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Biomedical subjects

G T Kinasewitz

Publications and source records attributed to G T Kinasewitz.

At least 19 recordsLinked to original sources
PubMed2000

Peritonitis in the baboon: a primate model which stimulates human sepsis.

The physiological, hemostatic, and immunological responses of 12 chronically instrumented conscious baboons with sepsis due to Escherichia coli peritonitis were compared with that of similarly instrumented controls. Chronic indwelling cannulae were placed in the aorta and pulmonary artery to monitor pressure, cardiac output, and obtain blood samples. At t = 0 a sterile or E. coli-laden fibrin clot containing 1.9-6.7 x 10(11) CFU/kg was introduced into the peritoneal cavity. The control animals were group 1 (n = 3). The animals with peritonitis were divided into three groups depending on their clinical response. Group 2 animals (n = 3) were clinically well at the time of sacrifice (day 14), group 3 (n = 4) survived but were obviously sick on day 14, and group 4 (n = 5) died of sepsis. Implantation of a sterile fibrin clot was well tolerated with little hemodynamic change and a transient minimal inflammatory response in group 1. Implantation of an E. coli-containing clot elicited a hyperdynamic cardiovascular response and evoked a marked inflammatory reaction and a disseminated intravascular coagulopathy. Five of 12 (42%) E. coli animals died from sepsis. In general, the physiological, hemostatic, and immunological disturbances tended to be greatest in these animals. Autopsy revealed residual peritoneal inflammation and varying degrees of inflammation in the lungs, adrenal, spleen, liver, and kidneys in all the animals that received E. coli with the inflammatory infiltrate increasing in severity from group 2 through group 4. Tissue necrosis was observed only in the latter group. We conclude that the cardiovascular, hemostatic, and immunological responses of baboons with sepsis due to E. coli peritonitis exhibit a variable course that resembles the clinical manifestations of gram-negative sepsis in humans.

Animals↗
PubMed1999

Hypoalbuminemia as a cause of pleural effusions.

BACKGROUND: Alterations in Starling forces that favor pleural fluid formation include an elevation in capillary hydrostatic pressure and a fall in plasma oncotic pressure. Although venous hypertension is a well-recognized cause of pleural effusion, the frequency with which hypoalbuminemia in the absence of volume expansion leads to pleural effusion is unclear. STUDY OBJECTIVE: We determined the frequency with which unexplained pleural effusions occur in patients with normal and low plasma oncotic pressures. DESIGN: A 2-month prospective screen of all admission patients to the University of Oklahoma Hospital and the Oklahoma City Veterans Administration (VA) Medical Center identified 152 patients who had chest radiographs and serum protein determinations on admission, but did not have an admission diagnosis that was a recognized cause of pleural effusion. In order to include more patients in the study with extremely low serum albumin levels, 20 additional study patients with serum albumin levels of < 2.0 g/dL were identified by a retrospective review of patients admitted during the previous 12 months. On the radiograph, pleural effusions were identified as a new blunting of the costophrenic angles. Study patients were divided into the following three groups: group 1 had serum albumin levels of > 3.5 g/dL; group 2 had serum albumin levels between 2.1 and 3.5 g/dL; and group 3 had serum albumin levels of < or = 2.0 g/dL. Finally, the frequencies with which pleural effusions occurred were compared among the three groups. RESULTS: Seven of 104 patients in group 1, 2 of 45 patients in group 2, and 3 of 21 patients in group 3 had pleural effusions. Within each group, there were no significant differences in serum albumin concentration or plasma oncotic pressure between patients with and without pleural effusions. In all but two study patients, a careful review of records and a prospective follow-up of the patients' clinical course identified a potential cause for the effusions other than hypoalbuminemia. None of the 68 study patients with serum albumin levels of < or = 3.5 g/dL had an unexplained pleural effusion. CONCLUSION: We conclude that hypoalbuminemia, per se, is an uncommon cause of pleural effusion. The recognition of pleural effusions in patients with low serum albumin levels should prompt careful clinical evaluations to identify other potential causes for the effusions.

Female↗
PubMed1997

Tissue factor expression in mesothelial cells: induction both in vivo and in vitro.

Exudative pleural effusions are characterized by a high protein content and frequently progress to loculation and fibrosis. To test the hypothesis that tissue factor (TF) plays an integral role in this process, we investigated the expression of TF by human mesothelial cells (HMC) both in vivo and in vitro, and measured the effect of serum on HMC expression of TF in vitro. In vivo TF expression was not detected in HMC of normal pleura, but was detected in HMC of pleura overlying inflamed lung. In vitro, quiescent HMC demonstrated negligible levels of TF expression; however, upon serum stimulation there was a marked induction in both TF protein level and activity, peaking at 8-9 h. In contrast, treating quiescent HMC with plasma resulted in a further small, but significant, decrease in TF expression. This serum-induced rise in TF was also reflected in TF mRNA levels and did not require de novo protein synthesis. These results suggest that induction of HMC TF expression may be important in triggering both the intrapleural activation of prothrombin and the deposition of fibrin characteristic of inflammatory effusions.

Blood↗
PubMed1997

Transudative effusions.

Transudative pleural effusions develop because the distribution of hydrostatic and oncotic pressure across the pleura is altered, so that the rate of pleural fluid formation exceeds that of its reabsorption. They are characterized by a low cell and protein content. Congestive heart failure is the most common cause of transudative effusion. The fluid that accumulates in a hepatic hydrothorax, urinothorax, during peritoneal dialysis, and in many patients with nephrotic syndrome may also have the characteristics of a transudate. The development of a transudative effusion indicates that the pleural membranes per se are intact, so that if the underlying problem can be corrected, the effusion will be reabsorbed.

Exudates and Transudates↗
PubMed1994

Resuscitation of canine hemorrhagic hypotension with large-volume isotonic crystalloid: impact on lung water, venous admixture, and systemic arterial oxygen saturation.

The objective of this study was to test the hypothesis that after hemorrhagic hypotension, reinfusion of the shed blood with threefold that volume of lactated Ringer's (LR) solution will significantly increase lung water and venous admixture and hence decrease systemic arterial oxygen saturation. A prospective, randomized, fixed-volume hemorrhage laboratory study was performed at the Oklahoma University Health Sciences Center on 18 anesthetized mongrel dogs. After 40 mL/kg of blood were withdrawn through a femoral artery catheter, the dogs were randomized either to the control group (n = 9) that received a reinfusion of the shed blood, or to the LR treatment group (n = 9) that received an intravenous mixture of the shed blood with 120 mL/kg of LR. After fluid resuscitation, pulmonary artery occlusion pressure (PAOP) and cardiac output (CO) were significantly increased in the LR group compared with control animals (PAOP, 18.7 +/- 1.1 vs 13.4 +/- 2.9 mm Hg; CO, 8.14 +/- 1.08 vs 4.59 +/- 0.47 L/min; P < .05 each). However, lung water, venous admixture, and systemic arterial PO2 were similar between groups. In this fixed-volume hemorrhage model, hemodiluting the reinfused shed blood with threefold the volume of LR did not significantly influence lung water, venous admixture, or systemic arterial oxygen saturation.

Animals↗
PubMed1993

Thrombophlebitis and pulmonary embolism in the elderly patient.

The incidence of deep venous thrombosis and subsequent pulmonary embolism is increased in the elderly but, because the clinical manifestations may be misleading, the diagnosis is often missed. The clinician must maintain a high index of suspicion and order specific tests for venous thrombosis or pulmonary embolism whenever these diagnoses are considered. Even though the risk of bleeding while anticoagulated is increased in the elderly, treatment with heparin followed by long-term anticoagulation with warfarin is the preferred course of therapy for most patients. Awareness of their increased risk and emphasis on prevention of venous thrombosis may be the most effective means of dealing with this clinical problem in the elderly.

Aged↗
PubMed1992

Cytokine-stimulated human mesothelial cells produce chemotactic activity for neutrophils including NAP-1/IL-8.

To test the hypothesis that mesothelial cells play a role in regulating inflammatory responses within the pleural space, we examined neutrophil chemotactic activity released by cytokine-stimulated mesothelial cells. Human mesothelial cells were isolated from patients with transudative pleural effusions and cultured. The purity of the cell population was assessed by morphologic, immunocytochemical, and biochemical characteristics. Confluent fourth passage mesothelial cell plates were exposed to varying concentrations of the recombinant human cytokines IL-1 alpha, TNF-alpha, or IFN-gamma, or Escherichia coli endotoxin (LPS). Polymorphonuclear neutrophil (PMN) chemotactic activity in the conditioned media was measured in microchemotaxis chambers. Although none of the cytokines demonstrated inherent chemotactic activity, each stimulated mesothelial cells to produce PMN chemotactic activity in a dose-dependent manner. TNF-alpha stimulated the release of the greatest quantity, whereas stimulation with IFN-gamma and IL-1 alpha resulted in the release of lesser but still significant quantities of PMN chemotactic activity. By contrast, LPS did not increase the basal level of chemotactic activity produced by the cells. The cytokine-induced chemotactic activity was proteinaceous, required de novo synthesis, and had a predominant m.w. of 10,000. Significant quantities of immunoreactive neutrophil-activating peptide-1 (NAP-1)/IL-8 were detected in mesothelial cell supernatants after stimulation with each of the cytokines. The neutrophil chemotactic activity of supernatants from mesothelial cells stimulated with either IL-1 alpha or IFN-gamma was completely neutralized with rabbit anti-human NAP-1/IL-8 polyclonal antiserum. The same antiserum neutralized the majority, but not all, of the neutrophil chemotactic activity in supernatants from TNF-stimulated mesothelial cells. Stimulated mesothelial cells also expressed an inducible mRNA transcript that hybridized with a specific oligonucleotide probe for human NAP-1/IL-8. These observations provide a mechanism whereby mesothelial cells could respond to inflammatory stimuli in the underlying lung and regulate inflammatory responses within the pleural space.

Base Sequence↗
PubMed1990

Exercise limitation in patients with polymyositis.

To examine the hypothesis that patients with inflammatory muscle disease have impairments in cardiac and/or pulmonary function that are masked by peripheral muscle weakness, complete PFTs, echo/Doppler studies and exercise testing were performed in 11 patients with polymyositis. Maximal inspiratory and expiratory pressures and expiratory flow rates were normal. One patient had evidence of restrictive lung disease; two had a reduced Dsb. Seven patients had evidence of pulmonary hypertension. Only three patients had normal aerobic capacity; VO2 max in the other 8 patients was 46 +/- 8 percent of predicted when they stopped exercising. Four patients had a normal O2 pulse; seven patients had a reduced O2 pulse while five of seven patients exceeded 85 percent of their target heart rate. We conclude that while asymptomatic impairments in pulmonary function are uncommon in polymyositis, the incidence of pulmonary hypertension is high, but symptoms may be masked by the peripheral muscle weakness.

Echocardiography, Doppler↗
PubMed1988

Sandblaster's lung with mycobacterial infection.

This report describes the development of alveolar silico-lipoproteinosis complicated by Mycobacterium kansasii infection in a previously healthy man who worked as a sandblaster. Alveolar silico-lipoproteinosis is a rare disease that usually is fatal within 1 year of onset of symptoms. There is a high incidence of mycobacterial infection, half being caused by atypical organisms.

Humans↗
PubMed1988

Comparative permeability of canine visceral and parietal pleura.

To determine the permeability of canine pleural mesothelium, visceral and intercostal parietal pleura from mongrel dogs was carefully stripped from the underlying tissue and mounted as a planar sheet in a Ussing-type chamber. The hydraulic conductivity (Lp) was determined from the rate of volume flux in response to hydrostatic pressure gradients applied to either the mucosal or serosal surface of the pleural membrane. The diffusional permeability (Pd) of radiolabeled water, sucrose, inulin, and albumin was determined under equilibrium conditions from the unidirectional tracer flux. The Lp of the visceral pleura was 0.39 +/- 0.032 (SE) X 10(-4) ml.s-1.cmH2O-1.cm-2 and that Lp of parietal pleura was 1.93 +/- 0.93 X 10(-4) ml.s-1.cmH2O-1.cm-2 (P less than 0.001). The Pd of the visceral pleura ranged from 12.21 +/- 0.45 X 10(-4) cm/s for 3H2O to 0.34 +/- 0.03 X 10(-4) cm/s for [3H]albumin. The Pd of the parietal pleura for water and sucrose was similar to that of the visceral membrane, whereas its Pd for the larger inulin and albumin molecules was greater than that of visceral pleura (P less than 0.01). A spontaneous potential difference could not be detected across either membrane. The relatively higher parietal pleural Lp and Pd for larger solutes is probably due to the presence of stomata in this membrane. These results indicate that both the parietal and the visceral pleura are extremely permeable tissues which offer little resistance to water and solute flux.

Albumins↗
PubMed1988

Clinical characteristics of the patient with nonspecific pleuritis.

To determine if patients with nonspecific pleuritis could be clinically distinguished from those with malignant or granulomatous pleural disease, the medical records and chest roentgenograms of all patients who had a closed needle biopsy of the pleura during a five-year period from January 1979 to December 1983 were reviewed. A total of 119 patients were categorized based upon their ultimate diagnosis as having malignant (n = 41), granulomatous (n = 25), or nonspecific pleuritis (n = 53). Weight loss, fever greater than 38 degrees, a positive PPD, a pleural fluid lymphocytosis of greater than 95 percent, and an effusion which occupied more than half a hemithorax were significantly more common in the patients with malignant or granulomatous disease. Based on these results, a conservative approach is recommended for the patient with an initial biopsy which reveals only nonspecific pleuritis who has none of the criteria, but an aggressive diagnostic work-up in the individual with two or more criteria is advocated.

Biopsy↗
PubMed1987

Concentration dependence of protein permeability across the canine visceral pleura.

Water and protein movement across the pulmonary endothelial-visceral pleural membrane of spontaneously breathing anesthetized dogs was analyzed to determine if the protein concentration at the microvascular membrane (Cpro) influences microvascular permeability. The left lung was enclosed in a water-impermeable membrane, creating a visceral pleural space (VPS); fluid and solute fluxes were determined as the filtration or reabsorption of water and protein in the VPS. The plasma protein concentration was experimentally varied by plasmapheresis with saline replacement while the pleural fluid protein concentration was varied by introducing different concentrations of plasma mixed with saline into the VPS. Hydrostatic pressures were maintained within a physiologic range (pulmonary capillary pressure 12.1-16.1 mm Hg). The plasma protein concentration fell as low as 1.98 g/dl, and Cpro, calculated as the mean of the plasma and pleural fluid protein concentrations, ranged from 1.73 to 6.23 g/dl. The relationship between Cpro and the apparent homoporous diffusional permeability for protein (Phs), Phs(cm/sec X 10(-6] = 0.95 Cpro (g/dl) + 2.28, was highly significant (r = 0.87, P less than 0.01). In contrast, the hydraulic conductivity was not affected by a reduction in Cpro to this level (r = 0.21, P greater than 0.4). Although the solute concentration at the endothelial membrane should be considered when evaluating changes in protein permeability, under most experimental conditions the magnitude of this effect will be small.

Animals↗
PubMed1987

Spatial heterogeneity and microvascular fluid exchange: a simple macroscopic equation.

The effect of the spatial distribution of capillary membrane "pores" on the estimate for the hydraulic conductivity (Lp) and the reflection coefficient (sigma s) in the presence of an axial gradient in the hydrostatic pressure difference (delta P) is examined. The differential fluid balance is integrated along the length of the capillary and a simple analytic solution is obtained for a capillary membrane of arbitrary structure. The effective hydrostatic pressure difference, (delta P)eff, is not simply the average of the arterial [(delta P)a] and venous [(delta P)v] pressure differences but is instead found to be (delta P)eff identical to [(delta P)a + (delta P)v]/2 + kappa [(delta P)a - (delta P)v]/2, where kappa identical to 1 - 2 (Lp1/Lp). The two macroscopic coefficients, Lp and Lp1, are related to integrals of the pore density along the length of the capillary. Failure to account for spatial heterogeneity may lead to an incorrect interpretation of the experimental data, e.g., the estimate for sigma s could be greater than 1 or less than 0 depending on the pore distribution and pressure gradient along the capillary. The single capillary hydraulic conductivity measurements of Gore [1982), Amer. J. Physiol. 242, H268-H287) and data on the microvascular pressure distributions (Bohlen and Gore (1977), Microvasc. Res. 14, 251-264) are used to estimate the magnitude of these effects.

Capillaries↗
PubMed1987

Clinical significance of an isolated reduction in residual volume.

To determine the significance of an isolated reduction in residual volume (RV), the medical records and chest radiographs of 69 patients who had a RV less than or equal to 65% of predicted and normal VC, DLCO, and expiratory flow rates were reviewed. Sixty-three of 69 patients (92%) had clinical conditions that could account for their decreased RV. Definite disease was considered to be present in the 39 patients with radiographically apparent parenchymal (n = 18) or chest wall (n = 21) abnormalities, whereas 24 others with clinical diagnoses such as congestive heart failure or toxic inhalation were considered to have probable disease. All patients who had a RV below 50% of predicted had either definite or probable disease. Follow-up testing of 19 patients 31 +/- 21 months after their initial reduction in RV was first documented indicated that the RV accurately reflected the patient's current clinical status in that it increased by 17 +/- 16% of predicted in those who were clinically improved and decreased by 27 +/- 7% in those who were clinically worse. In patients who were clinically stable, the isolated reduction in RV was a persistent finding. We conclude that an isolated reduction in RV is a clinically significant finding indicative of pulmonary or chest wall disease. Interval changes in RV reflect alterations in disease activity.

Female↗
PubMed1987

Influence of spirometry and chest roentgenography on the management of pulmonary outpatients.

Spirometry and chest roentgenography are frequently employed to evaluate patients with respiratory problems. To determine their impact on the management of outpatients with lung disease, both tests were performed on 100 consecutive patients (40 men and 60 women; mean age, 52 +/- 15 years) who returned for reevaluation 16 +/- 9 weeks after their previous clinic visit. Patients with obstructive (n = 45), restrictive (n = 35), and mixed (n = 20) lung diseases were initially assessed by history and physical examination and classified clinically as improved, stable, or worse. A clinical management plan (CMP) was formulated based on this initial evaluation. Changes in the proposed CMP due to spirographic or roentgenographic results were then noted. None of the 19 patients who were clinically improved and only two (3%) of the 64 clinically stable patients had a change in CMP. In contrast, five (29%) of the 17 patients whose conditions deteriorated clinically had their proposed CMP modified after review of the spirograms and roentgenograms. Therapy was intensified in three of the seven patients whose CMPs were modified, while in the other four, treatment was withheld because results of both tests were unchanged. These results indicate that routine spirograms and chest films have little influence on the CMP of clinically stable patients. However, unexpected roentgenographic and spirometric findings frequently alter the management of the individual whose condition has clinically deteriorated.

Adult↗
PubMed1987

Factors associated with a poor outcome in tularemia.

To identify the factors associated with a poor outcome, we reviewed the records of 28 patients with tularemia diagnosed between 1974 and 1984. Most of the patients were men between the ages of 35 and 45 years, who presented with ulceroglandular tularemia. Twelve patients had the anticipated rapid response to therapy, with resolution of their presenting symptoms within one week (group A). Surprisingly, the majority (16 [58%] of 28) had a more prolonged or fatal illness (group B). Group B patients more often had a serious underlying medical disorder, and waited longer before seeking medical attention. Only patients in group B presented with electrolyte or renal function abnormalities (31%), pneumonia and pleural effusions (25%), elevated serum creatine phosphokinase levels (25%), and Francisella tularensis bacteremia (12.5%). Sterile pyuria, however, was an unexpectedly frequent finding in both groups. Group B patients more often experienced a prolonged delay from the time of physician contact to therapy, and were not treated with an aminoglycoside; relapse (12.5%) and death (6.2%) occurred only in group B. Thus, earlier and more appropriate intervention by the physician may have prevented some of the increased morbidity in our patients. These findings suggest that rapid presumptive aminoglycoside therapy (gentamicin sulfate or streptomycin sulfate) should be considered soon after tularemia is suspected, especially for patients with serious underlying medical disorders.

Adult↗