Can brucellosis influence the course of chronic hepatitis C in dual infection?

Hepatitis C and brucellosis are infectious diseases that occur worldwide, and both are endemic in Egypt. Co-infection with both agents is possible, and this can involve the liver in various ways. In this study, we investigated serum tissue inhibitor metalloproteinase-1 (TIMP-1), viral load, and liver functions in patients co-infected with hepatitis C virus (HCV) before and after brucellosis treatment. Over 3 years, 241 consecutive HCV patients (before interferon therapy was received) with recurrent fever who had occupational contact with animals were tested for brucellosis co-infection by a standard tube agglutination test. In patients with dual infection, viraemia (RT-PCR), TIMP-1 measured by ELISA, and liver functions were assessed and re-evaluated 2 months after brucellosis treatment. The number of patients with HCV/brucellosis co-infection was 32 out of 241 (13.3%). TIMP-1, viraemia, AST, ALT and bilirubin showed significant decrease (improvement) after brucellosis treatment (p < 0.001) but an insignificant difference (p > 0.05) with regard to serum albumin and prothrombin concentration. The study revealed that brucellosis is an important infection in HCV-infected patients and can aggravate the course of disease, suggesting that early treatment and prevention are important.     

Future developments in the medical treatment of abnormal uterine bleeding: what can we expect?

New therapies for abnormal uterine bleeding have been slow to reach the marketplace for a variety of reasons. These reasons include the availability of cost-effective therapies already available and the extraordinarily difficult and expensive regulatory barriers emphasizing long-term safety. Common comorbidities like bleeding diatheses, adenomyosis, and leiomyomata further complicate clinical development, necessitating large study samples and making it more expensive. Even the accurate measurement of menstrual blood loss adds an additional hindrance to novel drug development. These obstacles and the currently available therapies will be reviewed in the context of developing new methods for approaching this complicated and prevalent clinical problem.     

Can we reduce the dosage of biologics in spondyloarthritis?

TNF blockers have revolutionized the management of spondyloarthritis (SpA). To date, four anti-TNFα agents (etanercept, infliximab, adalimumab, golimumab) have been approved for the management of ankylosing spondylitis (AS) and psoriatic arthritis (PsA). The first objective in the management of AS and PsA with TNF inhibitors is to reduce disease activity to clinical remission or low disease activity. After remission has been achieved, this state should be maintained as long as possible. However, the financial burden associated with the cost of anti-TNF agents as well as concerns about their long-term safety suggest reducing the dosage of the drug or discontinuing the therapy in the hopes of drug-free remission. The aim of this review is to examine what has, till now, been published on this topic in axial SpA, which includes AS and non-radiographic axial SpA (nr-axSpA), peripheral SpA and PsA. Discontinuation of therapy in axial SpA is not possible in the majority of patients, while on the contrary, reducing the dosage often is. In some patients with peripheral SpA and PsA it is also possible to discontinue therapy and to achieve drug-free remission.     

Can HCV affect the efficacy of anti-HIV treatment?

Summary.  To evaluate the impact of new antiretroviral combinations (HAART: Highly Active Anti Retroviral Therapy) on HCV replication and liver enzyme levels, we analysed the changes in HCV viremia and aminotransferase levels in HIV and HCV co-infected patients. Moreover, to evaluate the influence of HCV infection on the efficacy of HAART, we compared the virological, immunological and biochemical response to antiretroviral combinations in anti-HIV positive subjects with or without HCV infection. We enrolled eight consecutive outpatients with HIV-HCV coinfection and with indications for HAART (Group A). For each patient in group A, we selected an anti-HIV negative patient with indications for HAART, pair-matched for age, sex, risk factor for HIV infection, presumed duration of infection, number of CD4 cells, HIV viremia and treatment schedule (Group B). A statistically significant increase in CD4 in both groups was found at 1^st, 3^rd and 6^th month of antiretroviral therapy. A decrease in HIV-RNA in both groups was observed at 1^st and 6^th month of treatment. The percentage of patients with undetectable HIV-RNA at the 1^st month was higher in Group B than in Group A (8/8 vs. 3/8, p = 0.025). Basal HCV-RNA viremia was very high in each case and no variations during treatment were observed. During therapy the aminotransferase levels slightly decreased in Group A and consistently increased in Group B. In Group A the differences were not significant to the statistical analysis; in Group B the aminotransferase levels at 3^st and 6^th month were significantly higher than those observed at the baseline. Received September 28, 1999/Accepted December 7, 1999     

Does family interrelating change over the course of individual treatment?

Interrelating is a combination of each person's relating towards a specified other and each person's view of the other's relating towards him/her. Negative interrelating is a maladaptive form of interrelating. The study aims to (1) compare the negative interrelating within the families of neurotic and psychotic psychotherapy outpatients; (2) examine whether individual treatment has a beneficial effect upon negative interrelating; (3) examine whether the improvement extends beyond the patients' interrelating with their parents (i.e., between the parents and the patients' sibling and between the parents themselves); and (4) make similar comparisons within a sample of non‐patients. The negative interrelating between the psychotic patients and their parents was more marked than that between the neurotic patients and their parents. The negative interrelating between the patients and their parents dropped significantly over the course of therapy. There were also significant changes in the interrelating between the patients' siblings and their parents and between the parents themselves even though they had not been involved in the therapy. Many of the end of therapy scores of the patients and their parents approached more those of the non‐patients. Copyright © 2010 John Wiley & Sons, Ltd. Key Practitioner Message: ? It is useful to measure both the negative relating of patients and the negative interrelating between patients and other family members. ? The patients' therapy appears also to benefit the interrelating between those family members who were not involved in the therapy. ? These findings may be more marked in Greek families, in which young adults stay closer to their parents.     

What kind of research can we realistically expect from the practitioner?

This article attempts to revitalize the scientist-practitioner model of psychotherapy by focusing on the research component of the model. Specifically, it takes a realistic look at the types of research that can be conducted by clinicians in an effort to motivate them to engage regularly in clinical research. Towards this end, five experienced scientist-practitioners explore the advantages, disadvantages, and potential of practitioner-initiated research. The problems and solutions for such research are discussed, and recommendations are offered.     

Pancreatic islet autotransplantation combined with total pancreatectomy for the treatment of chronic pancreatitis – the Leicester experience

Islet autotransplantation offers the potential for preventing the surgically induced diabetes that is an inevitable consequence of total pancreatectomy. This paper describes the first islet autotransplant programme in the United Kingdom and the first series in the world to use the spleen as a site for the islet graft. Over an 11 month period, 7 patients underwent total pancreatectomy for chronic pancreatitis combined with a simultaneous islet autotransplant. All 7 patients had normal glucose-tolerance levels and normal C-peptide levels pre-operatively. In 6 patients, islets were embolized into the liver via the portal vein (median transplanted volume=8.5 ml). In addition, 3 patients received islets into the splenic sinusoids via a short gastric vein (median transplanted volume=4 ml). One patient received islets into the spleen alone. One patient died of a stroke 4 weeks post transplantation. Two patients have achieved insulin independence, with a further two patients achieving ”transient” insulin independence (<1 month). The remaining 2 patients, although requiring reduced insulin doses, have not achieved insulin-independence. However, all patients have C-peptide levels within the normal range. In trying to explain these findings, split proinsulin levels were measured and found to be elevated. High levels of split proinsulin cross react with the C-peptide assay and this would explain the falsely elevated C-peptide levels. Indeed insulin levels in these patients were all below the normal range. These findings would suggest that the use of C-peptide levels as the ”gold standard” for monitoring islet autograft function, may require reappraisal.     

Tuberculosis in the course of sarcoidosis treatment: is genotyping necessary for personalized therapy?

Pathological similarities between sarcoidosis (SA) and tuberculosis (TB) suggest that mycobacterial antigen(s), in genetically different predisposed hosts, may be a cause of SA. The authors’ work and other published comparative analyses of HLA and non-HLA alleles in patients with SA or TB from different ethnic groups in the world revealed that some antigens were connected with high risk of SA or TB development, but others were comparable in both patient populations. The authors also showed a possibility of predominant occurrence of HLA alleles characteristic for TB as a cause of TB in patients with SA on corticosteroid therapy. It is possible that an analysis of SA and TB patient’s genetic background may be helpful for protection from TB in SA patients on corticosteroids, especially on anti-TNF-α treatment. The authors suggest that the consideration of an immunosuppressive therapy in SA patients will need more attention and individual therapy based on genotyping study.     

Can the disease course in Parkinson’s disease be slowed?

Background

The diagnosis of Parkinson’s disease (PD), which is needed for useful symptomatic therapy, is based on clinical criteria. However, it became quite clear in recent years that the same features can occur through different etiopathogenic mechanisms. Even a pathological diagnosis of PD, based on the demonstration of α-synuclein deposits in a typical distribution, can result from different causes and, vice versa, nigral cell loss can occur without α-synuclein deposition.

Discussion

Thus far, attempts to influence the progression of PD have failed. However, since the clinical manifestations of PD can be the result of diverse mechanisms, a single intervention may not be able to slow the course of the disease in all patients. Indeed, targeting the underlying pathogenic processes, which differ among cases, may be more effective. PD may develop as a consequence of mitochondrial damage, which itself may result from a variety of genetic or environmental factors. Correction of the ensuing oxidative stress may theoretically be useful in these PD patients, but will not affect the progression of the disease among other PD patients in whom an identical clinical syndrome derives from defects in other pathways such as the ubiquitin-proteasome system and lysosomal dysfunction, among others.

Summary

Precision medicine can now be used to identify the underlying pathogenic mechanisms in individual patients, paving the way to the development of real disease modification through a pathway-oriented approach, aimed at the underlying biologic processes of disease occurrence and evolution.

     

Are we closer to understanding the pathophysiology of chronic rhinosinusitis?

Cite this as: M. Ling and D. L. Hamilos, Clinical & Experimental Allergy, 2011 (41) 144–146.     

Analysis of the course and treatment of toxocariasis in children—a long-term observation

Toxocariasis is a helminthozoonotic disease caused by ascarid larvae of Toxocara genus: Toxocara canis and Toxocara cati. In the reported study, the clinical course of toxocariasis and administered therapy were evaluated in 103 children. The majority of the children (68.9%) were from the rural environment, with a prevalence of boys (62.1%). At diagnosis of infection, 36 (35%) children reported recurrent abdominal pain, 19 (18.4%) headache, 6 (5.8%) loss of appetite, 2 subfebrile conditions, and 2 arthralgia, Moreover, 23 (22.3%) children demonstrated symptoms of atopic diseases; in 30 (29.1%) children, moderate enlargement of lymphatic nodes was noted. In five children (4.9%), ophthalmic examination revealed unilateral changes in the eye: in two cases retinitis; in one case fibrotic lesions in the vitreous body, complicated 1 year from diagnosis by retinal detachment; and in other children parafoveal lesions and cataract. Only two children with ocular changes at diagnosis reported visual disorders. In 64.3% of children, eosinophilia was observed. A covert form of the disease was diagnosed in 95.1% of the children and an ocular form in 4.9%. In all the children, antiparasitic treatment was implemented, repeated several times in some of them. After therapy, the mean titer of specific antibodies, the number of children with abdominal pains and enlarged lymphatic nodes were decreased, while headaches maintained at unchanged levels. In approximately one fourth of the children with negative results of antibodies after the therapy, the symptoms of the disease were still reported. Evaluation of the efficacy of treatment is not easy due to non-characteristic symptoms and low kinetics of specific anti Toxocara IgG decrease; however, high IgG titers suggest non-effective treatment of concomitant infection requiring subsequent therapy. Due to risk of ocular form, which may develop in any stage of the disease, irrespectively of specific antibodies concentrations, it seems justified to implement antiparasitic treatment in all children infected with T. canis.     

Can olfactory training change the psychosocial aspects of chronic pain?

Pain and smell are the oldest senses for apperceive our environment. It is known that chronic pain and olfaction share common limbic cortical regions which are the main parts of the pain neuromatrix such as the anterior cingulate cortex, amygdala, and orbitofrontal cortex. Also, these regions point out the psychosocial aspects of chronic pain. And currently, the most challenging part of chronic pain management is the psychosocial aspect such as kinesiophobia, catastrophizing, or depression. Thus, the connection between olfaction and pain has promising clues to determining new combined therapies with odor training. According to intriguing brain imaging and genetic studies, we hypothesized that patients with chronic pain may have differentiated olfactory thresholds. Further, the additional odor training to the traditional therapeutic approach could be beneficial regarding the patients’ pain perspective and psychosocial domains.     

Can we manage lupus nephritis without chronic corticosteroids administration?

The outcome of lupus nephritis (LN) has changed since the introduction of glucocorticoids (GCs), which dramatically reduced the mortality related to one of the most severe complications of systemic lupus erythematosus (SLE). Since the 1950′s, other immunosuppressants, including biologic drugs (i.e. rituximab) have aided in maintaining remission, preserving kidney function, but not preventing treatment-related toxicity.GCs still remain the cornerstone in the treatment of SLE, including LN, and they are widely used in clinical practice. However, GC administration represents a double-edged sword. Indeed, from one side they allow a fast and effective control of disease activity by dampening inflammation; from the other side, they have many and severe side effects leading to organ damage.In this paper, we will discuss pros and cons of the chronic use of GCs, especially focusing on LN.     

Can we use NOACS in APS?

Secondary thromboprophylaxis with low molecular heparin or vitamin K antagonists (VKAs) is recommended in patients with definite antiphospholipid syndrome (APS). Direct oral anticoagulant (DOACs) have been approved in different prothrombotic conditions and have numerous advantages compared to VKAs. Whether DOACs can be used for secondary prophylaxis in APS is an open question. Data from the TRAPS randomized controlled Trial, meta-analysis and case reports indicate that we should not treat patients with triple positive APS and/or arterial thrombi with routine doses of DOACS. On the other hand, data from the literature including, case series, meta- analysis and the RAPS trial indicate that there are low risk patients, such as patients who suffered from a venous but not an arterial thromboembolism and are LAC negative who may benefit from the treatment with DOACs. Prospective trials addressing these low risk patients are needed in order to consider DOAC treatment in such patients.