Berberine in Human Oncogenic Herpesvirus Infections and Their Linked Cancers.

Human herpesviruses are known to induce a broad spectrum of diseases, ranging from common cold sores to cancer, and infections with some types of these viruses, known as human oncogenic herpesviruses (HOHVs), can cause cancer. Challenges with viral latency, recurrent infections, and drug resistance have generated the need for finding new drugs with the ability to overcome these barriers. Berberine (BBR), a naturally occurring alkaloid, is known for its multiple biological activities, including antiviral and anticancer effects. This paper comprehensively compiles all studies that have featured anti-HOHV properties of BBR along with promising preventive effects against the associated cancers. The mechanisms and pathways induced by BBR via targeting the herpesvirus life cycle and the pathogenesis of the linked malignancies are reviewed. Approaches to enhance the therapeutic efficacy of BBR and its use in clinical practice as an anti-herpesvirus drug are also discussed.

Silicone implants and lymphoma: The role of inflammation.

The risk of hematological malignancies is mainly determined by genetic background, age, sex, race and ethnicity, geographic location, exposure to certain chemicals and radiation; along with the more recently proposed immune factors such as chronic inflammation, immunodeficiencies, autoimmunity, and infections. Paradigmatic examples include the development of lymphoma in Sjögren's syndrome and Hashimoto thyroiditis, gastric MALT lymphoma in Helicobacter pylori infection, or lymphomas associated with infections by Epstein-Barr virus, human herpes virus 8 (HHV 8) and leukemia/lymphoma virus 1 (HTLV-1). A growing number of reports indicates an increased risk of lymphoma, particularly of the anaplastic large cell (ALCL) type. The implants, specifically those used in the past, elicit chronic stimulation of the immune system against the prosthetic material. This is particularly the case in genetically susceptible hosts. We suggest that polyclonal activation may result in monoclonality in those at risk hosts, ultimately leading to lymphoma. We suggest that patients with an inflammatory response against silicone implants be monitored carefully.

Herpesvirus infections and allergic sensitization in children of families with anthroposophic and non-anthroposophic lifestyle - the ALADDIN birth cohort.

BACKGROUND: Growing up in families with an anthroposophic lifestyle has been associated with reduced risk of allergic disease in children. The aim of this report was to assess whether children with this lifestyle are infected earlier with Epstein-Barr virus (EBV), which has been associated with reduced risk of allergic disease, and three other herpesviruses potentially involved in allergy development, namely Human herpesvirus 6 (HHV6), Human herpesvirus 7 (HHV7) and cytomegalovirus (CMV). METHODS: Within the ALADDIN (Assessment of Lifestyle and Allergic Disease During Infancy), birth cohort study 157 children were categorized according to lifestyle into anthroposophic and non-anthroposophic. IgG-levels for EBV, HHV6, HHV7 and CMV were determined in plasma samples collected at ages 12 and 24 months and from parents. IgE levels against seven common allergens were analyzed at 24 months. RESULTS: No significant differences in seroprevalence of EBV, HHV7 or CMV were detected at any age between the two lifestyle groups. The seroprevalence of HHV6 was significantly lower in the anthroposophic group at 24 months of age (74.6% vs. 87.5%, p-value 0.048). Further, no significant associations between allergic sensitization and seropositivity to any of the viruses were detected; however, an interaction effect of lifestyle could not be ruled out. CONCLUSIONS: Our results indicate that there is no strong influence of exposure to the anthroposophic lifestyle on the time for infection with EBV, HHV6, HHV7 or CMV. These infections can therefore not be assumed to be important factors in the allergy-protective effect of this lifestyle.

A randomized, prospective study of efficacy and safety of oral tramadol in the management of post-herpetic neuralgia in patients from north India.

OBJECTIVE: To evaluate the safety and efficacy of oral tramadol therapy (50 to 200 mg/day) in the treatment for post-herpetic neuralgia (PHN). METHODS: The study was a prospective, single-blind, non-responder vs. responder, randomized trial conducted in 100 outpatients of PHN after oral administration of tramadol for 4 weeks. Those patients who had achieved 50% or greater pain relief after 14 days of oral tramadol treatment were categorized as responders and those reporting < 50% pain relief were categorized as non-responders. Rescue analgesia was provided by the topical application of a cream consisting of the combination of 3.33% doxepin and 0.05% capsaicin to the affected areas of PHN patients of both groups for at least 14 days, along with tramadol therapy. The rescue analgesia was extended to 4 weeks in patients of the non-responder group. The primary endpoints were measured using a numerical rating scale (NRS) at rest and with movement. Secondary endpoints included additional pain ratings such as global perceived effect (GPE), Neuropathic Pain Symptom Inventory scores (NPSI), daily sleep interference score (DSIS), quality of life (QOL) as per WHO QOL-BREF Questionnaire scores, patient and clinician ratings of global improvement. The 2 groups were compared on the basis of pain intensity scores, encompassing primary as well as secondary endpoints, and QOL after 28 days of the treatment regimen. RESULTS: Pain intensity scores measured by NRS (at resting and with movement), NPSI, and DSIS were consistently reduced (P < 0.001) over 28 days at varying intervals in both the groups, but the magnitude of reduction was higher in responders than non-responders. A concomitant improvement (P < 0.001) was observed in GPE on days 3, 14, and 28 as compared to the respective baseline scores in both the groups. Although the WHO QOL-BREF scores showed significant (P < 0.001) improvement in QOL of PHN patients at days 14 and 28 in both the groups, the magnitude of improvement was higher in responders as compared to non-responders. Significant improvement in pain intensity scores and QOL in non-responders is mainly attributed to the use of rescue analgesia for 28 days rather than recommended tramadol therapy. CONCLUSIONS: Treatment with tramadol 50 to 200 mg per day was associated with significant pain reduction in terms of enhanced pain relief, reduced sleep interference, greater global improvement, diminished side-effect profile, and improved QOL in PHN patients from North India. Further categorization of PHN patients may be helpful so that additional or alternative therapy may be prescribed to non-responders.

Introduction of sodium pentosan polysulfate and avoidance of urethral catheterisation: improved outcomes in children with haemorrhagic cystitis post stem cell transplant/chemotherapy.

PURPOSE: Haemorrhagic cystitis (HC) is an uncommon but potentially devastating complication of chemotherapy and bone marrow transplantation in children. We aimed to test the hypothesis that early recognition, sodium pentosan polysulfate (SPP), and avoidance of urethral catheterisation improve outcomes in children with HC. METHODS: A retrospective case note review was performed of all patients treated for HC in our hospital from 2002 to 2010. A protocol for the management of HC was introduced in 2007 advocating early detection, use of SPP, and avoidance of urethral catheterisation. Data collected on each patient included primary condition, medications at onset, blood transfusions, duration of symptoms, catheter usage, and outcome. Statistical analysis was performed using the Mann-Whitney U test, and Fisher's Exact test as appropriate, P < .05 being significant. RESULTS: Five patients were treated using protocol with 5 historical controls. There was no significant difference between the ages of the group, diagnosis, and treatment at onset of HC. In the historical group, 4 of 5 died with HC, but all recovered in the protocol group (P < .05). Blood transfusion requirements were also significantly reduced after protocol introduction (P < .05). CONCLUSION: Early identification, avoidance of urethral catheterisation, and use of SPP significantly reduces blood transfusion requirements and mortality from HC.

Evidence-based interventional pain medicine according to clinical diagnoses. 17. Herpes zoster and post-herpetic neuralgia.

Herpes zoster infection is caused by a reactivation of the latent varicella zoster virus that causes chicken pox. It appears predominantly in older adults whose immunity for the virus has waned. The natural course of the disease is usually favorable, and the symptoms disappear spontaneously within a few weeks. Some patients, however, have prolonged pain: post-herpetic neuralgia. The diagnosis of acute zoster infection is made on the clinical signs including the appearance of rash. Post-herpetic neuralgia is described as sharp, burning, aching, or shooting constantly present in the dermatome that corresponds with the earlier rash. The objectives of treating herpes zoster are: (1) acute pain reduction; (2) promotion of recovery of epidermal defects and prevention of secondary infections; and (3) reduction or prevention of post-herpetic neuralgia. The objective of the treatment of post-herpetic neuralgia is primarily pain alleviation and improvement of the quality of life. Early treatment of the infection and the pain is believed to reduce the risk for post-herpetic neuralgia. This persistent pain syndrome is difficult to treat. Antiepileptic drugs and tricyclic antidepressants are the first choice. Interventional treatments, such as epidural injections of corticosteroids and local anesthetic drugs, have an effect on the acute pain but are of limited use in preventing post-herpetic neuralgia. When conservative treatment fails in providing satisfactory relief of post-herpetic neuralgia, a sympathetic block may be considered (2 C+); if this treatment provides unsatisfactory results, spinal cord stimulation may be considered, in a study context (2 C+).

[Gabapentin--yet another antiepileptic agent for the treatment of neuropathic pain?]. / Gabapentin--endnu et antiepileptikum til behandling af neuropatiske smerter?

Gabapentin is a recently introduced anti-epileptic drug used as an adjuvant in partial and secondarily generalised tonic-clonic seizures. Its mechanism of action has not been fully elucidated, but it seems that gabapentin may regulate voltage-dependent calcium channels, presumably on a spinal level, in the nociceptive system. Two large, controlled clinical trials of painful diabetic neuropathy and postherpetic neuralgia have demonstrated its analgesic efficacy. The adverse effects associated with gabapentin treatment are relatively harmless, mild to moderate in severity, and usually transient, with tolerance developing 2-3 weeks after start of treatment. Gabapentin and tricyclic antidepressants are efficacious in the treatment of painful diabetic neuropathy and postherpetic neuralgia.

Stress-associated immune modulation: relevance to viral infections and chronic fatigue syndrome.

The frequent association of an active viral infection with the symptoms of CFS led researchers to hypothesize that chronic fatigue syndrome (CFS) is induced by a virus. Results of these studies indicated that despite clinical support for this hypothesis, there were no clear data linking viruses to CFS. In this overview, we will explore the interrelation of the immune, endocrine, and central nervous systems, and the possibility that stress and/or the reactivation/replication of a latent virus (such as Epstein Barr virus) could modulate the immune system to induce CFS. Relevant research conducted in the developing field of psychoneuroimmunology will be reviewed, with a particular focus on cytokine synthesis, natural killer (NK) cell activity, and T-lymphocyte function, as they relate to CFS.

Deep brain stimulation for intractable pain: a 15-year experience.

OBJECTIVE: During the past 15 years, we prospectively followed 68 patients with chronic pain syndromes who underwent deep brain stimulation (DBS). The objective of our study was to analyze the long-term outcomes to clarify patient selection criteria for DBS. METHODS: Patients were referred from a multidisciplinary pain clinic after conservative treatment failed. Electrodes for DBS were implanted within the periventricular gray matter, specific sensory thalamic nuclei, or the internal capsule. Each patient was followed on a 6-monthly follow-up basis and evaluated with a modified visual analog scale. RESULTS: Follow-up periods ranged from 6 months to 15 years, with an average follow-up period of 78 months. The mean age of the 54 men and 14 women in the study was 51.3 years. Indications for DBS included 43 patients with failed back syndrome, 6 with peripheral neuropathy or radiculopathy, 5 with thalamic pain, 4 with trigeminal neuropathy, 3 with traumatic spinal cord lesions, 2 with causalgic pain, 1 with phantom limb pain, and 1 with carcinoma pain. After initial screening, 53 of 68 patients (77%) elected internalization of their devices; 42 of the 53 (79%) continue to receive adequate relief of pain. Therefore, effective pain control was achieved in 42 of 68 of our initially referred patients (62%). Patients with failed back syndrome, trigeminal neuropathy, and peripheral neuropathy fared well with DBS, whereas those with thalamic pain, spinal cord injury, and postherpetic neuralgia did poorly. CONCLUSION: DBS in selected patients provides long-term effective pain control with few side effects or complications.

Postherpetic neuralgia: clinical experience with a conservative treatment.

Ninety-seven consecutive cases of postherpetic neuralgia (PHN) were retrospectively reviewed. Patients comprised 49 women and 48 men with a mean age of 71.6 years. The most common painful locations were the chest and upper back (34%), abdomen and lower back (25.2%), and face (20.2%). Burning pain was the most common type of pain (61.3%). Lancinating pain was reported by 40% and throbbing pain by 22.6%. Treatments included drugs (mainly tricyclic antidepressant, anticonvulsant, and neuroleptic drugs), transcutaneous electrical nerve stimulation (TENS), and dry needling of muscles in the affected dermatomes. Positive response to treatment occurred in 18.5% of the patients after one visit. In 9.3% of the patients, the pain still could not be controlled after 10 visits of 2-week intervals. TENS proved to be effective in patients whose skin sensation was preserved. It was concluded that in most PHN cases, pain can be effectively controlled by conservative noninvasive therapy.

Spinal cord stimulation in management of chronic pain. A 9-year experience.

Between 1978 and 1986, 109 patients with chronic pain underwent spinal cord stimulation (SCS) at the authors' institute as part of their pain treatment program. The results of SCS in these patients at the end of the test period and at the latest follow-up examination are analyzed in relation to the etiology of their pain. In 40 patients pain was associated with an obstructive peripheral vasculopathy, in 10 with a previous herpes zoster infection, in 15 with an incomplete traumatic spinal cord lesion, in nine with root and/or nerve damage, in 11 with cancer, and in 19 with previous back surgery. The etiology of the pain in five patients was uncertain. This experience supports the conclusion that the best indications for SCS are vasculopathic pain and post-herpetic neuralgia. No clinical usefulness was found for SCS in cancer pain or in central deafferentation types of pain.

Post-herpetic neuralgia: 208 cases.

Two hundred and eight patients with post-herpetic neuralgia (PHN) were assessed in a prospective, longitudinal study designed to evaluate demography, clinical features, treatment results and long-term status. PHN affected both sexes equally increasing in frequency and severity with age. There was a predilection for involvement of the ophthalmic division of the trigeminal nerve and for mid-thoracic dermatomes. The pain descriptors chosen reflected both steady and brief paroxysmal components in most patients. Scarring, sensory loss and the exaggerated sensations of hyperesthesia, dysesthesia and allodynia were common findings. Hyperalgesia and hyperpathia were less common. From these open-label, uncontrolled data, antidepressants (amitriptyline and nortriptyline) appeared useful in about 60% of patients. Topical capsaicin seemed to be a promising new approach. A variety of other pharmacological agents and treatment approaches were less successful. Many patients with PHN even of long standing continued to improve with time.

[So-called post-herpetic neuralgia and phantom limb pain: therapeutic concepts needing review]. / La cosidetta nevralgia posterpetica e l' arto fantasma doloroso: concetti terapeutici da rivedere.

After a brief review of the most recent findings on peripheral nerve nociception and deafferentation, the advisability of considering two so-called neuralgias - postherpetic neuralgia and phantom limb pain - in the more complex framework of deafferentation syndromes is examined together with the consequent need for a basic review of the therapeutic approaches pursued up to the present in the antalgic treatment of these two syndromes.

[Analgesic cutaneous electrostimulation in diseases of the nervous system (technic and indications)]. / Protivobolevaia nakozhnaia élektrostimuliatsiia pri zabolevaniiakh nervnoi sistemy (metodika i pokazaniia).

In 76 patients with various pathologies of the nervous system accompanied with the pain syndrome, cutaneous electric stimulation was used for analgesia. The optimal effect was attained by proper positioning of the electrodes, use (as usual) of the monopolar method of the stimulation simultaneously in two sites, and maintenance of the definite parameters of the electric current (rectangular impulse duration 0.1 to 0.2 msec, frequency 60 to 70 o. p. s., current strengh 30 to 50 mA). A prolonged analgesic effect depended little on the disease entity: it was the duration of the pain syndrome that was the main factor predetermining the degree of the analgesic effect.

Percutaneous electro stimulation of the trigeminal nerve in patients with atypical trigeminal neuralgia.

In eleven patients with atypical trigeminal neuralgia, following herpes infections or radiation therapy of cancer of the epipharynx, percutaneous electrical stimulation of the trigeminal tract or in the vicinity of the nucleus area was performed. Relief of pain lasting from fourteen days up to six weeks could be obtained.