistent than the Okuda in predicting survival in the Cox proportional hazard model. CONCLUSIONS: These data from patients with hepatocellular carcinoma in the Middle East suggest that the CLIP score is more reliable than the Okuda system in predicting survival and can be used efficiently to determine prognosis in patients who present with intermediate or late stage of the disease.

Adult↗

Postoperative multidetector computed tomography angiography after aneurysm clipping: comparison with digital subtraction angiography.

OBJECTIVES: To evaluate the usefulness of multidetector computed tomography angiography (MDCTA) as a noninvasive diagnostic modality for the detection of aneurysm remnants after clipping of intracranial aneurysms. METHODS: Thirty-eight patients who had aneurysm clipping and had undergone MDCTA and digital subtraction angiography (DSA) were enrolled in this study. In 16 of the 38 patients, MDCTA was performed with 16-channel MDCTA, in 20 patients with 4-channel MDCTA, and in 2 with both. Two neuroradiologists evaluated the image quality of MDCTA with a 3-point rating scale and the presence of the residual aneurysm sac with a 5-point rating scale. Receiver operating characteristic analysis was used to measure the diagnostic performance of MDCTA. RESULTS: Forty-nine surgically clipped aneurysms were evaluated in this study. The overall diagnostic accuracy of MDCTA was 88.1% (95% confidence interval: 0.761-0.954). The ability of 16-channel MDCTA to discriminate between surgical clips and parent vessels was superior to that of 4-channel MDCTA (P=0.005). CONCLUSION: Multidetector computed tomography angiography is a valuable noninvasive diagnostic modality for the assessment of aneurysm remnants in patients after aneurysm clipping.

Adult↗

Spontaneous opening of the Filshie clip as a cause of sterilisation failure.

An open Filshie clip is sometimes detected during the evaluation of a case of sterilisation failure. This spontaneous opening of the clip does not need to have been caused by material failure, but may be produced by jamming of the clip what can occur by incorrect squeezing during closure. On superficial observation, the clip will appear to be closed, but it may easily open itself by its spring mechanism when the clip is moved or merely touched. Especially in the teaching situation one should be careful for this lapse.

Equipment Failure↗

Subjective effects of peak clipping and compression limiting in normal and hearing-impaired children and adults.

Despite many advances in hearing-aid signal processing, compression limiting and peak clipping are still used. To date, perceptual studies have been conducted only with adults. The current study was designed to investigate the clarity of peak-clipped and compressed speech for both adults and children. Subjects were 30 normal-hearing and 30 hearing-impaired individuals in three age ranges (7-9, 10-12, and 16-50 years). Stimuli were processed at 60, 70, 75, and 80 dB SPL using peak clipping and at 80 dB SPL using compression limiting. Paired-comparison measures were used to assess the clarity of sentences, and a signal-to-distortion ratio (SDR) based on a measure of coherence between input and output was computed for each condition. For the peak-clipping conditions, there was a decrease in perceived clarity as the input increased from 60 to 80 dB SPL. This perceptual continuum was most apparent for the normal-hearing adults. The normal-hearing 10-12 year olds and the hearing-impaired adults showed a similar, but less pronounced, pattern. In contrast, the remaining three subject groups showed minimal differences in perceived clarity across conditions. Surprisingly, only the two oldest normal-hearing groups showed a clear preference for compression limiting over peak clipping at the highest input level, and only their results were consistent with the pattern of coherence across stimuli. Judgments of clarity by the normal-hearing subjects correlated best with the SDR in the 500-2000-Hz range, while clarity judgments of the hearing-impaired subjects correlated best with the SDR below 1000 Hz.

Adolescent↗

Self-release of CLIP in peptide loading of HLA-DR molecules.

The assembly and transport of major histocompatibility complex (MHC) class II molecules require interaction with the invariant chain. A fragment of the invariant chain, CLIP, occupies the peptide-binding groove of the class II molecule. At endosomal pH, the binding of CLIP to human MHC class II HLA-DR molecules was counteracted by its amino-terminal segment (residues 81 to 89), which facilitated rapid release. The CLIP (81-89) fragment also catalyzed the release of CLIP(90-105) and a subset of other self-peptides, probably by transient interaction with an effector site outside the groove. Thus, CLIP may facilitate peptide loading through an allosteric release mechanism.

Amino Acid Sequence↗

Prognostic factors for survival in patients with early-intermediate hepatocellular carcinoma undergoing non-surgical therapy: comparison of Okuda, CLIP, and BCLC staging systems in a single Italian centre.

BACKGROUND: Several prognostic models have been developed to stage hepatocellular carcinoma (HCC) but there is no general consensus on which is the most reliable. We compared three prognostic indices (Okuda, CLIP, and BCLC scoring systems) in a large series of cirrhotic patients with HCC undergoing non-surgical treatment in terms of their ability to classify patients into different risk groups METHODS: We retrospectively studied 268 Italian patients with HCC. A total of 146 patients were treated with ablation, 132 with percutaneous ethanol injection, and 14 with radiofrequency ablation; 103 underwent transcatheter arterial chemoembolisation and 19 had supportive care alone. Factors determining survival were analysed by univariate and multivariate analysis using the Kaplan-Meier method and Cox proportional hazard regression models. Okuda, CLIP, and BCLC scores evaluated before treatment were applied. RESULTS: Median survival was 25.7 months. In a multivariate analysis, portal vein thrombosis, alpha fetoprotein, total bilirubin, and tumour size were significant predictors of survival. Okuda, CLIP, and BCLC scores were all able to predict survival (p<0.001). They identified two, four, and six risk groups, respectively, with a median survival ranging from 27 to 19 months for Okuda, 30 to 5 months for CLIP, and 43 to 7 months for BCLC. CONCLUSIONS: Both CLIP and BCLC scores were more effective than the Okuda score in stratifying patients into different risk groups with early-intermediate HCC. However, the BCLC scoring system gave a better prediction of prognosis in patients with disease diagnosis at a very early stage.

Adult↗