Inherently fluorescent and porous zirconia colloids: preparation, characterization and drug adsorption studies.

Porous, fluorescent zirconia particles of nearly 380 nm diameter were prepared without template molecules or labeling dyes. The porous structure is the result of aggregation-induced particle formation. The inherent fluorescence is assigned to coordinatively unsaturated Zr4+ ions at the sol-gel derived ZrO2 surface. After physico-chemical characterization of the native zirconia particles carboxyl and/or amine bearing drug molecules (d,l-α-difluoromethylornithine - DFMO, ursolic acid - UA and doxorubicin - DOX) were adsorbed onto their surface, and the products were analyzed with Fourier-transform infrared spectroscopy (FTIR), thermogravimetry (TG), small-angle X-ray scattering (SAXS), fluorimetry and zeta potential vs. pH measurements. We have found that DOX complexes coordinatively unsaturated Zr4+ ions without dislocating them, while carboxyl-bearing drugs interact with basic surface Zr-OH sites eliminating some of the carbonate species. The adsorption of UA at the zirconia surface shifts considerably the isoelectric point of the surface and thus provides kinetic stability to the particles at physiological pH. An in vivo biodistribution study in two healthy dogs performed by SPECT/CT detection after 99mTc labeling of the nanocarriers has shown the possibility of drug delivery application.

Ovarian steroid cell tumor and a contralateral ovarian thecoma in a postmenopausal woman with severe hyperandrogenism.

A 49-year-old woman presented with rapidly progressing hirsutism, receding hairline, male-pattern baldness and deepening of voice, which had developed over the past 2 years. Hormonal evaluation showed a markedly elevated serum testosterone level (418 ng/dl) and no evidence of increased production of cortisol, dehydroepiandrosterone, dehydroepiadrosterone-sulfate, androstenedione, or 17-hydroxyprogesterone. Transvaginal ultrasound examination suggested the presence of a small mass within the left ovary, but all other radiological studies, including adrenal and ovarian computed tomography, magnetic resonance imaging, radio-labelled cholesterol scintigraphy and positron emission tomography, were negative. Subsequently, bilateral selective venous sampling showed a marked testosterone gradient in the right ovarian vein. Bilateral salpingo-oophorectomy was performed (the patient had had a previous vaginal hysterectomy), and histopathological examination revealed a 10-mm steroid cell tumor within the right ovary and a 15-mm thecal cell tumor within the left ovary. The postoperative serum testosterone level returned to normal and the patient showed a slow regression of clinical symptoms. The simultaneous occurrence of a virilizing ovarian steroid cell tumor and an apparently non-functioning thecoma within the contralateral ovary emphasizes the potential pitfalls that may exist in the preoperative evaluation of patients with markedly increased testosterone production.

[New intraoperative diagnostic methods in parathyroid surgery: intraoperative measurement of parathyroid hormone]. / Mútét alatti új diagnosztikus módszerek a mellékpajzsmirigy-sebészetben: intraoperatív parathormonszint-ellenórzés.

In thirty-seven patients undergoing parathyroidectomy from November 1999 to July 2000 with diagnosis of primary hyperparathyroidism the intraoperative intact parathyroid hormone level were studied. Preoperative samples of blood were taken from a peripheral vein before the beginning the operation. The second sample was taken 5 minutes after removal of parathyroid adenoma. The plasma intact parathyroid hormone concentration was measured by quick IRMA method. The preoperative high PTH levels reduced after excision of adenoma to the mean 18%. 33 patients had normal PTH levels after 5 minutes of removing. The total measuring time of quick PTH assay was about 30 minutes. The QPTH assay was a quantitative adjunct for the surgeon to ensure a successful parathyroidectomy. When the intraoperative QPTH level is not reduced to 50%, then the exploration should be continued and the probability of reoperation is decreased. They propose the application of the routine intraoperative measurement of QPTH level in all parathyroidectomy.

Angiography effectively supports the diagnosis of hepatic metastases in medullary thyroid carcinoma.

BACKGROUND: Medullary thyroid carcinoma (MTC) belongs in the group of neuroendocrine tumors with early lymphatic and hepatic dissemination. A high rate of undetectable metastases is hypothesized to be responsible for the frequent mismatch between the apparent relatively small tumor burden and the elevated plasma tumor marker level. METHODS: Thirty-six MTC patients with residual/recurrent biochemical signs (elevated basal calcitonin level) and/or characteristic general symptoms (diarrhea and/or flushing) were systematically examined by conventional radiology, whole-body 18F-deoxyglucose positron emission tomography (PET), dynamic liver computed tomography and magnetic resonance imaging, and hepatic angiography. RESULTS: Conventional diagnostic imaging revealed lymph node (LN) involvement in the cervical, mediastinal, supraclavicular, and axillary regions (16 cases), and multiple pulmonary (3 cases), bony (1 solitary and 1 multiple case), and breast (1 case) metastases. (18)F-deoxyglucose PET identified all these extralymphatic metastatic lesions (except 2 cases with multiple pulmonary metastases), and also supradiaphragmatic LN involvement in 34 (94%) patients. In 32 (89%) cases, multiple small (generally < or = 1 cm) hypervascular, hepatic metastases undetectable by other imaging methods were localized angiographically. Of the 23 original pathologic specimens investigated, 18 (78%) exhibited LN involvement. The smallest primary tumor in patients with hepatic metastases was 1 cm. CONCLUSIONS: Hepatic angiography is recommended for primary staging in MTC patients with a primary tumor measuring 1 cm or larger, and/or pathologically proven LN involvement, and also during restaging for suspected recurrences to avoid unnecessary extensive surgical LN dissection in the neck and mediastinum.

Primary hepatic carcinoid in a renal transplant patient.

There seems to be a world-wide increase in the incidence of tumors among immunosuppressed patients. Of 1350 renal allografts transplanted in the past 23 years at the Department of Transplantation and Surgery, 56 cases were malignant tumors. The case of a 58-year-old female patient is reported, with disseminated primary carcinoid in the liver detected 86 days after renal transplantation. According to the literature only 39 patients with primary liver carcinoids have been reported until 1997, but this is the first where the carcinoid developed in an immunosuppressed patient. The rapid progression of the carcinoid could be associated with the immunosuppression.

[Multiple endocrine neoplasia-type medullary thyroid carcinoma in three generations of a family]. / Multiplex endokrin neoplasia típusú medullaris pajzsmirigy-carcinoma egy család három generációjában.

The familial accumulation of a multiple endocrine neoplasia (MEN) type 2a medullary thyroid carcinoma, is described based on the retrospective analysis of a family history. The proband was characterized by medullary carcinoma (MC) combined with phaeochromocytoma, her child had been shown to suffer from MC. In the third generation of the family C-cell hyperplasia and bilateral adrenal hyperplasia occurred. It is shown that in order to arrive at a correct decision as regards the therapy to be used, modern laboratory tests (serum calcitonin, CEA-analysis) and diagnostic imaging methods (ultrasound, computer tomography, magnetic resonance imaging, positron emission tomography, metaiodobenzylguanidine scintigraphy) should be used. It is emphasized that the available therapeutic means (surgery, radiotherapy, nuclear medicine) have to be carefully selected and, if necessary, combined. In medullary thyroid carcinoma associated tumours in other endocrine organs should be expected to occur. Family screening using blood chemical and genetic tests are recommended in asymptomatic cases, since their surgical treatment can in this way lead to complete recovery.

Evaluation of the state of health of living related kidney transplantation donors.

Renal transplantation is the optimal mode of therapy for patients with end-stage renal disease; the results are even better with living related donors. This procedure, therefore, favours the recipients, but what are the consequences for the donor? At our Department, between 1973 and 1996, 1325 kidney transplantations were performed, 78 from living, related donors (5.89%). We decided to follow up these patients and investigate the function of the remaining kidney and also their current general health status. Thirty donors (38.4%) were investigated. Of these, 25 of had normal blood pressure and 5 were hypertensive, needing antihypertensive treatment. The average age was higher in the hypertensive group (60.2/53.25 years). The time interval since transplantation was longer in the hypertensive group than in the normal one. We carried out a scintigraphy of the kidney with Tc-99mMAG-3. The mean value of the glomerular filtration rate calculated from the MAG clearance was 98.1 ml/min and this value is higher than half of the normal isotope clearance value, i.e. higher then the expected value for a single kidney. We conclude that no impairment of renal function is observed in the living, related kidney donors. In 16.66% a mild hypertension developed. With isotope investigation we found hypertrophy of the remaining kidney. Thus, after a correct preoperative assessment, unilateral nephrectomy has no long-term consequences in healthy donors.

Investigation of effect of lesser curvature seromyotomy of the stomach in animal experiments.

The effectiveness of seromyotomy of the lesser curvature of the stomach--the simplified version of proximal selective vagotomy--was investigated in eleven dogs. Decreased acid secretion was proved with congo red test and pH measuring by glass electrode. No significant damage to the motor function of the stomach was found with scintigraphy. Histological examinations revealed neurofibre degeneration peripherally to the seromyotomy line after peripheral vagotomy and vacuolar degeneration in the ganglion cells and amputation neuromas in the seromyotomy line.

SPECT and TCD studies in cluster headache patients.

We investigated regional cerebral blood flow (rCBF) with Tc99m-HMPAO single photon emission computed tomography (SPECT) and blood flow velocity in the middle cerebral artery (MCA) with transcranial Doppler (TCD) ultrasound. Nineteen cluster headache patients participated in the study, 9 of them underwent both examinations, whereas in 6 patients only SPECT and in 4 patients only TCD was performed. Patients were examined during spontaneous and/or provoked attacks and when symptom-free in a cluster period. Six patients showed moderate frontal hyperperfusion, 2 had frontal hypoperfusion whereas no change from headache-free rCBF occurred in 7 patients. Statistical analysis of MCA velocities in 13 patients showed a significant decrease in the mean flow velocity compared with the headache-free values on the symptomatic side. Our findings suggest that the alteration of cerebral circulation during cluster attacks might be of secondary nature.

In vitro and in vivo motility studies of 99mTc HM-PAO labelled sperm cells.

The motility of 99mTc HM-PAO radiolabelled sperm cells, labelled as described previously (Balogh et al., 1992) was studied. The active migration of spermatozoa was demonstrated in capillary tubes containing bovine oestrous mucus, using an in vitro motility analyzer. Like nonlabelled sperm cells, the labelled spermatozoa covered a 4-5 cm distance in the capillary tubes during a 10-min run. In vitro motility testing of labelled spermatozoa from different animal species (cattle, rabbit, sheep, horse) did not reveal significant differences. The distribution of spermatozoa within the female genital tract was studied in a previously described animal model (rabbit) and in two new models (sheep, chicken). This method enables the determination and visualization of sperm distribution by a noninvasive technique. The results of in vivo motility tests pave the way for the introduction of a method of unprecedented specificity, which serves for studying the penetrability of the oviduct to spermatozoa.

[The effect of lesser curve seromyotomy of the stomach in animal experiments]. / A gyomron végzett kisgörbületi seromyotomia hatásának vizsgálata állatkísérletekben.

The authors investigated the efficiency of the seromyotomy of the lesser curvature of the stomach in 11 dogs. Reduction of the acid production was verified by glass electrode pH measuring of the gastric mucosa. Scintigraphic examination showed that the operation did not damage the motor function (motility) of the stomach. The fact of peripheral vagotomy was established by histological examination: degeneration of nerve fibres was detected on the peripheral side of the line of the seromyotomy, vacuolar degeneration was found in the cells of parasympathetic ganglions, and amputation neurinomas were shown in the line of the seromyotomy.

[Determination of cyclosporin concentration in blood by radioimmunoassay]. / Cyclosporin koncentráció meghatározása vérböl radioimmunoassay-vel.

Cyclosporin A treatment is unimaginable without continuous and periodical monitoring of the blood cyclosporin concentration. One of the best methods for measuring is the radioimmunoassay, because this method makes possible the monitoring of a large number of samples with good sensitivity. The method is suitable for measuring either only the cyclosporin A concentration (specific monoclonal antibody) or the cyclosporin A and its metabolites (nonspecific monoclonal antibody). The use of 125I labelled tracer has several advantages such as increased sensitivity, fast sample counting and so fast measuring of the concentrations.

[Scintigraphy of the adrenergic nervous system]. / A sympathicoadrenalis rendszer scintigraphiás vizsgálata.

The authors describe their experiences with 100 MIBG scintigraphies. The importance of the examination is stressed in the diagnostics of neuroblastoma in childhood, the determination of the clinical stage and follow-up of the disease. MIBG scintigraphy plays a primary role among the imaging examination procedures aimed at the localization of pheochromocytoma especially in the extra-adrenal, multiplex and malignant diseases. The disturbance of adrenergic innervation in Shy-Drager syndrome is demonstrable with radiopharmacon.