Risk assessment of vector-borne diseases for public health governance.

OBJECTIVES: In the context of public health, risk governance (or risk analysis) is a framework for the assessment and subsequent management and/or control of the danger posed by an identified disease threat. Generic frameworks in which to carry out risk assessment have been developed by various agencies. These include monitoring, data collection, statistical analysis and dissemination. Due to the inherent complexity of disease systems, however, the generic approach must be modified for individual, disease-specific risk assessment frameworks. STUDY DESIGN: The analysis was based on the review of the current risk assessments of vector-borne diseases adopted by the main Public Health organisations (OIE, WHO, ECDC, FAO, CDC etc…). METHODS: Literature, legislation and statistical assessment of the risk analysis frameworks. RESULTS: This review outlines the need for the development of a general public health risk assessment method for vector-borne diseases, in order to guarantee that sufficient information is gathered to apply robust models of risk assessment. Stochastic (especially spatial) methods, often in Bayesian frameworks are now gaining prominence in standard risk assessment procedures because of their ability to assess accurately model uncertainties. CONCLUSIONS: Risk assessment needs to be addressed quantitatively wherever possible, and submitted with its quality assessment in order to enable successful public health measures to be adopted. In terms of current practice, often a series of different models and analyses are applied to the same problem, with results and outcomes that are difficult to compare because of the unknown model and data uncertainties. Therefore, the risk assessment areas in need of further research are identified in this article.

Temporal artery compression sign--a novel ultrasound finding for the diagnosis of giant cell arteritis.

PURPOSE: In patients with suspected giant cell arteritis (GCA), a search for the perivascular halo sign, a sophisticated color duplex ultrasound (CDU) finding, at experienced centers reliably identifies inflamed temporal arteries (TA). We tested whether TA compression in patients with GCA, a simple, largely operator-independent maneuver, elicits contrasting echogenicity between the diseased artery wall and the surrounding tissue (compression sign). MATERIALS AND METHODS: 80 individuals with suspected GCA were prospectively enrolled in this single-center study. In all study participants, bilateral ultrasound examination of the TA established the presence/absence of the halo and compression sign. A positive compression sign was defined as visibility of the TA upon transducer-imposed compression of the artery. Based on ACR criteria, a team of specialized physicians independently grouped patients as GCA versus non-GCA. RESULTS: 43/80 study participants were grouped as GCA. Both the halo sign and the compression sign were positive in 34/43 patients in the GCA group, and negative in all 37/37 of the non-GCA group, resulting in a sensitivity of 79 % and a specificity of 100 % for both the halo and the compression sign. CONCLUSION: In this cohort of individuals with suspected GCA, the halo sign and the compression sign were equal in their diagnostic performance. The simplicity of the compression sign suggests a level of reliability warranting further evaluation.

[Of bugs and joints. Oligoarthritis caused by Tropheryma whipplei]. / Oligoarthritis durch Tropheryma whipplei. "Of bugs and joints".

Whipple's disease is a rare, chronic infection caused by Tropheryma whipplei, an ubiquitary gram positive bacterium. The disease is associated with a high mortality in absence of an antibiotic treatment. The disease can be detected in affected tissues and body fluids by light and electron microscopy, as well as by polymerase chain reaction (PCR). Musculoskeletal symptoms such as arthralgia and arthritis frequently represent the first manifestation of this multi-system disease; typical subsequent symptoms are weight loss, diarrhea, and abdominal pain. Symptoms of central nervous system involvement are present in 10-40% of cases. We report on a 67 year-old male with a history of migratory oligoarthritis over three decades in whom the causative agent was detected by PCR in synovial fluid only. This case illustrates that searches for the characteristic PAS-positive macrophages and PCR in biopsies from the duodenum may be insufficient and that diagnostic efforts should be complemented with PCR assays from affected tissues or body fluids. It is recommended that antibiotic treatment be carried out with an agent that penetrates well into the cerebrospinal fluid, e.g. ceftriaxone, followed by cotrimoxazole. Antibiotics should be maintained over several months to years. It is prudent to document the disappearance of the pathogen in the affected compartments prior to the discontinuation of the antibiotic therapy.

Estrogen binding, receptor mRNA, and biologic response in osteoblast-like osteosarcoma cells.

High specific activity estradiol labeled with iodine-125 was used to detect approximately 200 saturable, high-affinity (dissociation constant approximately equal to 1.0 nM) nuclear binding sites in rat (ROS 17/2.8) and human (HOS TE85) clonal osteoblast-like osteosarcoma cells. Of the steroids tested, only testosterone exhibited significant cross-reactivity with estrogen binding. RNA blot analysis with a complementary DNA probe to the human estrogen receptor revealed putative receptor transcripts of 6 to 6.2 kilobases in both rat and human osteosarcoma cells. Type I procollagen and transforming growth factor-beta messenger RNA levels were enhanced in cultured human osteoblast-like cells treated with 1 nM estradiol. Thus, estrogen can act directly on osteoblasts by a receptor-mediated mechanism and thereby modulate the extracellular matrix and other proteins involved in the maintenance of skeletal mineralization and remodeling.

Iatrogenically-related, fatal methotrexate intoxication: a series of four cases.

Since the early eighties, the folic antagonist methotrexate (MTX) has been used in long-term treatment of rheumatoid arthritis. Because of the high toxic potential clinical and laboratory controls at regular intervals and patient education in order to avoid misadventure is of overriding importance. We present four cases of fatal MTX intoxication due to medical malpractice from the Tübingen Institute of Forensic Medicine autopsy material, which show the severe consequences of MTX overdose. It becomes evident that among non-rheumatologists there still is need for information about toxicity and dose limitation in MTX low-dose treatment.

Familial inflammatory Sneddon's syndrome-case report and review of the literature.

Sneddon's syndrome (SNS) which originally was a clinical diagnosis, is now regarded as a common clinical manifestation of different disease entities. It has been divided into idiopathic, autoimmune and thromboembolic subsets or in systemic lupus erythematosus (SLE)-associated, antiphospholipid syndrome (APS)-associated and primary forms. Familial occurrence of Sneddon's syndrome is rare. We present a familial case of Sneddon's syndrome with inflammatory disease pattern, early disease onset and association with autoimmune thyroid disease and anticardiolipin antibodies. Although most authors reporting on adult cases of SNS consider it a non-inflammatory, thromboembolic process, the study of cases with early onset brings attention to the possible inflammatory origin of the syndrome.

Estrogen binding and estrogenic responses in normal human osteoblast-like cells.

A finite human cell line was established from trabecular bone explants obtained from a 48-year-old woman. These cells, designated BG688, were characterized as osteoblast-like in phenotype using the following independent criteria: (1) the presence of histochemically detectable alkaline phosphatase (AP) activity; (2) response to the calciotropic hormone 1,25-(OH)2D3 as assessed by increased AP activity; (3) synthesis and secretion of the osteoblast-specific marker bone gla protein; and (4) expression of alpha 1(I)-procollagen and alpha 1(III)-procollagen mRNAs in a pattern similar to that of other osteoblast-like cell lines. In addition to these classic osteoblast markers, BG688 cells also possess approximately 2400 high-affinity (Kd = 0.45 nM) 17 beta-estradiol (E2) binding sites per cell. The binding of E2 to these sites is specific, and of the steroid hormone agonists tested, E2 and diethylstilbestrol elicited the greatest amount of competition with radiolabeled E2. BG688 cells were also shown to respond to a physiologic concentration (10 nM) of E2. In vitro translation products of poly(A)+ RNA obtained from control and hormone-treated cells revealed a pleiotropic influence of E2 on the relative abundance of several mRNAs as assessed by two-dimensional gel electrophoretic analysis of their corresponding peptides. E2 also elicits a twofold increase in the steady-state concentration of alpha 1(I)-procollagen mRNA as demonstrated by northern blot hybridization. Thus, we here extend our previous data obtained in osteoblast-like osteosarcoma cells to indicate that a normal osteoblastic cell line is a target for the action of estrogen.(ABSTRACT TRUNCATED AT 250 WORDS)

High-affinity androgen binding and androgenic regulation of alpha 1(I)-procollagen and transforming growth factor-beta steady state messenger ribonucleic acid levels in human osteoblast-like osteosarcoma cells.

Clinical observations have demonstrated a positive effect of estrogens and androgens on the maintenance of structural bone integrity. This study examines the direct effects of androgenic hormones on the osteoblast-like human osteosarcoma cell line, HOS TE85. Employing radiolabeled dihydrotestosterone (DHT), 2800 saturable, high-affinity (dissociation constant = 0.66 nM) androgen binding sites were detected per HOS TE85 cell. Androgen binding was specific in that DHT and testosterone (T) displayed significantly greater competition than the progestins, progesterone and medroxyprogesterone. The expression of androgen receptors in HOS TE85 cells was further substantiated by Northern analysis. A human androgen receptor complementary DNA probe revealed a 9.5 kilobase transcript which corresponds to the predominant human androgen receptor transcript detected in human male reproductive tissues. Androgens were also found to elicit biological responses in HOS TE85 cells. Physiological concentrations of DHT and T decreased HOS TE85 cell proliferation as assessed by cell count. This finding suggests that DHT may also play a role in osteoblast differentiation. In support of this hypothesis, treatment with T (24 h, 10 nM) enhanced the abundance of both alpha 1(I)-procollagen messenger RNA (mRNA) (5-fold) and transforming growth factor-beta mRNA (2.2 fold). The nonaromatizable androgen DHT (24 h, 10 nM) elicited an increase in the steady state concentration of alpha 1(I)-procollagen mRNA similar to the increase observed with T treatment. Thus, in addition to the recent discovery of estradiol receptors and estrogenic regulation of HOS TE85 cells, it is now evident that these osteoblast-like osteosarcoma cells also express high affinity androgen binding sites and can respond biologically to androgens.

Ionophores alter hepatic concentrations of intermediary carbohydrate metabolites in steers.

The effects of ionophores on liver weight and function were determined in finishing steers (n = 24; avg weight 440 kg). Steers were group-fed one of three treatments (control, lasalocid or monensin at 33 mg/kg feed) for 46 d prior to slaughter. Three days prior to slaughter, blood was collected for the determination of serum Ca and Mg. At slaughter, the liver was removed, weighed, sampled, frozen in liquid nitrogen and subsequently analyzed for concentrations of carbohydrate metabolites and minerals. Liver weight (5.9 kg) was unaffected by treatment. Serum and hepatic Ca and Mg were not affected by ionophore treatment. Hepatic glycogen levels in steers fed ionophores were unaffected by treatment. Fructose 1,6-bisphosphate was 21% lower (P less than .10) in hepatic tissue of steers fed ionophores, whereas dihydroxyacetone phosphate was 15 to 37% greater in hepatic tissue of steers fed monensin (P less than .20) or lasalocid (P less than .10). Glyceraldehyde 3-phosphate was elevated more extensively by lasalocid than by monensin with increases of 72 (P less than .05) and 132% (P less than .001), respectively, over controls. Glycerol 3-phosphate levels were 37% (P less than .05) and 12% (NS) greater with these ionophores. Hepatic levels of pyruvate were elevated 12 (NS) to 36% (P less than .17) for monensin and lasalocid. Fructose 2,6-bisphosphate levels were 25% lower (P less than .25) in hepatic tissue of steers fed ionophores than in hepatic tissue from control steers. Other metabolites of carbohydrate metabolism in hepatic tissue were not altered appreciably. Changes in levels of intermediary metabolites of carbohydrate metabolism suggest alterations in hepatic carbohydrate metabolism favoring gluconeogenesis in steers fed ionophores.

[Semicircular, transurethral bladder neck resection in therapy of the overcorrected bladder neck]. / Die semizirkuläre, transurethrale Blasenhalsresektion zur Therapie des überkorrigierten Blasenhalses.

We report 4 cases of severe urinary obstruction after abdominal stress incontinence procedures in women. The operative procedure consisted in transurethral resection of the obstructive, overcorrected dorsal bladder neck. After resection of the highly elevated bladder neck between the 3- and 9-o'clock position in the dorsal lithotomy position, the patients were able to regain a normal micturition without residual urine. There was no recurrence of stress incontinence.

[Tuberculosis of the breast]. / Tuberkulose der Mamma.

The case of a 89-year-old women with mammary tuberculosis is reported. The diagnosis was based on histopathological and bacteriological examinations. Chest X-ray showed a lung-pleural tuberculosis, so we considered it a secondary organ manifestation.

[Ossification of the endometrium: an unusual finding in secondary sterility]. / Ossifikation des Endometriums: Ein ungewöhnlicher Befund bei sekundärer Sterilität.

The rare fact of endometrial ossification can be found after abortion or chronic inflammation. We describe a case from our clinic. Despite repeated curettages new ossifications occurred. The resulting secondary infertility is persisting.

[Treatment of vulvar cancer]. / Behandlung des Vulvakarzinoms.

125 patients with carcinoma of the vulva were evaluated with respect to corrected 5-year survival rates. In our study we try to answer two questions in the therapeutic management of vulval carcinoma: (1) Is organ-preserving surgery in stage I tumors adequate? (2) How important is the radiation therapy in the general treatment concept in more advanced stages of the disease? Our study shows that organ preservation seems to be possible in stage I disease, if resection of the tumor is complete with a margin of normal tissue. If inguinal lymph nodes are involved or the primary tumor is bulky, the best results are obtained with a combination of radical surgery and locoregional radiation therapy. Radiation therapy alone has a good effect during the early stage of the vulval cancer.

No increased sensitivity in brain activity of adolescents exposed to mobile phone-like emissions.

OBJECTIVE: To examine the potential sensitivity of adolescents to radiofrequency electromagnetic field (RF EMF) exposures, such as those emitted by mobile phones. METHODS: In a double-blind, randomized, crossover design, 22 adolescents aged 11-13 years (12 males) underwent three experimental sessions in which they were exposed to mobile phone-like RF EMF signals at two different intensities, and a sham session. During exposure cognitive tasks were performed and waking EEG was recorded at three time-points subsequent to exposure (0, 30 and 60 min). RESULTS: No clear significant effects of RF EMF exposure were found on the waking EEG or cognitive performance. CONCLUSIONS: Overall, the current study was unable to demonstrate exposure-related effects previously observed on the waking EEG in adults, and also provides further support for a lack of an influence of mobile phone-like exposure on cognitive performance. SIGNIFICANCE: Adolescents do not appear to be more sensitive than adults to mobile phone RF EMF emissions.

[Self-defense injuries in homicides caused by penetrating forces]. / Abwehrverletzungen bei Tötungsdelikten durch scharfe Gewalteinwirkung.

101 homicides caused by stabbing were examined for the presence of defence-injuries. 50 victims showed 174 defence-injuries on hands and forearms (133 incision wounds, 26 stab wounds and 15 cutting through). More than two thirds of lesions were found on left arm. That those lesions mostly were found on left arm is caused by the interaction between perpetrator and victim. Victims left arm is nearest to the perpetrator therefore it is used as a mean of defence first of all. The probability that defence-injuries can be seen is rising with the number of stab wounds. Localisation of a defence-injury on the extensor side ("passive") or on the flexor side ("active") is conditioned by accidentalities. Such a differentiation should be given up because no conclusions on the readiness of defence can be drawn.

The role of protein kinase C in carbachol-induced and of cAMP-dependent protein kinase in isoproterenol-induced secretion in primary cultured guinea pig parotid acinar cells.

Stimulation of secretion by muscarinic agonists in guinea pig parotid or pancreatic acini is accompanied by a translocation of protein kinase C (PKC) from the cytosol to the particulate fraction [Machado-De Domenech and Söling (1987) Biochem. J. 242, 749-754] and by a PKC-mediated phosphorylation of the ribosomal protein S6 [Padel and Söling (1985) Eur. J. Biochem. 151, 1-10]. In order to decide whether PKC is directly involved in the secretory process, the effect of down regulation of PKC by phorbol 12-myristate 13-acetate (PMA) was studied in primary cultured guinea pig parotid acinar cells. These cells secrete in response to carbachol and isoproterenol. Only the carbachol response is associated with an increase in cytosolic calcium. Carbachol plus isoproterenol lead to an over-additive stimulation of secretion, an effect which depends completely on the presence of external calcium. Down regulation of PKC by about 90% did not significantly affect carbachol-induced exocytosis, whereas isoproterenol-stimulated secretion was almost doubled. The secretory response to permeable cAMP analogues was also enhanced in PKC-down-regulated acini, indicating a post-receptor effect. The increased response to isoproterenol was also observed in the absence of external calcium. The isoproterenol effect was significantly inhibited by the relatively specific cAMP-dependent protein kinase inhibitor H-89, which had only a minor effect on carbachol-induced exocytosis. Although down regulation of total PKC by up to 90% did not significantly affect the secretory response to carbachol, RO 31-8220, a relatively specific inhibitor of PKC, abolished carbachol-induced secretion in normal as well as in PMA-down-regulated cells. This indicates that a PKC isoform resistant to down regulation by PMA is involved in carbachol- but not in cAMP-mediated secretion.

[Ocular pathology of child abuse]. / Okuläre Pathologie der Kindesmisshandlung.

BACKGROUND: In spite of a growing awareness in the population most cases of child abuse remain probably undetected. Ocular changes in this syndrome are manifold. Sometimes ocular signs can help to substantiate the suspicion of child abuse. On the other hand the ophthalmologist may be the first physician to be contacted. Thus, he plays an important role in diagnosis. Though there are a couple of clinical descriptions morphological data are almost completely missing in the German literature. PATIENT: A two-year-old girl died two days after severe abuse because of widespread intracranial hemorrhages with brain stem insufficiency. At autopsy both eyes were enucleated and sent for histological investigation. RESULTS: The anterior segments were unremarkable. Multiple hemorrhages were found in the inner retina bilaterally. Moreover there were preretinal, intrachoroidal, intrascleral (area of the circle of Zinn-Haller) and subdural hemorrhages. One eye showed a circular, perimacular fold of the central retina and a hemorrhagic retinoschisis. CONCLUSIONS: Intraretinal hemorrhages alone are typical though not pathognomonic for the "battered-child syndrome". However, in combination with a crater-like appearance of the central retina, a hemorrhagic retinoschisis; and intrascleral hemorrhages in the area of the circle of Zinn-Haller they suggest child abuse almost with certainty. The pathogenic mechanisms leading to the observed fundus changes lack definite clarification. The date of violence which is essential for legal prosecution can be difficult to evaluate on morphological grounds alone.

Effect of renal dysfunction in dogs on the disposition and marrow toxicity of melphalan.

The effect of renal failure on melphalan pharmacology and toxicity has been poorly understood. Such information is of interest because melphalan is the most commonly used anticancer drug in the treatment of multiple myeloma, which is frequently associated with renal failure. We have studied the disposition and marrow toxicity of parenteral melphalan in dogs before and after induction of renal failure with subtotal nephrectomy. The surgical procedure decreased the creatinine clearance by an average of 62% (P = 0.001). The lowest neutrophil counts following i.v. melphalan (1 mg/kg) averaged 4.9 x 10(3)/mm3 pre-nephrectomy and 0.9 x 10(3)/mm3 post-nephrectomy, respectively (P = 0.002). The mean lowest recorded platelet counts after melphalan (1 mg/kg) were 115 x 10(3)/mm3 in the pre-nephrectomized dogs, and 9.7 x 10(3/mm3 in those who had been nephrectomized (P = 0.002). Following nephrectomy, i.v. melphalan's terminal-phase plasma half-life and renal clearance were both raised (P = 0.02) to 75% over pre-nephrectomy values. These studies show that i.v. melphalan-induced myelosuppression is markedly increased and its plasma elimination and renal clearance significantly decreased in the presence of renal dysfunction in dogs. These data suggest that parenteral melphalan's starting dose be decreased by at least 50% when used in myeloma patients with renal failure.

Low-dose melphalan induces favourable responses in elderly patients with high-risk myelodysplastic syndromes or secondary acute myeloid leukaemia.

We treated 21 elderly patients with high-risk myelodysplasia (n = 14) or secondary acute myeloid leukaemia (n = 7) with 2 mg of melphalan orally once a day until a complete peripheral response was obtained or until there was evidence of treatment failure. We observed seven (30%) complete and two (10%) partial peripheral responses occurring within 4-16 weeks and lasting for 12 + to 55 weeks. In relapse, retreatment was successful in most of the patients. Responses were associated with the absence of complex cytogenetic abnormalities and with a normal or reduced bone marrow cellularity.

Enhanced levels of lipoperoxides in low density lipoprotein incubated with murine fibroblast expressing high levels of human 15-lipoxygenase.

There is strong experimental evidence that oxidized low density lipoprotein (Ox-LDL) plays an important role in atherosclerosis. However, the mechanisms by which Ox-LDL is formed in vivo are unknown. To test whether 15-lipoxygenase (15-LO) could play a role in oxidation of LDL by cells, we expressed 15-LO activity in murine fibroblasts, which do not normally have 15-LO activity, and tested their ability to modify LDL. Using a retroviral vector, we prepared fibroblasts that expressed 2- to 20-fold more 15-LO activity than control fibroblasts infected with a vector containing beta-galactosidase (lacZ). Compared with LDL incubated with lacZ cells, LDL incubated with 15-LO-containing cells were enriched with lipid hydroperoxides. When these LDL samples were subsequently subjected to oxidative stress, they were more susceptible to further oxidative modification, as judged by increased conjugated diene formation and by increased ability to compete with 125I-Ox-LDL for uptake by macrophages. These findings establish that cellular 15-LO can contribute to oxidative modification of LDL, but the quantitative significance of these findings to the in vivo oxidation of LDL remains to be established.