Working together to control postoperative pain.
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Analgesia, Patient-Controlled↗
Biomedical subjects
L Maxwell
Publications and source records attributed to L Maxwell.
Oxygen content of the fixative is important in the interpretation of the ultrastructure of ischaemic myocardium.
Isolated rat hearts were subjected to 15, 45, or 60 minutes of global ischaemia and then fixed by perfusion at 37 degrees C with glutaraldehyde containing various amounts of oxygen. This either had been bubbled with 100% oxygen (PO2 620 mm Hg) or with 100% nitrogen (PO2 40 mm Hg) immediately before use, or it had been routinely prepared and stored exposed to atmospheric oxygen (PO2 245 mm Hg). The ultrastructure of myocytes and endothelial cells subjected to 15 minutes of ischaemia was not affected by the treatment of the fixative. However, when the tissue subjected to longer periods of ischaemia was fixed with routinely prepared or oxygen-bubbled glutaraldehyde, ultrastructural changes characteristic of reoxygenation damage were uniformly evident in both the microvasculature and myocytes. These qualitatively distinct changes included mitochondrial swelling, cell swelling, endothelial bleb formation, and narrowing of capillary lumina. These abnormalities were not observed in tissue fixed with nitrogen-bubbled glutaraldehyde. These findings indicate that deliberate steps should be taken to reduce or eliminate dissolved oxygen from the fixatives used to study ischaemic tissues. Otherwise artefactual reoxygenation damage in vitro may occur and make valid ultrastructural interpretation difficult or impossible.
Animals↗
Interrelationships of ultrastructure and function in the microvasculature of normal and ischaemic myocardium.
This paper reviews various methods involving electron microscopy that have been used to investigate the ultrastructure of the vasculature of the normal and diseased heart. Whereas scanning electron microscopy is more commonly employed to record surface topography, it can be used to examine freeze-fracture planes within the myocardium and, using heavy-metal staining and back-scattered electron imaging, to examine large 2-mu-thick resin-embedded sections through the heart. The latter technique allows the comparison of structural alterations across the wall of the heart and thus accurate definition of the transmural progression of pathological processes. Transmission electron microscopy can then be used to provide more detailed information from precisely localised regions. Human myocardium can be usefully studied up to 12 hours post-mortem provided that suitable control material is included. Intravascular tracers including low-viscosity resin and nuclear track emulsion can be used to determine whether or not particular vessels allow flow at the time of fixation, and thus changes in the pattern of flow through the microvasculature due to ischaemia and reperfusion can be quantified and defined. Particular care is required in the fixation of ischaemic tissues because oxygen dissolved in the fixative can lead to the rapid formation of oxygen-free radicals on contact with the tissue. This produces artefactual reoxygenation damage characterised by membrane disruption and cell and organelle swelling, which has previously been attributed to ischaemic injury per se. Bubbling glutaraldehyde with nitrogen substantially reduces this artefact.
Animals↗
The contribution of ischaemia to the development of microvascular incompetence in the myocardium.
STUDY OBJECTIVE: The aim was to determine the contribution of ischaemia per se to the development of microvascular incompetence in the myocardium. DESIGN: Isolated, buffer perfused rat hearts were made globally ischaemic for 0-60 min, then fixed with nitrogen bubbled glutaraldehyde and perfused with nuclear track emulsion to identify and quantify competent blood vessels in scanning and transmission electron micrographs. SUBJECTS: Adult Male Wistar rats weighing between 275 and 350 g were used. MEASUREMENTS AND MAIN RESULTS: Thirty or more min ischaemia significantly (p less than 0.05) reduced the density of competent capillaries in the subendocardial third of the myocardium, as did 45 or more min in the subepicardial third and 60 min in the middle third. Following 60 min ischaemia virtually all vessels in the subendocardial third were not perfusable. Severely ischaemic myocardium showed relatively normal, open, unobstructed capillaries and an absence of the endothelial, myocyte and mitochondrial swelling which have previously been attributed to ischaemia. CONCLUSIONS: In severely ischaemic myocardium microvascular incompetence shows a transmural gradient in severity. It develops progressively, starting near the endocardium. These findings suggest that postischaemic reoxygenation may accelerate the development of microvascular incompetence.
Animals↗
Capacity of CD8+ T cells to reject immunogenic variants of a spontaneous murine carcinoma: lack of non-specific (NK1.1+) effector mechanisms.
Class I MHC-expressing (Ia-) immunogenic (imm +) variants, which elicit a strong syngeneic host immune rejection response, can be isolated following 5-azacytidine treatment from the MHC-negative non-immunogenic (imm-) murine carcinoma cell line SP1 (10.1 subclone). In the present study, we have shown that CD4-depleted CD8+ T cells are both necessary and sufficient for the rejection process. Treatment of semi-syngeneic B6 X CBA F1 mice with anti-NK1.1 antibodies had no effect on the rejection of immunogenic variants, although the splenic NK (natural killer) activity of recipients was fully abrogated. Thus NK1.1+ effectors, which include most NK and LAK (lymphokine activated killer) cells, are most likely not involved in the rejection process. This finding was supported by a complete lack of NK susceptibility of SP1 cells in vitro, although variable killing by LAK and poly-I: C-induced killer cells was observed. To assess the role of NK1.1-LAK and other non-T killers (e.g. cytolytic macrophages) in vivo, we determined the specificity of the rejection process. We examined the ability of immune animals to reject a mixture of non-immunogenic parent tumour cells (or cells of an unrelated syngeneic tumour) and of the variant tumour cells used for the initial immunization. Growth of the parent tumour cells was unaffected while the same animals rejected the immunogenic tumour cells. Our findings support a primary role of tumour-specific CD8+ T cells in the rejection of imm+ variants with no detectable involvement of non-specific effector cells in the tumour destruction process.
Adenocarcinoma↗
Uneven host tissue ongrowth and tissue detachment in stent mounted heart valve allografts and xenografts.
Following explanation from the mitral position because of primary tissue failure, 30 human antibiotic sterilised stent mounted aortic valve allografts and 28 glutaraldehyde treated porcine xenografts were examined for evidence of tissue detachment from the stents. These grafts had been in situ for 34 to 166 months. Graft detachment had occurred from one or two stent posts with displacement of the commissures and central valvular incompetence in 12 (67%) of 18 allografts supported on rigid stainless steel stents, in six (50%) of 12 allografts mounted on flexible acetal copolymer stents, but in only one (4%) of 28 xenografts mounted on polypropylene stents. In regions of detachment the aortic remnant of the graft was infiltrated by components of blood and phagocytic cells which had removed not only fibrin but also graft tissue. Detachment did not occur from stent posts where the graft margin had become coated by collagenous host tissue. This intimal fibrous sheath appeared not only to strengthen the attachment of the graft but also to limit the entry of fibrin and phagocytes into the graft tissue.
Animals↗
Differences between heart valve allografts and xenografts in the incidence and initiation of dystrophic calcification.
Following surgical removal because of primary tissue failure, 30 antibiotic-sterilized human aortic valve allografts and 27 glutaraldehyde-treated porcine aortic valve xenografts were examined for macroscopic and microscopic evidence of dystrophic calcification. These grafts had been mounted on stents and used for from 34 to 166 months to replace diseased mitral valves. After explantation the grafts were carefully examined then prepared for light microscopy, for transmission electron microscopy and for energy dispersive X-ray microanalysis. Gross calcification occurred significantly (p = 0.002) more frequently in xenografts (89%), and was more extensive than in allografts (53%). Calcification usually appeared as nodular excrescences on the cusps, although occasionally it formed plates within them. This reduced tissue pliability and was usually associated with either valvular stenosis or regurgitation. The calcified deposits contained calcium and phosphate in ratios approaching those of hydroxyapatite. In xenograft valves the smallest discrete deposits of calcification were spherical and usually associated with membranous debris of porcine donor fibroblasts, but allografts did not contain donor cell remnants and early calcification was linearly arranged along collagen fibres.
Adolescent↗
Expression of epithelial-like markers and class I major histocompatibility antigens by a murine carcinoma growing in the mammary gland and in metastases: orthotopic site effects.
A spontaneous murine mammary carcinoma, designated SP1, grew more aggressively in the mammary gland than in the subcutis exhibiting a 10-fold lower 50% lethal tumor dose and the ability to metastasize spontaneously from the orthotopic mammary gland site. The appearance of metastasis could be abrogated by resection of the primary tumor up to 21 days postinjection, arguing against the possibility that metastasis occurred due to trauma of the injection and/or healing processes. In addition, tumor cells recovered from lung metastases exhibited an increased ability to metastasize when reinjected into either the s.c. or mammary sites. Tumor cells from lung metastases showed low levels of Class I major histocompatibility (MHC) antigens, like the parental SP1 cells, but were found to express differentiation markers typical of normal basal and luminal mammary epithelium. SP1 tumors expressed increased Class I MHC antigens, as well as high levels of basal and luminal breast epithelial markers, within 7 days of implantation into the mammary gland. On the other hand, SP1 tumors growing in the subcutis never expressed increased Class I MHC levels and expressed the epithelial marker antigens at lower levels and not until at least 21 days of growth. Removal of host epithelium by cauterization of the mammary bud at 3 weeks had no effect on the increased growth, metastasis and acquired heterogeneity of MHC and epithelial associated antigens, suggesting that the mammary gland stroma was responsible for the observed phenomenon. These findings suggest that the mammary gland either selects distinct tumor subpopulations, or induces a phenotypic change leading to tumor progression and the generation of metastatic subpopulations.
Animals↗
Intracellular pathway of interleukin-2 receptors studied using immunogold electron microscopy.
The fate of internalized interleukin-2 receptors (IL-2R) on proliferating T cell blasts and Lyt-2-/L3T4- thymocytes was studied by immunogold electron microscopy. Immediately following labeling, IL-2R were found in coated pits and with time there was sequential appearance of gold particles in smooth vesicles or endosomes, multivesicular bodies and lysosomes. Thus the IL-2R appears to be a member of cell surface receptors internalized by endocytosis via coated pits.
Animals↗
The subacute hospital treatment of the borderline patient. II: An integrated focus on splitting.
A psychiatric inpatient unit with expertise in family treatment has developed an integrated effort to provide a one to three month treatment program for hospitalized borderline patients. Treatment goals are more ambitious than those obtainable by simple crisis intervention. Appreciation of staff splitting is enhanced by an intergenerational family systems approach. Early and sustained focus on splitting is aided by the use of a 15 minute educational tape and a weekly therapy group required for all nonpsychotic patients and recommended for their families. Cases illustrating the family perspective and a group therapy session are presented in detail. The therapy group, run by an interdisciplinary team (the authors) requires active staff initiative and confrontation to avoid responsibility-evading patient coalitions. Diagnostic considerations and impact of the program on patients and on staff are discussed.
Adult↗
The development and ultrastructure of Plasmodium falciparum damaged in vitro by human "crisis" sera and by chloroquine.
P. falciparum malaria was cultured in vitro in the presence of sera from patients with cerebral malaria, meningitis and also after chloroquine administration. Intra-erythrocytic parasite damage was seen by light and electron microscopy. The significance of the results is discussed with relevance to non-specific immune mechanisms, and the damage induced by these mechanisms compared with that from chloroquine.
Adolescent↗
Eccrine porocarcinoma: a case report with light microscopy and ultrastructure.
A case of eccrine porocarcinoma in a 63-yr-old man is reported. There was a 10 yr history of an abdominal skin lesion which recurred after cautery and metastasized to skin and abdominal lymph nodes. Histologically, the primary tumour was composed of small squamoid cells with ductal lumina. There was intraepidermal nesting spread and an invasive dermal component. Formation of intracytoplasmic lumina in cells with squamoid features, best seen on electron microscopy, pointed towards poral differentiation and was a useful diagnostic feature which persisted in the less well differentiated metastases. The role of hidroacanthoma simplex as a possible preinvasive precursor lesion is discussed. The differential diagnosis from other skin tumours is described. The literature is reviewed. Despite their sometimes innocuous histological appearance, eccrine porocarcinomas are aggressive lesions which require wide local excision of the primary site and consideration of regional lymph node dissection.
Adenoma, Sweat Gland↗
A survey of the graduates of the University of Alabama School of Optometry. Screening for hypertension.
Systemic hypertension is a major health problem in the United States. Almost 16 million people with this disease are estimated to be untreated or inadequately treated. Optometry graduates of the University of Alabama in Birmingham School of Optometry have always received clinical and didactic training in the routine assessment of blood pressure. This study reports the results of a survey of these graduates to determine the number who screened for high blood pressure following graduation, their criteria for referral, their management of hypertensive patients, and their patient characteristics. Over 90% of the optometrists surveyed screened for high blood pressure, and they screened 57% of their patients. Twenty percent of these patients were found to have high blood pressure. These results indicate that optometrists are an important and significant resource in the detection of hypertension in many high risk groups.
Age Factors↗
Observations on the development of the ovarian balls of Moniliformis (Acanthocephala).
Observations have been made on the ultrastructure of objects identified as ovarian balls from female Moniliformis after 1, 3, 5, 7 and 9 days in the rat. Similar objects are present in the body cavity of female cystacanths from cockroaches. The ovarian balls from 1-day-old worms are formed of several cells which are enclosed within a surface coat. During development, the ovarian balls increase in size and cell number and the interval organization appears to become more complex. After 9 days of development in the rat, the surface coat of the ovarian balls can no longer be observed and microvilli are present. It also appears that the supporting syncytium has been formed by this time.
Acanthocephala↗
Softening of drusen and subretinal neovascularization.
On the basis of clinico-pathological examination, drusen were divided into hard and soft. A few small, hard drusen with a hyaline composition were found in 50 per cent of the normal aged eyes examined. The appearance of drusen of softer consistency often heralded the onset of senile macular degeneration. Soft drusen resulted either from the breakdown of the hyaline content of hard drusen or from the focal aggregation into mounds of membranous debris which accumulated as a widespread shallow layer between the basement membrane of the pigment epithelium and Bruch's membrane. Softening of drusen was most evident when the retinal pigment epithelium demonstrated the greatest proliferative activity, with migration of cells into the retina and the formation of the basal laminar deposit. It was at this stage that subretinal neovascularization was first detected. A patient in whom the gradual development of small soft drusen and an associated pigmentary disturbance was followed by subretinal new vessel formation is reported. The eye was subsequently found to have five separate breaks in Bruch's membrane and the ultrastructural findings are described.
Aged↗
Endoscopic retrograde cholangio-pancreatography.
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Cholangiography↗
Further studies on the mitochondrial changes during the life cycle of Plasmodium berghei: electrophoretic studies on isocitrate dehydrogenases.
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Animals↗
Citric acid cycle activity and chloroquine resistance in rodent malaria parasites: the role of the reticulocyte.
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Animals↗