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Powered phlebectomy (TriVex) in treatment of varicose veins.

This study assesses the operation of transilluminated powered phlebectomy for removal of varicose veins. It was a prospective, noncomparative, multicenter, pilot study designed to evaluate the safety and efficacy of the powered varicose vein extractor for ablation of primary varicose veins. A total of 114 patients (117 limbs) were recruited from four centers in Europe and four centers in the United States. Safety of the varicose vein extractor was evaluated by recording nature and severity of all adverse events and complications. Efficacy was assessed by the patient, an independent study nurse, and the surgeon. Operations were performed under general, spinal, or epidural anesthesia and tumescent anesthesia was added with infusions of dilute lidocaine with epinephrine. Transillumination was achieved with a specially designed cannula, and the vein extraction was done using a vein resector with a rotating tubular inner cannula encased in a stationary outer sheath dissector. Demographic information regarding the 28 men and 89 women included in the study are detailed. Eighty-four percent of the limbs were CEAP class 2 with only 16% being in classes 3 and 4. Accompanying greater saphenous vein stripping was done in 67% of the limbs in the United States and 88% in those in Europe. Proximal ligation only was used in one limb in the United States and eight in Europe. The study showed that transilluminated powered phlebectomy used in varicose vein removal is swift and efficacious with a conservation of operating time and the results being satisfactory to the patient and clinician alike.

Female↗

Differential effects of dopamine agonists on acoustically and electrically elicited startle responses: comparison to effects of strychnine.

This study sought to determine where drugs that are known to alter sensorimotor reactivity measured with the acoustic startle reflex ultimately act within the acoustic startle pathway. To do this, startle was elicited either acoustically or electrically within various nuclei believed to comprise the acoustic startle pathway. Direct infusion of serotonin into the subarachnoid space of the lumbar spinal cord increased acoustic startle and startle elicited electrically through the ventral cochlear nucleus (VCN) to a comparable degree. Subconvulsant doses of strychnine increased startle elicited acoustically or electrically through either the VCN or the nucleus reticularis pontis caudalis (RPC), pointing to a spinal locus of action of strychnine after systemic administration. In marked contrast, the dopamine agonists d-amphetamine and apomorphine consistently increased acoustic startle but actually depressed startle elicited electrically through the VCN or the RPC. These later results suggest that dopamine agonists increase sensorimotor reactivity measured with acoustic startle by acting on sensory rather than motor parts of the reflex arc.

Acoustic Stimulation↗

Alteration by urethane of glutamatergic control of micturition.

The i.v. administration of MK-801 (0.001-3 mg/kg), a non-competitive NMDA receptor antagonist, did not alter reflex bladder activity in unanesthetized decerebrate rat recorded during fast infusion (0.21 ml/min) cystometry or under isovolumetric conditions, but did depress reflex bladder contractions in doses between 0.1 and 3 mg/kg i.v. in the urethane-anesthetized (1.2 g/kg s.c.) intact rat during fast infusion cystometry. The ED50 and the dose to produce maximal inhibition in urethane-anesthetized intact rats were 0.25 mg/kg and 3 mg/kg i.v., respectively. During slow infusion (0.04 ml/min) cystometry, in unanesthetized decerebrate rats, MK-801 (0.1-1 mg/kg i.v. or 6-60 micrograms i.t.) decreased by 12-44% the micturition volume threshold (VT) but did not change the amplitude and duration of the bladder contractions. The administration of a larger i.t. dose (60 micrograms) of MK-801 produced no further decrease in VT but decreased the amplitude of bladder contractions by 24%. External urethral sphincter electromyogram activity was reduced or abolished by MK-801 (0.01-3 mg/kg i.v.) in both unanesthetized decerebrate and urethane-anesthetized intact rats with ED50 of 0.12 mg/kg and 0.05 mg/kg, respectively. These results indicate that NMDA receptors play an important role in both facilitatory and inhibitory central neural control of voiding function and that there is a significant interaction between urethane anesthesia and NMDA glutamatergic transmission. Thus, even though urethane anesthesia has been useful for studying the physiological characteristics of the micturition reflex, it seems inappropriate for analyzing the normal transmitter role of glutamic acid in reflex voiding.

Analysis of Variance↗

Prodrug of proline analogue reduces hypoxic pulmonary hypertension in rats.

A polymeric prodrug of the proline analogue cis-4-hydroxy-l-proline (CHOP), poly(ethylene glycol)-lysine-CHOP or CHOP-PEG, prevents hypoxic pulmonary hypertension in rats by inhibiting collagen accumulation. A more potent prodrug was synthesized by increasing the loading of CHOP on the carrier from 14 to 100%. Pulmonary antihypertensive efficacy and pharmacokinetics are described in the rat hypoxia model. The antihypertensive effect of CHOP-PEG in rats exposed to 10% O2 for 7d showed approximately 2 x 10(2)-fold greater potency than monomeric CHOP. Routes of administration were compared to determine the lowest dose of CHOP-PEG that reduced right ventricular pressure approximately 50% vs. untreated hypoxic controls at 7d. Total doses required were: continuous s.c. via an osmotic minipump, 0.8 mg; single s.c., 10mg; single i.v., 40 mg; and single intratracheal 90 mg. Efficacy for at least 7d postdosing in pre-established pulmonary hypertension was shown. Using an ELISA-based assay, biphasic i.v. and stable s.c. pharmacokinetic profiles were observed 72 h after single injections and 7d after continuous s.c. infusion. Thus, this CHOP-PEG formulation prevents and reverses chronic hypoxic pulmonary hypertension in rats, is most effective when given by continuous s.c. infusion, and has favorable pharmacokinetic properties. Potent inhibitors of fibrosis appear to be promising agents in treating pulmonary hypertension and possibly other fibrosing diseases.

Animals↗

Use of antisense oligodeoxynucleotides to inhibit expression of glutamate transporter subtypes.

Antisense ODN are highly effective tools to selectively inhibit synthesis of glutamate transporter subtypes. They have been used to evaluate the biology of individual transporter subtypes in vivo and in vitro. Appropriate use of antisense ODN, however, requires a number of important controls to validate the specificity of their effects. Ultimately, the efficacy at inhibiting the synthesis of transporters proteins reflects several variables: the actual efficacy of the antisense to directly inhibit synthesis, the rate of degradation of the ODN, the rate of intracellular penetration of the ODN, the rate of new protein synthesis for the transporter subtype, and the actual penetration of the ODN into CNS tissue. The methods described in this chapter will help one to optimize each of these parameters.

ATP-Binding Cassette Transporters↗

The best route.

Explore the source record for details and available documents.

Female↗

Newer techniques of labor analgesia.

In maternity units in which central neuraxial techniques are frequently used, newer methods of epidural drug delivery (continuous infusion, patient-controlled) are well established and combined spinal-epidural analgesia is commonly used. Continuous spinal analgesia has reemerged as a useful approach after accidental dural puncture. Lumbar sympathetic block has been revisited and the safety of paracervical nerve block improved. The analgesic properties of systemic opioid in labor are poor, but PCIA at least has psychological benefits and allows rapid drug titration. PCIA is again under investigation because of the potent antinociceptive effects of the short-acting mu-opioid agonist, remifentanil. The premixing of nitrous oxide and a subanesthetic concentration of volatile anesthetic for patient-controlled administration has been tested under control of midwifery staff and without direct medical supervision.

Analgesia, Epidural↗

Remifentanil versus propofol as adjuncts to regional anesthesia. Remifentanil 3010 Study Group.

STUDY OBJECTIVE: To compare the safety and efficacy of remifentanil and propofol as adjuncts to regional anesthesia in patients undergoing orthopedic or urogenital surgery. DESIGN: Prospective, randomized study. SETTING: Multicenter university hospitals. PATIENTS: 107 ASA physical status I, II, and III adult patients who underwent orthopedic or urogenital surgery with axillary, ankle, or spinal block. INTERVENTIONS: Patients were randomized to receive either an infusion of remifentanil 0.2 microg/kg/min or propofol 100 microg/kg/min 5 minutes before nerve block placement. The infusions were decreased by 50% on block completion, increased by 50% for patient discomfort, and decreased by 50% for hypoventilation (< 8 breaths/min) or hemodynamic instability. MEASUREMENTS AND MAIN RESULTS: Pain, discomfort, anxiety, and sedation were assessed by both patient and investigator. Vital signs and adverse events were recorded. Fewer patients in the remifentanil group experienced pain during block placement (6%), and were oversedated (7%) than patients in the propofol group (23% and 26%, respectively; p < 0.05). Hypoventilation during and after block placement (21% and 25%, respectively) and nausea and vomiting during and after block placement (60% and 21%, respectively) were more common in the remifentanil group than in the propofol group (0% and 3%; 17% and 6%, respectively; p < 0.05). The incidence of hypoventilation in remifentanil-treated patients was higher in patients over 65 years of age (p < 0.05), but was transient, resolving within minutes of discontinuing the infusion. CONCLUSIONS: At the doses studied, remifentanil was more effective than propofol in minimizing pain without producing excessive sedation. Remifentanil was associated with more transient respiratory depression and short-term nausea. Our findings indicate that the initial remifentanil rate should be 0.1 microg/kg/min (50% lower than the study's initial rate) and should be further decreased an additional 50% in the elderly to minimize adverse effects.

Adult↗

Ketamine patient-controlled analgesia for dysesthetic central pain.

STUDY DESIGN: Case report. OBJECTIVES: To describe the first use of intravenous (IV) ketamine as the sole agent in a patient-controlled analgesic delivery system (ie PCA) in a patient with cervical syringomyelia. SETTING: A tertiary-care university teaching hospital in New York City. METHODS: A 41-year-old tetraplegic female on high-dose opioids suffering from intractable dysesthetic central pain received her best pain relief from a low-dose ketamine infusion after failing trials with multiple neuropathic medications. After several weeks of titrating her infusion rate up and down, she was switched to an IV ketamine PCA device. RESULTS: The patient was maintained on an IV ketamine PCA for almost 1 year under the following settings: 2.7 mg/h basal rate; 2.7 mg/h demand dose; 15 min lockout period. Although she continues to report some pain, it has dramatically decreased since the ketamine PCA was instituted, enabling us to significantly reduce her opioid dosage. CONCLUSIONS: Ketamine PCA may be a viable treatment option in patients suffering from intractable central pain. The rationale for this treatment, along with dosing guidelines and possible drawbacks, is discussed.

Adult↗

Preoperative spinal hydrodynamics versus clinical change 1 year after shunt treatment in idiopathic normal pressure hydrocephalus patients.

Nineteen consecutive cases treated for idiopathic normal pressure hydrocephalus (iNPH) with ventriculo-peritoneal shunts were clinically followed prospectively. Change in clinical state one year after shunt surgery was assessed as change on a 15-3 score NPH Grade Scale. Preoperative spinal hydrodynamics were assessed using a constant-rate lumbar infusion test. The pressure recordings were stored as raw data files and analysed retrospectively with regard to the mean cerebrospinal fluid pressure (CSFP), as well as mean CSFP wave amplitudes. Changes in NPH score 1 year after shunt surgery correlated significantly with the levels of single CSFP wave amplitudes, but not with the lumbar resistance to CSF outflow (R(out)). Mean CSFP wave amplitude was thus, in this cohort, a better predictor of clinical change one year after shunt treatment than R(out).

Aged↗

Role of the NMDA receptor complex in DMCM-induced seizure in mice.

We investigated the role of the NMDA receptor complex in DMCM (methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate)-induced seizures in mice. The seizure threshold of DMCM was evaluated using an i.v. infusion technique. Pretreatment with the non-competitive NMDA receptor antagonist MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d) cycloheptan-5,10-imine maleate) or phencyclidine (PCP) significantly increased the seizure threshold for DMCM. Furthermore, the seizure threshold of DMCM was increased by intracerebroventricular (i.c.v.), but not intrathecal (i.t.), pretreatment with MK-801. Moreover, 7-chlorokynurenic acid, a glycine site antagonist, also increased the seizure threshold of DMCM, whereas ifenprodil, a non-competitive polyamine site antagonist, did not. These findings indicate that the ion-channel binding site and the glycine binding site on the NMDA receptor complex in the brain may be involved in the expression of seizures induced by DMCM.

Animals↗

Efficacy and technical complications of long-term continuous intraspinal infusions of opioid and/or bupivacaine in refractory nonmalignant pain: a comparison between the epidural and the intrathecal approach with externalized or implanted catheters and infusion pumps.

OBJECTIVE: To compare efficacies, failure rates, and technical complication rates of intraspinal treatments in patients with "refractory" nonmalignant pain conditions in relation to the approach (epidural/intrathecal), the drug (opioid/opioid-bupivacaine or bupivacaine), and the type of system used (externalized/internalized). In these comparisons, recent data from a companion paper (Nitescu et al., Clin J Pain 1998;14:17-28) were used as a reference to be compared with data from a literature review of different intraspinal treatment modalities in nonmalignant pain. DESIGN: Prospective, cohort, nonrandomized, consecutive trial. SETTING: Tertiary care center, institutional practice, hospitalized, and ambulatory care. PATIENTS: Five groups according to treatment modality: (a) externalized, long-term intrathecal nylon catheters, connected to external, electronic infusion pumps (companion paper), n = 90; (b) internalized, long-term intrathecal catheters (Silastic) connected to implanted SynchroMed pumps, n = 330 (literature review); (c) externalized, "short-term" epidural catheters for "temporary" infusions, n = 565 (literature review); (d) externalized, long-term epidural catheters, n = 50 (literature review); (e) internalized, long-term epidural catheters, n = 111, connected to implanted systems: Port-A-Cath injection ports, n = 58; Infusaid pumps, n = 46; and SynchroMed pumps, n = 7 (literature review). INTERVENTIONS: In reviewing the literature, we found 21 studies that reported on the intraspinal (epidural or intrathecal) administration of opioids with or without local anesthetics (usually bupivacaine). These studies were analyzed with respect to the rates of the variables satisfactory pain relief (efficacy), failures, and technical complications. A rate is the number of observations of a variable divided by the number of patients or the number of catheters or infusion systems, as logically indicated (e.g., the numbers of complications, such as epidural abscess and meningitis, were related to the number of patients and those of catheter occlusion or leakage to the number of the catheters). The variables were expressed as the means of the rates of a variable from studies belonging to various treatment modalities: approach (epidural vs. intrathecal), duration (short vs. long term), drugs administered intraspinally (opioid vs. opioid and/or local anesthetic), and type of infusion system (externalized vs. internalized). Further, the sums of all observations of one variable in different studies with various treatment modalities were related to the corresponding sums of the patients (alternatively, catheters or implanted devices). The proportions of these sums were tested for significance in relation to treatment modality. MAIN OUTCOME MEASURES: Comparative rates of successful intraspinal treatment and its failures and complications. RESULTS: (a) The intrathecal approach, compared with the epidural approach, was associated with higher rates of satisfactory pain relief for both externalized (86/90, 95% vs. 17/40, 42.5%, p < .0001) and internalized (295/336, 89% vs. 33/56, 59%, p < .0001) catheters; higher rates of treatment failures with externalized epidural catheters than with internalized intrathecal catheters (24/47, 51%, vs. 36/338, 11%, p < .0001); lower rates of treatment failures with internalized intrathecal catheters than with internalized epidural catheters (36/338, 11% vs. 29/76, 38%, p < .0001); higher rates of system replacement with internalized epidural catheters than with internalized intrathecal catheters (23/32, 72% vs. 6/49, 12%, p < .0001; higher rates of system removal with internalized epidural catheters than with internalized intrathecal catheters (22/49, 45% vs. 5/49, 10%, p < .001); higher rates of catheter-related complications with epidural than with intrathecal catheters (dislodgement 13/126, approximately 10% vs. 6/150, 4%, p < .05; leakage 5/51, approximately 10% vs. 1/116, 0.9%, p < .05; obstruction 2

Anesthetics, Local↗

Amphotericin B and imidazole therapy for coccidioidal meningitis in children.

Coccidioidal meningitis is a fatal form of Coccidioides immitis infection. Amphotericin B (AMB) therapy has reduced mortality but is itself toxic, and experience with it in very young children is meager. We are treating six children for coccidioidal meningitis diagnosed at 19 to 74 months of age. All had acute hydrocephalus and ventriculitis. The first four patients were initially treated with AMB but were changed to imidazole therapy (miconazole and ketoconazole). In the last two patients therapy was begun with the imidazoles. Ommaya reservoirs for cisternal therapy have been of limited usefulness. AMB therapy has been limited by local and systemic toxicity and by failure in one case. All children have improved with 15 to 22 mg oral ketoconazole per kg per day and 3 to 5 mg intraventricular miconazole for instillation therapy, including those with noncommunicating hydrocephalus in whom the intraventricular drug does not reach the basilar cisterns. Peak concentrations of ketoconazole in ventricular fluid were 0.08 to 5.6 micrograms/ml. Shunt obstruction and bacterial superinfections have been the major causes of morbidity. Imidazole therapy of coccidioidal meningitis may be more effective than is AMB in young children, and it offers the advantages of fewer side effects and not requiring intrathecal or cisternal administration.

Amphotericin B↗