REVEALING THE VARIED REALITY OF MALARIA-RELATED DEATHS IN CHILDREN ACROSS GENDER, AGE, AND ETHNICITY IN FEDERAL TEACHING HOSPITAL GOMBE OVER 20 YEARS: AN ESSENTIAL EPIDEMIOLOGIC IMPERATIVE.

Introduction: Nigeria recorded 31% of 619,000 malaria deaths globally and accounts for 25-30% of all childhood mortality in the country. Few studies in Nigeria, have reported malaria's case fatality rate over a long period. Objective: To determine Malaria Case Fatality Rate among Children admitted from 2000-2019. Methodology: All severe malaria cases and deaths amongst children aged 0-18 over the last two decades were analysed using ICD-10. The diagnosis was based on clinical and microscopic findings. Results: 26,716 children were admitted, 2494 (9.3%) were diagnosed with malaria and 209 died. Malaria constituted 5.3% (209/3956) of all childhood mortality. Males constituted 58.9 % (1468/2494) while 65% (1642/2494) were aged 0-5 years. Of the malaria admissions, Fulani and Hausa constituted 948(38%) and 438(17.6%) respectively. Admissions were highest in October (15%) and in 2012 (9.6%). The overall malaria CFR was 8.3%; 8.8% in Females (91/1026) and 8.03% in Males P-value <0.05 (X2=54.735); 8.6% in children aged 0-5years, 8.2% in 6-10 years and 7.4% in 11-18 years, P-value <0.05 (X2=893.164). CFR was highest in April (11.4%)and lowest in November (5.2%). Kanuri and Igbo had CFR of 70% and 38.4% respectively while it was lowest in Tera tribe (4.3%), P-value<0.05. The CFR was highest in the year 2004 (22%), 3.5% in 2000 and 2006. Over the years, case fatality rate was 15.9% between 2000-2004, 6.1% from 2005-2009. Between 2010-2015, it was 7.3% and 8.5% from 2016-2019. Conclusion: This study revealed the deadly reality of severe malaria with increased CFR among females, aged 0-5 and the Kanuri tribe.

EPIDEMIOLOGIC TREND AND CASE FATALITY OF CHILDHOOD TETANUS IN FEDERAL TEACHING HOSPITAL GOMBE; A 20YEARS REVIEW.

Introduction: Tetanus is a vaccine-preventable disease, it remains a significant cause of morbidity and mortality in both neonatal and post-neonatal periods, especially in developing countries with limited health facilities and inadequate vaccination. The overall case fatality rate (CFR) is 13.2% globally, highest in the neonatal period and in sub-Saharan Africa. CFR is 64%, 47%, and 43% in Nigeria, Uganda, and Tanzania respectively. Objectives: To determine the Case Fatality Rate of Childhood tetanus in FTHG from 2000-2019. Methodology: All cases and deaths from tetanus amongst children aged 0-18 years in paediatric medical ward of FTHG over the last two decades diagnosed clinically and classified using ICD-10 were analysed. Results: 95 cases of tetanus out of 26,716 total admissions constituting 0.004%. There were 49 tetanus deaths out of 3956 total childhood deaths (0.012%) over the study period. Males constituted 66% (63/95). 30% (28/95) were aged 0-28 days; 23.1% (22/95) were adolescents. Fulani and Hausa constituted 37% (34/95) and 31% (29/95) respectively. Admission was highest in the dry season 52% (50/95 %). The overall tetanus CFR was 51.6%; 78% of deaths were in males (38/49), 30% in neonates, and 23% in adolescents. CFR was highest during the dry season (67.3%). Hausa and Fulani had CFR of 51% and 40% respectively. P-value <0.05 The CFR was 88% between 2000-2004, 72% from 2005-2009, 71% between 2010-2014 and 33% from 2015-2019. Conclusion: Tetanus CFR is still high among neonates and adolescents. Maternal tetanus vaccine and booster doses in children need strengthening.

IN-PATIENT PNEUMONIA BURDEN AND CASE FATALITY RATES IN CHILDREN OVER TWO DECADES IN FEDERAL TEACHING HOSPITAL, GOMBE (FTHG).

Introduction: Pneumonia is the leading cause of death among children globally accounting for an estimated 1.2 million (18%) total deaths annually. The number of childhood-related deaths from pneumonia is approximately 2000-fold higher in developing than in developed countries. Nigeria contributes the highest of pneumonia-related deaths globally. Objectives: To determine the case fatality rates (CFR) of pneumonia from 2000-2019 in paediatric ward, FTHG. Methodology: All cases of pneumonia admissions and deaths in patients aged 0-18 years, using ICD-10 classification, were retrieved and analysed. The mainstay of diagnosis is clinical and/or radiographic features. Results: A total of 26,716 children were admitted during this period, 1151 had pneumonia (4.3%) and 118 died. Males constituted 647 (56.2%) and females 43.8% of the total pneumonia admissions. Children aged 0-5 years had the highest pneumonia admissions, followed by 6-9 years. Admissions were highest in the wet than the dry season. Pneumonia CFR was 10.2%; 10.9% in females and 9.7% in males. Under-5 constituted 84% (969/1151) of pneumonia admission with a CFR of 9.3%. CFR were 10.3% and 21% in 6-10 years, and 11-18 years respectively. The CFR between2000-2004 was 14.1%, 2005-2009:21.1%, 2010-2014:10.2% and 2015-2019:7.2%. Kanuri had the highest CFR of 56.2%.(P <0.05) Other ethnic groups were 29.4% in Waja, 25% in Tula, 21.4% in Igbo, 16.6% in Yoruba, 12.1% in Tangale, 10.2% in Hausa, 8.8%in Bolewa and 8.3% in Fulani. The CFR was highest in February20.2%. Conclusion: Pneumonia Case fatality is high.

MOBILE PHONE UTILIZATION FOR ENHANCING CHILD HEALTH: KNOWLEDGE, ATTITUDES AND PRACTICE OF MOTHERS IN FEDERAL TEACHING HOSPITAL, GOMBE.

Introduction: Globally e-health interventions have expanded significantly and despite huge mobile phone penetration in Nigeria, its deployment in health remains largely unexplored. Objective: To establish the use of mobile phones for health by mothers of children admitted in the paediatric wards of Federal Teaching Hospital, Gombe. Methodology: Three hundred and eighteen structured questionnaires were administered to mothers of children on admission in the paediatric medical ward, emergency paediatric ward, and the special care babies unit over 10 weeks. Results: There were 96.7% (298/308) between 16 and 45 years; 35.1% and 33.8% of mothers had tertiary and secondary level education respectively, 89.3% (275) were married, 65.9% had monogamous marriages; 75.4.% (212/281) of mothers had 1-4 children 94.5% of mothers possessed a mobile phone, 68.5%(139/203) accessed the internet daily, 69.5% (210/302) had access to the internet, 77.5% (203/262) belonged to a social media platform, 64.7% mothers used internet for health, 81% of mothers with tertiary education accessed the internet for health (p<0.05), 66.7% (148/222) have used their phones for healthcare consultation, 54.9%(157/286) have called a healthcare worker which was highest among tertiary-educated mothers (p<0.05), and 88.5% would preferably call a doctor. Symptoms that necessitated the phone call were diarrhoea, convulsions, excessive crying, and vomiting. 59.3% preferred to call healthcare workers anytime, 27% at night. 36% received a prescription 35% were advised and 27% were referred. 87% were satisfied with the healthcare response via phone. 23% have children with chronic illness and 97.3% (291/299) would like to have a Paediatric call Centre for their children's health. Conclusion: Higher maternal education enhanced the use of mobile phones for child health.

Alterations in androgen deprivation enhanced prostate-specific membrane antigen (PSMA) expression in prostate cancer cells as a target for diagnostics and therapy.

BACKGROUND: Prostate-specific membrane antigen (PSMA) is a promising target for diagnostics and therapy of prostate carcinoma (PCa). Based on the hypothesis that PSMA expression can be modulated by variations in androgen deprivation therapy (ADT), we investigated the binding of a PSMA-directed radiopharmaceutical in vitro in order to get an insight of the interactions between altered premedication and PSMA expression before repetitive PSMA-directed PET/CT for therapy response and targeted therapy implementation. METHODS: The human castration-resistant PCa cell line VCaP (CRPC) was treated with either 1 nmol/L testosterone (T) over 20 passages yielding the androgen-sensitive cell line (revCRPC) or with 5 µmol/L abiraterone acetate (AA) generating the abiraterone-tolerant subtype CRPCAA. In these cell lines, T and AA were varied by either supply or withdrawal of T and AA. PSMA expression of the three cell culture models was detected by Western blot and immunohistochemical staining. For quantitative measurement of tracer uptake, 0.3 nmol/L (68)Ga-labelled PSMA-HBED-CC peptide (100-300 kBq/ml) was added to different treated parallel cultures (n = 9 each). Time-dependent uptake per 10(6) cells of each culture was calculated and evaluated. PSMA mRNA expression was investigated by qPCR. RESULTS: PSMA expression increased dependently on intensified ADT in all three basic cell lines. (68)Ga-PSMA-HBED-CC uptake almost doubled during 3 h in all cell lines (p < 0.01). Compared to the basic cells, pre-incubation with abiraterone for 48 h resulted in a significant increased uptake in CRPC (p < 0.001). In revCRPC, 48-h AA pre-incubation resulted in an eightfold higher uptake after 3 h (p < 0.001). Additional withdrawal of external testosterone increased the uptake up to tenfold (p < 0.01). The increase of PSMA expression upon ADT and AA treatments was confirmed by qPCR and Western blot data. Furthermore, in CRPCAA, 48-h AA withdrawal increased the uptake up to fivefold (p < 0.01). CONCLUSIONS: The investigated three PCa cell culture subtypes represent a serial preclinical model of androgen deprivation therapy as a proxy for clinical situations with differing basal PSMA expression. The uptake of PSMA-binding tracers could be stimulated by therapeutic effective short-term variation in premedication in all stages of ADT response. These complex interactions have to be considered in the interpretation of diagnostic imaging using PSMA ligands as well as in the optimal timing of PSMA-based therapies.

Pelvic lymph node dissection for nodal oligometastatic prostate cancer detected by 68Ga-PSMA-positron emission tomography/computerized tomography.

BACKGROUND: The first evaluation of pelvic extended lymph node dissection (pLND) in oligometastatic prostate cancer (PCa) detected by (68)Ga-PSMA PET/CT. METHODS: Retrospective analysis of 35 PCa patients underwent (68)Ga-PSMA PET/CT affected by biochemical recurrence (BCR) after curative treatment (n = 23) or before primary therapy of high-risk PCa (n = 12). We performed pLND associated with pathologic imaging in 17 men with nodal oligometastatic PCa. RESULTS: Indicative lesions for PCa in PET/CT were detected in 91.4% (32 of 35) of patients. Nodal, bone, visceral (pulmonary), and within the prostate suspected disease were detected in 72% (23 of 32), 16% (5 of 32), 6% (2 of 32), and 47% (15 of 32) of patients, respectively. Median serum PSA in patients with pathological radiotracer uptake in recurrent and high-risk PCa patients was 2.9 ng/ml (range 0.18-30) and 19.5 ng/ml (range 6-90), respectively. The median number of removed lymph nodes with pLND in recurrent and high-risk PCa was 10 (range 4-17) and 12 (range 8-29) per patient and the median number of positive lymph nodes was 1 (range 1-2) and 3 (2-3) per patient, respectively. In total, two false positive and one false-negative lymph node were found. Diagnostic accuracies per nodal lesion in total of 213 removed nodes: sensitivity, 94%; specificity, 99%; positive predictive value (PPV), 89%, and negative predictive value (NPV), 99.5%. After pLND, 53% (9 of 17) of patients received androgen deprivation therapy and/or radiation therapy and hormonal therapy, while 47% (8 of 17) of patients remained free of any post-surgery therapy. Follow-up PSA remained less than 0.2 ng/ml in 82% (14 of 17) of patients. After pLND, immediate BCR (PSA never measured less than 0.2 ng/ml) in 18% (3 of 17) of patients was recorded. CONCLUSIONS: This represents the first study of pLND in the setting of nodal oligometastatic PCa detected by (68)Ga-PSMA PET/CT. The use of (68)Ga-PSMA PET/CT could be to improve the accuracy for the detection of nodal micrometastases. These promising findings need validation in larger studies.

How reliable is secondary risk stratification with stimulated thyroglobulin in patients with differentiated thyroid carcinoma? Results from a retrospective study.

OBJECTIVE: Primary risk factors in patients with differentiated thyroid carcinoma (DTC) are well established. In our institution, secondary risk stratification has been performed with stimulated Thyroglobulin (sTg; TSH > 30 mIU/l) within six months after primary therapy since 2001. In this study, we evaluated the predictive value of sTg for long-term disease-free survival (DFS). PATIENTS, METHODS: Data of 202 consecutive patients with DTC were analyzed retrospectively. Median follow-up time was 6.4 years (12 months to 16.2 years). Patients were staged according to Union International Contre le Cancer (UICC) criteria. Primary risk stratification was carried out according to European Thyroid Association criteria. Initially, 134 patients (66%) were classified as low-risk and 68 patients (34%) as high-risk. The influence of established risk factors and sTg on DFS was analyzed at three different time points, up to 36 months after initial therapy. RESULTS: In total, 169 (84%) of all patients remained in complete remission after surgery followed by radioiodine-therapy. Six patients (3%) developed tumour recurrence after initial complete remission. Primary risk factors for persistent disease were male sex, follicular or oncocytic tumour, primary tumour > 4 cm in diameter, initial lymph node involvement, initial metastatic disease and microscopic or macroscopic residual tumor. sTg ≤ 0.3 ng/ml measured within six months after initial therapy was a highly significant predictor (p ≤ 0.001) for lasting DFS, 99% of patients with sTg ≤ 0.3 ng/ml were in complete remission 36 months after initial therapy. CONCLUSIONS: A stimulated Tg ≤ 0.3 ng/ml within six months after initial therapy is a reliable predictor for long-term disease-free survival independent of primary risk stratification.

Patients with autoimmune thyroiditis. Prevalence of benign lymphadenopathy.

UNLABELLED: The prevalence of cervical lymphadenopathy in autoimmune thyroiditis (AIT) patients is actually unknown. The aim of the study was the detailed retrospective evaluation of 6 index-patients with lymphadenopathy in Robbins level VI and a prospective study with high resolution ultrasound of lymphadenopathy in AIT patients compared with controls in all compartments of the neck, accessible to sonographic evaluation. PATIENTS, METHODS: The retrospective study comprises six patients with AIT, evaluated for enlarged Robbins level VI-LN. We report the findings of fine-needle aspiration Cytology, clonal analysis, histology, and serological testing. The prospective study evaluated the prevalence of lymphadenopathy in 49 consecutive patients with AIT (group 1) and 49 consecutive patients with normal thyroids or nontoxic goiter (group 2). RESULTS: In the retrospective study, cytology of paratracheal LN revealed reactive lymphoid hyperplasia in 5/6 of the cases and a centroblastic lymphoma in one patient. The presence of monoclonal lymphatic cells was excluded in 5/6 patients and proven in 1/6 patients. Actual viral-infections were ruled out. In the prospective study AIT-patients showed significantly more enlarged LN in Robbins level II-IV and VI compared to controls. We found no correlation between lymphadenopathy, age, thyroid volume and nodularity, or autoantibody levels. During follow-up in 34 group 1-patients, lymphadenopathy remained stable in 28 patients, and decreased in 6 patients. CONCLUSION: Lymphadenopathy in Robbins level II-IV and VI is common in AIT-patients and most probably related to the autoimmune process.

Targeting NCA-95 and other granulocyte antigens and receptors with radiolabeled monoclonal antibodies (Mabs).

During the last decade considerable effort has been made in the research for in vivo techniques of labeling neutrophils with peptides, labeled cytokines and (99m)Tc-labeled antigranulocyte monoclonal antibodies (AG-Mabs). In general the advantage of in vivo labeling is the simplicity of this approach compared with in vivo techniques. Three of these AG-Mabs have been evaluated in clinical studies: Besilesomab (Scintimun®), Sulesomab (Leucoscan®) and Fanolesomab (Leu-Tech®). White blood cells (WBCs) radiolabeled with AG-Mabs do not show the same behaviour as in vivo labeled white blood cells. Especially (99m)Tc-Sulesomab and (99m)Tc-Besilesomab image infectious foci mainly by non-specific extravasation with secondary binding to postmigratory leukocytes already present at the site of infection.

New approach for the synthesis of [18F]fluoroethyltyrosine for cancer imaging: simple, fast, and high yielding automated synthesis.

O-(2-[(18)F]fluoroethyl)-L-tyrosine ([(18)F]FET) is one of the first (18)F-labeled amino acids for imaging amino acid metabolism in tumors. This tracer overcomes the disadvantages of [(18)F]fluorodeoxyglucose, [(18)F]FDG, and [(11)C]methionine, [(11)C]MET. Nevertheless, the various synthetic methods providing (18)F[FET] exhibit a big disadvantage concerning the necessity of two purification steps during the synthesis including HPLC purification, which causes difficulties in the automation, moderate yields, and long synthesis times >60 min. A new approach for the synthesis of [(18)F]FET is developed starting from 2-bromoethyl triflate as precursor. After optimization of the synthesis parameters including the distillation step of [(18)F]-FCH(2)CH(2)Br combined with the final purification of [(18)F]FET using a simple solid phase extraction instead of an HPLC run the synthesis [(18)F]FET could be significantly simplified, shortened, and improved. The radiochemical yield (RCY) was about 45% (not decay corrected and calculated relative to [(18)F]F(-) activity that was delivered from the cyclotron). Synthesis time was only 35 min from the end of bombardment (EOB) and the radiochemical purity was >99% at the end of synthesis (EOS). Thus, this simplified synthesis for [(18)F]FET offers a very good option for routine clinical use.

FDG-PET in patients with fever of unknown origin: the importance of diagnosing large vessel vasculitis.

This review analyzes the impact of 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET) in the diagnostic work-up of classic fever of unknown origin (FUO) according to the criteria first proposed by Petersorf in 1961 and later modified by Durack et al. in 1991. Algorithms currently used in this diagnostic process are not strictly evidence based up to now. FDG accumulates in malignant tissues, but also in inflammatory cells by the overexpression of facultative glucose transporter-isotypes (mainly GLUT-1 and GLUT-3) and by an overproduction of glycolytic enzymes. Therefore, this technique covers a broad spectrum of possible etiologies for FUO. Once imaged, these lesions can be further investigated by other (e.g. invasive) and more specific methods. Until now, four prospective studies using FDG-PET in patients with classic FUO, encompassing 167 patients in total are published. Three retrospective studies with 125 patients are also available. These studies are discussed and weighted according to the control of selection-bias that was performed. An interstudy-bias may also be present resulting from a considerable variability in causes of FUO. A low number of diagnostic scans in a study may sometimes be related to a high rate of fevers caused by miscellaneous disorders or to a high rate of undiagnosed patients. In these disease categories, focal pathologies that can be imaged with FDG-PET, are rare. A high number of diagnostic scans is always related to a high prevalence of patients with medium- and large-vessel vasculitis. Available data indicate that FDG-PET has the potential to play an important role as a second line procedure in the management of about 1/3 of patients with classic FUO. It is expected that hybrid imaging (PET/computed tomography [CT]; PET/magnetic resonance imaging [MRI]) will improve the diagnostic impact of FDG-PET further, but prospective data about the value of this methods are currently not available. The question as to how these new techniques can be implemented into an evidence based diagnostic algorithm, can only be resolved within a multidisciplinary setting, avoiding both selection- and interstudy-bias whenever possible.

Simplified fast and high yielding automated synthesis of [18F]fluoroethylcholine for prostate cancer imaging.

(11)C- and (18)F-labeled choline analogues are successful tracers for prostate cancer imaging using positron emission tomography (PET). Due to the practical advantages of the longer-living radioisotope (18)F (t(1/2)=110 min) instead of (11)C (t(1/2)=20 min), [(18)F]fluoroethylcholine has been introduced to increase the opportunity of widespread clinical application. Nevertheless, the various known synthetic methods provide [(18)F]fluoroethylcholine for human use only in moderate overall yields of up to 30% so far. Here, a new simplified and high yield two-step-synthesis for [(18)F]fluoroethylcholine is described for potential clinical applications starting from 2-bromoethyl triflate (BETfO) using a modified, commercially available fully automated synthesis module. All synthesis parameters were subsequently optimized resulting in a total yield of 47+/-5% (not decay corrected) in only 40min. [(18)F]fluoroethylcholine could be obtained ready for human use as physiological solution after fixation on Sep-Pak Accell Light cartridges (waters((R))) and formulation with saline without the need of GC or HPLC purification. Radiochemical purity was >99.9% and no contamination of the sterile solution with chemicals used during the synthesis was detected.

High energy probe for detecting lymph node metastases with 18F-FDG in patients with head and neck cancer.

AIM: of this study was to validate a newly developed high energy probe (positron emission probe, PEP) optimised for localising PET tracers in vivo. PATIENTS AND METHODS: Physical investigations included determination of full width at half maximum (FWHM) values at a distance of 1 cm and angular resolution using different point sources. Values obtained with the new probe were compared to those of a conventional gamma probe (CGP). Additionally, PET studies were performed in 36 patients (6 women, 30 men) with proven head and neck cancer and suspected lymph node metastases (Axis, Marconi/Philips) after administering 250-320 MBq (18)F-FDG. Subsequent to PET investigations (18)F-FDG uptake in cervical regions was measured using the PEP. PEP investigations were carried out bilaterally in 5 lymph node (LN) levels (Robbins' classification of the neck). Results of probe studies were correlated with visual and semiquantitative PET evaluations, US and histological findings. RESULTS: FWHM of the new probe was 7 mm (CGP 22 mm) at 662 keV ((137)Cs) and angular resolution resulted in 8 degrees (CGP 60 degrees ). In 29 out of 36 patients LN metastases were suspected due to ultrasound investigations. After neck dissection, histology confirmed LN metastases in 21 patients. Sensitivity (sens.) of US amounted to 95% and specificity to 40%. In 18/21 patients LN metastases were detected by PET (sens. 86%). PET scans failed to diagnose the LN status correctly in 6/36 patients (accuracy 83%). Employing the PEP probe in 20/21 patients LN metastases were identified (sens. 95%), and LN status was determined accurately in 29/36 patients (accuracy 81%). Tumour/background ratios of PEP measurement and results of semiquantitative PET analyses were comparable. CONCLUSIONS: PEP measurement is a promising method for preoperative planning of the extent of neck dissection in patients with head and neck cancer and further for radioguided localising PET tracer accumulation during surgery.

[Reduced radioiodine uptake at increased iodine intake and 131I-induced release of "cold" iodine stored in the thyroid]. / Verminderter Radioiod-Uptake durch erhöhte Iodzufuhr und 131I-induzierte Freisetzung von thyreoidal gespeichertem "kalten" Iod.

AIM: The extent of urinary iodine excretion (UIE) provides information about iodine supply and release. In the present study we investigated correlations between UIE and radioiodine uptake (RIU) as well as effects of radioiodine therapy on UIE in patients with autonomous goitre. PATIENTS, METHODS: In 197 consecutive patients with thyroid autonomy, UIE was measured twice during radioiodine test (RITe) and correlated with RIU. In 98 of these patients, thyroglobulin and thyroid volume (V) were determined prior to therapy. Individual changes in urinary iodine excretion (DeltaUIE) and TG (DeltaTG) could be investigated four weeks (4W) and six months (6M) after radioiodine therapy. Additionally, DeltaV was determined 6M after therapy. DeltaUIE, DeltaTG and DeltaV were correlated with target dose and target volume. RESULTS: Patients with higher iodine excretion exhibited significantly lower thyroidal radioiodine uptake values. Twofold increased UIE prior to therapy decreased radioiodine uptake by 25%. Compared with pretherapeutic values, UIE and TG were significantly increased four weeks after radioiodine therapy (p < 0.001). Median values of both parameters were found to be doubled. The product of target dose and target volume was not only correlated with a decrease of thyroid volume 6M after therapy, but also with an increase of UIE and TG in the early phase after therapy. CONCLUSIONS: It was confirmed that UIE during RITe is a measure for iodine intake and can be used to investigate the competition between stable iodine and radioiodine. The increase of UIE and TG four weeks after therapeutic administration of radioiodine can be explained by disintegrated thyroid follicles. The therapy-induced iodine release may be one important cause for the development of hyperthyroidism in some patients during the first weeks after radioiodine therapy. It may contribute to the known decrease of radioiodine uptake after preapplications of 131I in various thyroid diseases.

Diagnostic 123I and 131I activities and radioiodine therapy. Effects on urinary iodine excretion in patients with differentiated thyroid carcinoma.

AIM: Urinary iodine excretion (UIE) provides information about iodine supply and release. In the present study we investigated effects of the application of different radioiodine isotopes on UIE in patients with differentiated thyroid carcinoma (DTC). PATIENTS, METHODS: In 91 consecutive patients with DTC UIE, measured as iodine/creatinine ratio, was determined before and after application of 123I and 131I for diagnostic or therapeutic purposes. Additionally, remnant volume (V) was determined prior to therapy. Group A consisted of 33 patients with supposed successful ablation of DTC. These patients received 370 MBq 131I for diagnostic use and served as controls. 58 patients (group B) with remnants, relapses and metastases received 370 MBq 123I for diagnostics prior to therapy with 1.5-22.2 GBq 131I. Factors influencing individual changes in urinary iodine excretion (deltaUIE) were investigated by using non-parametric tests. RESULTS: In group A UIE did not change significantly after application of 131I. As well, UIE remained unchanged after diagnostic application of 123I in group B. In contrast, UIE increased significantly already 24 h after therapeutic application of 131I in this group. In patients with small remnants (V < 2.5 ml) a significant but only moderate increase of UIE could be observed (average increase: 47 microg I/g crea). In patients with larger remnants, with relapses or metastases increase of UIE values was significant and more pronounced. CONCLUSIONS: It was confirmed that UIE increased significantly during radioiodine therapy in patients with DTC and radioiodine-accumulating tissue. The increase of UIE after therapeutic administration of radioiodine can be explained by the disintegrated thyroid follicles in thyroid remnants. The radioiodine-induced iodine release may be one reason for thyroid "stunning" even after application of diagnostic amounts of 131I.

Kinetics and organ distribution of allogeneic natural killer lymphocytes transfused into patients suffering from renal cell carcinoma.

The transfusion of natural killer (NK) lymphocytes into patients suffering from malignant diseases is an approach of current interest in the field of immunotherapy. Little is known about the organ distribution, survival, and clearance of donor immune effector cells in cellular therapy, and no reports exist on these important parameters considering NK cells in particular or any other type of allogeneic lymphocytes in humans. In the context of a clinical Phase I/II study we examined the distribution of transfused allogeneic NK cells in patients suffering from renal cell carcinoma. The NK cells were ex vivo cultivated and activated before transfusion. To assess the circulation of the transfused cells in the peripheral blood, we used a nested PCR technique to detect HLA DRB1 alleles of the NK cell donors. Post-transfusion, all patients showed evidence of circulating donor cells for up to 3 days. After 7 days, all donor cells were cleared from the blood to undetectable levels. To assess organ distribution, (111)In-labeled NK cells were injected and monitored by whole-body scintiscans. A distribution to the whole body, with preference for liver, spleen, and bone marrow, was observed after a short initial uptake in the lungs. No activity was observed in lymphatic nodes. A total of 2/4 evaluable metastases showed a clear accumulation of transfused NK cells. The half-life corrected activity in all body compartments remained almost constant over the 6-day observation period in concordance with the absence of any excretion of radioactivity. This may indicate an extended survival of the transfused cells, despite their foreign nature, in the host organism.

Comparing Early to Middle Miocene floras and probable vegetation types of Oberdorf N Voitsberg (Austria), Bohemia (Czech Republic), and Wackersdorf (Germany).

The Early Miocene vegetation of western Styria, Austria, is reconstructed on the basis of detailed investigations of leaves and diaspores from the mining area Oberdorf N Voitsberg. In this paper, the flora and probable vegetation are compared with other assemblages of similar age from the Czech Republic and Germany to elucidate the diversity of wetland and mesophytic plant communities. The floristic composition and the vegetational units represented in Oberdorf are compared to the middle part of the Most Formation (M Most Fm), Cypris Shale, Mydlovary Formation (Mydlovary Fm) of Bohemia, and the Wackersdorf mining area of Bavaria. Among these sites, Oberdorf is extremely poor in hydrophytes and reed-like monocotyledons, indicating rare pond-like habitats as well as possibly more closed swamp forest conditions than, e.g. in the M Most Fm. In Oberdorf, relatively high pH-values in the lignite-forming swamps and the possible scarcity of acidic, nutrient-poor (sandy) soils have probably influenced the floristic composition of the azonal communities. The peat-forming associations in all regions share the abundance of Glyptostrobus europaeus. However, distinct differences in the accompanying elements, such as Taxodium dubium (present and abundant only in the M Most Fm) indicate even stronger floristic variability of Early(/Middle) Miocene peat-forming and riparian plant communities than previously expected. The virtual absence of Pinus, Engelhardia, Comptonia, and probably also of Quercus kubinyii/Quercus drymeja in the megafossil record of Oberdorf can possibly be explained by the edaphic conditions. The abundance of Sequoia abietina (absent in all the other compared sites), which we assign to riparian (and mesophytic) forests in Oberdorf, may have been favoured by rich alluvial soils.In the mesophytic associations, thermophilous elements of the Lauraceae, Mastixiaceae, Symplocaceae, and Rutaceae are diverse. Usually they include Trigonobalanopsis rhamnoides/Trigonobalanopsis exacantha, an evergreen Fagaceae. This assemblage type corresponds with the Younger Mastixioid Flora sensu Mai. The Younger Mastixioid Flora is best developed in Wackersdorf, less distinct in Oberdorf, and likely in the Cypris Shale and Mydlovary Fm. It is not traceable in the M Most Fm.

Chronic inborn erythrocytosis leads to cardiac dysfunction and premature death in mice overexpressing erythropoietin.

The most common cause of an increase of the hematocrit is secondary to elevated erythropoietin levels. Erythrocytosis is assumed to cause higher blood viscosity that could put the cardiovascular system at hemodynamic and rheological risks. Secondary erythrocytosis results from tissue hypoxia, and one can hardly define what cardiovascular consequences are caused by chronic erythrocytosis or hypoxia. Herein, a novel transgenic (tg) mouse line is characterized that is erythrocytotic because of chronic overexpression of the human erythropoietin gene. These mice grow up well, reaching a hematocrit of about 0.80 in adulthood. Blood volume of adult tg mice was markedly increased by 75%. Unexpectedly, blood pressure was not elevated and cardiac output was not decreased. Still, the adult tg mice showed features of cardiac dysfunction with increased heart weight. In vivo, high-frequency echocardiography revealed marked ventricular dilatation that was confirmed by histologic examination. Furthermore, by transmission electron microscopy, a prominent intracellular edema of the cardiomyocytes was seen. Exercise performance of the tg mice was dramatically reduced, unmasking the severity of their compromised cardiovascular function. In addition, life expectancy of the tg mice was significantly reduced to 7.4 months. Our findings suggest that severe erythrocytosis per se results in cardiac dysfunction and markedly reduced life span.

Radioiodine therapy in Graves' hyperthyroidism: determination of individual optimum target dose.

UNLABELLED: The aim of this study was to investigate the results of different volume-dependent target doses on clinical outcome 6 months after radioiodine therapy (RITh) and its correlation with post therapeutic thyroid volumes (Vpost) in patients with Graves' disease. This analysis was designed to determine factors improving the results of radioiodine therapy without increasing target doses generally, as has been recommended recently. We studied consecutive data from 102 patients with Graves' disease, who had initial radioiodine therapy between 1991 and 1995. The 131I activities were calculated according to the formula of Marinelli. In addition to the normal calculation individual target doses were adjusted to the thyroid volumes of each patient before therapy. For statistical evaluation, the patients were divided into three subgroups of comparable sample sizes: Group I included those with a thyroid volume <15 ml before therapy. Group II included those ranging from a 15-25 ml volume before therapy and group III included those with thyroid volumes >25 ml. Laboratory thyroid parameters and thyroid volumes were measured in those groups before and 6 months after therapy. RESULTS: Analysis of all patients revealed a significantly higher rate of hypothyroidism (54%) and fewer cases of hyperthyroidism (15%) six months after therapy in cases with Vpost smaller than 8 ml. The median Vpost needed to achieve an optimum therapeutic success rate (rate of eu- or hypothyroidism) was smaller than 5 ml in group I and smaller than 10 ml in group II. Therapeutic success was associated with different target doses in each group, 150,220 and 260 Gy for groups I, II, and III respectively. CONCLUSIONS: Post therapeutic thyroid volumes correlated significantly with clinical outcome six months after therapy. An adjustment of the target doses based on thyroid volumes before therapy will lead to an appropriate reduction of thyroid volumes. Thus, in the individual case clinical outcome could be improved without applying higher target doses in all patients. This would ensure a better utilization of limited resources in medical care e.g. through a shorter hospital stay.