Elevated expression of tryptophan hydroxylase-2 mRNA at the neuronal level in the dorsal and median raphe nuclei of depressed suicides.

Deficient levels of serotonin are associated with suicide and depression. Paradoxically, in the dorsal raphe nucleus (DRN) there are more serotonin neurons and more neuronal tryptophan hydroxylase-2 (TPH2) expression postmortem in depressed suicides. In this study, we sought to determine whether greater TPH2 expression in depressed suicides was the result of more TPH2 expression per neuron. In situ hybridization and computer-assisted image analysis were performed on tissue sections throughout the extent of the raphe nuclei at the level of silver grains per neuron to systematically quantify TPH2 neuronal expression. Depressed suicides have 26.5% more TPH2 grain density per neuron in the DRN compared with matched controls (P=0.04). The difference in grain density is greater at mid- and caudal anatomical levels across the rostrocaudal axis of the DRN. Densitometric analysis of TPH2 expression in the DRN subnuclei showed that higher expression levels were observed at posterior anatomical levels of depressed suicides (121% of control in the caudal subnucleus). Higher TPH2 expression in depressed suicides may explain more TPH2 protein and reflect a homeostatic response to deficient serotonin levels in the brains of depressed suicides. Localized changes in TPH2 expression in specific subnuclei of the DRN suggest that the serotonergic compensatory mechanism in depression and suicide is specifically regulated within the DRN and has implications for regions innervated by this subnucleus.

Genetic architecture of the human tryptophan hydroxylase 2 Gene: existence of neural isoforms and relevance for major depression.

Impaired brain serotonin neurotransmission is a potential component of the diathesis of major depression. Tryptophan hydroxylase-2 (TPH2), is the rate limiting biosynthetic isoenzyme for serotonin that is preferentially expressed in the brain and a cause of impaired serotonin transmission. Here, we identify a novel TPH2 short isoform with truncated catalytic domain expressed in human brainstem, prefrontal cortex, hippocampus and amygdala. An exploratory study of 166 Caucasian subjects revealed association with major depression or suicide of a novel single nucleotide polymorphism (SNP) g.22879A>G located in exon 6 of this short isoform. This SNP and additional SNPs were discovered through a systematic characterization of the genetic architecture of the TPH2 gene for further genetic and functional investigations of its relationship to major depression and other psychopathology.

Pancreatic carcinoma with brain metastases: case report and literature review.

The case of a patient developing multiple brain metastases from carcinoma of the exocrine pancreas has been described. A 56-year-old man with stage IV pancreatic cancer attained a clinical and radiographic response while receiving the G-FLIP chemotherapy regimen (biweekly gemcitabine, irinotecan, 5-fluorouracil, leucovorin and cisplatin). After 4 months of therapy, he developed gait imbalance and weakness in the right hand. An MRI of the brain showed multiple 1-2 mm enhancing nodules in the cerebral hemispheres and pons. A subsequent biopsy confirmed that these were pancreatic carcinoma metastases. The patient experienced a rapid deterioration in his neurological status and died 3 days after brain biopsy. Previously reported cases of brain metastases from pancreatic cancer are reviewed.

Dysplastic nodules in cirrhotic liver: arterial phase enhancement at CT and MR imaging--a case report.

In a 65-year-old woman with cirrhosis, biphasic helical computed tomography (CT) and multiphase gadolinium-enhanced magnetic resonance (MR) imaging depicted 11 hepatic nodules that enhanced homogeneously during the hepatic arterial phase. At pathologic examination, all lesions were dysplastic nodules with unpaired hepatic arteries within. Hepatic arterial phase enhancement of cirrhotic nodules at CT and MR imaging is not diagnostic of hepatocellular carcinoma but may occur in dysplastic nodules. Results of a single biopsy yielding hepatocellular carcinoma may not be applicable to other nodules that enhance similarly.

Immunohistochemical detection of hepatitis C antigen by monoclonal antibody TORDJI-22 compared with PCR viral detection.

We sought to determine the sensitivity and specificity of immunohistochemistry using the TORDJI-22 MoAb (BioGenex, San Ramon, Calif), which is specific for the C-100 protein of the hepatitis C virus, compared with reverse transcriptase-polymerase chain reaction (RT-PCR) of tissue for viral RNA. RT-PCR had been performed on 52 fixed tissue specimens. Immunohistochemistry was performed using prediluted antibody with the alkaline phosphatase/fast red (BioGenex) technique. Predigestion with Protease XXIV (BioGenex) and other procedures followed the manufacturer's protocols. Positive immunohistochemistry was narrowly defined as tightly clumped, perinuclear red granules in hepatocytes. Of the specimens, 28 were positive by RT-PCR. With RT-PCR as the standard of comparison, immunohistochemistry yielded a sensitivity of 70% and specificity of 84%. Positive cells, when present, were usually very rare. With stringent criteria, immunohistochemistry with the TORDJI-22 monoclonal antibody is a very specific, fairly sensitive diagnostic test for hepatitis C virus in fixed liver tissues.

Dysplastic nodules and hepatocellular carcinoma: thin-section MR imaging of explanted cirrhotic livers with pathologic correlation.

PURPOSE: To evaluate detection and characterization of hepatocellular nodules in fresh whole explanted cirrhotic livers at thin-section magnetic resonance (MR) imaging. MATERIALS AND METHODS: T1-weighted spin-echo and T2-weighted fast spin-echo MR imaging (5-mm-thick sections) were performed in a head coil at 1.5 T in the whole cirrhotic livers of 28 consecutive patients within 4 hours of explantation. MR imaging findings were correlated with findings at pathologic examination, and new international terminology was used to classify the hepatocellular nodules. RESULTS: At pathologic examination, 42 suspect (other than regenerative) nodules were identified in 11 patients. MR imaging depicted 41 of 42 (98%) of these nodules (five of five hepatocellular carcinomas [HCCs {diameter, > or = 2 cm}], 10 of 10 small HCCs [diameter, < 2 cm], two of two dysplastic nodules with subfoci of HCC, three of three high-grade dysplastic nodules, and 21 of 22 low-grade dysplastic nodules. Lesions demonstrated the following combinations of signal intensity characteristics on thin-section T1- and T2-weighted images, respectively: HCC, hyperintense, hypointense (n = 3); hyperintense, hyperintense (n = 1); hypointense, isointense (n = 1). Small HCC, hyperintense, hypointense (n = 7); hypointense, hyperintense (n = 2); hyperintense, hyperintense (n = 1). Both dysplastic nodules with subfoci of HCC, hyperintense, hypointense. All seven nonsiderotic low-grade dysplastic nodules, hyperintense, hypointense. All 14 siderotic low-grade dysplastic nodules, hypointense, hypointense. All three high-grade dysplastic nodules, hyperintense, hypointense. CONCLUSION: The variable signal intensity characteristics of HCCs made reliable diagnosis impossible, but the thinsection unenhanced in vitro MR images were sensitive for detection of HCCs and dysplastic nodules in cirrhotic livers.

Intracranial inverting papilloma.

BACKGROUND: Inverting papillomas usually originate from the lateral wall of the nose and sporadically from the ethmoid, maxillary, sphenoid, or frontal sinuses. Intracranial extension and dural penetration is rare and often associated with recurrent disease that has degenerated into squamous cell carcinoma. A case of inverting papilloma with dural penetration in the absence of malignant degeneration has prompted an investigation into the incidence and treatment of dural invasion by benign inverting papilloma. METHODS: A literature search revealed 1468 cases of inverting papilloma. A detailed analysis was performed to obtain data on the incidence of intracranial invasion. RESULTS: Of the 1468 cases, 5 were noted to be associated with intracranial extension without histologic evidence of malignancy (0.34%). Treatment consisted of surgery alone in 3, radiotherapy in 1, and combined therapy in the last patient. Dural invasion was documented histopathologically in one case. CONCLUSION: Intracranial extension and dural penetration of benign inverting papilloma is extremely rare, and a uniform treatment plan has not been established. Further investigation is necessary in the pathophysiology and management of intracranial inverting papilloma.

Carcinosarcoma of urinary bladder: report of 5 cases with immunohistologic study.

We studied 5 cases of carcinosarcoma of the urinary bladder. Immunoperoxidase studies were performed to identify the nature of the tumor and to establish the diagnosis. We suggest that these tumors represent a transition of epithelial to mesenchymal malignancy. Three of our patients had a history of radiation therapy prior to development of carcinosarcoma; of which 2 had a long interval between exposure to radiation and tumor development. Radiation is a risk factor for endometrial carcinosarcoma, and in this report we strongly suggest such an association for the urinary bladder.

Accessory cardiac bronchus: CT features and clinical significance.

PURPOSE: The accessory cardiac bronchus is a rare congenital anomaly of the tracheobronchial tree that arises from the medial wall of the bronchus intermedius. This report documents the computed tomographic (CT) appearance of this anomaly. MATERIALS AND METHODS: Six patients with this anomaly were identified. All six underwent CT; three underwent correlative bronchoscopy, and one had both bronchoscopic and surgical confirmation. RESULTS: In all six cases, a distinct airway could be identified originating from the medial wall of the bronchus intermedius. Associated lung parenchymal tissue was identified in four cases, while in three cases a discrete soft-tissue mass was seen, presumably representing vascularized bronchial or vestigial parenchymal tissue. In two cases, the lumen of the airway was filled with debris. CONCLUSION: Recognition of this anomaly is important, as associated clinical complications, including recurrent episodes of both infection and hemoptysis, may be anticipated in a small percentage of patients.

Radioimmunolocalization of metastatic breast carcinoma using indium-111-methyl benzyl DTPA BrE-3 monoclonal antibody: phase I study.

Pharmacokinetics of radiolabeled BrE3 monoclonal antibody (Mab), reactive against a breast mucin epitope, were assessed in 15 patients with advanced breast cancer. Patients received 5 mCi (185 MBq) of 111In-methyl benzyl isothiocyanate DTPA (MX-DTPA) conjugated BrE-3 Mab intravenously with total antibody doses of 10, 50 or 100 mg. Serial quantitative imaging, blood and urine clearance were obtained to measure pharmacokinetics, assess tumor localization and estimate radiation dose. Organ function was followed to determine toxicity. Mild allergic reactions occurred in four patients. Eighty-six percent of 70 known lesions and 5 unsuspected lesions were detected by antibody imaging. Biexponential modeling of radiolabeled antibody in serum showed a T1/2 alpha = 9.5 +/- 2.7 hr and T1/2 beta = 56 +/- 25.4 hr. Total urinary excretion averaged 35.5% +/- 19.3% injected dose (ID) by Day 8. Quantitative imaging showed that 0.02-2.56% ID localized in tumors. Extrapolating dosimetry from 111In-MX-DTPA-BrE-3 to 90Y-MX-DTPA-BrE-3, we estimate therapeutic radiation doses could be delivered to some tumors with tolerable toxicity.

Cytologic features of poorly differentiated "insular" carcinoma of the thyroid. A case report.

A case of poorly differentiated "insular" carcinoma of the thyroid is presented. Fine needle aspiration cytology suggested the differential diagnosis of poorly differentiated carcinoma versus anaplastic carcinoma. Histologic examination of the resected specimen confirmed the diagnosis of insular carcinoma. The cytologic features of this uncommon primary thyroid malignancy are described and discussed with reference to the literature.

Angiosarcoma at the site of a Dacron vascular prosthesis: a case report and literature review.

Four of 32 reported sarcomas related to the aorta have arisen around previously placed aortic vascular prostheses suggesting that the graft may have been an etiologic factor. Our recent experience with such an angiosarcoma arising around a Dacron aortic graft prompted a review of the lesion to identify risk factors, diagnostic approaches, and treatment options. The diagnosis of these sarcomas is seldom made before operation. Animal studies have implicated plastic polymers including Dacron as carcinogenic materials capable of inducing sarcoma in 7% to 50% of exposures. Because of the rarity of these tumors and the thousands of vascular implants used over the past 30 years, it is unlikely that this degree of risk can be extrapolated to humans. However, a tumor should be included in the differential diagnosis of any mass or thromboembolic event associated with a vascular prosthesis.

Randomized trial interpreting sputum quality in a clinical laboratory.

The role for laboratory interpretation of microbiologic results remains controversial, and many laboratories leave the interpretation of culture results entirely to physicians. We examined the effects of furnishing a laboratory interpretation of sputum quality on physician decision making. Quality of sputum was determined on Gram-stained smears by using a modification of the criteria of Bartlett (R. C. Bartlett, Medical Microbiology: Quality, Cost, and Clinical Relevance, p. 24-31, 1974). A total of 301 poor-quality specimens were randomized either to receive written interpretation of Gram stain results or to a control group for which Gram stain results were reported without interpretation. Physicians were more likely to follow up a poor-quality specimen with a second specimen if they had been furnished an interpretation of the results from the original Gram stain (22 versus 12%; P = 0.025). We conclude that laboratory-based interpretation of microbiologic results can improve physician decision making.