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PubMed1992

A functional model of adult human prostate epithelium. The role of androgens and stroma in architectural organisation and the maintenance of differentiated secretory function.

A functional model of adult human prostate epithelium is described. This model shows that stromal cells, but not an androgenic stimuli, are required for architectural organisation of prostate epithelium. Within an organised structure, androgenic stimulation is required for the establishment of secretory epithelial cell morphology and associated function. In the absence of stromal cells but in the presence of androgens architectural organisation and secretory function are lost. Epithelial parenchymal units (organoids) from human prostate tissue were isolated, cultured within a three-dimensional collagen matrix, and xenografted subcutaneously into athymic mouse hosts. The grafted gels were rapidly invaded by host fibroblasts. Epithelial organisation initially disappeared but was re-established concurrently with the stromal cell invasion. In intact male hosts, cuboidal and columnar cells that expressed human prostate-specific secretory markers were found. In castrated male and in female hosts epithelial structures were lined with flattened epithelium with no secretory function. This phenomenon could be reversibly replicated by treating intact male hosts with the anti-androgen Flutamide. Gels containing organoids grafted within 0.45 microns Millipore chambers were not invaded by stromal cells and rapidly lost all epithelial organisation and secretory function. When organoids cocultured with human foreskin fibroblasts were grafted within chambers, structural organisation of the epithelium was supported. These results indicate that both heterologous human fibroblasts and mouse stromal cells are capable of permissively supporting adult human prostate epithelial function.

Aged↗

PubMed1980

[Changes in glucose metabolism and endocrine function in the remnant pancreas after major pancreatectomy, with special reference to the function of the anti-insulin system in Sandmeyer's diabetes (author's transl)].

Changes in glucose tolerance and the function of the anti-insulin system after a major resection of the canine pancreas were divided into three types. Immediately after the removal of 90 per cent or more of the pancreas, diabetes developed, and the function of the anti-insulin system was depressed, showing a poor response of glucagon secretion to hypoglycemia after insulin load and degeneration or destruction of the islet cells and both A and B cells, and the dosage of insulin required to control blood sugar was close to that of a total pancreatectomy. 6 to 24 weeks after the removal of 70 to 90 per cent of the pancreas, so-called Sandmeyer's diabetes occurred, in which glucose tolerance and the function of the anti-insulin system were within the normal range during the early postoperative periods, but the function of the anti-insulin system was highly activated later, showing a high response of pancreatic glucagon secretion to hypoglycemia after insulin load, accompanied by degeneration of B cells, but not A cells. These results could well explain the fact that the insulin dosage needed to control blood sugar in Sandmeyer's diabetes was 3 to 4 times more than it was in total pancreatectomy. After the removal of 70 per cent or less of the pancreas, diabetes did not occur, and glucose tolerance and the function of the anti-insulin system were maintained well, without any significant change in the islets of the remnant pancreas. Insulin therapy relieved the disturbed function of the anti-insulin system in diabetes following pancreatectomy.

Animals↗

PubMed1991

Comparison of subjective ratings of function with observed functional ability of frail older persons.

BACKGROUND: Important clinical decisions often hinge on patients' functional status. Previous studies have shown disagreement among sources of ratings of patients' functional status. This study compared patient self-ratings, family member ratings, and physician ratings of patient function to performance-based functional testing criteria. METHODS: Five activities of daily living of 73 older patients were studied at admission to a rehabilitation unit following discharge from an acute care community hospital. Data were collected from patients, family members, and physicians and were compared with performance-based function testing. RESULTS: Patient ratings were significantly more accurate than physician ratings for walking, transferring, and telephoning. Patients were significantly more accurate than family members for rating walking and telephoning, but patients were not significantly more accurate than family members or physicians for rating eating or dressing. CONCLUSIONS: We conclude that decisions about patients' functional level should be based on performance testing. If performance testing is unavailable, patients' own ratings are most accurate, followed by family ratings. Physicians' ratings are least accurate.

Activities of Daily Living↗

PubMedDate not supplied

Assessing the function of functional assessment: a consumer perspective.

The person who is most affected by the process of functional assessment is the consumer--the individual with a disability whose functional capacity is being assessed. Consumers want the functional assessment process to be conducted in a dignified manner and the results to be relevant to their needs. Many consumers, influenced by the independent living movement, focus primarily on their ability to live independently in their communities and on environmental barriers that prevent them from doing so. Yet, most functional status measures focus primarily on impairments and functional limitations, rather than on handicapping environmental factors. Consumers should be involved directly in the development and application of functional status measures so that these factors are considered appropriately. Such measures have important implications for defining programme eligibility, determining payment, assuring quality, and enhancing discharge planning.

Activities of Daily Living↗

PubMed1989

[Magnetic resonance image of pituitary adenoma--comparison of functioning tumor and non-functioning tumor].

Thirty three cases of pituitary adenoma were examined by MRI with 0.15 T system. Eight cases of functioning tumor showed iso-minimally low intensity, and 10 cases of non-functioning tumor did slightly-markedly low intensity on IR image. Functioning tumor cells contain well-developed rough-surfaced endoplasmic reticulum, Golgi complexes and numerous secretary granule, so that bound water more increases and T 1 relaxation time less prolongs in functioning tumor than in non-functioning tumor. Two cases of functioning tumor disclosed slightly low intensity on IR image because of its poor stroma. It is necessary to know the exact bleeding time so as to measure the signal intensity in pituitary apoplexy case. Microadenoma appeared spotty hypointensity and upward convexity of superior surface of the gland on IR image.

Adenoma↗

PubMedDate not supplied

[Hypothesis of possible evolution and functional specialization based on the recombination and transposition of elementary functional blocks].

A number of examples demonstrating that different cell and organ functions are being performed by a limited set of identical or similar functional blocks has been analysed. The latters are molecular or supramolecular structures fulfilling elementary functions. Functional evolution, functional and structural specializations, divergence, convergence and other processes have been considered as associated largely with the relationship, recombination and transposition of such elementary functional blocks, presumably, originated at the early stages of evolution.

Animals↗

PubMed1995

[Functional and anatomical results after surgical treatment of ruptures of the rotator cuff. 1: Preoperative functional and anatomical evaluation of ruptures of the rotator cuff].

PURPOSE OF THE STUDY: In a consecutive series of 98 patients presenting 100 full thickness cuff tears and managed by the same medico-surgical team, the authors studied the correlation between preoperative shoulder function values and the anatomic lesions found at surgery. Predictive factors of tear size were evaluated and any elements that were likely to improve preoperative function were determined so that patients could be best prepared for surgery. The validity of preoperative radiographic assessment of lesions was examined. MATERIAL AND METHODS: Prior to surgery, each patient was given the same rehabilitation program, the same arthrotomographic assessment of lesions and each was rated functionally using Constant's scoring method. Preoperative radiographic assessment of lesions showed supra-spinatus tears in 69 per cent, combined supraspinatus and infraspinatus tears in 22 per cent, and tears involving the supraspinatus, infraspinatus and subscapularis in 9 per cent. RESULTS: The preoperative Constant score averaged 46/100 points. The score was higher when patients had been prepared by preoperative rehabilitation to overcome stiffness. The optimum duration of rehabilitation was found to be 3 months (p < 0.05). Active range of motion was 90 per cent of normal in 84 per cent of cases. The patients in this series therefore underwent surgery more for continuing severe pain (25 per cent) and muscle weakness (86 per cent) than for reduced active motion. DISCUSSION: Examination of the correlations existing between an anatomic lesion and the preoperative rating of shoulder function shows that the Constant preoperative score provides a good prediction of the size of the tear to be repaired (p = 0.0063). The greater the tear size, the lower the preoperative Constant sore is. Active range of motion (especially in abduction and external rotation) and muscular strength are factors with the most predictive value contrary to pain and discomfort which are influenced by tear size. CONCLUSION: Preparing patients suffering full thickness cuff defects through preoperative rehabilitation to overcome stiffness provides the best conditions for surgery. Constant's functional scoring method gives a reproducible and reliable reflection of the anatomic rotator cuff lesion to be repaired. Its use for preoperative rating is useful for determining a reference value for function prior to surgery.

Adult↗

PubMed1995

Cognitive function and assessment of lung function in the elderly.

The feasibility of spirometry or respiratory impedance measurements for assessing lung function in the elderly was compared in 208 institutionalized patients with various degrees of cognitive function impairment. Respiratory impedance was determined by the forced oscillation technique. Cognitive function was assessed by the score for the mini-mental state (MMS) examination. Of the 208 patients, 126 had severe cognitive impairment (MMS < or = 17), 36 had mild impairment (18 < or = MMS < or = 23), and 46 had no impairment (MMS > or = 24). Of the 208 patients, respiratory impedance measurements were possible in 159, whereas in only 85 was spirometry possible. The overall difference between the feasibility rates for the spirometric and respiratory impedance measurements was highly significant (chi 2 = 71.4; p < 10(-6)). The difference between the feasibility rates for the two techniques was higher in the group of subjects with severe cognitive impairment than in the groups with mild impairment and no impairment, respectively. Among the 84 patients able to complete both tests, significant correlations were found between the spirometric and respiratory impedance measurements. These results indicate that respiratory impedance measurement seems a more useful tool than spirometry for assessing lung function in elderly patients whenever cognitive function is impaired.

Aged↗

PubMed1980

Functional correlates of lung involvement in Wegener's granulomatosis. Use of pulmonary function tests in staging and follow-up.

To examine the usefulness of pulmonary function testing in the clinical management of patients with Wegener's granulomatosis, 22 subjects with biopsy proved disease were evaluated using routine functional parameters. Although reduced lung volumes and diffusing capacity occurred frequently, the most common abnormality was in obstruction to airflow. Comparison of these functional parameters with roentgenographic and clinical findings revealed that reduced lung volumes were useful in detecting focal infiltrates, mass or cavitary lesions and diffuse interstitial involvement whereas airflow measurements were useful in detecting focal large airway lesions. In people with evidence of limitation of airflow, respiratory complications frequently developed in the form of acute tracheal obstruction of lobar collapse. In addition, serial evaluation of lung function during treatment revealed that although in most patients lung volumes and airflow obstruction improved or stabilized, a reduction of diffusing capacity was common. These studies suggest that routine pulmonary function testing may be a useful tool in the staging of patients with Wegener's granulomatosis and in following responses to therapy.

Adult↗

PubMed1988

Prospective prediction of post-radiation therapy lung function using quantitative lung scans and pulmonary function testing.

Surgeons have made use of quantitative perfusion lung scanning (QS) and forced expiratory volume in one second (FEV1) to predict a patient's ability to tolerate lung resection. In this study QS and FEV1 were used to predict prospectively pulmonary function following lung irradiation (XRT). Twenty-two patients have had QS and FEV1 determined before XRT and at planned intervals post-XRT. Serial determination of lung function post-XRT allows comment on the temporal nature of the XRT effect on lung function. Seventeen patients had QS and FEV1 determined at an interval of 2-6 months post-irradiation with a drop in the groups mean FEV1 from 1.91 to 1.87L. or 2% during that interval. In the interval from 6-12 months post-XRT, 13 patients had studies with the groups mean FEV1 dropping from 1.79 to 1.58L or 12% of the original. In the interval from 12-18 months, 6 patients had a decline in mean FEV1 from 1.73 to 1.56L. or 10% of the original. In 22 patients a predicted final FEV1 was compared with a measured value at an interval from XRT. Fourteen of these determinations were at intervals greater than 6 months from the start of XRT and 6 at intervals of greater than 1 year. FEV1 was seen to drop during the follow-up intervals toward the predicted value. In only 2 patients did the final FEV1 drop below the predicted FEV1 and never by more than 0.12L. (6%). In summary, a method for predicting post-XRT pulmonary function using QS and FEV1 is described. Serial follow-up revealed a latent period followed by a late phase where FEV1 fell toward, but not significantly below, the predicted value. Such a determination can be of value in formulating a treatment plan for patients with significantly diminished pulmonary function.

Forced Expiratory Volume↗

PubMed1991

Effects of nisoldipine on systolic and diastolic function in postinfarction patients with reduced left ventricular function: a randomized, double-blind, placebo controlled study.

The long-term effects of oral nisoldipine or placebo on clinical variables, exercise test results and echo Doppler-determined systolic and diastolic functions were studied in 30 consecutive patients with reduced left ventricular function (predischarge echocardiographic wall motion score greater than or equal to 8) following myocardial infarction. Groups were comparable in clinical variables, exercise results, echo Doppler measurements and coronary anatomy. During 6 months follow-up, death, reinfarction and bypass surgery or balloon angioplasty were equally distributed. A significant increase in exercise duration and time to onset of ST-depression was found in the nisoldipine treatment group, compared to the placebo group after 3 and 6 months. Time to onset of angina was not significantly different. Echocardiographic indices of left ventricular systolic function (ejection fraction and wall motion score) were unaltered; however, the time-velocity integral of the early diastolic filling phase and the early vs late diastolic flow velocity ratio were significantly increased while the atrial time-velocity integral vs total time-velocity integral was significantly decreased in the nisoldipine treatment group after 3 and 6 months of follow-up. In conclusion, nisoldipine reduced exercise-induced ischaemia, improved exercise capacity and diastolic left ventricular function in postinfarction patients with reduced left ventricular function.

Cardiac Catheterization↗

PubMed1977

Relation of immediate post-transplant renal function to long-term function in cadaver kidney recipients.

Renal function studies 12 to 41 months after transplantation have been performed on seven cadaver renal allograft recipients who demonstrated immediate primary function after transplant (group A) and seven similar recipients who had delayed primary function (group B). The groups were matched as closely as possible for major physical characteristics and their postoperative management; in particular, only one patient had a post-transplant renal biopsy. Glomerular filtration rate was determined by 24-hr creatinine clearance, endogenous creatinine clearance, and inulin clearance was usually lower in those patients having delayed primary function and they excreted more glucose per 24 hr and reabsorbed a smaller proportion of the filtered glucose load under infusion conditions. These results are discussed in relation to the effect of immediate and delayed primary function on the long-term prognosis of such patients.

Adult↗

PubMed1995

Language function after temporal lobectomy without stimulation mapping of cortical function.

We studied 95 patients who underwent standard anterior temporal lobectomy (ATL) without stimulation mapping of language areas, using neuropsychological parameters of language function preoperatively and 1 year postoperatively [Boston Naming Test and Verbal Fluency, and the Information, Comprehension, Arithmetic, Similarities, Digit Span, and Vocabulary subtests of the Wechsler Adult Intelligence Scale (WAIS)]. Verbal IQ (VIQ), Performance IQ (PIQ), Full-Scale IQ (FSIQ), and Verbal Deviation Quotient were also evaluated, as were parameters of memory function. All patients had hemisphere dominance for language assessed by an intracarotid amytal test. Fifty-three patients had a left dominant (LHDL) ATL with a mean extent of lateral resection of 4.8 cm, and 10 had a left ATL with right or mixed hemisphere dominance (RHDL, MDL). Thirty-two patients had a right nondominant ATL. Seizure outcome was 57 and 59% seizure-free for LHDH and right nondominant group, respectively, 1 year after operation. Comparison of preoperative scores showed the LHDL group to have significantly lower scores than the right nondominant group for several parameters of language function and memory. The group undergoing left dominant ATL showed no significant loss of language function postoperatively and actually showed gains in many parameters. Standard ATL without stimulation mapping of language areas and with conservative lateral resection is safe for long-term language function. In addition, evidence shows preexisting language dysfunction in patients undergoing left dominant ATL.

Adolescent↗

PubMed2026

Structural modeling and functional characterization of a novel gain-of-function TLR8 variant causing severe inflammatory syndrome.

With the increasing use of genetic sequencing to investigate inborn errors of immunity, rare variants are frequently identified, yet their clinical relevance often remains uncertain. Establishing pathogenicity requires a multidisciplinary approach that integrates genetic, structural, functional, and clinical data. Here, we used such a strategy to investigate a previously unreported hemizygous missense variant - alanine (A) to threonine (T) at residue 518 - in Toll-like receptor 8 (TLR8), identified in 2 male siblings with recurrent infections and systemic inflammation, characterized by a proinflammatory immune signature and B cell dysregulation. Functional studies showed that the TLR8 A518T variant enhanced NF-κB activation and increased secretion of proinflammatory cytokines compared with WT TLR8 upon stimulation, consistent with a gain-of-function effect. Protein degradation and turnover assays revealed reduced abundance of the mutant TLR8 protein due to faster turnover and increased proteasomal degradation. Computational modeling predicted enhanced structural stabilization of the active TLR8 homodimer interface via additional water-mediated hydrogen bonds introduced by the A518T substitution. Together, these findings integrating structural modeling with functional assays identify a novel TLR8 ligand-specific gain-of-function mutation resulting in complex immunopathology in 2 siblings.

Humans↗

PubMed1992

The effect of acute hypoxia on left ventricular function with special reference to diastolic function--an analysis using ultrasonic method.

In order to evaluate the effect of acute hypoxia on left ventricular (LV) contractility and diastolic function, hemodynamics and LV wall motion were investigated in anesthetized open-chest paced dogs using M-mode or pulsed Doppler echocardiography. Animals were ventilated with 10% oxygen (Hypo 1) and 6.3% oxygen (Hypo 2). LV contractility and diastolic functions were enhanced under "Hypo 1" and at an early phase of "Hypo 2". However, LV functions, both systolic and diastolic, were simultaneously reduced in the presence of hypercapnic acidosis by "Hypo 2". Peak velocities of diastolic rapid filling flow (R) and atrial contraction flow (A) were increased under "Hypo 1", but showed a biphasic change (an increase and a subsequent decrease) under "Hypo 2". The ratio of A/R, known as an index of LV diastolic function, was not altered under hypoxia alone or even under hypercapnic acidosis. Even when hypoxia seems to enhance LV contractility, LV function has already begun to be depressed with a reduction of pH. This seems, however, to be compensated for by LV dilatation and increase in preload, or preservation of left atrial performance.

Acidosis↗

PubMed1990

Regulation of macrophage activation by IL-3. I. IL-3 functions as a macrophage-activating factor with unique properties, inducing Ia and lymphocyte function-associated antigen-1 but not cytotoxicity.

Here we report that IL-3 (also referred to as multi-CSF because of its colony-stimulating activity on a variety of hemopoietic cell lineages) can function as a macrophage-activating factor (MAF). IL-3 was able to regulate the expression of class II MHC Ag and the cellular interaction molecule lymphocyte function-associated Ag-1 on the surface of murine peritoneal exudate cells. The kinetics of IL-3-induced Ia expression appeared to be distinct from that induced by either IFN-gamma, IL-4, or granulocyte-macrophage-CSF. IL-3 was also distinguished from these factors by the finding that it did not induce macrophage tumoricidal activity. In addition to its inherent MAF activities, IL-3 also showed a marked synergy with low doses of LPS (0.05 to 0.5 ng/ml) as well as IFN-gamma in Ia induction. When lymphocyte function-associated Ag-1 expression was evaluated, the effects of these stimuli appeared to be only additive. Although LPS has been shown to inhibit IFN-gamma-induced Ia expression, in our experiments this property of LPS is manifest only when present at doses greater than or equal to 50 ng/ml. At lower concentrations, LPS potentiated both IL-3- and IFN-gamma-induced class II MHC Ag expression. Data presented here also suggest that the synergistic interactions between low doses of LPS and IL-3 are not mediated by known LPS-inducible cytokines of macrophage origin, because rIL-1, TNF-alpha, or IL-6 did not enhance the response to IL-3. Because IL-3 can also participate in the regulation of IL-1 expression, it appears that IL-3 can function as a MAF which selectively regulates the accessory cell characteristics required for Ag presentation, as opposed to the cytolytic functions of the macrophage.

Animals↗

PubMed1987

Ambulatory ventricular function monitoring for serial assessments of cardiac function during exercise.

An ambulatory ventricular function monitor (VEST) facilitated measuring left ventricular (LV) function, and performing electrocardiography (ECG) in a natural environment. To assess cardiac response to a variety of exercises, LV function was serially recorded for each of 18 normal subjects using a VEST. The VEST detector was fixed over the LV region following the gated blood pool scan, and the beat-to-beat LV time-activity curve and ECG were continuously recorded. After a baseline recording was made with the subject sitting quietly, the subject performed on a bicycle exercise (n = 16), on a treadmill (n = 14), and by walking up 10-16 flights of stairs (n = 18) while wearing the VEST. The beat-to-beat radionuclide data were averaged for 15-30 seconds to calculate ejection fraction (EF), relative end-diastolic (EDV) and end-systolic (ESV) volumes, and the heart rate. Serial LV function monitoring during each exercise, particularly while walking upstairs and on a treadmill, documented rapid increases in EF during the early stages of exercise, with increases in EDV, decreases in ESV, and no change in EF in the later stages. Heart rate and systolic blood pressure increased progressively with successive stages. The pressure rate product at the peak exercise was highest during treadmill exercise (32,600) and lowest while climbing stairs (24,700). Immediately after exercise, EDV and ESV rapidly decreased and EF increased further, particularly after bicycle and treadmill exercise. These data demonstrate that the VEST can measure LV function continuously in an ambulatory environment, and that it is an effective means of evaluating normal cardiac physiology during various exercises.

Adult↗

PubMed1987

[Renal and adrenal function following acute administration of urapidil in hypertensive patients with normal and impaired renal function].

The effects of i.v. injection of urapidil (Ebrantil) (25 mg) on arterial blood pressure, renal function and renin-aldosterone system were studied in a group of patients with hypertension and normal renal function, in patients with hypertension and chronic renal failure and in normotensive controls. The pharmacokinetics of urapidil were evaluated simultaneously by measuring blood levels of the compound and its main metabolite. In the controls and in patients with hypertension, systolic and diastolic blood pressure were lowered few minutes after injection. Minimal blood pressure values were reached after 15-20 min. Hypotensive action was more pronounced in hypertensive patients as compared to controls. In contrast, increment in heart rate was greater in the controls. Despite the fall in blood pressure, renal plasma flow and glomerular filtration rate remained unchanged. Following the injection of urapidil, plasma renin activity increased with no change in plasma aldosterone levels. Plasma half-life of urapidil averaged 1.96 +/- 0.17 h in controls, 3.31 +/- 0.75 h in patients with hypertension and normal renal function and 2.52 +/- 0.46 h in patients with hypertension and chronic renal failure. Urapidil effectively lowers arterial blood pressure in patients with normal and impaired renal function with no deterioration in renal function.

Adrenal Glands↗