Laparoscopic Varicocelectomy in the Management of Chronic Scrotal Pain

Background and Objectives:

To evaluate the usefulness of laparoscopic varicocelectomy in the management of chronic scrotal pain.

Methods:

Between 2009 and 2011, 48 patients in total were treated with laparoscopic varicocelectomy for dull scrotal pain that worsened with physical activity and was attributed to varicoceles. All patients were followed up at 3 and 6 months and biannually thereafter with a physical examination, visual analog scale score, and ultrasonographic scan in selected cases.

Results:

The mean age was 38.2 years (range, 23–54 years). The mean follow-up period was 19.6 months (range, 6–26 months). Bilateral varicoceles were present in 7 patients (14.6%), and a unilateral varicocele was present in 41 (85.4%). The varicocele was grade 3 in 27 patients (56.3%), grade 2 in 20 (41.6%), and grade 1 in 1 (2.1%). The mean preoperative visual analog scale score was 4.8 on a scale from 0 to 10. The mean postoperative visual analog scale score at 3 months was 0.8. After the procedure, 42 patients (87.5%) had a significant improvement in the visual analog scale score (P < .001); 5 (10.4%) had symptom improvement, although it was not statistically significant; and 1 (2.1%) remained unchanged. During follow-up, we observed 5 recurrences (10.4%) whereas de novo hydrocele formation was identified in 4 individuals (8.3%).

Conclusion:

Laparoscopic varicocelectomy is efficient in the treatment of symptomatic varicoceles with a low complication rate. However, careful patient selection is necessary because it appears that individuals presenting with sharp, radiating testicular pain and/or a low-grade varicocele are less likely to benefit from this procedure.     

Identification of Nucleoside Analogs as Inducers of Neuronal Differentiation in a Human Reporter Cell Line and Adult Stem Cells

Nucleoside analogs (NSAs) were among the first chemotherapeutic agents and could also be useful for the manipulation of cell fate. To investigate the potential of NSAs for the induction of neuronal differentiation, we developed a novel phenotypic assay based on a human neuron‐committed teratocarcinoma cell line (NT2) as a model for neuronal progenitors and constructed a NT2‐based reporter cell line that expressed eGFP under the control of a neuron‐specific promoter. We tested 38 structurally related NSAs and determined their activity to induce neuronal differentiation by immunocytochemistry of neuronal marker proteins, live cell imaging, fluorometric detection and immunoblot analysis. We identified twelve NSAs, which induced neuronal differentiation to different extents. NSAs with highest activity carried a halogen substituent at their pyrimidine nucleobase and an unmodified or 2′‐O‐methyl substituted 2‐deoxy‐β‐D‐ribofuranosyl residue as glyconic moiety. Cladribine, a purine nucleoside with similar structural features and in use to treat leukemia and multiple sclerosis, induced also differentiation of adult human neural crest‐derived stem cells. Our results suggest that NSAs could be useful for the manipulation of neuronal cell fate in cell replacement therapy or treatment of neurodegenerative disorders. The data on the structure and function relationship will help to design compounds with increased activity and low toxicity.     

Exercise Therapy in Addition to an Orthosis Reduces Pain More Than an Orthosis Alone in Patients With Thumb Base Osteoarthritis: A Propensity Score Matching Study

ObjectiveTo compare the effect of exercises and orthotics with orthotics alone on pain and hand function in patients with first carpometacarpal joint (CMC-1) osteoarthritis (OA) and to predict outcomes on pain and hand function of exercises and orthotics.DesignProspective cohort study with propensity score matching.SettingData collection took place in 13 outpatient clinics for hand surgery and hand therapy in The Netherlands.ParticipantsA consecutive, population-based sample of patients with CMC-1 OA (N=173) was included in this study, of which 84 were matched on baseline demographics and baseline primary outcomes.InterventionsExercises and orthotics versus orthotics alone.Main Outcome MeasuresPrimary outcomes included pain and hand function at 3 months, measured using visual analog scale (VAS, 0-100) and the Michigan Hand Outcomes Questionnaire (MHQ, 0-100).ResultsA larger decrease in VAS pain at rest (11.1 points difference; 95% confidence interval, 1.9-20.3; P=.002) and during physical load (22.7 points difference; 95% confidence interval, 13.6-31.0; P<.001) was found in the exercise + orthotic group compared to the orthotic group. In addition, larger improvement was found for the MHQ subscales pain, work performance, aesthetics, and satisfaction in the exercise + orthotic group. No differences were found on other outcomes. Baseline scores of metacarpophalangeal flexion, presence of scaphotrapeziotrapezoid OA, VAS pain at rest, heavy physical labor, and MHQ total predicted primary outcomes for the total exercise + orthotic group (N=131).ConclusionsNon-surgical treatment of patients with CMC-1 OA should include exercises, since there is a relatively large treatment effect compared to using an orthosis alone. Future research should study exercises and predictors in a more standardized setting to confirm this finding.     

普瑞巴林剂量对腹腔镜子宫全切术患者术后疼痛的影响

目的探讨不同剂量(75、150和300 mg)普瑞巴林预先给药在腹腔镜子宫切除术患者中的术后镇痛效果。方法该研究为前瞻性、随机、安慰剂对照和双盲研究。共纳入82例美国麻醉医师协会(ASA)分级为Ⅰ～Ⅱ级并择期行腹腔镜子宫切除术的患者。患者随机分成4组,其中第1、2和3组(每组20例)术前1晚、术前30 min和术后6 h分别口服浓度为75、150和300 mg的普瑞巴林,而对照组(n=22)按照相同方案接受安慰剂治疗。主要临床结局是术后24 h静息和运动时的疼痛视觉模拟评分(VAS)。药物相关副作用评估作为次要观察指标。嗜睡采用Ramsay镇静评分评估,而恶心和呕吐用数值评分评估。结果不同浓度预先普瑞巴林给药的镇痛效果优于安慰剂。事后检验显示,4组间AVS评分差异有统计学意义,表明浓度下降,疼痛评分作为时间自变量而下降。普瑞巴林浓度达到最高(300 mg)时,镇静评分高于其他组。结论预先服用75、150和300 mg普瑞巴林对减轻腹腔镜子宫切除术后疼痛具有重要作用。比较不同浓度与副作用表明,口服150 mg普瑞巴林是减轻腹腔镜子宫切除术后疼痛的安全有效方法。     

Somatostatin analogs as primary medical therapy for acromegaly

Acromegaly is a debilitating disease usually caused by a growth-hormone secreting pituitary adenoma. Therapeutic goals include improvement of symptoms, reduction in tumor mass, biochemical normalization, and preservation of pituitary function. Treatment options include transsphenoidal surgery, radiation, and pharmacotherapy. In view of the good cure rate, surgery remains the therapeutic modality of choice for most patients with microadenomas or well-circumscribed macroadenomas. In contrast, >40% of patients with invasive macroadenomas (who make up the majority of patients with acromegaly) will have residual disease following surgery, and require additional therapeutic intervention. Somatostatin analogs result in biochemical normalization in >60% of non-operated patients, and are well tolerated. Therefore, somatostatin analogs have emerged as a rational first-line treatment for the appropriately selected patient with acromegaly.     

A prospective and comparative cohort study on efficacy and drug resistance during long-term lamivudine treatment for various stages of chronic hepatitis B and cirrhosis

Background and Aims: A prospective , non‐randomized cohort study on long‐term lamivudine treatment , comparing efficacy, drug resistance, and prognosis for various stages of chronic hepatitis B virus (HBV)–related liver disease was performed to elucidate the significance and indication of lamivudine for individual patients at each stage of disease. Methods: A total of 158 cases consisting of 87 chronic hepatitis, 28 compensated cirrhosis, and 43 decompensated cirrhosis, with serum HBV‐DNA > 5 log₁₀ copies/mL and with elevated alanine aminotransferase (ALT) over twice the upper normal limit or complications of hepatic insufficiency, were administered 100 mg of lamivudine daily and monitored for HBV markers, biochemistry, and prognosis. Results: Lamivudine reduced HBV‐DNA and ALT equally in all groups. Serum albumin, prothrombin time (%), and platelet count increased in all groups. The increased margin of albumin was the highest in the decompensated cirrhosis and higher in the compensated cirrhosis than the chronic hepatitis groups. Cumulative incidence of virologic breakthrough was 16%, 42%, 49%, and 53% at 12, 24, 36, and 48 months, respectively, and the strongest predictive factor for lamivudine resistance was persistent HBV‐DNA at 3 months. Ascites, encephalopathy, and jaundice improved in the majority of patients with decompensated cirrhosis. On the other hand, hepatic failure developed or deteriorated in 10 patients after virologic breakthrough, and nine of them had decompensated cirrhosis. Conclusions: Lamivudine was effective in reducing HBV‐DNA and improving hepatic reserve at all stages and was most beneficial and significant for decompensated cirrhosis. Meanwhile, close monitoring of viral load and immediate rescue treatment for lamivudine resistance is necessary to prevent hepatic failure in decompensated cirrhosis.     

Simple assessment of olfaction in patients with chronic rhinosinusitis

Conclusion: The brief-smell identification test (B-SIT) can substitute for the butanol threshold test (BTT) in screening of anosmia and postoperative assessment of olfactory outcomes in patients with chronic rhinosinusitis (CRS). A time-effective test battery composed of B-SIT and the visual analog scale (VAS) can be implemented for simple olfactory assessment in any otolaryngology clinic. Objectives: Anosmia is a distinct clinical entity requiring special attention. Unpredictable olfactory outcomes after surgery make preoperative assessment more important. We compared the results of the BTT, B-SIT, and VAS to investigate whether B-SIT or VAS can substitute for BTT in screening of anosmia and postoperative follow-up. Methods: We collected data on 68 CRS patients who had bilateral CRS and underwent endoscopic sinus surgery. Olfactory performance was graded using the BTT: normosmia, hyposmia, or anosmia. VAS and B-SIT were also performed. All tests were repeated 6 months after surgery. Postoperative improvement was defined by an increase of the BTT score ≥ 2. Results: The B-SIT and VAS scores of the anomics were significantly lower than those of the normosmics. B-SIT discriminated anosmia with high specificity. Within the improvement group, postoperative increase of B-SIT/VAS score showed significance. However, neither the B-SIT nor the VAS differentiated between no change and deterioration of olfaction.     

Mossy fiber-evoked subthreshold responses induce timing-dependent plasticity at hippocampal CA3 recurrent synapses

Dentate granule cells exhibit exceptionally low levels of activity and rarely elicit action potentials in targeted CA3 pyramidal cells. It is thus unclear how such weak input from the granule cells sustains adequate levels of synaptic plasticity in the targeted CA3 network. We report that subthreshold potentials evoked by mossy fibers are sufficient to induce synaptic plasticity between CA3 pyramidal cells, thereby complementing the sparse action potential discharge. Repetitive pairing of a CA3–CA3 recurrent synaptic response with a subsequent subthreshold mossy fiber response induced long-term potentiation at CA3 recurrent synapses in rat hippocampus in vitro. Reversing the timing of the inputs induced long-term depression. The underlying mechanism depends on a passively conducted giant excitatory postsynaptic potential evoked by a mossy fiber that enhances NMDA receptor-mediated current at active CA3 recurrent synapses by relieving magnesium block. The resulting NMDA spike generates a supralinear depolarization that contributes to synaptic plasticity in hippocampal neuronal ensembles implicated in memory.The CA3 area of the hippocampus exhibits a distinctive, highly recurrent circuitry proposed to support autoassociative memory representation (1, 2). This prediction has been confirmed by experimental work demonstrating the pattern completion capabilities of CA3 networks (3), as well as their roles in the spatial tuning of CA1 pyramidal cells, in one-trial contextual learning (4) and in certain forms of memory consolidation (5). CA3 pyramidal cells receive, via the mossy fibers, information processed by granule cells important for both pattern separation (6, 7) and pattern completion functions (7). The faithful transmission of mossy fiber input appears to be ensured by giant synapses composed of presynaptic boutons with up to 45 release sites (8) that target massive spines, the thorny excrescences, on the apical dendrite of CA3 pyramidal cells. Thus, the mossy fiber synapse is often referred to as a detonator synapse (9). In fact, mossy fiber signaling is more compatible with a gatekeeper function than a high-throughput data relay. Although high-frequency bursts of action potentials in a hippocampal granule cell can discharge a targeted CA3 pyramidal cell, the majority of responses evoked by granule cells in CA3 pyramidal cells do not attain the firing threshold (10). Nevertheless, mossy fibers generate powerful signals evoking subthreshold responses that are much larger than typical synaptic events in the brain, with excitatory postsynaptic potentials (EPSPs) and excitatory postsynaptic currents (EPSCs) reaching amplitudes of 10 mV and 1 nA, respectively (11). Here we examined in rat slice cultures how EPSPs generated at mossy fiber synapses are processed in CA3 pyramidal cell dendrites, and evaluated whether subthreshold synaptic responses evoked by mossy fiber stimulation can act as instructive signals to induce plasticity at the pyramidal cell synapses forming the CA3 recurrent network.     

The Factors Affecting Pain Pattern after Arthroscopic Rotator Cuff Repair

Background

We evaluated the factors that affect pain pattern after arthroscopic rotator cuff repair.

Methods

From June 2009 to October 2010, 210 patients underwent arthroscopic rotator cuff repair operations. Of them, 84 patients were enrolled as subjects of the present study. The evaluation of postoperative pain was conducted by visual analog scale (VAS) scores during postoperative outpatient interviews at 6 weeks, 3 months, 6 months, and 12 months. The factors that were thought to affect postoperative pain were evaluated by dividing into three categories: preoperative, operative, and postoperative.

Results

Pain after arthroscopic rotator cuff repair surgery showed a strictly decreasing pain pattern. In single analysis and multiple regression tests for factors influencing the strictly decreasing pain pattern, initial VAS and pain onset were shown to be statistically significant factors (p = 0.012, 0.012, 0.044 and 0.028, respectively). With regard to the factors influencing lower than average intensity pain pattern for each period, the stiffness of internal rotation at 3 months postoperatively was shown to be a statistically significant factor in single and multiple regression tests (p = 0.017 and p = 0.004, respectively).

Conclusions

High initial VAS scores and the acute onset of pain affected the strictly decreasing postoperative pain pattern. Additionally, stiffness of internal rotation at postoperative 3 months affected the higher than average intensity pain pattern for each period after arthroscopic rotator cuff repair.