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Biomedical subjects

A Bahoric

Publications and source records attributed to A Bahoric.

At least 37 records · Page 2Linked to original sources
PubMed1985

How laboratory dogs accommodate meals of different size but similar composition.

Healthy laboratory dogs appear to absorb a mixed meal from the gut at a constant rate. This rate is apparently not affected by meal size. If this is the case, then duration of absorption should depend on total or integrated meal size, whereas metabolite and hormonal levels would be independent of the number of feedings. To explore these hypotheses further, we compared the metabolite and hormonal responses with a single mixed meal and one divided in two halves, provided in two feedings 4 h apart. We detected no effect of the second meal in the metabolic response levels of glucose, lactate, pyruvate, alanine, free fatty acids, or 3-hydroxybutyrate or the hormonal responses of insulin, pancretic glucagon, gastrin, or secretin. Only minor differences were detectable in the hormonal response levels of pancreatic polypeptide, gastric inhibitory peptide, and enteroglucagon, consistent with a response to a second meal. We conclude that the observed change in circulating metabolite or hormone concentration is independent of the size of meal eaten, but the duration of the excursion depends on meal size. Thus, during the bulk phase of nutrient uptake, the absorption mechanism of the laboratory dog appears to be saturated.

Amino Acids↗
PubMed1983

Effect of prosthetic airway splint on the growing trachea.

Airway splints are now used clinically to treat tracheomalacia and may also have a place in the management of tracheal stenosis. These studies in 5 to 7 Kg piglets were designed to assess the effects of prosthetic airway splints on airway growth and to establish their usefulness in the reconstruction of tracheal defects. Three experimental groups were studied: group I (n = 8). Silastic reinforced Marlex mesh or Vicryl mesh prostheses were placed around 75% of the circumference of a 3 cm segment of trachea. Pigs were sacrificed at 4 months (average weight = 78.9 +/- 9.0 Kg) and the cross-sectional area of trachea was measured. Group II (n = 5). The same prostheses were used to replace the tracheal defect created by excising three rings (50% of tracheal circumference). Tracheas were examined grossly and histologically at sacrifice. Group III (n = 5). Same as Group II except tracheal defect covered by strap muscles. Prostheses placed external to them to prevent airway collapse. Group I had 4% to 14% (mean 8%) decrease from normal cross-sectional area of trachea at site of splint. No airway obstruction and no infection was encountered. Group II, severe airway obstruction, granulation tissue, and infection at site of defect was noted. Group III showed no signs of airway obstruction, no infection, and minimal airway narrowing. Re-epithelialization of the muscle surface in contact with airway occurred in all these animals. Silastic reinforced Marlex or Vicryl splints placed around the intact rapidly growing trachea do not significantly limit its growth. In addition, these synthetic materials appear to be well-tolerated when used to reconstruct tracheal defects if placed over well-vascularized tissue such as muscle.

Animals↗
PubMed1983

Unanticipated amyloidosis in dogs infused with insulin.

Highly purified regular porcine insulin was given by portable insulin pumps through indwelling vena caval catheters to 17 (13 normal, and 4 pancreatectomized) dogs initially weighing 15 +/- 2 kg at rates ranging from 2 to 10 mU/min (total 17-250 mg) over time periods ranging from 37 to 252 days. During the course of the study, many of the animals lost weight and became anemic. Since these conditions persisted and weight loss progressed even after cessation of insulin infusion, as many of the dogs as possible (15 of 17) were autopsied for microscopic studies. Large amounts of amyloid were demonstrated in the liver, kidney, spleen, and/or pancreas in 55% (6/11) of normal, and in 75% (3/4) of pancreatectomized dogs. The amyloid deposits were Congo red positive, exhibited classical apple green fluorescence under polarized light, and possessed the characteristic ultrastructural features of amyloid. Massive deposits of amyloid were observed in animals receiving as little as 17 mg of insulin over a time span of 52 days. In those animals with hepatic amyloid, marked hepatomegaly was present (i.e., 1200 +/- 250, X +/- SD, versus 300 +/- 25 g for normal animals) and preterminal serum alkaline phosphatase levels were markedly elevated (434 +/- 285 versus 30 +/- 14 IU/L for animals without hepatic amyloid). The magnitude of the hepatic amyloid deposits precludes the possibility that they represent insulin aggregates or insulin-derived products per se. No evidence of amyloid was present in any of the tissue biopsy specimens obtained prior to insulin infusion. Moreover, the possibility that this represents an immune response to the injected porcine insulin has to be viewed in light of the fact that the amino acid sequences of dog and porcine insulins are identical. It is of particular interest that the affinity of the amyloid deposits for Congo red stain was totally abolished by prior permanganate treatment, suggesting that the amyloid was derived from serum amyloid A protein rather than from immunoglobulin light chains or insulin aggregates per se. Further evidence that the protein was of the AA-type came from the initial biochemical characterization. Gel filtration on Sephadex G100 in 6 M guanidine hydrochloride identified two small molecular weight peaks of about 13,000 and 25,000 daltons, both of which inhibited the radioimmunoassay for human AA protein.(ABSTRACT TRUNCATED AT 400 WORDS)

Amyloid↗
PubMed1983

Intravenous infusions of sulfated insulin normalize plasma glucose levels in pancreatectomized dogs.

Sulfated insulin (SI) differs radically from regular crystalline zinc insulin (CZI). To date, SI has been used mainly for the subcutaneous treatment of diabetics with resistance or local allergic reactions to CZI. In this regard, SI exists as a soluble monomer at pH 7.4 and is not inclined to self-association even when agitated and exposed for long periods to materials known to aggregate CZI. To compare its stability and biologic activity when used in conjunction with intravenous infusion pumps, diabetic dogs were infused portally for 140 days with SI and for 140 days with CZI. These studies demonstrated a significant improvement of glycemic control obtainable with SI compared with CZI. Mean +/- SD fasting glycemias were normalized for the SI group (99 +/- 19 mg/dl) and were significantly (P less than 0.001) less than the mean of 148 +/- 64 mg/dl for the CZI group. Mean +/- SD coefficient of variation of the fasting plasma glucose concentrations was 18 +/- 1% for the SI- versus 43 +/- 3% for the CZI-infused dogs, both significantly greater than normal values of 4.5 +/- 0.5%. Basal insulin requirements under these conditions also differed significantly (P less than 0.001). The CZI group received 0.35 +/- 0.07 mU/kg/min compared with 0.20 +/- 0.05 mU/kg/min for the SI group, the former resulted in mean +/- SD plasma levels of 14 +/- 7 microU/ml and the latter resulted in concentrations of 47 +/- 12 microU/ml. Insulin clearance rates were 28 +/- 11 ml/kg/min with CZI compared with 5 +/- 3 ml/kg/min with SI (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1982

Treatment of segmental tracheomalacia and bronchomalacia by implantation of an airway splint.

A silastic reinforced marlex mesh splint was inserted surgically to support a collapsing airway in 3 children with tracheomalacia and 1 with bronchomalacia. The operation was well tolerated and no complications occurred. The splint successfully eliminated symptoms of airway collapse in all children. Its effect on airway growth is not yet certain. This method is applicable to patients with tracheomalacia in whom vascular suspension does not eliminate collapse and for those with bronchomalacia in whom pulmonary resection might otherwise be necessary.

Bronchi↗
PubMed1982

Responses to mixed meals in pancreatectomized dogs deprived of postprandial insulin.

Insulin plays a central role in metabolic control after a mixed meal. In the absence of adequate meal insulin release, abnormal circulating concentrations of most meal-derived metabolic substrates can be expected. To quantify these abnormalities in depth, responses of six pancreatectomized dogs on long-term intravenous insulin replacement were compared to those of five normal control dogs. Blood samples were drawn hourly for 24 h via a chronic indwelling catheter, and all animals ate a single mixed meal. To establish whether there were route-related differences, insulin was delivered into either the portal or the peripheral circulation of the diabetic animals at constant rates. These insulin infusion rates resulted in premeal fasting normoglycemia and in normal levels of insulin, glucagon, lactate, pyruvate, 3-hydroxybutyrate, nonesterified fatty acids, and 9 of 13 amino acids. In the absence of enhanced meal insulin infusion, the subsequent responses of glucose, lactate, pyruvate, alanine, and 10 of 13 other blood amino acids were exaggerated in terms of both amplitude and duration. Only minor or transient differences were attributable to the routes of insulin infusion. Remarkably, in spite of these abnormal postmeal responses, basal insulin alone (with constant circulating levels) succeeded in restoring all metabolite and hormonal levels during the postabsorptive period 16-23 h after the meal. Thus, with intravenous insulin infusions, the requirements for fasting metabolic normalization may be considered independently of those for metabolic control following caloric intake. It remains to be shown how prolonged deprivation of the postprandial insulin supplement results in metabolic decompensation under these conditions.

Animals↗
PubMed1981

The metabolic and hormonal responses to a mixed meal in unrestrained pancreatectomised dogs chronically treated by portal or peripheral insulin infusion.

The metabolic and hormonal consequences of long term intravenous insulin replacement were studied in 11 pancreatectomised dogs. Insulin was delivered into the portal circulation of six animals for 164-224 days and into the peripheral circulation of the remainder for 123-365 days. Infusion rates were initially adjusted to achieve normoglycaemia in the fasting (0.37 +/- 0.01 mU Kg-1 min-1 portal; 0.45 +/- 0.03 mU kg-1 min-1 peripheral) and post-prandial states (2.57 +/- 0.07 mU kg-1 min-1 for 7 1/2 h portal; 3.16 +/- 0.18 mU kg-1 min-1 for 7 h peripheral). Animals were fed their usual mixed diet and blood samples were drawn from indwelling catheters at regular intervals for 24 h. A matched group of six normal dogs was similarly studied. Significantly less insulin was needed for glycaemic normalisation with portal (1.05 +/- 0.03 U kg-1 day-1) compared with peripheral (1.27 +/- 0.08 U kg-1 day-1) infusions, but post-prandial insulin levels were not normalised. Glucagon levels were normal and unaffected by the route of insulin infusion. Lactate and pyruvate responses were exaggerated post-prandially in the diabetic compared with the normal dogs. Fasting non-esterified fatty acid levels were suppressed with peripheral but normal with portal insulin infusion. There were only minor differences in the branched chain, essential and other non-essential amino acids except for alanine which was significantly above normal in the diabetic animals. Fasting levels of insulin, lactate, pyruvate and non-esterified fatty acids were normalised only with portal infusion while glucose, glucagon, 3-hydroxybutyrate and most amino acids were normalised regardless of the route of infusion. We conclude that the metabolic regulation achieved with portal insulin replacement is closer to normal than that achieved with peripheral infusion.

3-Hydroxybutyric Acid↗
PubMed1980

Nonaggregating insulin solutions for long-term glucose control in experimental and human diabetes.

A physiologic additive for dissolving insulin crystals for parenteral application has been found. Insulin crystals are relatively insoluble in simple aqueous solutions. They will dissolve, however, in highly acidic solutions, but these are not suitable for parenteral use. Both neutral and acid pH insulin solutions have a tendency for the dissolved hormone to reaggregate. Notwithstanding possible changes in biologic activity, such formed aggregates must be prevented because they interfere with the flow in portable insulin delivery devices and result in the loss of glycemic control. The addition of 1.5% autologous serum to the aqueous diluent for insulin has eliminated these difficulties and increased by 37% the apparent biologic activity of insulin solutions prepared in this way. With this additive, continuous uninterrupted intravenous insulin infusion has provided near ideal blood glucose control in four pancreatectomized dogs for 5 mo and four patients with juvenile-onset diabetes for 18--23 days. Serum apparently contains factor(s) that promote the dissolution of insulin and prevent the formation of peptide aggregates in dilute solutions.

Adolescent↗
PubMed1979

An open-loop insulin delivery device for the control of experimental diabetes.

A new insulin delivery device has been developed and tested. It includes a reservoir, a pump, and a power pack. The reservoir holds 75 ml and is coupled to a precision peristaltic pump whose delivery can be set to any one of 128 different flow rates from 0 to 80 microliter/min (+/- 1.6% over 10 months) using the flow rate controller included in the battery power pack. The system weighs 525 g, consuming 50 mW at the maximum pumping rate, proportionately less at lower rates. Ten pumps have undergone bench tests for 30 days. One has been subjected to an extended life test of 16 months without change of tubing while seven complete systems have been used on dogs to demonstrate their capability for precise long-term (up to 16 months) intravenous insulin therapy. With this system, experimental diabetes has been controlled in 7 dogs for periods now extending beyond 16 months. This device now qualifies for-long term studies on hospitalized patients with diabetes mellitus.

Animals↗
PubMed1978

A portable precision pumping system for chronic, programmed insulin infusion.

This paper provides some details of a new insulin delivery system which includes a reservoir, a pump and a power pack. The reservoir holds 50 ml and is coupled to a precision peristaltic pump whose delivery can be set to any one of 128 different mean flow rates from 0 to 80 microliter/min (+/- 1.6% over 10 months) using the flow rate controller included in the battery power pack. The system weighs 525 g consuming 60 mW at the maximum pumping rate, proportionately less at lower rates. Ten pumps have undergone bench tests for 30 days. One has been subjected to an extended life test of 11 months while seven complete systems have been used on dogs to demonstrate their capability for precise longterm intravenous insulin therapy. With this system experimental diabetes has been reversed in 4 dogs for periods now extending beyond 6 months. This device now qualifies for long-term studies on hospitalized patients with diabetes mellitus.

Animals↗
PubMed1975

Electrical activity of phrenic nerve and diaphragm in utero.

Phrenic nerve activity, diaphragmatic EMG, and tracheal or pleural pressure changes were recorded in a chronic fetal sheep preparation. Three patterns of fetal phrenic nerve activity were observed: 1) a single burst; 2) irregular nonrhythmic bursts; and 3) prolonged rhythmic activity, seen only prior to fetal death. The total recording time was 54.53 h and the total duration of phrenic nerve activity was 65.34 min (2.16%). When an inactive period was defined as the absence of phrenic nerve activity for 60 s or more, active periods occupied 44.7% of the total time. Phrenic nerve activity was present in all fetuses and 97.5% of the time was coupled with diaphragmatic EMG. Both diaphragmatic EMG and intrapulmonary pressure changes occurred in the absence of phrenic nerve activity. In three fetal animals both phrenic nerves were transected. Tracheal pressure changes were seen which were not coupled with corresponding intrauterine pressure changes. Thus, changes in fetal tracheal pressure or diaphragmatic EMG do not necessarily represent the output of the fetal respiratory center. This study suggests that the fetal respiratory center is active in utero, but this activity is minimal and has a different pattern that that present after birth.

Animals↗
PubMedDate not supplied

Autotransplantation of epithelial cells in the pig via an aerosol vehicle.

A new method of delivery of epithelial suspensions with use of an aerosolization apparatus was examined in the pig. Full-thickness pig skin was harvested, and an epithelial suspension was created using standard techniques of dispase and trypsin. Twenty-four hours after skin harvest, four full-thickness wounds were created on the flanks of the pig. The control wound was sprayed with a solution without epithelial cells. The three experimental wounds were sprayed with epithelial cell suspensions (integral 10(6) cells/suspension). Weekly evaluation with photographs, biopsies, and tracings were done for 4 weeks. At 10 weeks, the entire process was repeated with new wounds on the pig's back. Thirty-five wounds in five pigs were evaluated: 10 control (5 flank, 5 back) and 25 experimental (15 flank, 10 back). Control wounds healed by contraction alone, with epithelium at the edges only. After 4 weeks, an open area remained. Central epithelial islands developed in experimental wounds at 2 weeks. These islands coalesced to close the wounds by 4 weeks. Histology at 1 week showed groups of epithelial cells deeply embedded in granulation tissue. These groups became immature epithelial layers on the surface by 2 weeks, and all layers of epithelium were present by 4 weeks. Overall, flank experimental wounds epithelialized sooner, but contracted at the same rate as control wounds. In conclusion, epithelial cells can be delivered by an aerosolization apparatus and remain viable and proliferative in a pig model.

Aerosols↗
PubMedDate not supplied

Evaluation of a new catheter for total parenteral nutrition.

Central venous catheters play an important role in the management of children with a variety of disorders. Desirable characteristics of such catheters include ease and reliability of placement, secure fixation, low rates of complication, and ease of removal. We describe our experience with a new form of catheter that displays all of these characteristics. One hundred twenty-nine catheters were inserted in 111 patients over a 2-year period for a total of 5,729 treatment days. This catheter is made of silicone rubber and is positioned by using P-wave changes seen during intraoperative electrocardiography. x-Ray confirmation is not routinely necessary. The catheter is fixed in position by use of a grommet, which is sutured in the neck at the site of the venotomy. This form of fixation allows the catheter to be easily removed by nonsurgical means while keeping it securely in position for the duration of use. Our experience with this catheter has been associated with a low incidence of septic (1.1-4.2 septic episodes per 1,000 patient days) and mechanical (2.3 episodes per 1,000 patient days) complications in a setting that includes both in-hospital and home total parenteral nutrition patients. It is felt that this new form of catheter and catheter fixation offers several advantages over other types of central venous catheters currently in use.

Adolescent↗