Apocrine (cutaneous) sweat gland carcinoma of axilla with signet ring cells: a diagnostic dilemma on fine-needle aspiration cytology

Carcinoma arising in the apocrine sweat glands is rare and there are few reports describing the cytological features of this neoplasm. We describe the cytological features of a histologically confirmed apocrine carcinoma occurring in a 55-year-old man who presented with an ulcerated mass in the right axilla. Fine-needle aspiration cytology revealed features of a signet ring adenocarcinoma. The significance of this infrequently encountered neoplasm lies in its potential for diagnostic confusion with more common lesions containing signet ring cells. In an axillary mass lesion, cytological features along with clinical correlation are essential to distinguish primary apocrine carcinoma from mammary neoplasms with signet ring cells and other metastatic adenocarcinomas.     

Pivotal advance: CTLA-4+ T cells exhibit normal antiviral functions during acute viral infection

Previous studies have shown that T cells, which are genetically deficient in CTLA-4/CD152 expression, will proliferate uncontrollably, resulting in lethal autoimmune disease. This and other evidence indicate that CTLA-4 plays a critical role in the negative regulation of effector T cell function. In contrast to expectations, BrdU incorporation experiments demonstrated that CTLA-4 expression was associated with normal or even enhanced in vivo proliferation of virus-specific CD4+ and CD8+ T cells following acute lymphocytic choriomeningitis virus or vaccinia virus infection. When compared with CTLA-4- T cells directly ex vivo, CTLA-4+ T cells also exhibited normal antiviral effector functions following stimulation with peptide-coated cells, virus-infected cells, plate-bound anti-CD3/anti-CTLA-4, or the cytokines IL-12 and IL-18. Together, this indicates that CTLA-4 does not directly inhibit antiviral T cell expansion or T cell effector functions, at least not under the normal physiological conditions associated with either of these two acute viral infections.     

Suggestive evidence of a locus on chromosome 10p using the NIMH genetics initiative bipolar affective disorder pedigrees

As part of a four-center NIMH Genetics Initiative on Bipolar Disorder, a genome screen using 365 markers was performed on 540 DNAs from 97 families, enriched for affected relative pairs. This is the largest uniformly ascertained and assessed linkage sample for this disease, and includes 232 subjects diagnosed with bipolar I (BPI), 32 with schizo-affective, bipolar type (SABP), 72 with bipolar II (BPII), and 88 with unipolar recurrent depression (UPR). A hierarchical set of definitions of affected status was examined. Under Model I, affected individuals were those with a diagnosis of BPI or SABP, Model II included as affected those fitting Model I plus BPII, and Model III included those fitting Model II plus UPR. This data set was previously analyzed using primarily affected sib pair methods. We report the results of nonparametric linkage analyses of the extended pedigree structure using the program Genehunter Plus. The strongest finding was a lod score of 2.5 obtained on chromosome 10 near the marker D10S1423 with diagnosis as defined under Model II. This region has been previously implicated in genome-wide studies of schizophrenia and bipolar disorder. Other chromosomal regions with lod scores over 1.50 for at least one Model Included chromosomes 8 (Model III), 16 (Model III), and 20 (Model I). Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:18-23, 2000 Copyright 2000 Wiley-Liss, Inc.     

Circulating procalcitonin and cleavage products in septicaemia compared with medullary thyroid carcinoma

OBJECTIVE: Raised plasma levels of procalcitonin (proCT) represent an early marker for septicaemia. They are related to disease severity and inversely to outcome and response to treatment. ProCT is presumably synthesised in tIssues other than the thyroid C-cells which are the source of calcitonin (CT) in normal physiology. This study compares proCT and its cleavage products in the serum of patients with septicaemia with those in medullary thyroid carcinoma (MTC). METHODS: Immunoreactive proCT and its cleavage products were extracted from the serum of patients with septicaemia or MTC using octadecylsilyl silica columns and characterised by reversed phase HPLC and Western blot analysis. ProCT, CT(1-32) and the flanking peptides PAS-57 and PDN-21 were recognised with antibodies specific for the individual peptides. RESULTS: ProCT and a 10 kDa polypeptide were recognised with antibodies to PAS-57, CT(1-32) and PDN-21. An 8 kDa proCT fragment was detected with antibodies to CT and PDN-21. However, intact CT(1-32), PAS-57 and PDN-21, found in the serum of MTC patients, were undetectable. The results indicate partial cleavage of proCT in septicaemia different from that in MTC patients. CONCLUSIONS: ProCT and 10 and 8 kDa proCT fragments were recognised in the circulation of septic patients. They were different from the known proCT-processing products PAS-57, CT(1-32) and PDN-21 identified in the serum of normal subjects and of MTC patients. Distinct cleavage of proCT may contribute to the symptoms of septicaemia.     

Heparin facilities proliferation of human osteoblasts in vitro

It is a well-known fact that long-term application of heparin can lead to osteoporosis. To learn more about the mechanisms of heparin-induced osteoporosis, we exposed human osteoblasts in vitro to heparin in various concentrations. We found an increased proliferation rate, especially in concentrations used therapeutically in humans (0.1-0.2 IU/ml). In our experiments fetal calf serum (FCS) was able to heighten the positive effect of heparin, showing a synergism between heparin and FCS.     

Effect of the CYP2D6 genotype on metoprolol metabolism persists during long-term treatment

The beta1 selective beta-blocker metoprolol is metabolized predominantly but not exclusively by CYP2D6. Due to the polymorphism of the CYP2D6 gene, CYP2D6 activity varies markedly between individuals. Consequently, after short-term administration metoprolol plasma concentrations were found to be several fold higher in poor metabolizers than in extensive metabolizers. However, it is currently not known, whether the impact of the CYP2D6 polymorphism persists during long-term therapy, since alternate mechanisms of elimination or metabolism could be effective in this setting. The study comprised 91 Caucasian patients on long-term treatment with metoprolol (median duration of treatment 12.6 months; median daily drug dose: 47.5 mg/day). Metoprolol and alpha-OH-metoprolol plasma concentrations were assessed by HPLC. Genotyping detected the null alleles (*0): *3, *4, *5, *6, *7, *8, *12, *14, *15, the alleles *9, *10 and *41 associated with reduced enzymatic activity as well as the fully functional alleles *1 and *2. Genotype and allele frequencies were in accordance with published frequencies for the German population. The plasma metabolic ratio of metoprolol/alpha-OH-metoprolol was markedly affected by the genotype (P < 0.0001). In accordance, median adjusted metoprolol plasma concentrations were 6.2- and 3.9-fold higher in patients with *0/*0 genotypes (n = 8) and intermediate genotypes (n = 10), respectively, as compared to those with two fully functional alleles (n = 31; P < 0.01). In summary, the pronounced effect of the CYP2D6 genotype persists during long-term therapy, affecting both metabolic ratio and metoprolol plasma concentration.     

Is there additional information from laparoscopic ultrasound in tumor staging?

Accurate preoperative staging of gastrointestinal malignancies is of major importance in the decision for adequate stage-related therapy. There is evidence that laparoscopy in combination with laparoscopic ultrasound is more accurate in the detection of intra-abdominal metastases than conventional preoperative imaging. Staging laparoscopy in combination with laparoscopic ultrasound is a minimally invasive technique that reveals intra-abdominal disseminated tumor spread and local tumor extent. Therefore laparoscopic ultrasound is an ideal adjunct to laparoscopy because this technique may compensate for the lack of tactile feedback with laparoscopic instruments. Color-coded Doppler imaging can be very valuable for the assessment of resectability in patients with pancreatic cancer. Current data confirm that laparoscopic ultrasound is capable of enhancing the accuracy of staging laparoscopy. Compared to standard laparoscopy, a combination of both techniques markedly increases the sensitivity of staging laparoscopy in the determination of unresectable disease. This is of major importance in the assessment of occult liver metastases and lymph node involvement. Laparoscopic ultrasonography improves the diagnostic accuracy compared to conventional imaging techniques and should be considered as integral part of staging laparoscopy.     

Pancreatic injury in severe trauma: early diagnosis and therapy improve the outcome

BACKGROUND: Pancreatic injury is a dangerous complication in multiple injury, and experience with its diagnosis and treatment is usually limited. METHOD: Retrospective analysis of 3,840 patients admitted after multiple trauma from January 1, 1982, until May 31, 2000. RESULTS: A laparotomy was performed in 121 cases (3.15%) due to suspected intra-abdominal lesion. 32% of the patients (39/121) had a pancreatic lesion; 23% (9/39) had a rupture of the major pancreatic duct. Primary laparotomy was performed in 72% of the patients (28/39). Superficial lesions were treated by explorative laparotomy alone (n = 7), debridement and external drainage (n = 20), or necrosectomy and lavage (n = 3). Complex pancreatic lesions were treated by pancreatojejunostomies (n = 5), pancreatic left resections (n = 2), or exploration alone (n = 2). 8 of 39 patients died (20%), 4 intraoperatively. Of the surviving 35 patients, a pancreas-associated complication developed in 8 patients (23%): pancreatic abscesses (n = 4), traumatic pancreatitis (n = 3), pancreatic fistulas (n = 2), and pseudocysts (n = 2). CONCLUSIONS: Pancreatic injury is an infrequent but dangerous complication in severe trauma. Superficial lesions not affecting the major pancreatic duct can be managed by debridement and external drainage. If the major pancreatic duct is ruptured, organ-preserving, complex reconstructive procedures are necessary. When diagnosed timely and treated according to severity and overall situation, pancreatic injuries have an acceptable morbidity, but usually a high mortality.     

Production of human chorionic gonadotropin-beta subunit associated with an osteolytic meningioma. Case report

An osteolytic meningioma in a 36-year-old woman was accompanied by elevated serum levels of human chorionic gonadotropin-beta subunit (beta-HCG), which returned to normal after removal of the tumor. Light microscopy examination demonstrated a transitional meningioma. Immunohistochemical analysis revealed that the tumor cells had a positive reaction for beta-HCG. This case illustrates the possibility that meningioma may be associated with clinically detectable secretion of beta-HCG. To the authors' knowledge, this is the first case in which meningioma has been shown to secrete beta-HCG. The authors believe that meningioma should be considered in the differential diagnosis of choriocarcinoma, embryonal cell tumor, germinoma, and metastatic ovarian tumor associated with elevated levels of beta-HCG.