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Biomedical subjects

S M Klein

Publications and source records attributed to S M Klein.

At least 19 recordsLinked to original sources
PubMed2002

Bilateral continuous paravertebral catheters for reduction mammoplasty.

Surgical procedures of the breast can result in significant postoperative pain. Paravertebral nerve blocks have been used successfully in the management of analgesia after breast surgery but are limited by a single injection. This report describes the use of bilateral paravertebral catheters to provide extended analgesia for reduction mammoplasty. A 48-year-old female underwent bilateral paravertebral catheter placement at thoracic level 3 and local anesthetic injections followed by general anesthesia for elective reduction mammoplasty. She reported no pain following the operation and required no supplemental opioids for pain management during her overnight recovery. This case demonstrates a method for extended bilateral thoracic analgesia. The technique may offer an alternative to traditional outpatient analgesics for reduction mammoplasty.

Analgesia, Epidural↗
PubMed2002

Ambulatory surgery with long acting regional anesthesia.

Ambulatory surgery has grown dramatically in the past 3 decades; however, advances in postoperative pain treatment have not kept pace with the proliferation of outpatient procedures. Two techniques that may offer a solution to part of this problem are long acting peripheral nerve blocks (PNB) and outpatient continuous peripheral nerve blocks (CPNB), but the safety of sending patients home with blocked extremities has also remained controversial. Unfortunately, only a few large, prospective studies have examined this issue directly. Those that have addressed this particular question support the concept that regional anesthesia and discharge with an insensate limb may be done safely. Our group prospectively studied 2,382 long-acting PNB with ropivacaine in both the upper and lower extremity noting a low incidence of block failure, rare use of opioids in the recovery unit and high patient satisfaction. This study also demonstrated a low incidence of accidental injury to the blocked extremity and a rare block complication rate after discharge (0.2%). Only 1 patient in this data set fell while exiting a car. Patients in our study appeared to uniformly protect themselves from further injury despite having a blocked extremity. In conclusion, PNB and perineural catheter techniques are an exciting aspect of ambulatory anesthesia and acute pain management that has undergone rapid development in recent years. Successful application of these techniques will require a substantial educational investment by anesthesiologists and anesthesiologists in training. The rewards in reduced postoperative pain, improved patient satisfaction, and anesthesiologist professional development make this endeavor worthy of our attention.

Ambulatory Surgical Procedures↗
PubMed2001

Two forms of mitochondrial DNA ligase III are produced in Xenopus laevis oocytes.

Full-length cDNAs for DNA ligase IV and the alpha and beta isoforms of DNA ligase III were cloned from Xenopus laevis to permit study of the genes encoding mitochondrial DNA ligase. DNA ligase III alpha and III beta share a common NH(2) terminus that encodes a mitochondrial localization signal capable of targeting green fluorescent protein to mitochondria while the NH(2) terminus of DNA ligase IV does not. Reverse transcriptase-polymerase chain reaction analyses with adult frog tissues demonstrate that while DNA ligase III alpha and DNA ligase IV are ubiquitously expressed, DNA ligase III beta expression is restricted to testis and ovary. Mitochondrial lysates from X. laevis oocytes contain both DNA ligase III alpha and III beta but no detectable DNA ligase IV. Gel filtration, sedimentation, native gel electrophoresis, and in vitro cross-linking experiments demonstrate that mtDNA ligase III alpha exists as a high molecular weight complex. We discuss the possibility that DNA ligase III alpha exists in mitochondria in association with novel mitochondrial protein partners or as a homodimer.

Amino Acid Sequence↗
PubMed2001

Analysis of chimeric receptors shows that multiple distinct functional activities of scavenger receptor, class B, type I (SR-BI), are localized to the extracellular receptor domain.

Scavenger receptor BI (SR-BI) mediates the selective uptake of high-density lipoprotein (HDL) cholesteryl ester (CE), a process by which HDL CE is taken into the cell without degradation of the HDL particle. In addition, SR-BI stimulates the bi-directional flux of free cholesterol (FC) between cells and lipoproteins, an activity that may be responsible for net cholesterol efflux from peripheral cells as well as the rapid hepatic clearance of FC from plasma HDL. SR-BI also increases cellular cholesterol mass and alters cholesterol distribution in plasma membrane domains as judged by the enhanced sensitivity of membrane cholesterol to extracellular cholesterol oxidase. In contrast, CD36, a closely related class B scavenger receptor, has none of these activities despite binding HDL with high affinity. In the present study, analyses of chimeric SR-BI/CD36 receptors and domain-deleted SR-BI have been used to test the various domains of SR-BI for functional activities related to HDL CE selective uptake, bi-directional FC flux, and the alteration of membrane cholesterol mass and distribution. The results show that each of these activities localizes to the extracellular domain of SR-BI. The N-terminal cytoplasmic tail and transmembrane domains appear to play no role in these activities other than targeting the receptor to the plasma membrane. The C-terminal tail of SR-BI is dispensable for activity as well for targeting to the plasma membrane. Thus, multiple distinct functional activities are localized to the SR-BI extracellular domain.

Animals↗
PubMed2001

Ambulatory surgery for multi-ligament knee reconstruction with continuous dual catheter peripheral nerve blockade.

PURPOSE: Major reconstructive surgery of the knee traditionally requires an extended hospital stay for pain management. Continuous peripheral nerve blockade is an alternative method of pain control but is seldom used in the ambulatory setting. This case illustrates the use of lumbar plexus and sciatic nerve peripheral catheters for major knee surgery using intermittent bolus dosing for outpatient analgesia. CLINICAL FEATURES: A 20-yr-old male presented for multi-ligamentous knee reconstruction (posterior collateral ligament and revision anterior collateral ligament and lateral collateral ligament). Anesthesia was managed with a lumbar plexus and a sciatic nerve peripheral catheter and a light general anesthetic. Post-operative analgesia was provided with a 12-hr infusion of 0.2% ropivacaine in an over night recovery care centre. Subsequent catheter dosing was performed as an outpatient, twice a day using 0.2% ropivacaine, 10 ml in each catheter (four injections total). This provided 96 hr of analgesia and low supplemental opioid use. CONCLUSION: The use of a lumbar plexus and sciatic nerve peripheral catheter offered an alternative to conventional pain control that worked well in the ambulatory setting. By providing prolonged unilateral lower limb analgesia, extensive knee surgery was performed that would normally require a hospital stay for pain control. Using a bolus dosing method the risk of local anesthetic complications occurring outside of the hospital with a continuous infusion was minimized.

Adult↗
PubMed2001

Interscalene brachial plexus block with continuous intraarticular infusion of ropivacaine.

Providing intraarticular analgesia with a continuous infusion of local anesthetic via a disposable infusion pump has gained popularity. Despite the prevalence of this technique, data comparing this method of analgesia to conventional regional anesthesia are not available. We present a prospective study that compared a single-dose interscalene block with a single-dose interscalene block plus continuous intraarticular infusion of local anesthetic. Forty patients scheduled for shoulder arthroscopy were entered in this prospective, double-blinded study. All patients received an interscalene brachial plexus block as their primary anesthetic. Patients were randomly assigned to 1 of 2 groups: 1. interscalene block with 1.5% mepivacaine (40 mL) followed by a postoperative intraarticular infusion of 0.5% ropivacaine at 2 mL/h, or 2. interscalene block with 0.5% ropivacaine (40 mL) followed by a postoperative intraarticular infusion of 0.9% saline (placebo) at 2 mL/h. Postoperative infusions were maintained for 48 h. Visual analog scale pain scores and postoperative oxycodone consumption were measured for 48 h. Visual analog scale scores at rest and with ambulation in the Mepivacaine/Intraarticular Ropivacaine group were reduced when compared with the Ropivacaine/Saline group (rest: P = 0.003, ambulation: P = 0.006). Oxycodone consumption was also decreased (28 +/- 21 mg vs 44 +/- 28 mg, P = 0.046), respectively. We conclude that a brachial plexus block with 1.5% mepivacaine and a continuous intraarticular infusion of 0.5% ropivacaine at 2 mL/h provides improved analgesia for minor surgery at 24 and 48 h versus a single-injection interscalene block with 0.5% ropivacaine.

Adult↗
PubMed2001

New murine cell line derived from a spontaneous lung tumor induces paraneoplastic syndromes.

LP07 is a new cell line derived from P07 lung tumor, spontaneously arisen in a BALB/c mouse. LP07 is composed of heterogeneous epithelioid polyhedric cells that proliferate at a slow rate, have low plating efficiency and are unable to grow in soft agar. Only some LP07 cells expressed cytokeratins while most of them were positive for vimentin. Ultrastructure studies showed that LP07 cells established rudimentary intercellular unions, formed glandular-like conducts and presented conspicuous secretory granules, suggesting an epithelial-glandular origin, with neuroendocrine components. Upon injection LP07 cells formed poorly differentiated non-invasive adenocarcinomas, and tumor bearing mice developed leukocytosis, hypercalcemia and cachexia. This tumor cell line constitutes a useful tool to study lung tumor biology and paraneoplastic syndromes.

Adenocarcinoma↗
PubMed2001

Scavenger receptor class B type I affects cholesterol homeostasis by magnifying cholesterol flux between cells and HDL.

Results from several laboratories clearly indicate that expression of scavenger receptor class B type I (SR-BI) enhances the bidirectional flux of cholesterol between cells and lipoproteins. Because the activity of HMG-CoA reductase, the key enzyme in cholesterol biosynthesis, is regulated by cell cholesterol content, we designed experiments to investigate the effect of SR-BI expression on the activity of this enzyme and on net cellular cholesterol mass. In addition, we compared the function of SR-BI with its human homolog, CD36 and LIMPII analogous 1. Our experiments demonstrate that both receptors enhance the flux of unesterified or free cholesterol bidirectionally, down a concentration gradient. Receptor-mediated cholesterol flux can effectively modulate multiple aspects of cellular cholesterol metabolism, including the pool that regulates the activity of HMG-CoA reductase. We also found that constitutive expression of SR-BI alters the steady state level of cellular cholesterol and phospholipid when SR-BI-expressing cells are maintained in medium containing serum lipoproteins. All of these effects are proportional to the level of receptor on the cell surface. These data indicate that the level of SR-BI expression determines both the rate of free cholesterol flux and the steady state level of cellular cholesterol.

Animals↗
PubMed2000

High density lipoprotein phospholipid composition is a major determinant of the bi-directional flux and net movement of cellular free cholesterol mediated by scavenger receptor BI.

The role of high density lipoprotein (HDL) phospholipid in scavenger receptor BI (SR-BI)-mediated free cholesterol flux was examined by manipulating HDL(3) phosphatidylcholine and sphingomyelin content. Both phosphatidylcholine and sphingomyelin enrichment of HDL enhanced the net efflux of cholesterol from SR-BI-expressing COS-7 cells but by two different mechanisms. Phosphatidylcholine enrichment of HDL increased efflux, whereas sphingomyelin enrichment decreased influx of HDL cholesterol. Although similar trends were observed in control (vector-transfected) COS-7 cells, SR-BI overexpression amplified the effects of phosphatidylcholine and sphingomyelin enrichment of HDL 25- and 2.8-fold, respectively. By using both phosphatidylcholine-enriched and phospholipase A(2)-treated HDL to obtain HDL with a graded phosphatidylcholine content, we showed that SR-BI-mediated cholesterol efflux was highly correlated (r(2) = 0.985) with HDL phosphatidylcholine content. The effects of varying HDL phospholipid composition on SR-BI-mediated free cholesterol flux were not correlated with changes in either the K(d) or B(max) values for high affinity binding to SR-BI. We conclude that SR-BI-mediated free cholesterol flux is highly sensitive to HDL phospholipid composition. Thus, factors that regulate cellular SR-BI expression and the local modification of HDL phospholipid composition will have a large impact on reverse cholesterol transport.

Animals↗
PubMed2000

Thoracic paravertebral block for breast surgery.

UNLABELLED: Cosmetic and reconstructive breast augmentation is a frequently performed surgical procedure. Despite advances in medical treatment, surgical intervention is often associated with postoperative pain, nausea, and vomiting. Paravertebral nerve block (PVB) has the potential to offer long-lasting pain relief and fewer postoperative side effects when used for breast surgery. We compared thoracic PVB with general anesthesia for cosmetic breast surgery in a single-blinded, prospective, randomized study of 60 women scheduled for unilateral or bilateral breast augmentation or reconstruction. Patients were assigned (n = 30 per group) to receive a standardized general anesthetic (GA) or thoracic PVB (levels T1-7). Procedural data were collected, as well as verbal and visual analog pain and nausea scores. Verbal postoperative pain scores were significantly lower in the PVB group at 30 min (P = 0.0005), 1 h (P = 0.0001), and 24 h (P = 0.04) when compared with GA. Nausea was less severe in the PVB group at 24 h (P = 0.04), but not at 30 min or 1 h. We conclude that PVB is an alternative technique for cosmetic breast surgery that may offer superior pain relief and decreased nausea to GA alone. IMPLICATIONS: Paravertebral nerve block has the potential to offer long-lasting pain relief and few postoperative side effects when used for breast surgery. We demonstrated that paravertebral nerve block, when compared with general anesthesia, is an alternative technique for breast surgery that may offer pain relief superior to general anesthesia alone.

Adult↗
PubMed2000

Thromboelastography as a perioperative measure of anticoagulation resulting from low molecular weight heparin: a comparison with anti-Xa concentrations.

UNLABELLED: Low molecular weight heparin (LMWH) is commonly used to prevent postoperative thromboembolism. Currently, there is no convenient test to measure the degree of anticoagulation from LMWH. This prospective study examines the relationship of thromboelastography and serum anti-Xa concentration in patients treated with enoxaparin. Twenty-four adult patients scheduled for orthopedic surgery using epidural anesthesia were enrolled. Epidural catheters were removed the morning after surgery before the commencement of subcutaneous enoxaparin 30 mg twice daily. Venous blood samples were obtained at 1) the induction of anesthesia (baseline), 2) immediately before the third dose of enoxaparin postoperatively (Day 2-trough), 3) 4 h after the third dose postoperatively (Day 2-peak), and 4) immediately before the fifth dose postoperatively (Day 3-trough). Whole blood samples were obtained for thromboelastography, activated clotting time, and anti-Xa level analyses at each of the four time intervals. At the four sample intervals, the r time (mean +/- SEM). (20 +/- 1, 25 +/- 2, 51 +/- 6, 31 +/- 3 mm) and the k time (9 +/- 0. 7, 12 +/- 1, 27 +/- 5, 14 +/- 2 mm) of the thromboelastograph were significantly correlated with the expected peak and trough levels of LMWH and serum anti-Xa levels (P: < 0.05). At the Day 3-trough, thromboelastograph r times exceeded the normal range in 6 of 25 patients (25%). Prolongation of r time and k time on postoperative Day 3 may indicate an exaggerated response to LMWH. Thromboelastography is a test that could potentially correlate with the degree of anticoagulation produced by low molecular weight heparin. IMPLICATIONS: Thromboelastography is a test that could potentially correlate with the degree of anticoagulation produced by low molecular weight heparin. The r time from the thromboelastogram correlates with serum anti-Xa concentration.

Aged↗
PubMed2000

Interscalene brachial plexus block with a continuous catheter insertion system and a disposable infusion pump.

Continuous interscalene brachial plexus blockade traditionally requires a hospital stay for local anesthetic infusion, and achieving consistent catheter insertion may be difficult. Incorporating long-acting pain relief from a continuous peripheral nerve block, with a reliable method of catheter insertion, and a self-contained infusion system would be a valuable asset for short-stay care. We compared the efficacy of single injection interscalene brachial plexus blockade to a continuous peripheral nerve block, with an insulated Tuohy system and a disposable infusion pump. Forty adult patients scheduled for open rotator cuff repair were entered in this randomized, double-blinded, placebo-controlled study. Patients received an interscalene brachial plexus blockade and a continuous peripheral nerve catheter as their primary anesthetic and then, were assigned to receive one of two different postoperative infusions: either 0.2% ropivacaine at 10 mL/h via a disposable infusion pump or normal saline at 10 mL/h via a disposable infusion pump (n = 18-20 per group). Visual analog pain scores and postoperative morphine consumption were measured for 24 h. The ropivacaine group showed less pain than the placebo group (P: = 0.0001) between 12 and 24 h after the initial injection of local anesthetic. In addition, initial interscalene blockade was successful in all patients and all redosed catheters were functional after 24 h with the continuous catheter insertion system. We conclude that it is possible to achieve a high rate of successful catheter placement and analgesia by using the continuous catheter insertion system and a disposable infusion pump in the ambulatory setting. This method of analgesia may offer improved pain relief after outpatient rotator cuff repair.

Adolescent↗
PubMed2000

Effect of tyrosine kinase inhibition on sepsis-induced vascular hyporesponsiveness, inos mrna expression and NF-kappaB nuclear translocation in rats.

The dependence of the critical steps in the sepsis cascade on the transcription factor NF-kappaB andation to nitric oxide (NO) production are controversial. Tyrosine kinase (TK) is involved in several of the steps, and TK inhibitors (TKI) inhibit lipopolysaccharide (LPS)-induced vascular hyporesponsiveness in septic animals. We studied the relationship of TK inhibition, hemodynamics, vascular contraction, iNOS mRNA expression and NF-kappaB translocation in anesthetized endotoxic rats. The TKI AG556 (2.5 mg/kg i.p.), given 1 h before i.v. endotoxin (LPS) resulted in attenuation of early (<60 min) and late (60-120 min) hypotension, improved contraction of mesenteric arteries to norepinephrine 4 h after LPS, and attenuated tissue iNOS mRNA expression. LPS-induced NF-kappaB translocation was unaffected. The observed dissociation between NF-kappaB translocation and the salutary effect of TKI in vivo and ex vivo and its effect on iNOS mRNA expression suggest that although NF-kappaB may be involved in the sepsis cascade, it may not be essential for some of the molecular and vascular consequences of septic shock.

Animals↗
PubMed1999

Comparison of class B scavenger receptors, CD36 and scavenger receptor BI (SR-BI), shows that both receptors mediate high density lipoprotein-cholesteryl ester selective uptake but SR-BI exhibits a unique enhancement of cholesteryl ester uptake.

Scavenger receptor BI (SR-BI) mediates the selective uptake of high density lipoprotein (HDL) cholesteryl ester (CE), a process by which HDL CE is taken into the cell without internalization and degradation of the HDL particle. The biochemical mechanism by which SR-BI mediates the selective uptake of HDL CE is poorly understood. Given that CE transfer will occur to some extent from HDL to protein-free synthetic membranes, one hypothesis is that the role of SR-BI is primarily to tether HDL close to the cell surface to facilitate CE transfer from the particle to the plasma membrane. In the present study, this hypothesis was tested by comparing the selective uptake of HDL CE mediated by mouse SR-BI (mSR-BI) with that mediated by rat CD36 (rCD36), a closely related class B scavenger receptor. Both mSR-BI and rCD36 bind HDL with high affinity, and both receptors mediate HDL CE selective uptake. However, SR-BI mediates selective uptake of HDL CE with a 7-fold greater efficiency than rCD36. HDL CE selective uptake mediated by rCD36 is dependent on HDL binding to the receptor, since a mutation that blocks HDL binding also blocks HDL CE selective uptake. These data lead us to hypothesize that one component of HDL CE selective uptake is the tethering of HDL particles to the cell surface. To explore the molecular domains responsible for the greater efficiency of selective uptake by mSR-BI, we compared binding and selective uptake among mSR-BI, scavenger receptor BII, and various chimeric receptors formed from mSR-BI and rCD36. The results show that the extracellular domain of mSR-BI is essential for efficient HDL CE uptake, but the C-terminal cytoplasmic tail also has a major influence on the selective uptake process.

Animals↗
PubMed1998

Lumbar plexus and sciatic nerve block for knee arthroplasty: comparison of ropivacaine and bupivacaine.

PURPOSE: Information about the onset time and duration of action of ropivacaine during a combined lumbar plexus and sciatic nerve block is not available. This study compares bupivacaine and ropivacaine to determine the optimal long-acting local anaesthetic for lumbar plexus and sciatic nerve block in patients undergoing total knee arthroplasty. METHODS: Forty adult patients scheduled for unilateral total knee arthroplasty, under lumbar plexus and sciatic block were entered into this double-blind randomized study. Patients were assigned (20 per group) to receive lumbar plexus block using 30 ml of local anaesthetic and a sciatic nerve block using 15 ml of local anaesthetic with either bupivacaine 0.5% or ropivacaine 0.5%. All solutions contained fresh epinephrine in a 1:400,000 concentration. Every one minute after local anaesthetic injection, patients were assessed to determine loss of motor function and loss of pinprick sensation in the L1-S1 dermatomes. The time to request first analgesic was documented from the PCA pump. This time was used as evidence of block regression. RESULTS: Blocks failed in four patients in each group. The mean onset time of both motor and sensory blockade was between 14 and 18 min in both groups. Duration of sensory blockade was longer in the bupivacaine group, 17 +/- 3 hr, than in the ropivacaine group, 13 +/- 2 hr (P < 0.0001). CONCLUSION: We conclude that bupivacaine 0.5% and ropivacaine 0.5% have a similar onset of motor and sensory blockade when used for lumbar plexus and sciatic nerve block. Analgesic duration from bupivacaine 0.5% was prolonged by four hours compared with an equal volume of ropivacaine 0.5%.

Adult↗