Fluorescence in situ hybridization analysis of chromosome 12p in paraffin-embedded tissue is useful for establishing germ cell origin of metastatic tumors.

The over-representation of chromosome 12p sequences is crucial for the development of invasive testicular germ cell tumors. Testicular cancer patients may have metastatic tumors of diverse histologic types, including adenocarcinoma, undifferentiated carcinoma, sarcoma, or other malignancies that lack features of germ cell tumors. We sought to investigate the possible germ cell origin of such tumors using interphase fluorescence in situ hybridization. In all, 10 metastatic malignant somatic-type tumors from patients with histories of testicular cancer, as well as one malignant somatic-type tumor from a patient with primary mediastinal germ cell tumor were studied and included: adenocarcinoma (five cases), poorly differentiated carcinoma (one), sarcoma (four), and neuroendocrine carcinoma (one). The tumors were analyzed using fluorescence in situ hybridization using 12p spectrum green and 12 centromeric spectrum orange probes in paraffin sections. The patients ranged in age from 27 to 55 years (mean, 43). Colon and lung cancers from patients without germ cell tumors were used as controls. Adequate signals were observed in all tumors. Gain of chromosome 12p was seen in six tumors. None of the control tumors showed 12p amplification. Fluorescence in situ hybridization for 12p amplification in routinely processed surgical specimens is a useful adjuvant diagnostic tool in confirming the germ cell origin of metastatic tumors having the histologic appearance of somatic-type neoplasms.     

Quantitation in gated perfusion SPECT imaging: The Cedars-Sinai approach

Cedars-Sinai’s approach to the automation of gated perfusion single photon emission computed tomography (SPECT) imaging is based on the identification of key procedural steps (processing, quantitation, reporting), each of which is then implemented, in completely automated fashion, by use of mathematic algorithms and logical rules combined into expert systems. Our current suite of software applications has been designed to be platform- and operating system-independent, and every algorithm is based on the same 3-dimensional sampling scheme for the myocardium. The widespread acceptance of quantitative software by the nuclear cardiology community (QGS alone is used at over 20,000 locations) has provided the opportunity for extensive validation of quantitative measurements of myocardial perfusion and function, in our opinion, helping to make nuclear cardiology the most accurate and reproducible modality available for the assessment of the human heart.     

Paternal and Maternal Smoking Habits before Conception and During the First Trimester: Relation to Spontaneous Abortion

PURPOSE: This study examined the association between maternal smoking before and during the first trimester of pregnancy and spontaneous abortion.

METHODS: We have been conducting a hospital-based case-control study on risk factors for spontaneous abortion in the greater Milan area. We collected information from 782 cases of spontaneous abortions and 1543 controls (women who delivered at term healthy infants).

RESULTS: With respect to never smokers, the odds ratio (OR) were 0.7 (95%, confidence interval (CI), 0.5–1.0) for women who quit smoking and 1.3 (95% CI, 1.0–1.6) for those who continued during pregnancy. Women who smoked more than 10 cigarettes/day in the first trimester were at increased risk of miscarriage, with an OR of 1.4 (95% CI, 1.0–2.1). No relationship was evident between the number of cigarettes smoked before conception and the risk of abortion. Likewise, no association emerged between paternal smoking and miscarriage. Moreover, no significant interaction or modification effect was obtained when strata of age and other major characteristics were investigated.

CONCLUSIONS: The risk of abortion associated with cigarette smoking during the first trimester of pregnancy was measurable and noticeable in this population, and accounted for 9% (95% CI, 6–13%) of all cases. The increased risk of spontaneous abortion in women smoking during pregnancy is a further reason to encourage pregnant women to quit.     

Functioning human insulinomas

Sixty-seven insulinomas were investigated by immunohistochemistry using site-directed antibodies against insulin, proinsulin, chromogranin A, HISL-19, and four proteins directly or indirectly involved in the proteolytic processing of proinsulin: the prohormone convertases PC2 and PC3, carboxypeptidase H (CPH) and 7B2. Results were expressed in a six-grade score according to the frequency of immunoreactive tumour cells. Insulin was expressed by all tumours, appearing in either a diffuse or a polarized pattern and being detected in more than 30% of tumour cells in all cases but three. Proinsulin was also expressed in all tumours, with more than 50% of tumour cells immunoreactive in all cases but 5. It was consistently localized in the Golgi apparatus. In about half the cases, moreover, it also showed diffuse cytoplasmic staining, usually with a very sparse distribution. Trabecular and solid insulinomas did not present specific, homogeneous patterns of insulin immunostaining. However, insulin immunoreactivity was much more abundant in trabecular than in solid neoplasms, being present in virtually all tumour cells (score 6) in 50% and 8% of cases, respectively. Virtually all insulinomas expressed PC2, PC3, CPH and 7B2, usually in 30–100% of tumour cells, with a frequency significantly related to that of insulin. However, detection of PC2 and 7B2 was slightly less frequent than that of PC3 and CPH. In consecutive sections these proteins were found to be mostly co-localized with insulin and chromogranin A but not with proinsulin. They were heavily expressed in all 10 tumours with more than 10% of cells showing cytoplasmic proinsulin immunoreactivity, indicating that the leakage of proinsulin from the Golgi compartment is not associated with faulty expression of converting enzymes and possibly reflects a saturated processing capacity. HISL-19 immunoreactivity was found in both Golgi apparatus and insulin stores, indicating that the relevant antigen is different from all other proteins investigated. These results do not support a defect in expression or localization of proinsulin-processing enzymes in most insulinomas.     

Responses of human primary sensorimotor and supplementary motor areas to internally triggered unilateral and simultaneous bilateral one‐digit movements. A high‐resolution EEG study

We modelled the responses of human primary sensorimotor areas and supplementary motor area to simple, self-initiated unilateral and simultaneous bilateral middle finger movements using a novel high-resolution electroencephalography technology. The results support the view that these cortical motor areas are involved in parallel and present similar activity in the preparation, initiation, and execution of the contralateral and bilateral movements. Furthermore, the left primary sensorimotor area (dominant hemisphere) appears to be activated more than the right primary sensorimotor area during the preparation and performance of the ipsilateral movements.     

Cyclotron production of carrier-free 66Ga as a positron emitting label of albumin colloids for clinical use

A method for producing carrier free ⁶⁶Ga (T_1/2:9.4h; ⁺) by ⁴He bombardment of natural copper targets is presented. ⁶⁶Ga is formed by means of the ⁶³Cu (⁴He, n) ⁶⁶Ga reaction. Production yields are given in the 17.5 to 8 MeV ⁴He energy range. Chemical purification of ⁶⁶Ga from the copper target is described. The only radionuclidic impurity found in the final product was ⁶⁷Ga. Albumin colloids from commercially available kits designed for use with ^99mTc could easily be labeled with ⁶⁶Ga and employed for studies of the lymphatic system by positron emission tomography.     

Histological score for cells with irregular nuclear contours for the diagnosis of reflux esophagitis in children

Histological criteria for the diagnosis of reflux esophagitis include basal zone hyperplasia, stromal papillae elongation, and inflammatory infiltrate. However, endoscopic esophageal biopsy specimens may include little or no lamina propria. Intraepithelial T lymphocytes, seen in hematoxylin and eosin-stained sections as cells with irregular nuclear contours (CINC), may have a higher density in children with esophagitis. We evaluated the diagnostic accuracy of a numerical score built up by grading the "classical" parameters and its correlation with CINC density in grasp biopsy specimens obtained from children undergoing esophagogastroduodenoscopy with and without esophagitis. We analyzed esophageal biopsy specimens from 349 children (median age, 5 years) subdivided in 4 groups according to the previous routine histology report: group 1, 144 children with esophagitis; group 2, 65 controls; group 3, 51 children with dubious esophagitis; and group 4, 75 children with esophagitis on endoscopy but a normal histology report. A numerical value was assigned to each parameter; the sum of these values represented the histological score. We also evaluated intraepithelial CINC density (ie, number of CINC per high-power field). We separately analyzed histological sections with and without lamina propria. For both total score and for CINC density, we calculated a cutoff using a receiver operating characteristic curve. Cutoffs of 6 for score and of 4 for CINC density provided the best sensitivity and specificity. Sensitivity of the histological score was better in biopsy specimens containing lamina propria (94%) than in those without lamina propria (4%). Sensitivity of CINC density was satisfactory in both specimens with (78%) and without (75%) lamina propria. Specificity was satisfactory for both parameters. In conclusion, when lamina propria was present in sections of endoscopic esophageal biopsy specimens, histological score provided a better diagnostic accuracy for the diagnosis of esophagitis. However, when no lamina propria was present, as was the case in 67% of our children, CINC density had better sensitivity. In addition, this latter parameter showed esophageal mucosa damage in 34% of previously dubious cases or cases with esophagitis at endoscopy but a previous routine histology report of normal mucosa.