Peripheral vascular disease, Part 2.
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Biomedical subjects
Publications and source records attributed to M A Khalid.
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Chest radiographs are obtained routinely in children hospitalized with asthma but are considered to be of low utility. We describe a previously unreported radiographic inversion of pulmonary artery flow patterns in the chest films of a majority of children and young adults hospitalized for asthma. Seventy-five hospital records of 65 patients aged 2 to 25 years (mean 9.2) admitted for asthma during the calendar year 1991 were reviewed. As compared with the normal pattern, patients with inverted vascularity were younger (mean age 6.75 years), tended to be admitted through the emergency department, and had significantly more signs of labored breathing, such as tachypnea, retractions, nasal flaring, and tachycardia. We propose that the exaggerated respiratory effort in these children raises the transmural pulmonary artery pressure, impeding pulmonary blood flow. This results in distension of the right ventricle, which then compresses the left ventricle in the confines of the pericardium by posterior displacement of the interventricular septum. The resultant loss of left-sided compliance raises the left atrial and pulmonary venous pressures, leading to inversion of vascular markings through the same mechanism as seen in left-heart failure. We conclude that attention to this easily recognized sign will detect presence of the hemodynamically significant respiratory obstruction in asthmatic patients.
In response to severe injury, extraordinary quantities of lactate that are released from the peripheral tissues serve as substrate for hepatic gluconeogenesis. It is possible that as a result of burn injury, reaction kinetics involving lactate could be directly changed within the liver. The metabolic fate of [U-14C]lactate was examined in vitro in fresh liver slices after a 20 per cent total body surface area injury. Glucose and CO2 were produced in vitro by the liver tissues after the injury and no differences were seen in the metabolism of these substrates between the injured and control animals. These findings suggest that the intrinsic enzymatic processes within the liver are not directly altered by injury itself or by any of the associated inflammatory mediators which appear early after burns.
Isolated adult rat cardiac myocytes were subjected to anoxia and substrate deprivation for 15, 30, 60, 90, and 120 minutes and reoxygenation for 120 seconds. The supernatant and cell extract were analyzed for hydroxyl radicals (.OH) with high-performance liquid chromatography using salicylate as a trapping agent. The production of intracellular H2O2 as a possible precursor of .OH was also documented using the fluorescent probe dichlorofluorescein diacetate. The release of the cytosolic enzyme lactate dehydrogenase (LDH) and malondialdehyde (MDA) formation were used as cell injury markers. Trypan blue and horseradish peroxidase stains were used as markers for altered membrane permeability. Maximum formation of .OH was observed in myocytes subjected to 15 minutes of anoxia/reoxygenation (2.83 +/- 0.27 nmol/mg protein), at which time no injury was observed at light and ultramicroscopic levels. On the other hand, there was no correlation between the amount of .OH production and different parameters of cell injury in myocytes subjected to anoxia/reoxygenation longer than 15 minutes. Myocytes developed extensive blebbing, loss of cell membrane permeability, and ultrastructural damage. The enzyme leakage was minimal at 15 minutes (0.094 +/- 0.021 units/mg protein) and increased fivefold after 120 minutes (0.428 +/- 0.069 units/mg protein). Similarly, MDA increased from 0.78 +/- 0.14 nmol/mg protein at 15 minutes to 1.65 +/- 0.35 nmol/mg protein at 120 minutes. Incubation with 1 mM deferoxamine reduced the .OH production at all anoxic intervals, most significantly at 15 minutes, but did not decrease LDH and MDA release or provide ultrastructural preservation. However, preincubation with 2.5 microM diphenylphenylenediamine markedly reduced both LDH and MDA release and offered prominent ultrastructural protection. These results suggest that 1) myocytes were able to generate .OH endogenously; 2) maximum .OH was produced at 15 minutes after anoxic reoxygenation without compromising cell viability; 3) prolongation of the anoxic period exacerbated cell damage without parallel increase in .OH generation; 4) there was no significant production of .OH after 15 minutes of anoxia/reoxygenation with or without treatment of deferoxamine, suggesting that prolonged anoxia/reoxygenation does not induce additional .OH formation and thus mediate cell injury; and 5) it is likely that the damage to myocytes in this system was still mediated by free radicals other than .OH, as indicated by the protection by diphenylphenylenediamine against the cellular injury.
Hydroxyl radicals (.OH) in isolated cultured cardiomyocytes upon reoxygenation (reoxy) were measured after graded anoxia (A) using high performance liquid chromatography (HPLC). Isolated myocytes were subjected to A for 15, 30, 60, 90 and 120 minutes and reoxy for 120 seconds. Supernatant was collected after reoxy, extracted with ether and injected into HPLC for measuring hydroxylation products of salicylic acid (2,5-DHBA) as an indicator of .OH formation. 2,5-DHBA was detected maximally after 15 minutes of A and 120 seconds of reoxygenation (34.2 +/- 3 pmol/mg protein), at which time 80% of cells had maintained their rod shape and 99% of cells excluded both trypan blue (TB) and horseradish peroxidase (HP). There was significantly less (P < 0.05) 2,5-DHBA in the group subjected to 15 minutes of A only without reoxy (7.95 +/- 1.2 pmol/mg protein). 2,5-DHBA decreased to 13.1 +/- 2 pmol/mg protein at 120 minutes of A/120 seconds reoxy. With increasing anoxic time, the number of rod-shaped cells decreased from 80% at 15 minutes to 30% at 120 minutes, while the number of TB/HP positive cells increased from 0% at 15 minutes to 100% at 120 minutes. The cell membrane blebs were nonexistent at 15 minutes, but at 120 minutes A intense bleb formation was observed. These data suggest that .OH is produced upon reoxygenation of anoxic cultured cardiomyocytes and their production is maximum when majority of myocytes are viable.
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Thirty patients underwent coaxial needle aspiration biopsies of lesions of the lung under CTG. Tissue obtained was adequate for diagnosis in 90 per cent of the patients. The incidence of pneumothorax was low using the coaxial needle technique. The limitations of the fine needle are diminished, and the risk of tumor implant during the procedure is greatly minimized. Additional studies should be conducted to further evaluate this technique and confirm its safety.