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B cell function in patients with chronic pancreatitis and its relation to exocrine pancreatic function.

Exocrine pancreatic function was evaluated by a Lundh meal test and a secretin-cholecystokinin test in 16 patients with chronic pancreatitis. B cell function was assessed by measuring the concentration of C-peptide after stimulation with oral glucose and intravenous glucagon. The Cc-peptide response to intravenous glucagon and oral glucose was closely correlated (r = 0.88, p less than 0.01). Plasma C-peptide after glucagon was significantly correlated to the post-prandial concentration of lipase (r = 0.72, p less than 0.001), amylase (r = 0.64, p less than 0.05) and to amylase output (r = 0.64, p less than 0.05). Eight out of nine patients treated with insulin had residual B cell function, but it diminished significantly with increasing duration of diabetes. We conclude that B cell function is correlated to pancreatic enzyme secretion and that patients with insulin-treated diabetes secondary to chronic pancreatitis have a residual insulin secretion similar to that of patients with Type 1 (insulin-dependent) diabetes.

Adult

Estimation of overall pulmonary function after irradiation using dose-effect relations for local functional injury.

PURPOSE: To predict the pulmonary function 3-4 months after irradiation for malignant lymphoma from the three-dimensional (3-D) dose distribution. METHODS: Dose-effect relations for the relative reduction of local perfusion (Q) and local ventilation (V), were calculated in 25 patients, using correlated SPECT (Single Photon Emission Computed Tomography) and CT data. By combining the 3-D dose distribution of an individual patient with the dose-effect relations averaged over all patients, the average reduction of local Q and V (i.e., the overall response parameters) in the whole lung was estimated for each patient. Correlation coefficients were calculated between these overall response parameters and the change in standard lung function tests. In addition, the relation between the overall response parameters and the incidence of radiation pneumonitis was determined. RESULTS: The overall response parameter for perfusion was correlated with the change in standard lung function tests, with correlation coefficients varying between 0.53 (p = 0.007) and 0.71 (p < 0.001) for the change of Vital Capacity and Forced Expiratory Volume at 1 s, respectively. For the overall response parameter for ventilation similar correlations were observed. Four out of the 25 patients developed radiation pneumonitis; in these four patients the overall response parameter for perfusion was on average somewhat higher (13.2 +/- 1.4% (1 standard error of the mean)) than in patients without radiation pneumonitis (10.5 +/- 1.0%), but this difference was not significant. A higher incidence of radiation pneumonitis was observed for larger values of the overall response parameter for perfusion; in patient groups with an overall response parameter for perfusion of 0-5%, 5-10%, 10-15%, and 15-20%, the incidence of radiation pneumonitis was 0 (0/1), 10 (1/10), 13 (1/8) and 33% (2/6), respectively. CONCLUSION: By combining the 3-D dose distribution with the average dose-effect relations for local perfusion or ventilation, an overall response parameter can be calculated prior to irradiation, which is predictive for the radiation-induced change in the overall pulmonary function, and possibly for the incidence of radiation pneumonitis, in this group of patients.

Adolescent

[The effect of acute cellular rejection on liver function following orthoptic liver transplantation. Quantitative functional studies with the 14C-aminopyrine breath test].

To test the effect of acute cellular rejection on liver function as represented by cytochrome-P-450 enzyme activity, the 14C-aminopyrine breath test (ABT) was performed prospectively in 46 patients (31 men, 15 women; mean age 48 [15-66] years) who had undergone a total of 50 orthotopic liver transplantations. Routine biochemical tests were performed daily until the 30th postoperative day, while the ABT was done daily on days 1-10 and three times weekly on days 11-30, and liver puncture biopsies were obtained once weekly or more often if there was clinical suspicion of rejection. Histologically confirmed cellular rejection occurred within the stated period of observation in eight patients (five women, three men; median age 45 [18-59] years). Results of routine laboratory tests (transaminases, bilirubin, thromboplastin time), as well as bile-flow and body temperature, did not vary uniformly. On the other hand, results of ABT at the time of rejection showed a decrease in all patients by an average of 65% (P < 0.01). Changes in the ABT preceded those in other tests by 1-2 days in four patients, being the only measurable functional abnormality in one. All rejection episodes responded to glucocorticoid pulse-treatment (three times 1 g methyl-prednisolone). Using ABT results as criterion, liver function became normal after the glucocorticoid injection within 4-11 days. These data indicate that the ABT is suitable in the routine monitoring of transplant function, thus facilitating early diagnosis and controlled treatment of acute cellular rejection.

Acute Disease

Indoor air pollution and its effect on pulmonary function of adult non-smoking women: II. Associations between nitrogen dioxide and pulmonary function.

The association between nitrogen dioxide levels in homes and pulmonary function of 97 non-smoking adult women was investigated in a rural area in the Netherlands. The study population was a sub-sample of a longitudinal field study on chronic non-specific lung diseases which was started in 1965. Pulmonary function tests were performed at three-yearly intervals. NO2 was measured for one week in the winter in kitchen, living room and bedroom of each home. Cross-sectional analyses showed negative associations between NO2 exposure and several pulmonary function parameters as measured in the 1982 study. No significant association could be found between NO2 exposure and pulmonary function decline since the start of the study.

Adult

Left ventricular diastolic function after anthracycline chemotherapy in childhood: relation with systolic function, symptoms, and pathophysiology.

OBJECTIVES: To examine left ventricular (LV) diastolic function in patients previously treated with anthracycline drugs for childhood malignancy. To consider clinical relevance, relations with systolic dysfunction, and the pathophysiology of anthracycline cardiotoxicity. DESIGN: Cross sectional echocardiographic study of LV function. SETTING: Supraregional centre for paediatric cardiology, principal centre for the treatment of childhood malignancy in southwest England. PATIENTS: 226 of 236 patients surviving between 6.5 months and 17 (median 5.3) years from initial anthracycline treatment for childhood malignancy attended for clinical and echocardiographic examination. Cumulative anthracycline doses were between 50 and 750 (median 300) mg/m2. 22 patients had also received cardiac irradiation. METHODS: Detailed assessment of transmitral diastolic pulsed wave Doppler flow patterns along with LV dimensions and systolic function measured by M mode echocardiography. MAIN OUTCOME MEASURES: Peak early (E) and atrial (A) phase filling velocities and EA ratio, time and acceleration and deceleration to and from peak E velocity, velocity integrals and ratio, isovolumic relaxation time (IVRT), and heart rate were measured. Results were examined in relation to LV cavity and posterior wall dimensions and shortening fraction (SF), and compared with paired control data matched for body surface area. RESULTS: Eleven (5%) patients had abnormal effort tolerance. Fifty one (23%) had SF < 30% and SF was inversely correlated with cumulative dose and time from treatment. The relative risk of symptomatic cardiac failure was greatly increased by prior irradiation; > 60% of irradiated patients who received > 400 mg/m2 of anthracycline were symptomatic. Early diastolic filling was relatively normal or enhanced at low anthracycline doses or when SF was preserved, with a shorter IVRT and increased atrial phase filling. Early filling was reduced at higher doses or with reduced SF, with longer IVRT and a further increase in atrial phase filling. A more "restrictive" pattern of diastolic filling (with high E and low A velocities) was seen in some patients, particularly after cardiac irradiation. CONCLUSIONS: Significant abnormalities of diastolic function are associated with anthracycline induced cardiac damage. These are not linearly related to anthracycline dose but appear to reflect the underlying myocardial pathophysiology associated with anthracycline toxicity, which is not demonstrated by the standard M mode echocardiogram. Although the overall clinical significance of such diastolic dysfunction is uncertain, some individual abnormalities may have significant management and therapeutic implications.

Adolescent

Relationship of lung function loss to level of initial function: correcting for measurement error using the reliability coefficient.

The regression of lung function change on the initial lung function level is biased when the initial level is measured with random error. Several methods have been proposed to obtain unbiased estimates of regression coefficients in such circumstances. We apply these methods to examine the relationship between lung function loss over 11 years and its initial level in 433 men aged about 20 when first seen. On theoretical and practical grounds the best method is the correction of the regression coefficient using the reliability coefficient. This is defined as the ratio of the error free variance to the variance of the variable measured with error, and is easily estimated as the correlation between repeat measurements of the underlying level. In young men the loss of some lung functions (forced vital capacity [FVC], forced expiratory volume in one second [FEV1], forced expiratory flow in the middle half of expiration, and the ratio FEV1/FVC) do not appear to be related to initial level.

Adult

Lung function in young adults: evidence for differences in the chronological age at which various functions start to decline.

In order to gather prospective information on the chronological age at which lung functions start to decline, follow-up measurements were carried out on 38 young adults (30 men and eight women) whose respiratory and cardiac function had been studied previously in the course of a survey of high school students. In the 15 subjects who had reached adult height at the time of the first study, only the vital capacity showed no change between studies, while forced expiratory flow rates (FEV1, MMEF), transfer factor (TLCO) and alveolar volume (VA) all decreased. By contrast, in the 23 subjects who had grown in stature since the previous tests, there was an increase in the slow and forced vital capacity, no consistent change in FEV1 and MMEF, and a decrease in TLCO. The findings are consistent with the view that the age-related decline does not start at the same chronological age for all lung functions, and suggest that structural changes associated with biological "aging" affect some functions before others. The results also illustrate the inadequacy of predicting values for early adulthood by backward extrapolation from later decades or forward extrapolation from the teens, and underline the need for comprehensive studies to elucidate the pattern of change which accompanies growth, maturation, and early adulthood.

Adult

Amino acid-enriched glucose-insulin-potassium infusion improves hemodynamic function after coronary bypass surgery. A double-blind study in patients with unstable angina and/or compromised left ventricular function.

OBJECTIVE: The goal of this study was to assess the effects of a combination of glucose-insulin-potassium (GIK) and the amino acids aspartate and glutamate upon perioperative hemodynamics in coronary surgery patients with unstable angina and/or compromised left ventricular function. DESIGN: Prospective, randomized, and double-blind clinical study. SETTING: Operating theatre and intensive care unit (ICU) of a university hospital. PATIENTS: 44 coronary artery bypass graft (CABG) patients with unstable angina and/or compromised left ventricular function. INTERVENTIONS: 22 patients (group A) were given 1l of an infusion with 250g glucose, 100 I.U. fast-acting human insulin, 72 mmol potassium, 32 mmol magnesium, 20 mmol phosphate, 65 mmol aspartate, and 65 mmol glutamate, while another 22 patients (group C) were given 1l of an infusion with 50 g glucose, 72 mmol potassium, 32 mmol magnesium, and 8 mmol phosphate. The infusion rate was 1.2 ml/kg/h from the anesthesia induction onward to the commencement of cardiopulmonary bypass, when it was reduced to 0.8 ml/kg/h. When 11 had been infused, but not later than 4 a.m., the infusion was continued by giving 10% glucose at the same rate to both groups. Additional insulin (median: 14.2 I.U., range: 0-41.5) or saline was given during bypass to the A and C patients, respectively. A blood cardioplegia technique containing aspartate and glutamate was used in both groups. RESULTS: At aortic cannulation, the cardiac index (CI) had increased from the pre-anesthetic level by 15.3% (mean) (SD: 31.7%) in group A and decreased by 7.7% (15.1%) in C patients, p = 0.0069. Also the changes in stroke index (SI; p = 0.022), left (LVSWI; p = 0.0037) and right ventricular stroke work index (RVSWI; p = 0.0097) were more favorable in group A. Despite longer aortic cross-clamp, p = 0.031, and perfusion times, p = 0.042, in A patients, the change in cardiac index was also better in this group after bypass: At decannulation, the difference between mean values was 31.8%, p = 0.0001, and at arrival in the ICU it was 16.1%, p = 0.028. The same was also seen 8 h postoperatively and on the 1st and 2nd postoperative mornings; p = 0.034, 0.040, and 0.037, respectively (Wilcoxon test). Favorable changes were seen for the A patients also regarding SI at decannulation (p = 0.0002) and after 8 h (p = 0.017); LVSWI at decannulation (p = 0.0002), at arrival in the ICU (p = 0.0023), and after 8 h (p = 0.0011); and RVSWI at decannulation (p = 0.0027), at the ICU (p = 0.021), after 8 h (p = 0.014), and on the 1st postoperative morning (p = 0.039). However, the response to a hemodynamic loading test (6% hydroxyethyl starch 5 ml/kg) was similar in the 2 groups, and there was no difference in the need for inotropic support. CONCLUSIONS: Amino acid-enriched GIK infusion improves hemodynamic function in CABG patients with unstable angina and/or compromised left ventricular function.

Aged

Deficiency of the adhesive protein complex lymphocyte function antigen 1, complement receptor type 3, glycoprotein p150,95 in a girl with recurrent bacterial infections. Effects on phagocytic cells and lymphocyte functions.

A patient presenting delayed umbilical cord detachment, severe recurrent bacterial infections, and inability to form pus exhibited a profound defect in the expression of alpha- and beta-chains of the receptor for the C3bi fragment of C3 (CR3), lymphocyte function antigen 1 (LFA-1) molecule, and the p150,95 molecule found on neutrophils, monocytes, and lymphocyte membranes. This was shown by immunofluorescence studies using specific monoclonal antibodies, rosette formation with C3bi-coated erythrocytes, and immunoprecipitation for the LFA-1 complex. These membrane defects were responsible for abnormal phagocytic cell functions including adherence to nylon wool, cell movement, phagocytosis, and opsonized particle-induced oxidative response and for defective natural killer cell activity. In addition, lymphocyte function deficiencies previously unobserved in this disease were found. Cytolytic T lymphocyte activity was profoundly reduced; alpha- and gamma-interferon production were impaired. Finally, there was no antibody production to vaccinal antigens whereas the antibody responses to polysaccharides and to cytomegalovirus were found to be normal. The cytotoxic T cell deficiency could be expected from previous blocking experiments of this function with monoclonal antibodies to LFA-1 and is probably related to an extremely severe deficiency in LFA-1 expression in this patient. Anomalies in interferon and in antibody production suggest additional role(s) of the LFA-1 complex in monocyte/T lymphocyte/B lymphocyte cell interactions that have not yet been envisaged.

Antibodies, Monoclonal

Clinical significance of pulmonary function tests. Pulmonary function after uncomplicated myocardial infarction.

Derangement of pulmonary function following myocardial infarction is related to the severity of hemodynamic dysfunction. Abnormalities of pulmonary function appear even in patients without clinical or radiologic evidence of congestive failure. There is a reduction in vital capacity and rates of air flow. There is evidence for dysfunction of "small airways" and diminished ventilation to dependent parts of the lung. Total lung capacity may be normal or reduced, and residual volume may be increased slightly in uncomplicated myocardial infarction. Residual volume falls with more pronounced pulmonary congestion and edema. Distribution of pulmonary perfusion is altered after myocardial infarction, with a shift of perfusion away from the dependent parts of the lung (bases) towards the apices. Pulmonary gas exchange is impaired, with hypoxemia (due to both ventilation-perfusion inequality and increased shunting); and the diffusing capacity for carbon monoxide is diminished. Dead space is increased. The basic pathophysiologic mechanism responsible for abnormalities of pulmonary function is increased pulmonary water, which may be very minimal with uncomplicated myocardial infarction and stay primarily in the pulmonary interstitial space, but becomes progressively more severe with eventual alveolar flooding and marked impairment of pulmonary function.

Humans

Amrinone therapy in patients with heart failure. Lack of improvement in functional capacity and left ventricular function at rest and during exercise.

Short-term amrinone therapy has been shown to exert beneficial hemodynamic effects in patients with heart failure. To determine whether this improvement persists longer, the effects of maximally tolerated doses of amrinone on exercise duration, oxygen consumption, and left ventricular function and volumes were examined during maintenance therapy. After four weeks of amrinone therapy, 75 to 150 mg three times a day (mean 292 +/- 70 mg daily), treadmill exercise duration, maximal oxygen consumption, and functional class were unchanged from control values. Radionuclide-derived ejection fraction and end-diastolic and end-systolic volumes were not altered at rest or during maximal supine exercise. Similarly, significant changes in echocardiographic end-systolic and end-diastolic dimensions did not occur. This lack of clinical benefit on functional capacity and left ventricular function, together with frequent adverse reactions, will limit the application of amrinone in the treatment of heart failure. These findings are relevant to the investigation of amrinone-like derivations presently being studied for the treatment of heart failure. Before their release, these agents will require careful evaluation and demonstration of a therapeutic action during maintenance therapy, together with a low incidence of adverse reactions.

Administration, Oral

Long-term deficits of goal-directed vestibulo-ocular function following total unilateral loss of peripheral vestibular function.

Brief whole-body movements (+/- 5 to 170 degrees/s peak velocity; approximately equal to 0.5 s duration), applied during 1.44-s intervals of total darkness while subjects "looked" at a just-viewed target, were used to examine vestibulo-ocular function in 3 patients who had compensated to total unilateral loss of peripheral vestibular function. We found that the combined effects of slow-phase and saccadic eye movements both tended to keep the eyes stabilized on the unseen target. Compensatory slow-phases elicited during rapid head movements ipsilateral to (i.e., towards) the lesion were only about 60% as effective as those elicited during rapid contralateral movements. Compensatory gaze-correcting saccades tended to supplement deficient slow-phase movements, especially during rapid ipsilateral head movement. However, the gaze-correcting effect of saccades was only about half of the required for perfect stabilization. Thus, two functional vestibular deficits were observed during rapid ipsilateral head movements: (1) reduced slow-phase stabilization, and (2) reduced saccadic ability to adequately supplement the deficient slow phases. However, overall vestibular functional capability, as assessed by observation of the net effect of both slow phases and saccades, was much better than would be indicated by conventional observation of slow-phase movements alone.

Adult

The relation between motor function development and vestibular function tests in four children with inner ear anomaly.

It is well known that the development of motor function is frequently retarded in children with congenital deafness, particularly in cases of inner ear anomaly. The relation between the results of vestibular function tests and the development of motor function in 4 children with inner ear anomaly is studied. CT scan obtained from these cases revealed the absence of lateral semicircular canals in both ears. There were no responses to caloric stimulation using 40 ml ice-water. However, damped rotation test elicited per-rotatory nystagmus in all cases. In contrast to this result, the same nystagmus was provoked only in 2 cases in Barany rotation test. Early development of motor functions, especially that of first walk, was more retarded in the 2 cases showing no per-rotatory nystagmus in Barany rotation test than in the other 2 positive cases.

Child

Regional time-based functional imaging of hepatocyte function.

Hepatocyte function was analyzed following the injection of 5 mCi of Tc-99m disofenin by the computer generation of three kinds of functional images designed to portray regional rates of hepatic uptake. Nineteen patients were analyzed, of whom eight had no overt liver disease, five had active hepatitis, five had cirrhosis, and one had acute cholecystitis. Functional images were graded according to lack of regional homogeneity of accumulation. Uptake kinetics were found to be significantly more homogeneous in normal subjects, becoming increasingly heterogeneous in hepatitis and cirrhosis patients, respectively. Thus functional imaging may provide a tool for the quantitative analysis of parenchymal disruption in liver disease.

Adult

[Respiratory function in extrinsic allergic alveolitis caused by pigeons. Clinical, pathological and functional correlation].

Lung function tests (LFT) were performed in 71 patients with proven extrinsic allergic alveolitis due to pigeons (EAA-P), and they were correlated with lung biopsy (LB) findings. Lung function studies were analyzed to evaluate the clinical course of these patients treated with corticosteroids. Restrictive pulmonary function impairment was found in all cases (vital capacity 38 +/- 4%), residual volume was increased in 9 out of 14 patients (64%) (RV = 0.51 +/- 0.06 L.) and bronchial obstruction was a feature in 11/14 patients (78%) (MMEF = 53 +/- 4%). In all cases a low Pa02 was observed (44 +/- 2 mmHg) and in six an increase in PaC02 was detected. The vital capacity did not correlate with the degree of inflammation or fibrosis observed by LB. A significant negative correlation was found between Pa02 and the degree of inflammation (r = 0.68, p X 0.05) as well as with fibrosis + inflammation degrees (r = -0.63, p less than 0.05). In general, initial LFT and clinical improvement occur simultaneously. Lung function tests support the diagnosis of EAA-P, but are not capable of separating inflammation from lung fibrosis.

Adolescent

[Deterioration of liver function following endoscopic injection sclerotherapy of esophageal varices--significance of the new liver function test "intravariceal injection (I.I.) index"].

Changes of liver functions associated with endoscopic injection sclerotherapy (EIS) were investigated in 143 patients with remarkable esophageal varices. The index used for evaluating hepatic reserve was the ratio between the increase of total bilirubin and the increase of LDH after EIS [I.I. index = (delta T.Bil./delta LDH) x 100] in cases treated by intravariceal injection of 5% ethanolamine oleate. I.I. index value caused by hemolysis was stable and always below 0.2, while the elevation of I.I. index above 0.2 was regarded as the reflection of the deterioration of liver function. After the entire sessions of EIS, the changes of liver function tests before and after EIS were estimated in 104 cases using 3 factors as follows; (1) delta T.Bil.; increase of total bilirubin more than 0.5 mg/dl (2) delta PT; decrease of prothrombin time more than 5% (3) delta ICG R15; increase of ICG R15 more than 5%. I.I. index of group I (without any changes of 3 factors mentioned above; n = 66) was 0.22 +/- 0.16, approximately within normal range. However, in group II (with 1 factor; n = 29), group III (with 2 factors; n = 5), group IV (with all factors; n = 4), I.I. index was elevated according to the severity of their liver dysfunction. The cases whose I.I. index value increased gradually during the course of EIS, were apt to deteriorate the liver functions and therefore, should be carefully observed. Also, I.I. index seems to reflect the prognosis of the patients treated by EIS for some extent, since the survival period of the cases treated by EIS were correlative with the value of I.I. index (r = -0.542, p < 0.01), and I.I. index of 32 cases who survived for longer than 5 years after EIS was almost normal (0.22 +/- 0.15).

Adult

Kinetics of hepatocellular proliferation as a function of the microvascular structure and functional state of the liver.

An analysis of hepatocellular proliferation in regenerating rat liver reveals a dependence of kinetic parameters on the microvascular structure of the liver. Influx kinetics of hepatocytes into DNA synthesis as well as cell cycle phases vary in different parts of the liver lobule between the afferent and efferent vascular poles. Heterogeneity of the proliferative response and size limitations on cell cycle compartments appear to be intimately related to the actual functional state of the individual liver cell. Modifications of liver cell functions result in variations of the proliferative activity. Phenobarbital-induced hypertrophy of hepatocytes reveals a permissive action on G1- S influx. Selective destruction of the subpopulations, by allyl formate, leads to a new functional determination of the residual liver and to a change in proliferative compartments. Maximum modulation of cell cycle compartments is obtained by hydroxyurea-induced synchronization of hepatocytes after partial liver resection. During hydroxyurea treatment, the regenerating liver shows a pronounced cellular hypertrophy. After release from hydroxyurea block, cells embark on DNA synthesis simultaneously. The DNA synthesizing compartment comprises almost the entire liver cell population. Heptotrophic factors might play a part in regulating or modifying hepatocellular function and proliferative response after cell loss.

Allyl Compounds

Longitudinal study of leukocyte functions in homosexual men seroconverted for HIV: rapid and persistent loss of B cell function after HIV infection.

The early effects of infection with human immunodeficiency virus (HIV) were investigated in homosexual men who had seroconverted for anti-HIV antibodies. Leukocyte functional activities were determined in longitudinally collected peripheral blood mononuclear cell samples. During the first 10 months following seroconversion, anti-CD3 monoclonal antibody-induced T cell proliferation, monocyte accessory function and T helper activity on B cell differentiation in a pokeweed mitogen-driven system were not affected. In contrast, from the moment of seroconversion on, B cells of seroconverted men failed to produce immunoglobulin in the pokeweed mitogen-driven system. This defect was not restored by addition of normal CD4+ T cells. Immunoglobulin synthesis induced by Staphylococcus aureus and interleukin 2 decreased gradually, until it was completely lost 10 months after seroconversion. In addition, proliferation in response to anti-IgM or Staphylococcus aureus by B cells from HIV seroconverted men was decreased. The lack of inducible in vitro B cell activity was not accompanied by elevated spontaneous Ig synthesis by B cells of the seroconverted men. In the second group of men studied during the 2nd year following seroconversion, T helper activity on normal B cell differentiation significantly decreased, whereas anti-CD3-induced T cell proliferation and monocyte accessory function were not significantly affected. Our results demonstrate that in almost all HIV-infected individuals B cell functional defects are the first leukocyte abnormalities observed preceding defects in T helper activity.

Antibody Formation