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PubMed1994

Functional and physical characterization of the cell cycle ubiquitin-conjugating enzyme CDC34 (UBC3). Identification of a functional determinant within the tail that facilitates CDC34 self-association.

Like several other ubiquitin-conjugating enzymes, the yeast cell cycle enzyme CDC34 (UBC3) has a carboxyl-terminal extension or tail. These tails appear to carry out unique functions that can vary from one ubiquitin-conjugating enzyme to the next. Using biophysical techniques we have determined that the tail of CDC34 constitutes a highly structured and extended domain. Although the tail of CDC34 is the largest tail identified to date (125 residues), we have found that only 39 residues lying adjacent to the catalytic domain are necessary and sufficient for full cell cycle function and that this region fulfills a novel function that may be common to the tails of other ubiquitin-conjugating enzymes. Cross-linking studies demonstrate that this region facilitates a physical interaction between CDC34 monomers in vitro. Furthermore, phenotypic analysis of various CDC34 derivatives expressed in different cdc34 mutant strains indicates that this region facilitates the same interaction in vivo. Based on these findings, it appears that the cell cycle function of CDC34 is dependent upon the ability of CDC34 monomers to interact with one another and that this interaction is mediated by a small region of the CDC34 tail. The similarity of this region with sequences contained within the tails of the UBC1 and UBC6 enzymes suggests that these tails may function in a similar manner.

Anaphase-Promoting Complex-Cyclosome↗

PubMed1978

Adherent cell function in murine T lymphocyte antigen recognition. II. Definition of genetically restricted and nonrestricted macrophage functions in T cell proliferation.

The mechanisms by which adherent cells, presumably of mononuclear phagocytic lineage, influence in vitro antigen-specific activation of murine T lymphocytes was examined. Two distinct functions for macrophages could be discerned. One macrophage function is dependent on a soluble factor produced by cultured adherent cells and is most easily studied with complex multideterminant antigens. This factor is neither antigen-specific nor MHC-restricted in its action in that PEC, regardless of haplotype, produce factor in the absence of antigen. A second function, antigen-specific T cell activation, is seen when antigens of more restricted heterogeneity are used, such as those under the control of Ir genes. This latter activity demands identity or partial identity between the antigen-presenting cell and the primed T cell, thus suggesting an additional specific, genetically restricted function for macrophages in in vitro antigen recognition. Whether these adherent cell functions are mediated by all or distinct subsets of cells was not established.

Animals↗

PubMed1993

Functional imaging in computed tomography. The use of contrast-enhanced computed tomography for the study of renal function and physiology.

RATIONALE AND OBJECTIVES: Computed tomography (CT) numbers may provide the raw material for calculations of important physiologic parameters, such as organ regional perfusion and glomerular filtration rate. Because, except in cases of severe renal dysfunction, iodinated intravascular contrast agents are excreted primarily by passive glomerular filtration, the decline in their concentration in blood or tissues will reflect renal function. The time evolution of contrast agent distribution within the kidney, from blood to tubules, can also be seen as a measure of renal function. The authors illustrate how CT numbers may be employed to obtain useful data regarding renal function. METHODS: Two CT methods were used to yield information on renal function. Delayed CT: 2 hours after administration of 200 mL of a contrast agent (iohexol) for a routine CT, a patient with normal renal function was brought back to the scanner, and a single fixed section through the abdomen, including the psoas muscles, was imaged; the scan was repeated at 2, 3, and 4 hours. Large regions of interest were selected in soft tissue, and six measurements of CT numbers were taken and averaged for each time; after taking logs, these were plotted against time. Dynamic CT: A rapid bolus of 40 mL nonionic contrast agent was injected into an antecubital vein at 5 mL/sec. At a fixed level, images were taken through the center of the kidneys at 5-second intervals for 2 minutes after injection. The patient was allowed to breathe gently throughout the examination. Regions of interest were selected over the kidney and the aorta, and curves of CT numbers against time were generated; a Patlak plot was performed using the parameters measured. Using the renal CT numbers collected during the first 2 minutes after injection, it was possible to analyze the handling of the contrast agent and to obtain a measure of the glomerular filtration rate. RESULTS: Delayed CT: Data yielded good values for glomerular filtration rate; the typical patient illustrated had a glomerular filtration rate per unit extracellular fluid volume of 0.005 min-1. Dynamic CT: The correlation coefficient for the line fit was 0.97, a value typically found in these studies, indicating the efficacy and ruggedness of this method in spite of the patient's shallow breathing throughout the examination. CONCLUSIONS: Computed tomography offers the potential for quantitative and physiologic measurement that has not been widely explored. The problem with the delayed CT technique is that since measurements are made at 2 hours and onward, it is applicable only to patients who have received larger doses of contrast. Otherwise, the CT numbers are low and the measurement error, large. Also, bringing the patient back to the scanner 2 hours later may be inconvenient to both patient and radiologist, and may disrupt case scheduling. This method is, however, less inconvenient than the established blood-level measurement. The dynamic CT method yields a new measure of renal clearance, namely, clearance per unit volume of kidney. The disadvantages of this method are the radiation burden involved in repeated rapid CT scans and the fact that, if renal disease is uneven, a nonrepresentative slice could be chosen. Its advantages are its simplicity and that it can be completed within the first 2 minutes of a CT examination. It may be expected to have an interesting application to situations in which there is known renal disease. Although difficulties are associated with both of these techniques that could prevent their general adoption as clinical routines, they nevertheless should find application in selected patients and should prove useful research tools in the study of renal disease.

Contrast Media↗

PubMed1993

Premorbid functioning, cognitive functioning, symptoms and outcome in schizophrenia.

In this study we examined the relationship between premorbid functioning, outcome, cognitive functioning and positive and negative symptoms of schizophrenia. Cognitive functioning and symptoms were examined longitudinally in a sample of 39 subjects with schizophrenia (according to the DSM-III criteria). Subjects were assessed at admission to hospital and six months later during a period of relative remission. Premorbid functioning was significantly associated with negative symptoms but not with positive symptoms at both the acute phase and the remitted phase of the illness. Outcome was also associated with negative symptoms at admission and with both positive and negative symptoms at follow-up. Deficits on cognitive tests of verbal reasoning and concept formation were significantly associated with poor premorbid functioning and outcome.

Adolescent↗

PubMed1995

Functional MR imaging in the evaluation of the patient with epilepsy. Functional localization.

Functional magnetic resonance imaging is able to define noninvasively the location of eloquent cortex responsible for speech, motor, and visual function, and it holds promise for localizing other important functional tissues in the future. Such localization is extremely important to the epileptologist and surgeon planning surgical resection of an epileptic focus. Early work identifies the actual seizure focus using similar techniques. Magnetic resonance, with functional magnetic resonance added to high-resolution magnetic resonance imaging and magnetic resonance spectroscopy, has the potential of providing, in a cost-effective manner with one noninvasive modality, the functional, anatomic, and chemical parameters pertinent to the management of the seizure patient.

Brain↗

PubMed1996

[Super selective amytal test for functional evaluation of the brain--a less invasive functional test].

In the neurosurgical field, it is very important to evaluate localized function of the affected region preoperatively. In order to investigate lateralized and localized brain function, we have developed an alternative to the original Wada test, and refer to it as the super selective amytal test (SSAT). We performed super selective catheterization of the target artery after conventional carotid angiography, injected Amytal (amobarbital, 30-100 mg) through a micro-catheter, and identified potential local function. In ten cases, including AVM, aneurysm, and brain tumor, we investigated localized function of the affected site preoperatively by SSAT, and chose our treatment based on the results of this test. There was a good correlation between the results of the SSAT and the results of surgery in every case. There were no prolonged neurological complications of this test. Evaluation of the results of the SSAT should be interpreted under precise DSA control, since blood flow in the brain differ among individuals. This test may contribute to our knowledge of localized function in the cerebral cortex and deep brain areas in neurosurgical patients.

Adult↗

PubMed1997

[Functional MRI of higher brain function with gradient echo on clinical MR unit].

MR imaging of brain function has been successfully performed at 1.5 T clinical MR unit. In the early studies, functional MRI were performed with simple stimulation such as visual and motor. Recently, many investigators have attempted to demonstrate the specific brain localization of higher brain functions such as memory, imagination, language and so on. In this study, we attempted the functional MRI for motor and word imagination with gradient echo sequences on clinical MR unit. In our experiences, motor cortex was activated on motor imagination task and Broca area was activated on word imagination task, respectively. We demonstrated the higher brain functions were able to be demonstrated on clinical MR unit with gradient echo sequences.

Frontal Lobe↗

PubMed1997

Functional magnetic resonance imaging of visual function in postpapilledema optic atrophy.

We studied a girl with intraventricular brain tumor who developed postpapilledema optic atrophy and severe concentric visual field constriction in both eyes. The patient had mild symptoms despite severe visual field loss. We performed functional magnetic resonance imaging using two kinds of visual stimulation to assess her residual visual function. The functional magnetic resonance imaging demonstrated that the activity in her association visual cortex was largely intact bilaterally, although the activation of the calcarine cortex was decreased in the left calcarine cortex. Her activity in the visual cortex seemed to correspond well to her visual symptom. Functional magnetic resonance imaging may be useful in objectively documenting residual visual function in patients with severe visual loss.

Adolescent↗

PubMed1997

[Relationship between systolic and diastolic function of the left ventricle in patients with impaired relaxation of the left ventricle without symptoms of heart failure. Attempt at quantitative estimation of diastolic function in the impaired relaxation stage].

UNLABELLED: Diastolic dysfunction of left ventricle appears very often in patients with coronary artery disease (CAD) and hypertension (HT) and is a main cause of heart failure in 30-40% of all cases. Relation between systolic and diastolic function of left ventricle (LV) is commonly known but not documented well enough. Moreover, no quantitative classification of diastolic dysfunction is still available. AIM OF THE STUDY: To find out the relations between the parameters of systolic and diastolic function of LV in patients with CAD or HT with impaired relaxation of LV without symptoms of heart failure and to make up the quantitative classification of diastolic dysfunction in the stage of impaired relaxation of LV. METHODS: Investigations were carried out in 57 patients (mean age 55.5 +/- 11.5) with angiographically proven CAD and in 91 patients (mean age 56.3 +/- 10.6) with HT and angiographically excluded CAD, all without regional myocardial contractility abnormalities and valvular heart diseases. Control group consisted of 54 healthy subjects (mean age 55.4 +/- 11.4). During 2D echocardiography examination left ventricular end-diastolic (LVEDD) and end-systolic diameters (LVESD) and left atrial dimension (LA) were obtained. Using Doppler method transmitral inflow indices: E velocity (E), A velocity (A), E velocity integral (E-VTI), A velocity integral (A-VTI), total velocity integral (T-VTI), E deceleration time (DT), isovolumic relaxation time (IVRT) and aortic flow velocity integral (Ao-VTI) were measured. Only patients with E/A < or = 1 and--to exclude pseudonormalization of mitral inflow--with DT > or = 140 ms were qualified to the study. We proposed diastolic dysfunction ratio (DDR) calculated from formula: DDR = E/A x E-VTI/T-VTI. Using AFVI, LV outflow diameter, heart rate (HR) and body surface area cardiac index (CI) was calculated. RESULTS: In studied group there were significantly higher values of LA, A, IVRT, DT and lower values of E, E/A, E-VTI and DDR compared to controls. There were no significant differences between these groups in HR, LVEDD, LVESD, T-VTI and CI. No significant differences in any of studied parameters were found between subgroups with CAD and HT. Among healthy subjects in subgroup with abnormal mitral inflow pattern (E/A < or = 1) there were significantly higher values of LA, IVRT, DT and lower values of DDR than in sugroup with normal one. Both subgroups did not differ in LVEDD, LVESD, CI. In the studied group there was positive correlation between DDR and CI (r = 0.69, p < 0.001), DDR and IVRT (r = 0.71, p < 0.001), DDR and DT (r = 0.61, p < 0.001), CI and E (r = 0.34, p < 0.01), CI and IVRT (r = 0.52, p < 0.001), CI and DT (r = 0.42, p < 0.001), CI and E/A (r = 0.54, p < 0.001), CI and E-VTI (r = 0.43, p < 0.001). In the control group significant correlation was found only between DDR and IVRT (r = 0.64, p < 0.02) and between DDR and DT (r = 0.52, p < 0.02) but not between DDR and CI. Using DDR DD was divided into 3 classes: class I with DDR > 0.47, class II with 0.47 > or = 0.30, and class III with DDR < 0.30. Applying of such intervals of values of DDR determined the groups which significantly differed between themselves in CI, IVRT and DT. CONCLUSIONS: (1) In patients with CAD or HT with impaired relaxation of LV without symptoms of heart failure there is relation between parameters of systolic and diastolic function of LV: the more advanced diastolic dysfunction, the more impaired systolic function. (2) In healthy subjects there is no relation between parameters of systolic and diastolic function of LV. (3) DDR is a good indicator of quantitative estimation of diastolic dysfunction in the stage of impaired relaxation of LV.

Adult↗

PubMed1998

[A modified method of cardiac functional analysis for ECG gated SPECT: study of functional G-maps].

To evaluate the cardiac function accurately using ECG gated SPECT images, we performed a modified method of cardiac functional analysis (Functional G-maps). One hour after the intravenous injection of 1,110 MBq of 99mTc-tetrofosmin, gated SPECT data was acquired dividing a cardiac cycle into 12 frames. Every short-axis images were usually reconstructed using first 11 of 12 frames. The reconstruction of these images was repeated performing slice thickness correction. Because the apex-to-base length is different at any frame during a cardiac cycle, 10 slices of short-axis images were obtained with the same thickness for each frame. Subsequently each short-axis image was divided by 40 radii, and the time activity curve was generated from the total counts included in each segment plus both neighboring segments. Afterwards the curve fitting was performed using the second reverse Fourier function. From fitted curves and their differentials, we estimated a variety of parameters including Max (End-systolic count), Min (End-diastolic count), %CI (Percent count increase), Uptake, PCR (Peak contraction rate), PDR (Peak distention rate) and CT (Contraction time). In 5 normal subjects, %Max was greater in the anterior and septal regions, whereas %Min was greater in the apex and lateral regions. %CI and %PCR were similarly greater in the septal, anterior and inferior regions. On the other hand, %PDR in the lateral or inferior region was lower than the values in the other regions. In conclusion, this modified method is expected to be useful for accurate assessment of regional cardiac function and myocardial perfusion.

Adult↗

PubMed1996

Enhanced effects of bleomycin on pulmonary function disturbances in patients with decreased renal function due to cisplatin.

We examined whether cisplatin-induced nephrotoxicity augmented bleomycin-induced pulmonary toxicity in patients with testicular cancer treated with etoposide and cisplatin with (BEP) or without bleomycin (EP). Before and at 3-week intervals during chemotherapy, creatinine clearance and lung functions were measured. In patients receiving BEP, deterioration of renal function correlated with a decrease in transfer factor of the lungs for carbon monoxide (TLCO) and vital capacity (VC), parameters known to reflect bleomycin-induced pulmonary effects. Other lung functions did not correlate with renal function. In the EP group, no relationships were observed at all. These observations suggest enhanced pulmonary effects of bleomycin when combined with cisplatin. Therefore, attention should be paid to the potential development of bleomycin-induced pulmonary toxicity in patients treated with BEP.

Adolescent↗

PubMed1992

RETRACTED: Right ventricular function in patients with reduced left ventricular function undergoing myocardial revascularization.

Complex interrelationships exist between the right (RV) and the left ventricles (LV). Therefore, in 30 consecutive patients with reduced LV function (left ventricular ejection fraction [LVEF]) less than 40% undergoing myocardial revascularization, RV hemodynamics were studied from the beginning of anesthesia until the end of the operation. The data were compared with 30 consecutive patients with normal LVEF (greater than 70%). Ventricular function was assessed during left heart catheterization, which was carried out within 1 month of the operation. In addition to standard hemodynamic variables, RV ejection fraction (RVEF), RV end-diastolic volume (RVEDV), and RV end-systolic volume (RVESV) were monitored by the thermodilution technique. The two groups did not differ preoperatively with regard to RVEF, pressure (MAP, PAP, PCWP, RAP, RVPsyst, RVEDP), cardiac index (CI), and volume variables (RVESV, RVEDV). However, when the group with preoperatively reduced LVEF was subdivided into patients with severely reduced LVEF (less than 30%; n = 14; mean value 25.1%) and patients with moderately reduced LVEF (30%-40%; n = 16; mean value 37.3%), RVEF was significantly lower in the patients with a LVEF below 30% throughout the entire investigation period. RVEDV and RVESV were significantly higher in these patients. In conjunction with the lower RVEF and normal PAP, this suggests reduced RV function. It can be concluded that a severely reduced preoperative LVEF (less than 30%) may also be associated with impaired RV function.

Analysis of Variance↗

PubMed1997

Dobutamine and nitroprusside infusion in patients with severe congestive heart failure: hemodynamic improvement by discordant effects on mitral regurgitation, left atrial function, and ventricular function.

OBJECTIVES: In patients with severe heart failure additional therapeutic support with intravenous inotropic or vasodilator drugs is frequently used in the attempt to obtain hemodynamic control. The nature and extent to which diastolic filling, atrial function, and mitral regurgitation are modified by these drugs have not been fully explored. The aim of this study was to compare the acute adaptations of the left ventricular performance, left atrial function, and mitral regurgitation that accompanied hemodynamic improvement during intravenous dobutamine and nitroprusside infusions in patients with severe chronic heart failure. METHODS: Forty consecutive patients with severe heart failure were evaluated by simultaneous echo-Doppler and hemodynamic investigations at baseline and during nitroprusside and dobutamine administration. Mitral flow velocity variables, left atrial and ventricular volumes, left atrial reservoir, conduit and pump volumes, and mitral regurgitation jet area were compared by analysis of variance for repeated measurements. RESULTS: Nitroprusside increased cardiac output (2.1 +/- .5 vs 2.6 +/- .5 L/min/m2, p < 0.004), reduced left ventricular filling pressure (25 +/- 6 vs 14 +/- 4 mm Hg, p < 0.0001), and improved left atrial pump volume (19 +/- 3 vs 26 +/- 12 ml, p < 0.02) without variations in left atrial reservoir and conduit volume. The restoration of preload reserve and improvement of the atrial contribution to left ventricular diastolic filling were demonstrated by the Doppler mitral flow pattern, which moved from a restrictive to a normal pattern. Furthermore mitral regurgitation decreased in all patients (9 +/- 4.6 vs 4.6 +/- 3.4 cm2, p < 0.0001). Dobutamine increased cardiac output (2.1 +/- .5 vs 2.8 +/- .6 L/min/m2), but the effects on pulmonary wedge pressure and mitral regurgitation were variable and unpredictable. Left atrial reservoir and conduit volumes increased, whereas left atrial pump volume did not change (19 +/- 13 vs 22 +/- 14 ml, p = NS). Furthermore Doppler mitral flow showed a persistent restrictive pattern. CONCLUSIONS: In patients with advanced congestive heart failure both nitroprusside and dobutamine improve cardiac output, with different adaptations of left ventricular performance and left atrial function. Nitroprusside seems to restore both atrial and ventricular pump function better. Careful echo-Doppler monitoring during drug infusion provides information relevant to the clinical treatment of individual patients.

Atrial Function, Left↗

PubMed1983

Hypothalamic-pituitary-gonadal function in relation to liver function in men with alcoholic cirrhosis.

Serum concentrations of oestrone, oestradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and sex hormone-binding globulin (SHBG) were significantly (P less than 0.01) raised in men with alcoholic liver cirrhosis (no. = 42) compared with age-matched controls (no. = 20). No significant difference was observed when comparing serum testosterone concentrations. Patients were divided into three groups in accordance with the severity of liver cirrhosis, using biochemical and clinical criteria. Patients with the best-preserved liver function (no. = 11) and patients with moderately affected liver function (no. = 18) had significantly (P less than 0.05) raised serum concentrations of testosterone, FSH, and LH when compared with both controls and patients with severely affected liver function (no. = 13). Serum concentrations of testosterone, FSH, and LH in the latter group showed no significant differences from the controls. Serum concentrations of oestrone and oestradiol were significantly (P less than 0.05) increased in all patient groups, and serum oestrone increased with decreasing liver function. No significant differences were observed concerning SHBG concentrations in the three groups of patients. Dexamethasone suppression did not change the concentration of testosterone significantly, but oestrone and oestradiol concentrations decreased significantly (P less than 0.01) in controls and patients. In patients, but not in controls, a significant (P less than 0.01) increase in FSH and LH concentrations was observed after dexamethasone suppression. The mean percentage increase of FSH and LH was higher the greater the severity of liver cirrhosis.

Adult↗

PubMed1991

Primary biliary cirrhosis: relation between hepatic function and pulmonary function in patients who never smoked.

We studied the relationship between selected variables of hepatic and pulmonary function in 47 patients with primary biliary cirrhosis, who were participating in a prospective study to assess sequential pulmonary function at yearly intervals. An additional 20 patients with primary biliary cirrhosis, who were liver transplant candidates awaiting transplantation, were studied. None of the 67 patients ever smoked cigarettes. Severity of primary biliary cirrhosis was characterized by histological stage and the Mayo risk score derived from a Cox regression model that used the following variables: serum bilirubin and serum albumin levels, age, prothrombin time and clinical severity of edema. Pulmonary function assessment included key variables describing expiratory airflow (forced expiratory volume in 1 sec divided by forced vital capacity) and efficiency of gas exchange (steady-state diffusing capacity for carbon monoxide). We found a significant relationship between histological stage of primary biliary cirrhosis and steady-state diffusing capacity (p = 0.02) and between the Mayo risk score for disease severity and steady-state diffusing capacity (p = 0.03). Progressive deterioration of steady-state diffusing capacity was associated with increasing severity of primary biliary cirrhosis. No relationship existed between pulmonary function and the presence of sicca complex or Sjögren's syndrome or the clinical manifestations of portal hypertension (e.g., esophageal varices, ascites and splenomegaly). No significant relationship existed between expiratory airflow and severity of primary biliary cirrhosis. We conclude that in patients with primary biliary cirrhosis who have never smoked, a statistically significant relationship exists between the severity of the liver disease and the efficiency of gas exchange measured by steady-state diffusing capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

PubMed1998

[The influence of left systolic ventricular function on right ventricular function after an acute myocardial infarct].

The aim of this study was to assess the interaction between left ventricular and right ventricular systolic function after acute myocardial infarction (AMI). The study population comprises 27 normal subjects and 71 patients assessed at predischarge (12 +/- 7 days) after AMI and divided into two subgroups, 24 with inferior AMI and 47 with non inferior AMI. The three groups were comparable for sex, age, heart rate and blood pressure. Right ventricular function was evaluated by two-dimensional assessment of tricuspid annular plane systolic excursion (TAPSE) and by Doppler analysis of right ventricular outflow tract. Left ventricular systolic function was evaluated by two-dimensional determination of ejection fraction and wall motion score index, and by Doppler analysis of left ventricular outflow tract. The overall AMI population showed reduced TAPSE, velocity-time integral (both p < 0.05) and peak velocity (p < 0.005) of right ventricular outflow tract, prolongation of Q-S2 interval and increase of pre-ejection period/acceleration time ratio (both p < 0.05) in comparison with normals. These alterations were accompanied by a decrease of left ventricular ejection fraction and increase of wall motion score index. (p < 0.0001) The changes of right ventricular indexes were confirmed in patients with inferior AMI who had also lower left ventricular ejection fraction (46 +/- 9%). Functional parameters of the right ventricle were not significantly modified in patients with non inferior AMI who had greater left ventricular ejection fraction (53 +/- 8.6%). In the overall AMI population, and in particular in inferior AMI, we found univariate relations between time-velocity integrals of left ventricular and right ventricular outflow tract and between left ventricular ejection fraction and TAPSE. Only in inferior AMI creatinkinase peak was related to time-velocity integral of right ventricular outflow tract (r = -0.59, p < 0.01). In conclusion, the magnitude of right ventricular systolic impairment developing after left ventricular AMI depends on the degree of left ventricular dysfunction, likewise by changes of hemodynamic load imposed to the right ventricle. AMI location and, only in inferior AMI, infarct extension participate in determining this dysfunction.

Analysis of Variance↗

PubMed1997

Quantitative liver function tests define the functional severity of liver disease in early-stage cirrhosis.

Some patients with early-stage cirrhosis preserve hepatic function, whereas others have little hepatic reserve and rapidly deteriorate. The aim of this study was to use quantitative tests of liver function (QLFTs) to define the degree of functional hepatic impairment in patients with early-stage cirrhosis (Child-Pugh score 5-7) and to determine whether the tests predicted subsequent hepatic decompensation. We recruited 10 cirrhotic (Cr) patients and 10 healthy controls (NI), who were well matched for race, age, weight, and gender. Clearances of caffeine (CF) and antipyrine (AP) after oral administration were measured from timed samples of saliva. The clearance of cholate (CA) was measured from serum samples obtained after simultaneous oral ([2,2,4,4-2H]CA) and intravenous ([24-13C]CA) administration. CA shunt was calculated as (Cl i.v./Clo x 100%). CF elimination rate (Cr v NI, mean +/- SD: 0.03 +/- 0.02 v 0.075 +/- 0.018 h-1, P < .0005) and AP clearance (24 +/- 16 v 40 +/- 7 mL/minute, P < .02) were reduced in Cr patients. CA shunt was increased in Cr patients (43 +/- 18 v 18 +/- 7%, P < .002). Five Cr patients decompensated during follow-up and had the worst CA shunts (76%, 66%, 51%, 48%, and 45%). Three subsequently received successful orthotopic liver transplantation, 1 died of hepatoma, and 1 is on the waiting list for transplantation. In conclusion, QLFTs define the degree of functional impairment in early cirrhosis and may identify Cr patients at greatest risk of decompensation who may require transplantation for survival.

Administration, Oral↗

PubMed1982

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↗