Interactions of volatile anesthetics and reactive oxygen intermediates on vascular smooth muscle.
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Anesthetics↗
Biomedical subjects
J Hart
Publications and source records attributed to J Hart.
Monoclonal anti-tumor necrosis factor-alpha antibody treatment of rat cardiac allografts: synergism with low-dose cyclosporine and immunohistological studies.
Tumor necrosis factor (TNF) levels have been reported to be elevated during episodes of human renal, hepatic, and cardiac transplant rejection. In addition, we have shown polyclonal anti-TNF antibodies to have immunosuppressive effects. The present study was performed to evaluate the efficacy of a monoclonal anti-TNF-alpha antibody in rat cardiac transplantation as the sole immunosuppressant and in conjunction with low-dose cyclosporine (CsA). We also performed immunohistological studies to localize intragraft TNF and evaluate graft infiltrating cells (GICs), and we measured serum TNF levels by an ELISA. Untreated Buffalo to Lewis heterotopic rat cardiac transplants reject in 10.5 +/- 0.4 days. A 10-day induction course of CsA (2 mg/kg/day, po) prolonged survival to 16.7 +/- 2.7 days (P less than 0.05 vs control), and 10 days of anti-TNF (2000 U/day, ip) prolonged survival to 22.6 +/- 0.8 days (P less than 0.05 vs control). Combination of anti-TNF plus CsA synergistically prolonged graft survival to 40.7 +/- 1.8 days. Three-day courses of anti-TNF were moderately effective (13.7 +/- 0.5 days, P less than 0.05 vs control) and were also synergistic with CsA (27.8 +/- 2.2). Intragraft TNF localization using immunoperoxidase showed extensive perivascular and mononuclear cell staining in control hearts vs minimal staining in anti-TNF-treated groups. Likewise, serum TNF levels were significantly lowered for treated groups vs control (83.1 +/- 14.0 pg/ml for control; 39.5 +/- 13.8 for anti-TNF; and 13.4 +/- 5.4 for anti-TNF + CsA; P less than 0.05 vs control for all groups).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
PGE1 reduces injury in hepatic allografts following preservation.
Prostaglandins of the E series have been shown to decrease renal and hepatic ischemic injury as well as improve hepatic function in patients with primary nonfunction following transplantation. We wished to determine the effect of prostaglandin E1 (PGE1) on hepatic allograft reperfusion injury in the isolated perfused rat liver (IPRL) model. Livers were harvested from adult male Sprague-Dawley rats and the bile duct, portal vein, and suprahepatic vena cava were cannulated. Control livers were placed immediately on the IPRL apparatus and perfused for 2 hr with a blood-Kreb's solution. Group A and B allografts were stored for 8 hr in heparinized lactated Ringer's solution at 4 degrees C. Group A livers were then perfused with a PGE1 infusion at 0.1 micrograms/kg/min while B livers received a placebo infusion of NS at the same rate. Temperature, pH, and inflow pressures were kept constant. Oxygen consumption, portal flow, and resistance were calculated for each group and found not to be statistically different. LDH, SGOT, superoxide anion (SOA), and bile flow were measured at 30-min intervals. At the end of the 2-hr perfusion, the placebo Group B (N = 5) had LDH, SGOT, and SOA higher than those of either Group A (N = 5) or control (N = 4) livers. The difference between Group A and Group B was significant for SGOT and SOA (P less than 0.05). Bile flow was highest in the control group (24.2 +/- 1.8 microliters/g/30 min).(ABSTRACT TRUNCATED AT 250 WORDS)
Alprostadil↗
Chromosomal anomaly and malformation syndrome with abdominal polyorchidism.
We describe a neonate who presented with multiple severe malformations including polyorchidism. To our knowledge this is the second case reported with ipsilateral testes located intra-abdominally. Chromosomal studies in cases of polyorchidism have been reported previously only once and the patient exhibited a normal karyotype. Our patient had a chromosome 21 long arm deletion. Interestingly, a trisomy 21 patient has been reported with agonadism. We suggest that genes on chromosome 21 may have some role in gonadal development.
Abnormalities, Multiple↗
The role of tumor necrosis factor in allograft rejection. III. Evidence that anti-TNF antibody therapy prolongs allograft survival in rats with acute rejection.
We have previously demonstrated that TNF-alpha levels are elevated in liver transplant patients experiencing acute rejection. In addition, prophylactic administration of anti-TNF-alpha or anti-TNF-beta antibodies prolonged graft survival in a rat heterotopic cardiac transplant model. This experiment was designed to evaluate anti-TNF therapy in the treatment of acute allograft rejection. Heterotopic cardiac transplants were performed using Buffalo donors and Lewis recipients. Histologic sections of transplanted grafts from untreated animals revealed significant rejection at day 4 with terminal rejection occurring on day 10.8 +/- 0.4. Animals in the experimental groups received antirejection therapy from postoperative days 4-13. Treatment with cyclosporine at 2 mg/kg/day prolonged graft survival to 16.5 +/- 2.0 days (P = 0.01 versus controls). Administration of polyclonal anti-TNF-alpha in combination with polyclonal anti-TNF-beta increased graft survival to 14.6 +/- 0.4 days (P less than 0.001 versus controls). Use of a monoclonal anti-TNF-alpha antibody was even more effective, with graft survival of 17.4 +/- 0.7 days (P less than 0.001 versus controls). Combination immunotherapy with monoclonal anti-TNF-alpha in conjunction with CsA extended survival to greater than 30 days. In contrast, recombinant TNF-alpha (5 micrograms/day, i.p.) markedly accelerated the time to graft failure (7.4 +/- 0.2 days, P less than 0.001 versus controls). Examination of explanted graft tissue on postoperative day 9 from animals treated with anti-TNF showed decreased mononuclear cell infiltrate when compared to untreated animals. Treatment with TNF-alpha markedly increased the inflammatory process. These results suggest that TNF may play a role in the pathogenesis of acute rejection.
Animals↗
Diffuse hepatocyte ballooning in liver biopsies from orthotopic liver transplant patients.
Mild to moderate liver injury to the orthotopically transplanted liver may result from acute rejection, mild ischaemia, or viral hepatitis. Because these conditions are often clinically indistinguishable, liver biopsy is frequently helpful. We previously characterized and reported the morphological spectrum of mild-to-moderate ischaemic injury from 170 liver biopsies (51 liver transplant patients). During this review, we found eight patients with a diffuse hepatocyte ballooning pattern. This pattern had some similarity to 'preservation injury' described by others, and in fact seven of the eight patients had these changes within the first 2 weeks post-transplant. However, two of the seven patients also displayed these changes up to 6 months post-transplant and the eighth patient developed these histological patterns only after the early post-transplant period. Follow-up data on patients with diffuse hepatocyte ballooning showed that some reverted to normal histology, some transformed to well-delineated perivenular ballooning, and some progressed to perivenular necrosis and/or infarction. Only when superimposed perivenular necrosis became apparent did the injury become irreversible, necessitating allograft removal or resulting in death. The pathogenesis of diffuse hepatocyte ballooning is unclear. However, the association of some of the cases with 'preservation injury' pattern in the early post-transplant period and the progression of others to necrosis and infarction, suggest an ischaemic basis for this lesion.
Autopsy↗
The concentration and temporal relationships of acetaminophen-induced changes in intracellular and extracellular total glutathione in freshly isolated hepatocytes from untreated and 3-methylcholanthrene pretreated Sprague-Dawley and Fischer rats.
Fischer rats are more sensitive to acetaminophen-induced hepatotoxicity than Sprague-Dawley rats, however, the mechanisms for this enhanced sensitivity remain unclear. The susceptibility to hepatotoxicity is determined largely by the balance between acetaminophen toxification and detoxification. Since glutathione plays a critical role in the detoxification process, it would be of interest to compare the effects of acetaminophen on hepatic glutathione homeostasis in the Sprague-Dawley and Fischer rat, and relate these effects to cytotoxicity. To this end, we measured the sequential changes of intracellular and extracellular total glutathione in freshly isolated hepatocytes from untreated and 3-methylcholanthrene pretreated Fischer and Sprague-Dawley rats, both in the absence (basal) and presence of acetaminophen. In the basal state, the intracellular total glutathione content was significantly (P less than 0.01) increased in hepatocytes from untreated Fischer rats. Nevertheless, the sequential release of total glutathione into the medium and the sequential depletion of intracellular total glutathione were quantitatively similar in hepatocytes from untreated Fischer and Sprague-Dawley rats. Following exposure to acetaminophen, there was a striking dose and time associated depletion of intracellular total glutathione in untreated hepatocytes from both rat strains, and quantitatively the depletion was similar in untreated hepatocytes from both rat strains. This degree of depletion of intracellular total glutathione was not associated with acetaminophen-induced cytotoxicity in Sprague-Dawley hepatocytes, whereas significant (P less than 0.05) cytotoxicity was demonstrated in Fischer hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
Acetaminophen↗
Expression of transferrin receptor on human maternal and neonatal peripheral blood lymphocytes.
The levels of peripheral blood lymphocytes expressing the receptor for transferrin (TSR) on untreated and phytohemagglutinin (PHA)-stimulated cell samples from maternal-neonate pairs were evaluated 4-12 h postpartum. Significantly increased levels of TSR+ cells were observed on fresh, unstimulated neonatal and maternal cells, as compared to control cells from young adult males and females, and the values seemed to correlate with the sex of the neonate and with birth order. The level of TSR+ cells in culture was found to be increased on neonatal cells and decreased on maternal cells.
Adult↗
Limb apraxia without aphasia from a left sided lesion in a right handed patient.
A right handed man had a massive left middle cerebral artery stroke. CT and MRI revealed extensive destruction of both anterior and posterior areas typically associated with language. There was, however, no aphasia, but instead a marked limb apraxia, dyscalculia, dense right visual neglect, and anosognosia. These uncommon dissociations and associations support the hypothesis that cerebral control of motor function of the limbs is not fundamentally related to the motor control involved in speech, and the notion that handedness is related to laterality of motor control, and only accidentally to laterality of language control.
Aged↗
Mapping the distribution of amobarbital sodium in the intracarotid Wada test by use of Tc-99m HMPAO with SPECT.
The intracarotid amobarbital sodium, or Wada, test has been used to localize speech and memory function prior to surgical treatment of temporal lobe seizures. The authors mixed technetium-99m hexamethyl-propyleneamine oxime (HMPAO) with amobarbital sodium and injected the mixture in 25 patients with epilepsy. Single photon emission computed tomography (SPECT) of the brain was then performed to determine intracerebral distribution of the amobarbital sodium. Results of SPECT were compared with those of conventional and digital subtraction angiography (DSA). The distribution of Tc-99m HMPAO and, presumably, amobarbital sodium varied from patient to patient. SPECT revealed a statistically different distribution from that predicted with conventional angiography. The distribution also often differed from that of DSA, although the difference was not significant. SPECT revealed infrequent delivery to mesial temporal lobe structures. This emphasizes the need for caution in the use of the intracarotid amobarbital sodium test to predict the outcome of removal of these areas.
Adolescent↗
Art appreciation courses can become "museum without walls.".
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Art↗
The effect of serum from patients with acute myocardial infarction on in vitro lymphocyte reactivity. II. Inhibition of IL-2 production.
Culture supernatants from concanavalin-A (con-A)-activated peripheral blood lymphocytes from healthy controls grown in the presence of sera from 20 patients 24 hours and 1 week after acute myocardial infarction (AMI) were tested for their mitogenic activity and for the presence of interleukin-2 (IL-2). Binding of exogenous IL-2 to activated lymphocytes from 10 patients was also determined. In supernatants prepared in the presence of patients' as compared to control sera, a significantly decreased mitogenic activity and IL-2 content were found. The mitogenic activity and IL-2 content in culture supernatants prepared with patients' sera collected 24 hours after the AMI (AMI I) and one week thereafter (AMI II) were significantly suppressed, and the degree of suppression in the 24-hour sera was significantly higher than in those collected after one week. No significant differences were observed in the binding capacity to exogenous IL-2 of activated patients' and control lymphocytes. The possibility is that immunosuppressive factors in the patients' sera, including cortisol, may suppress the patients' immune response acting through inhibition of IL-2 production.
Aged↗
The effect of serum from patients with acute myocardial infarction on in vitro lymphocyte reactivity. I. Inhibition of mitogen stimulation.
Sera from 20 patients obtained within 24 hours and one week after acute myocardial infarction (AMI) were tested for their immunomodulating effect on concanavalin-A (con-A) stimulated lymphocyte cultures from 11 healthy unrelated donors. Individual control sera from 21 healthy donors and 5 pools of control sera were used for comparison. Cortisol levels were tested in patients' and controls' sera. A significantly higher suppressive effect was seen in the presence of patients' sera taken at 24 hours than corresponding sera taken one week later. However, the suppressive effect after one week was increased as compared to control sera. A significant correlation between the degree of suppression and the cortisol level in corresponding sera was observed. An increased immunosuppression was observed with increased cortisol levels.
Adjuvants, Immunologic↗
Comparison of two pre-admission testing methods for elective surgery patients.
Patients admitted for elective surgery (inguinal hernia, varicose veins and hemorrhoids) were studied in order to evaluate the impact of performing pre-admission testing (PAT) by utilizing an automated multiphasic health testing (AMHT) technology on the rate of repeating the pre-operative routine laboratory tests during hospitalization. A slightly lower but statistically significant rate of repeated tests was found among patients who performed PAT by AMHTS compared with those who performed the tests via the conventional ambulatory system. This result suggests that performing routine tests before hospitalization in a single authorized AMHTS facility is preferred since it saves the patient time and reduces the need for repeated tests.
Adolescent↗
Effects of tumor necrosis factor (TNF) and immunotherapy directed against TNF on rat cardiac transplants.
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Animals↗
Prolongation of hepatic allograft survival in rat recipients treated with anti-lymphotoxin antibody.
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Animals↗
Consultants' perceptions of quality of referrals.
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Attitude of Health Personnel↗
Long-term cognitive sequelae of acyclovir-treated herpes simplex encephalitis.
Survival from untreated herpes simplex type 1 encephalitis is well known to be accompanied by severe cognitive impairments. Recently, acyclovir has been proven to be the most effective available treatment for this disease, with the expectation that it would appreciably reduce morbidity. We performed detailed assessments of four consecutive patients who received acyclovir in the early stages of biopsy-proven herpes encephalitis and who now have been followed up for 1.5 to 4 years. All four patients showed definite residual on either clinical or formal neuropsychological testing, most commonly dysnomia and impaired new learning for both verbal and visual material, even though three had normal performance on a standard clinical mental status test. All four patients were unable to function at their prior level of achievement. Therefore, despite early administration of acyclovir in herpes encephalitis, long-lasting neuropsychological residua are likely. Furthermore, cognitive deficits of prognostic importance may not be detected by clinical screening.
Acyclovir↗