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Biomedical subjects

P Novak

Publications and source records attributed to P Novak.

At least 19 recordsLinked to original sources

Disproportionation, metal-insulator transition, and critical interaction strength in Na(1/2)CoO2.

Charge disproportionation (CD) and spin differentiation in Na(1/2)CoO2 are studied using the correlated band local-density approximation + Hubbard U (LDA+U) approach. The simultaneous CD and gap opening seen previously is followed in detail through a first-order charge disproportionation transition 2Co(3.5+)-->Co3++Co4+. Disproportionation in the Co a(g) orbital results in half of the ions (Co3+) becoming electronically and magnetically dead, transforming the quarter-filled a(g) system into a half-filled subsystem that subsequently undergoes the observed charge ordering or metal-insulator transition. Comparing with data in the x approximately 0.3 regime suggests the system has moved into the multiband regime where the effective Coulomb repulsion U-->U(eff)=U/sqrt[3] strongly lessens correlation effects.

Journal Article↗

High-resolution ultrahigh-field MRI of stroke.

BACKGROUND: Ultrahigh-field MRI at 8 T offers unprecedented resolution for imaging brain structures and microvasculature. OBJECTIVE: The aim of this study is to apply high-resolution MRI for stroke imaging and to characterize findings at 1.5 and 8 T. METHODS: Seventeen subjects with minor ischemic infarcts were studied using T2-weighted gradient echo (GE) and rapid acquisition with relaxation enhancement (RARE) images at 8 T with resolution up to 200 microm. In 10 subjects, T1- and T2-weighted fast spin echo (FSE) and fluid-attenuated inversion recovery (FLAIR) images were also acquired at 1.5-T MRI. RESULTS: The 8-T images showed infarcts as sharply demarcated areas of high-signal intensity (n=21) and revealed more infarctions than 1.5-T images (n=14) (P<.003). The low-signal intensity areas that surrounded infarctions were suggestive of hemosiderin deposits. The 8-T characteristics of microvessels terminating within the infractions were distinct from normal vasculature. The 8-T images revealed an angioma at the site of a second stroke, not apparent on 1.5-T images. CONCLUSIONS: Ultrahigh-field MRI at 8 T is feasible for stroke imaging. The 8-T MRI visualized infarcts and microvasculature with high resolution, revealing infarcts and vascular pathologies that were not apparent at 1.5 T.

Adult↗

Localized versus regional hyperthermia: comparison of xenotransplants treated with a small animal ultrasound system and waterbath limb immersion.

The response of xenotransplants were compared with waterbath immersion vs focal ultrasound (US) hyperthermia using tumour growth delay, immunhistochemistry and histopathology assays. Waterbath hyperthermia was performed by limb immersion. Precautions were taken to minimize total body heating by surrounding the mouse with plastic insulators. Thermometry was performed with clinical-grade, 20-gauge needle thermocouples and monitored with a Labthermics unit. Significant differences in cytotoxicity between ultrasound and waterbath treatment of tumors at 43 degrees C were observed as determined by TUNNEL assay. Conversely, contralateral (non-treated) tumours in animals treated with similar temperature demonstrated no significant differences between modalities. Western blot analysis revealed increased hsp70 induction at 43 degrees C in waterbath vs focal ultrasound hyperthermia. Comparison of tumour growth delay between tumours heated with waterbath vs ultrasound at 43 degrees C but not at 41 degrees C revealed significant differences. This is the first study comparing localized vs regional hyperthermia using the small animal ultrasound system (SAHUS) delivery system. Consistent ultrasound hyperthermia can be achieved throughout a xenotransplant. At equivalent temperature of 43 degrees C for 60?min, waterbath hyperthermia demonstrated greater local response vs ultrasound hyperthermia.

Animals↗

Macromolecular prodrugs XI. Synthesis and characterization of polymer-estradiol conjugate.

Estradiol-3-benzoate (EB), an ester derivative of the main oestrogen hormone estradiol, was chemically modified and bound to poly(alpha,beta-(N-2-hydroxyethyl-DL-aspartamide))-poly(alpha,beta-(N-2-aminoethyl-DL-aspartamide)) copolymer (PAHA). EB was first converted to estradiol-3-benzoate-17-(benzotriazole-1-carboxylate), which readily reacted with amino groups in PAHA affording the polymer-drug conjugate PAHA-EB. In PAHA-EB estradiol moiety was covalently bound to the polymeric carrier by carbamate linkage, through non-toxic ethylenediamine spacer. The synthesized compound is a potential hydrosoluble estradiol prodrug.

Chemistry, Pharmaceutical↗

MicroPET-compatible, small animal hyperthermia ultrasound system (SAHUS) for sustainable, collimated and controlled hyperthermia of subcutaneously implanted tumours.

An external ultrasound system was developed for the heating of subcutaneously implanted tumours in small animals. This small animal hyperthermia ultrasound system (SAHUS) was designed to be compatible with a microPET (small animal positron emission tomography) scanner to facilitate studies of hyperthermia effects on tumour hypoxia. Collimation and localization of energy deposition, a specific goal for the new device to avoid regional and/or systemic heating of small animals, was demonstrated using thermoradiography following high-power short-time heating of a layered gel phantom. The in vivo heating capabilities of the SAHUS were tested using PC3 cell line tumours (2000-2700 mm(3)) grown in the lateral proximal thighs of Nu-/Nu- nuBR nude mice. Intratumour temperatures were recorded during heating trials with deep and superficial interstitial thermocouples. The experimental data showed that the SAHUS could produce hyperthermia in 8 +/- 2 mm diameter tumours in small animals to a target temperature of 41.5 degrees C and maintain it within a narrow temperature range (+/- 0.3 degrees C) for up to 4 h without raising the core temperature of the animals. PET imaging studies, data to be published separately, were conducted before and during SAHUS-induced hyperthermia. Both devices performed as expected and there was no significant decrease in image quality. In this paper, the new SAHUS is described and data from phantom and in vivo experiments presented.

Acrylic Resins↗

Altered cerebral vasoregulation in hypertension and stroke.

BACKGROUND: Autoregulation of blood flow that maintains steady perfusion over the range of systemic blood pressure is compromised by stroke. OBJECTIVES: To determine whether cerebral vasoregulation is impaired in stroke during orthostatic stress. METHODS: Subjects included 30 control subjects, 30 with hypertension, and 20 with minor stroke and were studied using transcranial Doppler. Bilateral blood flow velocities (BFVs) from middle cerebral arteries, heart rate, blood pressure (BP), and CO2 were obtained during hyperventilation and CO2 rebreathing during supine rest and tilt at 80 degrees. Side-to-side BFV difference, vasomotor range (VMR), and cerebrovascular resistance (CVR) were calculated during normo-, hypo-, and hypercapnia. RESULTS: Mean BFVs were similar between groups in supine position but differed during tilt. BFV diminished on the stroke side during tilt with hyperventilation and CO2 rebreathing (p < 0.0001). CVR increased (p < 0.0001) and VMR decreased (p < 0.01) on the stroke side. Vasoregulation was preserved on the normal side. BFV asymmetry differentiated patients with stroke from the other groups (p < 0.0001). BFV difference between the normal vs stroke side was the largest in stroke-normotensive (n = 7) compared with stroke-hypertensive (n = 13) patients and the two other groups (p < 0.0001). BFV asymmetry in stroke was associated with lower orthostatic BP (p < 0.0001). CONCLUSIONS: Cerebral vasoregulation is impaired with minor stroke, and cerebral blood flow depends on blood pressure. Decline of blood flow velocities during orthostatic stress may pose a risk of silent hypoperfusion.

Blood Flow Velocity↗

New derivatives of tylosin: chemical and electrochemical oxidation products of desmycosin.

Chemical and electrochemical oxidation of dienonic moiety of desmycosin were carried out. Successive chemical oxidation of desmycosin with m-chloroperbenzoic acid afforded a family of 12,13-dihydro-12,13-dihydroxy derivatives. Indirect electrochemical oxidation via hypobromite as an intermediate gave rise to the new bicyclo derivative of desmycosin, 13-hydroxy-3-dehydroxy-3,12-oxa-desmycosin.

Anti-Bacterial Agents↗

Peritoneal mesothelial hypoxia during pneumoperitoneum is a cofactor in adhesion formation in a laparoscopic mouse model.

OBJECTIVE: To develop a laparoscopic mouse model to evaluate the hypothesis that mesothelial hypoxia during pneumoperitoneum is a cofactor in adhesion formation. DESIGN: Prospective randomized trials. SETTING: Academic research center. ANIMAL(S): One hundred thirty female Naval Medical Research Institute (NMRI) mice. INTERVENTION(S): Adhesions were induced by opposing monopolar lesions in uterine horns and pelvic side walls during laparoscopy and evaluated after 7 or 28 days under microscopic vision during laparotomy. The following pneumoperitoneum variables were assessed: duration (10 or 60 minutes), insufflation pressure (5 or 15 cm of water), insufflation gas (CO(2) or helium), and addition of oxygen (0-12%). MAIN OUTCOME MEASURE(S): Adhesions were scored quantitatively and qualitatively for extent, type, and tenacity. RESULT(S): Scoring of adhesions 7 or 28 days after laparoscopic surgery was comparable. Adhesions increased with duration of pneumoperitoneum and with insufflation pressure and decreased with the addition of oxygen. Half-maximal reduction of adhesions was obtained at 1.5% oxygen, whereas a maximal reduction required only 2%-3%. The effect of CO(2) and helium was similar. CONCLUSION(S): These data demonstrate the feasibility of the intubated laparoscopic mouse model and confirm previous observations in rabbits, indicating that mesothelial hypoxia plays a key role in adhesion formation.

Animals↗

Intracranial ossifications and microangiopathy at 8 Tesla MRI.

UNLABELLED: Clinical evaluation and MR imaging of microangiopathy associated with hypertension is limited. We describe a case that illustrates sensitivity of MRI at 8 Tesla for imaging of microvasculature, iron, calcium deposits and silent white matter lesions (WML). A 60-year-old black hypertensive woman was evaluated for numbness in the face and extremities. MRI at 1.5 Tesla was unrevealing.MRI at 8 Tesla: Axial and sagittal Gradient Echo images were obtained with an 8T/80 cm human scanner and showed: 1) Large areas of signal voids due to ossifications and fat deposits within the falx. 2) Obstructed small vessels in the periventricular regions and distended cortical veins. 3) Numerous small WML, suggestive of mini-infarcts (<1 cm) and microhemorrhages. 4) Intracranial calcifications in the falx, tentorium, basal ganglia and chorioid plexus that were confirmed by CT scan. Atherosclerotic plaque in right carotid artery and reduced vasomotor reserve in middle cerebral arteries, documented by ultrasound, indicated large and small vessel disease. CONCLUSIONS: MRI at 8 Tesla improves visualization of microangiopathy, ossifications and iron deposits due to enhanced magnetic susceptibility at ultra high magnetic field.

Blood Pressure Determination↗

Eating habits, health status, and concern about health: a study among 1641 employees in the German metal industry.

BACKGROUND: Nutrition has been found to be associated with sociodemographic characteristics and concern about health. There is limited knowledge, however, of associations between blue-collar worker's diet, morbidity, and health care utilization. METHODS: We conducted a survey on eating habits, physical symptoms, health care utilization, health status, and concern about health in two German metal companies. A self-administered questionnaire was mailed to employees of whom 1641 participated in the study (response rate 54. 7%). RESULTS: Most employees were characterized by a combination of healthy and unhealthy eating elements. Using linear regression analyses adjusted for age, gender, and occupational status, healthy eating was negatively associated with stomach aches and headaches, but not with cardiovascular disease. Restricted activity days and days in hospital were associated with healthy eating, but self-assessed health status and physician consultations were not. Using stepwise multiple regression analysis, age, gender, and concern about health were strongly and morbidity was weakly related to diet. Occupational status, marital status, and number of children were not associated with nutrition. CONCLUSIONS: Health promotion programs should motivate younger and male employees to participate in and aim toward increasing concern about health.

Adult↗

[1998 social epidemiological analysis of caries incidence and degree of dental restoration in young men].

UNLABELLED: Basing on the hypothesis that adult dental health is co-determined by the conditions and influences prevailing in the family of origin during childhood and adolescence, we analysed the associations of socio-economic status of the family, personal dental care behaviour and other educational and structural factors, with caries prevalence (DMF-T) and the level of restoration in 642 young men between 18 and 24 years eligible for conscription. Additionally, we presented the changes in caries prevalence in conscripted persons during the 1990s comparing our results with those of a study conducted in 1989-90. RESULTS: The average number of DMF-T teeth was 5.7. 15% of subjects were caries-free. The mean level of restoration in those with a history of caries was 79.2%. The prevalence of caries and the level of restoration were strongly associated with the level of education, and the socio-economic status of the family of origin. Parental working time, number of siblings, structural deficiencies in the family, parental preventive education and training with regard to dental care, frequency of brushing the teeth, belief in the success of preventive health measures and prevalence of fissure sealings were significantly associated with DMF-T. Frequency of dental visits showed an association with the level of restoration. From 1989/90 to 1998 prevalence of caries in conscripts decreased by 42% (after adjusting for the different levels of education of both studies the decrease was 36%). Whereas in 1989/90 the average number of DMF-T in the 9-year elementary school graduates exceeded those of the high school graduates ("seniors") by 22%, this difference increased to 88% by 1998. More than 40% of the differences in the prevalence of caries among subjects of different educational levels were due to risk factors of social origin, preventive dental behaviour and utilisation of dental services, all of these being less favourable in elementary school or secondary school graduates compared to high-school graduates.

Adolescent↗

Time-frequency mapping of R-R interval during complex partial seizures of temporal lobe origin.

BACKGROUND: Activation of autonomic nervous system is common with seizures. No reliable biological markers of impending seizures have been found. Evaluation of autonomic changes might help elucidate the transition from interictal to ictal states. METHODS: We studied twelve patients (eight females, four males), from 19 to 62 years old with temporal lobe complex partial seizures (CPS). Dynamics of autonomic functions from oscillations in R-R interval (RRI) using time-frequency mapping based upon a Wigner distribution during pre-ictal, ictal and post-ictal periods. Oscillations in RRI at respiratory frequencies (RF) (> 0.1 Hz) are parasympathetically mediated and at nonrespiratory frequencies (NONRF) (0.01-0.09 Hz) are under combined sympathetic and parasympathetic influence. RESULTS: CPS evoked marked autonomic imbalance and tachycardia. Spectral powers at both RF_RRI and NONRF_RRI increased over the pre-ictal period. RF_RRI power then fell rapidly over the 30 s before seizure onset and remained markedly reduced during seizure (P < 0.004). NONRF_RRI power reached a maximum at seizure onset and declined to a minimum before the seizure cessation (P < 0.05). CONCLUSION: Time-frequency analysis revealed that autonomic activation hallmarks clinical seizure onset for several minutes. After combined parasympathetic and sympathetic activation, rapid parasympathetic withdrawal occurred approximately 30 s before the seizure, and sympathetic activation peaks at seizure onset. Therefore, the transition from interictal to ictal states is relatively long and associated with subclinical autonomic changes.

Adult↗

Time-frequency mapping of R-R interval during complex partial seizures of temporal lobe origin.

BACKGROUND: Activation of autonomic nervous system is common with seizures. No reliable biological markers of impending seizures have been found. Evaluation of autonomic changes might help elucidate the transition from interictal to ictal states. METHODS: We studied twelve patients (eight females, four males), from 19 to 62 years old with temporal lobe complex partial seizures (CPS). Dynamics of autonomic functions from oscillations in R-R interval (RRI) using time-frequency mapping based upon a Wigner distribution during pre-ictal, ictal and post-ictal periods. Oscillations in RRI at respiratory frequencies (RF) (> 0.1 Hz) are parasympathetically mediated and at nonrespiratory frequencies (NONRF) (0.01-0.09 Hz) are under combined sympathetic and parasympathetic influence. RESULTS: CPS evoked marked autonomic imbalance and tachycardia. Spectral powers at both RF_RRI and NONRF_RRI increased over the pre-ictal period. RF_RRI power then fell rapidly over the 30 s before seizure onset and remained markedly reduced during seizure (P < 0.004). NONRF_RRI power reached a maximum at seizure onset and declined to a minimum before the seizure cessation (P < 0.05). CONCLUSION: Time-frequency analysis revealed that autonomic activation hallmarks clinical seizure onset for several minutes. After combined parasympathetic and sympathetic activation, rapid parasympathetic withdrawal occurred approximately 30 s before the seizure, and sympathetic activation peaks at seizure onset. Therefore, the transition from interictal to ictal states is relatively long and associated with subclinical autonomic changes.

Journal Article↗

Cerebrovascular regulation in the postural orthostatic tachycardia syndrome (POTS).

Patients with the postural orthostatic tachycardia syndrome (POTS) have symptoms of orthostatic intolerance despite having a normal orthostatic blood pressure (BP), which suggests some impairment of cerebrovascular regulation. Cerebrovascular autoregulation refers to the maintenance of normal cerebral blood flow in spite of changing BP. Mechanisms of autoregulation include myogenic, metabolic and neurogenic vasoregulation. Beat-to-beat recording of blood-flow velocity (BFV) is possible using transcranial Doppler imaging. It is possible to evaluate autoregulation by regressing deltaBFV to deltaBP during head-up tilt. A number of dynamic methods, relating deltaBFV to deltaBP during sudden induced changes in BP by occluding then releasing peripheral arterial flow or by the Valsalva maneuver. The deltaBFV to deltaBP provides an index of autoregulation. In orthostatic hypotension, the autoregulated range is typically expanded. In contrast, paradoxical vasoconstriction occurs in POTS because of an increased depth of respiration, resulting in hypocapnic cerebrovascular constriction, and impaired autoregulation.

Blood Flow Velocity↗

Long-term results after surgical basal cell carcinoma excision in the eyelid region.

AIMS: To evaluate the data for patients with basal cell carcinoma (BCC) in the eyelid region, to demonstrate histologically controlled tumour excision, and to prove the efficacy of the treatment on the basis of long term observations. METHODS: Retrospective analysis of 382 microscopically controlled BCC excisions in the eyelid apparatus (350 patients) in a follow up study over 5.7 (SD 1.1) years. Tumour location, tumour size, and histological results were recorded. The same procedure was followed for recurrences. Follow up examinations were carried out 1, 3, 6, and 12 months after the operation, and then annually for a further 4 years or longer. RESULTS: A recurrence rate of 5.36% was observed after the primary operation. 60.3% of first recurrences occurred in the medial canthus, 41.2% showed in depth extension, and sclerosing types were overly represented at 35.3%. After the second operation the recurrence rate increased to 14.7% and reached 50% after a third and fourth operation. CONCLUSIONS: The greatest risk of recurrence exists for BCCs of the medial canthus with in depth extension, and for sclerosing types. The recurrence rate increases after every operation. For high risk cases, consideration should be given to adjuvant treatment such as radiotherapy.

Aged↗

Endoscopic laser recanalisation of presaccal canalicular obstruction.

AIM: To document the results of erbium (Er)-YAG laser treatment in presaccal canalicular obstruction in combination with the use of a flexible endoscope. METHODS: For the first time an Er-YAG laser (Schwind, Sklerostom) was attached to a flexible endoscope (Schwind, Endognost) and used to recanalise a stenosis of the upper, lower, or common canaliculus. In 17 patients (mean age 41.5 (SD 11.9) years), 19 treatments (two bilateral) were performed. In all cases the scar was observed using the endoscope and was excised by laser ablation. A silicone intubation was performed in all cases. In addition to the endoscopy an irrigation was performed to prove the intactness of the lacrimal pathway system after laser treatment. RESULTS: Membranous obstructions with a maximum length of 2.0 mm (14 procedures) in the canaliculus were opened easily using the laser, and the silicone intubation was subsequently performed without difficulty. Scars thicker than 2.0 mm could not be opened safely without canaliculus penetration (five procedures). Irrigation was positive in all cases up to the end of a 6 month period, providing the tubes remained in place. The maximum follow up is now 17 months (minimum 8 months) and in 16 cases (84.2%) the canaliculi are still intact. CONCLUSION: Endoscopic laser treatment combined with silicone intubation enables us to recanalise presaccal stenoses of canaliculi under local anaesthesia up to a scar thickness of 2.0 mm. Best results can be achieved in cases where much tissue can be saved. Under such conditions this procedure can substitute for more invasive surgical techniques, especially a conjunctivo-dacryocystorhinostomy (CDCR).

Adult↗