The use of the face-hand test to screen for organic brain syndromes. A pilot study

A reduced version of the Face-Hand Test (FHT), the FHT-R, was applied to a random sample of 91 elderly subjects living in the community (S. Paulo-Brazil), to study the instrument's ability to detect Organic Brain Syndrome (OBS). The scores of the FHT-R test were then compared with a psychiatric assessment using the Clinical Interview Schedule. Five persons were regarded as OBS "cases" and 86 as OBS "non cases". At the cut-off point 0/1 the validity coefficients were as follows: Sensitivity 60%, Specificity 94%, Positive Predictive Value 38%, Negative Predictive Value 98% and Overall Misclassification Rate 8%. The usefulness of this clinical test to screen for OBS in epidemiological surveys is discussed.     

Human isolated small intestine: motor responses of the longitudinal muscle to field stimulation and exogenous neuropeptides

Summary (1) Longitudinal muscle strips from the human small intestine (jejunum/ileum) responded to electrical field stimulation (1–50 Hz) with frequency-related primary contractions which were largely atropine- (3 M) sensitive. When the tone was raised by addition of galanin (0.3 – 1 M), prostaglandin (PG) E₂ (1–10 M) or neurokinin A (NKA, 0.1 M), a frequency-related relaxation was evident which was potentiated by atropine. All the responses to field stimulation were abolished by tetrodotoxin (1 M), thus indicating their neural origin. (2) The atropine-sensitive primary contraction to field stimulation was virtually abolished by omega conotoxin fraction GVIA (CTX, 0.1–0.3 M) while the relaxations were CTX-resistant. The field stimulation-induced relaxations, which were observed in the presence of atropine and guanethidine (3 M), were also unaffected by apamin (0.1 M). (3) NKA and substance P (SP) produced a concentration- (1 nM–1 M for both peptides) related contraction, NKA being about 53 times more potent than SP. [Pro⁹]SP sulphone and [MePhe⁷]-NKB, selective agonists of the NK-1 and NK-3 receptor, respectively, were barely effective. On the other hand, [\Ala⁸]NKA(4–10), a selective NK-2 receptor agonist, had a potent contractile activity, similar to that of NKA. (4) Galanin (1 nM–1M) produced an atropine- and tetrodotoxin-resistant concentration-related contraction of longitudinal muscle of human isolated small intestine. The response to galanin did not show any sign of fading and was particularly suitable to study the evoked relaxations. (5) Calcitonin gene-related peptide (CGRP) (10–100 nM) consistently inhibited the nerve-mediated contractions of strips from the ileum while the effect on the jejunum was less pronounced. Vasoactive intestinal polypeptide (VIP, 0.1–1 M) inhibited nerve-mediated contractions both in the ileum and the jejunum. (6) These experiments indicate that both cholinergic excitatory and non-adrenergic non-cholinergic nerves affect motility of the longitudinal muscle of the human small intestine. Furthermore, several neuropeptides produce potent motor effects, the contractile response to tachykinins being apparently mediated by activation of NK-2 receptors.     

Enhanced metabolic activation of chemical hepatocarcinogens in woodchucks infected with hepatitis B virus

The metabolism of chemical carcinogens was investigated in liverpreparations from 28 captive woodchucks (Marmotamonax). Of these,23 were naturally infected with the wood-chuck hepatitis virus(WHV), and eight also had primary hepatocellular carcinoma (PHC).Twenty-nine parameters were investigated in liver subcelhilarfractions, including cross-reactivity with HBsAg, and biochemicalparameters, such as -glutamyl transpeptidase, cytochrome P-450and mirosomal monooxygenases (aryl hydrocarbon hydroxylase,ethodycoumarin and ethoxyresorufin deethylases, amino-pyrineand dimethylnitrosamine demethylases, and testosterone 7-and16ß- and 6ß-hydroxylases), uridine 5'-diphos-phoglucuronosyltransferase, GSH and related enzymes (peroxidase, reductaseand S-transferase), as well as other cytosolic enzyme activities(glucose 6-phosphate and 6-phosphogluconate dehydrogenases,NADPH- and NADH-dependent diaphorases, and DT diaphorase). Inaddition, liver preparations were used in order to quantifythe metabolic activation into bacterial mutagens of five procarcinogens(aflatoxin B¹, the pyrolysis products Trp-P-2 and MelQ, 2-aminofluoreneand dimethylnitrosamine) and the decrease of potency of threedirect-acting mutagens (sodium di-chromate, ICR 191 and 4-nitroquinoline1-oxide). WHV infection produced a significant stimulation ofcarcinogen metabolism, as shown by the simultaneous change indetoxification parameters (GSH depletion) and activation indices(enhancement of microsomal monooxygenases and of pro-carcinogenactivation into mutagenic metabolites). There were no significantdifferences between WHV-positive samples from animals, withoutPHC and the noncancerous tissue of PHC-bearing animals, whereasa decrease of both activation and detoxification indices wasrecorded in the turmorous tissue. There was a considerable interindividualvariability among WHV carriers, which was tentatively ascribedto genetic factors. Pregnancy was the only known factor influencingthe results in WHV carriers. However, even by excluding pregnantanimals, the effects on carcinogen metabolism produced by WHVinfection were still statistically significant. These results,together with previous data obtained in humans, revealed thatmetabolic factors may play a role in the synergism between viralhepatitis and chemical hepato-carcinogens in the etiopathogenesisof PHC.     

Cranial sutures and craniometric points detected on MRI

The main goal of the study was to determine on MRI the cranial sutures, the craniometric points and craniometric measurements, and to correlate these results with classical anthropometric measurements. For this purpose, we reviewed 150 cerebral MRI examinations considered as normal (Caucasian population aged 2049 years). For each examination we individualized 11 craniometric landmarks (Glabella, Bregma, Lambda, Opisthocranion, Opisthion, Basion, Inion, Porion, Infra-orbital, Eurion) and three measurements. Measurements were also calculated independently on 498 dry crania (Microscribe 3-DX digitizer). To validate the MRI procedure, we measured four dry crania by MRI and with compass or digital caliper gauges. Cranial sutures always appeared without signal (black), whatever the MRI sequence used, and they are better visualized with a 5 mm slice thickness (compact bone overlapping). Slice dynamic analysis and multiplanar reformatting allowed the detection of all craniometric points, some of these being more difficult to detect than others (Porion, Infra-orbital). The measurements determined by these points were as follows: VertexBasion height=135.66±6.56 mm; EurionEurion width=141.17±5.19 mm; GlabellaOpisthocranion length=181.94±6.40 mm. On the midline T1-weighted sagittal image, all median craniometric landmarks can be individualized and the GlabellaOpisthocranion length, VertexBasion height and parenchyma indices can be calculated. Craniometric points and measurements between these points can be estimated with a standard cerebral MRI examination, with results that are similar to anthropometric data.     

Lymphoepithelioma-like carcinoma of the bladder: three cases with clinicopathological and p53 protein expression study

Lymphoepithelioma-like carcinoma of the bladder is an uncommon neoplasm, of which 49 cases have been described in the English literature, none of which has been studied for p53 protein expression. We studied three muscle-infiltrating cases of this tumor using immunohistochemical, in situ hybridization and polymerase chain reaction (PCR) methods. The three cases were positive for epithelial markers and negative for lymphoid antigens in the tumoral syncytial areas. The intensive infiltrate of small cells was negative for epithelial and positive for lymphoid markers. This population was mainly made up of cytotoxic T-lymphocytes, positive for TIA-1. p53 protein was intensely positive in more than 90% of the epithelial component nuclei, being negative in the lymphoid cells. PCR study did not show mutations on p53. Both lymphocytes and epithelium were negative for Epstein–Barr virus markers, such as the latent membrane protein and EBER (Epstein–Barr-encoded RNA). The prognosis was very good after radiotherapy and chemotherapy treatment, preserving the bladder despite the muscle infiltration. The presence of an intense cytotoxic T-lymphocyte population may be related to this good prognosis. Both aspects, p53 protein status and T-lymphoid population, had never been studied before in bladder lymphoepithelioma-like carcinoma.     

A uterine leiomyosarcoma that became positive for HMB45 in the metastasis

Uterine smooth muscle tumors are usually spindle cell lesions, but a minority is composed of epithelioid cells. Foci of clear cells can be found in these latter tumors. Recently, it has been shown that some of these tumors can be positive for HMB45, and some authors have advocated calling these lesions perivascular epithelioid cell (PEC) tumors or PEComas. The case we describe here clearly shows that the so called PEC is just a smooth muscle cell capable of changing its immunophenotype. The patient involved is a 29-year-old black woman who was found to have an epithelioid leiomyosarcoma of the uterus in November 1995. She was treated with a simple hysterectomy and bilateral salpingo-oophorectomy. A metastatic lesion was found in her liver. She, therefore, also received chemotherapy and was free of disease until October 2002, when a recurrent tumor was detected in her spine. After undergoing resection of the lesion at 2 different times, in 2002 and 2003, the patient was treated with radiotherapy and is currently receiving chemotherapy. On microscopic examination, the tumor in the uterus and liver both proved to be an epithelioid leiomyosarcomas that was diffusely positive for smooth muscle actin. Approximately 15% of the cells had clear cytoplasm, but sections from 2 different blocks were completely negative for HMB45. However, although the tumors resected from the spine in 2002 and 2003 showed features similar to those of the uterine neoplasm, but with a lower percentage of cells positive for smooth muscle actin and more clear cells, several of the clear cells were positive for HMB45. To the best of our knowledge, this is the first case of a uterine smooth muscle cell tumor that became positive for HMB45 when it metastasized.     

An ELISA serum assay for autoantibodies to HSP70 in immune-mediated hearing loss

A Western blot to detect anti-HSP70 autoantibodies has been reported to be of diagnostic value for immune-mediated hearing loss patients. While setting up this Western blot in our lab, we detected two main problems. First, some patients were positive for antibodies to a 70-kDa protein when tested against a whole cell lysate, but negative if the antigen used was purified HSP70. Second, if high amounts of purified HSP70 were loaded on the gel, both patients and healthy controls were positive. We have developed and optimized an ELISA as an alternative to the Western blot. This assay is more appropriate to identify positive and negative individuals because it is semi-quantitative. The ELISA is also more sensitive, requiring very low concentrations of the antigen and thus minimizing false positives. Finally, we demonstrated that immune-mediated hearing loss patients recognize mainly the native form of HSP70, a fact that potentially leads to false negatives when a denaturing Western blot assay is used for diagnosis. To test the diagnostic value of the ELISA, we performed a blind test with 70 hearing loss patients, as well as 30 healthy controls. A sensitivity of 84% and a specificity of 93% were obtained, superior to what has been reported so far for the Western blot.     

Evidence-based medicine, medical decision analysis, and pathology

Recent advances in molecular pathology and other technologies such as proteomics present pathologists with the challenge of integrating the new information generated with high-throughput methods with current diagnostic models based mostly on histopathology and clinicopathologic correlations. Parallel developments in the field of medical informatics and bioinformatics provide the technical and mathematical methods to approach these problems in a rational manner. However, it remains unclear whether pathologists or other medical specialists will become primarily responsible for the development and maintenance of these multivariate and multidisciplinary diagnostic and prognostic models that are hoped to provide more accurate, individualized patient-based information. Evidence-based medicine (EBM) and medical decision analysis (MDA) are relatively new disciplines that use quantitative methods to assess the value of information, differentiate fact from myth, and integrate so-called best evidence into multivariate models for the assessment of prognosis, response to therapy, selection of laboratory tests, and other complex problems that influence individual patient care. We review from an epistemological viewpoint the current approach to information in pathology and describe some of the concepts developed by the practitioners of EBM and MDA.     

Chromophobe renal cell carcinoma with sarcomatoid transformation

We present a rare case of a chromophobe renal cell carcinoma that progressed to a high-grade spindle cell sarcoma. The tumor affected a 50-year-old man who had presented with right upper quadrant discomfort and hematuria and subsequently underwent a right radical nephrectomy. Microscopically, the tumor was composed of two distinct components, a chromophobe renal cell carcinoma and a sarcomatoid component. The sarcomatoid component had exhibited aggressive behavior by spreading to a regional lymph node. This case report shows that chromophobe carcinoma can develop a sarcomatoid transformation with a high propensity for invasive growth and metastasis.