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Biomedical subjects

G L Freeman

Publications and source records attributed to G L Freeman.

106 records · Page 6Linked to original sources

Role of parietal pericardium in acute, severe mitral regurgitation in dogs.

Mitral regurgitation (MR) resulting from acute disruption of the mitral valve apparatus leads to serious hemodynamic sequelae. The lesion produces major elevation of left atrial (LA) and pulmonary artery pressures and decreases forward cardiac output. Clinical studies have shown hemodynamic patterns in acute MR similar to those seen in constrictive pericardial disease, suggesting that the pericardium serves to importantly limit cardiac filling in this condition. This hypothesis has not been tested in an animal model in which the intrapericardial pressure can be directly measured. In the present study intrapericardial and intracardiac pressures were measured in 8 dogs before and after the production of acute MR. After production of MR, mean LA pressure increased from 8 +/- 3 to 20 +/- 7 mm Hg (p = 0.004) and the peak LA V wave averaged 31 +/- 13 mm Hg. Mean right atrial pressure increased slightly, from 4 +/- 2 to 5 +/- 1 mm Hg (p less than 0.008). Intrapericardial pressure increased in each dog, but the increment was invariably small (1 +/- 2 to 3 +/- 2 mm Hg, p = 0.001) and there was no tendency to equalization of pressure between right- and left-sided cardiac chambers. Thus, the role of the pericardium in the immediate hemodynamic response to acute, severe MR is minor.

Animals↗

Pericardial adaptations during chronic cardiac dilation in dogs.

The manner in which the pericardium adapts to chronic cardiac dilation is not known. Recent work from our laboratory indirectly suggested that the size of the pericardium and/or its pressure-volume relation was altered by chronic cardiac enlargement. To examine this question further, we compared pericardial pressure-volume and stress-strain relations, surface area, mass, and average thickness in seven normal dogs and seven with chronic volume overload hypertrophy due to a systemic arteriovenous fistula. Dogs with significant cardiac hypertrophy had an increased pericardial volume at any pressure and a proportionality constant for the slope of the entire curve as determined by nonlinear regression analysis. This was associated with parallel increases in pericardial surface area and mass such that average thickness was unchanged. Stress-strain analysis of the data revealed that the mechanical properties of the pericardium were not significantly different in dogs with chronic cardiac dilation. These results indicate that during chronic cardiac dilation the pericardium enlarges in size and mass. The pericardial chamber is more compliant, although the intrinsic stiffness of the pericardium appears to be unchanged. Further, since pericardial mass is increased, the response to chronic dilation appears to also involve the addition of new pericardial tissue.

Animals↗

Evaluation of natural killer activity in human schistosomiasis.

Natural killer (NK) activity was assayed in peripheral blood mononuclear cells of patients with schistosomiasis, of patients following treatment, and of uninfected control subjects. The patient populations were from villages in the Qalyub Province, Egypt and around Belo Horizonte , Brazil. NK activity was assayed by the cytotoxicity of 51Cr-labelled K562 target tumor cells. In neither infected population were significant alterations from normal levels found in the percent cytotoxicity per 10(6) cells, or in the lytic units that expressed 25% cytotoxicity. Likewise, prior treatment (2 and 6 months previously) did not alter the group NK activity detected. Similarly, in the Egyptian study there was no difference in the percentage of large granular lymphocytes between the infected and uninfected groups. In parallel studies in Egyptian and Brazilian schistosomiasis patients we did not find any evidence that this chronic infection consistently altered circulating NK activity.

Adolescent↗

Regional venous return: nitroprusside effect in normal and chronically congested dogs.

The venous circulation is a key determinant of cardiac loading conditions. Although it may be altered by chronic congestive heart failure and vasodilating drugs, the mechanisms of these alterations have not been thoroughly studied, and their exact nature is unclear. We used venous return curves characterized by the pressure at zero flow (PZF) and resistance to venous return (RVR) to study the effect of nitroprusside and chronic congestion on regional venous return from the splanchnic and superior vena cava (systemic) venous beds in dogs. Chronic venous congestion was induced by prior creation of tricuspid insufficiency and pulmonic stenosis (TIPS). Nitroprusside lowered splanchnic PZF but not systemic PZF in both normal and TIPS animals. In normal animals systemic RVR increased during nitroprusside infusion but was unchanged in the congested animals. Resting values of PZF and RVR were different in the splanchnic and systemic venous beds in both normal and TIPS animals. We conclude that 1) nitroprusside works to selectively lower PZF in the splanchnic venous bed, 2) the regionally specific site of action of nitroprusside is not altered by TIPS, and 3) the independent behavior of the venous parameters of the two beds represents an important mechanism for the control of cardiac output.

Animals↗

Differences in adult Schistosoma mansoni worm burden requirements for the establishment of resistance to reinfection in inbred mice. II. C57BL/KsJ, SWR/J, SJL/J, BALB/cAnN, DBA/2N, A/J, B10.A(3R), and B10.A(5R) mice.

Eight strains of mice (C57BL/KsJ, SWR/J, SJL/J, BALB/cAnN, DBA/2N, A/J, B10.A(3R), and B10.A(5R) were studied in regard to the development of resistance to secondary challenge with Schistosoma mansoni following a primary infection. Also analyzed were the number of eggs recoverable from the livers of these strains after primary infection and the size of the hepatic, schistosome egg-focused granulomas newly formed at various times after infection. As previously observed by us and others, most often the degree of resistance conferred by an acute primary infection is related to the number of adult worms harbored due to the initial infection. The mean levels of protection observed in the different strains were seen to cover a spectrum from moderate to strong resistance, rather than demonstrating high or low resistance strains. There was no observable effect of the major histocompatibility complex on this resistance state. The number of eggs recoverable from the livers of the various strains was calculated on a total liver, per female worm basis, and was seen to be less in C57BL/KsJ, SWR/J and SJL/J mice. Granulomatous reactivity also varied considerably in a strain-dependent manner. These data are compared with previously reported strain differences in S. mansoni infections. Although some similarities are observed between laboratories certain strain-related discrepancies also exist and are discussed.

Animals↗

Allergic skin test reactivity to marijuana in the Southwest.

In a general allergy consultation practice in Arizona and western New Mexico, 129 patients were tested for immediate hypersensitivity skin test reactivity to marijuana pollen and tobacco leaf, as well as to a battery of other antigens. In all, 90 patients were diagnosed as allergic (atopic) and, of these, 63 (70 percent) were found to be skin test reactive to marijuana pollen and 18 (20 percent) to tobacco leaf. The incidence of skin test reactivity to marijuana was not significantly different for persons living at low, middle or high elevations throughout the Southwest. Marijuana sensitivity occurred in patients who were, in general, also sensitive to a variety of other airborne plant pollens. There was no close correlation, however, between sensitivity to marijuana pollen and sensitivity to pollens from elm, mulberry, hop and stinging nettle, which are botanically related to marijuana. The data suggest that marijuana pollen may be a relatively common airborne pollen pollutant in the Southwest, allergic persons being sensitized through inhalation. If this is confirmed by further studies, then clinical investigation of marijuana hyposensitization (immunotherapy) may be warranted. This is in contrast to tobacco allergy for which simple avoidance is recommended.

Adolescent↗

Primary in vitro sensitization to heterogeneous soluble antigens of Schistosoma mansoni adult worms.

Primary in vitro sensitization of normal mouse spleen cells was accomplished using a saline soluble heterogeneous antigenic preparation from the whole adult worms (SWAP) of Schistosoma mansoni. A SWAP-specific rosette-forming cell (RFC) assay, using antigen on sheep erythrocytes, was used to detect sensitization due to S. mansoni infection and primary in vitro SWAP exposure. The latter exposure was facilitated by SWAP adsorption to the culture vessel via poly-L-lysine. RFC expression was maximal on day 3 of culture. It was antigen-specific in regard to unexposed controls, SWAP and human gamma globulin, and as controlled by RFC detected by parallel treated (control) erythrocytes. The RFC assay was best read between 90 and 180 min after initiation of rosette formation. Assay erythrocytes gave reproducible results for at least 3 weeks after preparation.

Animals↗

Differences in adult Schistosoma mansoni worm burden requirements for the establishment of resistance to reinfection in inbred mice. I. CBA/J and C57BL/6 mice.

Schistosoma mansoni infections of CBA/J and C57BL/6 mice provided the hosts with partial protection against reinfection by S. mansoni cercariae. The level of protection, assayed by perfusion 21-25 days after challenge, varied over the course of infection. After patency the degree of resistance observed in CBA/J mice was related to the adult worm burden harbored by the mice. The same was initially true in C57BL/6 mice. Those C57BL/6 mice which lived until a chronic state of infection were rarely well protected and harbored few female worms. Strain differences were also apparent in that the number of worms required by C57BL/6 mice to establish the same level of protection as CBA/J mice was double that needed by CBA/J mice. Measurements were made of the newly formed egg-induced hepatic granulomas throughout the infection period (up to 30 weeks after infection). The data revealed that although the pattern by which C57BL/6 mice developed maximum granuloma formation and subsequent modulation was identical to that observed in CBA/J mice, C57BL/6 granulomas were consistently half the volume of their counterpart lesions in CBA/J mice.

Animals↗

Immune responses during human schistosomiasis mansoni. I. In vitro lymphocyte blastogenic responses to heterogeneous antigenic preparations from schistosome eggs, worms and cercariae.

In vitro lymphocyte blastogenesis assays were performed using peripheral blood lymphocytes obtained from patients with schistosomiasis mansoni. Their infection was well characterized both clinically and in regard to the duration and intensity of Schistosoma mansoni infection. Subjects who were either not infected with any helminths or who were negative for S. mansoni but infected with other helminths provided two control groups. Cultures were exposed to various concentrations of heterogeneous soluble antigens prepared either from S. mansoni eggs, worms, or cercariae. In this series there was no statistical correlation between the intensity of infection (as determined by eggs/ml of feces) and the degree of cell-mediated reactivity observed by lymphocyte blastogenesis to any of the antigenic preparations. Individual patient lymphocyte responsiveness varied considerably. However, analysis of the data by groups, based upon the longevity of their S. mansoni infection, demonstrated different patterns of reactivity in regard to the antigen preparations. Responses to the egg antigens were only present early in infection. In contrast, reactivities stimulated by either the worm or cercarial preparations increased in a direct relationship to the duration of S. mansoni infection.

Antigens, Heterophile↗

Immune responses during human schistosomiasis mansoni. II. Occurrence of eosinophil-dependent cytotoxic antibodies in relation to intensity and duration of infection.

Plasma samples from St. Lucians were tested for the presence of antibodies which cooperate in vitro with normal human leukocytes in causing cytotoxic damage to schistosomula of Schistosoma mansoni. The in vitro antibody activity, which has been previously shown to depend on eosinophil effector cells was detected in 56% of the individuals with known, current S. mansoni infections and in 14% of control subjects from the same endemic area. Quantitatively, eosinophil dependent cytotoxic antibody (EDCA) activity, when expressed as the maximum amount of damage to schistosomula induced at high plasma concentration, correlated significantly with the intensity of S. mansoni infection as determined by fecal egg count, the highest levels of activity occurring in patients with stool counts of 60 eggs/ml or greater. In addition, plasma EDCA activity was found to correlate with the in vitro blastogenic responsiveness of patients' lymphocytes to three different parasite antigen preparations. In contrast, titrations of EDCA activity failed to reveal a relationship between EDCA titer and the most recent egg count performed on each subject. However, a significant correlation was observed when titers were compared to egg counts averaged over a 3-year period. Neither maximal EDCA activity nor titer was found to correlate with the duration of known schistosome infection.

Antibodies↗

Alterations in myocardial free fatty acid clearance precede mechanical abnormalities in canine tachycardia-induced heart failure.

BACKGROUND: The purpose of this study was to evaluate whether abnormalities of free fatty acid metabolism are present before the onset of overt mechanical dysfunction in dogs with tachycardia-induced heart failure. We studied six dogs chronically instrumented to allow assessment of left ventricular function in the pressure-volume plane. METHODS AND RESULTS: Free fatty acid clearance was assessed according to the washout rate of a free fatty acid analog, iodophenylpentadecanoic acid ([123I]PPA or IPPA). IPPA clearance was measured within 1 hour of the hemodynamic assessment. The animals were studied under baseline conditions and 11.7 +/- 3.6 days after ventricular pacing at a rate of 240 beats/min. Hemodynamic studies after pacing showed a nonsignificant increase in left ventricular end-diastolic pressure (11.7 +/- 4.7 to 17.4 +/- 6.5 mm Hg) and a nonsignificant decrease in the maximum derivative of pressure with respect to time (1836 +/- 164 vs 1688 +/- 422 mm Hg/sec). There was also no change in the time constant of left ventricular relaxation, which was 34.8 +/- 7.67 msec before and 35.3 +/- 7.3 msec after pacing. However, a significant prolongation in the clearance half-time of [123I]PPA, from 86.1 +/- 23.9 to 146.5 +/- 22.6 minutes (p < 0.01) was found. Thus abnormal lipid clearance appears before the onset of significant mechanical dysfunction in tachycardia-induced heart failure. CONCLUSION: This suggests that abnormal substrate metabolism may play an important role in the pathogenesis of this condition.

Animals↗

Cooccurrence of latex and fruit allergies.

Clinically significant allergic reactions to latex have recently been reported with increasing frequency. Most instances of latex allergy have been noted in adults who are atopic and are in the healthcare or latex manufacturing industries. Relatively few cases of latex allergy occur in pediatric patients and in these an atopic diathesis is usually also recognized. The exception are the spina bifida children who have frequent mucosal exposure to latex medical items. The cooccurrence of hypersensitivity to certain fruits in latex-allergic patients was reported by M'Rahai et al. in 1991, and this observation has since been amply confirmed in the literature. The objective was to describe a 6-year-old Caucasian boy without known atopy who presented with a history of cutaneous and respiratory reactions to banana and avocado and from whom a history of adverse reactions to common latex products was also elicited. The results of the allergy evaluation of this patient are presented. MEDLINE was searched for reports in English of latex allergy and of latex plus fruit allergy in adults and children from 1979 through 1995. In the patient presented here, immediate hypersensitivity to latex and fruit was assayed by RAST and skin tests. The RAST to latex was strongly positive, equivocal to avocado and chestnut, and negative to banana and kiwi fruit. The prick skin test was positive for banana, avocado and chestnut. Clinically significant allergy to latex and to certain fruit cooccurs. If one component of the dyad is present, the other should be sought and evaluated.

Child↗

Gustatory sweating in the differential diagnosis of food allergy.

Herein reported is a 41-year-old white man with lifelong gustatory sweating over the vertex of the head induced by orange juice, tomatoes, onions, and certain nonchocolate candies and snack foods. IgE RAST and prick tests were negative to those offending foods for which test antigens were available. The types of gustatory sweating and their therapeutic modalities are summarized.

Diagnosis, Differential↗