TUBULAR PROTEINURIA AFTER PERINATAL HYPOXIA

ABSTRACT. Milt7eacute;nyi, M., Pohlandt, F., Bóka, G. and Kun, E. (2nd Department of Paediatrics, Semmelweis University, Medical School, Budapest, Hungary, and the Section of Neonatology, Centre of Paediatrics, University of Ulm, Federal Republic of Germany). Tubular proteinuria after perinatal hypoxia. Acta Paediatr Scand, 70:399, 1981.–Urinary total protein (UTP) and urinary protein pattern have been studied in 23 newborn infants with Apgar scores ±S3 at one minute or acidosis (pH ±7.15) on the first day. On the first and second day UTP excretion was increased in 13 out of 18 patients. At this time the excretion of low molecular weight microproteins (T-4 and T-5) was elevated in 12 patients without increased plasma urea concentration in any case. The increased excretion of the smallest microproteins T-4/T-5 is an early sign of an impaired tubular function.     

A study into predictors for the speed of response to electroconvulsive therapy

The efficacy of electroconvulsive therapy (ECT) has been firmly established in the treatment of depression. However, prediction of the speed of response to ECT is an issue that needs to be further explored. This study aims to examine the presence of predictors for the speed of response. In a retrospective chart review using 57 patients suffering from major depression who received ECT, the relation of several patient and ECT variables with the speed of response was explored. Response was defined as a drop of at least 35% in Hamilton rating scale of depression (HRSD) score from baseline after 3 or 4 ECT sessions. Patients received ECT with an aged-based stimulus dosage in a clinical setting. Multiple regression analysis showed that high baseline HRSD score and high seizure energy index (SEI) were significantly and independently associated with a rapid response. In a regression model, baseline HRSD score and SEI can be used to predict the speed of response to ECT. Rapid responders to ECT achieved remission significantly more often than slow responders did. SEI can be modified by the clinician. This offers the possibility to optimize ECT treatment.     

A clinical evaluation of carbohydrate antigen 19-9 and carcinoembryonic antigen in patients with pancreatic carcinoma

We have studied serum carbohydrate antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA) in 221 persons to assess their usefulness in the diagnosis of pancreatic carcinoma. Although serum CA 19-9 and CEA in all healthy controls were within normal limits, the positive ratings of serum CA 19-9 and CEA in all benign disease were 9.8% and 18.1%, respectively. Sensitivity of serum CA 19-9 for pancreatic carcinoma was 70.5%, which was higher than that found in healthy controls, benign disease, and other malignant disease except biliary carcinoma; but sensitivity of serum CEA levels (67.7%) was not different from that seen in malignant disease. Three of 34 patients (8.8%) with pancreatic carcinoma who had a above-normal levels of serum CA 19-9 but not serum CEA were resectable. Although there was no correlation between serum CA 19-9 and CEA, advanced stages of pancreatic, gastric, and colorectal carcinoma tend to show high serum CA 19-9 and CEA, but no statistical differences were observed in relation to the stages of these carcinomas. Comparative studies of serum CA 19-9 and CEA for sensitivity and the predictive value of true positive and negative results for detecting pancreatic, gastric, and colorectal carcinoma showed that serum CA 19-9 has significantly higher sensitivity and predictive value of true positive results for pancreatic carcinoma than for gastric and colorectal carcinoma (P less than 0.05). However, serum CEA measurements did not show any difference between these carcinomas, and the highest predictive value of a true negative result for excluding pancreatic carcinoma was also observed in serum CA 19-9. These results indicate that although the CA 19-9 assay is not specific for pancreatic carcinoma, it is more useful adjunct method for diagnosing pancreatic carcinoma, possibly in resectable stages.     

Effects of maintenance electroconvulsive therapy on cognitive functions

SUMMARY: BACKGROUND: This study examined cognitive side effects of maintenance electroconvulsive (ECT) in comparison with maintenance pharmacotherapy after index ECT. METHOD: Clinical outcome data and neuropsychological measurements were compared in 11 maintenance ECT patients and 13 control patients treated with maintenance pharmacotherapy after index ECT. Data were gathered in a prospective naturalistic study during follow-up. RESULTS: There were no significant differences in patient characteristics and effects of index ECT between groups. In control patients treated with maintenance pharmacotherapy, cognitive function as well as depression ratings remained stable. During maintenance ECT neuropsychological test performance and depression ratings improved slightly but not significantly. CONCLUSIONS: Neuropsychological functioning during the maintenance phase of treatment did not differ between the two treatment groups. Cognitive function remained stable during maintenance ECT.     

A model of corrective gene transfer in X-linked ichthyosis

Single gene recessive genetic skin disorders offer attractive prototypes for the development of therapeutic cutaneous gene delivery. We have utilized X-linked ichthyosis (XLI), characterized by loss of function of the steroid sulfatase arylsulfatase C (STS), to develop a model of corrective gene delivery to human skin in vivo. A new retroviral expression vector was produced and utilized to effect STS gene transfer to primary keratinocytes from XLI patients. Transduction was associated with restoration of full-length STS protein expression as well as steroid sulfatase enzymatic activity in proportion to the number of proviral integrations in XLI cells. Transduced and uncorrected XLI keratinocytes, along with normal controls, were then grafted onto immunodeficient mice to regenerate full thickness human epidermis. Unmodified XLI keratinocytes regenerated a hyperkeratotic epidermis lacking STS expression with defective skin barrier function, effectively recapitulating the human disease in vivo. Transduced XLI keratinocytes from the same patients, however, regenerated epidermis histologically indistinguishable from that formed by keratinocytes from patients with normal skin. Transduced XLI epidermis demonstrated STS expression in vivo by immunostaining as well as a normalization of histologic appearance at 5 weeks post-grafting. In addition, transduced XLI epidermis demonstrated a return of barrier function parameters to normal. These findings demonstrate corrective gene delivery in human XLI patient skin tissue at both molecular and functional levels and provide a model of human cutaneous gene therapy.      

A monokine regulates colony-stimulating activity production by vascular endothelial cells

Human umbilical vein endothelial cells were cultured in supernatants of peripheral blood monocytes that had been cultured for 3 days with and without lactoferrin. Colony-stimulating activity (CSA) was measured in supernatants of the endothelial cell cultures and appropriate control cultures using normal, T-lymphocyte-depleted, phagocyte-depleted, low- density bone marrow cells in colony growth (CFU-GM) assays. Monocyte- conditioned medium contained a nondialyzable, heat labile factor that enhanced 4-15--fold the production of CSA by endothelial cells. The addition of lactoferrin to monocyte cultures reduced the activity of this monokine by 69%. Lactoferrin did not inhibit CSA production by monokine-stimulated endothelial cells. Therefore, vascular endothelial cells are potent sources of CSA, the production of CSA by these cells is regulated by a stimulatory monokine, and the production and/or release of the monokine is inhibited by lactoferrin, a neutrophil- derived putative feedback inhibitor of granulopoiesis. Inasmuch as a similar monokine is known to stimulate CSA production by fibroblasts and T lymphocytes, we suggest that mononuclear phagocytes play a pivotal role in the regulation of granulopoiesis by recruiting a variety of cell types to produce CSA.     

Laser confocal endomicroscopy as a novel technique for fluorescence diagnostic imaging of the oral cavity

Malignancies of the oral cavity are conventionally diagnosed by white light endoscopy, biopsy, and histopathology. However, it is often difficult to distinguish between benign and premalignant or early lesions. A laser confocal endomicroscope (LCE) offers noninvasive, in vivo surface and subsurface fluorescence imaging of tissue. We investigate the use of an LCE with a rigid probe for diagnostic imaging of the oral cavity. Fluorescein and 5-aminolevulinic acid (ALA) were used to carry out fluorescence imaging in vivo and on resected tissue samples of the oral cavity. In human subjects, ALA-induced protoporphyrin IX (PpIX) fluorescence images from the normal tongue were compared to images obtained from patients with squamous cell carcinoma (SCC) of the tongue. Using rat models, images from normal rat tongues were compared to those from carcinogen-induced models of SCC. Good structural images of the oral cavity were obtained using ALA and fluorescein, and morphological differences between normal and lesion tissue can be distinguished. The use of a pharmaceutical-grade solvent Pharmasolve enhanced the subsurface depth from which images can be obtained. Our initial results show that laser confocal fluorescence endomicroscopy has potential as a noninvasive optical imaging method for the diagnosis of oral cavity malignancies.