[Life Course Epidemiology and the Social Sciences: Living Apart Together?] / Lebenslaufforschung in der Epidemiologie und den Sozialwissenschaften. Gemeinsam einsam?

Life course influences are being increasingly considered as a key to better understanding of health and social inequalities in health. Our aim is to examine the potential of a broader interdisciplinary perspective on the life course and health, one that integrates sociological and psychological theory and generates greater dialogue between epidemiology and the social sciences. The paper reviews major principles and concepts applied in different disciplines that deal with life course and proposes a theory-driven research framework which better informs interdisciplinary exchange and illustrates how a bio-psycho-social perspective on life course can be infused more fully into epidemiology. The paradigmatic principles of interdisciplinary life course research (human agency, timing in lives, linked lives, historical context) provide a strong theoretical framework for a holistic and theory-based view of life course and its interdependent pathways. The stress process represents an important aetiological mechanism between the organising concepts of the life course and health. To better understand the development of health and health inequalities across the life course, an interdisciplinary approach is required. The suggested theoretical contributions to models of epidemiological life course research supplement the long appreciated methodological focus of the field and will encourage interdisciplinary dialogue.

Pharmacologic stabilization of hypoxia-inducible transcription factors protects developing mouse brain from hypoxia-induced apoptotic cell death.

OBJECTIVE: Accumulation of hypoxia-inducible transcription factors (HIFs) by prolyl-4-hydroxylase inhibitors (PHI) has been suggested to induce neuroprotection in the ischemic rodent brain. We aimed to investigate in vivo effects of a novel PHI on HIF-regulated neurotrophic and pro-apoptotic factors in the developing normoxic and hypoxic mouse brain. METHODS: Neonatal mice (P7) were treated with PHI FG-4497 (30-100mg/kg, i.p.) followed by exposure to systemic hypoxia (8% O2, 6h) 4h later. Cerebral expression of HIFα-subunits, specific neurotrophic and vasoactive target genes (vascular endothelial growth factor (VEGF), adrenomedullin (ADM), erythropoietin (EPO), inducible nitric oxide synthase (iNOS)) as well as pro-apoptotic (BCL2/adenovirus E1B 19-kDa protein-interacting protein 3 gene (BNIP3), immediate early response 3 (IER3)) and migratory factors (chemokine receptor 4 (CXCR4), stromal cell-derived factor 1 (SDF-1)) was determined (quantitative real-time (RT)., Western blot analysis) in comparison to controls. Apoptotic cell death was analyzed by terminal desoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) and cleaved caspase 3 (CC3) staining. RESULTS: Under normoxic conditions, FG-4497 treatment significantly induced the accumulation of both HIF-1α and HIF-2α isoforms in developing mouse brain. In addition, there was a significant up-regulation of HIF target genes (VEGF, ADM, EPO, CXCR4, p<0.01) with FG-4497 treatment compared to controls supporting functional activation of the HIF proteins. Under hypoxia, differential target gene activation was observed in the developing brain including additive effects of FG-4497 and hypoxia on mRNA expression of VEGF and ADM as well as a dose-dependent down-regulation of iNOS. BNIP3 but not IER3 mRNA levels significantly increased in hypoxic brains pre-treated with high-dose FG-4497 compared to controls. Of special interest, FG-4497 treatment significantly diminished apoptotic cell death, quantified by TUNEL and CC3-positive cells, in hypoxic developing brains compared to controls. CONCLUSIONS: PHI treatment modulates neurotrophic factors known to be crucially involved in hypoxia-induced cerebral adaptive mechanisms as well as early brain maturation. Pre-treatment with FG-4497 seems to protect the developing brain from hypoxia-induced apoptosis. Present observations provide basic information for further evaluation of neuroprotective properties of PHI treatment in hypoxic injury of the developing brain. However, potential effects on maturational processes need special attention in experimental research targeting HIF-dependent neuroprotective interventions during the very early stage of brain development.

Genotoxic, antigenotoxic and phytochemical assessment of Terminalia actinophylla ethanolic extract.

Terminalia actinophylla has been used for anti-diarrheic and haemostatic purposes in Brazil. The fly spot data obtained after exposure of marker-heterozygous Drosophila melanogaster larvae to T. actinophylla ethanolic extract (TAE) in the standard (ST) and high bioactivation (HB) crosses revealed that TAE did not induce any statistically significant increment in any spot categories. Differences between the two crosses are related to cytochrome P450 (CYPs) levels. In this sense, our data pointed out the absence of TAE-direct and indirect mutagenic and recombinagenic action in the Somatic Mutation and Recombination Test (SMART). When the anti-genotoxicity of TAE was analyzed, neither mitomycin C (MMC) nor ethylmethanesulfonate (EMS) genotoxicity was modified by the post-exposure to TAE, which suggests that TAE has no effect on the mechanisms involved in the processing of the lesions induced by both genotoxins. In the mwh/flr(3) genotype, co-treatment with TAE may lead to a significant protection against the genotoxicity of MMC and a weak but significant effect in the toxic genetic action of EMS. The overall findings suggested that the favorable modulations by TAE could be, at least in part, due to its antioxidative potential.

[Experience with percutanous needle fasciotomy]. / Erfahrungen mit der Perkutanen Nadelfasziotomie (PNF).

The role of percutanous needle fasciotomy (PNF) in Dupuytren's disease is still discussed. Technique and own experience are shown. Due to our own experience and a brief review of the literature we recommend percutanous needle fasciotomy for patients who can't get surgery because of restricted general conditions. Furthermore the PNF is also useful in younger patients with a well defined visible and palpable cord which is responsible for flexion contracture of MP joint to avoid or delay the operation.

Cortical correlates of auditory sensory gating: a simultaneous near-infrared spectroscopy event-related potential study.

Sensory gating refers to the ability of cerebral networks to inhibit responding to irrelevant environmental stimuli, a mechanism that protects the brain from information overflow. The reduction of the P50 amplitude (an early component of the event-related potential/ERP in electrophysiological recordings) after repeated occurrence of a particular acoustic stimulus is one means to quantitatively assess gating mechanisms. Even though P50 suppression has been extensively investigated, neuroimaging studies on the cortical correlates of auditory sensory gating are so far very sparse. Near-infrared spectroscopy (NIRS) is an optical imaging technique perfectly suitable for the investigation of auditory paradigms, since it involves virtually no noise. We conducted a simultaneous NIRS-ERP measurement to assess cortical correlates of auditory sensory gating in humans. The multi-channel NIRS recording indicated a specific activation of prefrontal and temporo-parietal cortices during conditions of increased sensory gating (dual-click trials). Combining the hemodynamic data with an electrophysiological index of the "gating quality" (gating quotient Q) revealed a positive correlation between the amount of sensory gating and the strength of the hemodynamic response during dual-clicks in the left prefrontal and temporal cortices. The results are in line with previous findings and confirm a possible inhibitory influence of the prefrontal cortex on primary auditory cortices.

[Holmium laser ablation of the prostate. An alternative to GreenLight photoselective vaporization of the prostate]. / Holmiumlaserablation der Prostata. Eine Alternative zum KTP.

INTRODUCTION: Ablative laser methods for treating benign prostatic obstruction (BPO) have gained importance because of potentially lower complication rates than outpatient therapy methods. The aim of this prospective phase II study was to record the effectiveness and complications of holmium laser ablation of the prostate (HoLAP) in the first postoperative year. MATERIAL AND METHODS: June 2006 to December 2007, 86 of 343 consecutive patients with BPO [International Prostate Symptom Score (IPSS) >10] were treated with the VersaPulse 100-W laser (Lumenis), 2.0 J/50 Hz or 3.2 J/25 Hz. Preoperative and postoperative prostate-specific antigen (PSA), peak urinary flow rate (Q(max)), IPSS, prostate gland volume, and postvoid urine volume were prospectively measured. The median follow-up time was 8 months (3-21). RESULTS: Median patient age was 71 (50-83) years, and mean operating time was 77.5 (9-135) min. There was only one case of significant bleeding. In 14 of 86 cases (16%), HoLAP was combined with transurethral resection of the prostate (TURP). Short-term voiding complaints were expressed by 26.7% of the questioned patients. The length of hospital stay was in most cases <48 h. IPSS, Q(max), PSA, postvoid urine, gland volumes, and quality of life improved significantly after 3 months, and all parameters remained unchanged after 12 months. The reoperation rate within 12 months was 6.8%. CONCLUSIONS: The advantage of HoLAP over TURP is the very low bleeding rate and thus a shorter hospital stay and possible outpatient therapy. In particular, patients with prostate gland volume <50 ml profit from HoLAP. Postoperative voiding complaints are comparable to those with TURP. Long-term results are needed to confirm the low reoperation rate.

[Efficacy of specific physiotherapy for temporomandibular joint dysfunction of muscular origin]. / Efficacité de la physiothérapie spécialisée sur les Sadam musculaires.

INTRODUCTION: Little explanation is given to patients with temporomandibular disorders and muscles dysfunction on the mechanism and the expected results of conservative treatment. The purpose of this prospective study was to evaluate the efficacy of specific physical therapy prescribed after this explanation was given and also after using a flat occlusal splint adapted only if muscle pain remained after physical therapy. MATERIAL AND METHOD: Twenty-seven patients with temporomandibular joint dysfunction of muscular origin were evaluated after a mean of six sessions of specialized physical therapy with professionals. Patients were treated by oral and facial massages and were trained for self-reeducation. They were also trained for a specific exercise named the "propulsive/opening maneuver". Every patient was questioned on the subjective evolution of pain and the current maximal pain was evaluated with the Visual Analogical Scale (VAS). Clinical evaluation focused on tenderness of masticator muscles and also assessed the changes in the amplitude of mouth opening. RESULTS: Ninety-three percent of the patients treated by specific physical therapy had a significant reduction of their maximal pain feeling (p<0.05). The recovery of an optimal mouth opening without deviation was also improved as was the protrusion. For 33% of the patients a flat nighttime occlusal splint was necessary as a complementary treatment. Twenty-two percent of the patients decided to change their treatment for alternative therapies (osteopathy, acupuncture, etc.). Fifty percent of the patients were convinced of the efficacy of the prescribed treatment. DISCUSSION: Patients who undertake the specific physical therapy and who regularly practice self-physical therapy succeed in relaxing their masticator muscles and in decreasing the level of pain. Explanations given by the doctor concerning the etiology of pain, during temporomandibular joint dysfunction of muscular origin, and the purpose of specific physical therapy increase the capacity of self-relaxation. A flat occlusal splint is indicated for patients who grind their teeth and for those whose pain resists to physical therapy.

[Needle breakage: a rare and potentially dangerous complication during local anaesthesia]. / Bris d'aiguille: complication rare mais potentiellement dangereuse d'une anesthésie locale.

INTRODUCTION: Needle breakage is a rare complication during local oral anesthesia administration. The authors describe the surgical procedure used to remove a broken dental needle and how to prevent this complication. CASE REPORT: The authors present the case of a 52-year-old man who was referred by his general dental practitioner for needle breakage during an inferior alveolar nerve block. Surgical management involved localizing the broken needle using radioscopy and removing it under general atomax 00041 anesthesia. DISCUSSION: Today, needle breakage during local anesthesia is mainly attributed to an incorrect anesthetic injection technique. The prevention, investigation, and management of such complication are discussed.

Consensus meeting for the management of gastrointestinal stromal tumors. Report of the GIST Consensus Conference of 20-21 March 2004, under the auspices of ESMO.

BACKGROUND: The management of gastrointestinal stromal tumors (GIST) has evolved very rapidly in the last 4 years. The objectives of this international consensus meeting were to describe the optimal management procedures for patients with GIST in localized and advanced stages, as well as research issues for the future. MATERIALS AND METHODS: A panel of experts from six specialties, including pathology, molecular biology, imaging, surgery, medical oncology and methodologists for clinical practice guidelines from different European and extra European sarcoma societies were invited to a 2-day workshop. Several questions were selected by the organizing committee prior to the conference. Selected panelists reviewed the current levels of evidence for each point, and presented their conclusions during the meeting. These proposals were discussed, and consensus points were identified and categorized according to the Standard Options Recommandations (SOR) of the French Federation of Cancer Centers and National Comprehensive Cancer Network (NCCN). RESULTS: Thirty-two consensus points were identified, most from categories 2A of the NCCN and B2 of the SOR. Among these, the standard histological examination with immunohistochemical analysis using CD117, CD34, PS100, desmin and smooth muscle actin is considered standard. Molecular biology for the identification of KIT and PDGFRA mutation is an optional diagnostic procedure for GIST with negative CD117 staining, and otherwise is considered a research procedure. Complete tumor resection with negative tumor margins is the standard surgical treatment. Adjuvant imatinib after optimal tumor resection as well as neo-adjuvant imatinib remain experimental approaches to be performed within prospective clinical studies. Imatinib should be started at the date of diagnosis of metastatic relapse and given until development of intolerance or progressive disease. The optimal criteria for tumor response to imatinib remain to be delineated, and should include not only tumor size reduction or disease stabilization, but also reduction of tumor density (Hounsfield Units) on computed tomography and metabolic activity (i.e. reduction of FDG uptake on positron emission tomography). In a substantial proportion of patients, stable disease and even increase in tumor size may be associated with pathologic response to imatinib therapy, and available survival data indicate that the survival of these patients is similar to that of patients with conventional tumor response. Metastasis resection is an experimental procedure. CONCLUSIONS: Consensus points in clinical management of GIST as well as questions for future clinical trials were identified during this consensus conference on GIST management.

[Posterior dynamic stabilization as an alternative for dorso-ventral fusion in spinal stenosis with degenerative instability]. / Dorsale dynamische Stabilisierung als Alternative zur dorso-ventralen Fusion bei Spinalkanalstenose mit degenerativer Instabilität.

AIM: Our retrospective study analyzed the outcome of patients with degenerative lumbar instability with spinal stenosis, who underwent decompression surgery with dorsoventral fusion (Group I) and decompression surgery with posterior dynamic stabilization (Group II). METHOD: For 10 patients in each group intra- and postoperative data were obtained and the functional outcome was evaluated with the "Oswestry Low Back Pain Disability Questionnaire" (OQ) and the "Short Form 36 Health Survey Questionnaire" (SF-36). The average follow up was 14.4 months in Group I, 15.2 months in Group II. RESULTS: In Group I the OQ averaged postoperatively 32 points (preoperatively 46 points), the "Physical Component Summary" (PCS) of SF-36 averaged 34 points (preoperatively 24 points), the "Mental Component Summary" (MCS) averaged 43 points (preoperatively 36). In Group II the values at follow up were as follows: OQ 33 points (preoperatively 54), PCS 34 points (preoperatively 28) and MCS 46 points (preoperatively 36). The average hospitalization was 28.4 days in Group I, 19.3 days in Group II and the average operation time was 218 minutes in Group I, 163 minutes in Group II. CONCLUSION: When compared the functional outcome, the dynamic stabilization seems to be a promising alternative to fusion in patients with degenerative lumbar instability with spinal stenosis.

O-phenylphenol and its sodium and potassium salts: a toxicological assessment.

Ortho-phenylphenol (OPP) and its sodium (SOPP) and potassium (POPP) salts are used as fungicides and disinfectants. Due to the widespread use of especially OPP and SOPP, the potential for consumer exposure and some "critical" findings the toxicological database is quite extensive and complex. In experimental animals toxicity after single oral and dermal administration of these compounds is low. For the skin and mucous membranes, OPP has to be considered as irritating, and SOPP and POPP as corrosive. A large number of chronic toxicity and reproduction studies did not show any indication of oestrogen-like or other endocrine effects of OPP in the mammalian organism. No teratogenic effects were observed after the administration of OPP or SOPP in rats, mice, and rabbits. In two-generation studies in rats, OPP did not affect reproduction. The available data do not suggest a relevant potential for immunotoxic properties. The administration of high dietary concentrations of OPP to mice up to 2 years induced hepatocellular changes indicative of adaptations to metabolic demands, zonal degeneration, focal hepatocellular necrosis, and/or pigmentation of the liver. Only in male mice of one study, using a strain prone to develop hepatocellular tumors at high spontaneous incidences, the incidence of hepatocellular adenomas was increased. The incidence of hepatocellular carcinomas was not affected by treatment. The urothel of the urinary bladder (at very high doses also of the renal pelvis and the papilla) is the main target tissue after the repeated oral exposure of rats. The changes initially consist of increased mitosis, followed by simple epithelial hyperplasia, developing to a papillary and/or nodular form, later on to papillomas and transitional carcinomas. Crystals or stones in the bladder do not play a decisive role in this cascade. SOPP is more effective than OPP in this respect. Male rats are much more sensitive than females. In mice, hamsters, guinea pigs, and dogs, urothelial lesions do not develop even at very high oral dose levels. The findings in rats explain why there is a large genotoxicity/mutagenicity data base not only for OPP and SOPP but also for their metabolites on nearly all kinds of endpoints/targets. The weight of evidence suggests that genotoxicity of OPP/SOPP or their metabolites does not play a decisive role for the carcinogenicity at the urothel. Among them are lack of DNA binding of OPP to the rat bladder epithelium, the differences between OPP and SOPP, between male and female rats, between rats and mice (despite roughly comparable toxicokinetics), as well as the fact that tumors develop only at dose levels inducing hyperplasias. In addition, the strong dependence of the incidence and severity of the nonneoplastic and neoplastic bladder changes on urinary pH values (modified by feeding of ammonium chloride or sodium hydrogen carbonate) is consistent with the hypothesis of a nongenotoxic mode of action. Finally, there is no correlation between the urinary concentration of OPP or its metabolites and the incidence of hyperplasias/tumors in the urinary bladder. Both tumorigenic effects in rats and male mice are considered to represent high-dose, sex- and/or species-specific phenomena, based on nongenotoxic mechanisms of action and therefore allow the conclusion that the conventional margin of safety approaches are appropriate when assessing the risk of applications of OPP and its salts.

Cardiopulmonary function in horses during anesthetic recovery in a hydropool.

OBJECTIVE: To determine the cardiovascular and respiratory effects of water immersion in horses recovering from general anesthesia. ANIMALS: 6 healthy adult horses. PROCEDURE: Horses were anesthetized 3 times with halothane and recovered from anesthesia while positioned in lateral or sternal recumbency in a padded recovery stall or while immersed in a hydropool. Cardiovascular and pulmonary functions were monitored before and during anesthesia and during recovery until horses were standing. Measurements and calculated variables included carotid and pulmonary arterial blood pressures (ABP and PAP respectively), cardiac output, heart and respiratory rates, arterial and mixed venous blood gases, minute ventilation, end expiratory transpulmonary pressure (P(endXes)), maximal change in transpulmonary pressure (deltaP(tp)max), total pulmonary resistance (RL), dynamic compliance (Cdyn), and work of breathing (W). RESULTS: Immersion in water during recovery from general anesthesia resulted in values of ABP, PAP P(endXes), deltaP(tp)max, R(L), and W that were significantly greater and values of Cdyn that were significantly less, compared with values obtained during recovery in a padded stall. Mode of recovery had no significant effect on any other measured or calculated variable. CONCLUSIONS AND CLINICAL RELEVANCE: Differences in pulmonary and cardiovascular function between horses during recovery from anesthesia while immersed in water and in a padded recovery stall were attributed to the increased effort needed to overcome the extrathoracic hydrostatic effects of immersion. The combined effect of increased extrathoracic pressure and PAP may contribute to an increased incidence of pulmonary edema in horses during anesthetic recovery in a hydropool.

[Is appendectomy really performed too frequently? Results of the prospective multicenter study of the Swiss Society of General Surgery]. / Wird tatsächlich zu häufig appendektomiert? Resultate der prospektiven Multicenterstudie der Schweizerischen Gesellschaft für Allgemeinchirurgie (SGAC).

Scientific publications and provoking criticism from the lay press have recently pointed out, that appendices may be surgically removed too frequent and without indisputable necessity. In an attempt to verify these questionable statements, the Swiss Society for General Surgery (SGAC) initiated a prospective controlled multi center trial. From September 1997 to December 1998, hundred and twenty-five institutions documented 4603 appendectomies performed due to a suspected appendicitis. Histological investigation of all specimens revealed a 7% rate of normal appendices, 7.2% for patients with national health service (NHS) and 5.9% for patients with private insurances respectively. Compared to the results of the literature, where a frequency of normal appendices around 15% is judged as standard, these results are excellent. In 17.2% of the patients (15.9% NHS and 23.6% privately insured patients) an "appendicitis perforata" was observed. This percentage remains in the range reported by other authors. The analysis of time of admission (i.e. day or night) and the delay from admission to surgery shows a distribution independent to the insurance of the patients. Therefore, the planned appendectomy for patients with private insurances does not exist. A different choice of the surgical technique could be observed depending on the insurance status. In 30.4% of the private insured patients a laparoscopic appendectomy was performed as compared to 22.6% of patients with NHS. Surprisingly, an identical median hospitalization time can be observed for both groups (laparoscopic 5.5 days, open surgery 5.5 days).

Affective disorders among Jews: a historical review and meta-analysis.

Descriptions of affective disorders among Jews date back to biblical times. For over a century the psychiatric literature has debated whether Jews are more vulnerable to affective disorders. To ascertain the validity of this finding we undertook a meta-analysis of data extracted from the literature published to date. Forty-three studies were identified that could be analysed statistically using Cohen's d and a Mantel-Haenszel summary odds ratio. An increased, but weak overall risk was found for males. Possible biases of the literature are discussed, including differential help-seeking patterns, lack of accounting for readmission rates, failure to control for confounding variables, and an anti-Semetic orientation on the part of researchers. Reasons for why Jews have higher rates of affective disorders than non-Jews are explored.

The role of radiotherapy in the management of operable locally advanced breast carcinoma: results of a randomized trial by the Eastern Cooperative Oncology Group.

BACKGROUND: The purpose of this study was to test the role of radiotherapy following total mastectomy, axillary dissection, and adjuvant systemic therapy in the management of operable locally advanced breast carcinoma. METHODS: After undergoing mastectomy and axillary dissection, 426 patients with locally advanced breast carcinoma were registered on study and stratified by patient characteristics and risk factors. All patients were then treated with six courses of chemohormonotherapy. After being restaged, the 332 patients remaining without recurrence were randomized to receive prophylactic radiotherapy or to undergo observation and receive radiotherapy only if and when there was locoregional recurrence. RESULTS: Three hundred twelve of 332 randomized patients were deemed eligible and analyzed for both time to relapse and survival. The median follow-up period was 9.1 years. There were no significant differences in time to relapse and overall survival between the two treatment arms. Of those assigned to radiation, 60% relapsed, with a median time to relapse of 4.7 years, and 46% were alive at last follow-up, with a median survival of 8.3 years. Of those assigned to observation, 56% relapsed, with a median time to relapse of 5.2 years, and 47% were alive at last follow-up, with a median survival of 8.1 years. The two treatment arms had significantly different patterns of sites of first recurrence. There were 9% fewer locoregional first recurrences among those assigned to radiation than among those assigned to observation (15% vs. 24%), whereas there were 15% more first relapses at distant sites (50% vs. 35%) among those assigned to radiation (P = 0.003). CONCLUSIONS: Radiotherapy for locally advanced breast carcinoma, following mastectomy, axillary dissection, and adjuvant systemic therapy, results in fewer locoregional but more distant recurrences at first relapse. No significant advantage was seen for consolidation radiotherapy over observation in terms of either time to relapse or survival, both of which were virtually identical in the two treatment arms. [See editorial counterpoint on pages 1061-6 and reply to counterpoint on pages 1067-8, this issue.]

[Effect of ultraviolet irradiation of autologous blood on cell volumes, cell adhesion and phagocytosis in normal probands and patients with multiple sclerosis]. / Einfluss von Ultraviolettbestrahlung des Blutes (UVB) auf Zellvolumen, Zelladhärenz und Phagozytose bei Normalprobanden und Patienten mit Multipler Sklerose (MS).

UVB induced changes of blood cell properties were investigated in 12 MS patients and in 10 healthy volunteers serving as normal controls. The mean cell volume (MCV) was determined by electronic sizing, the granulocyte and lymphocyte adherence was estimated in a capillary assay, and the phagocytic activity of granulocytes was measured in a test system based on the incorporation of opsonized baker's yeast (Saccharomyces cerevisiae). In MS patients the MCV of red cells and lymphocytes decreased rapidly within 6 UVB treatments. In contrast, the reduction of the granulocyte volume was delayed (between the 6th and 12th UVB). In the control group the mean value of the red cell and lymphocyte MCV remained rather unaffected. There was a slight rise of the granulocyte volume after the 6th UVB. The only significant change of adherence was an increase of granulocyte adherence in MS patients. Untreated patients had a significantly enhanced phagocytic activity in comparison to the control group. 6 UVB treatments included a significant reduction of the phagocytic activity in MS patients. However, subsequently the percentage of phagocytizing cells increased again, whereas the particle uptake per cell continued to decrease. In the control group only minor UVB induced changes of phagocytosis were observed. The in vitro UV irradiation caused an enhanced phagocytosis in the majority of cases in both controls and MS patients. In general, under the UVB treatment all parameters examined changed in the sense of a normalisation, in that the measured values reached a new level lying between the extreme pretreatment values accompanied by a reduced standard deviation. The effect of UVB was more pronounced in MS patients when compared with normal controls. This could result from an enhanced sensitivity to the influence of UVB of pathologically altered cells in MS patients. The monitoring of the MCV of red cells and lymphocytes as well as the repeated testing of granulocyte phagocytosis are recommended for supportion of therapy planning and follow-up of MS patients.

Current status of high linear energy transfer irradiation.

Based on laboratory investigations, high linear energy transfer (LET) particle irradiation is capable of more efficient cell kill than that associated with conventional or low LET irradiation. The advantages of high LET irradiation include: (1) a greater ability to damage hypoxic cells; (2) a lesser ability for repair of sublethal and potentially lethal radiation-induced damage; (3) less variation in radiation sensitivity relative to the cell cycle; and (4) a greater ability to deposit the radiation dose in the region of the tumor as opposed to the normal surrounding tissue (neutrons do not have this advantage compared to other particle therapy). Despite these laboratory advantages, it has been difficult to demonstrate any advantage of high LET irradiation in the clinic. A number of new developments have occurred to test the role of high LET: (1) sophisticated technology to enable treatment delivery with higher dose rate and improved depth dose; (2) the construction of hospital-based facilities; and (3) the development of randomized studies involving diseases in which the risk of early metastasis is minimized. It is hoped that careful study in the clinic over the next decade will elucidate the role of high LET particle therapy.

Intracellular elemental content of cardiac and skeletal muscle of normal and dystrophic hamsters.

To test the hypothesis that the genetic lesion causing muscular dystrophy might be reflected in an abnormal intracellular elemental content, the elemental content of individual cardiac and skeletal muscle fibers in 50-day-old male control and cardiomyopathic BIO 53.58 hamsters was determined. The technique of electron probe x-ray microanalysis of freeze-dried tissue was employed. No electrolyte content differences were found between control and diseased animals for nuclei, myofibrillar cytoplasm, or mitochondrially-enriched cytoplasm of cardiac myocytes. Sulfur was elevated in dystrophic cardiac myocytes and was the only element significantly different in heart tissue of control and cardiomyopathic animals. Sulfur was also elevated in dystrophic soleus muscle fibers. The pattern of electrolyte content of these cells reflected a mixture of normal cells and damaged cells with altered electrolyte content. In this hamster model, alteration of electrolyte content of myocytes appears to be a result of the disease process and not an inherent characteristic of muscular dystrophy. The elevated sulfur in dystrophic hamster myocytes reflects a biochemical lesion which deserves further study.

Surface-charge related actions of polylysine on thylakoid membranes.

Polycation binding to the negatively charged surface of chloroplast thylakoid membranes is known to cause an inhibition of photosystem I activity. It also interferes with the cation-dependent rearrangement of chlorophyll proteins in the thylakoid membrane. It was shown that added anions prevented or reversed the inhibition of photosystem I by polylysine without decreasing its binding to the membranes. Anions also caused a change in the interaction of the chlorophyll proteins in polylysine-treated thylakoids as indicated by an increase in the relative fluorescence intensity from photosystem II. In both cases, the relative effectiveness of the anions tested depended on their valence; for example, the tetravalent species Fe(CN)4-(6) was effective at concentration at least 2 orders of magnitude lower than the divalent species SO2-(4). These results suggest that anions act by screening the positive charge of the polylysine-coated membrane surface. Measurements of the response of the anionic fluorescent probe 1-anilinonapthalene-8-sulfonate to an addition of anions to polylysine-treated thylakoids supported this contention. It was concluded that the action of polylysine on photosystem I and on the chlorophyll proteins is mediated by changes of the electrical properties of the thylakoid membrane and may not involve a direct binding of the polycation to the affected membrane proteins.