Multiparametric imaging guided HDR interventional radiotherapy (brachytherapy) boost in localized prostate cancer: a multidisciplinary experience.

OBJECTIVE: The aim of this study was to report a monoinstitutional multidisciplinary experience about the use of multiparametric imaging to identify the areas with higher risk of relapse in localized prostate cancer, with the purpose of allowing a biologically planned target dose escalation. PATIENTS AND METHODS: We performed a retrospective evaluation of patients diagnosed with prostate cancer who received treatments at our Interventional Oncology Center with interstitial interventional radiotherapy from 2014 to 2022. Inclusion criteria were histologically confirmed localized prostate cancer; and National Comprehensive Cancer Network (NCCN) risk class unfavorable intermediate or high/very high risk. The diagnostic work-up included multiparametric Magnetic resonance imaging (MRI), multiparametric Transrectal ultrasound (TRUS), Positron Emission Tomography Computed Tomography (PET-CT) with choline or PSMA (or alternatively bone scan). All patients were assessed and received one treatment with interstitial high-dose-rate interventional radiotherapy (brachytherapy) delivering external beam radiotherapy (46 Gy). All procedures were performed using transrectal ultrasound guidance under general anesthesia and the prescribed doses were 10 Gy to the whole prostate, 12 Gy to the peripheral zone and 15 Gy to the areas at risk. RESULTS: We report the data of 21 patients who were considered for the statistical analysis with a mean age of 62.5 years. The mean PSA nadir was 0.03 ng/ml (range 0-0.09). So far, no biochemical nor radiological recurrences have been recorded in our series. Regarding acute toxicity, the most commonly reported side effects were G1 urinary in 28.5% of patients and G2 urinary in 9.5%; all recorded acute toxicities resolved spontaneously. CONCLUSIONS: We present a real-life experience of biologically planned local dose escalation by interventional radiotherapy (brachytherapy) boost, followed by external beam radiotherapy in patients with intermediate unfavorable- or high/very high risk. The local control and the biochemical control rates are proved to be excellent and the toxicity profile tolerable.

Layer-specific activity of tissue non-specific alkaline phosphatase in the human neocortex.

The ectoenzyme tissue non-specific alkaline phosphatase (TNAP) is mostly known for its role in bone mineralization. However, in the severe form of hypophosphatasia, TNAP deficiency also results in epileptic seizures, suggesting a role of this enzyme in brain functions. Accordingly, TNAP activity was shown in the neuropil of the cerebral cortex in diverse mammalian species. However in spite of its clinical significance, the neuronal localization of TNAP has not been investigated in the human brain. By using enzyme histochemistry, we found an unprecedented pattern of TNAP activity appearing as an uninterrupted layer across diverse occipital-, frontal- and temporal lobe areas of the human cerebral cortex. This marked TNAP-active band was localized infragranulary in layer 5 as defined by quantitative comparisons on parallel sections stained by various techniques to reveal the laminar pattern. On the contrary, TNAP activity was localized in layer 4 of the primary visual and somatosensory cortices, which is consistent with earlier observations on other species. This result suggests that the expression of TNAP in the thalamo-recipient granular layer is an evolutionary conserved feature of the sensory cortex. The observations of the present study also suggest that diverse neurocognitive functions share a common cerebral cortical mechanism depending on TNAP activity in layer 5. In summary, the present data point on the distinctive role of layer 5 in cortical computation and neurological disorders caused by TNAP dysfunctions in the human brain.

In vitro interaction of the truffle Terfezia terfezioides with Robinia pseudoacacia and Helianthemum ovatum.

The type of the in vitro root interactions of Terfezia terfezioides with the plants Robinia pseudoacacia and Helianthemum ovatum was investigated including detailed anatomical and ultrastructural characterization. No difference in growth was detected at different phosphate concentrations on agar synthetic medium between the inoculated and control plants during a short-time cultivation. The fungal colonization of the roots increased with higher phosphate level in both plant species, but was always lower in R. pseudoacacia roots. Septate hyphae formed frequently intracellular branched coils in dead cortical cells. In H. ovatum intercellular hyphae were observed forming finger-like structures reminiscent of Hartig-net structures in ectomycorrhizae. A loose hyphal envelope covered the root surface of both colonized and noncolonized roots. The features resembled similar structures described earlier during the mycorrhizae of different Terfezia species. Our detailed anatomical and ultrastructural study shows that the in vitro root interactions of the T. terfezioides cannot be considered unambiguously as mycorrhiza.

Effects of glucagon and insulin on plasma glucose, triglyceride, and triglyceride-rich lipoprotein concentrations in laying hens fed diets containing different types of fats.

The influence of dietary fat supplementations differing in the ratio of n-6 to n-3 polyunsaturated fatty acids (PUFA) on the effects of glucagon and insulin on plasma glucose, triglyceride (TG), and TG-rich lipoprotein concentrations was investigated in laying hens. Birds were fed either a low-fat control diet (LF) or diets supplemented with 4% pumpkin seed oil (PO; rich in n-6 PUFA) or 4% cod liver oil (CO; rich in n-3 PUFA). After 4 wk feeding of the experimental diets, hens were implanted with wing vein catheters and injected with porcine glucagon (20 microg/kg BW) and porcine insulin (0.5 IU/kg BW), 2 to 5 h after oviposition. Plasma glucose, TG, and TG-rich lipoprotein concentrations were determined from 10 min pre-injection to 60 min post-injection. PO diet resulted in a prolonged plasma glucose response to glucagon administration and altered hypoglycemic response to insulin. However, CO diet did not influence plasma glucose response to either glucagon or insulin administration compared to LF diet. The effects of glucagon and insulin on plasma TG and TG-rich lipoproteins were similar for all diets regardless of the amount or type of fat. The results suggest that feeding dietary fats with high n-6 to n-3 PUFA ratio alters the glucagon and insulin sensitivity of plasma glucose in laying hens. Fats rich in n-3 PUFA seem to have no influence on the plasma glucose response to glucagon and insulin.

Beta-CIT SPECT demonstrates reduced availability of serotonin transporters in patients with Fatal Familial Insomnia.

Fatal familial insomnia (FFI) is a rare hereditary human prion disease with unique clinical features including progressive sleep impairment and autonomic dysfunction. The serotonergic system is considered to be involved in the regulation of the sleep-wake cycle. In this study we demonstrate a reduced availability of serotonin transporters of 57% and 73% respectively in a thalamus-hypothalamus region of two FFI patients examined with beta-CIT SPECT as compared to age-expected control values.

Studies on the root associations of the truffle Terfezia terfezioides.

The paper contains an overview of the results of the studies made on the truffle Terfezia terfezioides, particularly the investigations related to the associations of this fungus with plants. Twelve plant species originated from a natural habitat of the fungus were supposed to be connected with T. terfezioides based on the anatomy of the endogenous fungal structures in their roots. Aseptic experiments were carried out on modified MMN substrates with different phosphate concentrations to study the interaction of T. terfezioides with Robinia pseudoacacia and Helianthemum ovatum. The colonization of the roots of black locust was always weaker than that of Helianthemum. The main characteristics were the intracellular coiled, branched, frequently septated hyphae in dead root cells. The intercellular hyphae formed Hartig-net with finger like structures only in Helianthemum, the interactions could not be considered unambiguously as mycorrhizae. There was no difference between the RFLP profiles of the nr DNA ITS of nineteen fruit bodies collected at the same time from the habitat and the ITS of three randomly chosen specimens were identical on sequence level, too. These invariability makes to design species specific PCR primers possible to check unambiguously the host plants.

Prostate preservation by combined external beam and HDR brachytherapy in nodal negative prostate cancer.

PURPOSE: The combined external beam- and high-dose rate brachytherapy (HDR-BT) of localized prostate cancer was introduced at Kiel University in 1986. The aim of this intermediate analysis was to judge the Kiel method of localized prostate cancer radiation treatment after ten years experience. PATIENTS AND METHODS: In the past ten years 174 patients with histological proven localized prostate cancer were subjected to combined tele-/HDR-brachytherapy. Local staging in all of the cases by transrectal ultrasound, nodal staging in the majority of the cases by CT or MRI. Average age of the patients was 68.2 years (44-84). According to AJCC/UICC staging T1B, T2, T3 was found in 2, 113 and 59 cases, respectively. Highly differentiated tumors (G1) were found in 27, moderately differentiated (G2) in 87, poorly differentiated (G3) in 60 cases. The mean follow-up was 47.1 months with the median of 51.7 months. Total prescribed dose 50 Gy on the small pelvis and 70 Gy on the prostate capsule due to the integration of two, 15 Gy each, HDR-brachytherapy fractions in 6 weeks. RESULTS: Ten patients died of prostate cancer and 18 of intercurrent diseases resulting in a 5 years overall survival rate of 83% and tumor specific survival rate of 94%. Twenty-one patients showed a clinical progression, of these 14 systemic, 5 local and 2 both systemic and local. Additional 16 patients had PSA elevation only. The 5-years biochemical and/or clinical progression-free survival in the cohort was 79% and 73% for the T3 tumors. Side effects were 27 cases of proctitis/colitis and 20 cases of dysuria/cystitis. CONCLUSION: The integrated HDR-BT combined with external beam radiation treatment is a method with excellent tumor control rates at five years superior to those of external beam treatment alone or external beam combined with iodine-125 implants. This form of radiotherapy would appear to be particularly well-suited to treatment of advanced localized (T3) tumors.

Multi-unit recording from regenerated bullfrog eighth nerve using implantable silicon-substrate microelectrodes.

Multi-microelectrode silicon devices were developed for extracellular recording from multiple axons in regenerated eighth cranial nerves of American bullfrogs. Each includes a photolithographically defined array of holes and adjacent metal microelectrodes. A device is implanted within a transected eighth nerve; regenerating fibers grow through the holes en route to the brainstem. Multiple spike trains were recorded from two animals at up to 21 weeks after implantation. Single units were tracked for over 8 h. Some responded to sound with tuning typical of fibers innervating the amphibian and basilar papillae. Units of vestibular origin also were recorded. Action potentials were 30-140 microV P-P amid noise of 5 10 microV RMS, an adequate signal-to-noise ratio for spike detection and sorting. Histology confirmed that bundles of myelinated fibers grew through holes near electrodes that recorded activity. The implantation success rate was low, due to surgical morbidity, device extrusion, and lack of nerve regeneration through some devices. Future designs will address these issues and incorporate transistor amplifiers on devices to increase signal-to-noise ratios. The potential of implanted silicon devices to simultaneously record from many axons offers an opportunity for multicellular studies of auditor, vestibular and seismic signal processing in the vertebrate inner ear.

[Study of the cost-effectiveness of sequential antibiotic (ciprofloxacin) therapy]. / Szekvenciális antibiotikum (ciprofloxacin) terápia hatékonyságának és költségének összevetése.

A multicenter, prospective, randomized study was performed to compare the cost-effectiveness of parenteral antibiotic versus parenteral antibiotic + oral ciprofloxacin sequential therapy in the treatment of moderate and severe infections in hospitalized patients. After deciding on inclusion (n = 298), the patients were randomly allocated in group "A" (evaluable 120 cases) receiving only parenteral antibiotics, or in group "B" receiving parenteral antibiotic + oral ciprofloxacin from the 3.-5. day of therapy on. The local physician decided on the starting parenteral therapy and the necessity of other therapeutic interventions, and in case of group "B" patients on the possibility of switching parenteral to oral therapy. The overall cure rate was 68% in group "A" and 82% in group "B" (improved 33 and 21, failure 5 and 1 cases resp.). Of the direct costs in patients, care, the costs of antibiotic treatments based on purchase prices was compared: the cost of antibiotic treatment in group "B" was 32% less than in group "A", and the sequential therapy saved 9000 Ft/patient in average. In conclusion, ciprofloxacin proved to be an effective antimicrobial agent that can also be used in sequential therapy and the oral administration resulted in a significant save of money with the same therapeutic effectiveness.

A feedback controlled silicon microprobe for quantitative mechanical stimulation of nerve and tissue.

The ability to apply and control the force and force velocity of mechanical stimulation is essential for the study of mechanoelectric transduction and adaptation processes. Silicon micromachining technology was used to produce miniature (20-70 microns wide) mechanical microprobes. Passive polysilicon, piezoresistive, force sensing elements were deposited onto the boron-doped epitaxial silicon and the individual devices were chemically etched from the bulk wafer. These microprobes display a linear force versus output voltage relationship. Stimulation forces up to 2 mN can be generated with a measurement resolution of 1.5 microN. The probes were mounted onto circuit board holders and their output sent to a proportional-integral controller which drives an electromagnetic actuator. By using this force-feedback control circuit coupled to a PC it is possible to define any stimulus wave form pattern and independently control and measure the actual stimulus force and velocity. A computer controlled 3-axis stepper motor (0.025 micron step capability) manipulator is used to position the silicon microprobe-actuator assembly relative to the mechanoreceptive field. Sensor feedback control coupled to the 3-axis stepper motor manipulator allows automatic touchdown control and/or preloading of the probe prior to stimulation. Three-dimensional topographic manipulator feedback position control allows automated receptive field mapping.

[Effect of recombinant human erythropoietin on autologous blood donation for heart surgery]. / A rekombináns humán erythropoetin hatása a preoperatív autológ vérgyüjtésre szívmütétek kapcsán.

Pharmacological stimulation of erythropoiesis was studied in patients selected for open heart surgery, and undergoing a programme of autologous blood predonation prior to surgery. Sixteen patients (group I: ery) received 4000 I. U. of recombinant human erythropoietin (r-huepo) subcutaneously weekly three times during a 3-week period preoperatively, another group of 21 patients (group II: control) were not given r-huepo. Patients in both groups received orally 2 x 80 mg iron daily. Predonation of five units of blood was planned in each patients, beginning on the 21. preoperative day; no blood was taken from patients if the hematocrit dropped below 0.34, or if any other complications occurred. The average amount of blood taken from patients in the ery group was 4.8 +/- 0.4 Units, and in the control group: 3.7 +/- 1.1 Units. In the ery group the planned 5 Units of blood could be taken from 13/16 patients, while in the controls only from 7/21. The differences are statistically significant. Reticulocyte counts were significantly higher consecutively during the preoperative period in the ery group than in the controls. In the postoperative period erythropoiesis was less pronounced in the ery group than in the controls. It is concluded that 1. r-huepo is an effective drug in preventing (or reducing) the anaemia due to repeated preoperative blood withdrawals, and thus larger amounts of autologous blood will be available for predonation. 2. More pronounced decrease of circulating reticulocytes observed in the postoperative period points to a possible suppression of endogenous erythropoietin production in the ery group.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of cocaine on the contents of neurohypophyseal hormones in the plasma and in different brain structures in rats.

The effects of acute and chronic cocaine treatments on the levels of the neurohypophyseal hormones oxytocin (OXT) and vasopressin (AVP) in the plasma and in different brain structures in rats were measured by radioimmunoassay (RIA). Acute cocaine treatment had no effect on the level of OXT in the plasma or in the amygdala, but increased OXT contents were measured in the hypothalamus and in the hippocampus. The OXT levels in the basal forebrain structures (including the septum and the nucleus accumbens) were decreased by a single dose of cocaine. The acute injection of cocaine increased the level of AVP in the plasma, and decreased contents of OXT were measured in the amygdala and in the basal forebrain. Repeated treatment with cocaine decreased the level of OXT in the plasma, hypothalamus and hippocampus. The AVP contents were decreased in all of the brain structures investigated, but no change was caused in the plasma level of AVP by repeated injections of cocaine. These results demonstrate complex, region-specific interactions between cocaine and the neurohypophyseal hormones in the brain and in the periphery underlying the alteration in behavioral and autonomic functions caused by acute and chronic cocaine exposure.

Antipyretic effect of central arginine8-vasopressin treatment: V1 receptors specifically involved?

Intracerebroventricular (i.c.v.) administration of the neurohypophyseal neuropeptide arginine8-vasopressin (AVP) results in a dose-dependent attenuation of endotoxin-induced fever (EIF) in rats. Specific antagonists of the neuropeptided(CH2)5[Tyr(Me)2]AVP for V1 receptors, d(CH2)5[dlle2lle4]AVP for the V2 receptors and Des-Gly,NH2d(CH2)5[Tyr)Me2)Thr4Orn8]vasotocin, an antagonist of the oxytocin receptors (AOXT), failed to modify EIF when administered i.c.v. Relatively high doses (100 ng) of all three peptide antagonists effectively blocked the antipyretic effect of AVP. Administered in smaller doses (10 or 30 ng), however, a more specific interaction was observed, i.e. the V1 antagonist being the only effective compound in preventing the effect of AVP. Although the data indicate that peptide-antagonist interactions should be interpreted carefully, the present experiments confirm previous observations on the involvement of V1-type receptors in the antipyretic action of AVP and suggest additional interactions with V2 vasopressinergic and oxytocinergic receptors.

Hypothalamus and puberty.

The effect of a transitory increase in plasma FSH and LH levels during the prepubertal period on puberty has been investigated. Twenty-day-old rats had been bilaterally ovariectomized and 24 hr later they received two ovaries of infantile rats beneath the kidney capsule. These rats exhibited precocious puberty. Animals into which two additional ovaries had been transplanted first and the next day their own ovaries removed showed puberty at the same time as controls. Additional investigations provided evidence that the ovariectomized and ovary implanted rats plasma FSH and LH levels were in the control range four days after implantation. The findings support the assumption that the hypothalamic lesion-induced precocious puberty is due rather to a transitory enhanced release of gonadotropin releasing hormone by the lesion than to the destruction of sex-steroid sensitive structures inhibiting the release of gonadotropic hormones in prepubertal rats.

Effects of beta-endorphin2-9 on arginine-8-vasopressin and oxytocin levels in hypothalamic and limbic brain regions.

Immunoreactive arginine-8-vasopressin (AVP) and oxytocin (OXT) were measured in rat hypothalamic and limbic brain regions after the intracerebroventricular administration of beta-endorphin fragment 2-9 (beta E2-9). The peptide decreased the AVP content of the hippocampus and the OXT levels in the septum and amygdala. The present data favor the view that beta E2-9 interacts with limbic AVP- and OXT-systems.

The effect on brain 5-HT of central lysine-vasopressin administration into different cerebral ventricular compartments depends on the site of injection.

The influence of lysine-8-vasopressin (LVP) on the steady-state level of serotonin was studied in different brain regions four hours after microinjection into the lateral ventricle (icv) or cisterna magna (cm). LVP (200 pg) increased the serotonin (5-HT) level in the hypothalamus and mesencephalon after cm application, while icv administration caused an opposite tendency. The findings suggest that the site of peptide administration is of decisive importance in the mediation of various effects of LVP on the transmitter metabolism. A possible link exists between opposite effects of cm versus icv injection of LVP on central serotoninergic mechanisms, as well as on behavioral and autonomic correlates of these treatment.