Isolation and characterization of sea urchin egg cortical granules.

A method has been developed to isolate cortical granules (CG) free in suspension. It involves the mechanical disruption of the CG from CG lawns (CGL; Dev. Biol. 43:62-74, 1975) and concentration of the CG by low speed centrifugation. The isolated CG are intact and are a relatively pure population as judged by electron microscopy. Granule integrity is confirmed by the fact that isolated intact CG are radioiodinated to only 0.05% of the specific activity of hypotonically lysed CG. Purity of the CG preparation is assessed by the enrichment (four- to sevenfold) of CG marker enzymes and the absence or low activity of plasma membrane, mitochondrial, cytoplasmic, and yolk platelet marker enzyme activities. CG isolated from 125I-surface-labeled eggs have a very low specific radioactivity, demonstrating that CG contamination by the plasma membrane-vitelline layer (PM-VL) is minimal. CG yield is approximately 1% of the starting egg protein. The CG isolation method is simple and rapid, 4 mg of CG protein being obtained in 1 h. Isolated CG and PM-VL display distinct electrophoretic patterns on SDS gels. Actin is localized to the PM-VL, and all bands present in the CGL are accounted for in the CG and PM-VL. Calmodulin is associated with the CGL, CG, and PM-VL fractions, but is not specifically enriched in these fractions as compared with whole egg homogenates. This method of isolating intact CG from unfertilized sea urchin eggs may be useful for exploring the mechanism of Ca2+-mediated CG exocytosis.

Unilateral diaphragm paralysis: etiology, impact, and natural history.

AIM: The etiology, clinical impact, natural history and best therapy of unilateral diaphragm paralysis (UDP) are incompletely understood. This condition is not amenable to pacing, which requires an intact phrenic nerve. METHODS: Clinical records of patients with UDP referred to our diaphragm center were reviewed. RESULTS: Thirty-six patients (28 male, 8 female) aged 1 month to 78 years (mean 47.8 years) with UDP evaluated from 1983 to February 2007 were reviewed. Etiology was postsurgical in 13 (36%), tumor (with surgery or radiation therapy) in 7 (19%), idiopathic in 6 (17%), trauma (motor vehicle accident or head injury) in 5 (14%), polio in 3 (8%), and viral in 2 (6%) patients. 28 patients (78%) were symptomatic; 8 (22%) carried a diagnosis of coexisting chronic obstructive pulmonary disease. Mean duration of paralysis was 57.9 months (range up to 261 months). The left diaphragm was involved in 23 cases (64%) and the right in 13 (36%). Mean forced expiratory volume (FEV1) was 1 915 mL (61.3% of predicted) and mean forced vital capacity (FVC) was 2 432 mL (62.9% of predicted). Mean pO2 was 69.9 mmHg (range 49 to 124), indicating considerable shunting through underventilated lung. Pulmonary infection affected 3 patients (8.4%). Diaphragm function returned in 17% of patients (mainly children) at mean of 10.3 months. Four incapacitated patients (11 %) were treated surgically, with resection of the hemi-diaphragm. Surgical exploration revealed neurogenic atrophy of the diaphragm muscle. All 4 resected patients showed clinical, oxymetric, and spirometric improvement. CONCLUSION: The conclusion is drawn that: 1) UDP may be traumatic, tumor-related, iatrogenic, or idiopathic; 2) UDP decreases pO(2) substantially and breathing capacity by more than 1/3; 3) spontaneous recovery is possible; 4) UDP is not intrinsically lethal; 5) occasional patients are incapacited; 6) diaphragm resection produces clinical improvement via lower lobe re-expansion; 7) the incapacity incurred by UDP is mild compared to the clinical spectrum of bilateral diaphragm paralysis.

Targeting of a germ cell-specific type 1 hexokinase lacking a porin-binding domain to the mitochondria as well as to the head and fibrous sheath of murine spermatozoa.

Multiple isoforms of type 1 hexokinase (HK1) are transcribed during spermatogenesis in the mouse, including at least three that are presumably germ cell specific: HK1-sa, HK1-sb, and HK1-sc. Each of these predicted proteins contains a common, germ cell-specific sequence that replaces the porin-binding domain found in somatic HK1. Although HK1 protein is present in mature sperm and is tyrosine phosphorylated, it is not known whether the various potential isoforms are differentially translated and localized within the developing germ cells and mature sperm. Using antipeptide antisera against unique regions of HK1-sa and HK1-sb, it was demonstrated that these isoforms were not found in pachytene spermatocytes, round spermatids, condensing spermatids, or sperm, suggesting that HK1-sa and HK1-sb are not translated during spermatogenesis. Immunoreactivity was detected in protein from round spermatids, condensing spermatids, and mature sperm using an antipeptide antiserum against the common, germ cell-specific region, suggesting that HK1-sc was the only germ cell-specific isoform present in these cells. Two-dimensional SDS-PAGE suggested that all of the sperm HK1-sc was tyrosine phosphorylated, and that the somatic HK1 isoform was not present. Immunoelectron microscopy revealed that HK1-sc was associated with the mitochondria and with the fibrous sheath of the flagellum and was found in discrete clusters in the region of the membranes of the sperm head. The unusual distribution of HK1-sc in sperm suggests novel functions, such as extramitochondrial energy production, and also demonstrates that a hexokinase without a classical porin-binding domain can localize to mitochondria.

Signal transduction processes leading to acrosomal exocytosis in mammalian spermatozoa.

Many components of intercellular signaling involved in species-specific sperm binding to the egg's extracellular matrix, the zona pellucida, and the induction of acrosomal exocytosis, an absolute prerequisite to successful fertilization, have properties similar to intercellular signaling mechanisms controlling somatic cell function. Sperm-associated receptors for zona pellucida glycoproteins have been postulated to serve as the initial components of signal transduction cascades leading to the stimulation of cellular effector systems that modulate sperm function. Such receptor-effector systems appear to be coupled through guanine nucleotide-binding regulatory proteins (G proteins).

Adenylate cyclase in human cytotrophoblasts: characterization and its role in modulating human chorionic gonadotropin secretion.

Our previous work demonstrated that 8-bromo-cAMP promotes the secretion of both hCG and progesterone by cultured cytotrophoblasts. This study was conducted to characterize the adenylate cyclase of cytotrophoblasts and to examine the effects of agents that stimulate adenylate cyclase on hCG secretion. Adenylate cyclase activity was detected in purified cytotrophoblasts, as were membrane-bound stimulatory and inhibitory guanine nucleotide regulatory proteins, Gs and Gi. Adenylate cyclase was stimulated by MnCl2 and MgCl2, and the effects of MgCl2 were amplified by the GTP analog guanylylimidodiphosphate. Cholera toxin stimulated both cAMP and hCG production by cultured cytotrophoblasts, confirming the coupling of Gs to the adenylate cyclase. Forskolin also stimulated adenylate cyclase, cAMP synthesis, and hCG secretion. Pertussis toxin did not affect hCG secretion in either the absence or presence of forskolin. 8-Bromo-cAMP stimulated cytotrophoblast protein kinase activity, resulting in the increased phosphorylation of a protein with a mol wt of about 70,000, and produced a marked stimulation of hCG secretion. Our findings suggest that the level of expression of adenylate cyclase activity is one determinant of the endocrine function of the differentiating trophoblast.

Variability in electrophoretic mobility of Gi-like proteins: effect of SDS.

Two forms of Gi-like protein are resolved in both somatic cells and mouse gametes when Sigma SDS (95% grade) is used during polyacrylamide gel electrophoresis, whereas only a single species is resolved when Bio-Rad SDS (electrophoresis grade) is used. These two Gi-like proteins are likely to reflect two distinct species, since (i) the two species resolved in the presence of Sigma SDS migrate with the same electrophoretic mobility upon re-electrophoresis in the presence of Sigma SDS and (ii) exchanging Sigma SDS for Bio-Rad SDS resolves a single species, whereas exchanging Bio-Rad SDS for Sigma SDS resolves two species.

Dual regulation of the T-type Ca(2+) current by serum albumin and beta-estradiol in mammalian spermatogenic cells.

This study provides evidence for a novel mechanism of voltage-gated Ca(2+) channel regulation in mammalian spermatogenic cells by two agents that affect sperm capacitation and the acrosome reaction (AR). Patch-clamp experiments demonstrated that serum albumin induced an increase in Ca(2+) T current density in a concentration-dependent manner, and significant shifts in the voltage dependence of both steady-state activation and inactivation of the channels. These actions were not related to the ability of albumin to remove cholesterol from the membrane. In contrast, beta-estradiol significantly inhibited Ca(2+) channel activity in a concentration-dependent and essentially voltage-independent fashion. In mature sperm this dual regulation may influence capacitation and/or the AR.

Biological versus mechanical valves. Analysis of 1,116 valves inserted in 1,012 adult patients with a 4,818 patient-year and a 5,327 valve-year follow-up.

All surviving patients between 18 and 88 years of age receiving biological or mechanical prosthetic heart valves at the Yale-New Haven Hospital from January 1974 through January 1985 were analyzed for thromboembolism, anticoagulation-related hemorrhage, endocarditis, perivalvular leak, valve failure, need for reoperation, late cardiac death, and valve-related death. The rates of these events were analyzed in linear and actuarial terms over the 11 year period. A total of 533 patients received 606 biological valves (328 aortic, 252 mitral, 24 tricuspid, and two pulmonary, consisting of 482 Carpentier-Edwards, 108 Hancock, 15 Ionescu-Shiley, and one other), with a mean follow-up of 2,571 patient-years and 2,935 valve-years. They were compared with 479 patients with 510 mechanical valves (330 aortic, 175 mitral, and five tricuspid, consisting of 178 Starr-Edwards, 166 St. Jude Medical, 164 Björk-Shiley, and two others), which were implanted for 2,247 patient-years and 2,392 valve-years. We found a significantly increased incidence of thromboembolism (p less than 0.001) and reoperation for perivalvular leak (p less than 0.05) in the mechanical valves compared with the biological valves, but a significantly increased rate of valve failure (p less than 0.001) in the biological valves compared with the mechanical valves. The overall analysis comparing total morbidity and valve-related mortality significantly (p less than 0.01) favored the biological valves in the first 5 years of the study and the mechanical valves (p less than 0.001) in the second 5 years of the study. However, the net 10 year results showed no significant difference between the two types of valves. In summary, we found little direct evidence to strongly support the generalized use of one type of valve over another.

What is the appropriate size criterion for resection of thoracic aortic aneurysms?

Although many articles have described techniques for resection of thoracic aortic aneurysms, limited information on the natural history of this disorder is available to aid in defining criteria for surgical intervention. Data on 230 patients with thoracic aortic aneurysms treated at Yale University School of Medicine from 1985 to 1996 were analyzed. This computerized database included 714 imaging studies (magnetic resonance imaging, computed tomography, echocardiography). Mean size of the thoracic aorta in these patients at initial presentation was 5.2 cm (range 3.5 to 10 cm). The mean growth rate was 0.12 cm/yr. Overall survivals at 1 and 5 years were 85% and 64%, respectively. Patients having aortic dissection had lower survival (83% 1 year; 46% 5 year) than the cohort without dissection (89% 1 year; 71% 5 year). One hundred thirty-six patients underwent surgery for their thoracic aortic aneurysms. For elective operations, the mortality was 9.0%; for emergency operations, 21.7%. Median size at time of rupture or dissection was 6.0 cm for ascending aneurysms and 7.2 cm for descending aneurysms. The incidence of dissection or rupture increased with aneurysm size. Multivariable regression analysis to isolate risk factors for acute dissection or rupture revealed that size larger than 6.0 cm increased the probability by 32.1 percentage points for ascending aneurysms (p = 0.005). For descending aneurysms, this probability increased by 43.0 percentage points at a size greater than 7.0 cm (p = 0.006). If the median size at the time of dissection or rupture were used as the intervention criterion, half of the patients would suffer a devastating complication before the operation. Accordingly, a criterion lower than the median is appropriate. We recommend 5.5 cm as an acceptable size for elective resection of ascending aortic aneurysms, because resection can be performed with relatively low mortality. For aneurysms of the descending aorta, in which perioperative complications are greater and the median size at the time of complications is larger, we recommend intervention at 6.5 cm.

Thirty-year follow-up of superior vena cava-pulmonary artery (Glenn) shunts.

The first superior vena cava-pulmonary artery shunt (Glenn shunt) in our series was performed in February 1958. From then through September 1988, 91 patients have undergone this procedure for a wide variety of congenital defects. We here report follow-up data available on all patients. Ages ranged from 2 days to 46 years (mean 6.8). Diagnoses were as follows: tricuspid atresia, 27; single ventricle, 22; tetralogy of Fallot, 14; D-transposition of the great arteries, ventricular septal defect, and pulmonary stenosis, 9; D-transposition, 5; Ebstein's anomaly, 4; pulmonary atresia + intact septum, 4; and others, 6. The hospital mortality rate was 7.7% (one death in the last 53 patients, 1.9%). Five deaths occurred in patients less than 6 months old. There were 20 late deaths (22%) with actuarial survival rates of 84% and 66% at 10 and 20 years, respectively. Pulmonary arteriovenous fistula formation was seen in 18 patients (19.7%), six of whom have undergone therapeutic embolization with improvement in saturation. The prevalence of pulmonary arteriovenous fistula increases with time after shunt. No long-term shunt thrombosis or stricture formation was seen. Fifty percent of shunts were still functioning at 20 years. Palliation was limited because of decrease in blood flow to the contralateral pulmonary artery, collaterals between the inferior and superior venae cavae, and pulmonary arteriovenous fistula formation. Improvement in saturation was obtained in eight otherwise inoperable patients by creation of a right axillary arteriovenous fistula up to 19 years after the Glenn shunt. Three patients had conversion of a Blalock-Taussig shunt to a Glenn shunt with improvement in congestive heart failure. Twenty-six patients have undergone a Fontan procedure with two deaths. Compared with the group having a Fontan procedure without a prior Glenn operation, there was no difference in early or late mortality. Thirty years after a Glenn shunt, the first patient in this series is working full time after having undergone a modified Fontan procedure in 1981. We conclude that the Glenn connection, usually with supplemental procedures to enhance oxygenation, has provided excellent physiologic palliation with low mortality up to 30 years with no late thrombosis or stricture formation. The incidence of pulmonary arteriovenous fistula increases with time and can be effectively treated with embolization. Physiologic repair after the Glenn shunt carries a low mortality. Although currently used infrequently, superior vena cava-pulmonary artery shunting remains a useful method of palliation in selected patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Stroke in surgery of the thoracic aorta: incidence, impact, etiology, and prevention.

OBJECTIVES: To determine the incidence, impact, etiology, and methods for prevention of stroke after surgery of the thoracic aorta. METHODS: A total of 317 thoracic aortic operations on 303 patients (194 male, 109 female) aged 13 to 87 years (mean 61 years) were reviewed. There were 218 procedures on the ascending aorta and arch and 99 on the descending aorta. Of the 218 procedures on the ascending aorta and arch, 86 involved cardiopulmonary bypass, 122 involved deep hypothermic circulatory arrest, 2 involved antegrade cerebral perfusion, and 8 involved "clamp and sew" or left heart bypass. Of the 99 procedures on the descending aorta, 20 involved "clamp and sew," 69 involved left heart or full bypass, and 10 involved deep hypothermic circulatory arrest. A total of 206 cases were elective and 97 were emergency operations. RESULTS: Twenty-three (7.3%) of 317 patients had a stroke. Fifteen strokes occurred in operations on the ascending aorta and 8 in operations on the descending aorta (6.9% vs 8.1%; P =.703). Stroke occurred in 16 (16.5%) of 97 emergency operations and 7 (3.4%) of 206 elective operations (P =.001). In the 300 patients surviving the operation, stroke was a significant predictor of postoperative death (9/23 [39.1%] vs 23/277 [8.3%]; P =.001). Analysis of operative reports, brain images, and neurologic consultations revealed 15 of the 23 strokes were embolic, 3 were ischemic, 3 hemorrhagic, and 2 indeterminate. Patients with stroke had longer intensive care unit stays (18.4 vs 6.8 days; P =.0001), longer times to extubation (12.7 vs 3.8 days; P <.0012), longer postoperative stays (31.4 vs 14.3 days; P =.001), and decreased age-adjusted survival (relative risk 2.775; P =.0013). After implementation of a rigorous antiembolic regimen, both strokes and mortality trended downward. CONCLUSIONS: (1) Stroke complicates surgery of both the ascending and descending thoracic aorta and warrants consideration in decision making. (2) Strokes are largely embolic. (3) Antiembolic measures for particles and air are essential, including gentle aortic manipulation, thorough debridement, transesophageal echocardiography to identify aortic atheromas, carbon dioxide flooding of the field, and (in descending cases) proximal clamp application before initiating femoral perfusion.

Fenestrated Fontan operation with delayed transcatheter closure of atrial septal defect. Improved results in high-risk patients.

Ten patients, each with two or more risk factors for morbidity and death, underwent a fenestrated Fontan procedure in which a 4 to 6 mm circular fenestration was left between the systemic and pulmonary venous chambers. None died; a similar group of high-risk patients without fenestration had a mortality rate of 2 of 8. Patients with fenestration had significantly less drainage from the chest tube, less need for inotropic support, and shorter intensive care and hospital stays than did patients without fenestration. Comparison with a group of low-risk patients undergoing the Fontan operation showed no statistical difference in these postoperative parameters. Fenestrations were closed in all 10 patients at from 9 days to 6 months after operation by means of the transcatheter clamshell occluder device. Two patients had left pulmonary artery balloon angioplasty and three patients had other atrial communications closed with additional clamshell devices. During short-term follow-up periods averaging 18 months, all patients were clinically well; however, one patient with mitral atresia required reoperation for obstruction between the left atrium and the tricuspid valve, not related to the clamshell device. These data indicate that fenestration may be one method of achieving lower morbidity and mortality rates among high-risk patients undergoing the Fontan procedure.

Mechanisms of signal transduction in mouse spermatozoa.

Sperm from all species studied thus far contain G-proteins. The presence of such signal-transducing proteins in these cells suggests that the regulation of sperm function might have control elements that are similar to ligand:receptor:G-protein:second messenger systems common to many somatic cells. This hypothesis is supported by experiments that demonstrate a potential intermediary role for the mouse sperm Gi-like protein in the acrosome reaction induced by ZP3. The specific function of this Gi-like protein in this important physiologic event is not known at this time, although possible roles in regulating ionic movements, cyclic nucleotide metabolism, and polyphosphoinositide turnover are possible candidates. Studies directed at the localization and biochemical identity of the mouse sperm Gi-like protein, as well as the nature of the second messenger system(s) modulated by this protein, are in progress and should help to delineate the sequence of events involved in some of the early steps of sperm-ZP interaction.

Fate of left-sided cardiac bioprosthesis valves in children.

To avoid anticoagulation and minimize thromboembolic phenomena, between 1975 and 1980 we used 18 porcine bioprosthetic valves (BPVs) to replace 11 aortic and seven mitral valves in 17 children ranging from 7 to 18 years of age (mean, 8.2 years). Ten BPVs (91%) in the aortic position had to be replaced one to six years (mean, 4.2 years) after insertion. Nine of these valves developed severe calcification with leaflet immobility and severe stenosis. The tenth valve became insufficient with a disrupted cusp. Six (86%) of seven BPVs inserted in the mitral position required replacement two to four years (mean, 3.1 years) after insertion. Massive mitral regurgitation developed in three, while in the other three mitral stenosis was prominent. All explanted BPVs exhibited calcification with disruption and loss of mobility of the leaflets. Hemodynamic deterioration often occurred catastrophically, with nine patients requiring emergency valve replacement. Elective valve replacement carried no hospital mortality, whereas emergency valve replacement carried a 33% mortality. The BPV failure rate of 94% within six years leads us to recommend against the use of biologic valves in the pediatric age group in the aortic or mitral position. Bioprosthetic valve failure may occur catastrophically and replacement should be carried out early to avoid the higher operative mortality associated with emergency surgery.

Fenestration revisited. A safe and effective procedure for descending aortic dissection.

Although it was initially performed in 1935, aortic fenestration has been infrequently employed and reported in recent years. We have continued to use fenestration for descending aortic dissection with complicating organ ischemia (lower-extremity ischemia, renal ischemia, and paraplegia). Our technique involves complete transection of the infrarenal abdominal aorta, removal of a generous intimal flap proximally, and reconstitution of layers distally. We report our experience with 12 patients, all of whom survived the operative procedure. Nine patients were discharged from the hospital, and with a mean follow-up of 6.8 years, 7 are still alive. Fenestration immediately restored organ perfusion in all but 1 of the patients, and no patient died of late rupture. We recommend fenestration for descending aortic dissection in patients presenting with organ ischemia. Fenestration is not recommended for acute dissection with rupture or for chronic enlarging dissection.

Interval or permanent nonoperative management of acute type A aortic dissection.

HYPOTHESIS: Selected patients with acute type A (ascending) aortic dissection who are treated with delayed operation or nonoperative therapy may have better early and short-term outcomes than was previously expected. DESIGN AND SETTING: Retrospective cohort at a university hospital. SUBJECTS: Data on 75 patients with acute or chronic type A aortic dissection treated at one institution from January 1, 1985, to November 30, 1997, were analyzed. Of these 75 patients, 34 (21 male and 13 female, with a mean age of 65.5 years) did not undergo initial operative treatment, and 15 (10 male and 5 female, with a mean age of 72.6 years) never underwent surgery. For the 19 patients who underwent delayed surgery, the mean period between aortic dissection and intervention was 11.4+/-4.83 days. The follow-up period ranged from 0.27 to 149 months, with a mean of 20.2 months. MAIN OUTCOME MEASURES: Vascular complications, hospital mortality, and early survival. RESULTS: Reasons for interval delay in surgical treatment included initial misdiagnosis or delay in diagnosis (13 [68%] of 19), need to address significant comorbidity (4 [21%] of 19), and initial refusal of operative intervention (2 [11%] of 19). For the 15 patients treated entirely by medical therapy, reasons for electing nonoperative management included extensive comorbidity (5 [33%] of 15), refusal of surgical intervention (6 [40%] of 15), and misdiagnosis or long delay in diagnosis (4 [27%] of 15). Of the 34 patients, 15 (44%) presented with moderate or severe aortic insufficiency, 5 (14%) had evidence of pericardial effusion, 6 (21%) had evidence of concomitant coronary ischemia on electrocardiogram, and 8 (24%) had extension of the dissection into the descending aorta. Four patients (11.8%) died while in the hospital. Of the 34 patients, 30 (88%) who underwent either delayed or no surgery received aggressive medical treatment (beta-adrenergic blocking agents and afterload-reducing agents) and were discharged from the hospital. All patients who were operative candidates in the interval treatment group survived to reach definitive operation. There was no statistically significant difference in short-term survival between the group of patients undergoing delayed surgery or medical treatment only and the group of 41 patients undergoing early operation (P = .42). CONCLUSIONS: Immediate surgical therapy is still recommended for acceptable operative candidates with acute type A aortic dissection who seek immediate treatment. However, this study permits the following 2 conclusions: (1) patients with type A aortic dissection who are referred or whose conditions are diagnosed several days after presentation have survived the early dangerous period and can safely undergo surgery semielectively (rather than emergently); and (2) selected patients who are not considered operative candidates and who survive the initial type A aortic dissection without complication may be treated with aggressive medical therapy and achieve acceptable early and short-term outcomes, which is better than previously expected.

Is cardiopulmonary bypass effective for treatment of hypothermic arrest due to drowning or exposure?

Various techniques have been advocated for resuscitation from hypothermic arrest caused by ice-cold freshwater drowning or exposure. We have resuscitated five such patients after emergency hospital admission using cardiopulmonary bypass initiated via median sternotomy. All patients presented to our facility with core temperatures less than 26 degrees C. Three patients had been in full cardiopulmonary arrest for more than 30 minutes prior to arrival. The fourth patient presented in ventricular fibrillation; the fifth was admitted to the hospital in sinus bradycardia that quickly deteriorated to asystole. All had cardiopulmonary bypass emergently initiated via median sternotomy. All were rewarmed on bypass to 37 degrees C and all survived at least 24 hours. Three of the five patients are currently alive and well with normal neurologic function. Cardiopulmonary bypass is an effective technique for resuscitation after hypothermic arrest due to near drowning and/or exposure.

Familial patterns of thoracic aortic aneurysms.

HYPOTHESIS: To provide evidence that genetic factors contribute to the development of thoracic aortic aneurysms (TAA) by demonstrating familial patterns of the disease. DESIGN: Retrospective review. SETTING: University hospital. PATIENTS AND METHODS: We sought to identify familial patterns of TAA from a database of 598 patients evaluated or treated for TAA at the Yale Center for Thoracic Aortic Disease, New Haven, Conn, from January 1985 to August 1998. Of the 598 patients, 45 patients had a diagnosis of Marfan syndrome and 553 patients had no known history of any collagen vascular disorder. Of the 553 patients in the latter category, 398 patients had confirmed TAA, 66 had TAA with concomitant aortic dissections, and 89 had aortic dissections. From the group of 464 patients with TAA with or without concomitant aortic dissections, 2 interviewers attempted to contact 150 randomly selected patients for telephone screening to determine the presence of familial patterns of aortic disease. Fifteen of these patients were lost to follow-up. Complete medical and family histories of the remaining 135 patients (85 men, 50 women) were reviewed. Of the 135 individuals screened, 26 (18 men, 8 women) (19.3%) were found to belong to multiplex pedigrees. These 26 patients with familial nonsyndromic TAA were compared with the remaining 109 patients with sporadic TAA and the 45 patients with Marfan syndrome-associated TAA. MAIN OUTCOME MEASURES: Groups were examined for statistical differences in age and aortic size at the time of diagnosis, growth rates of TAA, and rates of concomitant diseases. Nonsyndromic family pedigrees were analyzed and potential modes of inheritance were determined. RESULTS: The mean age at presentation for patients with familial nonsyndromic TAA (56.8 years) was significantly younger than the mean age of presentation in sporadic cases (64.3 years, P< or =.03), and significantly older than that of patients with Marfan syndrome (24.8 years, P< or =.001). Patients with a family history of aortic aneurysms had faster growth rates (0.22 cm/y) compared with patients with sporadic TAA (0.03 cm/y) (P< or =.001) and patients with Marfan syndrome (0.10 cm/y) (P< or =.04). Familial nonsyndromic TAA in patients with a concomitant aortic dissection had a growth rate of 0.33 cm/y, which was greater than that of patients with sporadic TAA (0.10 cm/y) and patients with Marfan syndrome (0.08 cm/y) with associated aortic dissection. This growth of 0.33 cm/y was significantly faster than the overall growth rate estimate of aneurysms in patients with aortic dissection (0.14 cm/y) (P< or =.05). Ten pedigrees (38.5%) showed direct father to son transmission, consistent with an autosomal dominant mode of inheritance. Six family pedigrees (23.1%) suggested an autosomal dominant or X-linked mode of inheritance. Seven pedigrees (26.9%) suggested a recessive mode of inheritance; 2 an autosomal recessive mode, and 5 an X-linked recessive or autosomal recessive mode. The remaining 3 pedigrees displayed more complex modes of inheritance. CONCLUSIONS: This study supports the role of genetic factors influencing familial aggregation of TAA. Thoracic aortic aneurysms in association with multiplex pedigrees represent a new risk factor for aneurysm growth. Pedigree analysis suggests genetic heterogeneity. The primary mode of inheritance seems to be autosomal dominant, but X-linked dominant and recessive modes are also evident.

Mechanical circulatory support decreases neurologic complications in the treatment of traumatic injuries of the thoracic aorta.

The surgical treatment of traumatic injuries of the thoracic aorta is controversial because a number of technical approaches have been recommended. Despite the technique employed, spinal cord ischemia continues to be a persistent problem. Nineteen patients with confirmed aortic injuries secondary to blunt trauma were treated at the Yale-New Haven (Conn) Medical Center from 1984 to 1991. The patients were analyzed in two groups: group 1 (n = 10) underwent repair using mechanical circulatory support and group 2 (n = 9) underwent repair without mechanical circulatory support. Sixteen patients survived. Three patients died of complications of multiple trauma. The groups were comparable with respect to aortic cross-clamp time, preoperative systolic blood pressure, and Injury Severity Score. Three patients in the nonmechanical support group developed neurologic complications (P less than .05). No patient in the mechanical support group had a neurologic complication. We believe that mechanical circulatory support reduces the incidence of neurologic complications following traumatic injuries of the thoracic aorta and should be used whenever clinically feasible.

Intraoperative use of nifedipine for hemodynamic collapse due to coronary artery spasm following myocardial revascularization.

Sudden hemodynamic collapse in the perioperative period following myocardial revascularization may be due to coronary artery spasm. Nitroglycerin has been the standard treatment for this; however, it is not always effective, and the resultant morbidity and mortality are high. We present the case of a patient in whom sudden hemodynamic collapse due to coronary artery spasm was refractory to intravenously administered nitroglycerin but was relieved quickly with sublingually administered nifedipine. In certain selected patients in whom coronary artery spasm is responsible for myocardial collapse, the drug nifedipine may be effective in relieving this spasm and allowing for myocardial recovery.