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Changes in venous blood lactate, venous blood gases, and somatosensory evoked potentials after tourniquet application.

The effects of inflation of a 7-cm tourniquet applied to the upper arm of eight volunteers on venous lactate, venous blood gases, and ulnar nerve somatosensory evoked potentials (SSEPs) were investigated. The inflation pressure was 100 mmHg over the systolic pressure. Venous blood samples for lactate and blood gas determinations were withdrawn before tourniquet inflation; immediately and at 2, 5, 10, 15 min after tourniquet deflation; and additionally at 30, 45, and 60 min after deflation in the last four volunteers. SSEP stimulating surface electrodes were placed over the ulnar nerve at the wrist. Recording electrodes were placed over the ipsilateral ulnar groove of the elbow, Erb's point, and on the contralateral cortex. Averaged responses were acquired before inflation of the tourniquet, every 5-10 min during tourniquet inflation, and every 5-10 min for 45-60 min after tourniquet deflation. The tourniquet was inflated for 36 +/- 11 min. After deflation of the tourniquet, postdeflation pain and paresthesias were felt by five volunteers; these occurred at 30-120 s after deflation and lasted for 75-120 s. The postdeflation pains were characterized as burning, cramping, paresthesias, buzzing, or severe expansion of the hand. The venous blood lactate levels were significantly elevated for 10 min, and the time course of its change did not correlate with reperfusion pain. The PO2 and O2Hb saturation in venous blood were significantly elevated for 10-15 min after deflation. The elevated lactate and PO2 levels in the presence of a restored blood flow probably result from continued anaerobic muscle metabolism secondary to capillary closure from the tourniquet-induced ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Ulnar nerve pressure: influence of arm position and relationship to somatosensory evoked potentials.

BACKGROUND: Although the ulnar nerve is the most frequent site of perioperative neuropathy, the mechanism remains undefined. The ulnar nerve appears particularly susceptible to external pressure as it courses through the superficial condylar groove at the elbow, rendering it vulnerable to direct compression and ischemia However, there is disagreement among major anesthesia textbooks regarding optimal positioning of the arm during anesthesia. METHODS: To determine which arm position (supination, neutral orientation, or pronation) minimizes external pressure applied to the ulnar nerve, we studied 50 awake, normal volunteers using a computerized pressure sensing mat. An additional group of 15 subjects was tested on an operating table with their arm in 30 degrees, 60 degrees, and 90 degrees of abduction, as well as in supination, neutral orientation, and pronation. To determine the onset of clinical paresthesia compared to the onset and severity of somatosensory evoked potential (SSEP) electrophysiologic changes, we studied a separate group of 16 male volunteers while applying intentional pressure directly to the ulnar nerve. Data are presented as mean (median; range). RESULTS: Supination minimizes direct pressure over the ulnar nerve at the elbow (2 mmHg [0; 0-23]; n = 50), compared with both neutral forearm orientation (69 mmHg [22; 0-220]; P < 0.0001), as well as pronation (95 mmHg [61; 0-220]; P < 0.0001). Neutral forearm orientation also results in significantly less pressure over the ulnar nerve compared to pronation (P < or = 0.04). The estimated contact area of the ulnar nerve with the weight-bearing surface was significantly (P < 0.0001) smaller in the supine position (2.2 cm2 [0.5; 0-9]; n = 50) compared with both neutral orientation (5.5 cm2 [5.0; 0-13]) and pronation (5.8 cm2 [6; 0-12]). With the forearm in neutral orientation, ulnar nerve pressure decreased significantly (P < or = 0.01; n = 15) as the arm was abducted at the shoulder from 0 degrees to 90 degrees. In the 16 male subjects tested, notable alterations in ulnar nerve SSEP signals (decrease > or = 20% in N9-N9' amplitude) were detected in 15 of 16 awake males during application of intentional pressure to the ulnar nerve. However, eight of these subjects did not perceive a paresthesia, even as SSEP waveform amplitudes were decreasing 23-72%. Two of these eight subjects manifested severe decreases in SSEP amplitude (> or = 60%). CONCLUSIONS: Extrapolating these results to the clinical setting, the supinated arm position is likely to minimize pressure over the ulnar nerve. With the forearm in neutral orientation, pressure over the ulnar nerve decreases as the arm is abducted between 30 degrees and 90 degrees. In addition, up to one half of male patients may fail to perceive or experience clinical symptoms of ulnar nerve compression sufficient to elicit SSEP changes.

Adult↗

Dose-finding study of paclitaxel and carboplatin in patients with advanced non-small cell lung cancer.

This dose-finding study was designed to determine the maximum tolerated dose (MTD), efficacy and toxicity of combined paclitaxel and carboplatin in 35 previously untreated patients with advanced non-small cell lung cancer (NSCLC). Paclitaxel was given as a 3-h infusion at escalating dose levels (100-250 mg/m2) immediately followed by carboplatin as a 30-min infusion (325 or 350 mg/m2) every 3 weeks. The dose-limiting toxicity, paresthesia, occurred at the highest dose level, therefore the recommended dose was established one level below (paclitaxel 225 mg/m2 with carboplatin 325 mg/m2). Neutropenia was the most common hematotoxicity; dose dependency was not apparent. Two patients, at different dose levels, had febrile neutropenia. Thrombocytopenia was rare. Non-hematological toxicities grade 3 or higher included infection, anorexia, alopecia and paresthesia. One patient had a hypersensitivity reaction (transient hypotension). The overall response rate was 23% and median survival time was 7.5 months. Promising activity and acceptable toxicity supports the development of this combination as a useful chemotherapeutic option in advanced NSCLC.

Adult↗

Painful polyneuropathy in patients with and without diabetes: clinical, neurophysiologic, and quantitative sensory characteristics.

OBJECTIVES: To study pain characteristics and peripheral nerve involvement in patients with painful diabetic and nondiabetic polyneuropathy in comparison with patients with non-painful polyneuropathy. PATIENTS AND METHODS: Fifty-five patients with polyneuropathy (37 with painful polyneuropathy, of whom 19 had diabetes and 18 had no diabetes; and 18 with painless polyneuropathy of different etiologies) were examined clinically using quantitative sensory tests and neurophysiology. Pain intensity and characteristics were analyzed by daily ratings on a 10-step verbal scale and by a questionnaire. RESULTS: Most patients experienced pain of more than one character. There was no clear difference in character or duration of pain between patients with and without diabetes. The mean value of the daily rating of pain intensity showed that pain was more severe in the evenings than in the mornings and that diabetic patients reported worse pain than nondiabetic patients. Thirty-two of the 37 patients with pain had paresthesias and/or dysesthesias, whereas only 7 of 18 patients without pain had paresthesias. Pain was always located in the feet, and, in most patients, also in the lower part of the legs. Some patients also experienced pain in the hands. Tactile sensibility, measured by quantitative tests, was more affected in both diabetic and nondiabetic patients with painful polyneuropathy compared with patients without pain (p = 0.02). Temperature, pain, and vibratory sensibility were equally affected in all patient groups. Nerve conduction velocity, amplitudes, and distal latency were equally affected in the pain group as compared with the control group, indicating that both thin and thick nerve afferents are affected in patients with painful as well as non-painful polyneuropathy and that etiology has no clear impact on nerve involvement. CONCLUSIONS: Neuropathy pain was always located in the feet and more severe in diabetic patients compared with patients with neuropathy pain of other etiologies. The authors also found evidence for a greater tactile sensibility involvement in patients with neuropathy pain, irrespective of etiology, whereas other quantitative sensibility and neurography parameters were equally affected in all patient groups.

Adult↗

Computed tomography in the "thalamic syndrome".

A 50-year-old man was evaluated for paresthesia and pain affecting the left side of his body and face. The paresthesia and pain developed and progressed concomitantly with a resolving left hemiparesis attributed to a lacunar infarct occurring 5 months prior to admission. Computed tomography (CT) revealed a discrete lesion in the region of the dorsomedial margin of the nucleus ventralis posterior. To the many pathological reports localizing the lesion of the "thalamic syndrome," one can now add the CT verification of the lesion in vivo.

Brain Diseases↗

Complete response to twice-a-day interferon-beta with standard interferon-alpha therapy in acute hepatitis C after a needle-stick.

A 25-year-old male physician with acute hepatitis C after needle-stick injury was treated with combination therapy including twice-a-day interferon-beta (IFN-beta) and standard interferon-alpha (IFN-alpha). The infecting strain was of genotype 1b. Pretreatment hepatitis C virus (HCV) RNA levels were high. Because severe paresthesias occurred with initial daily administration of 5 million units (MU) of lymphoblastoid IFN-alpha, the dose was reduced to 3 to 6 MU of IFN-alpha2b three times a week. However, HCV RNA was not cleared from serum after 20 weeks of standard IFN-alpha2b treatment. A 4-week course with IFN-beta, at the dosage of 3 MU twice daily i.v. drip, was then started and followed by an 18-week course with IFN-alpha2b, 6 MU thrice weekly. After IFN-beta treatment, HCV RNA was cleared from serum without severe adverse effects, including paresthesias. Total amounts of IFN administered were 20 MU of lymphoblastoid IFN-alpha, 648 MU of IFN-alpha2b, and 252 MU of IFN-beta. Complete response and avoidance of chronic HCV infection were achieved. Thus, combination therapy with twice-a-day IFN-beta and standard IFN-alpha was effective in treating an acute hepatitis C patient with a high viral load and sensitivity to adverse effects of high-dose IFN-alpha.

Acute Disease↗

Personal experiences and algorithm of endoscopically assisted subperiosteal face lift in orientals for 5 years.

Orientals are anatomically distinct from Caucasians and are characterized by a thick dermis, a Mongoloid slant of the palpebral fissure, a relatively prominent zygoma and mandible angle, and a relatively flat nose. Given these characteristics, it was believed that the subperiosteal face lift was not suitable for Orientals. However, at our institution, endoscopically assisted subperiosteal face lifts were performed from May of 1994 to October of 1998 on 236 patients; variable pitfalls, as well as satisfying results, were reported. Patient ages ranged from 29 to 66 years (mean age, 55.2 years), and follow-up ranged from 6 to 44 months (mean follow-up, 23 months). All forehead and brow lifts were performed using an endoscopic guide, and routine corrugator resections and procerus myotomies were performed. Three slanted cortical tunnels were made at the corresponding locations on the outer table of the calvarium, and 1-0 nylon or screw suspension and fixation were performed after a 1-cm to 2-cm lift. Midface lifts were performed through lower blepharoplasty incisions and vertical temporal incisions instead of through conventional preauricular and postauricular incisions. Dissections were made subperiosteally and over the deep layers of deep temporal fascia. Malar fat pads were suspended with 1-0 nylon and affixed to deep temporal fascia. Most patients have been satisfied with their postoperative results, but unfavorable results and complications have been reported. Complications were classified as early or late complications or unfavorable results on the basis of the 3-week postoperative evaluation. There were 28 early complications (11.9 percent), consisting of ecchymosis with edema (persisting for up to 4 weeks), paresthesia, lagophthalmos, accentuated Mongoloid slant, small dimpling on the scalp, and scalp fold formation on the fixation site. There were 13 late complications/unfavorable results (5.5 percent), consisting of insufficient lift, exaggeration of sunken upper eyelids, intermittent headaches, itching sensations, and paresthesia on the scalp. The unfavorable results occurred in the patients who had previously undergone blepharoplasty and in those who had a history of foreign body injections into the face, fatty and thick faces, sunken upper eyelids, Mongoloid slants, and asymmetric facial expressions. Through understanding the anatomic characteristics of the Oriental face (i.e., thick dermis, Mongoloid slant of palpebral fissure, prominent zygoma and mandible angle, and flat nose), satisfying results were achieved by appropriate application of the modified procedures.

Adult↗

Gasless endoscopic thyroidectomy via an axillary approach: experience of 30 cases.

Surgery for thyroid disease requires skin incisions that can result in postsurgical problems such as prominent scars, adhesions, hypesthesia, and paresthesia in the neck. To overcome these problems we performed gasless endoscopic thyroidectomy via an axillary approach. Between May 2004 and April 2005, 30 patients underwent gasless endoscopic thyroidectomy via an axillary approach. The mean operating time was 126.8+/-32.4 minutes, and the mean length of hospital stay was 4.3+/-1.1 days. No cases required conversion to open surgery and none involved significant intraoperative complications. Three patients (10.0%) complained of slight hypesthesia or paresthesia in the anterior chest wall, and only 2 patients (6.7%) complained of discomfort while swallowing 4 months after surgery. All patients were satisfied with the cosmetic results. Gasless endoscopic thyroidectomy via an axillary approach is feasible and safe and provides excellent cosmetic results with a minimal degree of postoperative complaints.

Adolescent↗

First carpometacarpal joint denervation: anatomy and surgical technique.

The main goal of first carpometacarpal arthritis surgery is to relieve pain. The main disadvantage of the classic techniques (trapeziectomy, implant arthroplasty) is that they are extensive surgeries with potential complications, such as radial nerve paresthesia and synovitis. In the author's opinion, denervation of the first carpometacarpal joint is a viable option in selected cases. He describes the technique of denervation based on his previous anatomic investigations. Two incisions are needed to sever all the articular branches derived from the superficial branch of the radial nerve, the palmar cutaneous branch of the median nerve, the thenar branch of the median nerve, and the lateral antebrachial cutaneous nerve. Results comparable with trapeziectomy or first carpometacarpal joint fusion are obtained concerning pain. Complications are uncommon, except for temporary paresthesia of the radial nerve sensory branch.

Journal Article↗

Acellular dermal composite allografts for reconstruction of the radial forearm donor site.

PURPOSE: Since its description in the 1970s, the radial forearm free flap has earned a clearly defined role in the armamentarium of reconstructive head and neck surgery. Three decades later, the donor site remains an intrinsic drawback primarily due to its esthetic impact, although functional morbidity is significant in a minority. These points do not outweigh significant advantages but are occasionally reasons for the choice of alternative flaps. Modifications evolved in an effort to improve these undesirable features include primary closure, rotation-advancement, proximal paddle placement, full-thickness skin graft (FTSG) and suprafascial dissection. We describe a novel technique of engineering a composite graft of cadaveric acellular dermal matrix and autologous split-thickness skin graft (STSG) for a better donor-site closure. METHODS: From December 1995 to August 2003, 23 patients underwent radial forearm reconstruction of head and neck defects. Control patients (Group I; n = 5) had donor sites closed by conventional STSG technique (0.014-0.016 inch). In 18 patients (Group II), the donor site was closed with a composite technique (dermal allograft, 0.020-0.030 inch, and an ultrathin STSG, 0.0080 inch). Both groups of patients were retrospectively studied for comparative defects. Contralateral upper extremities also served as controls. All patients underwent a standardized functional examination of the donor and contralateral extremities, as well as an outcome questionnaire. All extremities were photographed for visual comparison by the author. RESULTS: Three of the 5 group I patients were available for follow-up, which averaged 64 months (60-72 months). Thirty-three percent had a decrease in functional parameters and 67% complained of paresthesia. Patient satisfaction was 3.5/5. Six of the 18 patients were excluded from Group II due to insufficient follow-up or inability to follow. Follow-up averaged 8 months (1-24 months). Functional parameters in all patients were comparable to the contralateral extremity, except in 1 patient. In this case, a 0.030-inch allograft was used which never revascularized, inhibiting wrist motion. Other patients exhibited excellent range of motion of the wrist and fingers. This was the only patient in this group that exhibited paresthesia of the donor site. Patient satisfaction was 4.6/5. Esthetic results were extremely gratifying as judged by the author. Esthetic results were better than those observed in Group I. CONCLUSIONS/SIGNIFICANCE: Composite grafting with acellular dermal matrix and STSG provides a comparable (trending to superior) result with traditional STSG for the treatment of radial forearm graft donor sites. Even if functionally equivalent, it is esthetically superior and therefore a technique warranting further investigation.

Collagen↗

Safety, tolerability and pharmacokinetics of BIBN 4096 BS, the first selective small molecule calcitonin gene-related peptide receptor antagonist, following single intravenous administration in healthy volunteers.

BIBN 4096 BS ([R-(R*,S*)]-N-[2-[[5-amino-1-[[4-(4-pyridinyl)-1-piperazinyl]carbonyl]pentyl]amino]-1-[(3,5-dibromo-4-hydroxyphenyl)methyl]-2-oxoethyl]-4-(1,4-dihydro-2-oxo-3(2H)-quinazolinyl)-,1-piperidinecarboxamide) is the first selective, highly potent, small molecule, nonpeptide calcitonin gene-related peptide (CGRP) receptor antagonist, which has been developed for the treatment of acute migraine. The objective of this study was to obtain information on the safety, tolerability and pharmacokinetics of BIBN 4096 BS following single intravenous administration of rising doses (0.1, 0.25, 0.5, 1, 2.5, 5 and 10 mg) in 55 healthy male and female volunteers. The study was of single-centre, double-blind (within dose levels), placebo-controlled, randomized, single rising dose design. Blood pressure, pulse rate, respiratory rate, ECG, laboratory tests and forearm blood flow did not reveal any clinically relevant, drug-induced changes. Sixteen adverse events (AEs) were reported by eight of 41 volunteers after BIBN 4096 BS compared to five AEs reported by four of 14 volunteers after placebo. Approximately two-thirds of all AEs related to active treatment occurred at the highest dose of 10 mg. At this dose level, all AEs were confined to the three BIBN 4096 BS-treated females, and consisted mainly of transient and mild paresthesias. Paresthesias were the single most frequent AE, whereas fatigue was the AE which occurred in the highest number of subjects. Only two AEs were of moderate intensity, all remaining AEs were of mild intensity. No serious AEs were reported. The local tolerability after intravenous administration was good. In summary, intravenously administered BIBN 4096 BS revealed a very favourable safety profile over the dose range tested in both genders. Generally well tolerated at all dose levels, it was of satisfactory tolerability in female subjects at the highest dose of 10 mg. The plasma concentration-time courses of BIBN 4096 BS showed multicompartmental disposition characteristics. Mean maximum concentration (Cmax) values appeared to be dose-proportional. Based on the results from the two high dose levels (5 and 10 mg) with sufficient individual subject data, BIBN 4096 BS exhibited a total plasma clearance (CL) of approximately 12 l/h and an apparent volume of distribution at steady state (Vss) of approximately 20 l, resulting in a terminal half-life (t1/2) of approximately 2.5 h. Inter-individual variability was moderate with a coefficient of variation of approximately 45% based on the area under the plasma concentration-time curve (AUC) values. The mean renal clearance (CLR) was approximately 2 l/h, suggesting that renal excretion plays only a minor role in the elimination of unchanged BIBN 4096 BS.

Adult↗

Stimulation characteristics, complications, and efficacy of spinal cord stimulation systems in patients with refractory angina: a prospective feasibility study.

OBJECTIVES: In a prospective study with a 1-year follow-up we evaluated: (1) the feasibility of a method for the adjustment of spinal cord stimulator (SCS) parameters, (2) complications of SCS, and (3) efficacy of SCS. METHODS: In patients receiving an SCS for severe angina unresponsive to standard therapies, SCS characteristics were evaluated within 1 week and at 4, 14, 26, and 52 weeks after SCS treatment. Step-by-step adjustment of pulse output parameters was performed at the electrode configuration at which paresthesias occurred ("sensory threshold"), covered the anginal area ("adjusted setting"), or provoked pain ("motor threshold"). In addition, the number of anginal attacks and intake of glyceryl trinitrate (GTN) tablets were recorded at regular intervals. RESULTS: Twenty-two patients with either a bipolar (14) or a unipolar (8) system were evaluated. In the 14 patients with bipolar systems, alteration in paresthesias required 26 reprogrammings of the configuration. In the eight patients with bipolar systems who completed the follow-up without lead dislocation, the mean "sensory threshold" was 3.3 V (1.7-5.6), the mean "adjusted stimulation" output was 4.5 V (2.8-7.6), and the mean "motor threshold" was 4.9 V (2.8-7.7) after 4 weeks SCS. The mean stimulation duration per 24 hours was 14.1% (5%-24%), and the mean standardized impedance was 821 omega (748-893) after 4 weeks SCS. The unipolar group demonstrated comparable results. After 1-year follow-up the parameters had not changed significantly. During the 1-year follow-up, 6 of 22 patients experienced lead dislocation that required surgery. In all patients, anginal attacks (P < 0.003) and GTN intake (P < 0.005) were reduced significantly with SCS. The effect lasted during the 1 year. CONCLUSIONS: During a 1-year follow-up, the stimulation parameters did not change significantly in the 16 patients without lead dislocations. Our standardized method appears to be feasible for follow-up of SCS. Moreover, SCS seems to be an effective adjuvant therapy for intractable angina, despite a relatively frequent dislocation of the electrode.

Aged↗

Outpatient metrizamide myelography: prospective evaluation of safety and cost effectiveness.

A group of 228 consecutive patients undergoing metrizamide myelography was prospectively evaluated for postprocedure symptoms. The observed prevalence of these symptoms concurs with previously reported inpatient studies, with the most common sequelae being exacerbation or onset of spine or extremity pain, headache, nausea, and paresthesia. Limitation of administered dose of metrizamide in lumbar myelography may slightly reduce the occurrence of common symptoms, but withdrawal of contrast medium at the completion of examination had no impact on their occurrence. There was a higher occurrence of paresthesia in cervical myelography, but otherwise there was no significant difference in symptoms between cervical and lumbar studies. Outpatient metrizamide myelography can be performed with relative safety with the potential for significant cost savings.

Adolescent↗

Pure sensory syndromes in thalamic stroke.

We studied 25 patients with an acute thalamic stroke (infarct or hemorrhage) on CT or MRI scan and sensory dysfunction, among the 3,628 patients with first-time stroke included in the Lausanne Stroke Registry. Twelve patients had a right-sided infarct, 11 a left-sided infarct, and 2 a left-sided thalamic hemorrhage. Sensory symptoms or signs were the only clinical abnormality. The presumed causes of stroke were small artery disease in 21 patients including both cases of hemorrhage, emboligenic heart disease in 2, while the etiology of ischemic stroke was undetermined in 2 patients. Nine patients had a loss of all modalities of sensation with faciobrachiocrural distribution, 5 patients suffered dissociated sensory loss with faciobrachiocrural distribution and 11 patients showed a dissociated involvement of sensation with a partial distribution pattern. The inferolateral region (thalamogeniculate arteries) was involved in all patients. Six patients complained of pain and/or dysesthesias during the stroke; 5 of them had involvement of the nucleus ventrocaudalis (in 3 with damage to the nucleus ventro-oralis intermedius, and in one to the pulvinar) and 1 patient had involvement of the nucleus ventro-oralis intermedius. Eighteen patients complained of paresthesias in the contralateral part of the body; 16 of them had involvement of the nucleus ventrocaudalis (in 4 with damage to the nucleus ventro-oralis intermedius, in 1 with damage to the nucleus ventro-oralis intermedius, and nucleus ventro-oralis externus, and in one with damage to the nucleus parvocellularis and pulvinar). Four patients developed delayed pain and/or dysesthesias; all of them had involvement of the nucleus ventrocaudalis (in 1 with damage to the nucleus parvocellularis and pulvinar). Time lag from stroke onset to developing pain ranged from 2 to 15 days (mean 10.5 days). One patient with dissociated involvement of sensation with a partial distribution pattern had paresthesias and dissociated hemisensory loss involving position sense without pain and temperature sensations. This patient had involvement of the posterolateral part of the nucleus ventrocaudalis. In conclusion, sensory dysfunction and delayed pain are more often found in thalamic lesions that involve the nucleus ventrocaudalis, and nucleus ventro-oralis intermedius. Restricted sensory abnormalities correlate with very small lesions located in critical areas within these nuclei.

Adult↗

Clinical evaluation of the efficacy and safety of calcium dobesilate in patients with chronic venous insufficiency of the lower limbs.

Several venotonic drugs have been used in the treatment of chronic venous insufficiency (CVI) of the lower limbs, most of them from natural sources. Calcium dobesilate, from synthetic origin, has been shown to improve clinical symptoms of these venous conditions. Three hundred fifty-two patients with CVI in grades I and II of Widmer's classification were included from an open population between January 1999 and June 2000; patients received calcium dobesilate 500 mg every 8 hours for 9 weeks. A basal recording and recordings every 3 weeks were made of heaviness, pain, cramps, and paresthesias of the lower limbs with a severity scale, and edema was assessed by measurement of the circumference of ankles and calves. Two hundred eighty-six patients (81.3%) were women and 66 (18.7%) were men with a mean age of 45.7 +/-14.1 years; 200 patients (56.8%) were grade I and 150 (42.6%) were grade II of Widmer's classification, and two patients had no classification, with a mean duration of symptoms of 6.5 +/-7.4 years. All of the symptoms had a significant reduction from the first to the final visit of treatment; 70% of the patients complained of moderate to severe heaviness of the lower limbs at the beginning of the study, whereas 10% of the patients presented this symptom at the end of treatment. Likewise, 75%, 37%, and 41% of the patients, respectively, complained of moderate to severe pain, cramps, and paresthesias of the lower limbs at the beginning of the study, with a reduction in this prevalence to 6%, 2%, and 4%, respectively, at the end of treatment (p<0.001, Wilcoxon test). In regard to edema of ankles and calves, a significant reduction in circumferences was registered in both sites at the end of treatment; for instance, the mean circumference of the right ankle was reduced from 23.78 +/-0.27 to 22.71 +/-0.31 cm while the right calf had a reduction from 35.08 +/-0.41 to 33.83 +/-0.5 cm (p<0.001, paired t test). Side effects were registered in 17.9% of the patients. This trial shows that calcium dobesilate had significant efficacy in the improvement of all the symptoms in patients with CVI, achieving this effect with an acceptable safety profile.

Adolescent↗

From symptoms to leg edema: efficacy of Daflon 500 mg.

This article reviews the mechanisms by which micronized purified flavonoid fraction (MPFF; Daflon 500 mg) acts on symptoms as well as on edema in patients with chronic venous disease, in the light of new advances in the understanding of the pathophysiology of this chronic condition. Deterioration of venous wall tone followed by valve dysfunction leading eventually to varicose veins are the key pathophysiologic features that produce venous hypertension. Both mechanical and biological factors are responsible for the deterioration of the venous wall in large veins. These are decreased shear stress and hypoxia of the media and of the endothelium, which act as triggering factors for biochemical reactions leading to inflammation. There is a body of evidence that inflammation in chronic venous insufficiency (CVI) plays a role right from the early stages of venous dysfunction and venous valve restructuring. The whole process of venous wall stretching and dilation is painful and may present as leg heaviness, a sensation of swelling, and paresthesia. Daflon 500 mg relieves symptoms, edema, and red blood cell aggregation, which cause paresthesia and restless legs. At the level of the microcirculation, dysfunction of microvessels is observed, characterized by an increase in capillary permeability followed by skin changes. The earliest manifestation of microcirculatory disorder is edema. At this level, Daflon 500 mg acts favorably on microcirculatory complications by normalizing the synthesis of prostaglandins and free radicals. It decreases bradykinin-induced microvascular leakage and inhibits leukocyte activation, trapping, and migration. Its efficacy in decreasing CVI edema and ankle swelling has been proven in rigorous studies that are reviewed in this paper. Daflon 500 mg, a well-established oral flavonoid that consists of 90% micronized diosmin and 10% flavonoids expressed as hesperidin, may be prescribed from the very beginning of the disease for the relief of pain and edema, and in any CVI patient presenting with symptoms as well. Daflon 500 mg is thus the first-line treatment for edema and symptoms of CVI at any stage of the disease. At advanced disease stages, Daflon 500 mg may be used in conjunction with sclerotherapy, surgery, and/or compression therapy or as an alternative treatment when other treatments are not indicated or not feasible.

Diosmin↗

Peripheral neurotoxicity following high-dose cisplatin with glutathione: clinical and neurophysiological assessment.

The use of high-dose cisplatin is limited by development of severe peripheral neurotoxicity and gradual worsening of renal function. In an ongoing study of high-dose cisplatin glutathione has been employed with the aim of preventing major cisplatin-induced toxicities. Neurotoxicity was examined in detail in 32 patients with ovarian cancer treated with cisplatin (160 mg/m2) and cyclophosphamide (600 mg/m2) every 3-4 weeks for five courses. In addition to serial complete neurological examination, sensory action potentials (SAPs) and motor conduction velocities (MCVs) were also assessed. We confirmed the development of a predominant sensory involvement, characterized by mild distal paresthesias and decrease in vibratory sensibility and in deep tendon reflexes, with a slight reduction of SAPs, observed after three courses of treatment. After five courses, distal paresthesias and disesthesias, decreased proprioception and loss of vibratory sensibility with ataxic signs, absence of deep tendon reflexes, unobtainable SAPs and only moderately reduced MCVs were seen. We did not observe any case of disabling neuropathy. There was a tendency to a more severe involvement of peripheral nerves in patients aged more than fifty. The 3 patients presenting the most serious neuropathy were the oldest in the whole group. Low degree of neurotoxicity observed in this study supports a glutathione protection against cisplatin-induced neurotoxicity. As the urinary excretion of platinum indicated no changes in the renal clearance of cisplatin following repeated courses, the lack of drug accumulation and high plasma peak due to preserved renal function might explain the reduced neurotoxicity observed.

Adult↗

Peripheral diabetic neuropathy: current concepts in treatment.

OBJECTIVE: To review pathophysiology and current concepts in the treatment of diabetic peripheral neuropathy (PN). DATA SOURCES: References were identified through a MEDLINE search of the English-language literature from 1976 through 1994. Additional references were obtained from reference lists of articles identified through the search. STUDY SELECTION AND DATA EXTRACTION: All articles were considered for possible inclusion in the review. Clinical trials that involved an adequate number of patients and review articles were selected. Information from articles that was judged by the authors to be significant was selected for discussion. DATA SYNTHESIS: PN affects 5-50% of people with diabetes in the US and most commonly is characterized by tingling or burning sensations, particularly in the calves, ankles, and feet, with a loss of vibratory sense. Treatment of PN, for the most part, has been unsatisfactory. Therapy has been directed toward either improving nerve function or alleviating symptoms of PN, including pain and paresthesia. Glycemic control may slow the progression of PN. Hyperglycemia also is associated with decreased pain threshold in patients with diabetes mellitus. The aldose reductase inhibitors, particularly tolrestat, have been shown to improve objective and subjective neurologic function. Pain or paresthesia has been treated effectively with antidepressants, lidocaine, mexiletine, and capsaicin. The anticonvulsants phenytoin and carbamazepine may be effective, but are associated with a greater degree of adverse effects. Experimental treatments, such as gamma-linolenic acid, gangliosides, uridine, and the corticotropin4-9 analog ORG 2766, have been effective in improving neurologic function. CONCLUSIONS: Treatment of PN remains unsatisfactory. Therapy should be directed toward prevention with glycemic control and symptomatic treatment of existing PN.

Aldehyde Reductase↗