Counting primes, groups, and manifolds

Let Lambda=SL(2)(Z) be the modular group and let c(n)(Lambda) be the number of congruence subgroups of Lambda of index at most n. We prove that lim(n--> infinity )(log c(n)(Lambda)/((log n)(2)/log log n))=(3-2(sqrt)2)/4. The proof is based on the Bombieri-Vinogradov "Riemann hypothesis on the average" and on the solution of a new type of extremal problem in combinatorial number theory. Similar surprisingly sharp estimates are obtained for the subgroup growth of lattices in higher rank semisimple Lie groups. If G is such a Lie group and Gamma is an irreducible lattice of G it turns out that the subgroup growth of Gamma is independent of the lattice and depends only on the Lie type of the direct factors of G. It can be calculated easily from the root system. The most general case of this result relies on the Generalized Riemann Hypothesis, but many special cases are unconditional. The proofs use techniques from number theory, algebraic groups, finite group theory, and combinatorics.     

Spinal epidural hematoma occurrence in the absence of known risk factors: a case series

Spinal epidural hematoma in the absence of coagulopathy or anticoagulation therapy is an extremely rare occurrence, with a reported incidence of less than 1 in 1 million. We present seven cases of documented epidural hematoma in the absence of coagulopathy or anticoagulation therapy to alert the clinician to consider spinal or epidural hematoma when suspicious signs and symptoms are present after neuraxial block in the absence of coagulopathy or anticoagulation therapy. The need for immediate diagnosis and therapy is emphasized as the only potential for meaningful recovery.     

Hepatitis B vaccination in prison with a 3-week schedule is more efficient than the standard 6-month schedule

A randomized study of injecting drug users in a Danish prison comparing vaccination at 0, 1 and 3 weeks with the 0, 1 and 6 months schedule (20microg Engerix B i.m.) was conducted. Due to a low participation rate, a second nonrandomized study was conducted in Estonia where all prisoners were vaccinated with the short schedule. In the randomized study, the compliance with three doses was 63% (12/19) in the 3-week schedule compared to 20% (3/15) in the 6-month schedule (P = 0.017). In the nonrandomized study, the compliance was 81% (457/566) and the seroprotection rate at month 7 was 67% (97/145), resulting in protection of 54% of the population at risk. This was significantly higher than the estimated 34-42% protection that would have been achieved with the 6-month schedule.     

Healing of gastric mucosal erosions induced by indomethacin and restoration of glucocorticoids levels in the blood of rats

The study was made of the effects of low production of glucoorticoids and subsequent replacement with these hormones on healing of hemorrhagic erosions of rat gastric mucosa emerging 4 hours after administration of indomethacin (25 mg/kg percutaneously). Corticosteroid deficiency was produced by adrenalectomy or blocking function of the hypothalamo-hypophyseo-adrenocortical system by introduction of supraphysiological dose of hydrocortisone i week before indomethacin administration. Replacement therapy was conducted 4 hours after indomethacine administration by subcutaneous injection of corticosterone in a dose of 4 mg/kg. Healing was evaluated by changes in the area of damaged surface of gastric mucosa for 2 days after indomethacin administration. Plasma levels of corticosteroids were controlled. It was found that animals with corticosteroid deficiency had a larger area of mucosal lesion and slow healing vs control rats. Administration of corticosterone in physiological dose to animals with deficient production of corticosteroids stimulated healing of gastric mucosa erosions.     

Steady-state blood volume measurements in experimental tumors with different angiogenic burdens a study in mice

PURPOSE: To experimentally validate the effectiveness of magnetic resonance (MR) imaging enhanced with long-circulating iron oxide for measurement of vascular volume fractions (VVFs) as indicators of angiogenesis in different experimental tumor models. MATERIALS AND METHODS: Tumors with differing degrees of angiogenesis-9L rodent gliosarcoma, DU4475 human mammary adenocarcinoma, HT1080 human fibrosarcoma, and EOMA hemangioendothelioma--were implanted in nude mice. Tumoral VVFs were measured at submillimeter voxel resolutions by using 1.5-T MR imaging. A technetium-labeled intravascular radiotracer was injected into a subset of the animals to validate the MR imaging measurements. Microvessel density and vascular endothelial growth factor (VEGF) also were measured. Statistical analysis was performed with analysis of variance. RESULTS: High-resolution multisection MR maps of tumor blood volume were obtained in all tumor models. Mean tumoral VVF differed significantly among the different tumors: 2.1% +/- 0.3 (standard error of mean) for 9L gliosarcoma, 3.1% +/- 0.4 for DU4475 mammary adenocarcinoma, 5.5% +/- 0.8 for HT1080 fibrosarcoma, and 6.6% +/- 0.9 for EOMA hemangioendothelioma (P <.01). There was a strong correlation between the MR imaging and radiotracer measurements. There was considerable intra- and intertumoral heterogeneity among the VVFs. MR imaging measurements were in accordance with conventional measurements of angiogenesis, such as microvessel density count and VEGF. CONCLUSION: Measurements of tumoral VVF at high-resolution MR imaging with long-circulating iron oxide are feasible and correlate with angiogenic burden in experimental tumor models.     

Follow-up results of surgical correction of ocular ischemic syndrome

The influence of surgeries in the carotid arteries produced on the visual functions and ocular blood circulation was studied in patients with ocular ischemic syndrome (OIS) during the remote postoperative period. A total of 180 patients with OIS (including 104 patients with an acute OIS clinical course and 76 patients with primary chronic clinical course) and with a pronounced stenosis of the carotid arteries were examined preoperatively and postoperatively within 1 or 2 years. A reliably improved visual acuity (preoperatively -0.37 +/- 0.05; and postoperatively -0.52 +/- 0.07; p < 0.01), positive dynamics in the electric sensitivity threshold and in a lability of the optic nerve were observed in patients with the acute OIS clinical course after reconstructive surgeries in the carotid arteries. An increase in contrast sensitivity of the visual analyzer was detected in 28.8% of patients with the acute clinical course and in 10.5% of patients with the chronic OIS clinical course. An improved blood circulation through the ocular artery was stated in patients of both groups. Reconstructive surgeries in the carotid arteries are most effective in correcting the acute OIS clinical variation.     

Role of 24-hour monitoring in assessing blood pressure changes in polycystic ovary syndrome

INTRODUCTION: Polycystic ovary syndrome (PCOS) is associated with higher risk of developing cardiovascular diseases including higher incidence of hypertension later in life. Absence of circadian blood pressure fluctuations is considered as a marker of pre-hypertensive state and correlates highly with target organ damage in hypertension. AIM: Characterization of the circadian blood pressure rhythms as well as comparison of the results from the clinical measurements and Holter-monitored blood pressure data in women with PCOS. MATERIALS AND METHODS: The study comprised 35 women (mean age 22.6 +/- 5.9 years, mean BMI 31.4 +/- 7.1 kg/m2) with proven diagnosis. 24-hour ambulatory Holter-monitoring using Oscar device (Sun Tech Medical Instruments, USA) was performed in parallel with clinical measurements of blood pressure. RESULTS: There were 25.7% of the subjects diagnosed with hypertension according to the criteria of ambulatory monitoring observing discrepancy with the criteria for normal clinically measured blood pressure in 7 cases (20%). The "white coat" effect was observed in 11.4%. Physiological nocturnal drop in the systolic pressure was not observed in 51.4% of the patients and in the diastolic pressure - in 22.9% of the cases. CONCLUSIONS: The results confirm the advantages and the importance of the 24-hour monitoring as a diagnostic and predictive method for assessment of blood pressure alterations even in the absence of overt hypertension. PCOS is characterized by higher incidence of unstable blood pressure that is an additional risk factor for further development of cardiovascular diseases in this relatively young age group.     

Optical imaging of apoptosis as a biomarker of tumor response to chemotherapy

A rapid and accurate assessment of the antitumor efficacy of new therapeutic drugs could speed up drug discovery and improve clinical decision making. Based on the hypothesis that most effective antitumor agents induce apoptosis, we developed a near-infrared fluorescent (NIRF) annexin V to be used for optical sensing of tumor environments. To demonstrate probe specificity, we developed both an active (i.e., apoptosis-recognizing) and an inactive form of annexin V with very similar properties (to account for nonspecific tumor accumulation), and tested the agents in nude mice each bearing a cyclophosphamide (CPA) chemosensitive (LLC) and a chemoresistant LLC (CR-LLC). After injection with active annexin V, the tumor-annexin V ratio (TAR; tumor NIRF/background NIRF) for untreated mice was 1.22+/-0.34 for LLC and 1.43+/-0.53 for CR-LLC (n=4). The LLC of CPA-treated mice had significant elevations of TAR (2.56+/-0.29, P=.001, n=4), but only a moderate increase was obtained for the CR-LLC (TAR=1.89+/-0.19, P=.183). The in vivo measurements correlated well with terminal deoxyribosyl transferase-mediated dUTP nick end labeling indexes. When inactive Cy-annexin V was used, with or without CPA treatment and in both CCL and CR-CCL tumors, tumor NIRF values ranged from 0.91 to 1.17 (i.e., tumor were equal to background). We conclude that active Cy-annexin V and surface reflectance fluorescence imaging provide a nonradioactive, semiquantitative method of determining chemosensitivity in LLC xenografts. The method maybe used to image pharmacologic responses in other animal models and, potentially, may permit the clinical imaging of apoptosis with noninvasive or minimally invasive instrumentation.     

Recognition molecule associated carbohydrate inhibits postsynaptic GABA(B) receptors: a mechanism for homeostatic regulation of GABA release in perisomatic synapses

Extracellular matrix molecules are important cues in the shaping of nervous system structure and function. Here, we describe a novel mechanism by which the HNK-1 carbohydrate carried by recognition molecules regulates perisomatic inhibition in the hippocampus. Neutralization of HNK-1 activity by an HNK-1 antibody results in GABA(B) receptor-mediated activation of K(+) currents in CA1 pyramidal cells, which elevates extracellular K(+) concentration and reduces evoked GABA release in perisomatic inhibitory synapses. This mechanism is supported by pharmacological analysis in hippocampal slices and data showing that the HNK-1 carbohydrate binds to GABA(B) receptors and inhibits GABA(B) receptor-activated K(+) currents in a heterologous expression system. We suggest that the HNK-1 carbohydrate is involved in homeostatic regulation of GABA(A) receptor-mediated perisomatic inhibition by suppression of postsynaptic GABA(B) receptor activity.     

Blood flow in ocular vessels in 2 types of ocular ischemic syndrome

Ultrasonic triplex scanning of the orbit (gray scale two-dimensional ultrasonic examination, color Doppler mapping (CDM), and dopplerography) was carried out in 148 patients with ocular ischemic syndrome (OIS) aged 35-70 years, 104 of these with acute and 44 with primary chronic course. Signs of disordered bloodflow in the orbital and central retinal arteries were detected in patients with acute disease: 2-fold decreased maximum systolic bloodflow velocity, 5-fold decreased end diastolic bloodflow velocity, and 1.5 times increased resistance index in comparison with the norm. Chronic course of OIS was characterized by decreased maximum systolic velocity (by 1.5 times) and end diastolic bloodflow velocity (3-fold) in comparison with the norm in both arteries. Studies of ocular bloodflow by CDM timely detected angiological disorders in OIS and help define (in cooperation with angiosurgeon) the indications for angioreconstructive operations.