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Biomedical subjects

R L Quigley

Publications and source records attributed to R L Quigley.

36 records · Page 2Linked to original sources

Alternative approach to the repair of a floppy anterior mitral valve leaflet.

Increased exertional dypsnea developed in a 25-year-old female with a long standing history of a myxomatous mitral valve. Transesophageal echocardiography demonstrated left atrial and ventricular dilatation and no significant functional impairment. In addition, there was prolapse of a voluminous anterior mitral valve leaflet as well as prolapse of the posterior leaflet. To avoid the risks of long term anticoagulation therapy including fetal teratogenicity, efforts were made to repair rather than replace this degenerated valve. Here we report a new technique of anterior or mitral valvuloplasty complementing a quadrangular resection of the mural leaflet and a ring annuloplasty. The elliptoid excision of the redundant anterior leaflet resulted in a competent valve apparatus without any significant gradient. This technique would not apply, however, when the chordae tendinae to the anterior leaflet were significantly stretched as a result of the myxomatous process. In that situation the valve would be replaced with a prosthesis.

Adult↗

Application of the popliteal lymph node assay to evaluate an immunosuppression protocol.

There exists a variety of experimental techniques which are used to evaluate host immunity. None of these in vitro assay systems are optimal, since they are performed ex vivo. Here is described an in vivo model, using four rat strain combinations and a modification of the popliteal lymph node assay, which quantifies the immune response to blood transfusion, in a sensitive and reproducible fashion. The subcutaneous injection of a 5 x 10(5) or 10 x 10(5) (depending on the rat strain) X-irradiated allogeneic lymph node cells into the hind footpad of a rat results in an increase in the weight of the draining popliteal lymph node harvested 7 days later. Injection of 100 x 10(5) X-irradiated cells results in the maximum nodal enlargement (fourfold). A dose of 50 x 10(5) cells results in lymph node enlargement just shy of maximum and so was selected for use in all experiments. When 50 x 10(5) nonirradiated allogeneic lymph node cells are injected, there is up to an eightfold increase in nodal size. To eliminate the effects of non-specific inflammation, as well as variation in node weights, a stimulation index (SI) was established. Transfusion of a rodent with blood from the same strain as the lymph node donor, 1 week prior to subcutaneous injection, resulted in a significantly lower SI, compared to the SI observed in untreated animals challenged with the same inoculum or third-party controls (P < 0.05). The significance of all comparisons was assessed by the Students' t test. This simple method of in vivo quantification of the immune response has obvious application to the evaluation of any experimental immunosuppression regimen.

Animals↗

A case of retrograde jejunoduodenal intussusception caused by a feeding gastrostomy tube.

A case is presented of migration of a gastrostomy feeding tube (Foley type) through the pylorus with duodenal obstruction and subsequent retrograde intussusception. Although feeding tube migration is not uncommon, retrograde intussusception of the jejunum into the duodenum is rare. In this case, surgery was required with resection of a segment of necrotic bowel. Recommendations are given for treatment of this unusual complication with emphasis on its avoidance through use of a retaining bar or disc at the tube's skin exit site.

Aged↗

Intraoperative procurement of autologous fibrin glue.

A method of intraoperative procurement of autologous fibrin glue is described. The relative efficacy of our autologous preparation is compared with that of fibrin glue made with homologous cryoprecipitate. Experimentally, the fibrinogen content and the strength are less than those found in cryoprecipitate and appear related to the fibrinogen content of the autologous plasma used as substrate in the fibrin glue reaction. Clinically, no significant differences are noted in the performance of autologous fibrin glue. We believe the absence of the risk of blood-borne infection with the autologous product is a major advantage.

Adhesiveness↗

Prognosis and management of anterolateral myocardial infarction in patients with severe left main disease and cardiogenic shock. The left main shock syndrome.

BACKGROUND: To identify the determinants of survival in patients with severe (> 75%) stenosis of the left main coronary artery (LM) and an acute (48 hours) anterolateral myocardial infarction (AAMI), we retrospectively analyzed the course of 34 such patients who presented to our institution over the last decade. METHODS AND RESULTS: LM disease was diagnosed arteriographically at presentation, and AAMI was determined by ECG, enzymatic, and kinetic criteria. Of the nine patients (26%) managed medically, seven patients (78%) were in cardiogenic shock (cardiac index < 2.0, left ventricular end-diastolic pressure > 25, and pulmonary edema), and all seven died in hospital. Twenty-five (74%) of the 34 patients were managed surgically or with angioplasty. Nine of these patients, of whom eight were in cardiogenic shock, also died in hospital. Regardless of the method of treatment, the presence of cardiogenic shock in this population was reproducibly a grave prognostic indicator. That is, 15 (94%) of the 16 patients in cardiogenic shock at presentation died in hospital, and only 1 (5%) of the 18 patients without cardiogenic shock died (P < .001). CONCLUSIONS: Thus, we propose that, because patients presenting with AAMI, severe LM stenosis, and cardiogenic shock (left main shock syndrome) have such a grave prognosis regardless of management, conservative measures may be indicated.

Aged↗

Primary hypertrophic pyloric stenosis in the adult.

Analysis of 100 consecutive patients with pyloric outlet obstruction revealed that 37% of the obstructions were secondary to peptic ulcer disease and 42% were caused by malignant neoplasm. Only a single patient with primary hypertrophic pyloric stenosis was identified, and whether this lesion is a cause or effect of peptic ulcer disease remains unclear. Similarly, the association of this entity with congenital pyloric stenosis is unknown.

Adult↗

Transfusion induces blood donor-specific suppressor cells.

Transfusion with blood from the organ donor before transplantation can prolong the survival of renal allografts in the rat. To determine if the beneficial effect of preoperative blood transfusion was due to the generation of donor-specific suppressor cells, in vivo and in vitro adoptive transfer experiments were performed. Lymphoid cells were harvested from transfused and untreated rats. These cells were then either (1) transferred to lightly irradiated (200 R) syngeneic hosts which were subsequently challenged with a kidney allograft (in vivo assay) or (2) titrated as regulator cells into naive unidirectional MLC such that the regulator and responder populations were syngeneic. In the LEW-RT1 to DA-RT1av1 strain combination, the adoptive transfer of thoracic duct lymph (TDL) or lymph node (LN) cells (5 x 10(7) to 7.5 x 10(7) cells) from DA animals transfused with LEW blood, 7 days previously into syngeneic (DA), lightly irradiated (200 R) hosts resulted in the indefinite survival of LEW kidney allografts. The phenomenon was blood donor-specific and dose-dependent. In contrast the adoptive transfer of spleen cells (10(7) to 10(8] from blood transfused hosts 7 days after transfusion had no effect on renal allograft survival. In vitro the addition of LN or TDL regulator cells, harvested from DA rats transfused with LEW blood, to a unidirectional MLC (DA responders, LEW stimulators) resulted in a significant depression of the proliferative response when compared with the proliferation of these same cells without the addition of these regulator cells or with the addition of LN or TDL regulator cells from a DA rat transfused with third party (PVG-RT1c) blood. The depression of the proliferative response observed in vitro, was blood donor specific. When LN or TDL regulator cells from a DA rat transfused with PVG-RT1c blood were added to a unidirectional MLC between DA responders and PVG stimulators, a significant depression in the proliferative response was observed. These in vitro findings were confirmed in two other strain combinations (LEW-PVG, and DA-PVG). Thus a single blood transfusion results in the induction of donor-specific suppressor cells detectable both in vivo and in vitro 7 days after transfusion in some but not all lymphoid compartments.

Animals↗

Mediation of antigen-induced suppression of renal allograft rejection by a CD4 (W3/25+) T cell.

The mechanism of induction of specific immunosuppression by preoperative donor-specific blood transfusion in the rodent remains unclear. In a previous study we demonstrated that a single LEW blood transfusion in a DA rat results in the generation of donor-specific suppressor cells in the lymph node and thoracic duct lymph, detectable both in vivo and in vitro 7 days after DST. In contrast, no such activity was found in the splenic compartment. In this study lymphoid cells were harvested from either untreated DA rats or DA rats transfused 7 days previously with LEW blood and purified by rosette depletion using appropriate monoclonal antibodies. The purified lymphocyte subpopulation from transfused rats, of splenic or TDL origin, was adoptively transferred into syngeneic, lightly irradiated (200 rads) DA rats, where the adoptive transfer of 4.25 x 10(7) T (OX12-negative) cells (98.9% pure) or 2.5 x 10(7) CD4 (i.e., W3/25-positive, OX8 and OX12-negative) cells (97.9% pure), both of TDL origin, resulted in the indefinite survival of a LEW kidney (median survival time [MST]greater than 100 days), but not a PVG kidney (MST = 11 days). In contrast lymphocytes of splenic origin, regardless of the phenotype, did not prolong graft survival. Thus we have phenotypically characterized a CD4 (W3/25+) T suppressor cell that is generated after a single DST and is detectable 7 days later in the TDL but not the splenic compartment. Although there was no significant difference in the lymphocyte subset composition of lymphoid organs from transfused and untreated hosts, as determined by flow cytometry, the mean channel fluorescence of the lymphocyte population markers of cells harvested from transfused animals was significantly less than that observed with untreated controls, a finding which remains unexplained.

Animals↗

Mediation of the induction of immunologic unresponsiveness following antigen pretreatment by a CD4 (W3/25+) T cell appearing transiently in the splenic compartment and subsequently in the TDL.

We have previously demonstrated in a rat renal allograft model, using adoptive transfer studies, that a single blood transfusion results in the generation of blood donor-specific W3/25+ (CD4) T suppressor cells detectable in the thoracic duct lymph, but not in the spleen, 7 days after transfusion. In this study, again using the LEW-to-DA strain combination, we have investigated the time of appearance of suppressor activity in different lymphoid compartments in vivo and in vitro following a single blood transfusion. Cells (5 x 10(7) unfractionated TDL or 1 x 10(8) unfractionated spleen cells) were harvested from DA rats on days 1-6 after a single LEW blood transfusion and were adoptively transferred into syngeneic (DA), lightly irradiated (200 rads) hosts. The following day these animals received a kidney allograft (LEW or PVG). Specific suppressor activity, as demonstrated by the prolongation of survival of LEW, but not PVG, renal allografts was noted in the spleen 4 days after transfusion (MST greater than 100 days). Suppressor cells were not found in the TDL at this stage--but 6 days after transfusion suppressor activity could be detected in the TDL (median survival time [MST]greater than 100 days), while at this time no such activity was demonstrable in the spleen. The suppressor activity in the spleen on day 4 after transfusion was shown to be mediated by a W3/25+ (CD4) T cell. The proliferative response in a mixed lymphocyte culture of DA spleen cells, prepared 4 days after transfusion, or TDL cells prepared 6 days after transfusion, to LEW stimulator cells was significantly suppressed when compared with the response of cells harvested from untreated controls. In contrast, the proliferative response of spleen cells examined 6 days after transfusion, when no suppressor activity was detected in vivo, was significantly augmented in comparison with untreated controls. Thus we have demonstrated that a DST results in the generation of W3/25-positive (CD4) T cells capable of suppressing renal allograft rejection that appear transiently in the splenic compartment (4 days after transfusion) and subsequently in the TDL (six days after transfusion).

Animals↗

Investigation of the mechanism of active enhancement of renal allograft survival by blood transfusion.

Transfusion with donor blood before transplantation can prolong the survival of renal allografts in the rat. The phenomenon is donor specific. We have investigated the effect of blood transfusion on both lymphocyte proliferation and the generation of donor-specific cytotoxic cells. In the first instance the kinetics of the proliferative responses of lymph node, spleen and thoracic duct lymph (TDL) leucocytes (harvested 7 days after transfusion of donor-specific blood, third-party allogeneic blood, syngeneic blood or no treatment) to lymph node stimulator cells were determined in a one-way mixed lymphocyte culture (MLC). Four strain combinations (LEW to DA, LEW to PVG, PVG to DA and DA to PVG) were investigated in this study. Maximal proliferation was observed at 4 days in the MLC and this was not altered by prior blood transfusion. When lymph node and TDL cells from transfused recipients were used as responders and stimulation was provided by cells from the same strain of rat as the blood donor, there was a significant depression of the MLC response compared to the response of cells harvested from untreated animals or animals given a syngeneic blood transfusion. This correlated with the behaviour of renal allografts in the same strain combinations. Lymph node and TDL cells harvested from rats that had received a third-party blood transfusion produced variable results in the MLC, ranging from a normal to a depressed response. No prolongation of allograft survival was noted in any animals pretreated with third-party blood. In contrast, when spleen cells were used as responder cells there was a donor-specific increase in the proliferative response on Day 4 in all strain combinations tested. In the second instance, specific cytotoxic activity was generated by in vitro (MLC) stimulation of lymph node or TDL, but not spleen, cell responders harvested from transfused or untreated rats. The activity of cytotoxic cells generated in MLC was quantified in a 51Cr-release assay, using Con A blast lymph node target cells prepared from animals of the same strain as the blood donor or a third-party strain. The specific cytotoxic activity generated was significantly increased when the responding cells were harvested from an animal that had received a donor-specific transfusion and then been restimulated by the blood donor in MLC.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

The relative roles of major and minor histocompatibility antigens in the induction of immunologic unresponsiveness by blood transfusion.

Renal allograft survival may be prolonged indefinitely in some strains of rats following preoperative transfusion with whole blood from the organ donor. Similarly donor-specific transfusion results in a reduction in the proliferative response of lymph node (LN) white cells (WBCs) to donor-specific stimulators in mixed-lymphocyte culture (MLC). To determine the relative roles of major and minor histocompatibility antigens in the depression of the proliferative response, in vitro lymphocyte proliferation assays were performed using congenic rat strains as blood donors. Unidirectional MLCs were set up between haplotype-disparate responder and stimulator LN cells, in cases in which the responding cells had been harvested from rats transfused with blood that shared either some, all, or none of the major histocompatibility complex genes with the stimulator strain. The proliferative response of LN cells harvested from rats transfused with blood sharing major (class I or II) or minor antigens, or both, with the in vitro stimulator cells was significantly less than the response of cells harvested from nontransfused controls. No single-locus product was more or less effective than whole blood in depressing cell proliferation. These data suggest that the beneficial effect of preoperative random blood transfusions observed in clinical transplantation may arise from the fortuitous sharing by the blood donor and the subsequent organ donor of not only a single major histocompatibility antigen but also of minor histocompatibility antigens.

Animals↗

A modified thoracotomy for minimally invasive coronary artery bypass grafting.

The optimal technique of minimally invasive coronary artery revascularization using the in situ internal thoracic artery (ITA), without extracorporeal circulation, is yet to be defined. To obtain adequate exposure for both ITA harvest and left anterior descending coronary artery anastomosis, an anterior chest wall defect is created which can be difficult to reconstruct. Based on the vascular anatomy of the acromiothoracic axis and three described osteocutaneous composite tissue flaps, we present a novel dissection that not only improves exposure, but also preserves chest wall integrity.

Coronary Artery Bypass↗