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Biomedical subjects

B P Griffith

Publications and source records attributed to B P Griffith.

At least 325 records · Page 18Linked to original sources
PubMed1985

Procurement for combined heart-lung transplantation. Bilateral thoracotomy with sternal transection, cardiopulmonary bypass, and profound hypothermia.

A bilateral thoracotomy with cardiopulmonary bypass and profound hypothermia has become our preferred method of procurement of organs for combined heart-lung transplantation and has replaced the sternotomy without cardiopulmonary bypass as initially used. This technique has provided good exposure and has facilitated dissection and hemostasis of the posterior aspect of the middle mediastinum.

Adolescent↗
PubMed1985

General surgical complications in heart and heart-lung transplantation.

One hundred forty-three patients underwent cardiac transplantation from 1980 to 1985; 122 received a heart, 19 received a heart-lung, and two received a heart-liver transplant. All patients received immunosuppression with prednisone and cyclosporine. General surgical complications have developed since transplantation in 40 patients (28%). Of these, 17 patients have required surgery: exploratory laparotomy (10 patients), inguinal or ventral herniorrhaphy (two patients), repair of false aneurysm of the femoral artery (two patients), repair of lymphocele of the groin (two patients), and incision and drainage of a perirectal abscess (one patient). Of the 10 patients who required laparotomy, three underwent sigmoid resection for a perforated sigmoid diverticulum (all survived), two underwent small bowel resection for perforation (both died), two had free intraperitoneal air with no site of perforation found (one died), one underwent a cholecystostomy and one a cholecystectomy for acute calculous cholecystitis (one died), and one underwent an elective pyloroplasty for gastric outlet obstruction secondary to vagus nerve injury during heart-lung transplantation and survived. All patients who underwent elective surgery survived. Six patients died without operation and at autopsy were found to have unrecognized general surgical complications including pancreatitis (three patients), cecal ulceration with sepsis (two patients), and jejunal perforation secondary to peritoneal dialysis (one patient). Eleven other patients had severe abdominal pain and five had gastrointestinal hemorrhage not requiring operation. Proper management of these patients includes early and aggressive diagnosis of conditions requiring operative intervention, strict attention to surgical technique, and careful titration of dose of immunosuppressive drugs. The 28% incidence of general surgical complications associated with heart and heart-lung transplantation emphasizes the role of the general surgeon in the management of these complex patients.

Adolescent↗
PubMed1985

Use of autoperfusion for distant procurement of heart-lung allografts.

Heart-lung transplantation has been limited to on-site organ procurement because current methods of lung preservation are unreliable for periods in excess of one hour. A method of dynamic heart-lung preservation has been evaluated as a possible means for distant procurement for human transplantation. Canine and bovine heart-lung blocks were removed and preserved by autoperfusion for periods of two to nine hours. The key features of the method included normothermic coronary autoperfusion with donor blood by an autoregulating beating heart, and a stabilizing reservoir bag interposed between the donor aorta and the right atrium. The reservoir is positioned one meter above the aortic valve, and determines the pressure in the aorta. Flow from the bag to the right heart dictates venous return, pulmonary blood flow, and ventricular stroke volume. The lungs are ventilated with room air and 5% to 10% of CO2, at 4 liters/minute. Normothermia is ensured by immersion of the heart-lungs block in a temperature controlled crystalloid bath. Eleven canine and eight bovine heart-lung blocks were evaluated for two to nine hours. Lung function was excellent during this period, and cardiac output did not decline from pre-harvest levels. Five heart-lung allografts were transplanted after an average of four hours of autoperfusion and all functioned satisfactorily. All animals could be weaned from the extracorporeal circulation support. Two to three hours later, cardiac outputs and arterial pO2 were normal. The peak airway pressures averaged 29 cm H2O.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Heart-liver transplantation in a patient with familial hypercholesterolaemia.

A girl aged 6 years 9 months with severe heart disease secondary to homozygous familial hypercholesterolaemia underwent orthotopic cardiac transplantation and her liver was replaced with the liver of the same donor. In the first 10 weeks after transplantation serum cholesterol fell to 270 mg/dl from preoperative concentrations of more than 1000 mg/dl.

Child↗
PubMed1984

Reversibility of lymphomas and lymphoproliferative lesions developing under cyclosporin-steroid therapy.

Post-transplant lymphomas or other lymphoproliferative lesions, which were usually associated with Epstein-Barr virus infections, developed in 8, 4, 3, and 2 recipients, respectively, of cadaveric kidney, liver, heart, and heart-lung homografts. Reduction or discontinuance of immunosuppression caused regression of the lesions, often without subsequent rejection of the grafts. Chemotherapy and irradiation were not valuable. The findings may influence policies about treating other kinds of post-transplantation neoplasms.

Adolescent↗
PubMed1984

Asynchronous depression of responses to T- and B-cell mitogens during acute infection with cytomegalovirus in the guinea pig.

The nonspecific functional capacity of spleen cells, taken from female guinea pigs with primary acute cytomegalovirus (CMV) infection, was assessed using lipopolysaccharide (LPS), a B-cell mitogen, and concanavalin A (Con A), a T-cell mitogen. Proliferative responses to the two mitogens were found to be significantly depressed in animals inoculated with CMV as compared to control animals. The defect in Con A responsiveness occurred earlier during the course of the infection than the defect in LPS responses. Although responses to the mitogens were depressed at the time of peak virus activity in the spleen, the possibility of lytic destruction of the spleen cells by the virus during in vitro culture was excluded. In addition, the depression in Con A responsiveness was noted with a wide range of Con A concentrations, and preculture studies failed to result in enhanced reactivity of the cells from infected animals. We conclude that reductions of both B- and T-cell functions, which differ in their timing during the course of acute CMV infection, occur concurrently with an enhanced viral specific immune response in guinea pigs acutely infected with CMV.

Animals↗
PubMed1984

Vaccination against transplacental cytomegalovirus transmission: vaccine reactivation and efficacy in guinea pigs.

The guinea-pig model of cytomegalovirus (CMV) infection was used in continuing studies of experimental CMV vaccines for prevention of congenital CMV infection. Low-passage guinea-pig cytomegalovirus (GPCMV) vaccine, which has been shown to be effective in preventing transplacental CMV transmission, was tested for reactivation during pregnancy. In Hartley strain guinea pigs intraperitoneally given 10(5.5) 50% tissue culture infective doses (TCID50) of low-passage vaccine, 27 (41%) of 66 throat swabs obtained during subsequent pregnancies showed CMV, in contrast to 28 (24%) of 115 throat swabs obtained from nonpregnant control animals. High-passage GPCMV vaccine (approximately 5 X 10(3) TCID50) did not cause acute viremia, detectable generalized infection, or GPCMV reactivation during subsequent pregnancies. Immune pregnant animals and their fetuses were protected against generalized CMV infection when challenged with virulent GPCMV. In contrast, nonimmune pregnant controls developed generalized maternal, placental, and fetal infection. Experimental low-dose, high-passage GPCMV vaccine can protect against transplacental CMV transmission without apparent vaccine reactivation during pregnancy.

Animals↗
PubMed1984

Venous bypass in clinical liver transplantation.

A venous bypass technique (BP) that does not require the use of systemic anticoagulation is used routinely at our institution in all adult patients during the anhepatic phase of liver transplantation (LT). Complete cardiopulmonary profiles were obtained in a subset of 28 consecutive cases. During the anhepatic phase while on bypass, mean arterial pressure, central venous pressure, and pulmonary arterial wedge pressure were maintained at prehepatectomy levels. Oxygen consumption fell secondary to a decrease in temperature and the removal of the liver. Consequently, cardiac index fell without an increase in arterial-venous O2 content difference, reflecting adequate tissue oxygenation. Compared with 63 patients in a previous series given LT without bypass (NBP), the 57 total BP patients experienced better postoperative renal function (p less than 0.001), required less blood use during surgery (p less than 0.01), and had better survival 30 days after LT. The equivalency of 90-day survival in these groups results from the lack of effect of BP on the long-term survival of patients considered at high risk for metabolic reasons. BP patients at high risk for technical considerations, however, survived LT whereas NBP patients did not. BP offers other advantages important in establishing LT as a service-oriented procedure.

Adult↗
PubMed1984

Effect of acyclovir and phosphonoformate on cytomegalovirus infection in guinea pigs.

Adult Hartley guinea pigs infected with guinea pig cytomegalovirus (CMV) develop a mononucleosis syndrome with a brief viremia, splenomegaly, lymphadenopathy, and peripheral lymphocytosis with circulating atypical lymphocytes. The present study used this experimental model to evaluate in vivo the therapeutic efficacy of acyclovir (ACV) and phosphonoformate (PFA) during CMV infection. Guinea pigs were treated with ACV or PFA from day 3 to day 7 postinoculation. The course of the mononucleosis syndrome and the spread of virus in various tissues were similar in drug- and sham-treated infected guinea pigs. Infected animals treated with ACV or PFA developed disseminated CMV disease with severe interstitial pneumonia, whereas sham-treated infected and drug-treated noninfected animals did not. In addition, mortality rates in infected animals treated with ACV were significantly higher than those in sham-treated animals. Furthermore, the normal lymphoproliferative response to CMV infection appeared to be reduced in ACV-treated as compared to sham-treated animals, with fewer peripheral lymphocytes, less lymphoid tissue in the spleen and lymph nodes, and less mononuclear inflammation around the inclusion-containing cells of the liver and salivary gland. These results show that ACV and PFA are not useful in the treatment of CMV infection in guinea pigs but instead may have harmful effects.

Acyclovir↗
PubMed1984

Powerful but limited immunosuppression for cardiac transplantation with cyclosporins and low-dose steroid.

Cyclosporin and low-dose prednisone provide powerful but limited immunosuppression for orthotopic cardiac transplantation. Optimal long-term survival was possible only with rescue therapy using rabbit antithymocyte globulin (RATG) when myocyte necrosis could not be reversed with pulse steroid therapy. The continued absence of rejection following rescue therapy with RATG in six of the last 19 patients is responsible for the improved 79% cumulative survival rate at 9 months compared to the 61% cumulative survival rate at 1 year for the initial 23 patients. The difference is that among the latter group, seven patients had persistent histologic rejection with focal myocyte necrosis which was not reversed with pulse therapy of steroids (hydrocortisone) or an increased dose of maintenance prednisone (30 to 40 mg/day). Three of these seven died of acute rejection within 3 months and four died between 8 and 13 months. Consequently, the cumulative survival rate of these 23 patients at 2 years was 41%. The projected 2 year cumulative survival rate of the 19 patients should not decrease greatly, as new episodes of rejection have not occurred beyond 3 months in either group.

Adolescent↗
PubMed1984

A flexible procedure for multiple cadaveric organ procurement.

Techniques have been developed which permit removal of the kidneys, liver, heart and other organs from the same donor without jeopardy to any of the individual grafts. The guiding principle is avoidance with all organs of warm ischemia. This is achieved by carefully timed and controlled infusion of cold solutions into anatomic regions, the limits of which are defined by preliminary dissection.

Cadaver↗
PubMed1984

Targeted blood levels of cyclosporin for cardiac transplantation.

Forty-nine patients have undergone cardiac transplantation since July, 1982, and have been treated with maintenance cyclosporin and low-dose prednisone, 15 to 20 mg. Cyclosporin dose has been targeted to a whole-blood level of 1,000 ng/ml as measured by radioimmune assay. The actuarial survival rate in this group of patients has been 79% at 12 months and 71% at 21 months. Histologic rejection has occurred at all blood levels of cyclosporin, as has significant nephrotoxicity. The hepatic toxicity encountered has been more a clinical nuisance than significant problem. The administered dose of cyclosporin required to reach a target of 1,000 ng/ml has varied between 2 and 30 mg/kg/day. The average perioperative and late serum creatinine levels were 1.2 and 1.49 mg/dl and occurred with cyclosporin levels of 1,078 and 1,068 ng/ml, respectively. Late cyclosporin toxicity has persisted despite reduction in the dose of cyclosporin below the targeted 1,000 ng/ml. Some method of blood level monitoring is necessary in patients receiving cyclosporin immune suppression to assure adequacy of the administered dose. The 1,000 ng/ml target has provided adequate immune suppression. Significant nephrotoxicity has not correlated with the blood level measured.

Bilirubin↗
PubMed1983

The effects of cardiovascular drugs on the defibrillation threshold and the pathological effects on the heart using an automatic implantable defibrillator.

Internal defibrillating leads were implanted in 6 dogs through a left thoracotomy and in 6 pigs through a subxiphoid approach. The effects of digoxin (0.04 mg per kilogram of body weight), procainamide (15 mg per kilogram), and propranolol (0.2 mg per kilogram) on the defibrillation threshold was determined 30 to 60 minutes following intravenous administration. Resultant blood levels were equal to or greater than therapeutic levels. Individually these drugs resulted in no appreciable change in the defibrillation threshold from baseline. Pathological study of the myocardium obtained from 6 dogs that underwent more than two hundred shocks each did not demonstrate any abnormality. The 6 pigs were reliably defibrillated, this indicating that thoracotomy is not required for successful implantation. The automatic implantable defibrillator is not the definitive treatment for recurrent ventricular arrhythmias, but is a practical regimen of therapy for a select group of high-risk, out-of-hospital patients. These observations advance our knowledge of the use of this device and give more assurance for future implantation in this select group of patients.

Animals↗
PubMed1983

Changes in lung function after routine exposure manipulations during thoracotomy.

The effect of manual retraction and bronchial occlusion upon right lung function during a 2-hr thoracotomy was evaluated in sheep. Group 1 (seven sheep) underwent manual lung retraction. Group 2 (seven sheep) underwent right bronchial occlusion. Group 3 (seven sheep) served as controls. Radioisotopic indicators (51Cr-RBC, 125I-albumin, [14C]urea, 3H2O) were used to assess changes in capillary permeability-surface area product (PS-urea), extravascular lung water (VE), and intravascular blood volume (Vv). Lung water was further quantified by gravimetric technique. Pulmonary vascular resistance increased following thoracotomy in both groups (34% Group 1, 66% Group 2) and compliance decreased (16% Group 1, 33% Group 2). Mean right lung shunt increased in Group 1 from 17 to 37% (P less than 0.05) and for Group 2 from 18 to 36% (P less than 0.02). A reduction (greater than 25%) in both groups for PS-urea and VE occurred (P less than 0.05). The fall in PS-urea and VE and the increase in PVR indicate a reduction in the right lung perfusion for both groups. It is concluded that a similar marked reduction in ventilation, perfusion, and V/Q occurred after reexpansion whether the lung was retracted or the bronchus occluded.

Animals↗
PubMed1983

Enhancement of cytomegalovirus infection during pregnancy in guinea pig.

The effects of pregnancy on primary acute and chronic persistent infection with cytomegalovirus (CMV) were examined in the guinea pig model. Pregnant guinea pigs developed a more severe acute CMV infection than did nonpregnant animals. High death rate, pronounced splenomegaly, interstitial pneumonia, and necrosis with inclusions in various tissues were observed only in pregnant animals. Acutely infected pregnant animals also differed from nonpregnant animals by the absence of tissue inflammation and by a delay in the peripheral lymphoproliferative response. During persistent infection, salivary gland virus titers were significantly higher in pregnant animals than in nonpregnant guinea pigs. These results indicate that during acute guinea pig CMV infection, virus clearance and recovery from clinical disease are altered in the pregnant host. Furthermore, enhancement of persistent chronic guinea pig CMV infection occurs in the salivary glands during pregnancy.

Animals↗