[Hemodynamic effects of the synthetic analogue of endogenous nitric oxide (II) donors a dinitrosyl iron complex in hypertensive patients with uncomplicated hypertensive crisis].

AIM: To examine the antihypertensive effect of the synthetic analogue of the endogenous nitric oxide donors in patients with grades 2-3 hypertension and uncomplicated hypertensive crisis (HC). SUBJECTS AND METHODS: The study included 30 male patients aged 35 to 73 years (mean age 55.5 ± 10.8 years). All the patients had grades 2-3 essential or secondary hypertension. Thirteen (43.3%) patients were observed to have signs of HC; 17 (56.7%) patients had persistent blood pressure (BP) elevation. A dinitrosyl iron complex was injected in a dose of 1.5 or 3 mg per kg of body weight. The purpose of its administration was to lower BP by at least 20% of its baseline level. RESULTS: No significant side effects associated with the administration of the test drug were recorded when the clinical trial protocol was implemented. All the patients reported fever and facial hyperemia during and 10-20 minutes after injection. They all (100%) showed efficient blood pressure reduction of at least 20% of the baseline level. Blood pressure changes were similar when the agent was administered in doses of 1.5 or 3 mg/kg. At 6-8 minutes after the drug was injected, there was a maximal decrease in blood pressure, then its gradual rise and stabilization at a lower level than the baseline one within the following 8 hours. There were no significant differences in the magnitude of a blood pressure reduction after administration of 1.5 and 3 mg/kg. CONCLUSION: The findings suggest that the dinitrosyl iron complex is highly effective in treating uncomplicated HC. The antihypertensive effect of the drug persists for 8 hours after its injection, which is very important during prehospital therapy. The drug is well tolerated by patients and causes an insignificant number of side effects.

Reversal mechanism of an individual Ni nanotube simultaneously studied by torque and SQUID magnetometry.

Using an optimally coupled nanometer-scale SQUID, we measure the magnetic flux originating from an individual ferromagnetic Ni nanotube attached to a Si cantilever. At the same time, we detect the nanotube's volume magnetization using torque magnetometry. We observe both the predicted reversible and irreversible reversal processes. A detailed comparison with micromagnetic simulations suggests that vortexlike states are formed in different segments of the individual nanotube. Such stray-field free states are interesting for memory applications and noninvasive sensing.

Single-charge transistor based on the charge-phase duality of a superconducting nanowire circuit.

We propose a transistorlike circuit including two serially connected segments of a narrow superconducting nanowire joint by a wider segment with a capacitively coupled gate in between. This circuit is made of amorphous NbSi film and embedded in a network of on-chip Cr microresistors ensuring a sufficiently high external electromagnetic impedance. Assuming a virtual regime of quantum phase slips (QPS) in two narrow segments of the wire, leading to quantum interference of voltages on these segments, this circuit is dual to the dc SQUID. Our samples demonstrated appreciable Coulomb blockade voltage (analog of critical current of the SQUIDs) and periodic modulation of this blockade by an electrostatic gate (analog of flux modulation in the SQUIDs). The model of this QPS transistor is discussed.

[The study of hypotensive action of dinitrosyl-iron complex with glutathione containing drug oxacom in healthy volunteers].

On the basis of earlier executed studies of hypotensive effect of dinitrosyl iron complexes (DNIC) with glutathione, the drug has been created in industrial conditions named oxacom. Preliminary pharmacological studies of oxacom have not revealed negative qualities. The drug has been now tested in 14 healthy men in whom at single intravenous introduction it caused typical response - a decrease of diastolic as well as systolic arterial pressure on 24-27 mmHg through 3-4 min with subsequent very slow restoration in 8-10 hours. The heart rate after initial rise was quickly normalized. Echocardiography revealed unaltered cardiac output in spite of reduced cardiac filling by 28%. The multilateral analysis of clinical and biochemical data has revealed an absence of essential alterations which could lead to pathological consequences. The drug is recommended for carrying out of the second phase of clinical trial. The comparative study of the efficiency of hypotensive action of oxacom, S-nitrosoglutathione (GS-NO) and sodium nitrite (NO2) in rats has shown that the duration of effect was the greatest at oxacom action.

Quantum dynamics in a camelback potential of a dc SQUID.

We investigate a quadratic-quartic anharmonic oscillator formed by a potential well between two potential barriers. We realize this novel potential with a dc SQUID at near-zero current bias and flux bias near half a flux quantum. Escape out of the central well can occur via tunneling through either of the two barriers. We find good agreement with a generalized double-path macroscopic quantum tunneling theory. We also demonstrate an "optimal line" in current and flux bias along which the oscillator, which can be operated as a phase qubit, is insensitive to decoherence due to low-frequency current fluctuations.

[Platelet activation and inflammation markers in patients with coronary heart disease and depression].

AIM: To study morphological features and functional activity of platelets, their relations with the level of inflammation markers in coronary heart disease (CHD) patients with depression. MATERIAL AND METHODS: The study group consisted of 33 CHD patients with stable effort angina (NY-HA FC I-III), 14 had depression, 19 were free of depression. Sixteen healthy volunteers comprised the control group. Platelet aggregation was registered by a mean size of aggregates and turbidometrically. Platelets shape, leukocytic-thrombocytic and erythrocytic-thrombocytic aggregates (LTA, ETA) in the whole blood were studied electron-microscopically. The levels of IL-2, IL-6, TNF-alpha, sVCAM, hsCRP were measured in the blood, serotonin--in platelets. RESULTS: Spontaneous aggregation enhanced in 52.6% CHD patients (p < 0.05). The blood contained reticular platelets, high number of prothrombocytes (p < 0.05), mean volume of thrombocytes was greater (p < 0.05). This reflected changes in megakaryocytopoiesis. Some of the patients had LTA and ETA. Out of inflammation markers, only IL-6 and sVCAM were elevated (p < 0.01), hsCRP concentration rose, but not above normal range. Serotonin in platelets was the same in the patients and controls. Depression aggravated the disorders and elevated other indices. Spontaneous aggregation was high in 71.4% of depressive CHD patients. The count of reticular platelets, prothrombocytes, mean volume platelets were also elevated. LTA and ETA were high in all the depressive patients. Elevated were also concentrations of IL-6, sVCAM, IL-2, hsCRP. Serotonin in platelets was low (p < 0.05). CONCLUSION: Depression stimulates functional activity of platelets, is a factor of risk of intravascular inflammation and contributes to development of thrombotic complications in CHD patients.

The University of Rochester model of breast cancer detection and survival.

This paper presents a biologically motivated model of breast cancer development and detection allowing for arbitrary screening schedules and the effects of clinical covariates recorded at the time of diagnosis on posttreatment survival. Biologically meaningful parameters of the model are estimated by the method of maximum likelihood from the data on age and tumor size at detection that resulted from two randomized trials known as the Canadian National Breast Screening Studies. When properly calibrated, the model provides a good description of the U.S. national trends in breast cancer incidence and mortality. The model was validated by predicting some quantitative characteristics obtained from the Surveillance, Epidemiology, and End Results data. In particular, the model provides an excellent prediction of the size-specific age-adjusted incidence of invasive breast cancer as a function of calendar time for 1975-1999. Predictive properties of the model are also illustrated with an application to the dynamics of age-specific incidence and stage-specific age-adjusted incidence over 1975-1999.

Bloch inductance in small-capacitance Josephson junctions.

We show that the electrical impedance of a small-capacitance Josephson junction also includes, in addition to the capacitive term -i/(omega)CB, an inductive term i(omega)LB. Similar to the known Bloch capacitance CB(q), the Bloch inductance LB(q) also depends periodically on the quasicharge, q, and its maximum value achieved at q=e(mod 2e) always exceeds the value of the Josephson inductance of this junction LJ(phi) at fixed phi=0. The effect of the Bloch inductance on the dynamics of a single junction and a one-dimensional array is described.

[The role of an objective assessment of the heart right vientricle function for the anesthesiological maintenance and intensive therapy of surgical patients].

Latent dysfunction of the heart right ventricle and hypovolemia were assessed in 50 patients divided into 4 groups, operated on the heart, abdominal aorta and lungs. It was found that after revascularization of the myocardium the diastolic disorders prevailed. In patients operated for the heart valve (mitral and aortal) diseases prevailing were the systolic and pump dysfunction of the right ventricle. Insufficiency of the right ventricle in these groups was 13% and 22% respectively. After operations on the abdominal aorta a combination of the systolic and diastolic impairments of the right ventricle were observed. After extended resections of the lungs there was a characteristic combination of systolic, diastolic and pump dysfunctions. When the operation was followed by a decreased minute volume of circulation, its cause was hypovolemia in 29% of cases in the examined surgical patients. The investigation of the right ventricle functions with the help of pulmonary arterial volumetry can reveal their latent dysfunctions as well as hypovolemia in a considerable part of surgical patients.

Cooper pair cotunneling in single charge transistors with dissipative electromagnetic environment.

We observed current-voltage characteristics of superconducting single charge transistors with on-chip resistors of R approximately R(Q)=h/4e(2) approximately 6.45 kOmega, which are explained in terms of Cooper pair cotunneling. Both the effective strength of Josephson coupling and the cotunneling current are modulated by the gate-induced charge on the transistor island. For increasing values of the resistance R we found the Cooper pair current at small transport voltages to be dramatically suppressed.

[Parametric survival analysis in patients with cervical cancer following fractionated radiotherapy: a new procedures and results]. / Parametricheskii analiz vyzhivaemosti bol'nykh rakom sheiki matki posle fraktsionirovannoi radioterapii. Novyi metod i rezul'taty ego primeneniia.

A recent theoretical result of Kendal (1998) enabled us to develop a survival model which allows for proliferation of tumor clonogenic cells in the course of fractionated radiotherapy. We explored this model during an analysis of clinical data on survival of 982 patients with cancer of the cervix uteri. The model provided a good description of survival patterns in different groups of patients. The estimated cure probability did not correlate with the rates of cell proliferation between exposures to radiation. Also, our results showed that this parameter cannot be estimated from survival data. Some light has been thrown on the relationship of cell proliferations taking place between exposures, on the one hand, and end-results of treatment for cancer of the cervix uteri, on the other.

Modeling cancer detection: tumor size as a source of information on unobservable stages of carcinogenesis.

This paper is concerned with modern approaches to mechanistic modeling of the process of cancer detection. Measurements of tumor size at diagnosis represent a valuable source of information to enrich statistical inference on the processes underlying tumor latency. One possible way of utilizing this information is to model cancer detection as a quantal response variable. In doing so, one relates the chance of detecting a tumor to its current size. We present various theoretical results emerging from this approach and illustrate their usefulness with numerical examples and analyses of epidemiological data. An alternative approach based on a threshold type mechanism of tumor detection is briefly described.

Radio-frequency Bloch-transistor electrometer.

A quantum electrometer is proposed which is based on charge modulation of the Josephson supercurrent in the Bloch transistor inserted in a superconducting ring. As this ring is inductively coupled to a high- Q resonance tank circuit, the variations of the charge on the transistor island are converted into variations of amplitude and phase of oscillations in the tank. These variations are amplified and then detected. At sufficiently low temperature of the tank the device sensitivity is determined by the energy resolution of the amplifier, that can be reduced down to the standard quantum limit of 1 / 2Planck's over 2pi. A "back-action-evading" scheme of subquantum limit measurements is proposed.

An alternative stochastic model of generation of oligodendrocytes in cell culture.

According to our previous model, oligodendrocyte--type 2 (O-2A) astrocyte progenitor cells become competent for differentiation in vitro after they complete a certain number of critical mitotic cycles. After attaining the competency to differentiate, progenitor cells divide with fixed probability p in subsequent cycles. The number of critical cycles is random; analysis of data suggests that it varies from zero to two. The present paper presents an alternative model in which there are no critical cycles, and the probability that a progenitor cell will divide again decreases gradually to a plateau value as the number of completed mitotic cycles increases. In particular all progenitor cells have the ability to differentiate from the time of plating. The Kiefer-Wolfowitz procedure is used to fit the new model to experimental data on the clonal growth of purified O-2A progenitor cells obtained from the optic nerves of 7 day old rats. The new model is shown to fit the experimental data well, indicating that it is not possible to determine whether critical cycles exist on the basis of these experimental data. In contrast to the fit of the previous model, which suggested that the addition of thyroid hormone increased the limiting probability of differentiation as the number of mitotic cycles increases, the fit of the new model suggests that the addition of thyroid hormone has almost no effect on the limiting probability of differentiation.

Estimation problems associated with stochastic modeling of proliferation and differentiation of O-2A progenitor cells in vitro.

Our previous research effort has resulted in a stochastic model that provides an excellent fit to our experimental data on proliferation and differentiation of oligodendrocyte type-2 astrocyte progenitor cells at the clonal level. However, methods for estimation of model parameters and their statistical properties still remain far away from complete exploration. The main technical difficulty is that no explicit analytic expression for the joint distribution of the number of progenitor cells and oligodendrocytes, and consequently for the corresponding likelihood function, is available. In the present paper, we overcome this difficulty by using computer-intensive simulation techniques for estimation of the likelihood function. Since the output of our simulation model is essentially random, stochastic optimization methods are necessary to maximize the estimated likelihood function. We use the Kiefer-Wolfowitz procedure for this purpose. Given sufficient computing resources, the proposed estimation techniques significantly extend the spectrum of problems that become approachable. In particular, these techniques can be applied to more complex branching models of multi-type cell systems with dependent evolutions of different types of cells.

[Defects in autonomic regulation in myocardial ischemia]. / Narusheniia vegetativnoi reguliatsii pri ishemii miokarda.

AIM: To evaluate cerebral and peripheral mechanisms of autonomic regulation of the cardiovascular system, their role in development of myocardial ischemia in coronary heart disease (CHD) patients with coronary atherosclerosis and X syndrome. MATERIALS AND METHODS: Psychometric testing, questionnaires, cardiovascular tests (by D. Y. Ewing), automatic spectral analysis of cardiac rhythm variability were used in investigation of psychovegetative regulation in 36 patients and 19 healthy subjects. Group 1 consisted of 26 CHD patients with coronary atherosclerosis and stable angina class I-II. Group 2 consisted of 10 patients with symptoms of myocardial ischemia and coronarographically intact coronary arteries. RESULTS: Patients of both groups demonstrated initial activation of cerebral sympathicoadrenal mechanisms manifesting with high anxiety, depression, vegetative defects in regulation of both initial autonomic tone and autonomic support of the orthostatic test. CHD patients with coronary atherosclerosis were characterized by persistent activation of cerebral sympathicoadrenal mechanisms and resistance of homeostatic baroreflex sympathetic systems. Vagal insufficiency was moderate and arose only at rest. In X syndrome patients with the same initial cerebral activation of the sympathicoadrenal mechanisms had dystonic trend in hemodynamic autonomic parameters: higher systolic blood pressure in subnormal heart rate, lability of baroreflex and cerebral mechanisms under the orthostatic test. The above features of psychovegetative relations make such patients very close to those with psychovegetative syndrome. CONCLUSION: CHD patients with coronary atherosclerosis and patients with X syndrome differ by mechanisms of maladaptation of autonomic regulation.