Peripheral neuropathy in hepatitis-related mixed cryoglobulinemia: electrophysiologic follow-up study

A retrospective study was performed on 27 patients with hepatitis C (HCV)-related mixed cryoglobulinemia (purpura, arthralgia, hepatitis, glomerulonephritis, peripheral neuropathy) to assess peripheral nerve involvement during follow-up of up to 8 years. All patients had the same degree of organ/system involvement initially and were clinically evaluated at least annually. All 27 patients received steroids; 15 also received recombinant interferon-alpha 2b (rIFN-alpha 2b). At first examination, neurological signs and electrodiagnostic findings consistent with peripheral neuropathy were found in 20 (74%) and in 24 (88.8%) patients, respectively. Neurological evaluation and electrodiagnostic data at 3 and 8 years revealed worsening of neuropathy, whereas the other manifestations of mixed cryoglobulinemia (MC) were stable. At the last examination, clinical and electrodiagnostic signs of neuropathy were found in 25 patients (92.5%), occurring in 1 of 3 patients with normal initial findings, and worsened in 8. A more severe neuropathy was observed in 3 (25%) of the patients treated with prednisone alone and in 6 (40%) of the patients additionally treated with rIFN-alpha 2b. Our data confirm that in patients with HCV-related MC, peripheral nerve involvement is frequent, is progressive, and does not seem to benefit by addition of rIFN-alpha 2b to steroid treatment.     

Adult polyglucosan body disease: a case report of a manifesting heterozygote

A 62-year-old man developed progressive gait instability, bladder dysfunction, proximal weakness, distal sensory loss, and mild cognitive impairment over 6 years. Neurologic examination revealed upper and lower motor neuron dysfunction in the lower extremities, with distal sensory loss. Electrodiagnostic studies, magnetic resonance imaging of the brain, and sural nerve biopsy were consistent with adult polyglucosan body disease. Biochemical and genetic analyses demonstrated reduced glycogen brancher enzyme levels associated with a heterozygous point mutation (Tyr329Ser or Y329S) in the glycogen brancher enzyme gene on chromosome 3. Mutational heterozygosity in the glycogen brancher enzyme gene has not been previously reported as a cause for this rare disease. A review of the clinical presentation, pathogenesis, etiology, and diagnosis of this disease is presented.     

Peripheral arterial tonometry: a diagnostic method for detection of myocardial ischemia induced during mental stress tests: a pilot study

BACKGROUND: Mental stress testing is considered a reliable method for diagnosing patients with coronary heart disease (CHD) who may be at risk for future events. It has been shown recently that myocardial ischemia induced during mental stress tests is specifically associated with peripheral arterial vasoconstriction. HYPOTHESIS: The study was undertaken to test the diagnostic capability of peripheral arterial tonometry (PAT) to detect peripheral arterial vasomotor changes. METHODS: We monitored pulsatile finger blood volume changes using a specially designed finger plethysmograph, PAT that can detect peripheral arterial vasomotor changes. Equilibrium radionuclide angiography (ERNA) was simultaneously performed in 18 male patients at rest and during a mental arithmetic stress test with harassment. All patients had previously diagnosed coronary disease and positive exercise tests. Myocardial ischemia was diagnosed by ERNA when global ejection fraction fell > or = 8% during mental stress or new (or worsened) focal wall motion abnormalities occurred. Peripheral arterial tonometry tracings were considered abnormal when the pulse wave amplitude decreased by > or = 20% from baseline. RESULTS: In 18 patients there were 16 usable studies. In eight patients, both ERNA and PAT were abnormal, and in six patients the tests were negative by both methods. In two cases, the results were discordant. Therefore, when considering an abnormal PAT tracing as indicative of mental stress-driven myocardial ischemia, concordance of the two methods was 88%. CONCLUSION: The use of PAT may facilitate both clinical testing and research during mental stress.     

Missile severances of the radial nerve. Results of 131 repairs

Summary Background. Reports on missile-caused radial nerve injuries are relatively rare in current literature. We present the outcome after repair of such injuries as well as the factors influencing the result of treatment.Methods. Prospective study included 131 complete missile-caused radial nerve severances repaired with nerve graft or direct suture. Final outcome was defined 4 years postoperatively at least, on the basis of motor recovery (M), EMNG recovery (E) and patients judgement on the quality of outcome (P). Recovery was estimated with 0–5 points and final outcome was defined according to the total sum (0–15 points) as: poor, insufficient, good or excellent. Both the good and the excellent outcomes were considered as successful, and both the poor and the insufficient outcome as unsuccessful.Results. Excellent outcome was noted in 38.2% and good outcome in 47.3% of all patients. Average point score was 9.9±3.3 points for the whole series (domain of good outcome) and 6.6±3.0, 10.1±3.2 and 10.9±2.2 points for high, intermediate and low repairs, respectively (p<0.01). Useful motor recovery (M3), good EMNG recovery (E3) and affirmative patients judgement on the outcome (P3) had similar frequencies for intermediate (83.2–89.7%) and low repairs (85.7–92.8%), but for high repairs, good EMNG recovery was more frequent (70%) than were useful motor recovery and affirmative patients judgement (40%). Successful outcome was noted in 89.3% of direct sutures and in 82.7% of nerve grafts (p>0.05). Patients with a successful outcome had a significantly shorter nerve defect (p<0.001), shorter preoperative interval (p<0.001) and younger age (p<0.05) than patients with an unsuccessful outcome. Significant deterioration of results began with defects longer than 8cm, preoperative interval longer than 6 months and age above 40 years.Conclusions. The outcome is significantly worse after high radial nerve repairs than after intermediate and low repairs. The length of nerve defect, duration of preoperative interval and age of the patient also influence the repair outcome. Correlation of motor recovery with EMNG recovery and with patients judgement on the outcome is relatively good, but depends on the level of the repair.     

Intraosseous malignant peripheral nerve sheath tumor with local recurrence,lung metastases and death

Malignant peripheral nerve sheath tumor (MPNST) is almost always seen in soft tissue. Skeletal involvement by MPNST is uncommon and usually results from secondary invasion. Primary MPNSTs are exceptionally rare. We report a surgically proven case of intraosseous MPNST, with local recurrence and lung metastasis during follow-up. The imaging and histological features of the case are described and the literature on the subject briefly reviewed.     

Prospective decision analysis modeling indicates that clinical decisions in vascular surgery often fail to maximize patient expected utility

BACKGROUND: Applied prospectively to patients with peripheral arterial disease, individualized decision analysis has the potential to improve the surgeon's ability to optimize patient outcome. METHODS: A prospective, randomized trial comparing Markov surgical decision analysis to standard decision-making was performed in 206 patients with symptomatic lower extremity arterial disease. Utility assessment and quality of life were determined from individual patients prior to treatment. Vascular surgeons provided estimates of probability of treatment outcome, intended and actual treatment plans, and assessment of comfort with the decision (PDPI). Treatment plans and PDPI evaluations were repeated after each surgeon was made aware of model predictions for half of the patients in a randomized manner. RESULTS: Optimal treatments predicted by decision analysis differed significantly from the surgeon's initial plan and consisted of bypass for 30 versus 29%, respectively, angioplasty for 28 versus 11%, amputation for 31 versus 6%, and medical management for 34 versus 54% (agreement 50%, kappa 0.28). Surgeon awareness of the decision model results did not alter the verbalized final plan, but did trend toward less frequent use of bypass. Patients for whom the model agreed with the surgeon's initial plan were less likely to undergo bypass (13 versus 30%, P < 0.01). Greater surgeon comfort was present when the initial plan and model agreed (PDPI score 47.5 versus 45.6, P < 0.005). CONCLUSIONS: Individualized application of a decision model to patients with peripheral arterial disease suggests that arterial bypass is frequently recommended even when it may not maximize patient expected utility.     

Herpes simplex virus-based vectors

Herpes simplex virus (HSV)-based vectors have primarily been developed for neuronal gene delivery, taking advantage of the virus' natural neurotropism. Two types of vector are available: replication defective viruses, whose cytotoxicity has been abolished by deleting viral gene products, and amplicon vectors, which are plasmids packaged into HSV particles with the aid of a helper virus. In this review I discuss how the cytotoxicity of the wild-type virus has been abolished, the progress which has been made toward defining promoter elements capable of directing long-term transgene expression form the latent viral genome and some of the potential clinical uses of these versatile vectors.     

Primary peripheral T-cell lymphoma in subcutaneous tissue: sonographic findings

We describe the sonographic findings in a case of Lennert's lymphoma, a rare type of peripheral T-cell lymphoma, involving the subcutaneous tissues of the arm. The sonographic appearance was thought to be more helpful than MRI to establish the diagnosis.     

In vitro and ex vivo evidence for modulation of P-glycoprotein activity by progestins

The well known gender-related differences in drug action may partly be explained by changes in activity and expression of drug metabolising enzymes, but also by modulation of active drug transport systems (e.g. P-glycoprotein, Pgp) by sexual steroids, which is yet not well investigated. Because many women are using hormones (e.g. as oral contraceptives) we investigated the influence of different synthetic progestins on Pgp activity. Pgp inhibition of progesterone, medroxyprogesterone, chlormadinone, cyproterone, levonorgestrel, norethisterone, desogestrel, and norgestimate was measured in vitro in two Pgp over-expressing cell lines (L-MDR1, P388/dx cells) and the corresponding parental cell lines by means of calcein assay, and ex vivo in human peripheral blood mononuclear cells (PBMCs) by rhodamine123 efflux. For most progestins tested, concentrations needed to double baseline fluorescence (f2) in L-MDR1 cells were similar to that of the potent Pgp inhibitor quinidine, whereas levonorgestrel and norethisterone did not reach f2. The results in P388/dx cells essentially confirmed our findings in L-MDR1 cells. Additionally, Pgp inhibitory activity of all progestins tested was also shown ex vivo in PBMCs. The potent Pgp inhibition by several synthetic progestins in vitro and ex vivo suggests that such an interaction might be clinically relevant despite generally low plasma concentrations of progestins. The results may be of particular importance for Pgp substrates, such as protease inhibitors and chemotherapeutic agents, for which intracellular concentrations are critical.