Maternal pulmonary oedema during foetoscopic surgery.

We report a case of maternal pulmonary oedema necessitating intubation and ventilation with associated hyperchloraemic metabolic acidosis during foetoscopic laser surgery for twin-twin transfusion syndrome (TTTS), believed to be secondary to absorption of normal saline irrigation fluid. TTTS complicates 10% to 20% of monochorionic twin pregnancies and develops due to imbalanced vascular anastomoses and consequent unidirectional transfusion between the twins. The recipient is at risk of cardiac failure due to circulatory overload and the donor twin becomes hypoperfused. The recipient is polyhydramniotic and the donor is oligohydramniotic. Untreated severe TTTS has a mortality rate of up to 90%. Treatment options include delivery if viable, serial amnioreduction or foetoscopic laser ablation of the communicating vessels. Since the Eurofoetus study, laser ablation has been the mainstay of treatment for pre-viable TTTS, involving insertion of endoscopes transabdominally into the polyhydramniotic sac to allow visualisation and ablation of the anastosmotic vessels. Amnioreduction does not correct the underlying pathology and offers very little in advanced disease. Foetoscopic laser ablation leads to an improved survival past 28 days and a lower incidence of neurological complications compared to serial amnioreduction.

Brain and testicular tumors in mice with progenitor cells lacking BAX and BAK.

The proapoptotic BCL-2 family proteins BAX and BAK serve as essential gatekeepers of the intrinsic apoptotic pathway and, when activated, transform into pore-forming homo-oligomers that permeabilize the mitochondrial outer membrane. Deletion of Bax and Bak causes marked resistance to death stimuli in a variety of cell types. Bax(-/-)Bak(-/-) mice are predominantly non-viable and survivors exhibit multiple developmental abnormalities characterized by cellular excess, including accumulation of neural progenitor cells in the periventricular, hippocampal, cerebellar and olfactory bulb regions of the brain. To explore the long-term pathophysiological consequences of BAX/BAK deficiency in a stem cell niche, we generated Bak(-/-) mice with conditional deletion of Bax in Nestin-positive cells. Aged Nestin(Cre)Bax(fl/fl)Bak(-/-) mice manifest progressive brain enlargement with a profound accumulation of NeuN- and Sox2-positive neural progenitor cells within the subventricular zone (SVZ). One-third of the mice develop frank masses comprised of neural progenitors, and in 20% of these cases, more aggressive, hypercellular tumors emerged. Unexpectedly, 60% of Nestin(Cre)Bax(fl/fl)Bak(-/-) mice harbored high-grade tumors within the testis, a peripheral site of Nestin expression. This in vivo model of severe apoptotic blockade highlights the constitutive role of BAX/BAK in long-term regulation of Nestin-positive progenitor cell pools, with loss of function predisposing to adult-onset tumorigenesis.

Phentermine and anaesthesia.

We describe the case of a woman who had two penroperative hypertensive crises that may have been due to her use of phentermine, a little-known sympathomimetic anti-obesity medication. The currently available anti-obesity medications are discussed: phentermine, diethylpropion, and sibutramine; all of which are sympathomimetics possessing noradrenaline and serotonin reuptake inhibitor activity. These medications should be discontinued one week preoperatively and have potential interactions with tramadol and antidepressants. The drug orlistat inhibits gastrointestinal lipase and may lead to fat soluble vitamin (A, D, E, and K) deficiency, so consideration should be given to checking coagulation status preoperatively.

Combined spinal and epidural anaesthesia for caesarean section in a parturient with severe primary pulmonary hypertension.

We describe the management of a parturient with severe primary pulmonary hypertension who underwent caesarean section. A multi-disciplinary approach was used. She was admitted to the intensive care unit perioperatively for invasive monitoring and trial of inhaled nitric oxide. Anaesthesia was provided by combined spinal-epidural block. We discuss controversies about the management of obstetric patients with this rare and serious condition.

The effects of sevoflurane on isolated gravid human myometrium.

The volatile anaesthetic agents are known to influence uterine muscle tone. All of the agents studied to date have been found to produce uterine relaxation. This property has been used to produce therapeutic uterine relaxation for difficult obstetric deliveries and the Ex Utero Intrapartum Treatment (EXIT) procedure. This study describes the effects of sevoflurane on isolated human myometrium at concentrations of 0.1, 0.25, 0.5, 0.75, 1.0, 1.5, 2.5 and 3.5 MAC. Sevoflurane produces dose-dependent depression of uterine muscle contractility with an ED50 of 0.94 MAC. Frequency of contraction was increased at concentrations of 2.5 MAC and greater. At concentrations of 3.5 MAC and above, uterine activity was virtually abolished.

Airway management on placental support (AMPS)--the anaesthetic perspective.

Neonatal airway obstruction has been reported to have a high mortality. Antenatal diagnosis of this condition is now possible. Anaesthetic and surgical techniques have been developed that allow neonatal airway obstruction to be managed at delivery, while the fetus remains oxygenated via the placental circulation. Three case studies are presented, and the anaesthetic issues for mother and fetus/neonate are discussed with reference to previously published cases of airway management on placental support. In particular, techniques for uterine relaxation and maintenance of placental circulation are explored. The history of these procedures and issues of planning and logistics are also discussed.

Friend of GATA-1 represses GATA-3-dependent activity in CD4+ T cells.

The development of naive CD4+ T cells into a T helper (Th) 2 subset capable of producing interleukin (IL)-4, IL-5, and IL-13 involves a signal transducer and activator of transcription (Stat)6-dependent induction of GATA-3 expression, followed by Stat6-independent GATA-3 autoactivation. The friend of GATA (FOG)-1 protein regulates GATA transcription factor activity in several stages of hematopoietic development including erythrocyte and megakaryocyte differentiation, but whether FOG-1 regulates GATA-3 in T cells is uncertain. We show that FOG-1 can repress GATA-3-dependent activation of the IL-5 promoter in T cells. Also, FOG-1 overexpression during primary activation of naive T cells inhibited Th2 development in CD4+ T cells. FOG-1 fully repressed GATA-3-dependent Th2 development and GATA-3 autoactivation, but not Stat6-dependent induction of GATA-3. FOG-1 overexpression repressed development of Th2 cells from naive T cells, but did not reverse the phenotype of fully committed Th2 cells. Thus, FOG-1 may be one factor capable of regulating the Th2 development.

Acute food restriction increases collagen breakdown and phagocytosis by mature decidual cells of mice.

An ultrastructural study was undertaken on antimesometrial mature decidual tissue of fed and food-restricted mice, on day 9 of pregnancy. The mean ad libitum food intake was established on mice from the 8th till the 9th day of pregnancy. Fed mice were used as controls. Experimental animals were divided into two groups: one was allowed to feed 25% of normal diet and the other 50%. Extracellular collagen fibrils were scarce in fed animals and conspicuous in food restriction. Granular electron-dense deposits and filamentous aggregates of disintegrating collagen fibrils were observed in all food-deprived mice but were rarely noted in fed animals. Intracellular vacuolar structures exhibited other typical cross-banded collagen immersed in finely granular electron-translucent material (clear vacuole) or electron-dense material containing collagen fibrils with a faint periodicity (dark vacuole). The clear and dark vacuoles were scarce in fed animals and evident in food-restricted mice, mainly in those 25% food restricted. Although collagen breakdown may be part of the normal process of decidual tissue remodelling our results suggest that it is enhanced in food-restricted animals. Thus it seems that collagen breakdown is a normal mechanism that may be regulated by the food intake of the pregnant animal.

Coexpression of cytokeratin and vimentin in mice trophoblastic giant cells.

Trophoblastic giant cells reach their maximum size and exhibit a conspicuous synthetic and invasive activity during mouse placentation. The cytoskeleton, given the complex functions of the cells, shows a well-developed network of intermediate filament proteins. Immunohistochemistry combined with confocal and conventional immunofluorescence studies of intermediate filaments proteins cytokeratin and vimentin were performed in mice trophoblastic giant cells on days 9-11 of pregnancy. Specimens were fixed in phosphate-buffered formaldehyde and tissues were processed for routine paraffin embedding. Trophoblastic giant cells from antimesometrial, lateral or mesometrial uterine regions, through days 9-11 of pregnancy, expressed the same staining with both immunoperoxidase and immunofluorescent techniques. Cytokeratin filamentous structures were intensely immunoreactive and were detected throughout the cells cytoplasm; a few cells exhibited strongest fluorescence in the peripheral cytoplasm. Vimentin-positive staining was often distributed throughout the cells cytoplasm, most frequently and more intensely in the peripheral region; in some cells, it was present only in the peripheral regions. It is probable that expression of vimentin in midpregnancy trophoblastic giant cells may be associated with the rapid and conspicuous increase in size and synthetic activity of the cells and also with phagocytosis of degraded materials and invasion of decidual tissue.

Axillofemoral bypass for aortoiliac occlusive disease.

BACKGROUND: Although aortoiliac disease remains a common cause of lower extremity ischemia, the efficacy of axillofemoral bypass in this setting remains controversial. This report summarizes our institutional experience with axillofemoral bypass. METHODS: A retrospective review of consecutive axillofemoral bypass grafts was performed at a single institution between 1984 and 1997. Only patients presenting with chronic aortoiliac occlusive disease were included. Patient demographics, risk factors, indications for surgery and outcomes were recorded. Survival curves for primary patency were plotted using the Kaplan-Meier method according to the standards set by the Society of Vascular Surgery-International Society for Cardiovascular Surgery. Comparisons between groups were made using the log rank method. Statistical significance was assumed at P values <0.05. RESULTS: Sixty patients underwent axillofemoral bypass grafting of which 53 were bifemoral and 8 unifemoral. Forty-seven procedures were performed for limb salvage. Primary patency rates at 1, 3, and 5 years were 86%, 72%, and 63%, respectively. Thirty-day mortality rate was 4.9%. Sixty percent of graft occlusions occurred in the femorofemoral limb with continued patency of the axillofemoral limb. Risk factors, type of procedure and superficial femoral artery patency had no statistically significant effect on long-term patency. CONCLUSIONS: In the setting of diffuse, chronic aortoiliac occlusive disease, long-term patency rates of axillofemoral grafts approach those of aortobifemoral bypass and exceed those quoted for percutaneous transluminal angioplasty, with results that are highly reproducible. Axillofemoral bypass is an excellent option in those patients at prohibitive risk for direct aortic reconstruction or those with limited life expectancy.

FOG acts as a repressor of red blood cell development in Xenopus.

Members of the GATA family of zinc-finger transcription factors have critical roles in a variety of cell types. GATA-1, GATA-2 and GATA-3 are required for proliferation and differentiation of several hematopoietic lineages, whereas GATA-4, GATA-5 and GATA-6 activate cardiac and endoderm gene expression programs. Two GATA cofactors have recently been identified. Friend of GATA-1 (FOG-1) interacts with GATA-1 and is expressed principally in hematopoietic lineages, whereas FOG-2 is expressed predominantly in heart and brain. Although gene targeting experiments are consistent with an essential role for FOG-1 as an activator of GATA-1 function, reporter assays in transfected cells indicate that FOG-1 and FOG-2 can act as repressors. We have cloned a Xenopus laevis homologue of FOG that is structurally most similar to FOG-1, but is expressed predominantly in heart and brain, as well as the ventral blood island and adult spleen. Ectopic expression and explant assays demonstrate that FOG proteins can act as repressors in vivo, in part through interaction with the transcriptional co-repressor, C-terminal Binding Protein (CtBP). FOG may regulate the differentiation of red blood cells by modulating expression and activity of GATA-1 and GATA-2. We propose that the FOG proteins participate in the switch from progenitor proliferation to red blood cell maturation and differentiation.

Different sequence requirements for expression in erythroid and megakaryocytic cells within a regulatory element upstream of the GATA-1 gene.

The lineage-restricted transcription factor GATA-1 is required for differentiation of erythroid and megakaryocytic cells. We have localized a 317 base pair cis-acting regulatory element, HS I, associated with a hematopoietic-specific DNase I hypersensitive site, which lies approx. 3.7 kilobases upstream of the murine hematopoietic-specific GATA-1 IE promoter. HS I directs high-level expression of reporter GATA-1/lacZ genes to primitive and definitive erythroid cells and megakaryocytes in transgenic mice. Comparative sequence analysis of HS I between human and mouse shows approx. 63% nucleotide identity with a more conserved core of 169 base pairs (86% identity). This core contains a GATA site separated by 10 base pairs from an E-box motif. The composite motif binds a multi-protein hematopoietic-specific transcription factor complex which includes GATA-1, SCL/tal-1, E2A, Lmo2 and Ldb-1. Point mutations of the GATA site abolishes HS I function, whereas mutation of the E-box motif still allows reporter gene expression in both lineages. Strict dependence of HS I activity on a GATA site implies that assembly of a protein complex containing a GATA-factor, presumably GATA-1 or GATA-2, is critical to activating or maintaining its function. Further dissection of the 317 base pair region demonstrates that, whereas all 317 base pairs are required for expression in megakaryocytes, only the 5' 62 base pairs are needed for erythroid-specific reporter expression. These findings demonstrate differential lineage requirements for expression within the HS I element.

Percutaneous transluminal angioplasty of infrainguinal vessels.

In the last decade, percutaneous angioplasty (PTA) has been used with increasing frequency to treat infrainguinal atherosclerotic lesions. In hopes of better delineating the role of PTA, we undertook a retrospective analysis of infrainguinal PTA in one hospital over a 7-year period. The charts of all patients receiving infrainguinal PTA from 1989 to 1996 were reviewed. Demographics, site and type of lesion, and results of treatment were recorded. Survival curves were plotted using the Kaplan-Meier method following current Society of Vascular Surgery/International Society for Cardiovascular Surgery (SVS/ISCVS) guidelines. Differences in times to first failure were tested using the log rank method. Failures were documented by duplex ultrasound. All patients requiring repeat intervention underwent contrast angiography. In selected patients with stenotic lesions <3 cm, infrainguinal PTA may be an appropriate initial treatment modality. However, 5-year patency rates are significantly lower than those achieved by saphenous vein grafting. The efficacy of the procedure is markedly decreased when used to treat arterial stenoses >3 cm in length as well as occlusions, and surgical revascularization may be a more appropriate initial therapeutic procedure.

An 18q- syndrome breakpoint resides between the duplicated serpins SCCA1 and SCCA2 and arises via a cryptic rearrangement with satellite III DNA.

The 18q-syndrome is representative of a group of terminal deficiency or macrodeletion syndromes characterized by mental retardation and congenital malformations. To gain insight into the mechanism of chromosomal loss and stabilization in these disorders, we cloned a putative terminal deletion breakpoint from an 18q-syndrome patient. The 18q21.3 breakpoint occurred between two nearly identical serine protease inhibitor (serpin) genes, SCCA1 and SCCA2. Although cytogenetic studies suggested that this chromosomal aberration was formed by a simple terminal deletion, DNA sequence analysis, pulsed-field gel electrophoresis and fluorescence in situ hybridization showed that the breakpoint was contiguous with a 35 bp filler sequence followed by a satellite III DNA-containing telomeric fragment of 475-1000 kb. This type of satellite III DNA sequence was not detected on the normal chromosome 18, but was highly homologous with types of satellite III DNA sequences normally located on the short arms (p11) of the acrocentric chromosomes and other heterochromatic regions. This DNA sequence analysis suggested that the terminal deficiency in this 18q-syndrome patient arose via illegitimate (non-homologous) recombination. Moreover, these data raise the possibility that a subset of chromosomal aberrations appearing cytogenetically and molecularly as simple terminal truncations or deletions are caused by small (<1000 kb) cryptic rearrangements.

Demonstration of extracellular acid phosphatase activity in the involuting, antimesometrial decidua in fed and acutely fasted mice by combined cytochemistry and electron microscopy.

An ultrastructural cytochemical study of acid phosphatase activity in the antimesometrial decidua on days 9-11 of pregnancy was performed in fed and acutely fasted mice. Specimens were fixed in a buffered mixture of paraformaldehyde and glutaraldehyde and were incubated in a buffered medium containing sodium beta-glycerophosphate and cerium chloride for ultrastructural localization of acid phosphatase activity. Fed and fasted animals showed extracellular acid phosphatase reaction product in the decidual-trophoblast interface, in the region of loosely and tightly packed, mature decidual cells, and in the region of predecidual cells. Reaction product was absent in the region of nondecidualized stromal cells. Extracellular acid phosphatase activity was more conspicuous in the region of mature decidual cells in fasted mice than in fed mice, and it was apparently similar in the region of predecidual cells in both fed and fasted mice. Acid phosphatase reaction product was also observed in lysosomes in all cells studied. Because acid phosphatase activity reflects the presence of lysosomal hydrolases in general, our results suggest that there is matrix degradation by lysosomal enzymes in both fed and fasted mice. These events may be part of the process of tissue remodeling in regions of predecidual cells and mature decidual cells. However, it is also possible that, in the region of mature decidual cells, breakdown of matrix constituents is a mechanism to provide nutrients for the growing fetus. This mechanism is probably enhanced in fasted mice.

Does dextran 40 improve the early patency of autogenous infrainguinal bypass grafts?

PURPOSE: We determined whether the administration of dextran 40 would increase the early (30-day) patency of autogenous infrainguinal bypass grafts. METHODS: During a 4-year period, 244 patients undergoing 273 autogenous infrainguinal bypass grafts were prospectively enrolled into and completed this study. Patients were randomized into two groups; one of the groups received a 72-hour infusion of dextran 40 after surgery, and the other did not. Comparisons were made between those patients who did and did not receive dextran 40 with respect to risks factors, demographics, and early graft patency. RESULTS: One hundred twenty-six procedures were accompanied by the use of dextran; 147 were not. There was no significant difference between the two groups with respect to patient age, gender, perioperative risk factors, indication for surgery, or location of bypass graft (popliteal vs tibial). Among those patients receiving dextran, there were eight early occlusions (6.4%) and four deaths (3.2%); 89.7% of the patients were alive with patent grafts 30 days after surgery. In the group not receiving dextran, there were 10 early occlusions (6.8%) and 3 deaths (2%); 90.5% of the patients were alive with patent grafts 30 days after surgery. There was no significant difference between the two groups with respect to rate of early occlusion (p = 1.00), death (p = 0.71), or 30-day patency (p = 0.84). CONCLUSIONS: The administration of dextran 40 does not increase the early patency of autogenous infrainguinal bypass grafts. Its routine use during these procedures cannot be recommended.

Selective use of the intensive care unit after nonaortic arterial surgery.

PURPOSE: The purpose of this study was to determine whether the institution of a clinical protocol combining 6 hours of recovery room observation and guidelines for intensive care unit (ICU) admission would allow selected patients to be safely transferred directly to a surgical floor after nonaortic arterial reconstruction. METHODS: After a clinical pathway was formed, 134 consecutive patients undergoing 154 nonaortic arterial operations were prospectively enrolled in this study. Patients requiring ICU care and the responsible factors were identified. Comparisons of risk factors and demographics were made between those patients who did and did not require ICU care. RESULTS: Twelve (7.8%) patients spent a total of 27 days in the ICU (range 1 to 11 days). As per our guidelines four patients were transferred to the ICU for invasive monitoring, and four were sent to the ICU because of refractory hemodynamic instability or arrhythmia in the postanesthetic recovery room. An additional four patients were transferred to the ICU after having been on the surgical floor for 24 to 72 hours because of the following perioperative complications: prolonged chest pain (one), pneumonia (one), heart failure (one), and graft occlusion requiring a urokinase infusion. Patients admitted to the ICU were more likely to have heart disease (p = 0.02) and to have had an operation other than carotid endarterectomy (p = 0.04) than those who were not. The 30-day mortality rate was 1.4%. CONCLUSIONS: The implementation of a clinical protocol similar to the one used in this study will allow many patients undergoing nonaortic vascular surgery to avoid the use of the ICU. This approach will conserve hospital and financial resources without adversely affecting patient morbidity and mortality rates.

Does the choice of material influence early morbidity in patients undergoing carotid patch angioplasty?

BACKGROUND: This study was undertaken to determine whether the choice of material influences the early morbidity of patients undergoing carotid patch angioplasty. METHODS: Before undergoing carotid endarterectomy, 190 patients were randomized to receive 207 patch closures with either Dacron (USCI Sauvage knitted velour) or saphenous vein harvested from the thigh. RESULTS: One hundred seven Dacron and 100 vein patch angioplasties were performed. No significant difference was seen between the two groups in patient age, sex preoperative risk factors, or indication for operation (p > 0.25 for each variable). Among the patients undergoing Dacron patch angioplasty three strokes (two temporary and one permanent), seven episodes of bleeding requiring reoperation, and two neck wound infections requiring rehospitalization occurred. The final 32 patients with Dacron patch closures had their anticoagulation reversed and had no bleeding complications. Complications inpatients undergoing vein patch closure included one fatal perioperative stroke, two episodes of bleeding requiring reoperation including one patch rupture, and three groin infections requiring hospitalization. No significant difference was seen between the two groups in the rate of perioperative stroke (p = 0.62), episodes of bleeding (p = 0.17), or infection (p = >0.67). CONCLUSIONS: Carotid patch angioplasty can be performed with an acceptably low complication rate with either Dacron or vein, and the choice of patch material does not clinically affect patient morbidity. However, reversal of anticoagulation is recommended to minimize bleeding complications in patients undergoing Dacron patch angioplasty.

Extracellular and intracellular degradation of collagen by trophoblast giant cells in acute fasted mice examined by electron microscopy.

The fine structure of trophoblast giant cells and their interaction with collagen at the antimesometrial region on the 9th day of pregnancy was examined in fed and acute fasted mice. Collagen fibrils and filamentous aggregates (disintegrating collagen fibrils) were observed in the extracellular space. Three types of intracellular vacuoles containing collagen fibrils were present: vacuole type A exhibited typical cross-banded collagen immersed in finely granular electron-translucent material; and vacuoles type B and C showed electron-opaque granular material containing, respectively, faint cross-banded collagen and narrow clear stripes often with faint periodicity. In fed animals vacuoles type B were absent and the others were less evident. Only fasted animals showed extracellular acid phosphatase activity on collagen fibrils, filamentous aggregates and confined regions of the extracellular space. Intracellular acid phosphatase activity was observed in vacuoles type B and in lysosomes. The results indicate that trophoblast giant cells are capable of breaking down extracellular collagen and also of internalizing collagen for intracellular degradation. It is likely that these events are part of the process of invasion of the uterine wall. However, in fasted mice, collagen breakdown is more pronounced, and it may therefore contribute to the provision of amino acids and other nutrients for the undernourished fetus.

The percutaneous treatment of angioaccess graft complications.

BACKGROUND: In the last decade, percutaneous techniques have been used with increasing frequency to treat angioaccess graft complications. The role of these procedures and their outcomes in patients on hemodialysis remains unclear. PATIENTS AND METHODS: The records of all patients receiving percutaneous treatment of failed or failing angioaccess grafts were reviewed. Patient demographics, site and type of percutaneous intervention, and results of treatment were recorded. Survival curves were plotted using the Kaplan-Meier method, and differences in times to first failure between types of intervention were tested using the log rank method. RESULTS: Grafts not requiring thrombolysis had significantly higher patency rates than those that did (P < 0.0001). Patency of grafts undergoing angioplasty of sites remote from the venous anastomosis were significantly higher than those of grafts undergoing venous anastomotic dilatation (P = 0.0004). CONCLUSIONS: Percutaneous techniques are most effective in treating failing but patent angioaccess grafts, especially those with stenoses remote from the venous anastomosis. The efficacy of percutaneous techniques diminishes significantly when used to treat grafts that have progressed to occlusion.