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Biomedical subjects

C Abrahams

Publications and source records attributed to C Abrahams.

At least 19 recordsLinked to original sources

Acute eosinophilic pneumonia: a cause of reversible, severe, noninfectious respiratory failure.

We report a case of acute eosinophilic pneumonia associated with adult respiratory distress syndrome in an adolescent. This entity should be considered in the differential diagnosis in previously well children and adolescents who are seen with unexplained respiratory failure and who have many eosinophils in bronchoalveolar lavage fluid. Prompt recognition of this rapidly reversible noninfectious disorder and institution of corticosteroids may be lifesaving.

Acute Disease↗

Disseminated histoplasmosis in an infant with acquired immunodeficiency syndrome.

Disseminated histoplasmosis has been recognized as a serious opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS). However, cases reported in the literature have been predominantly in adult patients. Here we report an infant with AIDS who presented with fever, cough, rhinorrhea, hepatosplenomegaly, pancytopenia and coagulopathy, and died of respiratory failure. Autopsy revealed disseminated histoplasmosis involving multiple organs including lungs, intestines, liver, spleen, bone marrow, lymph nodes, kidneys, and meninges. The diagnosis was established based on histomorphology and confirmed by blood culture.

Acquired Immunodeficiency Syndrome↗

Salivary gland tumors after childhood radiation treatment for benign conditions of the head and neck: dose-response relationships.

We have investigated the dose-response relationships for the incidence of salivary gland tumors in a cohort of 2945 individuals who were irradiated as children between 1939-1962. Most of the patients were treated to reduce the size of their tonsils and adenoids. The mean dose to the salivary glands (+/-SD) was 4.2 +/- 1.7 Gy. Eighty-nine patients developed 91 salivary gland neoplasms; 22 had single malignancies, 64 had single benign neoplasms, 2 developed two separate benign neoplasms, and 1 developed a single neoplasm but did not have surgery. The majority (81 of 89) of the patients developed neoplasms in the parotid glands. Mucoepidermoid carcinomas were the most common malignancy and mixed (pleomorphic) adenomas were the most common benign neoplasm. For all salivary gland tumors, the excess relative risk per gray (ERR/Gy) was 0.82; however, the 95% confidence interval was wide (0.04, upper bound indeterminate). The trend was determined principally by benign tumors, as there was no dose-response relationship for salivary gland cancer, although there were too few cases to draw definitive conclusions. Overall, our study provides support for an association between salivary gland tumors and radiation exposure. Although most salivary gland tumors are benign and are usually readily detected, they may cause morbidity, and people who have been irradiated in the area should be monitored for their occurrence.

Adenoids↗

Pneumonic tularemia in a patient with chronic granulomatous disease.

We report the case of a 14-year-old boy with granulomatous pneumonia caused by Francisella tularensis. In addition, an autosomal recessive form of chronic granulomatous disease was diagnosed. Both F. tularensis and chronic granulomatous disease are associated with pulmonary granulomas. To our knowledge, this is the first report of F. tularensis infection in a patient with chronic granulomatous disease. The relationship between these two processes is discussed.

Adolescent↗

Multiple schwannomas and meningiomas associated with irradiation in childhood.

OBJECTIVE: To determine the pattern of neural tumors (schwannomas, vestibular schwannomas [acoustic neuromas], and meningiomas) that developed in 3013 people who received radiation treatment with x-ray beam therapy for benign conditions of the head and neck area before their 16th birthday. METHODS: The surgical and pathology reports and pathology slides were reviewed for all neural tumors in the cohort. Patients with more than 1 neural tumor were compared with those with 1 neural tumor and those with no neural tumors. RESULTS: There were 7 patients with multiple neural tumors and 63 with single neural tumors. The distribution of tumors in these 2 groups differed. The group with multiple tumors had more spinal nerve root schwannomas, while the group with single tumors had more cranial nerve schwannomas. Six of the 7 patients did not meet the diagnostic criteria for neurofibromatosis type 2. CONCLUSIONS: Our findings suggest that host factors that increase susceptibility to radiation may be involved in the development of the multiple neural tumors. Clinically, patients with multiple neural tumors who do not meet the diagnostic criteria for neurofibromatosis type 2 should be questioned about radiation exposure. If exposure is confirmed, then screening for other radiation-related tumors should be initiated.

Adult↗

Direct effects and augmentation of airway smooth muscle contraction caused by phospholipase A2.

We examined the effect of phospholipase A2 (PLA2; Naja naja) on isometric tracheal smooth muscle force generation in guinea pig trachealis in situ. Direct application of PLA2 to the surface of the trachea caused dose-related contraction of tracheal smooth muscle. In seven guinea pigs, a dose/density of 100 micrograms/cm2 PLA2 caused active tension (AT) that began immediately and was maximum (1.32 +/- 0.13 g/cm) at 5 min (p less than 0.01 versus baseline tension). PLA2 also augmented the contractile response to intravenously administered acetylcholine (ACh); AT caused by 3 x 10(-7) mol/kg ACh was 0.98 +/- 0.13 g/cm after PLA2 versus 0.64 +/- 0.09 g/cm in control animals (p = 0.003). PLA2 inactivated with bromophenacyl bromide (BPB) prior to topical application neither caused contraction (-0.18 +/- 0.18 g/cm AT, p = NS versus baseline tension) nor altered muscarinic responsiveness to 3 x 10(-7) mol/kg ACh. Contraction caused by 100 micrograms/cm2 PLA2 was greater after epithelium removal (2.73 +/- 0.40 g/cm AT versus 1.32 +/- 0.13 g/cm AT in epithelium-intact animals, p less than 0.005). However, epithelium removal (confirmed histologically) attenuated completely augmentation of muscarinic contraction caused by PLA2. Augmentation of muscarinic contraction also was blocked with 15 mg/kg 3-amino-1-(3-trifluoromethylphenyl)-2-pyrazoline hydrochloride (BW 755c), an inhibitor of eicosanoid synthesis, administered intravenously 30 min prior to topical application of 100 micrograms/cm2 PLA2. In contrast, contraction of tracheal smooth muscle caused by PLA2 was not affected significantly by blockade of eicosanoid synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

Dietary calcium and vitamin D modulate 1,2-dimethylhydrazine-induced colonic carcinogenesis in the rat.

To determine whether supplemental dietary calcium and/or vitamin D deficiency are involved in modulating colon cancer induced by 1,2-dimethylhydrazine (DMH), Sprague-Dawley rats were fed diets containing either: (a) a normal content of calcium (0.87%) and phosphorus (0.60%) with 2.2 IU of vitamin D3 per g of feed (group A); (b) the same diet as group A, but with calcium and phosphorus increased to 1.80 and 0.80%, respectively (group B); or (c) a vitamin D-deficient diet with supplemental calcium (1.80%) and phosphorus (0.80%) (group C). After 6 weeks on their respective diets, one-half the animals in each group were given s.c. injections of either vehicle or DMH (20 mg/kg body weight/week) for 26 weeks. Animals were then sacrificed and the incidence of tumors as well as the number of tumors per tumor-bearing rat were determined. Colonic mucosal polyamine levels were measured after 15 weeks of exposure to vehicle or DMH, before development of histologically recognizable neoplasms. The results of these experiments demonstrated that neither calcium supplementation alone nor supplemental calcium in conjunction with vitamin D deficiency altered the incidence of colonic cancer induced by this carcinogen. Supplemental calcium, however, significantly decreased the number of rats with multiple tumors and reduced tumor size. Moreover, vitamin D deficiency abolished these protective effects of calcium on colon cancer in this experimental model. DMH treatment increased polyamine levels in the premalignant colonic mucosa in group A rats. This carcinogen-induced effect was blunted by high dietary calcium. Vitamin D-deficient, calcium-supplemented rats (group C) showed an increase in N1-acetylspermidine, but not the other polyamines, with DMH treatment.

1,2-Dimethylhydrazine↗

Epithelial modulation of airway smooth muscle response to endothelin-1.

We investigated the role of epithelial modulation of contraction caused by endothelin-1 in airway smooth muscle in guinea pigs in situ. Airway responses were assessed isometrically as tracheal force and simultaneously as change in lung resistance. Intravenous administration of 10(-8) mol/kg endothelin-1 caused a biphasic response in tracheal active tension: initial relaxation (-0.82 +/- 0.22 g/cm after 30 s, p less than 0.05 versus baseline) followed by contraction (1.65 +/- 0.28 g/cm after 7 min, p less than 0.05 versus baseline). Endothelin-1 also elicited immediate bronchoconstriction; lung resistance increased from 0.148 +/- 0.030 to 0.992 +/- 0.274 cm H2O/L/s (p less than 0.005) after 10(-8) mol/kg endothelin-1 given intravenously. Active tension elicited by 10(-8) mol/kg endothelin-1 after removal of the epithelium from the tracheal segment (0.59 +/- 0.16 g/cm) was less than in segments with an intact epithelium (1.65 +/- 0.28 g/cm, p less than 0.01). Both tracheal contraction and bronchoconstriction were attenuated by pretreatment with indomethacin orally, BW 755C intravenously, or substitution of endothelin-C-terminal hexapeptide for endothelin-1. However, the initial tracheal relaxation response was similar after each intervention. These data suggest actions of endothelin-1 that have not been demonstrated previously: (1) endothelin-1 elicits a biphasic response in tracheal smooth muscle (an initial relaxation response elicited by the carboxy-terminal residues and a later contractile response that requires synthesis of a cyclooxygenase mediator) and (2) epithelium adjacent to the airway smooth muscle modulates contraction elicited by endothelin-1.

Animals↗

The incidence and distribution of Mycoplasma fermentans (incognitus strain) in the Chicago AIDS autopsy series: an immunohistochemical study. Chicago Associated Pathologists.

Mycoplasma incognitus is a recently described organism that was originally isolated by Shyh-Ching Lo from spleen and Kaposi's sarcoma (KS) tissue of patients with AIDS. The mycoplasm has since been found in selected AIDS autopsy cases in which there were tissues with unexplained areas of necrosis. Mycoplasma incognitus is now known to be closely related to Mycoplasma fermentans. In order to determine the incidence and distribution of M. fermentans/M. incognitus in an unselected series, we performed a retrospective immunohistochemical study of 42 HIV-positive autopsies from the Chicago AIDS autopsy series. One case (2.4%) was found to be positive. The patient was a 27-year-old white male homosexual who had no evidence of Kaposi's sarcoma nor of any other neoplastic disorder and who died of Pneumocystis carinii pneumonia. Antigen was present in the macrophages of the patient's spleen, liver, and bone marrow but was not associated with areas of necrosis. All other tissues sampled from this case (brain, heart, testis, lymph nodes) were negative. In the remaining autopsies, organs of the reticuloendothelial system as well as other randomly selected tissues (e.g., lung, heart, testis, pancreas) were screened and found to be negative. Tissues from several non-AIDS autopsies were also found to be nonreactive for M. fermentans/M. incognitus. We conclude that M. fermentans/M. incognitus is not a common agent found in the Chicago AIDS population; that it may be identified in tissue without morphologic abnormality; and that it is not randomly present in non-AIDS autopsies.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

Percutaneous gallstone lithotripsy. Results in acute and chronic swine models.

The authors describe here a rotary catheter for the percutaneous fragmentation of gallstones. Gallstones are drawn into the rotating impeller by a powerful vortex and mechanically fragmented. Fragments are aspirated from the gallbladder following use of the device. The safety and efficacy of the device was tested after placement of human gallstones in the pig's gallbladder in 19 acute, 15 chronic, and two control experiments. In 27 completed experiments, 206 human gallstones (6-20 mm) were implanted. Most residual fragments were less than 2 mm; 24 fragments were 2 to 4 mm and seven were 5 to 8 mm. Acute histologic changes included focal loss of mucosa, mucosal and submucosal hemorrhage, and deposition of biliary material in the mucosa and submucosa. At 30 and 90 days, gallbladder histology revealed regeneration of the mucosa with isolated granuloma formation.

Acute Disease↗

Percutaneous ablation of gallstones.

The purpose of this study was to determine if gallstones could be safely and effectively ablated in the pig using a proprietary percutaneous rotor-tipped catheter, the Kensey-Nash Lithotrite (KNL). All gallstones in a single human gallbladder were defined as a gallstone set. Human gallstone sets not meeting current treatment criteria for extracorporeal shock wave lithotripsy (ESWL) were placed in the gallbladder (GB) of male pigs (N = 8; 80-100 kg). A percutaneous transhepatic guide wire was put into the GB and the abdomen closed. The KNL was then introduced under fluoroscopy using the Seldinger technique and activated. Gallstone ablation was monitored by tactile and auditory feedback to the operator and by fluoroscopy. Once completed the device was withdrawn, the GB irrigated, and the 9F sheath removed. Animals were sacrificed immediately (Group 1, N = 4) and at 28 +/- 5 days (Group 2, N = 4). Gallstones were ablated in 26 +/- 8 min. No pig had significant hemorrhage, GB perforation, or pancreatitis. One acute animal had stone fragments greater than 2 mm in the gallbladder. No other animals had any fragments greater than 1 mm present in the GB, cystic duct, common duct, ampulla, or duodenum. Histologic examination of the GB showed acute hemorrhagic mucosal injury in Group 1 and extensive mucosal regeneration with some stone fragment granulomata and mural fibrosis in Group 2. We conclude that percutaneous gallstone ablation with the KNL is safe and effective in this short-term pig model and appears to be a safe procedure for gallstone ablation. Long-term safety and effectiveness remain to be demonstrated. This device should be useful for treatment of symptomatic gallstones in patients not treatable by ESWL.

Animals↗

Epithelium-dependent contraction of airway smooth muscle caused by eosinophil MBP.

We have identified two distinct functions of the epithelium of guinea pig airways that modulate airway smooth muscle contractility in the presence of the major basic protein (MBP) of human eosinophilic granules: 1) active force generation resulting less than 1 min after epithelial contact with MBP; and 2) sustained, augmented force generation that does not depend on cytotoxic interference with the synthesis of an epithelial-derived inhibitory factor. To evaluate these influences, an in situ preparation of guinea pig trachea was developed that permitted direct, on-line measurement of isometric force generation in the underlying muscle. Direct application of 10(-8) mol/cm2 MBP to the surface of the epithelium elicited force generation that did not require the presence of a contractile agonist. Force generation began less than 1 min after MBP application and reached maximum active tension (AT) of 0.97 +/- 0.38 g/cm at 30 min (P less than 0.05 vs. baseline). Denatured MBP did not elicit active tension. MBP also caused augmented contraction to intravenous acetylcholine (ACh); 30 min after topical application of MBP, AT generated by 3 x 10(-7) mol/kg iv ACh was 0.85 +/- 0.14 vs. 0.55 +/- 0.08 g/cm in control animals (P less than 0.05). Threshold response to ACh (-8.1 +/- 0.3 log mol/kg) also decreased significantly after MBP (-9.1 +/- 0.4 log mol/kg) vs. baseline (P less than 0.01). Removal of the epithelium (confirmed histologically) abolished both direct contraction and augmented force generation to ACh caused by topical application of MBP to the airway muscle. These data suggest actions of MBP that have not been demonstrated previously: 1) activation of epithelial function that causes direct contraction of airway smooth muscle; and 2) independence of the MBP-induced effects from active tone elicited by other agonists. We also demonstrate that augmented contraction that does not depend on MBP blockade of tonic inhibitory secretion from the epithelium.

Acetylcholine↗

Distribution of pulmonary vascular resistance during lactic acid infusion in dogs.

We sought to determine the longitudinal distribution of pulmonary vascular resistance (PVR) in acute lactic acidosis utilizing pulmonary artery and vein balloon occlusion techniques (Holloway et al. J. Appl. Physiol. 54: 840-851, 1983). In anesthetized dogs, both a systemic vein (I-V) infusion and systemic artery (I-A) infusion of L-lactic acid were studied to control for potential effects of factors other than pH on PVR. During progressive I-A infusion (n = 9) to a pH of 6.94 +/- 0.06 there was no significant change in PVR or its distribution. In contrast, I-V infusion (n = 9) to a pH of 7.08 +/- 0.09 increased median PVR from 3.6 to 21.7 mmHg.1(-1).min (P less than 0.001), due to an increase in middle segment resistance (0.0-15.4 mmHg.1(-1).min, P less than 0.02). Examination by light and electron microscopy demonstrated pulmonary capillary obstruction with hemolyzed erythrocyte (RBC) membranes with I-V infusion, but representative I-A animals did not demonstrate these findings. Conceivably, the systemic vascular bed filtered the fragmented RBC membranes in the I-A model, but this microvascular obstruction with altered RBCs and RBC fragments caused the pulmonary hypertension observed in the I-V infusion. We conclude that lactic acidosis does not increase pulmonary vascular tone in dogs, a finding compatible with most previous studies in which observed increases in PVR may be attributed to other effects from I-V acid infusion on circulating blood elements.

Acidosis, Lactic↗

Fibrosis-induced reduction of endomyocardium in the rat after isoproterenol treatment.

Isoproterenol treatment leads to endomyocardial fibrosis with muscle fibers encircled by fibrillar collagen. This study was undertaken in the rat to determine if muscle encased in collagen would subsequently become either necrotic or atrophic. For this purpose, we monitored the fibrillar nature of myocardial collagen, its alignment with muscle, and the morphology of the endomyocardium, together with the response in diastolic and systolic myocardial stiffness, immediately on completion (10 days) and 30 days after a course of subcutaneous isoproterenol (500 micrograms/kg/day). We found 1) left ventricular hypertrophy at 10 and 30 days with an increase in collagen volume fraction (p less than 0.01) that consisted of a meshwork of thick and thin collagen fibers that encircled endomyocardial muscle, 2) a variable reduction in endocardial muscle fiber diameter at 30 days with the greatest thinning seen in muscle encircled by fibrous tissue, and 3) an elevation (p less than 0.01) in the slope of the diastolic stress-strain relation at 10 and 30 days. The developed systolic stress-strain relation, which was elevated at 10 days (p less than 0.01), declined (p less than 0.05) with the reduction in endomyocardial muscle mass. Thus, endomyocardial muscle, encircled by fibrillar collagen, will atrophy over time, and this leads to a reduction in active stiffness. These findings may, in part, explain why progressive ventricular dysfunction accompanies chronic myocardial disease with endomyocardial fibrosis.

Animals↗

The Chicago AIDS autopsy study: opportunistic infections, neoplasms, and findings from selected organ systems with a comparison to national data. Chicago Associated Pathologists.

The Chicago acquired immunodeficiency syndrome (AIDS) autopsy study evaluated the first 38 AIDS autopsies through January 1, 1985 from 14 participating institutions in the Chicago area. A complete analysis of neoplasms and opportunistic infections from this material as well as a discussion of pathologic features that may be associated only with human immunodeficiency virus (HIV) infection is presented and compared with national data. Among the neoplasms nodular Kaposi's sarcoma was present post-mortem in only 15.8% of cases as compared with a national autopsy incidence of approximately 50%. This figure was highly significant (Z = -5.439 where significance occurs at more than +/- 1.96) and indicates that the Chicago AIDS population is distinct from the national AIDS population in terms of Kaposi's sarcoma. There were no parallel differences in possible cofactors to account for this lower incidence in Chicago. Inflammatory Kaposi's sarcoma was present in 3 cases but did not approach the near 100% figure reported by others. A discussion of this entity and possible reasons for confusion in its diagnosis are discussed. Chicago continues to have a low incidence of AIDS for a large metropolitan area (308 cases/million population) and a continuing low incidence of nodular Kaposi's sarcoma reported clinically. We hypothesize that either some as yet unidentified agent, not generally present in the Chicago population at risk for AIDS, is responsible for the initiation of Kaposi's sarcoma or that the particular HIV-1 isolate in Chicago is not associated with this malignancy.

Acquired Immunodeficiency Syndrome↗

Structural vs. contractile protein remodeling and myocardial stiffness in hypertrophied rat left ventricle.

Left ventricular pressure overload will result in the hypertrophic growth of the myocardium and in the rat may include a remodeling of both the structural and contractile proteins. As a result, an adaptive rise in active stiffness, or the force generating capacity of the myocardium, may occur. The relative importance of structural vs. contractile protein remodeling to the hypertrophic response and active stiffness is unclear. Accordingly, we monitored the ratio of V1/V3 isomyosin and the fibrillar nature and volume fraction of myocardial collagen, together with the developed systolic stress-strain relation of the intact myocardium in the adult male Wistar rat after 8 weeks of abdominal aorta banding. In comparison to controls and for the 20% increase in left ventricular mass obtained with banding we found: (a) collagen volume fraction had increased significantly (6.2 +/- 2.0 vs. 3.6 +/- 1.0%) while the V1/V3 ratio did not change; (b) interstitial compartment remodeling included a perivascular accumulation of collagen around small intramyocardial coronary arteries and the appearance of more extensive fibrillar collagens; and (c) active stiffness increased significantly. Thus, the increase in active stiffness of the hypertrophied adult rat myocardium, seen with abdominal aorta banding, appears to be related to interstitial fibrosis and not a conversion of myosin isoforms.

Animals↗

Pathologic changes in the kidneys and other organs of dogs undergoing extracorporeal shock wave lithotripsy with a tubless lithotripter.

Extracorporeal shock wave lithotripsy (ESWL) is an accepted method of treatment for renal calculi. Complications are rare, although most patients experience temporary hematuria. Shock waves generated by a spark plug in a tubless lithotripter administered to stones placed into the renal pelves of dogs, resulted in interstitial renal hemorrhage developing acutely, and interstitial fibroblastic reactions chronically. The latter were linear, and were in the cortex and/or medulla. They resulted from organisation of the interstitial hemorrhages. In addition interstitial nephritis was present and this could be the result of the surgery, the stones, preexisting infection or the ESWL. Other organs were intact, with the exception of a hematoma in the large bowel of one dog. Lithotripsy, in this dog model, produced a spectrum of kidney injury.

Animals↗