A model of brain arteriolar oxygen and carbon dioxide transport during anemia.

Existing experimental and theoretical evidence suggests that precapillary diffusion of O2 and CO2 occurs between arterioles and tissue under normal physiologic conditions. However, limited information is available on arteriolar gas transport during anemia. With use of a mathematical model of an arteriolar network in brain tissue, anemic hematocrits of 35, 25, and 15% were modeled to determine the effect of anemia on the exchange, the change in the equilibrium tissue O2 and CO2 tensions, and the increase in blood flow needed to restore tissue oxygenation. We found that the blood PO2 exiting the network fell from 66 mm Hg normally to 48 mm Hg during the severest anemia. Concurrently, the equilibrium tissue O2 tensions dropped from 44 to 23 mm Hg. For CO2 the exit blood PCO2 was 58 mm Hg for a 15% hematocrit, an increase of 4 mm Hg from the normal value, and equilibrium tissue PCO2 increased from 56 to 61 mm Hg. Blood flow increases from normal values necessary to offset the effects of the decreased O2 delivery to the tissue were 26, 86, and 222%, respectively, for hematocrits of 35, 25, and 15%. We compared our model results with recent experimental studies that have suggested that the amount of O2 diffusion is much higher than predicted values. We found that these experimental O2 gradients are three to four times larger than theoretical.

Prediction of prostatic obstruction with a combination of isometric detrusor contraction pressure and maximum urinary flow rate.

OBJECTIVES: Because isometric detrusor contraction pressure (Piso) increases with outlet obstruction and maximum urinary flow rate (Qmax) tends to decrease with obstruction, we hypothesize that specific criteria consisting of a combination of high Piso and low Qmax may be able to differentiate obstructive from nonobstructive voiding dysfunction better than either parameter alone. METHODS: Two hundred five men with lower urinary tract symptoms underwent uroflowmetry and videourodynamics, including cystometry, continuous outlet occlusion test, and micturitional urethral pressure profilometry. Combined threshold values of Qmax of less than 12 mL/s and Piso of 100 cm H2O or greater were used to predict obstruction, whereas threshold values of Qmax of at least 12 mL/s and Piso less than 100 cm H2O were used to predict nonobstruction. RESULTS: Of the 205 patients, 103 (50%) were significantly obstructed and 102 (50%) were only mildly obstructed or nonobstructed. Of the total population, 151 patients (74%) were categorized by the combined flow and contractility criteria. Of the categorized patients, 141 (93%) were correctly diagnosed with regard to infravesical obstruction (sensitivity 89%, specificity 97%, positive predictive value 97%, and negative predictive value 91%). CONCLUSIONS: A combination of Qmax and Piso criteria can predict obstructive and nonobstructive voiding dysfunctions with high positive and negative predictive values in most patients with lower urinary tract symptoms. Combining the results of uroflowmetry and isometric tests may help to guide treatment strategies that may improve the outcome of selected therapeutic options compared with strategies based on symptoms or uroflowmetry alone. Furthermore, this approach forms a basis for interpreting various noninvasive methods that have recently been introduced for the purpose of diagnosing bladder outlet obstruction.

Salivary gland changes in chronic fatigue syndrome: a case-controlled preliminary histologic study.

OBJECTIVE: The purpose of this preliminary study is to compare labial salivary gland changes of 11 patients with chronic fatigue syndrome with control subjects. STUDY DESIGN: Changes in labial salivary glands were graded from 0 to 3+ for acinar dilatation, ductal dilatation, periductal fibrosis, plasmacytic infiltrate, lymphocytic infiltrate, mast cell infiltrate, and lymphocytic aggregates or foci. RESULTS: Four of the 11 subjects had 2+ to 3+ changes in at least 4 of the 7 parameters examined. Only the presence of mast cells was statistically significant between the 2 groups. Two of these 4 patients had 1 lymphocytic focus per 4 mm(2) of tissue. CONCLUSIONS: The salivary gland changes in patients with chronic fatigue syndrome show varying degrees of ductal and acinar dilatation, periductal fibrosis, lymphoplasmacytic infiltrates, and occasional lymphocytic foci, all suggestive of primary gland damage. The one parameter that showed statistical significance was the presence of mast cells (Fisher exact test, 0.0125).

Lymphocyte subset differences in patients with chronic fatigue syndrome, multiple sclerosis and major depression.

Chronic fatigue syndrome (CFS) is a heterogeneous disorder of unknown aetiology characterized by debilitating fatigue, along with other symptoms, for at least 6 months. Many studies demonstrate probable involvement of the central and autonomic nervous system, as well as a state of generalized immune activation and selective immune dysfunction in patients with CFS. The aim of this study was to compare the lymphocyte subsets of patients with chronic fatigue syndrome to those of patients with major depression and multiple sclerosis as well as those of healthy control subjects. No differences were found in total numbers of T cells, B cells or natural killer (NK) cells. However, differences were found in T, B and NK cell subsets. Patients with major depression had significantly fewer resting T (CD3(+)/CD25(-)) cells than the other groups. Patients with major depression also had significantly more CD20(+)/CD5(+) B cells, a subset associated with the production of autoantibodies. Compared to patients with multiple sclerosis, patients with CFS had greater numbers of CD16(+)/CD3(-) NK cells. Further study will be required to determine whether these alterations in lymphocyte subsets are directly involved in the pathophysiology of these disorders, or are secondary effects of the causal agent(s).

A theoretical model of gas transport between arterioles and tissue.

A theoretical model of CO2 and O2 diffusion between arterioles and tissue was developed to determine if significant transport could occur in precapillary vessels. There is increasing evidence, both theoretical and experimental, that such exchange does occur. Using a model in which CO2 and O2 were coupled through the Bohr and Haldane effects, we quantified the radial and axial transport. We also examined the roles of axial diffusion in the arteriole wall and tissue and capillary structure on the transport. Capillary arrangements investigated included capillaries independent of the arteriole with the entering capillary PCO2 or PO2 equal to a constant, and capillaries branching off along the length of the arteriole with the entering capillary partial pressure equal to the arteriole partial pressure at the given axial location. We found that for CO2 in arterioles with an inner diameter ranging from 200 to 22 microns, the exiting blood was 6 to 45% of the way to complete equilibrium with the surrounding tissue, respectively. For O2, the range was 8 to 25%, respectively. We also determined that axial diffusion in the arteriole wall and tissue has little effect on the transport and that capillary structure can alter tissue PCO2 by as much as 12 mm Hg in the smallest arteriole, but has little effect on O2 transport.

Chronic fatigue syndrome: new insights and old ignorance.

Chronic fatigue syndrome (CFS) is a condition characterized by impairment of neurocognitive functions and quality of sleep and of somatic symptoms such as recurrent sore throat, muscle aches, arthralgias, headache, and postexertional malaise. A majority of patients describe an infectious onset but the link between infections and CFS remains uncertain. Findings show an activation of the immune system, abberations in several hypothalamic-pituitary axes and involvement of other parts of the central nervous system. The origin is bound to be complex and it may well be that the solution will come together with a more generally altered view about mind-body dualism, and the concept of illness and disease.

Combinations of maximum urinary flow rate and American Urological Association symptom index that are more specific for identifying obstructive and non-obstructive prostatism.

Uroflowmetry and the American Urological Association symptom index (AUASI) are often used clinically to evaluate patients with benign prostatic hyperplasia (BPH). Since results from these tests may be used to determine a treatment course, including surgical intervention, we investigated if specific combinations of uroflowmetry and AUASI parameters could better predict urodynamically confirmed prostatic obstruction. Data from 134 men (mean age: 67.8 +/- 8.9 years) with prostatism were analyzed. The patients underwent uroflowmetry in the standing position after completing the AUASI; the post-void residual volume (PVR) was determined. The presence and severity of prostatic obstruction was assessed by video urodynamics, which included micturitional urethral pressure profilometry (MUPP). Of the 134 total patients, 66 were found to be obstructed by MUPP. Correlations of maximum urinary flow rate (Qmax), PVR, and AUASI with the degree of obstruction were poor and not substantially improved using combinations of these parameters. Threshold values of Qmax and AUASI, when used in combination, allowed accurate prediction of obstruction or non-obstruction in a small subset of the patient population. Of 14 men with both Qmax < 10 ml/s and AUASI > or = 20, 13 were obstructed (specificity = 98%). Eight of 9 men with both Qmax > or = 15 ml/s and AUASI < 10 were non-obstructed. The combined Qmax and AUASI criteria categorized only 20% of the patients as obstructed or non-obstructed. Once other causes of urinary dysfunction are ruled out, use of these criteria will enable the urologist to make an accurate diagnosis of obstruction, select a treatment more likely to benefit the patient, and make further diagnostic testing unnecessary in this small subset of patients. In a large volume clinical practice of adult male voiding dysfunctions, diagnosis of even this small proportion of patients using this simple approach can reduce patient care costs.

Urodynamic risk factors for renal dysfunction in men with obstructive and nonobstructive voiding dysfunction.

PURPOSE: Urodynamic investigation of men with lower urinary tract symptoms, usually attributed to benign prostatic hyperplasia, often reveals bladder outlet obstruction, detrusor instability and/or diminished vesical compliance. We investigated whether these urodynamic abnormalities alone or in combination contribute to renal dysfunction. MATERIALS AND METHODS: A total of 161 men with lower urinary tract symptoms was evaluated by urodynamics, and outlet obstruction, detrusor instability and decreased compliance (30 ml./cm. water or less) were noted. Serum blood urea nitrogen (BUN) and creatinine were measured. Cases were categorized according to the urodynamic diagnosis. Mean values of serum BUN and creatinine as well as the incidence of elevated BUN and creatinine were compared among groups. RESULTS: Of the cohort 54 men (34%) had elevated BUN and 19 (12%) had elevated serum creatinine. No significant correlation was found between the degree of obstruction and BUN or creatinine level. Mean serum BUN and creatinine, and the incidence of abnormal laboratory tests did not significantly differ among those with outlet obstruction, detrusor instability, both conditions or neither condition. However, in patients with outlet obstruction and detrusor instability there was a significantly increased incidence of azotemia in the subgroup with diminished compliance (78%) versus the subgroup with normal compliance (36%). CONCLUSIONS: In men with voiding dysfunction of a nonneurogenic etiology outlet obstruction with or without detrusor instability does not appear to be a risk factor for elevated BUN and creatinine. However, when decreased bladder compliance is associated with a combination of outlet obstruction and detrusor instability, this risk is substantially increased.

Immunoglobulin subclass levels in chronic fatigue syndrome.

The levels of immunoglobulin subclasses were determined for 46 patients meeting the original Centers for Disease Control case definition of chronic fatigue syndrome and were compared to values obtained for 50 age- and gender-matched healthy volunteer blood donor controls. The levels of immunoglobulin subclasses in these groups were further compared to a third group of additional chronic fatigue syndrome cases from whom samples had been obtained and frozen prospectively over a period of 7 years. These data do not demonstrate significant immunoglobulin subclass deficiencies in patients with chronic fatigue syndrome.