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Abstract Background In diagnosis of rare genetic diseases we face a decision as to the degree to which the sequencing lab offers one or more diagnoses based on clinical input provided by the clinician, or the clinician reaches a diagnosis based on the complete set of variants provided by the lab. We tested a software approach to assist the clinician in making the diagnosis based on clinical findings and an annotated genomic variant table, using cases already solved using less automated processes. Results For the 81 cases studied (involving 216 individuals), 70 had genetic abnormalities with phenotypes previously described in the literature, and 11 were not described in the literature at the time of analysis (“discovery genes”). These included cases beyond a trio, including ones with different variants in the same gene. In 100% of cases the abnormality was recognized. Of the 70, the abnormality was ranked #1 in 94% of cases, with an average rank 1.1 for all cases. Large CNVs could be analyzed in an integrated analysis, performed in 24 of the cases. The process is rapid enough to allow for periodic reanalysis of unsolved cases. Conclusions A clinician-friendly environment for clinical correlation can be provided to clinicians who are best positioned to have the clinical information needed for this interpretation.

Objectives There is a need in clinical genomics for systems that assist in clinical diagnosis, analysis of genomic information and periodic reanalysis of results, and can use information from the electronic health record to do so. Such systems should be built using the concepts of human-centred design, fit within clinical workflows and provide solutions to priority problems.Methods We adapted a commercially available diagnostic decision support system (DDSS) to use extracted findings from a patient record and combine them with genomic variant information in the DDSS interface. Three representative patient cases were created in a simulated clinical environment for user testing. A semistructured interview guide was created to illuminate factors relevant to human factors in CDS design and organisational implementation.Results Six individuals completed the user testing process. Tester responses were positive and noted good fit with real-world clinical genetics workflow. Technical issues related to interface, interaction and design were minor and fixable. Testers suggested solving issues related to terminology and usability through training and infobuttons. Time savings was estimated at 30%–50% and additional uses such as in-house clinical variant analysis were suggested for increase fit with workflow and to further address priority problems.Conclusion This study provides preliminary evidence for usability, workflow fit, acceptability and implementation potential of a modified DDSS that includes machine-assisted chart review. Continued development and testing using principles from human-centred design and implementation science are necessary to improve technical functionality and acceptability for multiple stakeholders and organisational implementation potential to improve the genomic diagnosis process.

Background: Cloacal malformation represents the rarest and most complex congenital anorectal malformation in females and is characterized by the convergence of urinary, gynecological, and intestinal systems within a single common channel. Three-dimensional computed tomography reconstruction (3D CT cloacagram) has emerged as a valuable method for anatomical assessment and preoperative planning., Objectives: To evaluate our experience with 3D CT cloacagram and assess its results., Methods: This retrospective case series included all patients with cloacal malformation who underwent preoperative 3D CT cloacagram at a single institution during 2019-2023. Collected data included patient characteristics, timing of the 3D CT cloacagram, results of the 3D CT cloacagram, comparison with endoscopic results, surgical procedures, and postoperative outcome., Results: Six patients with cloacal malformation were included in this study, including two with posterior cloaca. The median common channel length on 3D CT cloacagram was 24.5 mm (range 9-48 mm) and the median urethral length was 15.5 mm (range 13-24 mm). The surgical approach involved a combined abdominoperineal approach in three patients and posterior sagittal anorectal vaginal urethral plasty in one patient. Two patients were awaiting surgical reconstruction at the time of publication., Conclusions: Our implementation of 3D cloacagram has facilitated precise measurements of both the urethra and common channel lengths, two key factors in formulating surgical strategies for cloacal reconstruction. Moreover, this technique has markedly improved our capacity for surgical planning contributing to colorectal, gynecological, and urological perspectives.

Introduction: Historically, neuroblastoma has been diagnosed by surgical open biopsy (SB). In recent decades, core needle biopsy (CNB) has replaced surgical biopsy due to its safe and adequate method of obtaining tissue diagnosis., Aim: Our study aimed to assess the effectiveness of CNB in obtaining tissue diagnosis for neuroblastoma and evaluate its safety profile in terms of post-operative complications, in comparison to SB., Methods: A retrospective cohort study, including all patients younger than 18 years who were diagnosed with neuroblastoma from 2012 until 2022 in a single tertiary medical center. Patients' demographics, tumor size and location, pathological results, and clinical outcomes were collected., Results: 79 patients were included in our study: 35 biopsies were obtained using image-guided CNB and 44 using SB. Patients' and tumor characteristics including age, gender, tumor volume, and stage were similar in both groups. The biopsy adequacy rate in the CNB group was 91% and 3 patients in this group underwent repeated biopsy. The safety profile in the CNB group was similar to the SB group., Conclusions: CNB is a safe method and should be considered the first choice for obtaining tissue diagnosis when feasible due to its high adequacy in terms of tumor histopathological features., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Hepatitis B virus (HBV) is a cause of hepatocellular carcinoma (HCC). Interestingly, this process is not necessarily mediated through cirrhosis and may in fact involve oncogenic processes. Prior studies have suggested specific oncogenic gene expression pathways were affected by viral regulatory proteins. Thus, identifying these genes and associated pathways could highlight predictive factors for HCC transformation and has implications in early diagnosis and treatment., Aim: To elucidate HBV oncogenesis in HCC and identify potential therapeutic targets., Methods: We employed our Search, Tag, Analyze, Resource platform to conduct a meta-analysis of public data from National Center for Biotechnology Information's Gene Expression Omnibus. We performed meta-analysis consisting of 155 tumor samples compared against 185 adjacent non-tumor samples and analyzed results with ingenuity pathway analysis., Results: Our analysis revealed liver X receptors/retinoid X receptor (RXR) activation and farnesoid X receptor/RXR activation as top canonical pathways amongst others. Top upstream regulators identified included the Ras family gene rab-like protein 6 (RABL6). The role of RABL6 in oncogenesis is beginning to unfold but its specific role in HBV-related HCC remains undefined. Our causal analysis suggests RABL6 mediates pathogenesis of HBV-related HCC through promotion of genes related to cell division, epigenetic regulation, and Akt signaling. We conducted survival analysis that demonstrated increased mortality with higher RABL6 expression. Additionally, homeobox A10 (HOXA10) was a top upstream regulator and was strongly upregulated in our analysis. HOXA10 has recently been demonstrated to contribute to HCC pathogenesis in vitro. Our causal analysis suggests an in vivo role through downregulation of tumor suppressors and other mechanisms., Conclusion: This meta-analysis describes possible roles of RABL6 and HOXA10 in the pathogenesis of HBV-related HCC. RABL6 and HOXA10 represent potential therapeutic targets and warrant further investigation., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States and globally. The currently understood model of pathogenesis consists of a 'multiple hit' hypothesis in which environmental and genetic factors contribute to hepatic inflammation and injury., Aim: To examine the genetic expression of NAFLD and non-alcoholic steatohepatitis (NASH) tissue samples to identify common pathways that contribute to NAFLD and NASH pathogenesis., Methods: We employed the Search Tag Analyze Resource for Gene Expression Omnibus platform to search the The National Center for Biotechnology Information Gene Expression Omnibus to elucidate NAFLD and NASH pathology. For NAFLD, we conducted meta-analysis of data from 58 NAFLD liver biopsies and 60 healthy liver biopsies; for NASH, we analyzed 187 NASH liver biopsies and 154 healthy liver biopsies., Results: Our results from the NAFLD analysis reinforce the role of altered metabolism, inflammation, and cell survival in pathogenesis and support recently described contributors to disease activity, such as altered androgen and long non-coding RNA activity. The top upstream regulator was found to be sterol regulatory element binding transcription factor 1 (SREBF1), a transcription factor involved in lipid homeostasis. Downstream of SREBF1, we observed upregulation in CXCL10, HMGCR, HMGCS1, fatty acid binding protein 5, paternally expressed imprinted gene 10, and downregulation of sex hormone-binding globulin and insulin-like growth factor 1. These molecular changes reflect low-grade inflammation secondary to accumulation of fatty acids in the liver. Our results from the NASH analysis emphasized the role of cholesterol in pathogenesis. Top canonical pathways, disease networks, and disease functions were related to cholesterol synthesis, lipid metabolism, adipogenesis, and metabolic disease. Top upstream regulators included pro-inflammatory cytokines tumor necrosis factor and IL1B, PDGF BB, and beta-estradiol. Inhibition of beta-estradiol was shown to be related to derangement of several cellular downstream processes including metabolism, extracellular matrix deposition, and tumor suppression. Lastly, we found riciribine (an AKT inhibitor) and ZSTK-474 (a PI3K inhibitor) as potential drugs that targeted the differential gene expression in our dataset., Conclusion: In this study we describe several molecular processes that may correlate with NAFLD disease and progression. We also identified ricirbine and ZSTK-474 as potential therapy., Competing Interests: Conflict-of-interest statement: None of the authors have any conflict of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

We present an interesting case of a 66-year-old male who had acute testicular infarction following a right common femoral artery to left profunda femoris artery bypass with advanced symptoms of claudication. Angiography in the preoperative period demonstrated the extent of peripheral arterial disease present, revealing a calcified aorta, partially occluded left hypogastric artery, occluded left external iliac, common femoral and superficial femoral arteries and an occluded right hypogastric artery. A bypass was performed without any initial complications and subsequent relief of symptoms of claudication and rest pain. Postoperative scrotal pain and follow-up duplex demonstrated lack of perfusion of the testicle necessitating orchiectomy. This case serves to illustrate the importance of preserving collateral vessels as a technical consideration, as well as presenting a rare potential complication., (Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. © The Author(s) 2019.)

The Human Phenotype Ontology (HPO)-a standardized vocabulary of phenotypic abnormalities associated with 7000+ diseases-is used by thousands of researchers, clinicians, informaticians and electronic health record systems around the world. Its detailed descriptions of clinical abnormalities and computable disease definitions have made HPO the de facto standard for deep phenotyping in the field of rare disease. The HPO's interoperability with other ontologies has enabled it to be used to improve diagnostic accuracy by incorporating model organism data. It also plays a key role in the popular Exomiser tool, which identifies potential disease-causing variants from whole-exome or whole-genome sequencing data. Since the HPO was first introduced in 2008, its users have become both more numerous and more diverse. To meet these emerging needs, the project has added new content, language translations, mappings and computational tooling, as well as integrations with external community data. The HPO continues to collaborate with clinical adopters to improve specific areas of the ontology and extend standardized disease descriptions. The newly redesigned HPO website (www.human-phenotype-ontology.org) simplifies browsing terms and exploring clinical features, diseases, and human genes.

Lower extremity angiogram is generally a safe and effective procedure with a low rate of vascular complications. We report here a unique case of a 33-year-old female with anterior tibial artery (ATA) to anterior tibial vein fistula formation after lower extremity endovascular intervention. This was initially treated with open repair of the fistula and ligation of ATA. However, patient continued to complain of claudication like symptoms. Patient subsequently had an endovascular embolization of ATA in a retrograde fashion. Recovery was unremarkable; patient was discharged home same day. Three months postoperatively patient denies leg pain, a follow-up arterial duplex failed to show presence of arterio-venous fistula. This case illustrates the effectiveness of an endovascular approach as a minimally invasive treatment for this uncommon complication that occurs after lower extremity endovascular intervention.

Endovascular retrieval of a foreign body is becoming an increasingly common procedure in the management of complications resulting from more frequent endovascular procedures. Many procedures are performed on a regular basis in assessment of vascular anatomy, endovascular-guided therapy, and catheter placement. This case report depicts a complication of a chemoport placement resulting in a foreign body. Evaluation of the foreign body raised attention to aberrant anatomy, a persistent left-sided superior vena cava. We further discuss briefly the embryology behind a persistent left-sided superior vena cava, technical errors leading to the foreign body, and assessing the nature of the foreign body through different imaging modalities. This is followed by the subsequent endovascular retrieval by Interventional Radiology and a literature review and individual case assessment of endovascular foreign body retrieval. We discuss considerations for practice based upon our literature review.

Deep phenotyping has been defined as the precise and comprehensive analysis of phenotypic abnormalities in which the individual components of the phenotype are observed and described. The three components of the Human Phenotype Ontology (HPO; www.human-phenotype-ontology.org) project are the phenotype vocabulary, disease-phenotype annotations and the algorithms that operate on these. These components are being used for computational deep phenotyping and precision medicine as well as integration of clinical data into translational research. The HPO is being increasingly adopted as a standard for phenotypic abnormalities by diverse groups such as international rare disease organizations, registries, clinical labs, biomedical resources, and clinical software tools and will thereby contribute toward nascent efforts at global data exchange for identifying disease etiologies. This update article reviews the progress of the HPO project since the debut Nucleic Acids Research database article in 2014, including specific areas of expansion such as common (complex) disease, new algorithms for phenotype driven genomic discovery and diagnostics, integration of cross-species mapping efforts with the Mammalian Phenotype Ontology, an improved quality control pipeline, and the addition of patient-friendly terminology., (© The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Computer imaging techniques are commonly used to preserve and share readable manuscripts, but capturing writing locked away in ancient, deteriorated documents poses an entirely different challenge. This software pipeline-referred to as "virtual unwrapping"-allows textual artifacts to be read completely and noninvasively. The systematic digital analysis of the extremely fragile En-Gedi scroll (the oldest Pentateuchal scroll in Hebrew outside of the Dead Sea Scrolls) reveals the writing hidden on its untouchable, disintegrating sheets. Our approach for recovering substantial ink-based text from a damaged object results in readable columns at such high quality that serious critical textual analysis can occur. Hence, this work creates a new pathway for subsequent textual discoveries buried within the confines of damaged materials.

Background: Negative attitudes towards patients with borderline personality disorder (BPD) may affect their treatment. We aimed to identify attitudes toward patients with BPD., Methods: Clinicians in four psychiatric hospitals in Israel (n = 710; psychiatrists, psychologists, social workers and nurses) were approached and completed questionnaires on attitudes toward these patients., Results: Nurses and psychiatrists reported encountering a higher number of patients with BPD during the last month, and exhibited more negative attitudes and less empathy toward these patients than the other two professions. The whole sample evaluated the decision to hospitalize such a patient as less justified than the decision to hospitalize a patient with Major Depressive Disorder. Negative attitudes were positively correlated with caring for greater numbers of patients with BPD in the past month and in the past 12 months. Nurses expressed the highest interest in studying short-term methods for treating patients with BPD and a lower percentage of psychiatrists expressed an interest in improving their professional skills in treating these patients., Conclusions: The findings show that nurses and psychiatrists differ from the other professions in their experience and attitudes toward patients with BPD. We conclude that nurses and psychiatrists may be the target of future studies on their attitudes toward provocative behavioral patterns (e.g., suicide attempts) characterizing these patients. We also recommend implementing workshops for improving staff attitudes toward patients with BPD.

Background: Intrusive cognitions that enter consciousness involuntarily are prominent symptoms of posttraumatic stress disorder (PTSD). The present study aimed to identify neuropsychological mechanisms involved., Method: Fifty PTSD outpatients and 50 healthy controls were tested using Finger Tapping, Simple and Choice Reaction Times and Stroop Tasks, to measure motor, psychomotor speed, response selection, and interference inhibition ability respectively., Results: PTSD patients performed poorly in all tests, presumably owing to their generalized slowness of information processing and motor reaction. Psychomotor speed was a predictor of slowness and high error rate during the Stroop. Impaired inhibition, as measured by the interference index of the Stroop task, explained 9.7% of the predicated variance in frequency of re-experiencing PTSD symptoms and 23.5% of the predicated variance in augmentation of the interference response time., Conclusion: Impaired interference control may be related to internal (re-experiencing) and external (sensory) stimuli that leads to cognitive deficits in PTSD patients., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: To determine the effect of prostate volume on the diagnostic yield of prostate biopsies., Materials and Methods: 155 consecutive patients underwent 12-core transrectal ultrasound guided needle biopsies. Data were collected prospectively on age, serum PSA, digital rectal examination (DRE), previous prostate biopsies, prostate volume and pathologic result. Univariate and multivariate logistic regressions were undertaken to determine the effect of prostate volume on the risk for a positive biopsy., Results: 45 patients (29%) were diagnosed with cancer. The median patient age was 63 (range 48-82) years, the median PSA level was 6.7 ng/ml (0.5-156 ng/ml), and the median prostate volume was 57 ml (16-273 ml). 42 patients (27%) had an abnormal DRE and 51 (33%) had undergone previous prostate biopsies. Positive biopsy rates were 39%, 33%, and 14% for prostate volume below 46 ml, between 45 and 73 ml, and above 72 ml, respectively. Univariate analysis showed that age, serum PSA, DRE and prostate volume were all associated with a positive biopsy. Multivariate analysis adjusted for age, PSA and DRE showed a significant risk increase for a positive biopsy in smaller prostates. (OR = 5.6 95% CI 1.75-17.89; and 8.86 95% CI 2.72-28.82, for prostate volume between 45 and 72 ml and below 45 ml, respectively)., Conclusion: The diagnostic yield of prostate biopsies is significantly lower in large prostates. As the result the standard 12-core biopsy may be insufficient for the diagnosis of cancer in large prostates., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objectives: To evaluate the concordance between testicular tumor size and benign histology in order to identify a cut-off size, below which the rate of benign lesions would be highest., Methods and Materials: During the years 1995-2008, we performed 131 consecutive testicular operations for testicular tumors. Ten of these were testicular preserving surgery, whereas the other 121 patients had radical orchiectomy. We searched for the rate of benign lesions in the following 3 groups of tumor diameter: 10 mm or less, 11-20 mm, and greater than 20 mm. ROC analysis was used to find the optimal size cut-off below which the rate of benign lesions would be highest., Results: Benign lesions were found in 11 patients (8%), including epidermoid cyst (n = 4), Leydig cell tumor (n = 3), fibrosis (n = 1), adenomatoid tumor (n = 2), and 1 patient with a simple cyst. Small tumor size strongly correlated with benign histology. The mean diameter of benign vs. malignant lesions was 15 mm and 41 mm, respectively (P < 0.05). The rate of benign lesions in tumors with a diameter of 10 mm or less, 11-20 mm and greater than 20 mm was 50%, 17%, and 2%, respectively. Receiver Operating characteristic (ROC) analysis with 87% sensitivity and 83% specificity revealed a cut-off value of 18.5 mm tumor diameter below which the proportion of benign lesions was 38.5% compared with 2% above it (P < 0.05)., Conclusions: While benign lesions comprise only 8% of all testicular tumors, their proportion among small lesions is much higher. With a size cut-off of 18.5 mm, 38.5% of smaller lesions are benign. These findings support consideration of testicular exploration for small testicular lesions aiming at preservation rather than predetermined radical orchiectomy., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objectives: To determine the proportion of benign testicular lesions among candidates for testicular sparing surgery (TSS) and to assess the safety and efficacy of this procedure., Methods and Materials: Sixteen patients underwent surgical exploration for testicular tumors with TSS intent in our center. Surgery was performed via an inguinal approach with temporary cord occlusion and frozen section (FS) analysis of the lesions. Benign findings allowed for TSS, whereas cancer prompted total orchiectomy., Results: The lesions measured 8-25 mm in the largest diameter. Eleven of the 16 lesions were benign (69%) and TSS was accomplished in these cases. Complete concordance was observed between the results of FS and permanent sections. Of the 5 patients with cancer, 3 had pure seminoma, and embryonal carcinoma and teratoma were found in 1 patient, each. Surveillance was applied in 4 of these patients, and chemotherapy was used in the patient with embryonal carcinoma. With an average follow-up duration of 48 months, all are alive and free of disease. All 11 patients in whom TSS was accomplished had an uneventful postoperative course, and with an average follow-up duration of 28 months, 9 have normal scrotal physical examination and ultrasound, whereas 2 patients were lost to follow-up., Conclusions: Sixty-nine percent of testicular lesions under 25 mm are benign. TSS is safe and effective in patients with small benign lesions. Cancer is reliably detected by FS, and testicular exploration is not associated with local or distant recurrence in any of our patients., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Previous reports described significant differences in serum creatine kinase (CK) activity in bipolar disorder and various forms of depression. The comorbidity of depression and alcohol syndromes was also widely described. We aim to examine potential differences in serum CK level in different alcohol-related syndromes. We assessed morning serum CK activity in 114 inpatients, diagnosed by the Structured Clinical Interview for DSM-IV: Fifty-five subjects with alcohol dependence, 28 with alcohol withdrawal and 31 with delirium tremens (DT's). We found low normal CK activity for the alcohol dependence, higher for alcohol withdrawal and the highest for DT's. Peripheral CK activity of four patients that were admitted during each of the three phases showed similar pattern. These findings may be related to enhanced dopamine activity in alcohol dependence and conversely, to a significant decrease in dopamine activity during withdrawal syndromes. We suggest a supplementary simple laboratory tool for the detection of alcohol-related states.

Various reports have described increased serum creatine kinase (CK) activity in the majority of hospitalized acutely disturbed schizophrenics and patients with affective psychoses. We investigated CK serum levels of 52 unmedicated bipolar inpatients, in manic versus depressive states. Additional 17 patients were evaluated in both states. Hamilton Rating Scale for Depression and Young Mania Rating Scale were used and blood samples were obtained from new admitted patients. Higher CK level was found in the manic patients compared with the depressed ones. Likewise, the CK level was higher in the manic phase than in the depressive one, when tested within the same patient. Our results suggest that the clinical differences between mania and depression states are supported by contrasting levels of CK. The lack of correlations between CK level and motor items suggest that CK level in mania versus depression could emphasize the "thinking speed" and not the motor one.

The frequently seen side effect of hyperprolactinemia thought to be the 'price' paid for the antipsychotic treatment of schizophrenia. Various reports have linked the use of risperidone, an atypical antipsychotic drug, with the significant rise of prolactin levels. Thus, we set to assess possible difference between prolactin levels among schizophrenia subtypes in 45 male patients treated with stable doses (2-6 mg/day) of risperidone as antipsychotic monotherapy. All patients showed increased prolactin levels beyond the normal range, with a significant difference between the paranoid and all other groups (P<0.0001). Specifically, the paranoid patients' prolactin levels were higher than those of the schizoaffective and the disorganized ones. These results suggest that the blockade of higher dopamine activity in the paranoid schizophrenia corresponds to the prolactin increase, more than in the schizoaffective and disorganized subtypes. These findings are opposite of what was observed in the previous study of unmedicated patients.

There is evidence for the involvement of the endocrine system in schizophrenia. This involment was widely investigated in female patients. In the current study, we examined prolactin and estradiol serum levels in hospitalized unmedicated men with first-episode and recurrent schizophrenia and then tested possible correlation with various subtypes of the disease. In addition, the estradiol and prolactin levels were compared with a healthy control group. The serum samples were assessed the morning following admission in fifty-seven schizophrenia male patients. There was a significant difference in prolactin serum levels between the paranoid and "nonparanoid" schizophrenia subgroups. However, no significant differences were found in estradiol serum levels between schizophrenia subtypes or between the patients and their healthy counterparts. Finally, a significant and positive correlation was found between the prolactin and estradiol levels in the paranoid subgroup alone. Thus, it appears that low estradiol levels are associated with low prolactin levels, alleged hyperdopaminergic tone and psychotic breakdown in paranoid schizophrenia. The results of the present study further support our previous report of the association between prolactin serum levels and the schizophrenia cluster subtypes, indicating a different dopaminergic activity for the various forms of the disease.

Creatine kinase (CK) level was previously found to be increased in the majority of hospitalized acute psychotic patients. We aimed to asses the possible differences in CK level in various forms of depression: major with and without psychotic symptoms, of bipolar depression and schizoaffective depression. Unmedicated hospitalized patients participated: nonpsychotic major depression (n=39), psychotic major depression (n=23), bipolar depression (n=23) and schizoaffective depression (n=24). The severity of depression was assessed by the Hamilton Depression Rating Scale (Ham-D) and blood samples were collected in the morning of admission day, prior to any treatment. Ham-D yielded a significantly higher score for psychotic major depression group, compared with all other groups which showed similar score. CK serum level was significantly higher in nonpsychotic major depression than in all other forms of depression. The results indicate a biological difference between the nonpsychotic major depression and the "psychotic" cluster of depressive syndromes.

In an attempt to determine if it is possible to distinguish hamartoma of the breast from fibroadenoma using fine-needle aspiration cytology, we reviewed the cytological slides of 13 histopathologically confirmed cases of hamartoma of the breast and compared them with the cytological features of 13 histologically confirmed fibroadenomas. In each case, we studied the epithelial and stromal features. Cytologic characteristics were retrospectively evaluated in a semiquantitative manner. In conclusion, the finding of intact lobular units and a relative paucity of stroma may suggest the diagnosis of hamartoma.

Various studies indicate that we must consider schizophrenia not as a single disease but as several distinct etiological processes that give rise to characteristic symptoms. In the current study, we aimed to examine prolactin serum levels in unmedicated first-episode and recurrent schizophrenic patients. The prolactin levels were compared among the different schizophrenia subtypes, i.e. paranoid, schizoaffective and disorganized. Prolactin serum samples were assessed on the morning after the admission in 48 first-episode and 38 recurrent unmedicated hospitalized schizophrenia patients. Two psychiatrists made the diagnosis without knowledge of laboratory results and completed the rating scales. Despite all prolactin levels being within or close to the normal range, we found significant differences in prolactin serum levels among schizophrenia subtype patients: the lowest values were for the paranoid type, intermediate for the schizoaffective and the highest for the disorganized patients. The results seem to indicate a pronounced hyperdopaminergic activity in paranoid schizophrenia, suggesting differences in dopaminergic tone between the schizophrenia subtypes, and support the clinical and the neuropsychological individuality of disease subtypes. There were no significant differences in prolactin serum levels of the schizophrenia subtypes between the first-episode and the recurrent patients. It appears that there are constant patterns of dopamine bioactivity in acutely psychotic unmedicated schizophrenia patients, whether the patients are first admitted or recurrent.

Objectives: Giant cell tumor of bone is typified by massive infiltration of a bland neoplastic stroma by osteoclasts and monocyte progenitors. The current study aimed at evaluating the nature of the neoplastic cells and the mechanisms underlying the massive giant cell recruitment., Methods: Five different giant cell tumors were evaluated by immunohistochemistry, and explant cell cultures were established from the same tumors. Antigen expression profiles of both the tumors and the derived cultures were assessed. In order to determine if the mesenchymal cells are capable of differentiating into mature osteoblasts, retinoic acid was added to cell cultures and osteocalcin and alkaline phosphatase levels were measured. The proliferative effects of the mesenchymal cells on histiocyte-like cells were evaluated using the U-937 cell line., Results: A large stromal subpopulation expresses fibroblast growth factor receptor 3 (FGF-R3), indicating a mesenchymal origin of these cells. Few cells express bone- or cartilage-specific markers. Cell cultures are predominated by mesenchymal cells, as indicated by a strong staining by FGF R3. Retinoic acid induces osteoblastic differentiation, i.e. osteocalcin expression and alkaline phosphatase production. Conditioned medium of giant-cell-tumor-derived stromal cell cultures induces proliferation of U-937 cells, derived from histiocytic lymphoma. Papain digestion and dialysis of the conditioned media indicates the effector molecule to be a protein over 40 kD in size. The giant cell tumors as well as stromal cell cultures derived from giant cell tumors express osteoprotegerin ligand, the osteoclast activator., Conclusions: The neoplastic stromal spindle-shaped subpopulation of cells in giant cell tumors are mesenchymal stem cells capable of inducing histiocyte proliferation. Retinoid acid is capable of inducing differentiation of the cells into mature osteoblasts. This should be further investigated in an in vivo model to ascertain whether induction of differentiation will prevent bone loss and retard tumor progression., (Copyright 2003 S. Karger AG, Basel)