A pituitary gene encodes a protein that produces differentiation of breast and prostate cancer cells

A cDNA clone of 1.1 kb encoding a 108-aa polypeptide was isolated from a human pituitary cDNA library by expression cloning. This protein was named tumor differentiation factor (TDF). The recombinant TDF protein and a 20-aa peptide, P1, selected from the ORF of the gene, induced morphological and biochemical changes consistent with differentiation of human breast and prostate cancer cells. Fibroblast, kidney, hepatoma, and leukemic lymphocytic cell lines were unaffected. Breast and prostate cancer cells aggregated in spheroid-like structures within 24 h of exposure to TDF. This effect was abrogated by a specific affinity-purified rabbit polyclonal anti-P1 Ab. E-cadherin expression was increased in a dose-dependent manner by TDF. Treatment of MCF7 cells with TDF led to production of a lactalbumin-related protein. Peptide P1 significantly decreased the growth of androgen-independent DU145 prostate cancer in severe combined immunodeficient mice. The presence of TDF protein in human sera was detected by the anti-P1 Ab, suggesting a role of TDF in endocrine metabolism. The fact that all activities of TDF can be mimicked by a peptide derived from the encoding TDF sequence opens the possibility of therapeutic applications.     

Vasculitis in the very elderly

BACKGROUND: Whatever may be their clinical presentation, vasculitis syndromes (VS) have a bad prognosis in the very elderly. OBJECTIVE: The aim of this work was to study VS particularities in very old people. Most published studies on VS in elderly people concern patients older than 60 years; studies concerning very old patients are unusual. METHODS: We studied retrospectively subjects older than 75 years with a diagnosis of VS from the Departments of Geriatrics and Internal Medicine at Dijon University Hospital. These subjects were hospitalized between January 1995 and December 1999. Data were obtained from the medical files of these patients. Several aspects were considered: type of VS, associated diseases, treatment, complications, and outcome. RESULTS: Twelve patients, 5 men and 7 women aged 79-91 (mean age 82.3) years, were included. Primary VS was observed in half of the patients and secondary VS in the others. The initial clinical presentation was often polymorphous and unspecific; 8 of the patients died, 2 developed progressive severe functional impairment, 1 was stabilized under therapy, and 1 patient with VS secondary to infection recovered. Most patients either died quickly or progressively deteriorated from infections, malnutrition, or functional impairment. CONCLUSION: The health of the majority of patients (83%) deteriorated dramatically, leading to death or severe functional impairment.     

Tentorial dural fistula with giant venous ampulae treated with embolisation and surgery. A case report

Tentorial dural arteriovenous fistulas are rare and complex lesions in deep locations with unusual vascular anatomy and critical surrounding neuroanatomy. A rare case presenting a complex fistula with a giant venous draining ampulae, causing headaches and visual troubles is presented. We describe the case of a 52-year-old woman admitted in our department for headaches and visual troubles. Magnetic resonance imaging and cerebral angiography showed a tentorial dural arteriovenous fistula draining in a giant tentorial venous ampulae and leptomeningeal veins. The patient was embolised via an arterial route with a good clinical and radiological result. However, 4 days later she presented a sudden change of her clinical status with coma, left hemiparesis and a right midriasis. The cerebral computed tomography scan showed a huge occipital haemorrhagic mass and a severe cerebral oedema. An emergent surgical procedure was decided realising evacuation of the occipital haematoma and a complete resection of the giant venous ampoule. The neck of the ampulae was sutured and clipped at its dural entrance. Postoperatively a new embolisation was realised because of persistent of a small dural fistulae with occipital leptomeningeal drainage. The patient recovered rapidly with only a residual hemianopsy. Treatment of dural AV malformation represent a serious challenge. Our report describes an unusual case of a tentorial dural complex fistula treated by an endovascular procedure with secondary clinical aggravation that needed emergent surgical therapy. Even in a case for good immediate radiological result after endovascular procedure, dural arteriovenous fistulas with giant venous ampulae and important venous engorgement, need closed follow-up, because of the possibility of aggravation secondary to venous thrombosis and haemorrhage. Treatment and patophysiology of the aggravation mechanism are discussed.     

Different Profile of Peripheral Antioxidant Enzymes and Lipid Peroxidation in Active and Non-active Inflammatory Bowel Disease Patients

Background

The role of oxidative stress in inflammatory bowel diseases (IBD) has been extended lately from a simple consequence of inflammation to a potential etiological factor, but the data are still controversial. Active disease has been characterized before by an enhanced production of reactive oxygen species and the increased peroxidation of lipids, but patients in remission were generally not considered different from healthy people in terms of oxidative stress.

Aims

We evaluated the antioxidant defense capacity and lipid peroxidation status in the serum of patients with active and non-active disease compared with healthy matched control subjects.

Methods

The study included 20 patients with confirmed IBD in clinical and biological remission, 21 patients with active disease, and 18 controls. We determined the serum levels of two antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GPX), and a lipid peroxidation marker, malondialdehyde (MDA).

Results

Active disease patients had an increased activity of both SOD and GPX, as well as significant high values of MDA versus controls. Furthermore, patients being in remission had significantly lower values of antioxidant enzymes (SOD and GPX) and increased lipid peroxidation measured by MDA serum levels, as compared with healthy control subjects.

Conclusions

Our study confirmed the presence of high oxidative stress in active IBD. More importantly, we have demonstrated a lower antioxidant capacity of patients in remission versus control group. This may represent a risk factor for the disease and can be an additional argument for the direct implication of oxidative stress in the pathogenesis of IBD.     

Genetic polymorphisms impact the risk of acute rejection in pediatric heart transplantation: a multi-institutional study

OBJECTIVE: The objective of this study was to determine the association between the genetic polymorphisms of proinflammatory and regulatory cytokines and long-term rates of repeat and late acute rejection episodes in pediatric heart transplant (PHTx) recipients. METHODS: Three hundred twenty-three PHTx recipients: 205 White non-Hispanic, 43 Black non-Hispanic, and 75 Hispanic were analyzed for time to first repeat and late acute rejection episodes by race, age at transplantation, and gene polymorphism (interleukin [IL]-6, -174 G/C, IL-10, -1082 G/A, -819 C/T, 592 C/A; vascular endothelial growth factor (VEGF) -2578 C/A, -460 C/T, +405 C/G; tumor necrosis factor alpha (TNF-alpha)-308 G/A). RESULTS: Recipient black race and older age at transplant were risk factors for both repeat and late rejections, though black race was more significantly related to late rejection (P=0.006). Individually, TNF-alpha high, IL-6 high, VEGF high, and IL-10 low phenotypes did not impact the risk of repeat or late rejection. However, the combination VEGF high/IL-6 high and IL-10 low was associated with increased estimated risk of late rejection (P=0.0004) and only marginally with repeat rejection (P=0.051). In a multivariate analysis, adjusting for age and race, VEGF high/IL-6 high and IL-10 low still remained an independent risk factor for late acute rejection (RR=1.91, P<0.001). CONCLUSION: This is the largest multicenter study to document the impact of genetic polymorphism combinations on PHTx recipients' outcome. The high proinflammatory (VEGF high/IL-6 high) and lower regulatory (IL-10 low) cytokine gene polymorphism profile exhibited increased risk for late rejection, irrespective of age and race/ethnicity.     

Retransplant candidates have donor-specific antibodies that react with structurally defined HLA-DR,DQ,DP epitopes

This report describes a detailed analysis how donor-specific HLA class II epitope mismatching affects antibody reactivity patterns in 75 solid organ transplant recipients with an in situ allograft and who were considered for retransplantation. Sera were tested for antibodies in a sensitive antigen-binding assay (Luminex) with single class II alleles. Their reactivity was analyzed with HLAMatchmaker, a structural matching algorithm that considers so-called eplets to define epitopes recognized by antibodies. Only 24% of the patients showed donor-specific anti-DRB1 antibodies and there was a significant correlation with a low number of mismatched DRB1 eplets. This low detection rate of anti-DRB1 antibodies may also be due to allograft absorption. In contrast, antibodies to DRB3/4/5 mismatches were more common. Especially, 83% of the DRB4 (DR53) mismatches resulted in detectable antibodies against an eplet uniquely found on DR53 antigens. Donor-specific DQB mismatches led to detectable anti-DQB antibodies with a frequency of 87%. Their specificity correlated with eplets uniquely found on DQ1-4. The incidence of antibodies induced by 2-digit DQA mismatches was 64% and several eplets appeared to play a dominant role. These findings suggest that both alpha and beta chains of HLA-DQ heterodimers have immunogenic epitopes that can elicit specific antibodies. About one-third of the sera had anti-DP antibodies; they reacted primarily with two DPB eplets and an allelic pair of DPA eplets. These data demonstrate that HLA class II reactive sera display distinct specificity patterns associated with structurally defined epitopes on different HLA-D alleles.     

The knowledge,awareness, and practice patterns of dermatologists toward psychocutaneous disorders: results of a survey study

Background To assess the level of training in, and awareness and attitude about, psychocutaneous disorders among dermatologists. Methods A mail‐in survey was sent to all members of Washington State Dermatology Society, who were requested to provide information on demographic variables; level of training, skills, and degree of comfort in managing psychodermatologic disorders; referral patterns, knowledge of patient and family resources on psychodermatology; and interest in continuing medical education on psychocutaneous disorders. Results Of 237 mailed surveys, 102 were returned for analysis. Only 18% of dermatologists reported a clear understanding of psychodermatology, and 42% of the respondents reported being very comfortable in diagnosing and treating psychocutaneous disorders. Acne, atopic dermatitis and psoriasis were reported as the most common diagnoses associated with psychiatric manifestations. Delusion of parasitosis, neurotic excoriations, and trichotillomania were the most common conditions wherein patients were referred by dermatologists to psychiatrists. About 90% of the survey respondents were not aware of any patient or family resources on psychodermatology. Overall, 39% of the dermatologists expressed interest in attending any kind of continuing medical education activity on psychodermatologic disorders. Conclusion Survey results showed that knowledge about the diagnosis, treatment and/or appropriate referral for psychocutaneous disorders is lacking. Significant information gaps were also identified in the knowledge of patient or family resources on psychocutaneous disorders. We recommend the incorporation of formal training and didactics on psychodermatology in dermatology residency programs and regular CME events. Dermatology–Psychiatry liaison services and psychodermatology clinics will prove helpful in the management of these patients in clinical settings.     

Extracorporeal Shock Wave Therapy for the Treatment of Chronic Pelvic Pain Syndrome in Males: A Randomised, Double-Blind, Placebo-Controlled Study

Background

There is no sufficiently validated therapy for chronic pelvic pain syndrome (CPPS).

Objective

To investigate the effects of extracorporeal shock wave therapy (ESWT) in 60 patients suffering from CPPS.

Design, setting, and participants

Sixty patients suffering from CPPS for at least 3 mo were investigated in two groups. Both groups were treated four times (once per week), each by 3000 impulses; group 2 was performed as a sham procedure. The investigation was designed as a placebo-controlled, prospectively randomised, double-blind phase 2 study. Standardised follow-up was performed 1, 4, and 12 wk after ESWT.

Interventions

Low-energy–density ESWT was performed using a perineal approach without anaesthesia. In the placebo group, the same setting was used without shock wave energy transmission.

Measurements

ESWT effects on pain, quality of life (QoL), erectile function (EF), and micturition were evaluated. The parameters were investigated using validated questionnaires (National Institutes of Health Chronic Prostatitis Symptom Index [NIH-CPSI], International Prostate Symptom Score [IPSS], International Index of Erectile Function [IIEF]) and the Visual Analog Scale (VAS) for pain evaluation.

Results and limitations

All patients completed outpatient treatments and follow-ups without any problems. All 30 patients in the verum group showed statistically (highly) significant improvement of pain, QoL, and voiding conditions following ESWT in comparison to the placebo group, which experienced a continuous deterioration of the same parameters during the follow-up period. Perineal ESWT was easy and safe to perform without anaesthesia or any side-effects.

Conclusions

This is the first prospectively randomised, double-blind study to reveal perineal ESWT as a therapy option for CPPS with statistically significant effects in comparison to placebo. ESWT may in particular be interesting because of its easy and inexpensive application, the lack of any side-effects, and the potential for repetition of the treatment at any time.     

Should we be more aggressive in the therapy against cardiovascular risk factors? Should we prescribe statin and aspirin for every diabetic patient, or is it time for a polypill?

The reality of primary and secondary prevention of cardiovascular complications in people with diabetes is alarming, even in developed countries with a well-structured medical system. Even though therapeutic targets have been more clearly defined during the last decades, their implementation is still suboptimal. Financial and structural reasons, insufficient information of physicians and patients, along with a low compliance of the latter are only a few reasons that have been incriminated. To eliminate some of these inconveniences, attempts to standardize and simplify therapies have been made. Treatment with aspirin and statin for every patient with diabetes has been postulated. Some went even further, developing the concept of a "polypill," an integrated pharmacological agent with up to six different compounds meant to prevent cardiovascular disease in the broad population. Likewise, the idea of a "polymeal" tries to implement healthy nutrients into the populations' lifestyle in a standardized fashion. Our article highlights some of the advantages and pitfalls of these concepts and reflects our point of view with regard to some treatment aspects in people with diabetes. As part of a pro and contra discussion, our article is arguing against the use of statins in all patients with diabetes and especially against the indiscriminate use of a polypill.     

Cardiovascular complications in diabetes: targets and interventions

Cardiovascular complications are mainly responsible for the high morbidity and mortality in people with diabetes. The awareness of physicians for the importance of primary prevention increased lately and numerous strategies have been developed. The spectrum ranges from pharmacologic treatment to vitamins and dietetic interventions. Some interesting concepts such as focusing on exogenous advanced glycation end products have emerged, but definitive results on their clinical relevance are still lacking. A major problem of the primary prevention is the choice of the method applied for screening, the criteria used to classify risk patients, as well as the choice of therapy. Guidelines provide goals to be achieved and offer alternatives for treatment, but the medical decision has to be made on an individualized basis. In this overview, we will comprehensively focus on the most important pathomechanisms and clinically relevant approaches, aiming at the early diagnosis and treatment of diabetes along with coronary heart disease. When primary prevention fails, we advocate a more aggressive treatment of critically ill patients, followed by optimal secondary prevention meeting on-target goals precisely.