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Biomedical subjects

J M Estes

Publications and source records attributed to J M Estes.

18 recordsLinked to original sources

The Balanced Budget Act: potential implications for the practice of vascular surgery.

PURPOSE: Previous study results have shown a favorable impact on stroke rate with an increasing hospital volume of carotid endarterectomies (CEAs). This is not only the most frequently performed peripheral vascular procedure in the United States but also perhaps the most widely dispersed procedure relative to hospital type. Medical centers have adopted various strategies to lower the cost of hospitalization by reducing the length of stay (LOS), the major component of hospital cost. By 2002, the Balanced Budget Act is projected to reduce Medicare provider payments to academic medical centers (AMCs) by 15.5%, a reduction that is twice that for minor or nonteaching hospitals. We assessed the relationships between hospital costs, CEA volume, and stroke-mortality rates in AMCs and non-AMCs in Massachusetts. METHODS: With patient level data from the Massachusetts Division of Health Care Finance and Policy and with hospital cost and charge reports from the Health Care Financing Administration, HealthShare Technology provided data for all the patients discharged from a Massachusetts hospital who underwent CEA (n = 10,211) during the fiscal years 1995, 1996, and 1997, including cost, LOS, and disposition. The outcomes were further defined with in-hospital stroke and mortality rates. Five high volume AMCs (HVAMCs) were compared with all other nonacademic hospitals, which were further subdivided by annual volume into high volume non-AMCs (> or =50 cases), medium volume non-AMCs (24-49 cases), and low volume non-AMCs (12-23 cases). Statistical analysis was performed with analysis of variance to compare the means of all the cost and LOS data, and chi(2) test was used for comparison of incidence (significance assumed for P < or =. 05). RESULTS: Hospital costs were comparable among the four hospital types during individual years and averaged $6200, but HVAMCs were significantly more expensive overall, with a mean cost of $7882. The only centers to decrease their costs during the years evaluated were the HVAMCs, from $8706 to $6784. Length of stay did not differ among the groups in any year or overall, with a mean of 3.8 days, but did decrease between years at HVAMCs from 3.9 to 2.5 days. The combined stroke-mortality rates were significantly less at the HVAMCs (0.9%) than at either the high volume non-AMCs (1.9%) or the medium volume non-AMCs (2.5%). There was no significance in the analysis results of all the data within the low volume non-AMCs. CONCLUSION: Patients in HVAMCs have the best outcomes after CEA. Despite the achievement of significant efficiencies, AMCs have a small cushion to reduce further either LOS or resources to maintain a competitive cost position and to compensate for the fixed expenses of academic medicine. The Balanced Budget Act raises an equity concern for AMCs because it differentially affects the centers with the best outcomes. The financial implication of this may be a direct incentive for procedures to be done in centers with less optimal outcomes.

Academic Medical Centers↗

Factors predicting prolonged length of stay after carotid endarterectomy.

BACKGROUND: Over the last several years, implementation of critical pathways in patients undergoing carotid endarterectomy has decreased postoperative length of stay significantly. Discharge the day after surgery has become commonplace in many centers, including our own. Unfortunately, managed care may interpret this refinement as a standard of care and limit reimbursement or even disallow admissions extending beyond 1 day. We therefore examined our carotid registry to identify risk factors associated with postoperative length of stay exceeding 1 day. METHODS: We retrospectively reviewed all patients undergoing carotid endarterectomy at our academic center from May 1996 through April 1999. Combined procedures and patients undergoing subsequent noncarotid-related procedures on those admissions were excluded. The charts were inspected for atherosclerosis risk factors, including sex and age, specific attending surgeon, side of the surgery, use of intravenous vasoactive drugs, actual preoperative blood pressure, and presence of neurologic symptoms or postoperative complications. Multiple regression analysis was performed on all collected variables. Statistical significance was inferred for P less than.05. RESULTS: A total of 188 patients met the study criteria and had complete, retrievable medical records. A mean postoperative length of stay of 1.65 +/- 0.08 days and a mean total length of stay of 2.17 +/- 0.14 days were observed. Fifty-seven percent of patients went home the day after surgery. There was a 1.6% stroke-mortality rate. Significant predictors of a prolonged stay, listed in order of decreasing importance on the basis of their calculated contribution to prolonging the postoperative length of stay, are as follows (P value; beta coefficient): postoperative complications (<.0001; 1.03), age > 79 years (.008; 0.547), diabetes mellitus (.011; 0.407), female sex (.007; 0.398), and intravenous vasodilator requirement (. 035; 0.382). Other atherosclerosis risk factors, prior neurologic symptoms, the postoperative use of vasopressors, and reoperative surgery did not contribute to extended length of stay. CONCLUSIONS: Discharge on the first postoperative day is feasible in many, but not all, patients undergoing carotid endarterectomy. Our data help define subsets of patients at risk for prolonged postoperative stay. Targeting these subsets for preoperative medical and social interventions may allow safe early discharge more frequently.

Aged↗

Relative distribution and crosslinking of collagen distinguish fetal from adult sheep wound repair.

BACKGROUND/PURPOSE: Collagen deposition in midgestation fetal skin wounds occurs rapidly and in a normal reticular pattern unlike adult scar. Although collagen types I, III, and V are present in both fetal and adult skin wounds, their relative distribution and pattern of crosslinking are unknown. We compared the quantity, distribution, and crosslinking of specific collagen types in fetal and adult sheep wounds. METHODS: Nine fetal lambs at 75, 100, and 120 days' gestation (term, 145 days) and their ewes received subcutaneous polyvinylalcohol (PVA) sponge implants. PVA sponges were harvested at 3, 7, or 14 days after implantation, were processed, and then analyzed for collagen content, distribution, and crosslinking by two-dimensional cyanogenbromide (2-D CNBr) peptide mapping. Collagen types were further analyzed in normal skin of fetal sheep at 75, 90, 125, and 140 days' gestation and in their ewes. RESULTS: Between days 3 and 14 after implantation, total collagen deposition within PVA sponges increased 25-fold in fetal lambs but only 10-fold in adult sheep. The type I to III ratios inside 14-day sponges of 75-day gestation fetuses and adult ewes were 6.4 and 1.3, respectively. Thus, by day 14 in both fetal and adult sponges, type I collagen emerged as the major constituent. Although type V comprised less than 2% of normal skin collagen, alpha1(V) chains constituted the greatest collagen fraction in 3-day fetal implants, whereas within 3-day adult sponges only alpha2(V) collagen was detected. The total collagen content of unwounded fetal sheep skin increased twofold from 75 to 90 days' gestation. However, noncrosslinked forms of collagen type I diminished rapidly after 90 days' gestation, corresponding with the transition to scarring of fetal sheep wounds. CONCLUSIONS: Collagen types I, III, and V are deposited rapidly in fetal wounds and display an ontogenic transition in their metabolism from a fetal to an adult phenotype. Crosslinking of type I collagen increases during development and corresponds with the transition to scarring of fetal wounds after midgestation. These observations may help design strategies that induce a more fetallike repair of adult wounds.

Animals↗

The impact of cardiac comorbidity after carotid endarterectomy.

PURPOSE: Myocardial infarction and other comorbidities contribute to complications after carotid endarterectomy (CEA). However, because the combined stroke and death rate after CEA is less than 5%, even relatively large series have small numbers of adverse events that preclude a detailed analysis of the association between the outcome and the patient factors, such as comorbidity and age. We sought to overcome this limitation by studying patients who underwent CEA in a large random sample of Medicare beneficiaries. METHODS: We used a database that contained a 20% random sample of all Medicare beneficiaries to identify patients who underwent CEA between the years 1988 to 1990 (n = 22,165), and we followed these cases until 1992. With multivariate logistic regression and Cox proportional hazards regression models, we examined the impact of age, race, gender, geographic location, hospital characteristics, and comorbidity, including acute myocardial infarction (AMI) and congestive heart failure (CHF), on the risk of stroke and death after CEA. RESULTS: AMI and CHF had the greatest negative impact on the long-term survival rates (adjusted hazard ratio [HR]: 2.40, P < .0001, and 2.85, P < .0001, respectively). Other variables with a significant impact on the long-term survival rates were an age of >80 years (HR, 2.16; P < .0001), an acute stroke (HR, 1.51; P < .0001), diabetes mellitus (DM; HR, 1.52; P < .0001), and male sex (HR, 1.32; P < .0001). In addition, AMI, CHF, DM, and advanced age were associated with an increased risk of perioperative stroke and death. CONCLUSION: Patients with AMI, CHF, DM, and an age of >80 years have diminished perioperative and long-term survival rates after CEA. These results may alter the risk/benefit analysis for such patients, especially those with asymptomatic disease.

Age Factors↗

Noninvasive characterization of plaque morphology using helical computed tomography.

BACKGROUND: Evidence suggests that atherosclerotic plaque composition and morphology are more important predictors of plaque stability and clinical behavior than the degree of vessel stenosis. Unfortunately, noninvasive methods of plaque characterization in situ using duplex ultrasound have been largely unsuccessful. We investigated the accuracy of helical computed tomography (HCT) in defining plaque morphology in patients undergoing carotid endarterectomy. METHODS: Candidates for endarterectomy were enrolled prospectively and underwent HCT with intravenous contrast injection. The attenuation values (in Hounsfield Units) of plaque features such as calcium, fibrous tissue, and lipid were measured and correlated with the tissue types seen on microscopic examination. Percent luminal stenosis derived from transverse HCT images was also compared to values obtained from duplex ultrasound. SETTING: Ambulatory patients referred to a tertiary, metropolitan medical center. RESULTS: A total of 21 out of 22 cases were suitable for comparison. Qualitatively, HCT accurately defined plaque features containing calcium, fibrous stroma, and lipid. Using tissue attenuation values (Hounsfield Units - H), HCT distinguished between lipid and fibrous stroma (means 39+/-12 H and 90+/-24 H, respectively, p<0.001). HCT-derived calculations of percent stenosis also correlated with the ultrasound data (p<0.001). CONCLUSIONS: HCT is an accurate, noninvasive means for studying detailed plaque morphology and composition. This technique provides the basis for further studies correlating plaque anatomy with clinical behavior.

Aged↗

A prospective study of the outcome for fetuses with diaphragmatic hernia.

OBJECTIVE: To establish the natural history and outcome of isolated congenital diaphragmatic hernia (CDH) diagnosed before birth. The mortality of CDH with currently available postnatal care, including extracorporeal membrane oxygenation (ECMO), reported in retrospective studies ranges from less than 25% to greater than 75%. This variation is attributable to a "hidden mortality" (infants who die with CDH that is not recognized) of unknown magnitude. DESIGN: Prospectively followed case series. SETTING: Patients were referred from practitioners in 18 states and evaluated and followed up by the University of California, San Francisco, Fetal Treatment Center. Arrangements were made for planned delivery at tertiary perinatal centers with ECMO capability. PATIENTS: All 83 fetuses with isolated, potentially correctable CDH diagnosed prior to 24 weeks' gestation referred to the University of California, San Francisco, Fetal Treatment Center between January 1989 and October 1993. MAIN OUTCOME MEASURES: Survival beyond 2 months after optimal postnatal care. RESULTS: Fifty-eight percent (48 of 83) died despite optimal postnatal care (95% confidence interval, 41% to 75%). Of the 48 nonsurvivors, seven suffered intrauterine fetal demise, four were too premature for ECMO, 16 died before ECMO could be started, and 21 died despite ECMO therapy. Twenty-two of the 35 survivors received ECMO, and nine of these have severe chronic illness attributable to the intensive management. CONCLUSIONS: In this study, the mortality for potentially correctable CDH diagnosed before 24 weeks' gestation is 58%, despite optimal care presently available after birth. Infants who die in utero and soon after birth constitute a substantial hidden mortality.

Extracorporeal Membrane Oxygenation↗

Plug the lung until it grows (PLUG): a new method to treat congenital diaphragmatic hernia in utero.

Fetal lungs normally produce fluid that flows through the upper airway into the amniotic fluid. In fetuses with congenital diaphragmatic hernia (CDH), obstructing the flow of lung fluid may expand the lungs and propel the viscera from the chest, alleviating the pulmonary hypoplasia associated with CDH. To test this hypothesis, left-sided diaphragmatic hernias were created in sixteen 75-day-gestation fetal lambs (full-term, 145 days). At 120 days, the trachea was ligated in eight lambs; it was left unligated in the other eight. At 135 to 140 days, the fetuses were delivered, and a tracheostomy performed. Newborns were ventilated for 1 hour and then killed. Blood gas analysis was performed at 0,5,20,40, and 60 minutes. Lung dry weight, DNA, protein, and lipid analyses, as well as plasma cortisol measurements were performed. At autopsy, in the ligated lambs, the abdominal viscera was reduced from the thorax; however, the unligated lambs had viscera completely occupying the left chest. The lungs of the ligated lambs had a higher dry weight (4.22 +/- 1.37 g/kg v 1.95 +/- 0.59 g/kg; P =.001), DNA (193.8 +/- 90.5 mg/kg v 91.5 +/- 66.4 mg/kg; P = .02), and protein (1798 +/- 691.6 mg/kg v 766.6 +/- 201 mg/kg; P = .004). Lung saturated phosphatidyl choline (SPC) levels, DNA:protein ratio, and plasma cortisol were not different between the groups. Neonatal Po2 at 60 minutes was higher in the ligated group (179.4 +/- 127.0 mm Hg v 60.9 +/- 62.4 mm Hg; P < .05), and Pco2 was lower (44.1 +/- 21.4 v 83.9 +/- 23.5; P < .05) in the ligated group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Congenital cystic adenomatoid malformation: a sheep model of fetal hydrops.

Congenital cystic adenomatoid malformation (CCAM) can be diagnosed in utero. Nonimmune hydrops associated with CCAM is a predictor of fetal demise. Fetuses with prenatally diagnosed large CCAM tumors and hydrops have undergone successful in utero resection. An animal model is needed to understand the pathophysiology of CCAM and hydrops. To create a model of CCAM and hydrops, the authors implanted an intrathoracic tissue expander in six fetal sheep at 120 days' gestation. The inflatable tissue expander was implanted in the right side of the chest, and arterial, venous, intrathoracic, and intraamniotic pressure catheters were placed. Each day, the expander was inflated with 25 to 50 mL of saline (maximum, 150 mL), ultrasound examination was performed, and all pressure measurements were taken. In all six fetuses, hydrops developed after expander inflation. Expander inflation correlated with an increase in central venous pressure (CVP) (4 +/- 2 mm Hg v 16 +/- 2 mm Hg [mean +/- SD]; P < .05). To simulate in utero CCAM resection, the expander was deflated in four hydropic sheep, resulting in return of the CVP to near baseline and resolution of hydrops. Silicone vascular casts of two postmortem sheep demonstrated lateral displacement and compression of the vena cavae by the expander. The authors successfully created a model of CCAM and hydrops by inflating an intrathoracic tissue expander in fetal sheep. Based on this model, hydrops associated with CCAM results from obstruction of cardiac venous return and central venous hypertension. This pathophysiology is reversed by expander deflation, which simulates in utero CCAM resection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Phenotypic and functional features of myofibroblasts in sheep fetal wounds.

The myofibroblast is a mesenchymal cell with functional and structural characteristics in common with fibroblasts and smooth muscle cells. These cells play a critical role in wound closure and in the pathologic sequelae of healing. It has been shown in adult humans and experimental animals that the myofibroblast expresses alpha -smooth muscle actin (ASMA) temporarily during wound contraction and more persistently during fibrocontractive diseases; however, it is unclear whether this cell makes any contribution to tissue repair in utero. Experimental work in fetal animal models has demonstrated that wound repair in fetal skin occurs by reconstitution of epidermal appendages and organized restoration of the dermal collagen network. Fetal lamb wound healing studies have shown that a transition from scarless tissue repair to healing with scar formation occurs late in gestation. In this study we examined the ontogeny of myofibroblasts in fetal lamb wounds at early through late gestation, using transmission electron microscopy (TEM) and ASMA immunohistochemistry. Dramatic differences were observed in ASMA content of early as compared to late gestation fetal wound granulation tissue: ASMA was absent in wounds made at 75 days gestation but was present in progressively greater amounts in wounds made at 100 and 120 days gestation (term = 145 days). TEM studies also demonstrated progressive development and organization of microfilament bundles. Early in development microfilament bundles were sparse and disorganized, but as gestation progressed the bundles became more prevalent and formed tightly parallel arrangements. The organization of microfilament bundles was also accompanied by fibronexus formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗

Hyaluronate metabolism undergoes an ontogenic transition during fetal development: implications for scar-free wound healing.

Wound healing in the fetus occurs by a different process from that in the adult. Instead of healing with scar formation, fetal cutaneous wounds heal by regeneration that results in complete restoration of normal skin architecture. The mechanisms responsible for this remarkable phenomenon involve factors in the fetal environment and properties intrinsic to fetal cells. Hyaluronic acid (HA) is a major component of the fetal extracellular matrix (ECM) and is believed to play an important role in this process. In this study, HA and HA-stimulating activity (HASA) in fetal and adult wound fluid were examined using sensitive, newly developed assays. In an ovine model, higher levels of HA and HASA were observed in fetal as compared with adult wound fluid. This difference was most prominent in wound fluid from fetal lambs at 75 and 100 days gestation (term = 145 days); these samples contained persistently elevated HA and HASA levels for up to 2 weeks after wounding (HA peak levels 145 micrograms/mL and 110 micrograms/mL, respectively). In contrast, wound fluid from 120-day-gestation fetuses had significantly lower levels (P < .001) that were transient and similar to that in the adult (HA peak levels 70 micrograms/mL and 10 micrograms/mL, respectively). These observations confirm an ontogenic transition in wound HA metabolism from a fetal to an adult-like phenotype. Levels of HASA as a function of time after wounding correlated with levels of HA, suggesting a role for HASA in controlling HA deposition during tissue repair. Two patterns of HASA and HA synthesis were noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Correction of congenital diaphragmatic hernia in utero: VI. Hard-earned lessons.

Extensive experimental work suggests that repair of congenital diaphragmatic hernia (CDH) in utero may salvage severely affected fetuses who otherwise have a high expected mortality despite optimal postnatal care including extracorporeal membrane oxygenation (ECMO). We have reported that repair of CDH in utero is physiologically sound and safe for the mother, but technically difficult especially when the liver is herniated into the fetal chest. In the 3 years since our last report (1989 to 1991), 61 additional patients were referred for consideration of in utero repair. Fetal repair was attempted in 14 with severe isolated left CDH diagnosed before 24 weeks gestation. Five fetuses died intraoperatively, from technical problems related to reduction of incarcerated liver and uterine contractions--problems which have subsequently been surmounted. Nine patients were successfully repaired. Four babies survived, two delivered prematurely and died, and three died in utero within 48 hours of repair. Intraoperative technical problems have been overcome; the factors limiting successful outcome are postoperative physiologic management of the maternal-fetal unit and effective tocolysis to control preterm labor.

Fetal Death↗

Fetal obstructive uropathy.

Congenital obstructive uropathy is a relatively common developmental malformation, and severely affected fetuses die soon after birth from oligohydramnios-induced pulmonary hypoplasia or renal failure. Prenatal ultrasonography can reliably diagnose the specific anatomic defect, and using fetal urine sampling we can determine the extent of renal damage in utero with reasonable certainty. With these diagnostic tools and an understanding of the natural history of congenital obstructive uropathy we can now make rational decisions regarding treatment. Clinical experience has demonstrated that the selected fetus may benefit from in utero decompression, either by percutaneous shunt placement or open fetal surgery. However, each of these procedures has certain risks that must be carefully weighed against the expected benefits. Future techniques using fetoscopic surgery may provide the ideal therapeutic approach.

Animals↗

New techniques in fetal surgery.

Optimal fetal management during and after fetal surgery has been limited by an inability to reliably monitor the fetal heart rate and temperature, and by a lack of access to the fetal circulation. In order to solve these problems, we used early third trimester fetal sheep to develop: (1) an implantable radiotelemetry device that transmits the fetal electrocardiogram and temperature, and (2) an intraosseous access technique. A miniaturized radiotelemeter was implanted subcutaneously in the axilla of four fetal sheep. Safe implantation of the radiotelemeter was technically feasible and the device reliably recorded the fetal electrocardiogram and temperature both intraoperatively and postoperatively. Although many possible routes for access to the fetal circulation have been tried experimentally and clinically for both resuscitation and blood sampling, none have proven satisfactory. We assessed the use of intraosseous access in fetal sheep (n = 6) for both infusion and blood sampling. Access with an intraosseous needle was obtained in both sheep fetuses and human fetal cadavers. Blood gas values (pH, PCO2, and PO2) obtained from the medullary cavity of fetal sheep accurately reflected peripheral venous values. Resuscitation drugs reached the fetal circulation via the intraosseous route: sodium bicarbonate elevated venous bicarbonate levels from 28.4 +/- 1.7 to 31.8 +/- 2.1 mEq/dL (P < .05); injected glucose increased venous glucose levels by 520 +/- 108 mg/dL (P < .01); and injection of calcium chloride elevated venous calcium levels from 11.8 +/- 0.7 to 15.2 +/- 2.2 mEq/dL (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Fetoscopic surgery for the treatment of congenital anomalies.

Fetoscopic techniques may broaden the indications for prenatal surgical intervention by obviating the risks of hysterotomy. For example, congenital obstructive uropathy has been treated by open vesicostomy and percutaneous catheter placement. The open approach is appropriate only for highly selected fetuses because of the inherent risks, whereas catheter drainage, though a safer procedure, is only useful for short-term therapy late in gestation due to frequent catheter obstruction and migration. The natural history of congenital obstructive uropathy mandates the need for improved therapy earlier in gestation, in order to salvage fetuses who would otherwise die of renal failure and pulmonary hypoplasia. We have developed a potential solution to this problem in which surgery is performed on the fetus without the risks of hysterotomy. Endoscopic fetal surgery uses a telescopic lens and operating instruments that are passed through small "ports" in the uterus. A bubble of CO2 is used to displace amniotic fluid and provides excellent visualization in a magnified field. This approach is considerably less invasive than open fetal surgery and, therefore, is less likely to provoke preterm labor. In this study we corrected obstructive uropathy in midgestation fetal lambs using a new, expandable wire mesh stent that is placed endoscopically and should provide more reliable bladder drainage than existing catheters. The fetoscopic surgical approach can potentially expand the indications for in utero surgery by decreasing fetal risks, facilitating intervention earlier in gestation, and reducing preterm labor. As a consequence, the potential now exists to correct non-life-threatening malformations in utero.

Animals↗

Endoscopic creation and repair of fetal cleft lip.

In utero repair of several life-threatening malformations in the human fetus is now a clinical reality, yet fetal surgery still poses significant risks to both the mother and the unborn child. Preterm labor is a major problem and is directly related to the large hysterotomy required for fetal exposure. Endoscopic surgical manipulation of the fetus, through small uterine "ports," solves this problem and may eventually permit fetal intervention for non-life-threatening malformations. In this pilot study we demonstrated the feasibility of performing endoscopic surgery on the fetus in situ. A lip incision was created and repaired using endoscopic microsurgical techniques in midgestation fetal lambs. This represents the first application of this technique for in utero fetal intervention.

Animals↗

Techniques for in utero endoscopic surgery. A new approach for fetal intervention.

In utero open surgery can salvage many fetuses with life-threatening anomalies. This approach carries risks, especially from preterm labor induced by the hysterotomy incision. In an effort to decrease uterine injury during hysterotomy, we developed techniques for endoscopic manipulation of the fetus. We developed these methods in fetal lambs. The uterus was exposed and insufflated with CO2. As a model for in utero surgery, a simulated cleft lip was created and immediately repaired using intracorporeal suturing and knot-tying procedures. The techniques for endoscopic suture placement and knot-tying were based on microsurgical principles. We also designed and created several specialized instruments to facilitate precise work in this highly magnified surgical field. The novel techniques of endoscopic fetal surgery described here offer an alternate approach to fetal intervention. Our future goals include the application of these techniques to a nonhuman primate model and the development of percutaneous access methods.

Animals↗