Diminished CXCR5 expression in peripheral blood of patients with Sjögren's syndrome may relate to both genotype and salivary gland homing.

Genetic investigations of Sjögren's syndrome (SS) have identified a susceptibility locus at p23.3 of chromosome 11, which contains the CXCR5 gene. C-X-C motif chemokine receptor 5 (CXCR5) is a chemokine receptor expressed on B and T cell subsets, and binds the chemotactic ligand C-X-C motif chemokine ligand 13 (CXCL13). In this study we aimed to link the genetic association with functional effects and explore the CXCR5/CXCL13 axis in SS. Expression quantitative trait loci analysis of the 11q23.3 locus was performed using B cell mRNA expression data from genotyped individuals. Lymphocyte surface markers were assessed by flow cytometry, and CXCL13 levels by a proximity extension assay. CXCR5+ and CXCL13+ cells in minor salivary glands were detected using immunohistochemistry. Our results demonstrated that SS-associated genetic polymorphisms affected the expression of CXCR5 (P < 0·01). Notably, a decreased percentage of CXCR5+ cells, with lower CXCR5 expression, was observed for most circulating B and T cell subsets in SS patients, reaching statistical significance in CD19+ CD27+ immunoglobulin (Ig)D+ marginal zone (P < 0·001), CD19+ CD27+ IgD- memory (P < 0·05) and CD27-IgD double-negative (P < 0·01) B cells and CD4+ CXCR3- CCR6+ Th17 cells (P < 0·05). CXCL13 levels were increased in patient plasma (P < 0·001), and immunohistochemical staining revealed expression of CXCL13 and higher numbers of CXCR5+ cells (P < 0·0001) within focal infiltrates and interstitially in salivary glands of SS patients. In conclusion, we link a genetic susceptibility allele for SS to a functional phenotype in terms of decreased CXCR5 expression. The decrease of CXCR5+ cells in circulation was also related to homing of B and T cells to the autoimmune target organ. Therapeutic drugs targeting the CXCR5/CXCL13 axis may be useful in SS.

Converting loss-on-ignition to organic carbon content in arable topsoil: pitfalls and proposed procedure.

Assessments of changes in soil organic carbon (SOC) stocks depend heavily on reliable values of SOC content obtained by automated high-temperature C analysers. However, historical as well as current research often relies on indirect SOC estimates such as loss-on-ignition (LOI). In this study, we revisit the conversion of LOI to SOC using soil from two long-term agricultural field experiments and one arable field with different contents of SOC, clay and particles <20 µm (Fines20). Clay-, silt- and sand-sized fractions were isolated from the arable soil. Samples were analysed for texture, LOI (500°C for 4 hours) and SOC by dry combustion. For a topsoil with 2 g C and 30 g clay 100 g-1 soil, converting LOI to SOC by the conventional factor 0.58 overestimated the SOC stock by 45 Mg C ha-1. The error increased with increasing contents of clay and Fines20. Converting LOI to SOC by a regression model underestimated the SOC stock by 5 Mg C ha-1 at small clay and Fines20 contents and overestimated the SOC stock by 8 Mg C ha-1 at large contents. This was due to losses of structural water from clay minerals. The best model to convert LOI to SOC incorporated clay content. Evaluating this model against an independent dataset gave a root mean square error and mean error of 0.295 and 0.125 g C 100 g-1, respectively. To avoid misleading accounts of SOC stocks in agricultural soils, we recommend re-analysis of archived soil samples for SOC using high-temperature dry combustion methods. Where archived samples are not available, accounting for clay content improves conversion of LOI to SOC considerably. The use of the conventional conversion factor 0.58 is antiquated and provides misleading estimates of SOC stocks. HIGHLIGHTS: Assessment of SOC contents is often based on less accurate methods such as LOI.Reliable accounts of changes in SOC stocks remain high on the agenda (4‰ initiative).Conversion of LOI to SOC is considerably improved by accounting for clay content.Converting LOI to SOC by the conventional factor 0.58 leads to grossly overestimated SOC stocks.

Water temperatures influence the marine area use of Salvelinus alpinus and Salmo trutta.

The migratory behaviour and spatial area use of sympatric Arctic charr Salvelinus alpinus and brown trout Salmo trutta were investigated during their marine feeding migration. The likelihood of finding individuals of both species in the inner or outer fjord areas was dependent on water temperature in the inner area (especially for S. alpinus), the temperature difference between the inner and outer areas (especially for S. trutta) and fish fork length (both species). The strongest predictor was the water temperature in the inner area, and particularly S. alpinus left this area and moved to the outer areas with increasing temperatures in the inner area. At 8° C in the inner area, the likelihood of finding S. alpinus in the outer areas was >50%. This predictor had a smaller effect on S. trutta, and the likelihood of finding S. trutta in the outer areas only started to increase at around 14° C. The relationships between temperature and area use did not correspond to the species' optimal growth temperatures, but to their previously documented temperature preferences. Individuals of both species used mainly the littoral fjord areas, and to a lesser extent the pelagic areas. In conclusion, temperature differences between the inner and outer marine areas probably resulted in the segregated area use between the species, because water temperatures or factors influenced by temperature affected their migratory behaviour and habitat use differently. The results indicate that increased marine temperatures with global warming may lead to increased spatial overlap between S. trutta and S. alpinus, which again may lead to increased interspecific competition during their marine phase, and with S. alpinus probably being the more negatively affected.

Task specialization in two social spiders, Stegodyphus sarasinorum (Eresidae) and Anelosimus eximius (Theridiidae).

Understanding the social organization of group-living organisms is crucial for the comprehension of the underlying selective mechanisms involved in the evolution of cooperation. Division of labour and caste formation is restricted to eusocial organisms, but behavioural asymmetries and reproductive skew is common in other group-living animals. Permanently, social spiders form highly related groups with reproductive skew and communal brood care. We investigated task differentiation in nonreproductive tasks in two permanently and independently derived social spider species asking the following questions: Do individual spiders vary consistently in their propensity to engage in prey attack? Are individual spiders' propensities to engage in web maintenance behaviour influenced by their previous engagement in prey attack? Interestingly, we found that both species showed some degree of task specialization, but in distinctly different ways: Stegodyphus sarasinorum showed behavioural asymmetries at the individual level, that is, individual spiders that had attacked prey once were more likely to attack prey again, independent of their body size or hunger level. In contrast, Anelosimus eximius showed no individual specialization, but showed differentiation according to instar, where adult and subadult females were more likely to engage in prey attack than were juveniles. We found no evidence for division of labour between prey attack and web maintenance. Different solutions to achieve task differentiation in prey attack for the two species studied here suggest an adaptive value of task specialization in foraging for social spiders.

The gill maggot Salmincola salmoneus as an indicator of repeat spawning in Atlantic salmon Salmo salar.

The potential of the gill maggot Salmincola salmoneus for use as an indicator of repeat spawning in Atlantic salmon Salmo salar was studied in adult fish captured during their return migration to the River Alta (n = 659) and River Namsen (n = 540) in Norway. Eighty-eight and 49% of previous spawners identified by scale readings were infected with S. salmoneus in the two rivers, respectively. Salmincola salmoneus can be used as a reliable, rapid and objective field indicator of repeat spawning in S. salar as nearly all infected fish (99·4%) were identified as repeat spawners, although it is important to have appropriate background information on S. salmoneus prevalence on the postspawning individuals within the same population.

Archival tags reveal that Arctic charr Salvelinus alpinus and brown trout Salmo trutta can use estuarine and marine waters during winter.

By tagging north-Norwegian anadromous riverine Arctic charr Salvelinus alpinus and brown trout Salmo trutta with simple archival tags that measured ambient water temperature and relating the recordings to the temperature in the surrounding environments, it was demonstrated that 91% of the S. trutta and 80% of the S. alpinus utilized the estuarine and marine environment during the winter. There was large individual variation in migratory behaviour. Salvelinus alpinus on average entered the estuary on 12 January and the marine environment on 26 February, had continuous marine migrations lasting up to 55 days, and spent on average 40 days in the estuary and 25 days in the sea during the winter. The corresponding numbers for S. trutta were 15 December and 4 January for first entry in the estuary and sea, maximum 39 days in the marine environment and average number of days in the estuary and sea were 34 and 50. Most individuals of both species frequently shifted between the three habitats. These findings thus contradict previous studies conducted on lake-dwelling populations, which suggested that northern populations of both species solely overwinter in fresh water. The use of inexpensive temperature recording archival tags gave detailed continuous information on seasonal migrations between habitats with different thermal characteristics.

Patients with non-Sjögren's sicca report poorer general and oral health-related quality of life than patients with Sjögren's syndrome: a cross-sectional study.

Understanding the impact of the disease on quality of life is crucial in patient management. In this cross-sectional study, general and oral health-related quality of life questionnaires, and thorough examinations of oral and ocular dryness were performed in age- and sex-matched patients with primary Sjögren's syndrome (pSS group), non-Sjögren's syndrome sicca (non-SS group) and healthy controls. General and oral health-related quality of life were investigated with the 36-Item Short Form Health Survey and the 14-Item Oral Health Impact Profile questionnaires, respectively. Subjective symptoms of xerostomia and ocular dryness were recorded using the Summated Xerostomia Inventory and Ocular Surface Disease Index, respectively. Clinical examinations included evaluation of clinical oral dryness scores, candida counts, unstimulated and stimulated saliva secretory rates, tear osmolarity, tear film break-up time, Schirmer I test and ocular surface staining. Both patient groups had pronounced signs and symptoms of xerostomia and ocular dryness. Even though the non-SS patients had less severe clinical signs than the pSS patients, they demonstrated much poorer general and oral health-related quality of life. In conclusion, non-SS patients require more attention in order to improve their quality of life.

Dysbiotic salivary microbiota in dry mouth and primary Sjögren's syndrome patients.

OBJECTIVES: Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by reduced lacrimal and salivary secretion. Sicca symptoms together with fatigue and musculoskeletal pain can significantly reduce the patients' quality of life. Furthermore, low salivary secretion may disrupt the oral microbial homeostasis. The aim of this study was to compare the salivary microbiota from pSS patients with patients with sicca symptoms not fulfilling the classification criteria for pSS (non-SS), and with healthy controls without sicca complaints. METHODS: Pellets from centrifuged chewing-stimulated whole saliva from pSS patients (n = 15), non-SS sicca patients (n = 15) and healthy controls (n = 15) were prepared. DNA was extracted and analyzed by 16S rRNA gene sequencing. The acquired sequencing data were performed using the human oral microbiome database (HOMD). RESULTS: We detected 42, 45, and 34 bacterial genera in saliva samples from pSS patients, non-SS sicca patients, and healthy controls, respectively. The most abundant genera in all samples were Prevotella, Veillonella, Streptococcus, and Haemophilus. At species level Streptococcus intermedius, Prevotella intermedia, Fusobacterium nucleatum subsp. vincentii, Porphyromonas endodontalis, Prevotella nancensis, Tannerella spp., and Treponema spp. were detected in the samples from pSS and non-SS only, while Porphyromonas pasteri was mostly found among the healthy controls. CONCLUSION: Our study indicated dysbiosis in the salivary microbiota from pSS and non-SS patients compared to healthy controls. Additionally, the results showed that the salivary microbiome in the pSS group differed significantly from the non-SS group.

A Survey to Determine Decision-Making Styles of Working Paramedics and Student Paramedics.

OBJECTIVE: Two major processes underlie human decision-making: experiential (intuitive) and rational (conscious) thinking. The predominant thinking process used by working paramedics and student paramedics to make clinical decisions is unknown. METHODS: A survey was administered to ground ambulance paramedics and to primary care paramedic students. The survey included demographic questions and the Rational Experiential Inventory-40, a validated psychometric tool involving 40 questions. Twenty questions evaluated each thinking style: 10 assessed preference and 10 assessed ability to use that style. Responses were provided on a five-point Likert scale, with higher scores indicating higher affinity for the style in question. Analysis included both descriptive statistics and t tests to evaluate differences in thinking style. RESULTS: The response rate was 88.4% (1172/1326). Paramedics (n=904) had a median age of 36 years (IQR 29-42) and most were male (69.5%) and primary or advanced care paramedics (PCP=55.5%; ACP=32.5%). Paramedic students (n=268) had a median age of 23 years (IQR 21-26), most were male (63.1%) and had completed high school (31.7%) or an undergraduate degree (25.4%) prior to paramedic training. Both groups scored their ability to use and favourability toward rational thinking significantly higher than experiential thinking. The mean score for rational thinking was 3.86/5 among paramedics and 3.97/5 among paramedic students (p<0.001). The mean score for experiential thinking was 3.41/5 among paramedics and 3.35/5 among paramedic students (p=0.06). CONCLUSION: Working paramedics and student paramedics prefer and perceive that they have the ability to use rational over experiential thinking. This information adds to our current knowledge on paramedic decision-making and is potentially important for developing continuing education and clinical support tools.

A mutant of E. coli that restricts growth of bacteriophage T4 at elevated temperatures.

After nitrosoguanidine mutagenesis, a Phage Host Defective (phd) mutant of E. coli HfrH was isolated that supported the growth of T4D wild-type bacteriophage at 30 degrees, but not at 40 degrees or higher. Eleven independent spontaneous mutants of T4 (go mutants) were isolated that overcame the growth restriction at high temperature. All of these mutants were located within three percent recombination of a gene 39 amber mutation in the clockwise direction on the standard map. In mixed infections, the representative go mutant chosen for further study seems to be recessive to its wild-type allele. Temperature-shift experiments suggested that the mutated host function involved in phage growth is a "late" function, beginning in mid-eclipse.--Electrophoresis of phage proteins labelled early and late in infection showed that under restrictive conditions early protein synthesis was normal, but that certain late proteins were absent. However, measurements of DNA synthesis showed that under restrictive conditions the amount of phage DNA synthesized, and especially the amount of DNA sedimenting as high molecular weight replicative intermediate, was reduced. Pulse-chase experiments showed that the phage DNA made under restrictive conditions was not rapidly degraded.

The Canadian National EMS Research Agenda: Impact and Feasibility of Implementation of Previously Generated Recommendations.

BACKGROUND: A recent mixed-methods study on the state of emergency medical services (EMS) research in Canada led to the generation of nineteen actionable recommendations. As part of the dissemination plan, a survey was distributed to EMS stakeholders to determine the anticipated impact and feasibility of implementing these recommendations in Canadian systems. METHODS: An online survey explored both the implementation impact and feasibility for each recommendation using a five-point scale. The sample consisted of participants from the Canadian National EMS Research Agenda study (published in 2013) and additional EMS research stakeholders identified through snowball sampling. Responses were analysed descriptively using median and plotted on a matrix. Participants reported any planned or ongoing initiatives related to the recommendations, and required or anticipated resources. Free text responses were analysed with simple content analysis, collated by recommendation. RESULTS: The survey was sent to 131 people, 94 (71.8%) of whom responded: 30 EMS managers/regulators (31.9%), 22 researchers (23.4%), 15 physicians (16.0%), 13 educators (13.8%), and 5 EMS providers (5.3%). Two recommendations (11%) had a median impact score of 4 (of 5) and feasibility score of 4 (of 5). Eight recommendations (42%) had an impact score of 5, with a feasibility score of 3. Nine recommendations (47%) had an impact score of 4 and a feasibility score of 3. CONCLUSIONS: For most recommendations, participants scored the anticipated impact higher than the feasibility to implement. Ongoing or planned initiatives exist pertaining to all recommendations except one. All of the recommendations will require additional resources to implement.

The DnaJ family of protein chaperones in Trypanosoma cruzi.

We have molecularly cloned four members of the DnaJ (heat shock protein 40) family of protein chaperones of the protozoan parasite Trypanosoma cruzi--tcj1, tcj2, tcj3 and tcj4. While all the proteins contain defining J domains at their N-termini, only tcj2, tcj3 and tcj4 contain glycine/phenylalanine-rich and zinc finger domains common to many other DnaJ homologues. Furthermore, tcj2 and tcj4 contain C-terminal CaaX motifs, substrates for prenyl modifications, suggesting that they are associated with cellular membranes. tcj1 is a divergent member of the family, containing neither glycine/phenylalanine-rich nor zinc finger domains. All the T. cruzi DnaJ genes are single copy, in contrast to other T. cruzi heat shock genes, which are arranged in multicopy direct tandem arrays. Among the tcj mRNAs, only tcj2 is heat inducible, which may result from posttranscriptional regulation involving a sequence found in the 3' untranslated regions of all heat-inducible T. cruzi mRNAs described to date. Further study of this important family of protein chaperones will aid our understanding of the protein folding and assembly processes in protozoans.

Meningioma-like tumor of the skin. An ultrastructural and immunohistochemical study.

Three unusual cutaneous tumors are described along with ultrastructural and immunohistochemical studies. All lesions were asymptomatic red-brown papulonodules. Light microscopic examination revealed a whorled configuration of spindle-shaped cells, some concentrically arranged around blood vessels. Immunohistochemical panels exhibited positive staining only with antibody to vimentin and negative staining with antibodies against S-100 protein, muscle markers, cytokeratin, epithelial membrane antigen, Leu 7, type IV collagen, and factor XIIIa, ruling out obvious nevomelanocytic, nerve sheath, meningothelial, smooth muscle, and perithelial differentiation. Electron microscopic examination demonstrated cells producing poorly formed collagen fibrils, sparse collagen fibers, and possessing occasional ill-defined intercellular junctions between their elongated cell processes. This rare tumor is considered to be either an immature fibrohistiocytic or possibly a nerve sheath neoplasm with striking similarities to so-called canine hemangiopericytoma. Because the prominent whorled pattern was reminiscent of meningioma, the lesion was referred to as meningioma-like tumor of the skin.

Malignant transformation of a Hürthle cell tumor: case report and survey of the literature.

Hürthle cell carcinoma is a relatively uncommon type of well-differentiated thyroid carcinoma. Its diagnosis has been controversial due to the difficulty in separating Hürthle cell adenoma from Hürthle cell carcinoma, thus the term Hürthle cell tumor is often used to describe both lesions. The present case of anaplastic giant-cell carcinoma in an 81-yr-old woman arose in a Hürthle cell tumor. This case illustrates the propensity of Hürthle cell tumor to undergo "malignant transformation" and argues for a more aggressive approach to such tumors.

Salivary acidic proline-rich proteins in rheumatoid arthritis.

In an ongoing attempt to investigate qualitative salivary parameters in diseases affecting salivary glands, patients with rheumatoid arthritis (RA) were examined. Patients were selected from the Oslo RA register for the present study if they fulfilled the following criteria: age 52-74 years, disease duration 10-20 years, and disability score as assessed by the Modified Health Assessment Questionnaire < or = 2.5. From these 105 patients, two subgroups of patients were selected, one group with pronounced sicca symptoms from eyes and mouth, and one group without such symptoms. Sicca symptoms were assessed using a postal questionnaire with the questions on dry mouth and dry eyes of the European classification criteria for Sjögren's syndrome. Patients were excluded from further examinations if they used medication that could cause dryness in eyes or mouth. Thus, nine patients remained in the sicca group (having four or more sicca symptoms), and ten matched RA patients were selected for the nonsicca group. A healthy sex- and age-matched control group (n = 10) was also examined. In a preliminary report we have shown that differences in flow rates between sicca and nonsicca RA patients were limited to lower values of unstimulated whole saliva. To further evaluate salivary changes in RA, a disease frequently associated with secondary Sjögren's syndrome, we have studied qualitative salivary parameters in these patients,' including secretory rates of proline-rich proteins (PRPs), statherins, and histatins. In the present report, phenotypes of PRPs, the ratio of PRPs derived from the two loci (PRH1 and PRH2), and PRP concentration and output in parotid and submandibular saliva derived from the two loci are presented. Parotid (PS) and submandibular saliva (SS) were collected from all individuals using 2% citric acid as a saliva stimulus. PRPs in PS and SS were identified using a SMART microchromatographic system with a Mono Q column and a Tris-HCl/NaCl gradient (method adapted from ref. 5). For PRPs, the primary polypeptide products are coded for on two loci (PRH1 and PRH2), which have three and two commonly occurring gene variants, respectively. On PRH1, the proteins PIF-s, Db-s, and Pa are coded for, whereas PRP-1 and PRP-2 are coded for on the PRH2 locus. As each protein variant has a postranscriptional cleavage product, individuals will exhibit four, six, or eight PRPs in their saliva, depending on whether they are homozygous at both, one, or neither of the two loci. Accordingly, 18 possible phenotypes may exist, but as few as three phenotypes were found in 79% of the 127 healthy individuals examined by Hay et al. The SMART system allows the determination of the different acidic PRPs present in saliva. Concentrations of the various phenotypes were calculated by peak integration versus pure PRP standards. Total PRP concentration derived from each locus was calculated as the sum of the concentrations of PRP variants from that locus.

Clinical implications of the dry mouth. Oral mucosal diseases.

Salivary hypofunction caused by salivary gland disease, medication, or radiation may predispose for secondary oral mucosal diseases. In these patients the protective coating of saliva is reduced or absent, leaving the oral mucosa more vulnerable. Candidiasis, burning mouth syndrome, and white lesions of the oral mucosa are increased in frequency. The aim of management is to prevent oral pathological changes. The management procedure may include proper oral hygiene, saliva-stimulating agents, or saliva substitutes, depending on the severity of the salivary dysfunction. Treatment includes antifungal therapy if candidiasis is diagnosed. In severely distressed patients, local or systemic corticosteroids may be indicated. Precautions, like refraining from smoking and avoiding toothpastes containing sodium lauryl sulfate, should also be taken. In the future, agents combining antibacterial and antiinflammatory actions, like triclosan, may show promising effects in patients with oral mucosal diseases secondary to salivary hypofunction.

Postural sensitivity to visual flow in aging adults with and without balance problems.

BACKGROUND: This study tested balance behavior of young adults and aging adults with and without balance problems in response to visual flow from a moving visual surround. METHODS: Balance behavior was indexed by force plate measures of maximum anterior/posterior displacement of the center of foot pressure and horizontal shear forces. The sample included normal young adults (n = 13; mean age 23 years, +/- 7.5), normal aging adults (n = 13; mean age 76 years, +/- 6.5), and aging adults with balance problems not directly attributable to a diagnosable neurological disease or dysfunction (n = 13; mean age 79 years, +/- 5.8). RESULTS: The balance-affected aging group had statistically greater sway responses than the young group when the stimulus was unexpected (as in the first trial; p < .05). Some individuals in each group had large responses that were statistical outliers from the group median. The balance-affected group had significantly greater shear forces than the young group. CONCLUSIONS: Greater sway responses suggest over-reliance on visual cues for posture control in the balance-affected aging group, which may be related to underlying, borderline somatosensory deficits, as indicated by the patterns of subclinical indications for somatosensory impairments on neurological exams in this group. Visually sensitive postural control, however, may issue from several different underlying processes. Elevated shear forces during balance responses in the balance-affected group suggest a greater use of hip movements in addition to ankle movements for postural adjustments.

Age-related changes in rate and magnitude of ankle torque development: implications for balance control.

BACKGROUND: One of the key components of postural control is the motor system's ability to produce appropriate torques to counteract perturbations that may lead to a loss of balance. Evidence exists to show that there is an age-related decline in absolute strength and in the ability to rapidly produce torque. The relationship between age-related decreases in these voluntary torque production capabilities and the ability to rapidly produce torques in a reactive balance task has not been studied. Thus, the purpose of this study was to examine the magnitude and rate of torque production in younger and older adults under reactive balance conditions. METHODS: Older (OA) and younger (YA) adults received forward and backward support surface translations of varying amplitudes and velocities. Maximum ankle muscle torque (maxMa) and rate of change of ankle muscle torque (Ma) following a perturbation were calculated. RESULTS: Two balance responses emerged: a no-step and a step response. With increasing perturbation difficulty, YA and OA used different responses. The no-step and step responses were examined for age-group differences in the force characteristics. No significant age-group differences were found for maxMa or rate of change of Ma within either no-step or step responses. CONCLUSION: The results of this study suggest that neither the magnitude nor rate of ankle muscle torque production, as produced during the initial balance response in this set of reactive balance control tasks, determines the different balance responses seen in younger versus older adults.

Predictive factors for outcome in treatment of metastatic nonseminomatous germ cell tumors.

In recent years less intensive chemotherapy programs for patients with metastatic nonseminomatous germ cell tumors with high likelihood of cure have been proposed, and the use of innovative more intensive treatments for patients with less favorable prognosis is being explored. The development of validated prognostic classifications has thus become important. In 77 patients with metastatic nonseminomatous germ cell tumors treated with chemotherapy, the ability of various prognostic factors to predict outcome of treatment was assessed. The multifactorial prognostic classification (Indiana classification) and a mathematical predictive formula correctly allocated patients to low- or high-risk groups in 84.4 percent and 87.0 percent of cases. The multifactorial classification system (M.D. Anderson system) correctly allocated patients in 61 percent of cases. The presence of serum beta HCG levels over 1,000 mg/mL, a pure choriocarcinoma histology and possibly an extragonadal primary origin of tumor were found to predict an adverse outcome in a small number of patients. It is concluded that use of the Indiana classification or mathematical predictive formula is an accurate means of allocating patients with metastatic germ cell tumors to high- or low-risk groups and that allocation of patients with pure choriocarcinoma histology, very high beta HCG levels, or extragonadal primary origin of tumor to the poor prognosis category will improve the accuracy of prediction in a few cases.