Relevant Clinical Conditions Research Articles

Serum Cytokeratin-18 Fragments as Quantitative Marker of Epithelial Apoptosis in Liver and Intestinal Graft-Versus-Host Disease.

Graft-versus-host disease (GvHD) is the main complication of allogeneic stem cell transplantation (SCT). However, diagnosis and differentiation of GvHD from infectious or toxic clinical conditions as well as evaluation of GvHD response to immunosuppressive treatment remains a challenge. Since apoptosis is a common histopathological finding in GvHD, we investigated whether the caspase-cleaved neo-epitope of cytokeratin 18 fragments (CK18F) might be a serum marker for ongoing GvHD-induced target organ inflammation.Longitudinal monitoring of serum CK18F kinetics by M30 antibody-based ELISA in 49 patients who fulfilled histopathological and/or clinical criteria diagnostic for GvHD following SCT showed that CK18F were highly elevated in hepatic and intestinal GvHD (6.3±3.8 fold and 4.6±0.8 fold, respectively, over baseline). Responses of GvHD to immunosuppressive therapy were paralleled by CK18F decreases. The extent of CK18F increases tended to correlate with serological severity of acute (r=0.96) and chronic (r=0.76) liver GvHD. Differentially relevant clinical conditions, such as non-complicated infection-related diarrhea and toxic hyperbilirubinemia were not associated with significant CK18F rises. In conclusion, CK18F monitoring provides a simple serum marker for quantitative assessment of GvHD-associated apoptotic activity in intestinal and hepatic GvHD and for distinguishing active GvHD from irreversible end organ damage. Prospective studies are warranted to demonstrate the significance of CK18F for diagnosis, differentiation, prognosis, and treatment guidance of GvHD.

Treatment of High-Risk Hypertensive Patients

Cardiovascular disease represents the leading cause of morbidity and mortality in Western countries, and hypertension-related cardiovascular events affect about 37 million people per year, worldwide. In this perspective, hypertension represents a reference paradigm to illustrate strategies aimed at achieving cardiovascular prevention. Hypertensive patients are at increased risk of experiencing a cardiovascular event during their life-time, and treatment of high blood pressure represents one of the most effective strategies to reduce the global cardiovascular risk of these patients. However, owing to its multifactorial pathophysiology and its frequent association with other relevant risk factors and clinical conditions, such as dyslipidaemia, diabetes mellitus, left ventricular dysfunction and renal impairment, hypertension requires an integrated approach to treatment, including life-style measures, antihypertensive drugs and other therapies (mostly lipid-lowering regimens). Yet worldwide, general practitioners continue to focus their attention on the management of a single risk factor, e.g. blood pressure, rather than on the global cardiovascular risk profile. Modern strategies of cardiovascular prevention should assess the global cardiovascular risk threshold to manage hypertensive patients at high risk, rather than to focus on the high level of a single risk factor, for achieving effective control of cardiovascular risk profile and reducing cardiovascular morbidity and mortality in the general population, as well as in the hypertensive population.

Cardiac neurotransmission SPECT imaging

The sympathetic nervous system has great influence on cardiovascular physiology. Cardiac neurotransmission single photon emission computed tomography (SPECT) imaging allows in vivo noninvasive assessment of presynaptic reuptake and storage of neurotransmitters, which offers characterization of the cardiac neuronal function in different diseases of the heart and other altered metabolic or functional conditions. Therefore assessment of the integrity of cardiac sympathetic innervation may help in the diagnosis of these disorders, as well as in prognostication, and will result in better therapy and outcome. At present, the most widely available SPECT tracer by which to assess cardiac neurotransmission is metaiodobenzylguanidine labeled with iodine 123. This article focuses on reviewing the characteristics of cardiac SPECT imaging with I-123 metaiodobenzylguanidine and its role in the assessment of pathophysiologic changes during relevant clinical conditions.

The role of cytokines in regulating protein metabolism and muscle function.

Multiple lines of evidence suggest that cytokines influence different physiologic functions of skeletal muscle cells, including anabolic and catabolic processes and programmed cell death. Cytokines play an important role not only in muscle homeostasis, therefore, but also in the pathogenesis of different relevant clinical conditions characterized by alterations in protein metabolism. Recently discovered cytokines, such as ciliary neurotrophic factor and growth/differentiation factor-8, as well as the more studied tumor necrosis factor-alpha, interleukin-1, interleukin-6, and the interferons, have been implicated in the regulation of muscle protein turnover. Their postreceptor signaling pathways, proteolytic systems, and the mechanisms of protein synthesis inhibition involved in different catabolic conditions have been partially clarified. Moreover, recent studies have shown that cytokines can directly influence skeletal muscle contractility independent of changes in muscle protein content. Even though several gaps remain in our understanding, these observations may be useful in the development of strategies to control protein metabolism and muscle function in different clinical conditions.

Effect of scattered radiation on image noise in cone beam CT.

Cone beam CT has a capability for the 3-dimensional imaging of large volumes with isotropic resolution, and has a potentiality for 4-dimensional imaging (dynamic volume imaging), because cone beam CT acquires data of a large volume with one rotation of an x-ray tube-detector pair. However, one of the potential drawbacks of cone beam CT is a larger amount of scattered x-rays, which may enhance the noise in reconstructed images, and thus affect the low-contrast detectablity. Our aim in this work was to estimate the scatter fractions and effects of scatter on image noise, and to seek methods of improving image quality in cone beam CT. First we derived a relationship between the noise in a reconstructed image and in an x-ray intensity measurement. Then we estimated the scatter to primary ratios in x-ray measurements using a Monte-Carlo simulation. From these we estimated the image noise under relevant clinical conditions. The results showed that the scattered radiation made a substantial contribution to the image noise. However, focused collimators could improve it by decreasing the scattered radiation drastically while keeping the primary radiation at nearly the same level. A conventional grid also improved the image noise, though the improvement was less than that of focused collimators.

Hydroxyl radical generation in oxygen-treated infants.

Because the hydroxyl radical is capable of oxidizing phenylalanine to O-tyrosine, we sought to determine whether increased levels of O-tyrosine are found in urine of infants treated with supplemental oxygen. A total of 39 consecutively admitted neonates to an intensive care unit were included. Twenty-seven received supplemental oxygen therapy for respiratory disease, and 12 did not. Urinary O-tyrosine levels were determined on two or more occasions using high-performance liquid chromatography with results expressed as a percentage of the urinary phenylalanine concentration. Using simple and stepwise multiple linear regression analyses, urinary O-tyrosine was examined for associations with relevant clinical conditions and laboratory measurements. Infants supplemented with oxygen showed significantly higher mean +/- SEM urinary O-tyrosine levels (0.40% +/- 0.028) compared with those remaining in room air (0.18% +/- 0.012). Mean daily FIO2 was the clinical and laboratory variable most highly correlated with urinary O-tyrosine (r = 0.66). In the stepwise regression, significant associations were also found for renal fractional sodium excretion and Apgar score at 5 minutes. Hydroxylation at the O position of phenylalanine, a specific direct marker for the hydroxyl radical attack, was strongly associated with oxygen treatment in neonates. This finding increases our understanding of the pathogenesis of oxygen injury and suggests a basis for developing therapeutic approaches.

Assessment of the relationship of sperm morphology with seminal and other clinical conditions of semen donors.

The occurrence of abnormal forms of spermatozoa in human semen is quite common. According to WHO, semen is considered normal even if it contains 50% morphologically abnormal spermatozoa. This study assessed whether the sperm morphology maintains any relation with the relevant clinical conditions of the semen donor. One hundred samples representing normal and different types of male factor etiologies underwent semen and morphological analysis. Clinical information such as race, age, weight, profession, medication, medical history, and smoking habit of the semen contributors were recorded. The influence of seminal and clinical features on sperm morphology was evaluated with multiple regression analysis. Head abnormalities were more common than tail abnormalities. Acrosomal defects and coiled tails were the most prevalent head and tail abnormalities, respectively. Regression analysis failed to confirm any strong association between sperm morphology and other seminal parameters. Accessory gland-related seminal parameters such as viscosity, volume, pH, and liquefaction showed the least association with the morphological variability. Sperm morphology also showed poor correlation with race, age, weight, smoking habit, and work environment.

Cataract surgery in a Swedish population: Observations and complications

Purpose: To describe relevant clinical conditions at cataract surgery in a defined Swedish population, examine variables and their influence on the operative procedure, and estimate the risk of complications at surgery.Setting: Department of Ophthalmology, Lund University Hospital, Sweden.Methods: Using the Cataract Analysis Systern™, data were prospectively collected on 5878 consecutive cataract surgeries performed in a single Swedish health care district from 1986 to 1990. Patients younger than 15 years were not included. The study population was complete enough to represent all cataract surgeries in the referral region of the Lund Health Care District during this period. The incidence of zonular or lens capsule rupture at surgery was used as a measure of surgical complications and assessed as a function of other preoperative and surgical parameters. A logistic regression model was used to assess the probability of complications at surgery.Results: Glaucoma was the highest statistically significant preoperative risk factor for capsular or zonular rupture at surgery, with or without vitreous loss, with a relative risk of 2.7 (i.e., a 2.7-fold increase in risk over patients without glaucoma). Surgeons performing fewer than 40 operations in 5 years had a relative risk of zonular or capsular rupture of approximately 2.9 (i.e., a 2.9-fold increase in risk over highvolume surgeons). The overall risk was 2.5%.Conclusion: Cataract patients with glaucoma have an increased risk of complications at surgery. Surgeons performing few operations tended to have more capsular or zonular ruptures.

Calibration of semiconductor detectors for dose assessment in total body irradiation

The aim of this paper is to discuss the measurements carried out to implement ‘in vivo dosimetry’ with EDP-30 diodes in total body irradiation (TBI) techniques. Exit calibrations and calibrations behind cerrobend protection blocks showed the importance of calibrating diodes in all relevant clinical conditions. Special attention was given to calibration of diodes behind cerrobend blocks. Dependence of the calibration factors on the thickness of the shielding blocks was, therefore, studied. This dependence was again studied after adding a wax cap to the diode and when the ionisation chamber was placed at the same depth as the measuring point of the diode. Temperature dependence in diode sensitivity and dependence on accumulated dose for diodes response and for temperature correction factors were also examined.

Magnetic resonance imaging of the caudate nuclei in depression. Preliminary observations.

A role of the caudate nucleus in depression has been suggested from relevant clinical conditions, such as patients with Huntington's disease or caudate infarcts, as well as animal studies. Correlations of caudate nucleus disease with depressive symptoms have been limited to autopsy studies and cases of gross pathological disorder, such as large infarcts. We used serial axial high-field magnetic resonance images and an unbiased stereological technique to estimate the volumes of the caudate nuclei in 50 patients who met DSM-III criteria for major depression (23 men, 48.3 +/- 17 years old) in comparison with 50 age- and gender-matched normal controls free of major neurological and psychiatric disorders. Depressed patients had smaller caudate nucleus volumes (5.2 +/- 1.6 cm3) compared with controls (6.2 +/- 1.7 cm3). Right and left caudate nucleus volumes were smaller in depressed patients compared with controls. Age was negatively correlated with caudate nucleus volumes in depressed patients as well as in controls. Caudate nucleus volumes in depressed patients were inversely correlated with the bicaudate and bifrontal indices. These results may be the first demonstration of diminished caudate nucleus volumes in depression and suggest a role for the caudate nucleus in the pathogenesis of major depression.

Contact angles in a biological setting: measurements in the human oral cavity

A clinical method was developed to allow the direct or photographic recording of contact angles on solid surfaces within the oral cavity. This method, which was tested on four subjects, allows for relatively accurate and precise recordings of contact angles to be taken under relevant clinical conditions and without disruption of the surfaces in their normal state. When the results of this study were examined the precision of the measurements was remarkably high, considering that recordings were made under complete clinical conditions. No major systematic differences were found in the performed studies of errors of the method and this indicates that the described method is both valid and reliable. The clinical method of determining contact angles on solid surfaces and the resultant calculation of the critical surface tension of wetting of the tissue opens the door to a variety of future studies. For the first time, a methodology exists for studying in situ the surface activity in the presence of a disease process. These clinical methods may also serve to better characterize the surface chemical conditions in a caries-prone mouth, or in a mouth prone to high plaque formation, as well as other biologic conditions.

A clinical method for the study of in-vivo adhesiveness of teeth.

For the present study a clinical method was developed to allow the direct or photographic recording of contact angles on solid surfaces within the oral cavity. This method, which was tested on four subjects, allows for relatively accurate and precise recordings of contact angles to be taken under relevant clinical conditions and without disruption of the surfaces in their normal state.