Relation between reduced electrophoretic mobility of human lymphocytes and the inhibition of spreading of human monocytes caused by the same anti-human lymphocyte globulin

Slowing of electrophoretic mobility of human peripheral blood lymphocytes after adding anti-human lymphocyte globulin (AHLG) in vitro correlated with indices of the monocyte spreading inhibition obtained by the same AHLG. Consequently, electrophoretic results may be associated with the prolongation of skin allograft survival in primates - the best and the only practical in vivo test for determination of the immunosuppressive potency of AHLG. If so, the simple electrophoretic test could be used in combination with other in vitro tests, preferably for monitoring of the AHLG production.     

Use of antilymphocyte globulin in autoimmune nervous system diseases]

The pathogenetic bases for the indication of immunosuppression in multiple sclerosis are represented in a survey, rested upon experiences in the clinical compatability test of AHLG Dessau. The knowledge gained in animal experiments and epidemiology in recent years is considered and problems of membrane, slow-virus hypothesis, genetic problems and changes of immunoglobulins and lymphocytes are critically referred to.     

Preoperative [131I]metaiodobenzylguanidine therapy of neuroblastoma at diagnosis ("MIBG de novo").

The observed response of [131I]metaiodobenzylguanidine (131I-MIBG) therapy in advanced neuroblastoma after conventional therapy had failed, the noninvasiveness of the procedure, and the high metabolic activity of untreated tumors led to a new protocol to use 131I-MIBG therapy in newly diagnosed patients instead of combination chemotherapy prior to surgery. The objectives of this study are to improve the overall outcome of patients with neuroblastoma by introducing 131I-MIBG therapy as the first therapy in the treatment schedule, in order to reduce the tumor volume, enabling adequate surgical resection and avoiding toxicity and the induction of early drug resistance. The advantages of this approach are that the child's general condition is unaffected before surgical resection is performed and that chemotherapy is reserved to treat minimal residual disease. So far, 13 patients with inoperable neuroblastoma (stage III and IV) were treated with 131I-MIBG initially and then submitted to surgery. More than 50% decrease of the volume of the primary tumor was noted in 7 of 10 evaluable patients; 8 patients have so far been operated with complete resection in 2, greater than 95% resection in 5 and 80% resection in one patient. Three patients are still undergoing 131I-MIBG treatment. The toxicity of 131I-MIBG de novo is in contrast with the previous experience of 131I-MIBG therapy after conventional therapy: only 4 patients had thrombocytopenia and only 1 of 7 patients with bone marrow involvement developed bone marrow depression.(ABSTRACT TRUNCATED AT 250 WORDS)     

Melanoma: Where we are and where we go

Melanoma is known as an aggressive tumor which shows an increasing incidence and poor prognosis in the metastatic phase. Hence, it seems that diagnosis and effective management (including early diagnosis, choosing of the effective therapeutic platform, caring, and training of patients for early detection) are major aspects of melanoma therapy. Early detection of melanoma is a key point for melanoma therapy. There are various diagnosis options such as assessing of biopsy, imaging techniques, and biomarkers (i.e., several proteins, polymorphism, and liquid biopsy). Among the various biomarkers, assessing circulating tumor cells, cell-free DNAs, cell-free RNAs, and microRNAs (miRNAs) have emerged as powerful diagnosis tools for melanoma patients. Deregulations of these molecules are associated with melanoma pathogenesis. After detection of melanoma, choosing of effective therapeutic regimen is a key step for recovery of melanoma patients. Several studies indicated that various therapeutic approaches including surgery, immunotherapy, systematic therapy, radiation therapy and antibodies therapy could be used as potential therapeutic candidates for melanoma therapy. Caring for melanoma patients is one of the important components of melanoma therapy. Caring and training for melanoma patients could contribute to better monitoring of patients in response to various therapeutic options. Here, we summarized various diagnosis approaches such as assessing biopsy, imaging techniques, and utilization of various biomarkers (i.e., proteins, CTCs, cfDNAs, and miRNAs) as a diagnostic biomarker for detection and monitoring patients with melanoma. Moreover, we highlighted various therapeutic options and caring aspects in patients with melanoma.     

Failure of sequential therapy to eradicate Helicobacter pylori in previously treated subjects

BACKGROUND: Recently, studies in adults and subsequently in children have demonstrated a very high success rate for sequential therapy as a primary therapy when compared to traditional therapy regimens. METHODs: We report our experience with a sequential therapy regimen for the eradication of Helicobacter pylori in five infected children and a young adult, whose conventional therapy regimens had been unsuccessful. RESULTS: Five patients failed the sequential therapy. All of them experienced between two and four failures of traditional therapy prior to the sequential treatment protocol. The only patient who succeeded on the sequential therapy had just one previous failure. All of our patients who had failed sequential therapy achieved eradication of the bacteria with quadruple therapy. CONCLUSIONS: In view of our disappointing results, sequential therapy is unsuccessful as a therapy for children and young adults who have failed previous treatment regimens. At the present time, quadruple therapy is indicated for this group. Well-designed placebo-controlled trials are indicated to further characterize this group of patients.     

Prolactinomas, Cushing's disease and acromegaly: debating the role of medical therapy for secretory pituitary adenomas

Pituitary adenomas are associated with a variety of clinical manifestations resulting from excessive hormone secretion and tumor mass effects, and require a multidisciplinary management approach. This article discusses the treatment modalities for the management of patients with a prolactinoma, Cushing's disease and acromegaly, and summarizes the options for medical therapy in these patients. First-line treatment of prolactinomas is pharmacotherapy with dopamine agonists; recent reports of cardiac valve abnormalities associated with this class of medication in Parkinson's disease has prompted study in hyperprolactinemic populations. Patients with resistance to dopamine agonists may require other treatment. First-line treatment of Cushing's disease is pituitary surgery by a surgeon with experience in this condition. Current medical options for Cushing's disease block adrenal cortisol production, but do not treat the underlying disease. Pituitary-directed medical therapies are now being explored. In several small studies, the dopamine agonist cabergoline normalized urinary free cortisol in some patients. The multi-receptor targeted somatostatin analogue pasireotide (SOM230) shows promise as a pituitary-directed medical therapy in Cushing's disease; further studies will determine its efficacy and safety. Radiation therapy, with medical adrenal blockade while awaiting the effects of radiation, and bilateral adrenalectomy remain standard treatment options for patients not cured with pituitary surgery. In patients with acromegaly, surgery remains the first-line treatment option when the tumor is likely to be completely resected, or for debulking, especially when the tumor is compressing neurovisual structures. Primary therapy with somatostatin analogues has been used in some patients with large extrasellar tumors not amenable to surgical cure, patients at high surgical risk and patients who decline surgery. Pegvisomant is indicated in patients who have not responded to surgery and other medical therapy, although there are regional differences in when it is prescribed. In conclusion, the treatment of patients with pituitary adenomas requires a multidisciplinary approach. Dopamine agonists are an effective first-line medical therapy in most patients with a prolactinoma, and somatostatin analogues can be used as first-line therapy in selected patients with acromegaly. Current medical therapies for Cushing's disease primarily focus on adrenal blockade of cortisol production, although pasireotide and cabergoline show promise as pituitary-directed medical therapy for Cushing's disease; further long-term evaluation of efficacy and safety is important.     

THE TREATMENT OF METASTATIC BREAST CANCER IN BONE

The author report clinical experience with 212 cases of mammary cancer metastatic to bone, in 186 of which radiotherapy was given, and in 26 steroid hormone therapy.At least 70 per cent of patients with bone metastasis from breast cancer were relieved of pain by adequate roentgen therapy, the relief lasting for most of the survival time in many instances.About 25 per cent of patients had recalcification or reossification of bony lesions with roentgen therapy; while dramatic, this is not always an indication that relief of pain will continue or that survival time will be lengthened.If and when adequate radiotherapy has not been effective or cannot be administered (for example, in a patient with extremely widespread metastasis, or one residing at a considerable distance from radiotherapeutic service) steroid hormone therapy in adequate dosage is frequently beneficial. From 40 per cent to 75 per cent of patients with bone metastases from breast cancer are relieved of pain by steroid hormone therapy. In about 15 per cent of cases recalcification of the lesion occurs.Effective roentgen therapy may usually be given in a relatively brief period of time (one to two weeks). Effective steroid hormone therapy usually requires from 12 to 24 weeks.Complications of steroid hormone therapy are numerous. Some patients are made considerably worse by such therapy. These complications may only be controlled by reduction or discontinuation of the hormones. For this reason, it is recommended that irradiation always be used as the initial method of palliation.     

吉兰-巴雷综合征的研究进展

吉兰-巴雷综合征是一种由于感染等原因所致的自身免疫性多发性神经疾病,主要的感染菌为空肠弯曲杆菌。男性患者多于女性。目前临床较为支持的发病机制为分子模拟理论,临床最主要的两大分类是轴索型及脱髓鞘型。欧美等国家以脱髓鞘型为主,亚洲国家以轴索型为主。另外还有一些在吉兰-巴雷综合征中所占比例较低的临床特殊分型,如:Miller Fisher综合征和咽-颈-臂变异型。吉兰-巴雷综合征最有效的治疗方法为静滴丙种球蛋白与血浆置换,且这两种方法的有效性已有循证医学证据支持。激素治疗目前循证医学证据提示无效,基础支持疗法不可轻视。大部分吉兰-巴雷综合征患者为单相病程,仅极少部分患者可复发。Miller Fisher综合征临床预后较好,高龄、轴索型等预后较差。     

Proton Beam Therapy for Localized Prostate Cancer 101: Basics,Controversies, and Facts

Proton beam therapy for prostate cancer has become a source of controversy in the urologic community, and the rapid dissemination and marketing of this technology has led to many patients inquiring about this therapy. Yet the complexity of the technology, the cost, and the conflicting messages in the literature have left many urologists ill equipped to counsel their patients regarding this option. This article reviews the basic science of the proton beam, examines the reasons for both the hype and the controversy surrounding this therapy, and, most importantly, examines the literature so that every urologist is able to comfortably discuss this option with inquiring patients.Key words: Prostate cancer, Proton beam therapy, External beam radiation therapy, Intensity modulated radiation therapyProton beam therapy (PBT) has become a source of controversy in the urologic community. It is not uncommon to hear mixed messages regarding the issue, from zealous advocates to cost-conscious skeptics, leaving many urologists unsure what to tell their patients with prostate cancer. What is clear, however, is that the technology is disseminating across the nation, and as our patients turn to the internet to learn more about their diagnosis, they are going to encounter increasingly more information about PBT, both scientific and promotional in nature. Hence, it is necessary for every urologist to understand the basics of PBT to help guide our patients through treatment options. This article reviews and compares the basic science of conventional external beam radiation therapy (EBRT) with PBT, examines the reasons for both the hype and the controversy surrounding this therapy, and, most importantly, examines the literature so that all urologists are adequately equipped to counsel their patients on this subject.     

Rehabilitation of Paralytic Dysphonia

Vocal rehabilitation has been successful for patients with paralytic dysphonia. At the discretion of the laryngologist, vocal rehabilitation is used alone or in combination with intracordal injection. Except for post-surgical patients, a complete diagnostic evaluation is advisable before vocal therapy is undertaken. During vocal rehabilitation, pitch, volume, quality, breath support and the vocal image are realigned to afford an optimal and efficient voice.For the 18 patients completing vocal therapy, the results were excellent in 14 and good in four. Vocal therapy was completed within six months for 11 patients; seven were treated for periods ranging from six months to a year.     

Is voice therapy an effective treatment for dysphonia? A randomised controlled trial

ObjectivesTo assess the overall efficacy of voice therapy for dysphonia.Design Single blind randomised controlled trial.Setting Outpatient clinic in a teaching hospital.Participants204 outpatients aged 17-87 with a primary symptom of persistent hoarseness for at least two months.Interventions After baseline assessments, patients were randomised to six weeks of either voice therapy or no treatment. Assessments were repeated at six weeks on the 145 (71%) patients who continued to this stage and at 12-14 weeks on the 133 (65%) patients who completed the study. The assessments at the three time points for the 70 patients who completed treatment and the 63 patients in the group given no treatment were compared.ResultsVoice therapy improved voice quality as assessed by rating by patients (P=0.001) and rating by observer (P<0.001). The treatment effects for these two outcomes were 4.1 (95% confidence interval 1.7 to 6.6) points and 0.82 (0.50 to 1.13) points. Amplitude perturbation showed improvement at six weeks (P=0.005) but not on completion of the study. Patients with dysphonia had appreciable psychological distress and lower quality of life than controls, but voice therapy had no significant impact on either of these variables.ConclusionVoice therapy is effective in improving voice quality as assessed by self rated and observer rated methods.

What is already known on this topic

Many patients with dysphonia are treated by voice therapyThe effectiveness of voice therapy in a diverse group of patients is unknown

What this study adds

Voice therapy is an effective treatment for dysphonia in terms of report by patients and perceptual ratings by an expertPsychological distress and reduction in general health status are common in patients with dysphonia but are not significantly affected by a course of voice therapy     

Personalized Treatment of Patients With Primary Aldosteronism

Primary aldosteronism (PA) is a highly prevalent yet underdiagnosed secondary cause of hypertension. PA is associated with increased cardiovascular and renal morbidity compared with patients with primary hypertension. Thus, prompt identification and targeted therapy of PA are essential to reduce cardiovascular and renal morbidity and mortality in a large population with hypertension. Unilateral adrenalectomy is preferred for lateralized PA as the only potentially curative therapy. Surgery also mitigates the risk of cardiovascular and renal complications associated with PA. Targeted medical therapy, commonly including a mineralocorticoid receptor antagonist, is offered to patients with bilateral PA and those who are not surgical candidates. Novel therapies, including nonsteroidal mineralocorticoid receptor antagonists and aldosterone synthase inhibitors, are being developed as alternative options for PA treatment. In this review article, we discuss how to best individualize therapy for patients with PA.     

Elderly heart failure patients and the role of beta-blocker therapy

In this article different aspects of chronic heart failure in old age are described. We mainly focus on the place of beta-blocker therapy in chronic heart failure. Beta-blockers are recommended for the treatment of stable chronic heart failure with left ventricular systolic dysfunction. There is additional information from recent studies that there is proven efficacy for beta-blocker therapy in patients with heart failure up to the age of 80 years. For patients with heart failure aged 80 and over the evidence to prescribe beta-blockers is limited. However, it is known that also in very elderly patients beta-blocker therapy is well tolerated. In patients with heart failure with preserved systolic ventricular function there is still no evidence that there is a beneficial effect of beta-blockers. It is still not clear if there are differences between beta-blocking agents. Of all beta-blockers, only bisoprolol, carvedilol, nebivolol and metoprolol CR are proven effective in stable chronic heart failure with impaired left ventricular systolic function and can be recommended in elderly patients on standard treatment with diuretics and ACE inhibition.     

Selection of salvage cryotherapy patients

Radiation therapy is a main form of therapy for patients with localized prostate cancer. Despite advances in delivering radiation beams to the gland, urologists will be faced with managing patients with rising prostate-specific antigen values and radiation-recurrent cancer. If the cancer is detected early, salvage therapy can be initiated. Recent modifications in the technique of salvage cryosurgery have led to the ability to eradicate these tumors with a decrease in morbidity. The management and selection of these patients, as well as the results of salvage cryoablation, are discussed in this article.     

Guidelines for treating epilepsy in the age of felbamate,vigabatrin, lamotrigine,and gabapentin.

For the first time in 15 years, new antiepileptic medications are available for the treatment of patients with seizure disorders. These drugs have demonstrated efficacy in animal models of epilepsy and in controlled clinical trials. Felbamate was licensed in 1993 for use as adjunctive therapy or monotherapy in adults with partial or tonic-clonic seizures and as adjunctive therapy for children with the Lennox-Gastaut syndrome. Gabapentin was approved January 1994 as adjunctive therapy in patients 12 years or older with partial seizures, with or without secondary generalization. Lamotrigine is expected to be approved this year for the treatment of partial and tonic-clonic seizures in adults. Last, a new drug application has been filed for vigabatrin this year, with possible licensing next year. These four anticonvulsants present new options in the treatment of patients with refractory epilepsy and are not merely congeners of previously available treatments. They have unique clinical spectrums and are reported to be safer and better tolerated than conventional therapy. Trials to compare their use with that of conventional therapy have not been done, and their use in the initial treatment of patients with epilepsy is not completely clear.     

The role of radiation therapy for carcinoma of the lung

A large proportion of patients with carcinoma of the lung may benefit from the use of radiation therapy. Operable patients have not been shown to benefit from preoperative irradiation, but postoperative irradiation has improved survival in those found to have involvement of hilar or mediastinal lymph nodes. Radiation therapy is the only potentially curative treatment for patients who are inoperable, but do not have distant metastasis. Control of the local tumor is very dependent upon dose-fractionation-time relationships. Patients who are relatively asymptomatic, i.e., they have a high performance status, are curable if treated promptly with radiation therapy. Small cell carcinoma requires both radiation therapy and chemotherapy. The optimal method of combining the two modalities is yet to be determined, but prophylactic cranial irradiation is necessary to control microscopic metastases that are not affected by systemic chemotherapy, and thoracic irradiation is necessary to give the highest probability of control of the primary tumor. Prophylactic cranial irradiation has also been shown to reduce the frequency of brain metastasis in patients with squamous carcinoma, large cell carcinoma, and adenocarcinoma; it may become more important in these cell types when more effective chemotherapy is developed.     

The Promher Study: An Observational Italian Study on Adjuvant Therapy for HER2-Positive,pT1a-b pN0 Breast Cancer

BackgroundThe management of pT1a-b pN0 HER2-positive breast cancer is controversial and no data about the efficacy of trastuzumab in this setting are available from randomized clinical trials. The aims of this retrospective study were to assess how patients are managed in clinical practice in Italy, which clinical or biological characteristics influenced the choice of adjuvant systemic therapy and the outcome of patients.MethodsData of consecutive patients who underwent surgery from January 2007 to December 2012 for HER2-positive, pT1a-b pN0 M0 breast cancer were retrospectively collected from 28 Italian centres. Analysis of contingency tables and multivariate generalized logit models were used to investigate the association between the baseline clinical and biological features and the treatment strategy adopted.ResultsAmong 303 enrolled patients, 204 received adjuvant systemic therapy with trastuzumab, 65 adjuvant systemic therapy without trastuzumab and 34 did not receive adjuvant systemic therapy. At the multivariate analysis age, tumor size, proliferation index and hormone receptor status were significantly associated with the treatment choice. Five-year disease-free survival (DFS) probability was 95%, 94.3% and 69.6% for patients treated with adjuvant systemic therapy and trastuzumab, with adjuvant systemic therapy without trastuzumab and for patients who did not receive adjuvant systemic therapy, respectively (p<0.001).ConclusionsThe majority of patients (66%) with pT1a-b pN0 HER2-positive breast cancer enrolled in this retrospective study received adjuvant systemic therapy with trastuzumab, whereas only 11% patients did not receive any adjuvant systemic therapy. The choice of treatment type seems to be mainly influenced by tumor size, proliferation index, hormone receptor status and age. The 5-year DFS probability was significantly higher for patients receiving adjuvant systemic therapy with trastuzumab compared with patients not receiving adjuvant systemic therapy or receiving adjuvant systemic therapy without trastuzumab.     

Addition of basal insulin to oral antidiabetic agents: a goal-directed approach to type 2 diabetes therapy

The objective of this article is to review current findings in the published literature on the efficacy of insulin therapy in combination with oral antidiabetic agents, with a focus on practical information that might help to provide an evidence-based template for selecting how best to combine oral agents and basal insulin in patients with type 2 diabetes. Here we review the current oral agents used to treat type 2 diabetes, their mechanisms of action, and how they can be combined with insulin therapy to help patients achieve guideline-recommended glycemic goals. While practical advice exists for initiating a therapeutic regimen comprised of basal insulin and oral agent(s), direction as to appropriate therapy for individual patients with differing physiologic requirements is needed. Oral antidiabetic therapy in combination with insulin provides an effective therapeutic option for patients who are unable to achieve or maintain glycemic goals on oral therapy alone.     

Salvage cryosurgery of the prostate after radiation failure

Radiation therapy is one option for patients with localized prostate cancer. Despite advances in delivering radiation to the prostate gland with therapies such as brachytherapy and/or external beam radiation therapy, urologists will be faced with managing patients with rising prostate-specific antigen values and with positive biopsy results secondary to radiation-recurrent prostate cancer. If the cancer is detected early, salvage therapy can be initiated. Since salvage prostatectomy is associated with significant morbidity, patients are often left with the option of either watchful waiting or temporary palliation with hormone deprivation therapy, with its attendant toxicity. The introduction of third-generation cryotechnology using 17-gauge CryoNeedlestrade mark (Oncura, Inc., Plymouth Meeting, PA) and the recent modifications in the technique of salvage cryosurgery have enabled cryosurgeons to eradicate these tumors safely and with significantly decreased morbidity. Selection and management of patients, as well as the contemporary results of salvage cryosurgery, are discussed in this article.     

Delayed-immediate breast reconstruction

In patients with early-stage breast cancer who are scheduled to undergo mastectomy and desire breast reconstruction, the optimal timing of reconstruction depends on whether postmastectomy radiation therapy will be needed. Immediate reconstruction offers the best aesthetic outcomes if postmastectomy radiation therapy is not needed, but if postmastectomy radiation therapy is required, delayed reconstruction is preferable to avoid potential aesthetic and radiation-delivery problems. Unfortunately, the need for postmastectomy radiation therapy cannot be reliably determined until review of the permanent tissue sections. The authors recently implemented a two-stage approach, delayed-immediate breast reconstruction, to optimize reconstruction in patients at risk for requiring postmastectomy radiation therapy when the need for postmastectomy radiation therapy is not known at the time of mastectomy. Stage 1 consists of skin-sparing mastectomy with insertion of a completely filled textured saline tissue expander. After review of permanent sections, patients who did not require post-mastectomy radiation therapy underwent immediate reconstruction (stage 2) and patients who required postmastectomy radiation therapy completed postmastectomy radiation therapy and then underwent standard delayed reconstruction. In this study, the feasibility and outcomes of this approach were reviewed. Fourteen patients were treated with delayed-immediate reconstruction between May of 2002 and June of 2003. Twelve patients had unilateral reconstruction and two patients had bilateral reconstruction, for a total of 16 treated breasts. All patients completed stage 1. Tissue expanders were inserted subpectorally in 15 breasts and subcutaneously in one breast. The mean intraoperative expander fill volume was 475 cc (range, 250 to 750 cc). Three patients required postmastectomy radiation therapy and underwent delayed reconstruction. Eleven patients did not require postmastectomy radiation therapy. Nine patients had 11 breast reconstructions (stage 2), six with free transverse rectus abdominis musculocutaneous (TRAM) flaps, one with a superior gluteal artery perforator flap, and four with a latissimus dorsi flap plus an implant. The median interval between stages was 13 days (range, 11 to 22 days). Two patients who did not require postmastectomy radiation therapy have not yet had stage 2 reconstruction, one because she wished to delay reconstruction and the other because she required additional tissue expansion before permanent implant placement. Six complications occurred. The stage 1 complications involved two cases of mastectomy skin necrosis in patients who required post-mastectomy radiation therapy; one patient required removal of the subcutaneously placed expander before postmastectomy radiation therapy and the other patient had a subpectorally placed expander that only required local wound care. The stage 2 complications were a recipient-site seroma in a patient with a latissimus dorsi flap, a recipient-site hematoma in the patient with the superior gluteal artery perforator flap, and two arterial thromboses in patients with TRAM flaps. Both TRAM flaps were salvaged. Delayed-immediate reconstruction is technically feasible and safe in patients with early-stage breast cancer who may require postmastectomy radiation therapy. With this approach, patients who do not require postmastectomy radiation therapy can achieve aesthetic outcomes essentially the same as those with immediate reconstruction, and patients who require postmastectomy radiation therapy can avoid the aesthetic and radiation-delivery problems that can occur after an immediate breast reconstruction.