Biomedical subjects

D C Stokes

Publications and source records attributed to D C Stokes.

At least 37 records · Page 2Linked to original sources

PubMed1988

Effect of scavengers of oxygen-derived free radicals on mortality in endotoxin-challenged mice.

Oxygen-derived free radicals have been implicated as mediators of cellular injury in several model systems. Recently, a role for free radicals has been proposed in the mortality associated with Gram-negative bacterial sepsis. To determine if pretreatment with free radical scavengers can prevent endotoxin-induced mortality, mice rendered sensitive to endotoxin with actinomycin D were treated with either superoxide dismutase (SOD), N-acetylcysteine (NAC) or saline and were then challenged with a dose of endotoxin calculated to cause a mortality of greater than 80%. Mortality was assessed at 12-h intervals after challenge. Increased survival was seen in the SOD-treated group compared to the control group (p less than or equal to .05). In contrast, survival in mice treated with NAC, another potential scavenger, was not significantly different from the control group. These results support the hypothesis that superoxide and hydroxyl radicals contribute to mortality in Gram-negative bacterial sepsis.

Acetylcysteine↗

PubMed1988

Spirometry and chest wall dimensions in achondroplasia.

Standard values for pulmonary function in short-limbed dwarfism are not available. Therefore, chest diameters and expiratory spirograms were measured in 58 female and 44 male subjects between 7 and 60 years of age with achondroplasia, the most common form of dwarfism. Standing height in adults was 49.6 +/- 3.2 (SD) inches with a sitting/standing height ratio of 0.66 (normal 0.52-0.53). Despite extremely short stature, only AP chest diameters in males were smaller than control subjects of similar age. The following equations were derived for forced vital capacity (FVC): males (under 25 years), FVC(L) = -3.56 + 0.162 X sitting height (in) + 0.067 X age (yrs); males (over 25 years), FVC(L) = -0.73 + 0.162 X sitting height (in) -0.047 X age (yrs); females (under 20 years), FVC(L) = -3.56 + 0.150 X sitting height (in) + 0.067 X age (yrs); females (over 20 years), FVC(L) = -1.92 + 0.150 X sitting height (in) -0.016 X age (years). Similar prediction equations were derived for FEV1 and FEF25-75%: FEV1/FVC % was 84.2 (+/- 6.5) for females and 88.0 (+/- 6.5) for males. We also compared the observed FVC measurements to values calculated using standing heights derived from the subject's sitting height, assuming a normal body proportion. The observed vital capacity in achondroplasia was only 67.6 (+/- 19.2) percent of that predicted for normally proportioned females and 72.4 (+/- 13.6) percent for males, suggesting reduced vital capacity in achondroplasia, due to reduced chest wall compliance or abnormal lung growth.

Achondroplasia↗

PubMed1988

Presentation of Pneumocystis carinii pneumonia as unilateral hyperlucent lung.

Pneumocystis carinii pneumonia (PCP) presented as unilateral hyperlucent lung in a 27-month-old patient with a brain tumor who was receiving chemotherapy. Although unilateral pneumonia is an uncommon presentation of PCP in non-AIDS patients, PCP must be suspected in any pediatric cancer patient not receiving trimethoprim-sulfamethoxazole prophylaxis and receiving intensive chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1988

Cryptosporidiosis in ferrets.

The diagnosis of cryptosporidiosis in two ferrets who died from unrelated causes prompted a survey to determine the prevalence and incidence of the infection in ferrets at our facility. The survey of the existing ferret population and all new arrivals indicated cryptosporidiosis occurred as a subclinical disease in a high percentage of young ferrets: 40% of the ferret population and 38 to 100% of the new arrivals had cryptosporidial oocysts in their feces. The infection was found to persist for several weeks in both immunocompetent and immunosuppressed ferrets. The interspecies transmission of Cryptosporidium implies that infected ferrets should be considered a potential source of infection for the general population.

Animals↗

PubMed1987

Polymyxin B moderates acidosis and hypotension in established, experimental gram-negative septicemia.

Polymyxin B (PMB), an antibiotic, and sodium deoxycholate (NaD), a bile salt, are surface-active agents. Each protected mice against an otherwise lethal challenge with purified endotoxin (P less than .001). To determine if either of these agents was effective in treating established, overwhelming gram-negative septicemia, we infected rabbits by intraperitoneal injection of Escherichia coli K1. Animals were treated with moxalactam 1 hr after infection, then randomly assigned to groups receiving either saline, PMB, or NaD. Serial samples of blood were assayed for bacterial concentration, levels of plasma endotoxin, arterial blood gases, and complete blood cell counts. Physiologic functions were monitored continuously. Although levels of bacteremia and endotoxemia were similar in all three groups, rabbits receiving PMB had significantly higher mean arterial blood pressure, blood pH, and bicarbonate concentrations than did control rabbits (P less than .05). Rabbits receiving NaD fared no better than controls. In this model, PMB moderates some of the deleterious effects of established, overwhelming gram-negative bacterial sepsis.

Acidosis↗

PubMed1987

In situ management of confirmed central venous catheter-related bacteremia.

Thirty-one patients with suspected central venous catheter-related bacteremia were evaluated with comparative quantitative cultures of central venous and peripheral blood specimens. Using criteria developed from studies in bacteremic animals, 19 patients were confirmed to have catheter-related bacteremia. Antibiotic therapy was administered through the catheter (in situ therapy) in 17 of those patients to evaluate the feasibility of treating patients with true central venous catheter-related bacteremias without catheter removal. Bacteremia was successfully eradicated in 11 of 17 patients (65%), allowing 7 patients to retain their catheter a median of 157 days. This study validates the use of comparative quantitative blood cultures in the diagnosis of catheter-related bacteremia and indicates that in situ therapy is a rational alternative to catheter removal in patients with catheter-related bacteremia.

Adolescent↗

PubMed1987

Varicella zoster and herpes simplex virus pneumonias.

Varicella zoster (VZV) and herpes simplex (HSV) viruses commonly cause self-limited infection of the skin and mucous membranes. However, certain groups of subjects, including neonates, cancer patients, organ and bone marrow transplant recipients and those with congenital or acquired deficiencies of cell mediated immunity, are at increased risk for dissemination of either virus to the lungs and/or other viscera. The highest risk for VZV pneumonitis is in bone marrow transplant recipients, 44%, and in children with acute leukemia, 32%. The mortality from this complication of VZV infection in the preantiviral era was at least 25%. Except for neonates, dissemination and mortality rates for HSV infections are less than for VZV infections in the high risk groups. Cell-mediated immunity has a major role in both recovery from primary infection and modulation of latent infection, but antiherpes antibodies also have an important role in moderating the extent and severity of infection. Both viruses cause a patchy nodular pneumonia with scattered necrotic and hemorrhagic foci. Physical examination is often misleading and rapid progression of pneumonia can occur within hours. Intravenous acyclovir, administered early in the course of HSV and VZV infection at dosages of 250 mg/m2 and 500 mg/m2 every eight hours, respectively, has nearly eliminated the risk of severe symptomatic pneumonitis. Treatment of established pneumonitis with acyclovir at these doses has also reduced the mortality of herpesvirus pneumonias.

Adult↗

PubMed1987

Experimental Pneumocystis carinii pneumonia in the ferret.

Pneumocystis carinii pneumonia (PCP) was provoked in the ferret, Mustela pulorius furo, by immunosuppression with daily long-term administration of cortisone acetate, 10-20 mg/kg subcutaneously for 9 to 10 weeks, Microscopically P. carinii was observed in the lungs of all 11 treated animals: mild to moderate in five and extensive disease in six. The histopathological features of PCP in the ferret included interstitial pneumonitis, scant mononuclear cell alveolitis, with abundant cysts and trophozoites visible in a focal distribution. There were few neutrophils present. Electron microscopy showed large numbers of both cysts and trophozoites in close association with type I cells. No bacterial pathogens were isolated from the lungs of immunosuppressed animals but an unexplained eosinophilic enteritis was present in treated animals. P carinii pneumonia developed without significant body weight loss during corticosteroid administration, unlike previously described studies using corticosteroid-treated rodents. Ferrets thus appear to be a 'steroid resistant' animal, like man, and therefore a more suitable model for immunological studies of host response to PCP than rodents. This new model also has practical advantages over previously described animal models of PCP, including larger lung and airway size.

Animals↗

PubMed1986

Development of murine monoclonal antibodies to Pneumocystis carinii.

Relatively little is known about the antigenic structure of Pneumocystis carinii and the immunopathogenesis of pneumonitis caused by P. carinii. To begin to define the antigenic character of the surface of this organism, we have produced murine monoclonal antibodies that react with the surface of P. carinii (obtained from rats), as detected by immunofluorescence and immunoelectron microscopy. Immunoblot analysis revealed that the six antibodies described in this report bound an antigen with an apparent molecular mass of 90,000-95,000 daltons. Although all six monoclonal antibodies bound P. carinii obtained from rats, only one (5E12) was also able to bind P. carinii obtained from rabbits, ferrets, and a human; this result demonstrated that isolates of P. carinii obtained from different species are not antigenically identical.

Animals↗

PubMed1986

Effect of methylprednisolone on bacterial clearance and endotoxin liberation during experimental sepsis induced by gram-negative bacteria.

To determine the effect of methylprednisolone administration on the clearance of bacteremia and the release and clearance of endotoxin during antibiotic therapy of gram-negative bacterial sepsis, Escherichia coli K1 sepsis was induced in paired rabbits. Moxalactam and either methylprednisolone or placebo were administered to infected rabbits 1.5 h after intraperitoneal administration of live bacteria. Serial blood samples were obtained for quantitation of bacteremia and endotoxemia, arterial blood gases, and complete blood count. Arterial blood pressure, heart rate, and core body temperature were also monitored. There were no significant differences between the methylprednisolone-treated and placebo-treated groups in either the levels of bacteremia or endotoxemia or in the physiologic, metabolic, or hematologic parameters that were measured. We conclude that methylprednisolone administration has no acute effect on bacterial clearance or on the kinetics of endotoxin release and clearance during antibiotic therapy of gram-negative bacterial sepsis in this experimental model.

Animals↗

PubMed1986

Surfactant phospholipids and lavage phospholipase A2 in experimental Pneumocystis carinii pneumonia.

The effect of Pneumocystis carinii pneumonia on surfactant phospholipids and lavage phospholipase A2 was investigated. Pneumocystis carinii infection was induced in adult rats by immunosuppression with dexamethasone administered in the drinking water (2 mg/L) for 6 to 8 wk. Surfactant phospholipids were isolated from lung lavage and lung tissue. Dexamethasone administration significantly increased total lung and lavage phospholipids in corticosteroid-treated animals receiving prophylaxis against P. carinii with trimethoprim-sulfamethoxazole (TMP-SMZ) when compared with no treatment control animals. Lavage surfactant phospholipids from P. carinii-infected rats were 25% that of no treatment control rats and less than 10% that of corticosteroid control animals receiving TMP-SMZ. Phospholipid composition of lavage phospholipids was also altered in P. carinii pneumonia, with slight increase in the percentage of sphingomyelin and reduced percentage of total phosphatidylcholine. Postlavage tissue phospholipids of P. carinii-infected rats were 4 times that of no treatment control animals, although only about 50% that of corticosteroid control animals. There was no significant difference in lavage phospholipase A2 activity for the P. carinii-infected and corticosteroid control groups, although the enzyme activity was at least 4 times that of the no treatment control group. The surfactant changes were associated with abnormal excised lung pressure-volume curves and decreased deflation stability in the animals with P. carinii. These results indicate that the corticosteroids used in this model induce an increase in both lung surfactant phospholipids and phospholipase A2. Despite this increase in lavage phospholipids, P. carinii pneumonia in this model causes an alveolar surfactant phospholipid deficiency without significant increase in phospholipase A2 activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Lung mechanics, radiography and 67Ga scintigraphy in experimental Pneumocystis carinii pneumonia.

Respiratory system pressure-volume (P-V) studies, 67Ga-citrate scans, and chest radiographs were made in the corticosteroid-treated rat model of Pneumocystis carinii pneumonia. The steroid treatment used to provoke Pneumocystis infection in this model resulted in a reduction in body weight, lung weight and lung volumes compared to age-matched controls but no change in the normalized pressure-volume curve. P. carinii infection was associated with increased lung wet weight and flattening of the respiratory system P-V curve when compared to either age matched controls or steroid-treated animals on trimethoprim-sulfamethoxazole prophylaxis for P. carinii. Radiographs were interpreted as positive in only three of 11 animals with P. carinii, whereas 10 of 12 animals showed positive gallium-67 lung scans. We conclude that both gallium uptake and altered lung mechanics occur in the rat with Pneumocystis carinii and may reflect increased alveolar permeability and surfactant abnormalities noted in other studies.

Animals↗

PubMed1985

Thymoma and myasthenia gravis in a 4-year-old child. Case report and review of the literature.

Thymomas are exceedingly rare in the first 20 years of life, and only a few well-documented cases are present in the literature. Thymomas in adults are commonly associated with other diseases, the most frequent being myasthenia gravis (MG). However, this association has been reported not to occur in childhood. The authors report the case of a 4-year and 10-month-old girl who presented with clinical evidence of MG before thoracotomy and who developed florid MG after thoracotomy for removal of an anterior mediastinal mass later documented to be a thymoma.

Autoantibodies↗

PubMed1985

Transbronchial lung biopsy in pediatric and adolescent patients.

Since data are unavailable on the role of transbronchial lung biopsy (TBB) in pediatric and adolescent patients, we reviewed our two-year experience in 12 patients (median age, 14.5 years). In all 12, the indication for TBB was a persistently abnormal chest roentgenogram (nine with multilobar infiltrates, two with unilateral infiltrates, and one with a cavitary lesion). Overall, a specific diagnosis was made by TBB in six patients, including three patients with sarcoidosis, one with lymphoma, and two with eosinophilic granuloma. In three additional patients, nonspecific histologic findings on TBB combined with clinical findings, roentgenographic patterns, and supplemental laboratory data helped support a diagnosis. Although the need for general anesthesia and the small size of the biopsy specimens may limit the usefulness of TBB in most pediatric patients, TBB may be a useful alternative in carefully selected patients.

Adolescent↗

PubMed1985

Lack of antibacterial activity after intravenous hydrogen peroxide infusion in experimental Escherichia coli sepsis.

The intravenous administration of hydrogen peroxide has been reported to benefit patients with pneumonia and to reduce Plasmodium parasitemia in experimentally infected mice. We assessed the antibacterial activity of intravenously infused hydrogen peroxide against hydrogen peroxide-susceptible Escherichia coli (MBC of hydrogen peroxide, 0.23 mM) in experimentally infected rabbits. No decrease in the level of bacteremia was detected at the maximum intravenous infusion rate of hydrogen peroxide physiologically tolerated by the rabbits (2.0 mumol/h). Moreover, the addition ex vivo of greater amounts of hydrogen peroxide to human or murine blood containing E. coli resulted in no detectable antibacterial action. In contrast, ethyl hydrogen peroxide, which is not affected by catalase, was bactericidal when added ex vivo to human blood containing E. coli. These results suggest that extracellular hydrogen peroxide, whether of exogenous or endogenous origin, does not have antibacterial activity in the blood of animals having even low levels of catalase.

Animals↗

PubMed1985

Postural hypoxemia in cystic fibrosis.

We measured arterial blood gases in the sitting and supine position in 33 patients with cystic fibrosis (CF). Arterial PO2 ranged from 48 to 97 mm Hg in the sitting position and fell by 1 to 23 mm Hg in 26 patients, rose by 1 to 4 mm Hg in five, and was unchanged in two when supine. Mean PO2 change for the group was a 6.5 (+/- 6.8) mm Hg decrease (sitting to supine), and substantial falls were more likely to occur in patients with mild to moderate, rather than severe, obstructive lung disease. There were no significant changes in PCO2 or pH with posture. Postural hypoxemia was not completely explained by greater airway closure as measured by the single-breath nitrogen method in 11 patients or by worse radiographic change in the upper lung zones. Arterial PO2 should always be compared in the same body position in CF patients, preferably while supine. Postural hypoxemia also may contribute to the lower PO2 at night in CF patients.

Adolescent↗

PubMed1984

Chronic obstructive airways disease after bone marrow transplantation.

The clinical course, serial pulmonary function studies, lung histopathologic findings, and treatment in two patients after bone marrow transplantation for acute monoblastic leukemia or aplastic anemia are presented. The course in one patient has been slowly progressive for 2 years and characterized by chronic obstructive airways disease and recurrent pneumothoraces. Histopathologic changes were nonspecific, characterized by chronic interstitial pneumonitis and interstitial fibrosis. In the second patient there was insidious onset of disease with increasing dyspnea on exertion and rapid clinical deterioration; he died within 4 months of severe obstructive airways disease. Necrotizing bronchitis and bronchiolitis characterized the lung findings. Neither patient responded to conventional bronchodilator therapy, and prednisone was the only agent to produce subjective, though transient, improvement. Symptomatic obstructive airways disease associated with chronic graft-versus-host disease is emerging as a potentially major cause of morbidity and mortality after marrow transplantation.

Adolescent↗

PubMed1984

Use of oral contraceptives in women with cystic fibrosis.

Oral contraceptive pills (OCP) represent the most common contraceptive method among teenagers and young adults. Because many women with cystic fibrosis (CF) are now surviving into childbearing age and are at risk for the complications of pregnancy in CF, oral contraceptive use may be indicated. However, it has been suggested that OCP use by CF patients may be associated with deterioration in pulmonary function. Ten adolescent and young adult women with CF and moderate-to-severe obstructive lung disease were studied while taking a combination oral contraceptive pill (Ovral 28). No significant deterioration was found in clinical status or pulmonary function. Careful follow-up should nevertheless be continued to monitor for other adverse effects of oral contraceptive use in CF, such as cholelithiasis.

Adolescent↗