Surgical reminiscence: Zora: a potluck case.
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Adult↗
Biomedical subjects
H Najafi
Publications and source records attributed to H Najafi.
An unusual combination of cardiovascular surgical disorders.
A 53-year-year-old man presented with aortic regurgitation, subvalvular and supravalvular aortic stenoses, and aneurysms involving the ascending aorta, the arch, and the innominate, right subclavian, and left common carotid arteries. Surgery consisted of resection of the obstructive lesions, replacement of the aortic valve, graft replacement of the ascending aorta, and the arch resection of innominate and subclavian artery aneurysms and reconstruction with a side limb to which the right carotid artery was anastomosed. The patient has remained asymptomatic with full employment.
Aneurysm↗
Glucose regulation of glutaminolysis and its role in insulin secretion.
Leucine or the nonmetabolized leucine analog +/- 2-amino-2-norbornane-carboxylic acid (BCH) (both at 10 mmol/l) induced biphasic insulin secretion in the presence of 2 mmol/l glutamine (Q2) in cultured mouse islets pretreated for 40 min without glucose but with Q2 present. The beta-cell response consisted of an initial peak of 20- to 25-fold above basal and a less marked secondary phase. However, BCH produced only a delayed response, while leucine was totally ineffective when islets were pretreated with 25 mmol/l glucose plus Q2. With Q2, 10 mmol/l BCH or leucine caused a nearly threefold increase, a twofold increase, or had no effect on cytosolic Ca2+ levels in islets pretreated for 40 min with 0, 5, or 15 mmol/l glucose, respectively. Thus, pretreatment of islets with high glucose inhibited BCH- and leucine-induced cytosolic Ca2+ changes and insulin release. Glucose decreased glutamine oxidation in cultured rat islets when BCH was present at 10 mmol/l, but not in its absence, with a lowest effective level of approximately 0.1 mmol/l, a maximum of 18-30 mmol/l, and an inhibitory concentration, 50%, of approximately 3 mmol/l. The data are consistent with the hypothesis that glucose inhibits glutaminolysis in pancreatic beta-cells in a concentration-dependent manner and hence blocks leucine-stimulated insulin secretion. We postulate that in the basal interprandial state, glutaminolysis of beta-cells is partly turned on because glutamate dehydrogenase (GDH) is activated by a decreased P-potential due to partial fuel depletion and sensitization to endogenous activators such as leucine. Additionally, it may contribute significantly to basal insulin release, which is known to be responsible for about half of the insulin released daily. The data explain "leucine-hypersensitivity" of beta-cells during hypoglycemia and contribute to the elucidation of the GDH-linked syndrome of hyperinsulinism associated with elevated serum ammonia levels. Thus, understanding the precise regulation and role of beta-cell glutaminolysis is probably central to our concept of normal blood glucose control.
Amino Acids↗
Experience with antegrade bihemispheric cerebral perfusion in aortic arch operations.
BACKGROUND: Various techniques have been used for cerebral protection in aortic arch operations. Antegrade cerebral perfusion has lost its popularity to hypothermic circulatory arrest to overcome the so-called cluttered operative field. Hypothermic circulatory arrest has its own problems of coagulopathy, time constraints, and prolongation of cardiopulmonary bypass time. METHODS: Since June 1986 we have used antegrade bihemispheric cerebral perfusion with moderate hypothermia in 20 patients with aortic arch disease. Twelve patients had aneurysm, 7 had dissection, and 1 had traumatic tear. Five patients had had previous sternotomy for ascending aortic replacement. In addition to arch reconstruction, 7 patients had aortic valve replacement or repair, 2 patients had Bentall procedure, and 3 had selective innominate reconstruction. The mean cerebral perfusion time was 51+/-29 minutes. In 7 patients the cerebral perfusion time was between 60 and 120 minutes. RESULTS: There was no in-hospital or 30-day mortality. The blood product requirements were significantly less with moderate hypothermia. One patient suffered cerebrovascular accident (5%). None of the 7 patients with cerebral perfusion times of 60 to 120 minutes had any neurologic deficits. These results are superior to those reported for hypothermic circulatory arrest with or without retrograde cerebral perfusion. CONCLUSIONS: Antegrade bihemispheric cerebral perfusion is an optimal adjunct for cerebral protection during aortic arch operations.
Adolescent↗
How to do it: aortic and mitral valve replacement through aortotomy.
Combined replacement of the aortic and mitral values is a relatively common operation. Occasionally it is feasible to replace the mitral value through the aortic root. This remarkable approach eliminates the need for a second atrial incision, and in reoperation it avoids extensive dissection and release of adhesions. Injury to the heart is minimized and the incidence of perioperative bleeding is reduced. The exposure is excellent and the operation is performed safely and expeditiously.
Aged↗
Regulation of insulin preRNA splicing by glucose.
Glucose tightly regulates the synthesis and secretion of insulin by beta cells in the pancreatic islets of Langerhans. To investigate whether glucose regulates insulin synthesis at the level of insulin RNA splicing, we developed a method to detect and quantify a small amount of RNA by using the branched DNA (bDNA) signal-amplification technique. This assay is both sensitive and highly specific: mouse insulin II mRNA can be detected from a single beta cell (betaTC3 cells or mouse islets), whereas 1 million non-insulin-producing alpha cells (alphaTC1.6 cells) give no signal. By using intron and exon sequences, oligonucleotide probes were designed to distinguish the various unspliced and partially spliced insulin preRNAs from mature insulin mRNA. Insulin RNA splicing rates were estimated from the rate of disappearance of insulin preRNA signal from beta cells treated with actinomycin D to block transcription. We found that the two introns in mouse insulin II are not spliced with the same efficiency. Intron 2 is spliced out more efficiently than intron 1. As a result, some mRNA retaining intron 1 enters the cytoplasm, making up approximately 2-10% of insulin mRNA in the cell. This partially spliced cytoplasmic mRNA is quite stable, with a half-life similar to the completely spliced form. When islets grown in high glucose are shifted to low glucose medium, the level of insulin preRNA and the rate of splicing fall significantly. We conclude that glucose stimulates insulin gene transcription and insulin preRNA splicing. Previous estimates of insulin transcription rates based on insulin preRNA levels that did not consider the rate of splicing may have underestimated the effect of glucose on insulin gene transcription.
Animals↗
Thoracic aortic operations: management of maldistribution of arterial flow during cardiopulmonary bypass.
On three occasions during operations for aortic aneurysm involving the ascending aorta it was noted that upon the release of the aortic clamp the grafted segment remained collapsed, indicating very little or no flow reaching the lumen of the reconstructed aorta. This was promptly and successfully remedied in 2 patients by perfusing the graft directly with a pediatric arterial catheter attached to a pump head while the femoral arterial line maintained systemic arterial inflow. This simple, safe, and highly effective technique adds to the surgeon's repertoire to manage yet another intriguing intraoperative development during thoracic aortic operations.
Aged↗
Measurement and modeling of glucose-6-phosphatase in pancreatic islets.
In the beta-cells of the pancreas, glucose phosphorylation carried out by glucokinase is the rate-controlling step in glycolysis, and the kinetic characteristics of glucokinase govern to a high degree the dose-response relationship between glucose and insulin release. Because glucose-6-phosphatase (G-6-Pase) opposes the action of glucokinase, it may have a regulatory role in the release of insulin in response to glucose if the enzyme is present in the beta-cells. A number of researchers have reported finding high levels of G-6-Pase in islets, but quantitation of its activity remains controversial, mainly because of difficulties in solubilizing a particulate enzyme. Therefore a method developed to measure functional glucose phosphorylation activity in intact brain was applied (Chi, M. M.-Y., M. E. Pusateri, J. G. Carter, B. J. Norris, D. B. McDougal, Jr., and O. H. Lowry. Anal. Biochem. 161: 508-513, 1987), and the rates of accumulation and disappearance of 2-deoxyglucose 6-phosphate (DG-6-P) in freshly harvested islets were determined as a measure of glucose cycling. Islets were incubated in the presence of 30 mM 2-deoxyglucose (DG) for 60 min, and subsequently the incubation medium was replaced with medium containing no DG, but instead high levels of mannoheptulose as a blocker of phosphorylation. The content of DG-6-P in the islets was measured at strategic times during the protocol. As predicted by a mathematical model, DG-6-P accumulated in the presence of DG and decayed after its washout. Both of these results are consistent with islets containing dephosphorylation activity for this substrate. The kinetic curves were fit using a mathematical model, and the maximal G-6-Pase activity was estimated to be 0.13 +/- 0.005 micromol x g(-1) x min(-1). However, when the physiological effect of this amount of G-6-Pase activity was assessed by use of a model of glycolysis, it was found that the impact on glucose cycling and usage was insignificant. It was concluded that normal islets do contain measurable activity for dephosphorylating glucose 6-phosphate but that this enzymatic reaction does not play a role in glucose metabolism and sensing by the normal beta-cell.
Animals↗
Sudden death caused by retrograde aortic dissection during repair of a descending thoracic aneurysm.
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Aged↗
Effect of a glucokinase inhibitor on energy production and insulin release in pancreatic islets.
Glucokinase has exclusively high control strength on glucose usage in the pancreatic beta-cell. However, glucokinase also has extraordinarily high control strength on insulin secretion, which is linked to the phosphate potential, [ATP]/([ADP][Pi]) (F.M. Matschinsky, Y.Liang, P. Kesavan, L. Wang, P. Froguel, G. Velho, D. Cohen, M.A. Permutt, Y. Tanizawa, T.L. Jetton, K. Niswender, and M.A. Magnuson. J. Clin. Invest. 92: 2092-2098, 1993). We propose that the ATP produced via the tricarboxylic acid cycle is approximately constant, irrespective of the glucose level. Furthermore, the component of ATP production that is derived from glycolysis and glycolytically derived NADH, which is shuttled into the mitochondria, is a critical signal controlling the ionic events leading to insulin secretion, as suggested previously (M. J. MacDonald. Diabetes 39: 1461-1466, 1990 and I.D. Dukes, M.S. McIntyre, R.J. Mertz, L.H. Philipson, M.W. Roe, B. Spencer, and J.F. Worley III. J. Biol. Chem. 269: 10979-10982, 1994). To test this hypothesis, glucose usage, oxidation, and insulin secretion were measured in cultured rat islets over a wide range of concentrations of glucose and mannoheptulose, an inhibitor of glucokinase. These data were fit to a mathematical model that predicts that glucokinase will govern the rate of glucose usage and ATP production and will also have a strong, but not complete, control over the rate of glucose oxidation, the phosphate potential, and insulin release. Mannoheptulose caused an inhibition of all three fluxes. The estimates of the mechanistic parameters of the model [maximal velocity (Vmax) and Michaelis constant for glucokinase, Vmax for hexokinase and glucose transport, and the inhibition constant of mannoheptulose to glucokinase] were similar to those obtained in vitro. Thus the data are consistent with a model in which the primary importance of glycolysis in transducing the glucose signal into changes of the phosphate potential imparts to glucokinase a high control strength on glucose-induced insulin secretion.
Animals↗
Blepharophimosis syndrome (BPES) and additional abnormalities in a female with a balanced X:3 translocation.
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Blepharophimosis↗
Intentional delayed repair of acute dissection of the ascending aorta complicated by stroke.
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Adult↗
Aortic valve replacement 13 years following Bentall procedure.
Aortic valve dysfunction secondary to leaflet degeneration of porcine bioprosthesis incorporated in a conduit poses a challenge to the surgeon. An adult male required repeat aortic valve replacement 13 years following insertion of an intraoperatively constructed conduit composed of a Carpentier-Edwards bioprosthesis and Dacron tube graft. At surgery, the extremely difficult situation was easily resolved by excising the degenerated leaflets and inserting a St. Jude aortic valve within the frame of the bioprosthesis. The patient has remained Class I during the 3-year follow-up period, enjoying normal aortic valve function.
Aortic Valve↗
Declining risk of reoperative valvular surgery.
One hundred eleven patients underwent their second to fifth open heart operation, excluding isolated coronary revascularization. The procedures included repeat, single and multiple valve replacements, concomitant redo valve surgery, plus aortic root, and/or aortic arch reconstruction with or without coronary bypass graft. Six patients had heart transplantation as the final procedure. The article is based on the analysis of the experience of one surgeon with particular emphasis on technical considerations and factors enhancing outcome. There were two deaths for an early (hospital--30 days) mortality of 1.8%. There were three sternal wound complications. Two patients suffered cerebrovascular accident (one with permanent residual deficit), and one patient required reoperation for tamponade. The text contains a relatively detailed description of the technical maneuvers applied for several different categories of procedures used.
Aortic Valve↗
Selectivity in aortic root reconstruction.
Anatomical variations in aortic root pathology, including combinations of dissection, aneurysmal dilatation, annuloaortic ectasia, and valve disease, defy standardized repair and mandate application of various surgical reconstructions. To examine these techniques, and their influence on morbidity and mortality, we reviewed 53 consecutive patients undergoing aortic root procedures. Thirty-two patients underwent total root reconstruction. Of these, 21 underwent Bentall procedures, 9 had a modification thereof, and 2 underwent a Cabrol reconstruction. Less extensive pathology was corrected in 21 patients with a partial root reconstruction. These included aortic valve replacement (AVR) and a separate tube graft in 14 patients, AVR and primary aortic repair +/- wrapping in 4 individuals, and AVR and patch aortic root enlargement in 3 patients. Mean age was 53.2 years (range 20 to 79). Nearly 20% had undergone previous cardiac surgery and 7.5% were emergencies. Early mortality was 4%. Complications included dysrhythmias (48%), myocardial infarction (4%), stroke (4%), pneumonia (14%), and pancreatitis (2%). There were no reoperations for bleeding. Three late complications, one pseudoaneurysm and two perivalvular leaks, were successfully repaired. Late deaths (13.7%) were caused by congestive heart failure (3), myocardial infarction (MI) (1), cancer (1), stroke (1), and accidental fall (1). Kaplan-Meier analysis reveals 1-, 5-, and 10-year survivals of 98%, 81%, and 66%. Survival and mortality data did not differ between groups, and except for the incidence of atrial dysrhythmias, complication rates also were not significantly different. This series illustrates the need for and the successful application of a selective approach to aortic root reconstruction.
Aorta↗
Effects of glucose on insulin secretion, glucokinase activity, and transgene expression in transgenic mouse islets containing an upstream glucokinase promoter-human growth hormone fusion gene.
We have analyzed in organ culture the effects of glucose on glucose-induced insulin secretion, glucokinase (GK) activity, and human growth hormone (hGH) expression in pancreatic islets from transgenic mice containing an upstream GK promoter-hGH fusion gene. Freshly isolated islets from these mice had a normal insulin secretory response to glucose but showed subtle defects after culture in low or high glucose for 4 days that may have been due to the accumulation of hGH in the culture media. Islets cultured from both normal and transgenic mice had approximately a fourfold induction of GK activity in response to an increased concentration of glucose in the culture media, whereas no such change in total islet hGH production was observed. Immunocytochemical localization of hGH in islets cultured in 3 mM glucose showed a pattern similar to that in freshly isolated islets. However, after culture in 30 mM glucose, hGH immunostaining became strikingly more heterogeneous. We conclude 1) that GK-hGH transgene expression does not appear to adversely affect glucose-stimulated insulin secretion in vivo or in freshly isolated islets, 2) that glucose does not induce transgene expression, thus providing additional evidence against an effect of glucose on GK gene transcription in the islet, and 3) that glucose stimulates the co-release of hGH with insulin, thereby enhancing the heterogeneous staining pattern seen among pancreatic beta-cells.
Animals↗
Thoracic aortic aneurysm: evaluation and surgical management.
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Aortic Dissection↗
Extended aortic valvuloplasty for recurrent valvular stenosis and regurgitation in children.
Recurrent significant aortic valvular stenosis or regurgitation, or both, after balloon or open valvotomy in pediatric patients often necessitates aortic valve replacement. In an attempt to preserve the aortic valve, we performed extended aortic valvuloplasty in 21 children with recurrent aortic valve stenosis or regurgitation from January 1989 to March 1993. Previous related procedures were one open aortic valvotomy or more (n = 15), balloon valvotomy (n = 4), balloon valvotomy after surgical valvotomy (n = 1), and repair of iatrogenic valve tear (n = 1). Mean age at the time of the extended aortic valvuloplasty was 6 +/- 3.4 years. Mean pressure gradient across the aortic valve was 56 +/- 12 torr. Regurgitation was moderate (grade 2 to 3) in nine and severe (grade 4) in 12 patients. Extended aortic valvuloplasty techniques consisted of thinning of valve leaflets (n = 15), augmentation of scarred and retracted leaflets with autologous pericardium (n = 11), resuspension of the augmented leaflet (n = 14), release of the rudimentary commissure from the aortic wall (n = 5), extension of the valvotomy incision into the aortic wall on both sides of the commissure (n = 20), patch repair of the sinus of Valsalva perforation (n = 1), reapproximation of tears (n = 5), and narrowing of the ventriculoaortic junction (n = 2). No operative deaths occurred. The postoperative mean pressure gradient, assessed by most recent Doppler echocardiography or cardiac catheterization at a follow-up of 18 +/- 6 months, was 19 +/- 6 torr (p < 0.01 versus the preoperative gradient). Aortic regurgitation was absent in 13, mild in 6, and moderate-to-severe, necessitating subsequent aortic valve replacement, in 2. This short-term experience indicates that extended aortic valvuloplasty is a safe and effective surgical approach that minimizes the need for aortic valve replacement in children with significant recurrent aortic valve stenosis or regurgitation.
Actuarial Analysis↗