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Biomedical subjects

S Gordon

Publications and source records attributed to S Gordon.

At least 487 records · Page 27Linked to original sources

Cardiovascular pathology in dialysis patients with spinal cord injury.

Necropsy findings were examined in 20 male patients with end-stage renal disease associated with longstanding spinal cord injury and treated with maintenance hemodialysis. All patients exhibited cardiovascular abnormalities. Fibrinous pericarditis was found in 50% of the patients. Left and right ventricular hypertrophy was present in 45% and 20% of the cases, respectively. The respective incidences of left and right ventricular dilatation were 40% and 30%. Cardiac amyloidosis was noted in 25% of the cases, whereas myocardial fibrosis was found in 45% of the patients. Valvular abnormalities were limited to one case of aortic stenosis and two cases of mitral ring dilatation. No evidence of infective endocarditis was observed despite the high incidence of infections in this population. Whereas 45% of the patients exhibited some degree of coronary arteriosclerosis, none exhibited evidence of acute myocardial infarction and only one showed pathologic changes consistent with old myocardial infarction. Aortic atherosclerosis was noted in the majority of patients.

Adult↗

The significance of surface changes on explanted polyurethane pacemaker leads.

Although over 140,000 polyurethane leads have been implanted in humans, a controversy has recently arisen dealing with the significance of frequently detected irregularities on explanted insulator surfaces by scanning electron microscopy (SEM), and their relationship with lead failure. We therefore implanted ten, 6 Fr atrial polyurethane leads and an equal number of 4 Fr ventricular leads in dogs for a mean 26 +/- 2 and 29 +/- 2 weeks, respectively. Fourteen leads were removed utilizing metered force. The remaining leads were removed surgically without force at the termination of the study. Specimens were stored in saline prior to physical testing (tensile strength and elongation) of intravascular and extravascular lead segments. Similarly stored samples were prepared for SEM analysis. The polyurethane insulator disconnected from the electrode on forcible removal in three atrial and two ventricular leads (concordant connected from the electrode on forcible removal in three atrial and two ventricular leads (concordant for two pairs). There was no significant relationship between the results of physical testing and extraction force, lead size, integrity on removal, sample location or SEM scores. Chemical analysis of surface changes employing both x-ray and electron emission spectroscopy failed to reveal evidence of protein adsorption or liquid impregnation. Samples soaked in sodium hydroxide displayed the same SEM irregularities. The combined effects of fissuring and fluid absorption by polyurethane did not affect chronic anodal or cathodal thresholds. In conclusion, a clear relationship between chronic surface irregularities and the insulator function of polyurethane, its relationship between chronic surface irregularities and the insulator function of polyurethane, its integrity in situ, or its strength at explant has not been established by this relatively short-term study. On the other hand, a potential time-dependent impact of these changes on lead performance has not been excluded. Moreover, only a single species of medical grade polyurethane has been clinically evaluated. Thus, the ultimate place of polyurethane leads in pacing systems has yet to be determined.

Animals↗

Macrophage activation in murine African trypanosomiasis.

African trypanosomiasis is accompanied by a profound general immunosuppression in which both suppressive T cells and macrophages (M phi) have been implicated. The present studies define changes in the M phi surface, endocytic and secretory properties, during the infection of mice by Trypanosoma brucei. Peritoneal M phi obtained after the control of the first wave of parasitemia displayed characteristics similar to those activated by intracellular pathogens, such as Mycobacterium bovis bacillus Calmette-Guérin, e.g., the enhanced expression of Ia antigen, decreased M phi-specific antigens, receptors mediating the pinocytosis of mannose-terminal glycoproteins, and an increased ability to secrete plasminogen activator, superoxide anion, and H2O2. Some markers of macrophage activation persisted during the subpatent period before the recurrence of parasitemia, whereas others reverted to normal. Mature T cell function appears not to be essential for M phi activation by T. brucei since the infection of athymic nude mice also induced Ia antigens and plasminogen activator. These studies show that M phi activated by different pathways express common features which may contribute to immune dysfunction observed in trypanosomiasis, as well as in other infections.

Animals↗

Frequency and spectrum of pulmonary diseases in patients with chronic renal failure associated with spinal cord injury.

We reviewed autopsy records from 20 patients with long-standing spinal cord injury and chronic renal failure. Only 1 patient had normal pulmonary findings at autopsy. Acute and chronic pulmonary diseases were found in 16/20 and 17/20 patients, respectively. Pneumonia and fluid overload were the most common acute diseases. Interstitial and pleural fibrosis were the most common chronic diseases. However, a variety of illnesses including pulmonary amyloidosis, calcification, and arteriosclerosis were also found. Arterial blood gas studies indicated a high prevalence of hypoxemia. We concluded that significant pulmonary abnormalities are present in almost all spinal cord injury-chronic renal failure patients.

Adult↗

Severe transient left ventricular "hypertrophy" occurring during acute myocarditis.

We report an unusual sequence of echocardiographic abnormalities observed during the course of acute myocarditis in a young woman. Striking left ventricular "hypertrophy" transiently followed the normalization of marked segmental wall motion abnormalities. These rapid and marked alterations in left ventricular wall thickness suggest that myocardial inflammation and edema resulted in the transient appearance of myocardial hypertrophy. Our findings also indicate that contractility may be nonhomogeneously depressed in acute myocarditis.

Acute Disease↗

Hemoglobin Setif and in vitro pseudosickling noted in a family with co-existent alpha and beta thalassemia.

A Turkish Cypriot family was investigated for suspected heterozygous sickle cell disease, which had been reported in a maternal branch of the family resident in England. Two maternal grandparents were of African Negro origin. Pseudosickling was noted in members of the family who were found to have an abnormal hemoglobin fraction. This abnormal fraction proved to be Hemoglobin Setif (alpha 94 Asp leads to Tyr). Family studies demonstrated the presence of this hemoglobin in varying proportions in the mother and 2 of the 4 children. alpha and beta thalassemia traits are also present in several family members.

Adolescent↗

Superoxide release by peritoneal and bone marrow-derived mouse macrophages. Modulation by adherence and cell activation.

Macrophages (M phi) activated by BCG and other immune stimuli differ from thioglycollate-elicited M phi (TPM) in releasing O-2 upon initial contact with a foreign substratum. During adherence and spreading, activated M phi release approximately 50% of O-2 levels triggered by phorbol myristate acetate (PMA). The response requires divalent cations (Ca++ or Mg++) and is sensitive to lignocaine, a reversible inhibitor of adhesion. These features distinguish this reaction from the response to PMA, which also triggers substantial release of O-2 from TPM, 60-80% of bacille Calmette--Guérin-activated peritoneal M phi (BCG-PM) activity. During prolonged cultivation as monolayers, peritoneal and bone marrow derived M phi (BMDM) progressively lose their ability to release O-2 in response to PMA and serum-treated zymosan (STZ), although the cells continue to secrete other products and to phagocytose STZ. This loss can be prevented by maintaining peritoneal and BMDM as non-adherent cells in teflon beakers or poly-(2-hydroxyethylmethacrylate) (poly HEMA) coated vessels. High levels of O-2 activity were observed after cultivating TPM on poly-HEMA (300 nmoles O-2/mg/hr after PMA), 10-fold more than adherent controls. BMDM could be induced to release four-fold more O-2, greater than 100 nmoles O-2/mg/hr, after cultivation as non-adherent cells in the absence of L cell-conditioned medium. Our results show that heterogeneity in M phi respiratory burst activity depends on (i) intrinsic differences between populations, (ii) differential responses by activated and non-activated M phi to selective surface stimuli and (iii) modulation by environmental factors which control adherence and growth.

Animals↗

Modulation of macrophage mannosyl-specific receptors by cultivation on immobilized zymosan. Effects on superoxide-anion release and phagocytosis.

Unopsonized zymosan effectively induces a respiratory burst (O-2 release, hexose monophosphate (HMP) shunt stimulation) in thioglycollate-elicited and BCG-activated macrophages (M phi). These M phi are known to express lectin-like receptors specific for mannose or fucose-terminated glycoconjugates (MFR). A role for the MFR in phagocytosis of zymosan was demonstrated by cultivating M phi on a glutaraldehyde-fixed layer of zymosan, a procedure which depleted M phi of MFR-mediated pinocytic activity, but not other surface antigens (F4/80, Mac-1) or receptors (FcR, C3R). After modulation of MFR, M phi lost the ability to phagocytose zymosan, but ingested antibody or complement-coated zymosan vigorously via alternative receptors. Challenge with free zymosan failed to enhance respiratory burst activity in M phi which had been cultivated on zymosan. Such M phi were also refractory to zymosan taken up by alternative receptors or other ingested particles (EIgG), but responded to a non-particulate challenge, PMA. These studies show that the MFR, like other receptors, can mediate phagocytosis and elicit a respiratory burst in suitably primed M phi, but indicate that phagocytosis via specific receptors (FcR, C3R) need not trigger a respiratory burst.

Animals↗

Acute renal failure after enhanced computed tomography.

Acute renal failure has been reported after the administration of a variety of radiographic contrast media. We treated a patient with preexisting renal insufficiency who received contrast media during computed tomography (CT) and had acute renal failure. The fractional excretion of sodium (FENa) was observed to be 0.2% before contrast media exposure and 3.5% after exposure. Patients with risk factors leading to contrast media-induced acute renal failure should be carefully screened before receiving enhanced CT.

Acute Kidney Injury↗

Down-regulation of mannosyl receptor-mediated endocytosis and antigen F4/80 in bacillus Calmette-Guérin-activated mouse macrophages. Role of T lymphocytes and lymphokines.

Bacillus Calmette-Guerin (BCG) infection alters the surface and endocytic properties of mouse peritoneal macrophages (PM) compared with thioglycollate- elicited (TPM) or resident PM (RPM). Expression of Ia antigen (Ag) is enhanced up to fourfold, but plasma membrane receptors that mediate binding and uptake of mannosyl/fucosyl-terminated glycoconjugates (MFR), Fc receptors, and the macrophage (mphi)-specific Ag F4/80 are reduced by 50-80 percent. Levels of Mac-1 remain relatively stable. These changes are accompanied by enhanced secretion of O(2)(-), after further stimulation with phorbyl myristate acetate, and of plasminogen activator. Both these products are released by TPM, but not RPM. The characteristic surface phenotype of BCG-PM can also be induced by injection of C. parvum, another mphi- activating agent, but not by thioglycollate broth, lipopolysaccharide, or proteose peptone. Purified protein derivative (PPD) and N-acetylmuramyl-L- alanyl-D-isoglutamine. 2H(2)0 are soluble agents with partial activity. Alteration of mphi markers by BCG infection depends on T lymphocyte function, although studies with nude mice indicate that other pathways may also serve to modify the surface of the mphi. Mphi from uninfected animals displayed all markers of activation after adoptive transfer of specifically-sensitised lymphocytes with PPD, intraperitoneally, or after co- cultivation. Treatment of primed lymphocytes with anti-Thy-1 antibody and complement ablated this effect. Lymphokines obtaned by Ag or mitogen stimulation induced similar changes in TPM and RPM. Mannose-specific endocytosis decayed rapidly, time 1/2 approximately equal to 16 h and stabilized at approximately 25 percent of control values. Single-cell analysis showed that residual MFR activity was uniform in the target population. Loss of Ag F4/80 after activation by lymphocyte and PPD was less marked than after infection (35 percent vs 80 percent), unlike MFR activity, which declined to a similar extent. Induction of mphi Ia by lymphokine reached a peak after 2-3 d and was lost within 2 d of its removal. Recovery of MFR and F4/80 was incomplete under these conditions. These studies establish that activated mphi known to display enhanced antimicrobial/anticellular activity express markedly different surface properties distinct from elicited or resident cells. The role of antigen- stimulated T cell products in regulating mphi function is confirmed, and down-regulation of mannosyl-receptor-mediated endocytosis provides a sensitive, quantitative, and cell-specific new marker to study their properties and mechanism of action. Extensive, but selective remodeling of mphi plasma membrane structure could play an important role in controlling recognition and effector mechanisms of the activated mphi.

Animals↗

Intracoronary streptokinase in clinical practice.

The candidacy for streptokinase (SK) infusion was studied in 95 patients displaying ECG evidence of acute or impending infarction who were catheterized within 5 hours of the onset of chest pain. Intracoronary SK was administered to 84 patients in whom occlusions of the infarct-related vessel were identified, with early recanalization having been achieved in 74 (88%). Because of completeness of studies, a data base of 72 patients was employed for further analysis. Recanalization was sustained at follow-up in 45 of 55 patients (82%). Spontaneous thrombolysis was demonstrated at follow-up in five patients (8%) initially resistant to SK, and rethrombosis occurred in 10 patients (18%). Preservation of R waves relative to Q wave depth was limited to patients with less than 90% residual stenosis. Eight of nine patients with continuing thrombolysis and patients with recanalized occlusions of the left anterior descending coronary artery displayed more impressive increases in mean (+/- SEM) ejection fraction (47% +/- 4% to 53% +/- 5% [p less than 0.05], and 47% +/- 3% to 52% +/- 5, respectively). The ejection fraction also increased significantly in 15 patients with pre-SK values of less than 50% (41% +/- 2% to 48% +/- 3%; p less than 0.05). Ventricular function deteriorated in SK failures. Reperfusion arrhythmias occurred in 28 of 62 recanalized patients (45%). Minor bleeding tendencies were displayed in 18 of 72 patients (25%). Major hemorrhages, one of which may have been fatal, occurred in four patients (5.6%). Of 84 patients, four (4.7%) died, two of whom were in cardiogenic shock when first seen. In contrast, there were 11 deaths (11.8%) in a consecutive simultaneously enrolled series of 93 control patients with similar entry criteria (p less than 0.05). Two additional SK-treated patients died, 16 and 30 days after treatment, both more than a week after surgical revascularization. It is concluded that SK recanalization is a promising new therapy that may decrease mortality and preserve myocardial function in certain circumstances. Its efficacy in a setting closer to the mainstream of cardiologic practice extends the favorable experience issuing from earlier clinical investigations.

Adult↗

The use and limitation of monoclonal antibodies against mononuclear phagocytes.

Monoclonal antibodies have been used to study receptors on the plasma membrane of macrophages, as well as the processes of membrane synthesis, internalization, recycling and macrophage differentiation and activation. Various immunisation and screening procedures have been employed. Most reagents produced so far are not restricted to macrophages in their binding specificity. Monoclonal antibodies have been of great use in characterising murine Fc receptors and in studying the composition of the membrane of pinocytic vesicles. Antibody F4/80 has been used to examine the behaviour of the 160K membrane protein it defines during macrophage differentiation and activation. This antigen is absent on macrophage precursors, is expressed in relatively large amounts on mature macrophages, but expression is diminished on activated populations. No macrophage subset heterogeneity has been defined by ag F4/80 or 2 other monoclonal antibody-defined macrophage antigens, as all bone marrow-derived macrophage clones express these antigens. Anti-macrophage antibodies have already proved useful as diagnostic markers and in cell separation. Reagents such as these will help to sort out relationships between macrophages and other presumptive mononuclear phagocytes.

Animals↗

Lipid abnormalities in chronic renal failure associated with spinal cord injury.

Serum lipid fractions were studied in ten patients with chronic renal failure (CRF) associated with long-standing spinal cord injury (SCI). A group of age-and-sex-matched patients with long-standing SCI but normal renal function were included for comparison. Serum triglycerides were markedly elevated in SCI-CRF patients. Both SCI groups exhibited moderate hypocholesterolemia. High density lipoprotein (HDL) cholesterol was severely reduced in the SCI-CRF group and moderately reduced in the SCI-control group. Chronic renal failure, reduced physical activity and several other factors may be operative in the genesis of hypertriglyceridemia and reduced HDL-cholesterol levels in this condition. Further investigations are necessary to examine the possible effect of these lipid abnormalities on the cardiovascular system in these patients.

Adult↗