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A method for the simultaneous evaluation of exocrine pancreatic function and intestinal absorptive function in dogs.

Exocrine pancreatic function was evaluated in 13 dogs, using the chymotrypsin-labile peptide N-benzoyl-L-tyrosyl-p-aminobenzoic acid (BT-PABA). This peptide releases p-aminobenzoic acid (PABA) in the presence of pancreatic chymotrypsin. The amount of PABA in blood or urine after BT-PABA administration then served as an index of pancreatic function. Similarly, a xylose absorption test has been described in the literature to evaluate absorptive function of the small intestine. Here, the pentose sugar d(+)xylose was given orally, and blood xylose concentrations were then measured at intervals. Since both tests were performed in nearly the same way, they were combined into a single test. A solution containing BT-PABA (30 mg/ml) and xylose (100 mg/ml) was administered perorally to dogs with and without pancreatic duct ligation. In the unoperated (control) dogs, peak blood concentrations for PABA occurred between 60 and 120 minutes and xylose concentrations were maximal between 30 and 90 minutes. Pancreatic duct ligation reduced PABA concentrations at 90 minutes to one-sixth of the values in control dogs. Xylose absorption, however, was not altered by pancreatic duct ligation. In this way, digestive and absorptive functions were both evaluated, using a single 90-minute test.

4-Aminobenzoic Acid

[Characteristics of disorders of renal function in circulatory insufficiency (according to I131-hippuran clearance and diurnal rhythm of the indicators of renal function].

The paper is based on a study of 270 cases of different stages of chronic circulatory insufficiency. A whole set of functional-diagnostic (radio-isotope including) methods of examination was employed to solve the task in question. It was found that one of the early signs of functional disorders in the kidneys in cases of circulatory insufficiency is, along with renal ischaemia, the pathology that is discovered during the examination of the functional phases of renograms. The characteristics of the circadian fluctuations of some renal function parameters are given. Two stages of the formation of the so-call renal syndrome in cases of chronic circulatory insufficiency were distinguished and discussed.

Adult

Exocrine pancreatic function in protein-deficient patas monkeys studied by means of a test meal and an indirect pancreatic function test.

Exocrine pancreatic secretion was studied in 9 patas monkeys before and during protein depletion, and in 4 of them also during recovery from protein depletion. Pancreatic function was estimated by measuring enzymatic activities in the duodenal contents after a test meal and by determination of urinary excretion of p-aminobenzoic acid (pancreatic function test) after oral ingestion of the chymotrypsin-labile peptide N-benzoyl-L-tyrosyl-p-aminobenzoic acid. The average serum albumin dropped by 34.8% to 2.6 g per 100 ml. Significant decrease of trypsin, lipase, amylase, and chymotrypsin was observed in the duodenal samples during protein deficiency. Urinary excretion of p-aminobenzoic acid was also reduced significantly. The two tests correlated well. In 3 of 4 animals, recovery of pancreatic function was noted after refeeding a full protein diet. Pancreatic atrophy was noted in 2 animals which died. The study shows that exocrine pancreatic secretion can be seriously impaired even at a moderate protein deficiency and may not be reversibly in all instances. Therefore, function tests have to be evaluated with caution when hypoproteinemia, i.e., hypoalbuminemia, is present.

Aminobenzoates

Maximal expiratory flows at functional residual capacity: a test of lung function for young children.

Maximal expiratory flows at functional residual capacity were measured noninvasively from partial expiratory flow-volume curves in 65 awake, healthy children, 4 to 6 years of age. The variabilities within and between subjects were nearly identical to those reported for flows low in the vital capacity obtained from older subjects. This test of maximal expiratory flow at functional residual capacity has the advantage that the subject does not have to inspire to total lung capacity, exhale to residual volume, or make a maximal effort, and it is therefore applicable to the testing of young children who cannot perform a vital capacity maneuver. Measurement of this flow rate in 20 patients of the same age with lung disorders of varying severity revealed abnormal flow rates in more than 50 per cent of patients. Functional residual capacity was measured by the closed-circuit helium-equilibration method. When flow rates in liters per sec were compensated for lung size, girls had significantly larger flow rates than did boys. This suggests that the lungs of young children may grow differently according to genetic determinants related to sex.

Adolescent

In vitro functional studies of mononuclear cells in patients with CLL: evidence for functionally normal T lymphocytes and monocytes and abnormal B lymphocytes.

In vitro functional studies of mononuclear cells from 34 patients with B-cell type CLL were investigated and the results of these studies were as follows: 1) The T lymphocytes from patients with CLL were capable of responding normally to PHA or PWM, of inducing allogeneic normal B lymphocytes to respond to these mitogens and of stimulating normally to allogeneic lymphocytes in "one-way" mixed lymphocyte reaction; 2) The monocytes from these patients were capable of enhancing the T lymphocyte response to mitogens and of stimulating normally to allogeneic lymphocytes; and 3) The leukemic B lymphocytes were incapable of responding to mitogens even in the presence of normal T lymphocytes and their enhancer cell activity on T lymphocyte response or their stimulating capacity on allogeneic lymphocytes was depressed. These observations suggest that the T lymphocytes and monocytes from patients with CLL are functionally normal while the leukemic B lymphocytes from these patients are functionally abnormal.

Adult

Clinical and Functional Characterization of Gain-of-Function ABL1 Variants Expands the Phenotypic Spectrum of CHDSKM.

Germline gain-of-function (GOF) variants in ABL1 cause congenital heart defects and skeletal malformations syndrome (CHDSKM), a multisystem developmental disorder characterized by congenital heart disease, skeletal abnormalities, dysmorphic features, and variable developmental delay. More recently, biallelic loss-of-function variants and ABL haploinsufficiency have been associated with distinct phenotypes, expanding the allelic spectrum of ABL1-related disorders. We report three individuals with ABL1 variants. A female infant with tetralogy of Fallot, critical pulmonary stenosis, covered omphalocele, and a lethal outcome was found by rapid trio genome sequencing to harbor a de novo likely pathogenic ABL1 variant, NM_007313.2:c.354G>T p.(Trp118Cys). We also provide updated clinical follow-up of a previously reported individual and describe a third individual, both carrying the recurrent p.(Tyr245Cys) variant. Functional studies were performed and support a GOF mechanism. Similar activation was observed for Tyr245Cys despite the differences in clinical severity. Our findings expand the phenotypic spectrum of ABL1-related CHDSKM to include severe conotruncal heart disease and covered omphalocele. The comparison of two biochemically activating ABL1 variants demonstrates substantial clinical variability despite a shared molecular mechanism. Furthermore, the overlap between ventral body wall abnormalities in GOF disease and omphalocele associated with ABL1 haploinsufficiency suggests that precise regulation of ABL1 signaling is critical for normal ventral body wall formation.

ABL1

Structural and functional changes in an identified cricket neuron after separation from the soma. II. Functional changes.

Physiological and behavioural effects of separation from the soma were examined in isolated arborization and isolated axon segments of an identified motor neuron in the Polynesian field cricket, Teleogryllus oceanicus. The identified neuron, the contralateral dorsal longitudinal motor neuron of the metathoracic ganglion (CDLM), has an arborization most of which lies contralateral to its soma within the ganglion. Midline lesions in the ganglion separated CDLM into a distal segment composed of the axon and most of the arborization, and a proximal segment made up of the remaining arborization, neurite and soma. Isolated axonal segments were produced by cutting the nerve containing the CDLM axon. The function of the neuron-muscle system composed of CDLM, its pre-synaptic inputs, and its innervated muscle bundle was examined in contrl and experimentally operated animals. Extracellular recording assessed function in the axon. Electrical or tactil stimulation was used to excite pre-synaptic inputs to the CDLM arborization. Intracellular recording determined changes in post-synaptic potentials and miniature end-plate potentials in the muscle bundle innervated by CDLM. Normal axonal conduction, competence to respond to pre-synaptic input, neuron-muscle transmission, and miniature end-plate potential appearance can remain in the isolated arborization preparation. Physiological viability is longer in the cricket isolated arborization than in other insect distal segments described. Survival times of axonal conduction and the competence of the isolated arborization to respond to pre-synaptic input are roughly correlated with disappearance of the whole distal segment at 100 or more postoperative days. A naturally-occurring breakdown of the metathoracic dorsal longitudinal muscles in Teleogryllus eventually prevents measurements of post-synaptic potentials and miniature end-plate potentials. Normal post-synaptic function mediated by the distal arborization is maintained up to this breakdown, to a maximum of 44 days postoperative. The distal axonal segment of CDLM degenerates physiologically within four days postoperative, a time course approximating that of degeneration in vertebrate peripheral nerve distal axons.

Animals

[Carbenicillin induced disturbance of platelet function: a study in patients with normal renal function (author's transl)].

After therapeutic doses of carbenicillin (3X10 g/24 h) prolongation of bleeding time, measured according to Ivy, was observed (median time prior to therapy 4 min 08 s-4 min 18 s; 24 h after therapy 15-20 min; 72 h after therapy greater than 30 min) in 5 patients with normal renal function and 2 patients with slight impairment of renal function (Ccr60-70 mlX1.73 m(2)). Prolongation of bleeding time was observed at serum concentrations between 13 and 180 microgram/carbenicillin/ml. After carbenicillin was withdrawn, prolongation of bleeding time was demonstrable for 4 days, i.v. even after the drug had been eliminated completely by urinary excretion. Higher doses of carbenicillin caused more severe disturbances of platelet function. The finding of prolonged bleeding time after carbenicillin may have clinical relevance (e.g. interaction with other anticoagulants, p.o. wound bleeding, gastro-intestinal hemorrhage, thrombopenia).

Adult

Ovarian cancer: a solid tumor with evidence of normal cellular immune function but abnormal B cell function.

Immunologic assays of B and T lymphocyte function were performed on 21 patients with epithelial ovarian cancer prior to either chemotherapy or radiotherapy. The results were compared to similar studies on 12 age-matched normal women. The total peripheral blood lymphocyte counts, proportion of E rosette positive cells, stimulation of T cells by phytohemagglutinin and concanavalin A, recall skin tests, and the ability to have a primary delayed hypersensitivity response to keyhold limpet hemocyanin did not differ between patients and controls. However, patients with ovarian cancer had statistically significant reduction in surface immunoglobulin positive cells, proliferative response to pokeweed mitogen and primary antibody response to keyhole limpet hemocyanin. In contrast to results in patients with other solid tumors, these data indicate that untreated patients with ovarian cancer have evidence of normal cellular immune function but abnormal B cell function.

Adult

Augmentation of macrophage complement receptor function in vitro. I. Characterization of the cellular interactions required for the generation of a T-lymphocyte product that enhances macrophage complement receptor function.

The function of complement receptors of mouse peritoneal macrophages was converted in vitro from mediating only attachment of macrophage complement receptor function was achieved by treating freshly explanted macrophages with supernates from cultures containing T lymphocytes and appropriately triggered macrophages. Fc receptor-mediated phagocyctosis by macrophages was required for the production of active supernates, for neither ingestion via the cells' complement receptors nor ingestion via nonimmunologic means was a sufficient stimulus for the macrophages' participation in the generation of supernatant activity. Fc receptor-triggered macrophages interacted by a contact dependent, but histocompatibility independent, mechanism with T lymphocytes, thereby signalling the lymphocytes to elaborate the active product. The possible significance of enhanced macrophage complement receptor function in inflammation, host defense against microbial pathogens, immune complex disease, and neoplasia is discussed.

Animals

Clinical application of the functional matrix: mandibular reconstruction and monobloc functional therapy.

A 13-year-old black girl with an extensive ameloblastoma of the mandible required subtotal mandibular resection and immediate reconstruction with use of an autogenous, ipsilateral, corticocancellous graft from the iliac crest and monobic functional therapy. Twenty-seven months later, clinical evaluation showed normal mandibular function and no facial asymmetry. Bony architectural changes after 27 months included reformation of the coronoid process, angular process, and external oblique ridge; preservation of mandibular length and thickness; and maintenance of the alveolar ridge height. The reformation of the coronoid process suggests the importance of the functional matrix (temporalis muscle) in skeletal tissue growth. The monobloc appliance in conjunction with bone grafting is an effective means for transmission of biophysical stimuli and for maintenance of appropriate stress for remodeling of bone in the mandible.

Activator Appliances

Renal pelvic function following total alloplastic replacement of ureter in pigs. Electrophysiology, renal function and morphology.

Total replacement of one ureter was under-taken in pigs. After an observation period of 2-3 months further studies were made. Pelvic peristaltic activity as reflected by pelvic pressure waves and electrical activity was indistinguishable from that in normal pigs. In particular, retrograde activity was not observed. It appears that ureteric peristalsis is not a prerequisite of normal pelvic function. Providing only that the calibre is sufficient, function of a ureteric prosthesis is satisfactory, and no changes in kidney or pelvis function and morphology are apparent.

Action Potentials

Long-term functional results of surgery for coronary artery disease in patients with poor ventricular function.

Thirty-two patients with coronary artery disease and an ejection fraction (EF) below 0.40 had coronary bypass and/or left ventricular aneurysm (LVA) resection. Twenty-four patients had a previous infarction, 12 had congestive heart failure (CHF), and left ventricular end-diastolic pressure averaged 15 mm. Hg. Nineteen patients had three-vessel involvement and there was an average of 2.4 vessels involved per patient. Bypass was accomplished on 87 per cent of vessels; 11 patients had resection of LVA; 11 had coronary endarterectomy. There were no hospital deaths, 63 per cent of the patients were improved, and 56 per cent were able to return to work or full activity. There were five late deaths (16 per cent). There was good functional improvement in 83 per cent of the survivors, followed 1 to 4 years. We believe that patients with poor ventricular function due to severe coronary artery disease should not categorically be denied surgery, and that operation can be done with a low hospital mortality rate and good functional results.

Adult

[Breath rate as a function of parameters of pulmonary function in body plethysmography (author's transl)].

Parameters of pulmonary function were measured at resting breathing rates (mean 15-17/min) and at breathing rates of 20-40/min in 238 subjects (79 normals, 44 patients with normal pulmonary function in spite of lung disease, and 115 patients, most of whom had obstructive-emphysematous lesions) in a constantvolume body plethysmograph with a respiratory bag. In the subjects with normal pulmonary function the resistance increased significantly by 25 and 45 percent, resp., with more rapid respiration (p smaller than 0,01). Nevertheless it is assumed that this rarely accounts for false interpretations in everyday routine practice. No relationship of breathing rate to respiratory passage resistance was observed in patients with increased total resistance. By way of contrast, ventilation work of breathing (pV diagram) and the index of ventilation work of breathing (defined Vp ratio) showed a close correlation to breathing rate in all 3 groups. This leads us to conclude that these parameters provide more exact information on the breathing mechanism than does total resistance. Studies on ventilation work of breathing must be conducted under clearly defined breathing rates and consideration of the respiratory volume. intrathoracic gas volume was not correlated to the breath rate.

Adult

[Study of the somatotropic function of the pituitary gland and the glucocorticoid function of the adrenal glands in rats with alloxan diabetes].

The somatotropichormone (STH) content was studied in the hypophysis and the peripheral blood of rats with alloxan diabetes; the corticosterone content was determined in their peripheral blood. The STH content in the peripheral blood and the hypophysis of these rats failed to differ from that in the control group, but the blood STH content rose considerably in the sick animals. Exclusion of the insular apparatus function was accompanied by the adrenal gland hypertrophy, which correlated with the rise of the blood corticosterone level. The data obtained indicated that the insular apparatus insufficiency induced by alloxan was accompanied by changes in the somatotropic function of the hypophysis and of glucocorticoid function of the adrenal glands.

Adrenal Cortex

Gliding function following flexor-tendon injury. A biomechanical study of rat tendon function.

Gliding function of flexor tendons one hour to eight weeks after a standard injury was studied in rat digits by determining terminal force of flexion, tendon excursion, and work of flexion using a tensile testing machine. A rapid decrease in gliding occurred within hours of injury, indicating that the postoperative hematoma and edema restrict gliding long before collagenous adhesions are synthesized. The improvement in gliding function with time implies that fibrous adhesions can be remodeled. Surgical methods and therapeutic agents, therefore, should be directed toward limiting early tissue injury and seeking ways to enhance the late remodeling of fibrous peritendinous adhesions along functional lines.

Animals

Lung function in infants and young children: functional residual capacity, tidal volume, and respiratory rats.

Functional residual capacity was measured by the closed-circuit, helium-equilibration method in 121 normal children 3 months to 6 years of age. Prediction equations for functional residual capacity for normal children of this age range are presented for the first time. This study demonstrates that some aspects of lung functiok can be studied relatively conveniently in young children.

Body Height

Clinical significance of pulmonary function tests. Alterations in pulmonary function following respiratory viral infection.

Respiratory viral illness is a major cause of morbidity in both adults and children. This report focuses on both the acute and chronic effects on respiratory function of these ubiquitous infections. Infant airways are particularly vulnerable due to the relatively low conductance in immature peripheral airways. Bronchiolitis, caused predominantly by respiratory syncytial virus, is the most important of these viral illnesses and is emerging as a major risk factor for the subsequent development of obstructive airway diseases in adults, possibly by interference with normal alveolar proliferation. The basic pathogenic mechanism involved in adult respiratory viral infection is bronchial hyperreactivity, presumably secondary to epithelial damage and resultant sensitization of rapidly adapting airway receptors. In addition, there may be virus-related alterations in the autonomic and humoral regulation of airway tone. Viral infections may alter the effects of common air pollutants on respiratory function.

Adult