The Clinical Relevance of Beta Blockers in Ovarian Carcinoma: A Systematic Review.

The last ten years have seen hardly any improvement in the prognosis of ovarian carcinoma. There is a great need for new treatment strategies, and a recent retrospective study showing a survival advantage with the use of beta blockers met with a very positive response. This systematic review summarizes the current state of knowledge and research on the topic: A database analysis identified six clinical studies showing inconsistent results with respect to the administration of beta blockers and disease course. The 13 preclinical studies identified showed almost without exception both that catecholamines had detrimental effects on tumour progression, and that these effects could be influenced by pharmacological blockade. Overall the available evidence does not justify the use of beta blockers in clinical practice for ovarian carcinoma at the present time. This article also outlines details of research design required for further studies needed on the subject. Preclinical research findings are however very impressive: They not only form an important basis for the development of future clinical studies but also, through revealing new pathomechanisms, they already make an important contribution towards the development of new treatment strategies for ovarian carcinoma.

[Endonasal Dacryocystorhinostomy (DCR) with Transcanalicular Endoillumination (TCE) of the Saccus Lacrimalis]. / Endonasale Dacryozystorhinostomie (DCR) mit transkanalikulärer Endoillumination (TCE) des Saccus lacrimalis.

Endonasal dacryocystorhinostomy (DCR) has been established as a standard procedure of lacrimal surgery, since it causes much less tissue damage than ab externo procedures. Diffiulties in visualization of the target area has been a limitation to the transnasal approach. An improvement of the classical endonasal DCR was achieved by the introduction of a transcanalicular endoillumination (TCE) of the lacrimal sac using a 23-Gauge vitreoretinal light probe, which can easily be intubated into the cannaliculi and advanced into the the lacrimal sac. Illumination of the lacrimal sac guides the endonasal approach and facilitates the creation of a lacrimal bypass. In our standard procedure a bicanalicular silicone intubation through the osteotomy is finally placed. Due to the introduction of TCE of the lacrimal sac, the surgical procedure of endonasal DCR became less traumatic and needed a significantly reduced operating time.

[Conservative treatment of dry eye]. / Konservative Therapie des trockenen Auges.

The use of topic anti-inflammatory drugs has become very important in the treatment of dry eye disease. Besides the basic therapy including tear replacement, use of serum eye drops and mucolytic eye drops, the topical application of corticosteroids and cyclosporin A is more commonly used in moderate to severe forms of dry eye disease. The consistent treatment of Meibomian gland dysfunction as a frequent reason for evaporative dry eye is also of particular importance. Understanding the chronicity of the disease and long-term compliance are the essential for successful therapy of this widespread disease.

Factors related to psychosocial quality of life for children with cerebral palsy.

Background. Current health services interventions focus on the treatment of the musculoskeletal impairments of cerebral palsy (CP). The goal of this study was to explore whether the severity of physical symptoms correlates with psychosocial quality of life (QOL) among pediatric patients with CP. Methods. A sample of 53 caregivers of children with CP was surveyed and health status information was extracted from patient medical records. Descriptive analysis explored the association between the main outcome variable, psychosocial QOL (CP QOL-child), and patient demographics, comorbidity (e.g., visual, hearing and feeding impairments, language delays, and epilepsy), CP severity (GMFCS), and the receipt of family centered care (MPOC-20). Results. Child psychosocial QOL decreased with increasing comorbidity but was not associated with CP symptom severity or any measured demographic factors. Reporting high levels of family centered care (FCC) was associated with higher psychosocial QOL in univariate analysis but was not significant when controlling for comorbidities. Conclusion. There is no clear connection between symptom severity and psychosocial QOL in children with CP. Comorbidity however is strongly associated with psychosocial QOL. Focusing on reducing CP comorbidities could have a positive impact on psychosocial QOL.

[Stress and pancreatic carcinoma--ß-adrenergic signaling and tumor biology]. / Stress und Pankreaskarzinom. ß-adrenerge Signaltransduktion und Tumorbiologie.

In several carcinomas, ß-adrenergic signaling has been found to regulate relevant processes of cancer biology. Until recently, pancreatic cancer has not been in the focus of respective research. But in view of the incidence and poor prognosis of pancreatic cancer, new insights in biology and therapeutic strategies are of prime importance. Nowadays, several reports describe influences of the catecholaminergic system on pancreatic cancer in vitro and in vivo. Effects were shown on proliferation and apoptosis of carcinoma cells as well as on interactions with tumor-microenvironment and dissemination and metastasis formation. In contrast to other entities, evidence even suggests links between ß-adrenergic signaling and initiation of the disease. The following report summarizes the most relevant results demonstrating implications for further research and possible interventions.

High prevalence of distress in patients after allogeneic hematopoietic SCT: fear of progression is associated with a younger age.

Little is known about the psychological burden patients are left with after successful allogeneic hematopoietic SCT (HSCT). With the main focus on physical condition and common transplant complications, psychological symptoms often remain neglected in daily practice. To assess the prevalence of distress in patients who have undergone allogeneic HSCT, we conducted a cross-sectional pilot study in 50 consecutive patients from our outpatient transplant clinic using standardized questionnaires. Distress was categorized by symptoms of anxiety, fear of progression, depression and post-traumatic stress disorder (PTSD). Forty-one patients completed self-administered questionnaires. The median age was 53 years (21-74 years) and the mean time after transplantation was 614 days (25-2070 days). In total, 18 patients (44%) showed symptoms of distress. Among these 18 patients, 11 patients reported symptoms of anxiety, 12 patients suffered from fear of progression, 11 patients showed symptoms of depression and 6 patients of PTSD. Age below 55 years was significantly associated with fear of progression (P=0.004). This study demonstrates the high prevalence of distress in patients who have undergone allogeneic HSCT. Our results suggest an unmet need for professional support and intervention. These findings may be relevant as distress could have an influence on the outcome after HSCT.

Aplasia of the os odontoideum: Skeletal manifestation from Thailand.

Os odontoideum is a rare craniocervical abnormality of the axis resulting in absence (aplasia) of the dens and, possibly, dislocation of the atlantoaxial articulation. Skeleton 0202 from the Osteology Collection at Khon Kaen University, Thailand exhibits aplasia of the os odontoideum with torticollis, accompanied by an unusual constellation of skeletal features that include craniosynostosis, platybasia with mild basilar invagination, unilateral Kimmerle anomaly, disuse atrophy resulting in "wasting" of the upper and lower limbs, and marked stenosis of the right foramen transversarium of the axis. The remains of this individual provide anthropologists and clinicians the rare opportunity to study the combined effects of os odontoideum, craniosynostosis, torticollis, platybasia and skeletal atrophy in a known-identity individual from Thailand.

[Hypnotherapy for irritable bowel syndrome--a systematic review]. / Hypnotherapeutische Interventionen beim Reizdarmsyndrom - eine systematische Ubersicht.

The Irritable bowel syndrome (IBS) is a highly prevalent functional disorder with a remarkable clinical and economic impact. Several pathogenetic factors of IBS are discussed and summarised within a bio-psycho-social model. Data from published hypnotherapeutic interventions with approximately 800 patients show long-lasting symptom relief. The underlying mechanisms of action are not well understood. Nine mechanism studies show influences of hypnosis on colorectal sensitivity, colorectal motility and mental strain (anxiety, depression, maladaptive cognitions). Results are often contradictory and effects of hypnosis on several of the proposed pathogenetic factors are not examined at all. This paper reviews previous studies on hypnotherapy in IBS patients with a focus on symptom relief and mechanisms of action.

[Kallmann syndrome--a form of hypogonadotropic hypogonadism]. / Das Kallmann-Syndrom--eine Form des hypogonadotropen Hypogonadismus.

HISTORY: Two men (aged 44 and 47 years) were admitted with the diagnosis of Kallmann's syndrome, but they had widely different symptoms. The first patient (A) suffered from significant secondary symptoms, i.e. weight gain and skeletal pain, which had caused him to seek medical assistance. The second patient (B) had been admitted because of symptoms of depression, caused by separation from his female partner. INVESTIGATION: Patient A showed major somatic symptoms characteristic of the syndrome: eunuchoidism (physique, boyish voice, gynecomastia, micropenis and absent secondary sex characteristics). Further diagnostic tests revealed low testosterone concentrations (0.958 ng/ml; reference range 1.8 - 7.58 ng/ml) and low luteinizing hormone (LH) concentrations (<0.7 IU/l; reference range 0.8 - 7.6 IU/l), as well as infertility. Radiology showed marked osteoporosis, providing the indication for total hip replacement. Magnetic resonance imaging (MRI) of the skull and chromosomal analysis gave normal results. The physical development of patient B had progressed ever since hormone substitution after a suspected diagnosis of mumps orchitis in early childhood. However infertility was still present. Abnormal laboratory findings at admission: LH 0.10 IU/l (reference range 0.8 - 7.6 IU/l), follicle stimulating hormone 0.10 IU/l (reference range 1.2 - 10.1 IU/l), testosterone 10.0 ng/ml (reference range 1.8 - 7.58 ng/ml). A hypoplastic olfactory sulcus was shown by MRI, but no olfactory bulb. Mineral density of the femur was slightly diminished. Combined stimulation test of the pituitary gland revealed hypogonadotropic hypogonadism and anosmia in both patients. TREATMENT AND COURSE: In patient A administration of testosterone, calcium, colecalciferol and biphosphonates improved virilization and reduced skeletal pain. Continuation of testosterone, calcium and colecalciferol treatment, psychotherapy and antidepressive medication with paroxetine were initiated in patient B. His symptoms of depression were treated successfully, but personal and sexual relationships remained difficult and had many problems. CONCLUSION: Early diagnosis of Kallmann's syndrome and symptomatic treatment with hormone replacement prevent patients from developing pernicious sequelae. However, sexual identity will be difficult even for patients treated after early diagnosis.

[Kallmann syndrome. Fundamentals and two medical histories]. / Kallmann-Syndrom. Pathophysiologische Grundlagen und Darstellung zweier Patientengeschichten.

Kallmann syndrome is defined as a combination of isolated hypogonadotropic hypogonadism (IHH), hyposmia or anosmia and several optional neurological or anatomical particularities. The genetically caused illness affects mechanisms of neuronal migration, first of all concerning GnRH-producing neurons and those of the olfactory bulb.The first, nowadays rather seldom case, serves as an example of a patient suffering from grave, especially somatic symptoms of the disease. IHH, anosmia, eunuchoidism (physique, puerile voice, gynecomastia, micropenis, missing secondary sex characteristics) and distinct osteoporosis were verified.With the case of the second patient, late psychosexual sequelae of the syndrome are elucidated. The patient had been treated with testosterone after contracting mumps orchitis in early childhood. The physical development of the second patient progressed well since initiation of hormone substitution; however, infertility was still present. Now he complains of symptoms of depression caused by the separation from his female partner. Intermittent disorders of sexual functions and difficulties in establishing a male sexual identity lowered his self-esteem. Diagnostic and therapeutic capabilities and limits are particularized and items of future concern are emphasized.

[Spirituality and cancer]. / Viele Krebspatienten möchten mit ihrem Arzt auch spirituelle Fragen besprechen. Sind Sie auf solche Themen vorbereitet?

According to recent studies, the significance of spirituality in patients coping with cancer has been evidently underestimated. Fox example, an interrelationship between spirituality and quality of life and between spirituality and mental comorbidity was observed. It is at least assumed that there is a connection to the progression of a disease. Although historical reservations make the integration of spirituality into medicine difficult, needs assessments and clinical studies provide grounds for a reorientation in modern oncology.

[Psychosocial stress as a risk- and prognostic factor in coronary artery disease and myocardial infarction]. / Psychosoziale Belastungen als Risiko- und Prognosefaktoren bei KHK und Herzinfarkt.

Cardiovascular diseases (CVD) challenge patients and social systems alike. Epidemiologic and economic data underscores demands for additional knowledge and therapeutic options. As recent data shows, psychosocial stress is underestimated as a risk- and prognostic factor in CVD. Cardiac mortality rises sharply whithin a small time-frame after a catastrophic event. But even common daily hassles, anxiety, depression or personality traits can impair cardiac health. Social networks are thought of being cardio-protective. However, if not perceived as supportive, social networks may influence cardiac health negatively. Therefore new approaches emerge against one of the most relevant disease of our time.

[Stress and myocardial infarction]. / Stress als Risikofaktor bisher unterschätzt. Mieser Ehepartner fördert den lnfarkt.

Most people throughout the world die from the consequences of cardiovascular disease. Stress and psychosocial burdens have, in the past, been underestimated with regard to the importance of their impact on the development and course of such diseases. In the INTERHEART study, psychosocial burdens occupy third place among the risk factors for developing acute myocardial infarction. The relevance of these factors is underscored by more recent studies, also with regard to the prognosis in already manifest CAH. The causes of mental stresses may be intrapsychic problems (e.g. depression). The roots may, however, also be found in the private sphere or at the workplace. On the basis of specific history-taking, relevant risk constellations can be identified for a comparatively low expenditure of time. Specific therapeutic approaches aimed at reducing and coping with stress may, in future, help prevent diseases of the heart and lower the risk of contracting a myocardial infarction.

Cloning and functional expression of a cDNA encoding geranylgeranyl diphosphate synthase from Taxus canadensis and assessment of the role of this prenyltransferase in cells induced for taxol production.

Geranylgeranyl diphosphate synthase supplies the essential acyclic precursor for Taxol biosynthesis in methyl jasmonate-induced Taxus canadensis suspension cell cultures. A cDNA encoding this prenyltransferase was cloned from an induced T. canadensis cell library. The recombinant enzyme expressed in yeast was confirmed by radiochromatographic analysis to produce geranylgeranyl diphosphate from farnesyl diphosphate and [4-14C]isopentenyl diphosphate and was subjected to preliminary kinetic characterization. The deduced amino acid sequence of this gymnosperm geranylgeranyl diphosphate synthase (393 residues) resembles those of geranylgeranyl diphosphate synthases of angiosperm origin, except for the 90-100 N-terminal residues that correspond to the plastidial transit peptide. The full-length preprotein (42.6 kDa) and two truncated versions, corresponding to putative "mature proteins" from which the transit peptide was deleted, were transformed into a yeast mutant defective for the beta-subunit of type II geranylgeranyl transferase. Under conditions of regulated expression, both the full-length construct and the longest of the truncations (at Phe 99) were able to complement the mutant. However, when these two constructs were overexpressed in a wild-type yeast strain, they were apparently toxic, most probably due to depletion of endogenous farnesyl diphosphate as the cosubstrate for the geranylgeranyl diphosphate synthase reaction. In vitro activity of the corresponding recombinant enzymes paralleled the expression level of the constructs as determined by SDS-PAGE analysis of the appropriate proteins of predicted size, and was correlated with toxicity in the wild-type yeast strain and with ability to complement the mutant strain. Results from the analysis of geranylgeranyl diphosphate synthase activity levels and measurement of the corresponding steady-state mRNA levels during the time course of Taxol production in induced T. canadensis suspension cell cultures, and comparison to similar data for activity and message levels for taxadiene synthase, the committed step of the pathway, indicated that for each enzyme both the level of corresponding message and catalytic activity rapidly increased after methyl jasmonate induction.

Cytochrome P450-catalyzed hydroxylation of taxa-4(5),11(12)-diene to taxa-4(20),11(12)-dien-5alpha-ol: the first oxygenation step in taxol biosynthesis.

BACKGROUND: The structural complexity of taxol dictates continued reliance on biological production methods, which may be improved by a detailed understanding of taxol biosynthesis, especially the rate-limiting steps. The biosynthesis of taxol involves the cyclization of the common isoprenoid intermediate geranylgeranyl diphosphate to taxa-4(5), 11(2)-diene followed by extensive, largely oxidative, modification of this diterpene olefin. We set out to define the first oxygenation step in taxol biosynthesis. RESULTS: Microsomal enzymes from Taxus stem and cultured cells were used to define the first hydroxylation of taxadiene. We confirmed the structure of the reaction product (taxa-4(20), 11(12)-dien-5alpha-ol) by synthesizing this compound. The responsible biological catalyst was characterized as a cytochrome P450 (heme thiolate protein). In vivo studies confirmed that taxadienol is a biosynthetic intermediate and indicated that the hydroxylation step that produces this product is slow relative to subsequent metabolic transformations. CONCLUSIONS: The structure of the first oxygenated intermediate on the taxol pathway establishes that the hydroxylation reaction proceeds with an unusual double bond migration that limits the mechanistic possibilities for subsequent elaboration of the oxetane moiety of taxol. The reaction is catalyzed by a cytochrome P450, suggesting that the seven remaining oxygenation steps in taxol biosynthesis may involve similar catalysts. Because the first oxygenation step is slow relative to subsequent metabolic transformations, it may be possible to speed taxol biosynthesis by isolating and manipulating the gene for the taxadiene-5-hydroxylase that catalyzes this reaction.

Oocyst output, periodicity, and immunity of two deer mouse (Peromyscus maniculatus) eimerians (Eimeria arizonensis and Eimeria delicata).

We compared the life histories of 2 eimerians (Eimeria arizonensis and Eimeria delicata), which co-occur in the deer mouse (Peromyscus maniculatus). Laboratory-reared deer mice were given 10(3), 10(4) (E. delicata), or 10(3), 10(4), or 10(5) (E. arizonensis) oocysts by stomach intubation. Eimeria arizonensis infections lasted longer (11-13 days) than E. delicata infections (9-10 days). Eimeria arizonensis infections also produced more oocysts for each oocyst ingested at both levels compared. Both parasites exhibited periodicity in oocyst output at all levels compared. However, peaks in E. arizonensis output occurred at approximately 20-24-hr intervals, whereas peaks in E. delicata output occurred at 12-16-hr intervals. Finally, deer mice developed immunity to both eimerians after only 1 inoculation at all levels tested. Based on these parameters, we expect E. arizonensis to have a greater reproductive potential than E. delicata in free-living deer mice.