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Biomedical subjects

D L Brown

Publications and source records attributed to D L Brown.

At least 271 records · Page 15Linked to original sources

Substituted (aryloxy)alkanoic acids as antagonists of slow-reacting substance of anaphylaxis.

A series of compounds in which the 4-acetyl-3-hydroxy-2-propylphenoxy moiety of the standard SRS-A antagonist, FPL-55712, is linked by a polymethylene or a polyether chain to substituted (aryloxy)alkanoic acids was prepared. The compounds were evaluated for their ability to antagonize SRS-A-induced contractions of guinea pig ilea and LTE-induced bronchoconstriction in the guinea pig. The results showed that the compounds were all less potent than FPL-55712 in vitro, yet surprisingly, most were more potent by the inhalation route of administration. Some of the most potent analogues were selected for further pharmacological evaluation and, by inhalation, exhibited selective antagonism of leukotrienes as compared with PAF or histamine. In comparison to FPL-55712, compounds 28 and 37 were more potent against LTE (40- and 80-fold, respectively), LTD (4- and 3-fold, respectively), and LTC (27- and 20-fold, respectively) induced bronchoconstriction when tested by inhalation.

Animals↗

Delayed excretion of 3-methylhistidine in goats.

The purpose of this study was to evaluate the use of 3-methylhistidine (3MH) as an index of muscle protein degradation in dairy goats. The criterion for validation was the rapid and quantitative excretion of radiolabeled 3MH. Three adult dry does and four bucks were confined to metabolism cages and injected with 5 ml of L-3-[14C]methylhistidine dihydrochloride (4 microCi/mL) diluted in normal saline. The does' urine was collected from catheters and the bucks' urine from stainless steel separators protected with fecal collection bags. The daily urine samples were analyzed for labeled amino acid. Urinary recovery of radioactivity from all does was less than 33% after 3 d and was proceeding at less than 5% d. After 9 d, total recovery was less than 50% of total dose for the does. Elimination rates were slightly higher and more variable for the yearling bucks (25-63% after 4 d). On the basis of these data, 3MH does not appear to be a valid index of muscle protein degradation in either male or female dairy goats.

Animals↗

Modification of a critical care ventilator for anesthesia use.

Some critically ill patients require ventilatory support during surgery that exceeds the capabilities of most anesthesia ventilators. We modified an Emerson 3MV ventilator for anesthesia use and measured delivered concentrations of isoflurane during simulated ventilation of a test lung with oxygen flow rates ranging from 5 to 45 L/min. Each measurement was made at atmospheric pressure and incremental levels of 5, 10, 15, and 20 cm H2O PEEP. The delivered anesthetic concentrations were stable at oxygen flow rates of 12.5 to 20 L/min and were unaffected by PEEP changes.

Anesthesia, Inhalation↗

Anesthetic agents in trauma surgery: are there differences?

Overall, no ideal induction or maintenance technique is available for the traumatized, hypovolemic patient. As a result of the multiple insults that produce hypovolemia and the heterogeneous population of patients sustaining trauma, it is unlikely that a controlled human study of this anesthetic dilemma will ever be performed. One must balance the potential incidence of recall of operation or unacceptable sympathectomy-induced vasodilation against the anesthetic techniques available. Bogetz and Katz addressed the recall issue by documenting how many patients sustaining major trauma and requiring operation were really anesthetized. They stressed that many of the patients evaluated were too hemodynamically unstable to tolerate the usual dose of anesthetics administered during elective operations. They postulated that hypotension, hypothermia, and acute alcohol intoxication found in many trauma patients should make recall infrequent. Two groups of patients were analyzed for incidence of recall. The groups were separated based on the continuity of anesthetic administered. In 37 patients given ketamine for induction and low-dose inhalational agent for maintenance, with no gaps in anesthetic administration of over 20 minutes, 4 of 37 (11%) patients had recall. Recall was reported by 6 of 14 (43%) patients in whom it was considered clinically unwise to administer an anesthetic for intubation or whose anesthetic needed to be interrupted for more than 20 minutes secondary to hemodynamic instability. If these figures are representative of the worldwide incidence of recall in our traumatized patients, we may need to redefine the role of anesthesia in trauma. We may need to consider ourselves, not inappropriately, resuscitologists rather than anesthesiologists.

Anesthetics↗

Feed efficiency, growth rates, body composition, milk production and milk composition of Targhee sheep selected for increased weaning weight.

Lactation and growth of three contemporary lines of grade Targhee sheep developed from the same genetic base were characterized by three experiments performed over a period of 2 yr. Two lines (HW and DH) had been selected for 120-d weaning weights for 24 yr prior to beginning these experiments. A third line (C) was a randomly selected control. Year I experiment contrasted 10 DH with 7 C ram lambs fed to 58 kg. Year II experiments utilized 9 C, 14 DH and 10 HW ram lambs and 11 ewes suckling twins from each line. All Year II ram lambs were born and weaned as twins, then fed to 50 kg. Mature DH and HW ewes were heavier (P less than .05) than C ewes (65.2 and 68.8 vs 54.9 kg), and the DH and HW lambs grew faster than C lambs both before (P less than .05) and after weaning (P less than .05). While both DH and HW lambs drank more milk (2,419 and 2,368 vs 2,059 g X d-1 X pair-1; P less than .10) only HW ewes showed a trend towards greater potential milk production than controls (HW = 2,774 vs C = 2,155 g X d-1 X ewe-1 P less than .12). The HW lambs tended to be leaner than C lambs (P less than .05), but DH lambs did not differ from either line. Lambs from DH and HW lines required less post-weaning feed (121.9 and 129.3 vs 152.0 kg P less than .05) and exhibited 17 and 16% greater weight per day of age at 50 kg than controls (P less than .05). The DH line displayed lower feed: gain ratios than controls in both post-weaning trials (6.68 vs 7.30 to 58 kg; 5.83 vs 6.24 at 50 kg; P = .06).

Animals↗

Effects of feeding monensin to lactating goats: acetyl coenzyme A carboxylase, hormone-sensitive lipase, plasma glucose, and circulating hormones.

These trials explored metabolic events associated with monensin-induced changes in milk composition. In trial 1, diets containing 0 or 33 ppm monensin sodium were fed ad libitum to separate groups of 7 mature lactating goats. In trial 2, diets containing 0 or 18 ppm monensin sodium were fed ad libitum to two groups with 5 mature (greater than 2 yr) and seven young (less than 2 yr) lactating does in each group. Blood was sampled at 1200 h and at 3 min after morning milking in both trials. Diets containing 33 ppm monensin increased serum growth hormone and plasma glucagon. Monensin (33 ppm) increased growth hormone from 13 to 60 ng/ml in samples taken 3 min after milking. Monensin (33 ppm) decreased insulin in these postmilking samples from 432 to 317 pg/ml but increased midday insulin in the samples taken between milkings from 279 to 349 pg/ml. Monensin did not affect plasma glucose or serum prolactin concentrations. Monensin fed at 18 ppm did not affect growth hormone, glucagon, adipose acetyl CoA carboxylase activity, hormone-sensitive lipase, or glucose concentrations. Young animals had higher growth hormone, glucose, and glucagon than mature does. The results indicate that effects of milk production intensity can be more important than monensin treatment on milk composition and circulating hormone concentrations.

Acetyl-CoA Carboxylase↗

Neurolytic celiac plexus block for pancreatic cancer pain.

Neurolytic celiac plexus block (NCPB) is an effective method for relief of the pain of pancreatic cancer, but many physicians are reluctant to use the technique because of the perception that the incidence of complications is high. We analyzed the incidence of complications and the quality of pain relief obtained during the use of NCPB in 136 patients with pancreatic cancer. Eighty-five percent of the patients had good pain relief that, in 75% of cases, lasted through the patients' remaining life. No permanent neurologic complications resulted, although two patients had a pneumothorax. Radiographically guided needle placement did not affect quality of pain relief or the incidence of complications. This neurolytic pain block is effective, has a low incidence of neurologic complications, and deserves more widespread use in patients with pancreatic cancer.

Adult↗

Cardiac tamponade and constrictive pericarditis complicating endoscopic sclerotherapy.

We report a case of suspected esophageal perforation with injection of a sclerosing agent into the pericardium during endoscopic sclerotherapy of esophageal varices. Immediately after the procedure, the patient developed fever and a pericardial friction rub. Eight months later, he presented with cardiac tamponade and constrictive pericarditis. This complication should be considered whenever a patient presents with inadequate cardiac output, venous congestion, and a pulsus paradoxus following sclerotherapy.

Adult↗

On the spatial spread of rabies among foxes.

We present a simple model for the spatial spread of rabies among foxes and use it to quantify its progress in England if rabies were introduced. The model is based on the known ecology of fox behaviour and on the assumption that the main vector for the spread of the disease is the rabid fox. Known data and facts are used to determine real parameter values involved in the model. We calculate the speed of propagation of the epizootic front, the threshold for the existence of an epidemic, the period and distance apart of the subsequent cyclical epidemics which follow the main front, and finally we quantify a means for control of the spatial spread of the disease. By way of illustration we use the model to determine the progress of rabies up through the southern part of England if it were introduced near Southampton. Estimates for the current fox density in England were used in the simulations. These suggest that the disease would reach Manchester within about 3.5 years, moving at speeds as high as 100 km per year in the central region. The model further indicates that although it might seem that the disease had disappeared after the wave had passed it would reappear in the south of England after just over 6 years and at periodic times after that. We consider the possibility of stopping the spread of the disease by creating a rabies 'break' ahead of the front through vaccination to reduce the population to a level below the threshold for an epidemic to exist. Based on parameter values relevant to England, we estimate its minimum width to be about 15 km. The model suggests that vaccination has considerable advantages over severe culling.

Animals↗

Unit activity in nucleus paragigantocellularis lateralis during cerebral ischemia in the rat.

In urethane-anesthetized, paralyzed and respirated rats with both vertebral arteries ligated between atlas and axis, bilateral occlusion of the common carotids produces a 19-85 mm Hg rise in mean arterial pressure. This pressor response is entirely mediated by the activation of the sympathetic system, is unaffected by brainstem transection at midpontine levels and is completely eliminated by bilateral lesions of the anterior ventrolateral medulla (including nucleus paragigantocellularis lateralis or PGCL). The magnitude of the response is unaltered following the bilateral section of the 9th-12th cranial nerves. The pressor response is preceded by a rise (25-250%) in the rate of discharge of a specific group of 'vasomotor' neurons present in the pressor area of the PGCL which exhibit the following characteristics: axonal projection to the thoracic spinal cord, spontaneous discharges at low blood pressure, pulse-synchronous activity, discharge rate inversely related to mean arterial pressure and total inactivity above 140-160 mm Hg. It is suggested that the same population of vasomotor neurons relays the sympathoexcitation produced by cerebral ischemia to the cord and also mediates baroreceptor reflexes and generates the basal sympathetic tone.

Animals↗

Rearrangement of tubulin, actin, and myosin in cultured ventricular cardiomyocytes of the adult rat.

Antitubulin, phalloidin, and antimyosin were used to study the distribution of microtubules, microfilaments, and myofibrils in cultured adult cardiomyocytes. These cells undergo a stereotypic sequence of morphological change in which myotypic features are lost and then reconstructed during a period of polymorphic growth. Microtubules, though rearranged during these events in culture, are always present in an organized network. Myosin and actin structures, on the other hand, initially degenerate. This initial degeneration is reversed when a cell attaches to the culture substratum. Upon attachment, new microtubules are laid down as a cortical network adjacent to the sarcolemma and, subsequently, as a network in the basal part of the cell. Actin and then myosin filament bundles appear next, in a pattern corresponding to the pattern of the microtubules. Finally, striated myofibrils are formed, first in the central part of the cell, and subsequently in the outgrowing processes of the cell. A mechanism is suggested by which the eventual polymorphic shape of a cell is related to the shape of its initial area of contact with the culture substratum. Finally, a model of myofibrillogenesis is proposed in which microtubules participate in the insertion of myosin among previously formed actin filament bundles to produce myofibrils.

Actins↗

Sickle cell gnathopathy: radiologic assessment.

To provide objective evaluation of sickle cell gnathopathy, lateral skull radiographs of fifty patients with sickle cell anemia and twenty-five controls, matched for age and sex, were evaluated with respect to hard palate length and palate--alveolar ridge (PAR) angle. These measurements were compared to the angle formed between sella, nasion, and a point just below the anterior nasal spine of the maxilla (SNA angle), which is widely used in evaluation of the midfacial skeletal profile. The maxillary protrusion was found to be due to an increase in the PAR angle, as there was significant difference in this measurement between the two groups while there was no difference in the hard palate and SNA angle measurements. In keeping with prior explanations, marrow hyperplasia is the cause of maxillary overgrowth. Although often detected clinically, sickle cell gnathopathy can be evaluated radiographically simply and accurately by measurement of the PAR angle.

Adolescent↗

Monoclonal antibodies against nuclear matrix detect nuclear antigens in mammalian, insect and plant cells: an immunofluorescence study.

We have applied monoclonal antibodies generated against nuclear matrix in an immunofluorescence study of a variety of plant and animal species. Antibodies P1 and I1 detected antigens in all species examined, including higher and lower plants. Antibodies PI1 and PI2 stained only animal cells, and showed some tissue and/or species-specific variability in staining pattern. The presence of similar nuclear matrix components in such diverse species suggests that nuclear order may be maintained by similar mechanisms in all eukaryotes.

Animals↗