Biomarker responses of Peromyscus leucopus exposed to lead and cadmium in the Southeast Missouri Lead Mining District.

Biomarker responses and histopathological lesions have been documented in laboratory mammals exposed to elevated concentrations of lead and cadmium. The exposure of white-footed mice (Peromyscus leucopus) to these metals and the potential associated toxic effects were examined at three contaminated sites in the Southeast Missouri Lead Mining District and at a reference site in MO, USA. Mice from the contaminated sites showed evidence of oxidative stress and reduced activity of red blood cell δ-aminolevulinic acid dehydratase (ALAD). Histological examinations of the liver and kidney, cytologic examination of blood smears, and biomarkers of lipid peroxidation and DNA damage failed to show indications of toxic effects from lead. The biomagnification factor of cadmium (hepatic concentration/soil concentration) at a site with a strongly acid soil was 44 times the average of the biomagnification factors at two sites with slightly alkaline soils. The elevated concentrations of cadmium in the mice did not cause observable toxicity, but were associated with about a 50% decrease in expected tissue lead concentrations and greater ALAD activity compared to the activity at the reference site. Lead was associated with a decrease in concentrations of hepatic glutathione and thiols, whereas cadmium was associated with an increase. In addition, to support risk assessment efforts, we developed linear regression models relating both tissue lead dosages (based on a previously published a laboratory study) and tissue lead concentrations in Peromyscus to soil lead concentrations.

Humanized theta-defensins (retrocyclins) enhance macrophage performance and protect mice from experimental anthrax infections.

Retrocyclins are humanized versions of the -defensin peptides expressed by the leukocytes of several nonhuman primates. Previous studies, performed in serum-free media, determined that retrocyclins 1 (RC1) and RC2 could prevent successful germination of Bacillus anthracis spores, kill vegetative B. anthracis cells, and inactivate anthrax lethal factor. We now report that retrocyclins are extensively bound by components of native mouse, human, and fetal calf sera, that heat-inactivated sera show greatly enhanced retrocyclin binding, and that native and (especially) heat-inactivated sera greatly reduce the direct activities of retrocyclins against spores and vegetative cells of B. anthracis. Nevertheless, we also found that retrocyclins protected mice challenged in vivo by subcutaneous, intraperitoneal, or intranasal instillation of B. anthracis spores. Retrocyclin 1 bound extensively to B. anthracis spores and enhanced their phagocytosis and killing by murine RAW264.7 cells. Based on the assumption that spore-bound RC1 enters phagosomes by "piggyback phagocytosis," model calculations showed that the intraphagosomal concentration of RC1 would greatly exceed its extracellular concentration. Murine alveolar macrophages took up fluorescently labeled retrocyclin, suggesting that macrophages may also acquire extracellular RC1 directly. Overall, these data demonstrate that retrocyclins are effective in vivo against experimental murine anthrax infections and suggest that enhanced macrophage function contributes to this property.

[Burden of illness. First routine report on socio-medical consequences of inflammatory rheumatic disease in Germany]. / Krankheitslast. Erste Routineberichterstattung zu sozialmedizinischen Folgen entzündlich-rheumatischer Erkrankungen in Deutschland.

A synopsis of different socio-medical consequences of inflammatory rheumatic diseases is not yet available for Germany. Therefore, the data reported during the past decade for rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, systemic sclerosis, systemic lupus erythematodes, and Wegener's granulomatosis are summarized in this article. Apart from clinical studies, relevant data sources were the national data base of the German collaborative arthritis centres, statistical figures from the compulsory health insurance and the national pension insurance scheme. Data were mainly available for sick leave and work disability showing limitations, which frequently occurred during the early course of diseases and increased with disease duration. Furthermore, different risk factors were identified. Measures to maintain continued participation in the labour force, such as part-time employment, partial work disability instead of full work disability, were not being adequately utilized. Only few data regarding the need of help and care were available. The proportion of patients in need of help and care increased with the duration of rheumatoid arthritis to more than 50% after more than 2 decades. This review presents detailed information concerning aspects of the burden of rheumatic diseases, which are frequently not adequately taken into account. They may be useful for the advice and care of individual patients as well as for decision processes concerning the health care system.

The effect of anti-tumour necrosis factor alpha treatment on the antibody response to influenza vaccination.

OBJECTIVES: The effect of anti-tumour necrosis factor (TNF) therapy on the antibody responses to vaccines is the subject of ongoing debate. Therefore, we investigated the effect of the three currently available anti-TNF agents on influenza vaccination outcomes in a patient population with long-standing disease. METHODS: In a prospective cohort study, we assessed the antibody response upon influenza vaccination in 112 patients with long-standing autoimmune disease treated with immunosuppressive medication either with anti-TNF (etanercept, adalimumab or infliximab; n = 64) or without anti-TNF (n = 48) and a control group of 18 healthy individuals. Antibody responses were determined by haemagglutination inhibition assay, before and 4 weeks after vaccination. RESULTS: The proportion of individuals with a protective titre (>or=40) after vaccination was large (80-94%) and did not significantly differ between the three groups. Post-vaccination geometric mean antibody titres against influenza (A/H3N2 and B) were significantly lower in the 64 patients treated with anti-TNF compared with the 48 patients not receiving anti-TNF, and the healthy controls. CONCLUSIONS: The antibody response to influenza vaccination in patients treated with anti-TNF is only modestly impaired. The proportion of patients that achieves a protective titre is not significantly diminished by the use of TNF blocking therapies.

Transmeatal cochlear laser (TCL) treatment of cochlear dysfunction: a feasibility study for chronic tinnitus.

Low-level-laser-therapy (LLLT) targeting the inner ear has been discussed as a therapeutic procedure for cochlear dysfunction such as chronic cochlear tinnitus or sensorineural hearing loss. Former studies demonstrate dose-dependent biological and physiological effects of LLLT such as enhanced recovery of peripheral nerve injuries, which could be of therapeutic interest in cochlear dysfunction. To date, in patients with chronic tinnitus mastoidal and transmeatal irradiation has been performed without systematic dosimetric assessment. However, light-dosimetric studies on human temporal bones demonstrated that controlled application of laserlight to the human cochlea depends on defined radiator position within the external auditory meatus. This feasibility study first presents a laser application system enabling dose-controlled transmeatal cochlear laser-irradiation (TCL), as well as preliminary clinical results in patients with chronic cochlear tinnitus. The novel laser TCL-system, consisting of four diode lasers (lambda=635 nm-830 nm) and a new specific head-set applicator, was developed on the basis of dosimetric data from a former light-dosimetric study. In a preliminary clinical study, the TCL-system was applied to 35 patients with chronic tinnitus and sensorineural hearing loss. The chronic symptoms persisted after standard therapeutic procedures for at least six months, while retrocochlear or middle-ear pathologies have been ruled out. The patients were randomised and received five single diode laser treatments (lambda=635 nm, 7.8 mW cw, n=17 and lambda=830 nm, 20 mW cw, n=18) with a space irradiation of 4 J/cm2 site of maximal cochlear injury. For evaluation of laser-induced effects complete otolaryngologic examinations with audiometry, tinnitus masking and matching, and a tinnitus-self-assessment were performed before, during and after the laser-irradiation. The first clinical use of the TCL-system has been well tolerated without side-effects and produced no observable damage to the external, middle or inner ear. Changes of tinnitus loudness and tinnitus matching have been described. After a follow-up period of six months tinnitus loudness was attenuated in 13 of 35 irradiated patients, while two of 35 patients reported their tinnitus as totally absent. Hearing threshold levels and middle ear function remained unchanged. Further investigations by large double-blind placebo-controlled studies are mandatory for clinical evaluation of the presented TCL-system and its therapeutic effectiveness in acute and chronic cochlear dysfunction.

Whole bladder photodynamic therapy with 5-aminolevulinic acid using a white light source.

OBJECTIVES: To determine whether whole bladder photodynamic therapy after intravesical administration of 5-aminolevulinic acid using a white light source would destroy urothelial carcinoma. We sought to define the optimal target group of patients for this therapy. The side effects of treatment were also assessed. METHODS: We performed whole bladder photodynamic therapy with 100 J/cm(2) white light 2 to 4.5 hours after intravesical administration of 17% 5-aminolevulinic acid in 12 patients with recurring, multifocal, Stage pTa, grade I to III, urothelial tumors of the bladder and carcinoma in situ. RESULTS: Immediately after whole bladder irradiation, histologic examination of biopsies taken from flat suspicious lesions showed no viable cells; remnants of malignant cells were found in papillary tumors. Of the 12 patients, 11 returned for follow-up examination. At a median follow-up of 18 months (range 3 to 25), 3 of the 7 patients with carcinoma in situ and 2 of the 4 patients with papillary tumors were free of disease. In all patients, urinary frequency and urgency subsided within 3 weeks. No decreased bladder capacity or systemic side effects were observed. CONCLUSIONS: Our preliminary data show that whole bladder photodynamic therapy with intravesically applied 5-aminolevulinic acid using a white light source is effective in destroying flat malignant lesions of the bladder such as carcinoma in situ. The procedure is easy to perform and is not associated with any major side effects. The findings warrant long-term and multicenter studies.

A novel 'sort-suicide' fusion gene vector for T cell manipulation.

Retroviral suicide gene vectors have successfully been used in clinical studies to improve the safety of adoptive immunotherapy with allogeneic T lymphocytes in the treatment of malignant and viral diseases. At the same time these studies have revealed several problems that are yet to be resolved including impaired T cell function due to long ex vivo culture. Here we present new retroviral vectors co-expressing truncated CD34, a gene transfer marker which ensures rapid enrichment of transduced cells using commercially available GMP-approved devices, and a splice-corrected variant of Herpes simplex virus thymidine kinase (scHSVtk) which confers high sensitivity to the prodrug ganciclovir. We show that a retroviral hybrid vector, MP71, based on the myeloproliferative sarcoma virus (MPSV) and the murine embryonic stem cell virus (MESV), encoding a tCD34/scHSVtk fusion protein mediates high expression of the 'sort-suicide' selection marker, thereby allowing for highly efficient purification and selective elimination of transduced cells.

Immunisation with Salmonella typhimurium-delivered glyceraldehyde-3-phosphate dehydrogenase protects mice against challenge infection with Echinococcus multilocularis eggs.

Recombinant glyceraldehyde-3-phosphate dehydrogenase of the cestode parasite Echinococcus multilocularis was expressed in Escherichia coli and in Salmonella typhimurium. The potential of different forms of the recombinant antigen to protect BALB/c mice against oral challenge infections with E. multilocularis eggs was evaluated. Oral or intraperitoneal immunisation with live attenuated S. typhimurium as a carrier for recombinant glyceraldehyde-3-phosphate dehydrogenase of the E. multilocularis resulted in significant protection, reducing the number of developing metacestodes up to 79.8%. The sera of protected animals did not contain detectable amounts of antibody against glyceraldehyde-3-phosphate dehydrogenase of E. multilocularis. By contrast, although anti-glyceraldehyde-3-phosphate dehydrogenase of E. multilocularis antibodies were detectable in the sera, immunisation with E. coli-expressed recombinant glutathione-S-transferase-fusion protein or with glyceraldehyde-3-phosphate dehydrogenase of E. multilocularis fused to a 6HIS-tag failed to protect the animals against oral challenge infections. These data emphasise that antigen delivery systems play a critical role in vaccination and the induction of protective immunity against helminth parasites.

Lightdosimetric quantitative analysis of the human petrous bone: experimental study for laser irradiation of the cochlea.

BACKGROUND AND OBJECTIVE: Application of laser irradiation targeting the inner ear has to be investigated for therapeutic effectiveness in cochlear injury and dysfunction. In vitro data demonstrate low-level laser-induced photochemical and photobiologic cell response, depending on cell type and irradiation parameters such as light dose. The aim of the presented study was to determine the light dose received by the cochlear hair cells by using different irradiation modalities for the human petrous bone. STUDY DESIGN/MATERIALS AND METHODS: Lightdosimetric assessment was performed in human cadaver temporal bones (n = 13) after removing the cochlear membranous labyrinth. The external auditory meatus, the tympanic membrane (quadrants), and the mastoid bone were illuminated by a helium-neon laser (lambda = 593 nm) and diode lasers of different wavelengths (lambda = 635, 690, 780, and 830 nm). The spatial distribution of transmitted light in the cochlear windings was measured by means of a retrocochlearly positioned endoscopic CCD camera for image processing and was assigned to acoustic frequencies according to the tonotopic organization of the cochlea. For an estimation of the corresponding space irradiance in an intact cochlea, correction factors have been calculated by a Monte Carlo procedure on the basis of experimentally determined optical properties of skull bone. RESULTS: The transmission of light across the tympanic cavity and the promontory depends strongly on wave-length of the laser and the position of the radiator. Transtympanal irradiation results in spatial intensity variations of a factor 4 to 10 within the cochlear windings. The space irradiance in an intact cochlea is 10 to 20 times the measured irradiance. For an irradiation of the mastoid, the light transmission within the cochlea is 10(3) to 10(5) times smaller compared with an irradiation of the tympanic membrane and is extremely variable for different specimens. CONCLUSION: The strong dependence of the cochlear light distribution on various irradiation parameters demonstrates the impact of preclinical lightdosimetric investigations for effective individual laser irradiation of the human cochlea. Because of the observed spatial intensity variations, the optimal external light dose has to be chosen with regard to the tonotopy of the human cochlea. The obtained results are enabling us to apply defined laser light doses to different cochlear winding areas. Mastoidal irradiation leads to therapeutically insufficient light doses within reasonable treatment times, whereas transmeatal irradiation is recommendable. Further studies are mandatory for development of clinical devices for transmeatal irradiation of the cochlea.

Impact of FDG PET on patients with differentiated thyroid cancer who present with elevated thyroglobulin and negative 131I scan.

UNLABELLED: FDG PET is increasingly performed in patients with differentiated thyroid cancer who present with elevated human thyroglobulin (hTG) levels and negative 131I scan. The aim of this study was to evaluate the impact of FDG PET on treatment in these patients. METHODS: A total of 118 FDG PET studies were performed on 64 patients, and follow-up data were available for all patients. Whole-body images were acquired 1 h after intravenous injection of 370 MBq (10 mCi) FDG using a PET scanner with an axial field of view of 16.2 cm. Tumor-suspicious FDG PET studies were evaluated by histology, cytology, 131I uptake, CT or MRI, and follow-up of hTg levels. The therapeutic consequence was noted for each patient. Moreover, results of FDG PET were correlated with hTg levels. RESULTS: Forty-four patients had positive scans, which were proven to be true-positive in 34 patients, whereas 7 patients had false-positive findings. Two patients exhibited a secondary malignancy. One patient did not fit in any category, having true-positive, false-positive, and false-negative findings. On the other hand, 20 patients had negative scans. These were true-negative findings in 5 patients, whereas the remaining 15 patients had false-negative results. Accordingly, the positive predictive value of FDG PET was 83% (34/41), whereas the negative predictive value was 25% (5/20). Treatment was directly changed in 19 of 34 patients with true-positive PET studies: 18 patients had further surgery, and 4 patients were referred for external irradiation, 3 of them after incomplete removal of local recurrences. FDG PET showed widespread disease in 7 patients; thus, palliative treatment, rather than curative therapy, was initiated. True-positive FDG PET findings were correlated positively with increasing hTg levels (i.e., FDG PET was true-positive in 11%, 50%, and 93% of patients with hTg levels of <10, 10-20, and >100 microg/L, respectively). CONCLUSION: FDG PET is a valuable diagnostic tool in patients with differentiated thyroid cancer who present with increased hTg levels and negative 131I scans because it permits selection of patients for surgery, which may be curative. FDG PET is most promising at hTg levels of >10 microg/L.

Activation of the erythropoietin receptor by the gp55-P viral envelope protein is determined by a single amino acid in its transmembrane domain.

The spleen focus forming virus (SFFV) gp55-P envelope glycoprotein specifically binds to and activates murine erythropoietin receptors (EpoRs) coexpressed in the same cell, triggering proliferation of erythroid progenitors and inducing erythroleukemia. Here we demonstrate specific interactions between the single transmembrane domains of the two proteins that are essential for receptor activation. The human EpoR is not activated by gp55-P but by mutation of a single amino acid, L238, in its transmembrane sequence to its murine counterpart serine, resulting in its ability to be activated. The converse mutation in the murine EpoR (S238L) abolishes activation by gp55-P. Computational searches of interactions between the membrane-spanning segments of murine EpoR and gp55-P provide a possible explanation: the face of the EpoR transmembrane domain containing S238 is predicted to interact specifically with gp55-P but not gp55-A, a variant which is much less effective in activating the murine EpoR. Mutational studies on gp55-P M390, which is predicted to interact with S238, provide additional support for this model. Mutation of M390 to isoleucine, the corresponding residue in gp55-A, abolishes activation, but the gp55-P M390L mutation is fully functional. gp55-P is thought to activate signaling by the EpoR by inducing receptor oligomerization through interactions involving specific transmembrane residues.

Photodynamic therapy in women with cervical intraepithelial neoplasia using topically applied 5-aminolevulinic acid.

Photodynamic therapy (PDT) is a novel treatment modality that produces local tissue necrosis with laser light after prior administration of a photosensitizing agent. We performed a study of topically applied 5-aminolevulinic acid (5-ALA) in the photodynamic treatment of women with high-grade cervical intraepithelial neoplasia (CIN) using fixed 5-ALA doses and application protocols derived from previous in vitro and in vivo results. Three to 5 hr prior to PDT, 10 ml of a 20% solution of 5-ALA was topically applied using a cervical cap. PDT was performed with irradiation of 100 J/cm2 at an irradiance of 100-150 mW/cm2 with an argon-ion-pumped dye laser at 635 nm. For the endocervix, a specifically designed cylindrical applicator was used. Ten treatment cycles of PDT using 5-ALA were performed in 7 patients with high-grade CIN. Non-thermal laser treatment with 100-150 mW/cm2 was well tolerated. Local toxicity was minor as several patients reported burning sensations and vaginal discharge, but no necrosis, sloughing or scarring occurred. After 3 months, a significant reduction in the size of the ectocervical CIN lesions was noted in only 3 patients, who underwent a second PDT cycle. However, no significant improvement in CIN lesions was noted since cold knife conization revealed persistent CIN in all 7 cases. Therefore, PDT after topical application of 5-ALA using an irradiation of 100 J/cm2 produces only minimal side effects. However, it does not appear to be effective in treating CIN.

[Chest X ray: routine indication in the follow-up of differentiated thyroid cancer?]. / Der Röntgenthorax: Routineindikation in der Nachsorge des differenzierten Schilddrüsenkarzinoms?

AIM: This retrospective study sought to elucidate whether routine chest x-ray is still useful for detection of pulmonary metastases in low risk patients despite the high sensitivity of the tumor marker thyroglobulin. METHOD: The hospital files of 609 patients with well-differentiated thyroid cancer were analysed. Pulmonary formation of metastases was diagnosed in 50 patients. The thyroglobulin value at the time of diagnosis was compared with the chest x-ray findings and, if present, additional diagnostic information such as Iodine-131 whole body scintigraphy (WBS) and thorax CT. RESULTS: The sensitivity of the chest x-ray to detect pulmonary metastases was at 52% lower than that of WBS (64%), thorax CT (82%) and thyroglobulin during suppression therapy (86%). Among the patients with papillary carcinoma stage I and II (UICC 1987), only 1 patient developed pulmonary metastases during follow up. In this low risk group of patients, detection of lung metastases exclusively by chest x-ray, without elevation of thyroglobulin level is extremely rare (calculated probability 1/4000) and associated with considerable costs. CONCLUSION: Routine, life long chest x-ray in low risk patients without a suspected recurrence (e.g. positive thyroglobulin) needs to be reconsidered.

[Phosphate deficiency as a rare cause of osteomalacia--case report of several years of enteral feeding and antacid therapy]. / Phosphatmangel als seltene Ursache einer Osteomalazie--Fallbericht einer mehrjährigen enteralen Sondenernährung und Antazidatherapie.

HISTORY AND CLINICAL FINDINGS: Floor-of-the-mouth cancer had been diagnosed and surgically treated in a 55-year-old man 4 years before the latest admission. For the last 3 years he had been fed through a percutaneous endoscopic gastrostomy (PEG). Since then he had experienced reflux oesophagitis which was being treated with aluminium-containing antacids. He was hospitalized for the surgical treatment of bilateral fractures of the neck of the femur. A surgical biopsy revealed osteomalacia but no metastasis. INVESTIGATIONS: The serum phosphate level was significantly reduced (0.21 mmol/l) and there was no detectable phosphate excretion in the 24-hour urine. Serum calcium concentration was unremarkable, but there was hypercalciuria (34.4 mmol/d). Alkaline phosphate activity was significantly raised (393 U/l) and parathormone level reduced (7 ng/l). Vitamin D concentration was unremarkable. TREATMENT AND COURSE: The phosphate content in the parenteral feed was at first increased and additional phosphate was given by mouth. The calcium and phosphate levels slowly became normal only after medication had been changed from antacids to H2-blockers. CONCLUSIONS: In this case osteomalacia was caused not by vitamin D deficiency but by a lack of phosphate. The reduced intestinal phosphate absorption by the antacids only partially explains the pronounced clinical signs. If antacids are taken over long periods the phosphate balance should be carefully monitored to avoid osteomalacia.

Histological verification of positive fluorine-18 fluorodeoxyglucose findings in patients with differentiated thyroid cancer.

Fluorine-18 fluorodeoxyglucose and positron emission tomography (FDG-PET) is a new imaging modality used in the follow-up of patients with differentiated thyroid cancer if the results of (131)I scintigraphy are negative in spite of an elevated thyroglobulin level. The aim of this retrospective analysis was to estimate the value of FDG-PET regarding the operability of patients with positive findings. From January 1994 to October 1997, we investigated 60 patients with differentiated thyroid carcinoma by FDG-PET. Thirteen patients were operated on after positive findings. Most of these lesions were suspected of having lymph-node involvement or local recurrences in the thyroid bed. One patient showed a solitary distant metastasis in the scapula. Thirteen of 16 operations in these 13 patients confirmed the suspected involvement of thyroid cancer. The false-positive findings were caused by inflamed lymph nodes in two cases and benign thymus tissue in one case. We conclude that PET is a useful diagnostic tool to guide early surgical therapy in patients with (131)I negative differentiated thyroid carcinoma.

[Computerized tomography and F-18-FDG positron emission tomography in staging of malignant lymphomas: a comparison]. / Computertomographie und F-18-FDG-Positronen-Emissions-Tomographie im Staging maligner Lymphome: ein Vergleich.

PURPOSE: To determine the value of F-18-FDG-positron emission tomography (FDG-PET) compared with computed tomography (CT) in the staging of malignant lymphomas. MATERIAL AND METHOD: 50 patients with biopsy-proven lymphoma were studied with FDG-PET and CT. The results in initial, posttherapeutic and staging of recurrence were compared. RESULTS: 37 of 65 FDG-PET were identical with CT. 28 studies showed differences. 14 post-therapeutically and one of the initial studies led to downstaging by FDG-PET were as upstaging resulted in one case of initial staging. In two cases false positive pulmonary FDG accumulations caused an upstaging. CONCLUSION: FDG-PET was at least comparable to CT in recording the extension of a newly diagnosed lymphoma, or its recurrence. Upstaging according to FDG-PET occurred only once in initial staging. FDG-PET plays its most important role in the evaluation of residual mass in CT after therapy by accumulating FDG in viable tumour rather than in fibrotic tissue. 14 cases of downstaging according to FDG-PET resulted.

The anemic Friend virus gp55 envelope protein induces erythroid differentiation in fetal liver colony-forming units-erythroid.

The gp55 envelope proteins of the spleen focus-forming virus initiate erythroleukemia in adult mice. Because the gp55 from the polycythemic strain (gp55-P), but not from the anemic strain (gp55-A), activates the erythropoietin receptor (EpoR) for proliferation of hematopoietic cell lines, the mechanism by which gp55-A initiates erythroleukemia has remained a mystery. We show here that gp55-A activates the EpoR in fetal liver cells. In contrast to previous studies using bone marrow cells from phenylhydrazine-treated, anemic mice, we find that both gp55-A and gp55-P induce erythroid differentiation from colony-forming unit-erythroid (CFU-E) progenitors in fetal liver cells. The effects on CFU-Es of both gp55-A and -P are mediated by the EpoR, because no colonies are seen upon expression of either gp55 in EpoR-/- fetal liver cells. However, only gp55-P induces erythroid bursts from burst-forming unit-erythroid progenitors and only gp55-P induces Epo independence in Epo-dependent cell lines. Using chimeric gp55 P/A proteins, we extend earlier work showing that the transmembrane sequence determines the capacity of gp55 proteins to differentially activate EpoR signaling. We discuss the possibilities for different signaling capacities of gp55-A and -P in fetal liver and bone marrow-derived erythroid progenitor cells.

Whole-body positron emission tomography (PET) for diagnosis of residual mass in patients with lymphoma.

BACKGROUND: PET using 18fluorodesoxyglucose (FDG) may offer the possibility of differentiating vital from necrotic residual masses. PATIENTS AND METHODS: Seventeen patients with HD and 17 patients with NHL underwent FDG-PET following therapy. According to staging by routine methods at diagnosis, 7 patients presented stage I, 13 stage II, 5 stage III, and 9 stage IV. A dose of 250-400 MBq FDG was injected and whole-body PET was performed 30-60 minutes later. RESULTS: Residual mass was found in 32 patients with routine methods. FDG-PET was negative in 17 patients, who were considered to be in CR. None of them relapsed (median follow-up 63 weeks ). FDG-PET was positive in 17 patients. Sixteen patients had residual mass with routine methods. Four patients received radiation after PET. Their median follow-up is 58 weeks without relapse. Two other patients with lasting CR had FDG uptake outside the residual mass--one with confirmed pneumonia. Five patients had histologically confirmed lymphoma, 2 patients relapsed according to routine methods. One patient is likely to be false positive because of fracture at lymphoma site. Seven of 10 patients with FDG uptake in the residual mass after completed therapy relapsed. According to routine restaging, 2 patients achieved CR. In 1 patient an additional focus was found in the humerus in spite of normal scintigraphy with histologically confirmed lymphoma. There were no false-negative results, but 3 false-positive results inside and 2 false-positive results outside the residual mass after completed therapy. CONCLUSIONS: PET performed for evaluation of residual mass after treatment of lymphoma has a high predictive value.

Systems for light application and dosimetry in photodynamic therapy.

Successful photodynamic therapy requires homogeneous irradiation and light detection for dosimetry. Light delivery devices and detectors for treatment of spherical and cylindrical hollow organs have been developed. For photodynamic therapy of multifocal superficial bladder tumours a catheter with an isotropic emitter is centred by a balloon. Light which is backscattered from the tissue surface is used for on-line dosimetry. The irradiation and dosimetry concept has been proven by computer simulations for a non-spherical bladder shape. Larynx, bronchi, oesophagus and cervix have been irradiated by devices adapted to the shape of the organ. The light distribution is homogenized by multiple backscattering from a nearly white layer in contact with tissue, a promising method also for hollow organs with irregular geometry. The homogeneity of the light distribution as well as the dosimetry have been improved by the devices to be presented.

Pharmacokinetics of 5-aminolevulinic-acid-induced porphyrins in tumour-bearing mice.

Photodynamic therapy and photodynamic diagnosis help to support efficient treatment of superficial and early-stage cancer. During the last few years, 5-aminolevulinic acid (5-ALA), a precursor of haemoglobin in the haem biosynthetic pathway, was used to stimulate endogenous porphyrin production. In the following the time dependence of 5-ALA-induced porphyrin concentration will be investigated on several tissues in an in-vivo tumour model. 5-ALA was administered intravenously at a concentration of 50 mg-1 body weight. According to a certain time schedule the animals were sacrificed and 12 different organs as well as the tumour were removed. During excitation with the violet light of a Kr+ laser, porphyrin fluorescence spectra in the range 550-750 nm could be detected on the tissue samples. The intensity of the emission spectra at lambda = 635 +/- 2 nm was taken as a measure of the porphyrin concentration. All tissues showed porphyrin fluorescence. Brightest fluorescence was found on the tumour. A maximum contrast of the fluorescence intensity between the tumour and the non-malignant organs of up to 30 was observed at 4-6 h post-injection. The kinetics of the porphyrin concentration depend on the organ. Simple mathematical models will be derived and discussed.