Review of patient experience with bilateral sagittal split osteotomies as a day case procedure.

Historically, patients who received bilateral sagittal split osteotomies (BSSO) required an inpatient admission for at least one night. Since March 2015, the Oral and Maxillofacial Department at the Royal Gwent Hospital has performed bilateral sagittal split osteotomies (BSSO) as a day case procedure for their medically and socially fit patients. Our team's service evaluation by Davies et al (2018) for this procedure, demonstrated that this could be done both routinely and successfully, whilst conforming to national day case procedural standards. The aim of this satisfaction survey was to evaluate this procedure from a patient's perspective, to further consolidate our results from 2018. The forty-five patients who underwent day case BSSO (DCBSSO) between February 2015 and February 2020 were retrospectively identified and deemed eligible for inclusion. Participation involved completion of a 10-part questionnaire via telephone consultation. Patients were asked questions focussing on their experience of discharge timing, management of postoperative symptoms, and overall recovery at home. Twenty-four patients consented to partake in the survey (response rate of 73%). Twenty-three (96%) were extremely happy to be discharged the day of their surgery and felt that the timing of discharge was appropriate. Only 17% of patients experienced discomfort overnight and 96% of these stated they could manage their symptoms at home. From this survey, we can confirm that the majority of patients receiving DCBSSO at the Royal Gwent Hospital were happy to be discharged the day of their surgery and recover at home.

The immunoglobulin octanucleotide: independent activity and selective interaction with enhancers.

The thymidine kinase (tk) promoter of herpes simplex virus includes an octanucleotide sequence motif (ATTTGCAT) that is also an essential component of immunoglobulin kappa gene promoters. In the absence of an enhancer, tk promoter derivatives that contain this element support a higher rate of transcription than those that lack it. The action of the kappa enhancer augments that of the octanucleotide in B lymphoid cells; when both elements are present, tk promoter activity is increased by more than an order of magnitude. In contrast, the presence of the octanucleotide in this promoter markedly reduces its response to a nonimmunoglobulin enhancer. These results suggest that the octanucleotide may mediate a selective interaction among promoters and enhancers.

Blocking FcRn in humans reduces circulating IgG levels and inhibits IgG immune complex-mediated immune responses.

The neonatal crystallizable fragment receptor (FcRn) functions as an intracellular protection receptor for immunoglobulin G (IgG). Recently, several clinical studies have reported the lowering of circulating monomeric IgG levels through FcRn blockade for the potential treatment of autoimmune diseases. Many autoimmune diseases, however, are derived from the effects of IgG immune complexes (ICs). We generated, characterized, and assessed the effects of SYNT001, a FcRn-blocking monoclonal antibody, in mice, nonhuman primates (NHPs), and humans. SYNT001 decreased all IgG subtypes and IgG ICs in the circulation of humans, as we show in a first-in-human phase 1, single ascending dose study. In addition, IgG IC induction of inflammatory pathways was dependent on FcRn and inhibited by SYNT001. These studies expand the role of FcRn in humans by showing that it controls not only IgG protection from catabolism but also inflammatory pathways associated with IgG ICs involved in a variety of autoimmune diseases.

Day-case bilateral sagittal split osteotomy.

In the UK, patients who have bilateral sagittal split osteotomy (BSSO) have generally been thought to require inpatient admission and an overnight hospital stay. However, since the introduction of national standards on day case surgery in the UK in 2011, patients at the Royal Gwent Hospital, Newport, have been treated as day cases, and have been pleased with the results. The aim of this paper was to show that these procedures conform to current national standards, and can be done successfully and safely. We retrospectively reviewed all patients who had isolated BSSO planned as day cases between March 2015 and February 2017. Thirty-four were eligible. Of them, 32 were discharged on the day of operation and two were admitted postoperatively: one because of severe nausea and vomiting and the other because of bleeding. No patients were readmitted within 48hours of the procedure. BSSO can be done successfully and routinely as a day-case procedure. However, to reduce the rate of unplanned admissions, we recommended that operations start early in the morning.

A mutation in the lipoprotein lipase gene is the molecular basis of chylomicronemia in a colony of domestic cats.

Members of a domestic cat colony with chylomicronemia share many phenotypic features with human lipoprotein lipase (LPL) deficiency. Biochemical analysis reveals that these cats do have defective LPL catalytic activity and have a clinical phenotype very similar to human LPL deficiency. To determine the molecular basis underlying this biochemical phenotype, we have cloned the normal and affected cat LPL cDNAs and shown that the affected cat has a nucleotide change resulting in a substitution of arginine for glycine at residue 412 in exon 8. In vitro mutagenesis and expression studies, in addition to segregation analysis, have shown that this DNA change is the cause of LPL deficiency in this cat colony. Reduced body mass, growth rates, and increased stillbirth rates are observed in cats homozygous for this mutation. These findings show that this LPL deficient cat can serve as an animal model of human LPL deficiency and will be useful for in vivo investigation of the relationship between triglyceride rich lipoproteins and atherogenic risk and for the assessment of new approaches for treatment of LPL deficiency, including gene therapy.

A novel 7-nucleotide motif located in 3' untranslated sequences of the immediate-early gene set mediates platelet-derived growth factor induction of the JE gene.

A cohort of the serum and growth factor regulated immediate-early gene set is induced with slower kinetics than c-fos. Two of the first immediate-early genes characterized as such, c-myc and JE, are contained within this subset. cis-acting genomic elements mediating induction of the slower responding subset of immediate-early genes have never been characterized. Herein we characterize two widely separated genomic elements which are together essential for induction of the murine JE gene by platelet-derived growth factor, serum, interleukin-1, and double-stranded RNA. One of these elements is novel in several regards. It is a 7-mer, TTTTGTA, found in the proximal 3' sequences downstream of the JE stop codon. The 3' element is position dependent and orientation independent. It does not function in polyadenylation, splicing, or destabilization of the JE transcript. Copies of the 7-mer or its inverse are found at comparable 3' sites in 25 immediate-early genes that encode transcription factors or cytokines. Given its general occurrence, the 7-mer may be a required cis-acting control element mediating induction of the immediate-early gene set.

Evidence for a novel signal transduction pathway activated by platelet-derived growth factor and by double-stranded RNA.

Platelet-derived growth factor (PDGF) and the synthetic double-stranded RNA poly(I).poly(C) [poly(I.C)] stimulate transcription of the JE gene in BALB/c-3T3 fibroblasts. The response of JE to poly(I.C) does not appear to be channeled through any known component of the PDGF receptor signal transduction apparatus. In addition, JE sequences upstream of the transcription start site are devoid of previously identified poly(I.C)-responsive elements, such as those found in the beta-interferon gene. These data suggest that a novel signal transduction pathway regulates the JE response to PDGF and double-stranded RNA. The c-myc and c-fos proto-oncogenes also respond to this pathway but with poor efficiency. However, this pathway operates very efficiently on other PDGF-inducible genes that encode the secretory proteins KC and M-CSF.

Production and Characterization of Monoclonal Antibodies against Aspartate Aminotransferase-P1 from Lupin Root Nodules.

Six hybridoma clones were obtained that secreted monoclonal antibodies against the aspartate aminotransferase-P1 (AAT-P1) isoenzyme from root nodules of Lupinus angustifolius [L.] cv Uniharvest. This enzyme is found constitutively in the plant cytosol fraction. The monoclonal antibodies produced were all of the immunoglobulin G1 class, recognized two distinct epitopes on the protein, and represented the major paratopes found in the immunoglobulin fraction of sera taken from mice and rabbits immunized with the pure AAT-P1 protein. One of these epitopes was unique to lupin nodule AAT-P1. The other epitope was shown to be present on enzyme from lupin bean, white clover and tobacco leaves, lupin roots and nodules, and potato tubers. Both epitopes were recognized by the appropriate monoclonal antibodies in both their native and denatured forms. None of the monoclonal antibodies produced reacted with Rhizobium lupini NZP2257, Escherichia coli extracts, or with the inducible aspartate aminotransferase-P2 (AAT-P2) isoform also found in root nodules. A sandwich enzyme-linked immunosorbent assay utilizing two monoclonal antibodies recognizing the two distinct epitopes was developed and was capable of quantitating AAT-P1 in plant extracts. The limit of detection of AAT-P1 was less than 15 pg/mL and AAT-P1 protein could be quantified in the range 80 to 1000 pg/mL. Using this assay, AAT-P1 protein was shown to remain relatively constant during nodule development. Use of an AAT-P2-specific monoclonal antibody that inhibits the enzyme activity of this isoform enabled the direct determination of AAT-P1 enzyme activity in nodule extracts. Using these assays, specific activities of the individual isoforms were calculated; that of the AAT-P1 isoform was shown to be 7.5-fold higher than that of the AAT-P2 isoform.

Adenosine is a selective pulmonary vasodilator in cardiac surgical patients.

OBJECTIVE: The purpose of this study was to examine and compare the systemic and pulmonary hemodynamic effects of a central venous infusion of adenosine in cardiac surgical patients. DESIGN: Prospective; each subject served as his/her own control. SETTING: University Hospital and Veteran's Affairs Medical Center. PATIENTS: Ten cardiac surgical patients (age 56 +/- 6 years) were studied in the operating room under general anesthesia after weaning from cardiopulmonary bypass. Pulmonary vascular resistance (PVR), systemic vascular resistance (SVR), mean pulmonary arterial pressure (MPAP), and mean systemic arterial pressure (MAP) were determined before, during, and after central venous infusion of adenosine (50 micrograms/kg/min) for 15 min. Statistical analysis was by analysis of variance; significance was accepted at p < 0.05. RESULTS: Adenosine produced selective vasodilation of the pulmonary vascular bed: both PVR and MPAP were significantly reduced during adenosine infusion without changes in either SVR or MAP. PVR and MPAP returned to preinfusion levels after cessation of the infusion. Adenosine effectively reduced PVR and pulmonary arterial pressure without decreasing SVR or systemic arterial pressure. CONCLUSIONS: Adenosine may be used clinically as a selective pulmonary vasodilator to optimize pulmonary hemodynamics without adverse systemic hemodynamic effects in cardiac surgical patients. It may be particularly valuable in patients with right heart dysfunction by selectively lowering right ventricular afterload.

Effective control of pulmonary vascular resistance with inhaled nitric oxide after cardiac operation.

Increased pulmonary vascular resistance may greatly complicate the perioperative management of cardiac surgical patients. Inhaled nitric oxide may be a promising new therapy to selectively lower pulmonary vascular resistance. The purpose of this study was to examine the effects of inhaled nitric oxide on pulmonary and systemic hemodynamics in cardiac surgical patients. Twenty patients (age 57 +/- 6 years) were studied in the operating room after weaning from cardiopulmonary bypass. Mean pulmonary artery pressure, pulmonary vascular resistance, systemic vascular resistance, and mean aortic pressure were determined at four points of data collection: before nitric oxide, with 20 ppm nitric oxide, with 40 ppm nitric oxide, and after nitric oxide. Statistical analysis was by analysis of variance; significance was accepted for p < 0.05. Inhaled nitric oxide produced selective pulmonary vasorelaxation. Pulmonary vascular resistance was lowered from 343 +/- 30 before nitric oxide to 233 +/- 25 dynes.sec-1.cm-5 with 20 ppm nitric oxide. Pulmonary vascular resistance was not further lowered by 40 ppm nitric oxide (p < 0.05). Mean pulmonary arterial pressure was 29 +/- 1 mm Hg before nitric oxide and was lowered to 22 +/- 1 mm Hg by 20 ppm nitric oxide and 21 +/- 1 mm Hg by 40 ppm nitric oxide (p < 0.05). Both pulmonary vascular resistance and mean pulmonary arterial pressure returned to baseline after withdrawal of inhaled nitric oxide. Inhaled nitric oxide produced no changes in either systemic vascular resistance or mean aortic pressure. We conclude that nitric oxide may be used as an effective pulmonary vasodilator after cardiac operations. It may be particularly valuable for selectively lowering right ventricular afterload in patients with right ventricular dysfunction.

Proliferation kinetics of a murine fibrosarcoma during fractionated irradiation.

Accelerated growth of tumor clonogens during the course of fractionated irradiation has been considered one of the major causes of radiation treatment failure. Alterations in clonogen growth rate could occur through three basic mechanisms: changes in cell-loss factor, changes in cell-cycle time, and recruitment of previously quiescent cells into the proliferative pool. This study was designed to assess changes in the cell-cycle time of clonogens of a murine fibrosarcoma during fractionated irradiation using an artificial pulmonary micrometastasis model. Lung colonies of various ages (4 h, 1 day, or 4 days) were exposed to single doses of irradiation ranging from 5-13 Gy; the fraction of surviving colonies was used to determine the preirradiation growth kinetics. The growth kinetics during fractionated irradiation was derived from colony-survival data of 4-day-old micrometastasis exposed to single doses or to 2, 5, 9, and 15 fractions separated by 4, 12, or 24-h intervals. The size of dose fractions used ranged from 1.7 to 14 Gy. The estimated clonogen doubling times before irradiation and during overall treatment periods of up to 14 days were 0.71 and 1.1 days, respectively. This significant (P less than 0.0001) increase in the doubling time was most likely a consequence of lengthening of the overall cell-cycle time of the clonogens by radiation-induced division delay. This observation suggests that accelerated growth, when it occurs in some tumors during fractionated treatment, is the result of a decreased cell-loss factor or recruitment of quiescent cells, but not a shortening of the cell-cycle time of the clonogens.

Hormone-replacement therapy increases serum paraoxonase arylesterase activity in diabetic postmenopausal women.

The paraoxonase (PON1) enzyme is associated with high-density lipoproteins (HDL) in the blood and is low in patients with type 2 diabetes. Hormone-replacement therapy (HRT) can increase HDL cholesterol levels, but its effect on serum PON1 arylesterase activity is uncertain. The aim of the present study was to determine the effect of 6 months' HRT with conjugated equine estrogen and medroxyprogesterone acetate on serum PON1 arylesterase activity in postmenopausal women with type 2 diabetes. Serum PON1 activity was measured immediately before and at the end of the second arm of a randomized, placebo-controlled, crossover with washout study originally designed to test the effect of HRT on plasma lipids in diabetic postmenopausal women. Baseline serum PON1 arylesterase activity was significantly (P <.001) lower in the postmenopausal diabetic women (149 +/- 38 micromol/mL/min; n = 47) than values in healthy postmenopausal women (173 +/- 32 micromol/mL/min; n = 51). Serum PON1 activity increased (10%) significantly (P =.009) in diabetic women treated with HRT compared with placebo. A significant (P =.02) interaction between baseline PON1 activity and treatment indicated a greater increase in PON1 activity during HRT in women with lower baseline activities. At baseline, serum PON1 arylesterase activity was correlated significantly with plasma HDL cholesterol levels in diabetic women (r = 0.333, P =.01, n = 47), and the increase in serum PON1 activity was correlated significantly with the change in plasma HDL cholesterol during HRT (r = 0.659, P =.0001, n = 28). These data suggest that serum PON1 activity is abnormally low in postmenopausal women with type 2 diabetes and increases during HRT, particularly in women with lower baseline levels and in those who show a concomitant increase in HDL cholesterol.

Adenosine for refractory pulmonary hypertension.

We report 2 patients with refractory acute pulmonary hypertension. In both, a central venous infusion of adenosine into the circulation effectively lowered pulmonary arterial pressure when standard treatment measures had failed, and reversed the clinical state of shock by achieving pulmonary vasodilatation. We conclude that adenosine may help lower pulmonary arterial pressure without lowering systemic arterial pressure in the setting of acute pulmonary hypertension when standard measures have failed.

Adenosine effectively controls pulmonary hypertension after cardiac operations.

BACKGROUND: Pulmonary hypertension secondary to increased pulmonary vascular resistance may greatly complicate the perioperative management of patients having cardiac operations. Adenosine may have a therapeutic role as a selective pulmonary vasodilator. The purpose of this study was to examine the pulmonary hemodynamic effects of a central venous infusion of adenosine in cardiac operative patients with pulmonary hypertension. METHODS: Ten cardiac patients with pulmonary hypertension (age, 62 +/- 6 years) were studied in the operating room under general anesthesia after weaning from cardiopulmonary bypass. Cardiac output, pulmonary vascular resistance, systemic vascular resistance, mean pulmonary arterial pressure, and mean systemic arterial pressure were determined before, during, and after central venous infusion of adenosine (50 micrograms x kg-1 x min -1) for 15 minutes. Statistical analysis was by analysis of variance, and significance was accepted at p < 0.05. RESULTS: Adenosine produced significant pulmonary vasodilation. Mean pulmonary arterial pressure was lowered from 36 +/- 1 to 28 +/- 2 mm Hg (p < 0.05), and pulmonary vascular resistance was lowered from 560 +/- 30 to 260 +/- 30 dynes x s x cm-5 (p < 0.05) during adenosine administration. At the same time, cardiac output rose from 4.0 +/- 0.6 to 6.2 L/min (p < 0.05). Pulmonary vascular resistance, mean pulmonary arterial pressure, and cardiac output returned to baseline after the adenosine infusion was stopped. There was no change in systemic mean arterial pressure during adenosine infusion. CONCLUSIONS: Adenosine may be used clinically as a selective pulmonary vasodilating agent to optimize pulmonary hemodynamic indices without adverse systemic hemodynamic effects in patients with pulmonary hypertension having cardiac operations. It may be particularly valuable in patients with right heart dysfunction by selectively lowering right ventricular afterload.

Transmission of Lactobacillus pneumonia by a transplanted lung.

Herein we report Lactobacillus pneumonia in a lung transplant recipient. The organism may have been normal flora in the donor but was a pathogen in the immunosuppressed recipient. Antibiotic therapy should include penicillin or clindamycin.

Technique to stent the open sternum after cardiac operations.

Extreme myocardial edema may preclude sternal closure after a cardiac operation. We describe a technique to stent the sternum open to optimize cardiac function.

Heart transplantation in children and young adults: early and intermediate-term results.

The purpose of this article is to report our short- and intermediate-term follow-up of cardiac transplantation for congenital heart disease and cardiomyopathy in children (age greater than 6 months), adolescents, and young adults. Thirty patients (ages 8 months to 24 years) with end-stage heart failure have undergone cardiac transplantation in our program: 12 (40%) for postoperative end-stage heart failure, 9 (30%) as primary treatment for congenital heart disease, 5 (17%) for dilated cardiomyopathy, and 4 (13%) for restrictive/hypertrophic cardiomyopathy. Nineteen patients (63%) had undergone prior operations; 4 patients received transplants for failed Fontan procedures. Induction therapy with antithymocyte therapy was used routinely, and long-term immunosuppression was by cyclosporine and azathioprine alone. Rejection surveillance/diagnosis was based on echocardiographic criteria. Posttransplantation follow-up ranges from 3 to 78 months. Operative mortality was 3.3% (1/30). No patients have been diagnosed with either accelerated allograft atherosclerosis or posttransplantation lymphoproliferative disease. We conclude that cardiac transplantation may be performed with excellent early and intermediate-term results.

Cardiac allograft failure: successful use of biventricular assist device.

Nonspecific primary allograft dysfunction is an important cause of perioperative death in cardiac transplant recipients. We report a case of severe nonspecific allograft dysfunction that was ultimately reversible after 18 days of biventricular mechanical circulatory support. Allograft recovery was echocardiographically recognized by a positive inotropic response to isoproterenol and milrinone. This case illustrates the potential for recovery of even extreme allograft dysfunction.

Failure of ambulance crew to initiate cardiopulmonary resuscitation.

The Utstein style of reporting out-of-hospital cardiac arrests requires that all confirmed cardiac arrests considered for resuscitation are analysed and that a record is made of the number of cases where no resuscitation is attempted. We report a series of 942 confirmed cardiac arrests considered for resuscitation by South Glamorgan Emergency Medical Service (EMS). There were 370 (39.3%) cases where no resuscitation was attempted by the EMS. The ages, male/female ratio and EMS response times were similar in both the group that received ambulance resuscitation and those that did not. Those not receiving resuscitation were less likely to have had an arrest of cardiac aetiology (51.3% vs. 75%, P < 0.00001). Rigor mortis or decomposition of the body was present in 50.8% of cases and in 20% a doctor had already confirmed the patient dead. In the remainder the ambulance crew failed to start resuscitation for a variety of reasons.

Outcome of out-of-hospital cardiorespiratory arrest in south Glamorgan.

During 138 weeks an emergency medical service (EMS) of mixed skill-level attempted to resuscitate 954 patients from prehospital cardiac arrest (883 attempts per million population per year); 75% of the arrests were of cardiac cause. This paper is one of the first analyses from europe to use the 'Utstein template' to report outcomes of such arrests. In cases where an arrest rhythm could be recorded, 38.4% were ventricular fibrillation (VF), 45.5% were asystolic, and the remainder were either electromechanical dissociation or respiratory arrests. Using univariate analysis factors associated with a greater likelihood of survival include the presence of a witness, bystander-initiated cardiopulmonary resuscitation (CPR), early CPR and VF as the arrest rhythm. Twenty of 155 cases (13%) survived where VF arrest was witnessed by non-EMS personnel.