A phase IIa, randomized, double-blind, safety, immunogenicity and efficacy trial of Plasmodium falciparum vaccine antigens merozoite surface protein 1 and RTS,S formulated with AS02 adjuvant in healthy, malaria-naïve adults.

BACKGROUND: To improve the efficacy of Plasmodium falciparum malaria vaccine RTS,S/AS02, we conducted a study in 2001 in healthy, malaria-naïve adults administered RTS,S/AS02 in combination with FMP1, a recombinant merozoite surface-protein-1, C-terminal 42kD fragment. METHODS: A double-blind Phase I/IIa study randomized N = 60 subjects 1:1:1:1 to one of four groups, N = 15/group, to evaluate safety, immunogenicity, and efficacy of intra-deltoid half-doses of RTS,S/AS02 and FMP1/AS02 administered in the contralateral (RTS,S + FMP1-separate) or same (RTS,S + FMP1-same) sites, or FMP1/AS02 alone (FMP1-alone), or RTS,S/AS02 alone (RTS,S-alone) on a 0-, 1-, 3-month schedule. Subjects receiving three doses of vaccine and non-immunized controls (N = 11) were infected with homologous P. falciparum 3D7 sporozoites by Controlled Human Malaria Infection (CHMI). RESULTS: Subjects in all vaccination groups experienced mostly mild or moderate local and general adverse events that resolved within eight days. Anti-circumsporozoite antibody levels were lower when FMP1 and RTS,S were co-administered at the same site (35.0 µg/mL: 95 % CI 20.3-63), versus separate arms (57.4 µg/mL: 95 % CI 32.3-102) or RTS,S alone (62.0 µg/mL: 95 % CI: 37.8-101.8). RTS,S-specific lymphoproliferative responses and ex vivo ELISpot CSP-specific interferon-gamma (IFN-γ) responses were indistinguishable among groups receiving RTS,S/AS02. There was no difference in antibody to FMP1 among groups receiving FMP1/AS02. After CHMI, groups immunized with a RTS,S-containing regimen had âˆ¼ 30 % sterile protection against parasitemia, and equivalent delays in time-to-parasitemia. The FMP1/AS02 alone group showed no sterile immunity or delay in parasitemia. CONCLUSION: Co-administration of RTS,S and FMP1/AS02 reduced anti-RTS,S antibody, but did not affect tolerability, cellular immunity, or efficacy in a stringent CHMI model. Absence of efficacy or delay of patency in the sporozoite challenge model in the FMP1/AS02 group did not rule out efficacy of FMP1/AS02 in an endemic population. However, a Phase IIb trial of FMP1/AS02 in children in malaria-endemic Kenya did not demonstrate efficacy against natural infection. CLINICALTRIALS: gov identifier: NCT01556945.

A rare case of a 123I-MIBG SPECT/CT positive, but 68Ga-DOTA-TOC PET/CT negative pheochromocytoma of the bladder. / Caso infrecuente de feocromocitoma vesical positivo en la SPECT/TC con 123I-MIBG, pero negativo en la PET/TC con 68Ga-DOTA-TOC.

Pheochromocytoma (PHEO) is rare and belongs to the group of neuroendocrine tumours (NETs). These tumours can be found anywhere from the neck to the pelvis associated with sympathetic ganglia. Morphological imaging, for example CT, provides excellent anatomical detail and high sensitivity but lacks specificity as difficulties may occur when distinguishing between tumours derived from the sympathetic nervous system and other tumour entities. In contrast to anatomical imaging, functional imaging (123I-MIBG, 68Ga-DOTA-TOC PET) provides high sensitivity and specificity in detecting NETs. Early detection of PHEO is crucial and has a major effect on treatment and prognosis. This case report describes the important role of anatomical and functional imaging in a patient with a neuroendocrine tumour of unusual origin.

[Position paper on medication-related osteonecrosis of the jaw (MRONJ)]. / Positionspapier zur medikamentenassoziierten Osteonekrose des Kiefers (MRONJ).

It is now 12 years since the first article on medication-related osteonecrosis of the jaw (MRONJ) was reported in 2003. The recognition of MRONJ is still inconsistent between physicians and dentists but it is without doubt a severe disease with impairment of oral health-related quality of life. This position paper was developed by three Austrian societies for dentists, oral surgeons and osteologists involved in this topic. This update contains amendments on the incidence, pathophysiology, diagnosis, staging and treatment and provides recommendations for management based on a multidisciplinary international consensus. The MRONJ can be a medication-related side effect of treatment of malignant and benign bone diseases with bisphosphonates (Bp), bevacizumab and denosumab (Dmab) as antiresorptive therapy. The incidence of MRONJ is highest in the oncology patient population (range 1-15 %), where high doses of these medications are used at frequent intervals. In the osteoporosis patient population, the incidence of MRONJ is estimated to be 0.001-0.01 %, marginally higher than the incidence in the general population (< 0.001 %). Other risk factors for MRONJ include glucocorticoid use, maxillary or mandibular bone surgery, poor oral hygiene, chronic inflammation, diabetes mellitus, ill-fitting dentures as well as other drugs, including antiangiogenic agents. Prevention strategies for MRONJ include elimination or stabilization of oral disease prior to initiation of antiresorptive agents, as well as maintenance of good oral hygiene. In those patients at high risk for the development of MRONJ, including cancer patients receiving high-dose BP or Dmab therapy, consideration should be given to withholding antiresorptive therapy following extensive oral surgery until the surgical site heals with mature mucosal coverage. Management of MRONJ is based on the stage of the disease, extent of the lesions and the presence of contributing drug therapy and comorbidity. Conservative therapy includes topical antibiotic oral rinses and systemic antibiotic therapy. Early data have suggested enhanced osseous wound healing with teriparatide in those patients without contraindications for its use. The MRONJ related to denosumab may resolve more quickly with a drug holiday than MRONJ related to bisphosphonates. Localized surgical debridement is indicated in advanced nonresponsive disease and has proven successful. More invasive surgical techniques are becoming increasingly more important. Prevention is the key for the management of MRONJ. This requires a close teamwork for the treating physician and the dentist. It is necessary that this information is disseminated to other relevant health care professionals and organizations.

[Diabetes and osteoporosis: pathophysiological interactions and clinical importance for geriatric patients]. / Diabetes und Osteoporose: Pathophysiologische Interaktionen und klinische Bedeutung für geriatrische Patienten.

Osteoporosis is an age-associated disease, resulting in impaired bone quality and increased risk for bone fractures. Patients with type 2 diabetes mellitus have--despite a normal or even increased bone mineral density--an increased risk for fractures, which is related to an imbalance between osteoblastic bone formation and osteoclastic resorption. Complex pathophysiological mechanisms associated with insulin resistance and hyperglycemia are involved in the deleterious effects on osteoblast function and bone formation. The quality and regimen of antidiabetic therapy are discussed as modulators of bone metabolism. Of great clinical importance is an assessment of the fall risk especially for diabetic patients, because late complications, such as neuropathy, but also side effects of medication can result in a significantly increased risk for falls. Lifestyle intervention is of advantage with respect to diabetes and osteoporosis prevention and therapy. Vitamin D supplementation results in favorable effects with a reduced risk for falls and also improvements of insulin sensitivity. According to published data, the safety and efficacy of specific medication for the treatment of osteoporosis (bisphosphonates, denosumab, selective estrogen receptor modulators) reveal no difference between patients with and without diabetes mellitus.

Surgeons save bones: an algorithm for orthopedic surgeons managing secondary fracture prevention.

Postmenopausal osteoporosis has a big impact on health care budget worldwide, which are expected to double by 2050. In spite of severe medical and socioeconomic consequences from fragility fractures, there are insufficient efforts in optimizing osteoporotic treatment and prevention. Undertreatment of osteoporosis is a well known phenomenon, particularly in elderly patients. Treatment rates remain low across virtually all patient, provider, and hospital-level characteristics, even after fragility fractures. In-hospital initiation is one of the options to increase treatment rates and improve osteoporosis management. However, multiple factors contribute to the failure of initiating appropriate treatment of osteoporosis in patients with fragility fractures. These include a lack of knowledge in osteoporosis and an absence of a comprehensive treatment guideline among family physicians and orthopedic surgeons. Furthermore, orthopedic surgeons are hardly willing to accept their responsibility for osteoporosis treatment due to the fact that they are usually not familiar with the initiation of specific drug treatments. The presented algorithm offers trauma surgeons and orthopedic surgeons a safe and simple guided pathway of treating osteoporosis in postmenopausal women appropriately after fragility fractures based on the current literature. From our point of view, this algorithm is useful for almost all cases and the user can expect treatment recommendations in more than 90 % of all cases. Nevertheless, some patients may require specialized review by an endocrinologist. The proposed algorithm may help to increase the rate of appropriate osteoporosis treatment hence reducing the rates of fragility fractures.

Bone mineral density and bone metabolism in patients with major depressive disorder without somatic comorbidities.

BACKGROUND: Major depressive disorder (MDD) has been linked with accelerated bone loss leading to the development of low bone mineral density (BMD). Several mechanisms have been discussed as causative factors, e.g. lifestyle, selective serotonin reuptake inhibitor (SSRI) intake, or the influence of proinflammatory cytokines. METHODS: In a cross-sectional study of in-patients with a current episode of MDD, without somatic comorbidities, we determined various parameters of bone metabolism, inflammatory parameters and parameters of depression. BMD was measured by dual x-ray absorptiometry. RESULTS: Of 50 patients, only one had low BMD in any of the measure sites. Body mass index (BMI) correlated positively with Z-scores. 83.3% of the examined patients had elevated osteoprotegerin (OPG) levels. SSRI intake did not have an effect on BMD. BMD in the femoral neck was significantly lower in smokers. We also found a positive correlation between the level of physical activity and osteocalcin levels. CONCLUSIONS: In our sample, young to middle-aged, somatically healthy, and acutely depressed patients with a history of MDD showed no reduction of BMD. This could be due to compensatory mechanisms, as suggested by elevated OPG levels. Physical activity and high BMI could also have served as protective factors. Still, as patients with MDD often suffer from comorbidities or take medication with a negative effect on bone, this population should be appreciated as a high-risk group for the development of osteopenia and osteoporosis.

Molecular characterization of Thelastomatoidea (Nematoda: Oxyurida) from cockroaches in Australia.

A molecular approach was used to genetically characterize 5 species (Aoruroides queenslandensis, Blattophila sphaerolaima, Cordonicola gibsoni, Desmicola ornata and Leidynemella fusiformis) belonging to the superfamily Thelastomatoidea (Nematoda: Oxyurida), a group of pinworms that parasitizes terrestrial arthropods. The D3 domain of the large subunit of nuclear ribosomal RNA (LSU) was sequenced for individual specimens, and the analysis of the sequence data allowed the genetic relationships of the 5 species to be studied. The sequence variation in the D3 domain within individual species (0-1.8%) was significantly less than the differences among species (4.3-12.4%). Phylogenetic analyses, using maximum parsimony, maximum likelihood, and neighbour-joining, tree-building methods, established relationships among the 5 species of Thelastomatoidea and Oxyuris equi (a species of the order Oxyurida). The molecular approach employed provides the prospect for developing DNA tools for the specific identification of the Thelastomatoidea, irrespective of developmental stage and sex, as a basis for systematic, ecological and/or population genetic investigations of members within this superfamily.

Isolation and characterization of class II myosin genes from Haemonchus contortus.

In this study, cDNAs encoding myosin from the parasitic nematode Haemonchus contortus were isolated and characterized. Several exhibited a considerable degree of sequence variation at the nucleotide and limited divergence at the amino acid levels within the various functional domains. The results suggest that the cDNAs isolated represented a single myosin heavy chain, which, by comparison with a number of other myosins, is inferred to represent a homologue of a muscle myosin (CeMHCA) of the free-living nematode Caenorhabditis elegans. The findings could have implications for investigating cytoskeletal dynamics and/or signalling pathways.

Spirometra erinacei / S. erinaceieuropaei in a feral cat in Manawatu with chronic intermittent diarrhoea.

CASE HISTORY: A feral cat captured in the Manawatu region of New Zealand was treated for worms and fleas, and kept confined in a metabolic cage. It showed good appetite and weight gain but had intermittent watery, yellow diarrhoea. CLINICAL FINDINGS: Clinical examination under sedation was unremarkable and routine blood tests showed no significant abnormalities. The cat was negative for feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV). Different canned cat foods did not alter the course of the diarrhoea, and the cat was euthanised 6 months after capture. At necropsy, two sections of adult Spirometra tapeworms were found in the jejunum and typical Spirometra eggs were found in colonic contents. Molecular identification of the parasite was undertaken, using the cytochrome-c oxidase subunit-1 gene (cox1) sequence. DIAGNOSIS: Chronic intermittent diarrhoea associated with Spirometra erinacei / S. erinaceieuropaei infection. CLINICAL RELEVANCE: Spirometra has not been reported in New Zealand before but has been associated with gastrointestinal disease in cats in other parts of the world. It requires species targeted treatment to be eliminated effectively, and is zoonotic. Diagnosis could be difficult for clinicians who are not familiar with the parasite and its life cycle.

Survey of intestinal parasites in pigs from intensive farms in Guangdong Province, People's Republic of China.

The prevalence of intestinal parasites was investigated in intensive pig farms in Guangdong Province, China between July 2000 and July 2002. Faecal samples from 3636 pigs (both sexes and five age groups) from 38 representative intensive pig farms employing different parasite control strategies were examined for the presence of helminth ova and protozoan oocysts, cysts and/or trophozoites using standard techniques. Of the 3636 pigs sampled, 209 (5.7%) were infected with Trichuris suis, 189 (5.2%) with Ascaris, 91 (2.5%) with Oesophagostomum spp., 905 (24.9%) with coccidia (Eimeria spp. and/or Isospora suis) and 1716 (47.2%) with Balantidium coli. These infected pigs were mainly from farms without a strategic anti-parasite treatment regime. Concurrent infection of multiple parasites was common, and T. suis was the most common nematode infecting breeding, young and mature pigs. The results of the present investigation provide relevant 'base-line' data for assessing the effectiveness of control strategies against intestinal parasitism in intensively raised pigs in Guangdong Province, China.

Increase in thyroid follicular cell tumors in nelfinavir-treated rats observed in a 2-year carcinogenicity study is consistent with a rat-specific mechanism of thyroid neoplasia.

The carcinogenic potential of nelfinavir mesylate (nelfinavir) was evaluated in a 2-year oral (gavage) study on Sprague-Dawley rats at dose levels of 0 (control), 0 (vehicle control), 100, 300 and 1000 mg/kg per day. At the end of the treatment, increased incidences of thyroid follicular cell hyperplasia and neoplasms were observed at 300 (males) and 1000 mg/kg per day (both sexes). There were no other treatment-related effects and no tumors at other sites. Results from previous studies indicated a number of effects in the liver and thyroid, as well as metabolic profiles that suggested nelfinavir might cause thyroid hyperplasia/neoplasia secondary to hormone imbalance by altering thyroid hormone disposition. To investigate this hypothesis, the effects of nelfinavir on gene expression in rat hepatocytes and liver slices (in vitro), thyroxine plasma clearance, and thyroid gland function were evaluated. Compared to controls, gene expression analyses demonstrated an increased expression of glucuronyltransferase (UDPGT) and CYP450 3A1 in nelfinavir-treated rat hepatocytes and liver slices. In rats treated with nelfinavir (1000 mg/kg per day) for 4 weeks, liver weights and centrilobular hepatocellular hypertrophy were increased and minimal to mild diffuse thyroid follicular cell hypertrophy and follicular cell hyperplasia were evident in the thyroid gland. Thyroid-stimulating hormone (TSH) levels were significantly increased (three-fold), while tri-iodothyronine (T3)/tetra-iodothyronine (T4) and reverse T3(rT3) levels were unchanged, indicating that a compensated state to maintain homeostasis of T3/T4 had been achieved. Plasma 125I-thyroxine clearance was increased and the plasma thyroxine AUC0-48 was decreased (24%) compared to control. In conclusion, these data indicate that thyroid neoplasms observed in the nelfinavir-treated rats were secondary to thyroid hormone imbalance. Increased thyroxine clearance contributes to the effects of nelfinavir on thyroid gland function and is probably a result of UDPGT induction that leads to elevated TSH levels in the rat and eventual thyroid neoplasia. These results are consistent with a well-recognized rat-specific mechanism for thyroid neoplasms.

A male-specific (cysteine-rich) protein of Oesophagostomum dentatum (Strongylida) with structural characteristics of a serine protease inhibitor containing two trypsin inhibitor-like domains.

A cDNA was isolated from an adult male Oesophagostomum dentatum gene library by screening with a male-specific, partial expressed sequence tag (EST) probe identified previously using a differential display technique. The full-length cDNA of 642 bp included 5' and 3' untranslated regions of 44 and 121 nucleotides, respectively, and encoded a predicted protein with a putative 18 amino acid signal sequence and a mature polypeptide of 14.7 kDa comprising approximately 15% cysteine residues. The amino acid sequence showed similarity with a number of proteins from Caenorhabditis elegans, parasitic nematodes, insects and amphibia, all of which contain a trypsin inhibitor-like cysteine-rich domain. A 3-dimensional structure model constructed for the O. dentatum protein (designated OdmCRP) inferred that it is composed of 2 domains, each with 5 disulfide bonds, which are indicative of the Ascaris family of serine protease inhibitors. These findings indicate that OdmCRP, with 2 structural domains relating to functionally active sites, is a new member of this inhibitor family.

G-455A polymorphism of the fibrinogen beta gene and deep vein thrombosis.

BACKGROUND: Elevated fibrinogen levels have been linked to increased risk for deep venous thrombosis, although it is not clear whether fibrinogen is causal or rather a marker for the presence of other risk factors. A common G/A polymorphism in the gene for the fibrinogen beta-chain (FGB G-455A) is associated with elevated fibrinogen levels. The present study was designed to analyze the role of this genetic marker for deep venous thrombosis. MATERIALS AND METHODS: We performed a case-control study including 307 patients with documented deep venous thrombosis and 316 control subjects. beta-fibrinogen genotypes were determined by allele-specific polymerase chain reaction. RESULTS: GG, GA and AA genotype frequencies were similar among the patients (53.1%, 41.0, 5.9) and controls (51.6%, 42.1, 6.3; P = 0.92). Fibrinogen levels of the patients (median 3.72 g l-1; range 1.93-11.6) did not differ significantly from those of the controls (3.76; 2.17-9.99). Carriers of the homozygous AA genotype had significantly higher fibrinogen levels than noncarriers (patients: 5.32 vs. 3.59; P = 0.024; controls: 6.29 vs. 3.72; P = 0.048). CONCLUSION: Our data suggest that the fibrinogen-elevating FGB G-455A gene polymorphism is not linked to an increased risk for deep venous thrombosis.

Cardiac failure and multiple organ dysfunction syndrome in a patient with endocrine adenomatosis.

In this case report, we present the successful therapy of severe cardiac failure in pituitary adrenal insufficiency. A previously healthy 56-year-old-man in pituitary coma due to an atypical variant of multiple endocrine adenomatosis (pituitary adenoma and pheochromocytoma) suffered from cardiac failure resistant to catecholamine and standard hydrocortisone therapy. After two bolus injections of dexamethasone (2 x 24 mg) mean arterial pressure and cardiac function dramatically improved, probably due to restoration of permissive effects on catecholamine action and reversal of pathophysiological mechanisms of cardiac failure. We conclude that in patients with severe cardiovascular failure in pituitary coma the administration of potent glucocorticoids may be more effective in reversing cardiovascular failure than standard dosages of hydrocortisone.

[Is there new knowledge on embryology and functional anatomy of human mimetic muscles and the upper lip? A contribution to point selection, skin incision and muscle reconstruction in primary lip-nose reconstruction of uni- and bilateral lip-jaw-palatal clefts]. / Gibt es neue Erkenntnisse zur Embryologie und funktionellen Anatomie der humanen mimischen Muskulatur und der Oberlippe? Ein Beitrag zur Punktewahl, Hautschnittführung und Muskelrekonstruktion bei der primären Lippen-Nasen-Plastik ein- und doppelseitiger LKG-Spalten.

BACKGROUND: The great variety of primary cheiloplastic procedures in CLP patients shows that there is disagreement regarding the embryological development of this part of the face, the point selection, skin incision philosophy, and the macroscopic and microscopic functional anatomy of the human muscles of facial expression. We suppose from findings in Asian and African populations that the real embryological development of the upper lip differs from current textbook descriptions. Our own anatomical and embryological investigations serve as a basis for a critical discussion of different techniques of muscle reconstruction, point selection, and skin incision and for a description of an embryologically, functionally, and anatomically oriented operation technique for different entities of CLP. METHODS: The findings of this study result from investigations of the embryonal and early fetal development from the 26th to the 112th i.u. day in REM pictures of the Anatomical Institute of the University of Göttingen (n = 8) and serial histological investigations of the Carnegie and Hooker-Humphrey Collections at the Armed Forces Institute of Pathology, Washington, D.C. (n = 40). Furthermore, we carried out microsurgical dissections of the muscles of facial expression, the osseous and cartilaginous parts of the nose, and the midfacial sutures in two adult heads without congenital disorders and one newborn head with a primary unilateral complete cleft of the lip and alveolus. RESULTS AND DISCUSSION: The formation of the lower third of the upper lip is the result of contact of the maxillary bulges in the midline below the prolabium. According to this finding, the point selections and skin incisions have to be modified in the midline region in different types of uni- and bilateral CLP. Our technique of primary dissection, reorientation, and suturing of the muscles of facial expression is presented. The muscle reconstruction has to be performed independently from the skin preparation.

Elevated inferior petrosal sinus levels of PTHrP in a patient with Cushing's disease.

PTHrP has been found in various tissues, including prolactinomas and growth hormone producing adenomas. The function and clinical importance of PTHrP are poorly understood. We report the case of a 25-year-old female patient with hirsutism. Autonomous ACTH-dependent hypercortisolism was documented by endocrine testing. Magnetic resonance imaging (MRI) revealed a 3-mm intrasellar hypointense lesion in the left side of the pituitary gland. The inferior petrosal sinus sampling disclosed a gradient of ACTH left central/peripheral of 30.5 and right central/peripheral of 2.0 and suggested the diagnosis of a left-sided pituitary ACTH secreting microadenoma. Interestingly, we found elevated PTHrP levels in the left inferior petrosal sinus with a gradient of 4.7 compared to peripheral venous blood and of 3.6 compared to the right sinus. Our results fit very well to the concept of a para-/autocrine secretion of PTHrP which has been proposed recently and suggest a role in the regulation of cell growth of pituitary adenomas.

[Androgen therapy from the viewpoint of the internal medicine physician]. / Androgentherapie aus der Sicht des Internisten.

The partial androgen deficit of the ageing male is an essential part of the age-related changes of the endocrine system. Clinically relevant disturbances (co-) caused by a relative testosterone-deficit are: changes of body composition (increase of fat mass, decrease of lean tissue mass), decrease of muscle strength and mass, changes of the lipid profile, cardiovascular disease, osteoporosis and anemia. Controlled studies revealed a positive effect of testosterone substitution on body composition, muscle strength, bone metabolism and erythropoesis. Moreover, a protective effect on the development of coronary artery disease could be demonstrated by an improvement of the lipid profile, decrease of obesity and insulin resistance and by a direct effect on the coronary vessels. Clinically evident hypogonadism is a clear indication for testosterone-substitution also in the ageing male, whereas in the case of the partial testosterone-deficit in the absence of sufficient data at this time no general recommendation for substitution can be given; one has to decide about a (experimental) therapy in the individual patient. In every case the contraindications of a testosterone-supplementation (carcinoma of the prostate, elevated PSA-values, polyglobulia, sleep-apnea-syndrome) have to be observed, a continuous survey of the therapy, especially of the prostate is essential. A general recommendation for a substitution with dehydroepiandrosterone (DHEA) can not be given.

Partial laparoscopic adrenalectomy for aldosterone-producing adenoma: short-and long-term results.

BACKGROUND AND PURPOSE: Laparoscopic surgery for adrenal gland tumors is the gold standard operative approach now. Adrenal-sparing surgery has special indications. We demonstrated the safety and feasibility of performing adrenal-sparing surgery by means of laparoscopy for aldosterone-producing adenoma (Conn's syndrome). PATIENTS AND METHODS: Between 1995 and 1999, seven patients with Conn's syndrome had laparoscopic adrenal-sparing resection of their tumors. These patients were followed up by means of radiology and biochemistry. RESULTS: All seven patients had successful laparoscopic surgery without complications. Most patients were discharged in 2 to 6 days (mean 3 days). At follow-up, the six patients investigated had normal blood pressure. No recurrences have been encountered with a median follow-up of 12 months in these six patients. CONCLUSIONS: Adrenal-sparing resection of tumors causing primary hyperaldosteronism is technically feasible by means of laparoscopy. This procedure has the advantage of keeping a greater reserve of normal adrenal tissue and of rapid postoperative recovery.

Isolation and characterisation of sex-specific transcripts from Oesophagostomum dentatum by RNA arbitrarily-primed PCR.

In light of the lack of molecular data on the sexual differentiation, maturation and interaction of parasitic nematodes of livestock, the present study investigated sex-specific gene expression in the nodule worm, Oesophagostomum dentatum (Strongylida). Using the technique of RNA arbitrarily-primed polymerase chain reaction (RAP-PCR), 31 expressed sequence tags (ESTs) differentially-displayed between the sexes were cloned. Northern blot analysis proved ten ESTs to be expressed exclusively in males (adults and fourth-stage larvae), while two were expressed solely in female stages. None of the ESTs were expressed in infective third-stage larvae. Sequence analysis and subsequent database searches revealed two male-specific ESTs to have significant similarity to Caenorhabditis elegans (predicted) proteins, a protein containing an EGF-like cysteine motif and a serine/threonine phosphatase. Another two male-specific ESTs had similarity to non-nematode sequences. The two female-specific ESTs had similarity to vitellogenin-5 and endonuclease III (predicted) from C. elegans. The remaining ESTs had no similarity to any nucleic acid or protein sequences contained in the databases. The isolation and characterisation of sex-specific ESTs from O. dentatum provides a unique opportunity for studying the reproductive biology of parasitic nematodes at the molecular level, with a view toward novel approaches for parasite control.

Elevated levels of serum secretoneurin in patients with therapy resistant carcinoma of the prostate.

PURPOSE: The majority of prostate cancers show some degree of neuroendocrine differentiation. It was previously demonstrated that chromogranin A, a constituent of large dense core vesicles of neuroendocrine cells, is frequently elevated in patients with metastatic prostate cancer. We evaluate the expression of secretoneurin, which is generated by proteolytic processing of secretogranin II (chromogranin C), in patients with prostate disease. MATERIALS AND METHODS: Secretoneurin was measured in sera of 16 healthy men whose blood was drawn for prostate cancer screening (controls), and in 9 patients with prostatitis, 19 with benign prostate hyperplasia and 54 with prostate cancer detected by radioimmunoassay. Therapy resistant disease (clinical stage D3) was noted in 20 prostate cancer cases. Serum prostate specific antigen was measured in all patients and controls. In addition, chromogranin A, prostate acid phosphatase and interleukin-6 were determined in patients with D3 prostate cancer. Molecular properties of secretoneurin immunoreactivity were analyzed by gel filtration chromatography followed by radioimmunoassay. RESULTS: Mean secretoneurin was 58.9+/-8 fmol./ml. in patients with therapy resistant prostate cancer. Levels were significantly higher than those measured in sera from controls and patients with prostatitis, benign prostatic hyperplasia and pT2 or pT3 prostate cancer. There was a statistically significant correlation between secretoneurin and chromogranin A in patients with endocrine therapy failure (r = 0.543, p<0.05). There was no correlation between serum secretoneurin and prostate specific antigen, prostate acid phosphatase or interleukin-6. Gel filtration chromatography analysis of sera of 3 patients with D3 prostate cancer revealed a peak of secretoneurin immunoreactivity where intact secretoneurin elutes, thus showing that the processed peptide is circulating in the blood. CONCLUSIONS: Secretoneurin is elevated in sera of patients with endocrine therapy refractory prostate cancer. Our results support the concept that neuroendocrine differentiation is associated with prostate cancer progression.