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Biomedical subjects

J Barr

Publications and source records attributed to J Barr.

At least 109 records · Page 6Linked to original sources
PubMed1994

In vitro metabolism of theophylline by rat and human liver tissue.

1. The metabolism of theophylline was studied in the recently developed, precision-cut, liver slice system. Metabolism of theophylline by rat and human liver slices increased over a 6 h incubation period. 2. Rat liver slices produced 1,3-dimethyluric acid, 1-methyluric acid, and uric acid. Human liver slices produced the same metabolite, as well as 3-methylxanthine. 3. Liver slices and microsomes obtained from the Aroclor-1254 pretreated rats metabolized theophylline at a 10-15-fold greater rate than those obtained from control rats. 4. When theophylline was administered orally to the control and Aroclor-1254 pretreated F-344 rats, the same metabolites were present in the urine as were produced in both in vitro systems. Much less theophylline and more metabolites were found in the urine of the Aroclor-1254 pretreated rat. 5. This study demonstrates that precision-cut slices maintained in the roller culture system can serve as a reliable in vitro method to assess the metabolism of xenobiotics.

Adult↗
PubMed1994

Phenothiazine treatment and respiratory distress syndrome in a child.

An 11-year-old boy who was treated with a relatively high dose of methotrimeprazine meleate (Levemepromazine) a phenothiazine antipsychotic drug, was admitted to the pediatric intensive care unit suffering from respiratory distress syndrome. He required intensive treatment and support for 13 days. The persistent effects of methotrimeprazine meleate on various organs are typical of the prolonged biological action of the phenothiazine metabolites. The association of phenothiazine overdose and respiratory distress syndrome merits consideration.

Child↗
PubMed1994

Airway obstruction in neonates and children: surgical treatment.

OBJECTIVE: This review of 54 infants and children with airway obstruction who were treated surgically emphasizes the importance of the surgical indications with respect to various anomalies causing airway obstruction and the surgical approach to their management. PATIENTS: There were 4 etiologic groups of airway obstruction. Group A comprised 12 infants with subglottic stenosis; Group B--20 infants with tracheomalacia; 21 patients (Group C) with anatomic narrowing of the trachea; and 1 infant (Group D) with laceration of a main bronchus. METHODS: The surgical procedures performed included anterior laryngotracheal decompression in 12 infants, aortopexy in 19; 1 pulmonary arteriopexy; tracheal stenting with an autologous rib graft in 3 and with Marlex mesh in 1. Tracheal widening, using a free tibia autologous graft, was performed in 3 patients; transbronchoscopic excision in 12; anterior tracheal wedge resection in 4, and segmental tracheal resection and anastomosis in 1 patient. The lacerated bronchus was repaired with fine Dexon sutures. RESULTS: There were no operative deaths. With respect to the original indications for surgery, there were 3 failures--2 in Group A and 1 in Group C. Two patients died from causes unrelated to the procedures--one 10 days postoperatively, and the other 3 months after surgery. CONCLUSIONS: The surgical approach to tracheal obstruction in infants and children offers effective treatment, with no operative mortality, a low complication rate, and good long term survival.

Age Factors↗
PubMed1994

Influence of biological response modifiers: measurement of tumor blood flow and temperature.

Human recombinant interferon-alpha-2b (IFN) is known to inhibit growth of both normal and tumor cells and to stimulate immune effector cell function. We have previously shown that IFN and other biological response modifiers augment accumulation of radiolabeled antibodies in tumors. This investigation demonstrates that 30 min post i.m. administration of IFN significantly (p < 0.01) enhances tumor perfusion in tumor-bearing mice and persists for a much longer time than in normal tissue, which, in part, may contribute to the enhanced tumor uptake of radiolabeled monoclonal antibodies within 1.5 h of their administration. Histological examinations of tumors obtained from animals receiving IFN 72 h previously did not show changes in inflammatory cells. Our investigation shows that laser Doppler flowmetry and color Doppler imaging can provide an excellent means of measuring tumor perfusion changes in small living animals where radioactive tracers cannot be used.

Animals↗
PubMed1994

Studies of aluminium mobilization in renal dialysis patients using the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one.

The oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1, deferiprone, CAS 30652-11-0) has been tested in 11 renal dialysis patients, 10 for aluminium and 1 for iron mobilization. L1 was administered just after the patients were placed on the haemodialyser and blood samples were collected before haemodialysis at 1 h and for some patients at longer intervals. Plasma aluminium levels before treatment ranged from 12 to 264 micrograms/l. A mean increase of 90% was observed within the first hour of oral administration in 6 patients who received a dose of L1 of 40-60 mg/kg. Plasma aluminium levels then progressively decreased after this period. Three patients with plasma aluminium of 30-66 micrograms/l who received a dose of L1 of less than 30 mg/kg had no significant changes in their plasma aluminium. In 2 other cases administration of L1 resulted in an over 30-fold increase of aluminium concentration in the dialysate of a continuous ambulatory peritoneal dialysis patient and of over 3 times the iron concentration in the dialysate of an iron loaded haemodialysis patient. In the last patient HPLC analysis of the dialysate samples obtained from the haemodialyser has shown complete clearance of L1 within 4 h but not of its glucuronide metabolite within 6.5 h of the L1 administration. No toxic side effects were observed in any of the 11 patients who received oral L1. These are the first clinical trials of an oral chelator in renal dialysis patients which suggest that oral L1 and possibly other alpha-ketohydroxypyridine chelators may have a use in the treatment of patients with aluminium overload.

Adult↗
PubMed1994

Intra-operative ultrasonography as a routine screening procedure in biliary surgery.

Intra-operative cholangiography and ultrasonography were compared in screening for unsuspected common bile duct stones. In 57 consecutive patients both procedures were performed, and in 60 only ultrasonography was used. Although the study was conducted during the initial self-teaching period (regarding ultrasonography) the results show an advantage of this relatively new diagnostic technique. The false positive rate was lower and consequently the predictive value of a positive test was higher for intraoperative ultrasonography. The main benefit would thus be a lower rate of negative common bile duct explorations. Our early results suggest that the general surgeon would need only a short adaptation period to this imaging modality, which would seem to be a valuable alternative to intra-operative cholangiography.

Adult↗
PubMed1994

CT after intracranial intraarterial thrombolysis for acute stroke.

PURPOSE: To determine the incidence, appearance, and clinical significance of lesions mimicking intraparenchymal hemorrhages on CT in patients treated with intracranial intraarterial thrombolysis for acute strokes. METHODS: Ten cases of acute stroke treated with direct intraarterial urokinase infusion were retrospectively reviewed. Clinical and radiographic findings before and after therapy were all evaluated. RESULTS: Six (60%) of the 10 patients showed areas of increased attenuation on CT shortly after thrombolytic therapy. The lesions were associated with clinical deterioration in two cases (20%); in these two cases the lesions persisted on CT for several days. The lesions were asymptomatic in two (20%) cases; the lesions cleared on CT within 24 hours in those two patients. In two (20%) patients, immediate clinical improvement was evident despite the radiodense areas. These lesions also cleared within 24 hours. CT Hounsfield unit measurements of four of the lesions revealed very high Hounsfield units in two lesions, only one of which was a symptomatic lesion. MR in two cases revealed residue of hemorrhage. CONCLUSION: Intraparenchymal areas of increased attenuation may be seen on the CT scans of patients after intraarterial thrombolysis. The density is often at least partially attributable to contrast extravasation. The lesions should not necessarily be interpreted as hemorrhage alone, especially in the absence of clinical deterioration. Rapid clearing may be a positive prognostic sign.

Acute Disease↗
PubMed1993

Selection of a new generation of orally active alpha-ketohydroxypyridine iron chelators intended for use in the treatment of iron overload.

The prospect of selecting oral alpha-ketohydroxypyridine chelators intended for clinical use in iron overload has been examined using several animal models of efficacy and toxicity. Studies using iron dextran-loaded mice labelled with 59Fe have shown that only the 1-substituted methyl, ethyl, (n)propyl, allyl, cyclopropyl, 2'-methoxyethyl, 3'-ethoxypropyl, or 2-methyl- or 2-ethyl-3-hydroxypyrid-4-one chelators were orally effective in increasing iron (59Fe) excretion by comparison to intraperitoneally administered desferrioxamine at the same dose (250 mg/kg). In contrast, chelators containing -H, mono- or dihydroxyalkyl and diethoxyethyl 1-substituents caused very little or no increase in iron (59Fe) excretion by the oral or intraperitoneal routes. In vitro studies using ferritin and haemosiderin have shown that equivalent iron release took place with both groups of chelators irrespective of their in vivo effects. In most cases there was no correlation between the n-octanol/water partition coefficient (Kpar) and iron removal efficacy but positive correlation between the lipophilicity and acute or subacute toxicity of these chelators in rats. The most toxic chelator in the chronic toxicity studies in rats was the lipophilic 1,2-diethyl-3-hydroxypyrid-4-one (EL1NEt). The most effective chelator in increasing iron excretion in mice and rabbits was 1-allyl-2-methyl-3-hydroxypyrid-4-one (L1NAII), and the chelator with the highest safety margin in mice and rats was 1,2-dimethyl-3-hydroxypyrid-4-one (L1). Overall the oral effectiveness in increasing iron excretion by these chelators in animals does not appear to be related to their lipophilicity or their ability to mobilise polynuclear iron in vitro but rather to other properties possibly related to their rate of biotransformation and excretion.

Absorption↗
PubMed1993

High-dose adrenaline in adult in-hospital asystolic cardiopulmonary resuscitation: a double-blind randomised trial.

Forty intensive care unit patients requiring cardiopulmonary resuscitation were randomised to receive either the standard dose of adrenaline (1 mg every five minutes) or high-dose adrenaline (10 mg every five minutes). In the majority of patients, overwhelming sepsis was the major contributing factor leading to cardiac arrest. In this group of patients no difference could be detected in response to high-dose adrenaline compared with the standard dose. Although no side-effects were noted with this high dose of adrenaline, more investigation is required prior to its routine use in cardiopulmonary resuscitation.

Adult↗
PubMed1993

Acute lung injury at Baragwanath ICU. An eight-month audit and call for consensus for other organ failure in the adult respiratory distress syndrome.

To test the expanded definition of acute lung injury (ALI), we prospectively, over a period of 8 months, studied all adult ICU admissions who fitted the definition. Our study consisted of 83 patients with the adult respiratory distress syndrome (ARDS) and 60 with mild to moderate ALI. Sepsis and trauma were the most common diagnoses on admission. The overall mortality rate was 45 percent for ARDS and 38 percent in the other group. Mortality rose significantly with associated other organ failure, the incidence of which was as follows: hepatic, 39 percent; cardiac, 38 percent; hematologic, 22 percent; renal, 21 percent; neurologic, 5 percent. Sepsis syndrome eventually occurred in 73 percent and septic shock in 38 percent of all cases of ALI. We found the expanded definition a useful grading system and consider this definition of ARDS to be currently the best. There are, however, problems with the determination of lung compliance, the effect of inverse ratio ventilation, and the lack of consensus in defining other organ failure.

Adult↗
PubMed1993

Evaluation of gender differences in urine specific gravity and serum electrolytes in response to varied fluid intake and ibuprofen use.

Heat casualties and other conditions related to suboptimal fluid intake (FI) are common in the military. Current methods to assess FI do not address gender differences or medication use, specifically non-steroidal anti-inflammatory drugs (NSAIDs), which are commonly used in the field. Nine men and six women were prospectively studied while stationed in Saudi Arabia. Urine specific gravity and serum electrolytes were monitored as FI was varied before and after daily ibuprofen (IBP) ingestion. IBP impaired urinary dilution in both men and women, but differences were not statistically significant pre- and post-IBP or between genders. Use of IBP or other NSAIDs may confound usual methods to ensure adequate FI, and soldiers should be specifically questioned about their use before such assessments.

Adult↗
PubMed1992

Biguanide-associated lactic acidosis. Case report and review of the literature.

PURPOSE: The biguanides are a class of oral hypoglycemic agents that are commonly used in the treatment of diabetes mellitus. Such agents include metformin, phenformin, and buformin. The use of phenformin was discontinued in the United States in 1976 because of probable association with lactic acidosis. However, metformin is currently in common use in many parts of the world. In this report, we describe a patient with severe lactic acidosis secondary to metformin administration, and review the literature relevant to biguanide-associated lactic acidosis. PATIENT: We describe a diabetic man with end-stage renal failure and diabetes mellitus who was hospitalized with life-threatening lactic acidosis (lactate, 10.9 mmol/L). Unbeknownst to the hospital staff, he was being treated with metformin, which had been prescribed in Indonesia. RESULTS: Arterial blood gas analysis revealed a pH of 6.76 and a bicarbonate level of 1.6 mmol/L prior to treatment. Following therapy, which included oxygen, volume expansion, other supportive therapy, and hemodialysis, the patient completely recovered and was discharged from the hospital. CONCLUSIONS: Lactic acidosis can complicate biguanide therapy in diabetic patients with renal insufficiency. We review the literature relevant to the pathogenesis and therapy of biguanide-associated lactic acidosis. Physicians who have completed their training after 1976 may not be familiar with metformin and other biguanides, but with the increasing numbers of immigrants to the United States, physicians should be aware of the potential complications of these medications.

Acidosis, Lactic↗
PubMed1992

Septic shock: does adrenaline have a role as a first-line inotropic agent?

Fifteen adult patients, admitted to Baragwanath Hospital ICU with septic shock after adequate fluid loading and on no other inotropic agents, were given adrenaline in incremental doses. Oxygen transport and haemodynamic variables were monitored with each dose increment until a systolic blood pressure of 120 mmHg was obtained. This was reached on an average dose of adrenaline of 0.16 +/- 0.02 micrograms/kg/min. Mean arterial blood pressure increased by 22 +/- 2 mmHg mainly due to an increase in cardiac index (1 +/- 0.2 l/min/m2) and systemic vascular resistance index (130 +/- 41 dyn.s.cm.-5m-2) with a small increase in heart rate of 8 +/- 3 beats per minute. Oxygen delivery was increased with no significant increase in oxygen consumption and lactate levels increased. Adrenaline is therefore an effective initial inotropic agent. Patients may respond to lower doses than when used concurrently with other inotropic agents but there was still a significant dose variation in response. We cannot, however, exclude a deleterious effect on oxygen utilization.

Adult↗
PubMed1991

Autosomal recessive lethal infantile cytochrome C oxidase deficiency.

Three bedouin children with mitochondrial myopathy due to cytochrome c oxidase deficiency presented with progressive muscle weakness, failure to thrive, proximal renal tubular acidosis, and lactic acidemia leading to death. Two died by age 5 months and one by age 16 months. Cytochrome c oxidase was markedly reduced in skeletal muscle extracts of all three. Three other children of the same family with most probably the same metabolic aberration are also described. We suggest an autosomal recessive inheritance for this lethal mitochondrial myopathy.

Acidosis, Renal Tubular↗