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Biomedical subjects

D P Bichell

Publications and source records attributed to D P Bichell.

18 recordsLinked to original sources
PubMed2001

Minimal sternotomy approach for congenital heart operations.

BACKGROUND: In recent years, minimal access cardiac operations have increased in application in both the adult and pediatric population. As our experience has grown with these approaches to atrial septal defect closure, we have expanded the same approach to the repair of more complex congenital heart disease. METHODS: At the Children's Hospital in Boston, from August 1996 to November 1999, a minimal sternotomy approach was used to surgically correct 104 children with congenital heart defects other than atrial septal defect. The approach, in most patients, consisted of a skin incision based over the xiphisternum, 3.5 to 5 cm in length, with division of the xiphoid only and elevation of the sternum by fixed retractor. All patients underwent cannulation for cardiopulmonary bypass through the great vessels in the chest using this same incision. The lesions corrected included ventricular septal defect in 41 patients, tetralogy of Fallot in 27, common atrioventricular canal in 15, mitral valve operation in 3.5, and other defects in 18 patients. There were 53 male and 51 female patients. Mean age at operation was 1.4 years (range, 2 weeks to 11 years). RESULTS: There were no deaths. The mean cardiopulmonary bypass time was 71 minutes (standard deviation, 19 minutes), mean cross-clamp times 40.8 minutes (standard deviation, 13 minutes), and length of stay 4.5 days (standard deviation, 1.9 days). Complications included transient atrioventricular block in 2 patients, pleural effusion requiring drainage in 4, and pericardial effusion in 3 patients. When compared to similar lesions repaired using a full sternotomy approach there was no difference in operating times and length of stay tended to be shorter in the minimal sternotomy group. CONCLUSIONS: A minimal sternotomy approach can be used to repair congenital cardiac lesions other than atrial septal defects. It gives good exposure, particularly for transatrial repairs, does not prolong ischemic times, and may lead to shorter hospital stay.

Child↗
PubMed2000

Minimal access approach for the repair of atrial septal defect: the initial 135 patients.

BACKGROUND: From May 1996 to August 1998 a minimal access approach was used for 135 of 200 consecutive surgical atrial septal defects closures in children through young adults ranging in age from 6 months to 25 years (median 5 years). METHODS: A 3.5- to 5-cm midline incision was centered over the xiphoid with division of the xiphoid alone (transxiphoid) or of the lower sternum (ministernotomy); both groups underwent bicaval venous cannulation through the incision. Cardioplegia and aortic cross-clamping were administered through the incision. Cephalad retraction of the sternum with a fixed-arm retractor aided exposure. RESULTS: There have been no early or late deaths and no bleeding or wound complications. No procedure required conversion to a full sternotomy, and no cannulation attempt was abandoned for an alternate site. Cross-clamp and cardiopulmonary bypass times were equivalent to those in the full sternotomy group. The mean length of hospital stay in the ministernotomy group was 2.7 days. CONCLUSIONS: The closure of atrial septal defects can be performed through a transxiphoid or ministernotomy approach, conferring a satisfactory cosmetic result without compromising the safety or accuracy of the repair.

Adolescent↗
PubMed2000

Postoperative recovery in children after minimum versus full-length sternotomy.

BACKGROUND: Minimal access incisions for pediatric cardiac surgery have been reported to hasten postoperative recovery. This prospective study compared recovery after a minimum versus full-length sternotomy for repair of atrial septal defects in children. METHODS: We studied 35 children undergoing atrial septal defect repair using a full-length sternotomy (n = 18) or ministernotomy (n = 17) according to the surgeon's preference. All children were managed according to an established clinical practice guideline. Intraoperative comparisons included patient demographics, bypass and cross-clamp times, and, as a measure of stress response, epinephrine, norepinephrine, and lactate levels at six time intervals throughout the surgical procedure. Postoperative comparisons included pain scores at 6, 12, and 24 hours, frequency of emesis, analgesic requirements, respiratory rate and gas exchange, and length of intensive care unit and total hospital stay. Nurse and parent assessment scores of overall recovery were constructed using visual analog and Likert scales. RESULTS: No significant differences between mini- versus full-length sternotomy were detected for the measured outcome variables. No adverse outcomes were detected. CONCLUSIONS: In this prospective study, a ministernotomy did not enhance postoperative recovery, and the primary advantage appears to be an improved cosmetic result.

Adolescent↗
PubMed1999

Developmental outcome after surgical versus interventional closure of secundum atrial septal defect in children.

BACKGROUND: The assessment of the impact of cardiopulmonary bypass (CPB) on developmental outcomes in children who undergo open heart surgery is hampered by the absence of a suitable comparison group. The development of interventional catheterization techniques for the repair of certain types of congenital heart lesions provides the opportunity to study children who have not been exposed to CPB. METHODS AND RESULTS: We performed standardized neuropsychological testing on children after closure of a secundum atrial septal defect through the use of surgery (n=26) or a transcatheter device (n=19). Device patients, compared with surgical patients, were similar in age at defect closure (mean, 6 years) but older at follow-up testing (12.3 versus 10.6 years). The mean weight percentile at closure was greater and the defect size was smaller in the device patients. Families of device patients tended to have a higher parent IQ, higher level of maternal education, and higher level of maternal occupation. In general, however, children's IQ and achievement scores were in the normal range for both groups. In regression analyses with adjustment for age at testing and parent IQ, surgical repair was associated with a 9.5-point deficit in Full-Scale IQ (P=0. 03) and a 9.7-point deficit in Performance IQ (P=0.05). Block Design was the IQ subtest on which treatment groups differed the most (P=0. 01). Surgical patients achieved significantly better scores on errors of commission (P=0.05) and attentiveness index (P=0.03) on a continuous performance test of attention. Scores on tests of achievement and other neuropsychological domains did not differ significantly between the groups. Regression analyses within the surgical group failed to identify significant CPB-related risk factors. CONCLUSIONS: A prospective randomized trial or a study that includes prerepair and postrepair assessments is necessary to establish whether the observed advantages of device closure in neuropsychological outcome represent deleterious effects of CPB or a methodological artifact.

Cardiac Catheterization↗
PubMed1999

Evaluation and management of pulmonary atresia with intact ventricular septum.

Pulmonary atresia with intact ventricular septum (PA/IVS) is a spectrum of diseases with varying severity of right ventricle hypoplasia and potential for biventricular, univentricular, or hybrid repairs. Pessimistic outcome measures for PA/IVS may give way to optimism with the refinement of early diagnosis and early intervention to encourage right ventricle flow and optimize growth. To this end, PA/IVS has become a focus of innovative interventions (e.g., fetal surgery) and new catheter-based and surgical techniques.

Child, Preschool↗
PubMed1997

Axilloaxillary cardiopulmonary bypass: a practical alternative to femorofemoral bypass.

BACKGROUND: Peripheral arterial and venous cannulation for cardiopulmonary bypass is used increasingly for patients undergoing minimally invasive cardiac operations, complex reoperations, or repair of aortic dissection or aneurysm, and for patients with extensive arteriosclerotic aortic disease in whom aortic cannulation is a prohibitive embolic risk. The common femoral artery and vein are most commonly used for peripheral cannulation, but these sites may be predisposed to complications, primarily because the femoral vessels are commonly involved with arteriosclerotic disease. We have recently begun to use the axillary artery and axillary vein as alternative cannulation sites, achieving full cardiopulmonary bypass, providing antegrade aortic flow, and avoiding many of the complications associated with other sites. METHODS: Seven patients with peripheral vascular or aortic disease, or both, prohibiting safe aortic or femoral cannulation underwent cardiopulmonary bypass through axillary artery and axillary vein cannulation, approached through a small single subclavicular incision. RESULTS: All patients were successfully cannulated and axilloaxillary cardiopulmonary bypass was possible without the need for additional cannulas. All axillary vessels were closed primarily without complication. CONCLUSION: For an expanding population of patients with peripheral vascular and aortic disease, axilloaxillary bypass is a safe and practical alternative to aortic or femoral cannulation.

Aged↗
PubMed1997

Minimally invasive cardiac valve surgery improves patient satisfaction while reducing costs of cardiac valve replacement and repair.

OBJECTIVE: This study compares the quality of valve replacement and repair performed through minimally invasive incisions as compared to the standard operation for aortic and mitral valve replacement. SUMMARY BACKGROUND DATA: With the advent of minimally invasive laparoscopic approaches to orthopedic surgery, urology, general surgery, and thoracic surgery, it now is apparent that standard cardiac valve operations can be performed through very small incisions with similar approaches. METHODS: Eighty-four patients underwent minimally invasive aortic (n = 41) and minimally invasive mitral valve repair and replacement (n = 43) between July 1996 and April 1997. Demographics, procedures, operative techniques, and postoperative morbidity and mortality were calculated, and a subset of the first 50 patients was compared to a 50-patient cohort who underwent the same operation through a conventional median sternotomy. Demographics, postoperative morbidity and mortality, patient satisfaction, and charges were compared. RESULTS: Of the 84 patients, there were 2 operative mortalities both in class IV aortic patients from multisystem organ failure. There was no operative mortality in the patients undergoing mitral valve replacement or repair. The operations were carried out with the same accuracy and attention to detail as with the conventional operation. There was minimal postoperative bleeding, cerebral vascular accidents, or other major morbidity. Groin cannulation complications primarily were related to atherosclerotic femoral arteries. A comparison of the minimally invasive to the conventional group, although operative time and ischemia time was higher in minimally invasive group, the requirement for erythrocytes was significantly less, patient satisfaction was significantly greater, and charges were approximately 20% less than those in the conventional group. CONCLUSIONS: Minimally invasive aortic and mitral valve surgery in patients without coronary disease can be done safely and accurately through small incisions. Patient satisfaction is up, return to normality is higher, and requirement for postrehabilitation services is less. In addition, the charges are approximately 20% less. These results serve as a paradigm for the future in terms of valve surgery in the managed care environment.

Adult↗
PubMed1997

Minimally invasive aortic valve replacement.

Aortic valve replacement has proven reliable, relieves life-threatening symptoms, and improves long-term survival of patients with aortic stenosis and aortic regurgitation. Minimally invasive aortic valve replacement uses small incisions; reduces exposure of the patient to surgical trauma, blood utilization, and operative dissection; although still using cardiopulmonary bypass and achieving the same general quality as with the open operation. Early and medium term results for minimally invasive aortic valve replacement approaches show a reduction in pain, improved patient satisfaction, and improved mobility and return to full-time activity. Concomitantly, there should be decreased cost and a decreased reliance on post-hospital rehabilitation.

Adult↗
PubMed1996

Thigh ischemia complicating femoral vessel cannulation for cardiopulmonary bypass.

Compartment syndrome of the lower leg is an occasional complication of prolonged ischemia and reperfusion. Compartment syndrome of the thigh is a less well-recognized complication. We present 2 patients with compartment syndrome of the ipsilateral thigh after femoral arterial and venous cannulation for cardiopulmonary bypass. Early diagnosis and urgent decompressive fasciotomy may limit the extent of local tissue damage and subsequent myonephropathic syndrome.

Aged↗
PubMed1995

Repair of mitral regurgitation from myxomatous degeneration in the patient with a severely calcified posterior annulus.

Severe posterior annular calcification poses a particular challenge to mitral valve repair. In a series of 252 mitral valve repairs for myxomatous degeneration performed between 1980 and 1993, 14 patients had a severely calcified posterior mitral valve annulus. Ages ranged from 61 to 81 years. Twelve patients were preoperative NYHA Class III or IV, and five patients required concurrent coronary artery bypass procedures. Operative techniques included complete resection of the calcified posterior annulus, resections of portions of the posterior leaflet with leaflet advancement, and placement of an annuloplasty ring. There were no operative deaths and all patients had a postoperative echocardiographic confirmation of relief from mitral regurgitation. During a mean follow-up time of 36 months (6 months to 8 years), there has been one late valve reoperation and only one late death, from thromboembolism in a patient with atrial fibrillation. These data indicate that even in the presence of severe calcification of the posterior mitral annulus, mitral valve repair for myxomatous degeneration can be performed with a low-operative risk and satisfactory long-term results.

Aged↗
PubMed1995

Characterization of deoxyribonucleic acid-protein interactions at a growth hormone-inducible nuclease hypersensitive site in the rat insulin-like growth factor-I gene.

Many of the growth-promoting effects of GH are mediated by insulin-like growth factor-I (IGF-I), a highly conserved, 70-residue basic peptide. Previous studies have demonstrated that GH rapidly stimulates IGF-I expression in vivo, and our laboratory has identified a GH-regulated alteration in chromatin configuration, manifested as a hormonally induced deoxyribonuclease-I (DNase-I)-hypersensitive site in the second IGF-I intron. In the current study, we have used in vivo DNase-I footprinting to map this hormonally responsive chromatin domain to an approximately 350-nucleotide region and have identified DNA-protein interactions within the hypersensitive site by in vitro gel mobility shift experiments and DNase-I footprinting studies. DNA-protein binding was localized to two adjacent segments of 32 and 48 nucleotides. In 1 of these regions, protein-DNA contacts were also detected in vivo on guanine residues by dimethylsulfate footprinting. DNA-binding activity was present in GH-deficient rats, but was not modified by hormone treatment. Our results define a rapid and reversible genomic alteration in response to GH in a GH-regulated gene and delineate a target within chromatin for GH action.

Animals↗
PubMed1994

Rapid activation of rat insulin-like growth factor-I gene transcription by growth hormone reveals no alterations in deoxyribonucleic acid-protein interactions within the major promoter.

Insulin-like growth factor-I (IGF-I) is an important mediator of prenatal and postnatal growth, but little is known about the control of IGF-I gene expression. Previously, we demonstrated that GH rapidly stimulates hepatic IGF-I transcription in vivo in hypophysectomized (hypox) rats. In this study, we show that GH induces IGF-I gene transcription through the major promoter, promoter 1, and identify and characterize DNA-protein interactions throughout the promoter. In vitro deoxyribonuclease-I footprinting was used to analyze 1711 nucleotides of promoter 1 and the entire 328-nucleotide 5'-untranslated region of exon 1, using hepatic nuclear protein extracts from male juvenile hypox rats given a single ip injection of GH or saline 60 min before death. Fourteen DNA-protein binding sites were identified, with 6 located in the highly conserved 5'-untranslated region of exon 1. These latter sites were further characterized for specificity and regulation by GH, using gel mobility shift assays. Two of these DNA-protein interactions were also detected by in vivo dimethylsulfate footprinting. All DNA-protein binding was seen using hepatic nuclear protein extracts from hypox rats and did not change within 15, 30, 60, or 120 min after treatment with GH. Our results thus define a series of constitutive DNA-protein interactions within the major rat IGF-I gene promoter that may be involved in mediating GH-activated nuclear signals to initiate IGF-I transcription.

Amino Acid Sequence↗
PubMed1993

Multifactorial regulation of IGF-I gene expression.

Insulin-like growth factor-I (IGF-I) is a highly conserved 70-residue circulating peptide with diverse biological effects. In mammals IGF-I is an essential mediator of normal postnatal growth and its expression is influenced by hormonal, nutritional, tissue-specific, and developmental factors. Recent studies have demonstrated that the IGF-I gene is more complicated than might have been predicted from its simple protein sequence. In rats and in humans the single-copy six-exon gene is transcribed by adjacent promoters into nascent RNAs with different 5' leader sequences that undergo both alternative RNA splicing and differential polyadenylation to yield multiple mature transcripts. These observations suggest that trophic agents may modulate expression of IGF-I at any of several nodal points. In this report we review several of the mechanisms responsible for regulating production of IGF-I in the rat. During neonatal development IGF-I gene transcription is progressively activated, leading to a rise in both hepatic IGF-I mRNA and in serum IGF-I. The induction of IGF-I expression is limited to mRNAs directed by promoter 1, the more 5' of two rat IGF-I gene promoters, and precedes the ontogenic appearance of liver growth hormone (GH) receptors, indicating that mechanisms independent of GH activate IGF-I expression during early postnatal life. By contrast, in adult GH-deficient rats, a single intraperitoneal injection of GH causes a prompt rise in IGF-I gene transcription that is mediated equivalently by promoters 1 and 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1993

Prostaglandin E2 rapidly stimulates insulin-like growth factor-I gene expression in primary rat osteoblast cultures: evidence for transcriptional control.

Osteoblast-enriched (Ob) cultures isolated from fetal rat bone synthesize insulin-like growth factor-I (IGF-I), which functions as a locally acting growth and differentiation factor in the skeleton. Consistent with prior studies demonstrating that IGF-I production is enhanced in bone by agents that induce cAMP, prostaglandin E2 (PGE2) stimulates both cAMP synthesis and IGF-I mRNA in Ob cells. However, little is known about how cAMP regulates IGF-I expression in this or any other cell system. In rat tissues, multiple mechanisms influence levels of IGF-I mRNA, including transcription from two promoters, differential RNA splicing and stability, and alternative RNA polyadenylation. To determine how cAMP influences IGF-I gene expression in Ob cultures, we examined the responses of these cells to treatment with PGE2. PGE2 rapidly enhanced the accumulation of both large and small IGF-I transcripts, with increases in IGF-I mRNA detected within 2 h of treatment and persisting for 24 h. Analysis of precursor RNA by a highly specific and sensitive ribonuclease protection assay demonstrated a rise in nascent IGF-I mRNA within 30 min of exposure to PGE2, with a peak stimulation of 4-fold above control levels seen by 2 h and levels remaining elevated for up to 24 h. IGF-I transcripts in Ob cells were directed only by promoter 1, the more 5' of the two rat IGF-I gene promoters. As additionally assessed using the RNA polymerase II inhibitor 5,6-dichloro-1-beta-D-ribofuranosyl benzimidazole, PGE2 treatment had little effect on IGF-I mRNA stability. In aggregate, these studies show that in fetal rat Ob cultures, PGE2 enhances IGF-I gene expression primarily through transcriptional mechanisms that are limited to a single IGF-I gene promoter. Ob cells, therefore, may be an excellent model for determining how cAMP regulates IGF-I gene transcription.

Animals↗
PubMed1992

Chromatin changes accompany the developmental activation of insulin-like growth factor I gene transcription.

Insulin-like growth factor I (IGF-I) is a potent regulator of postnatal growth in mammals, yet little is known about the developmental control of IGF-I synthesis. We have investigated the regulation of IGF-I expression in the rat in order to gain insight into the mechanisms of growth factor induction during early postnatal life. Steady-state levels of liver IGF-I mRNA increased by more than 15-fold during the period from fetal day 18 to postnatal day 7 and reached 50% of adult values by day 14. Transcription run-on experiments using isolated hepatic nuclei and direct analysis of nuclear RNA each demonstrated a comparable rise in nascent IGF-I mRNA over the same time period. Over 90% of transcripts were directed by promoter 1, the more 5' of the two IGF-I gene promoters. By contrast IGF-II gene transcription rates and mRNA levels fell during the first 3 weeks after birth, and albumin expression rose slightly. Analysis of chromatin structure around the IGF-I gene revealed 15 DNase I-hypersensitive sites in adult rat liver in the 120 kilobases (kb) comprising the 6 exon gene and its flanking regions (8 sites within 10 kb at the 5'-end including exons 1-3, 5 sites in the 50-kb third intron, and 2 sites in the 15-kb fifth intron). During development there was a progressive appearance of DNase I-hypersensitive sites that coincided with activation of IGF-I gene expression. One site that became fully hypersensitive by postnatal day 7 was mapped by in vivo DNAse I footprinting to the proximal 200 nucleotides of promoter 1. Since serum IGF-I values rose from 10 to 120 micrograms/liter during the initial postnatal week, these results indicate that transcriptional mechanisms are principally responsible for the stimulation of IGF-I synthesis that occurs shortly after birth. Because discrete changes in chromatin organization coincided with induction of IGF-I gene transcription, it is likely that a series of developmentally modulated transcription factors are involved the activation process.

Animals↗
PubMed1992

Growth hormone rapidly activates insulin-like growth factor I gene transcription in vivo.

Many of the growth-promoting properties of GH are mediated by insulin-like growth factor I (IGF-I), a highly conserved circulating 70-amino acid peptide. Recent studies have shown that multiple mechanisms influence IGF-I gene expression, including transcription from two promoters, alternative RNA splicing, and variable polyadenylation. In order to determine how GH regulates IGF-I gene expression we have analyzed the response of hypophysectomized rats to a single ip injection of recombinant GH. A rise in hepatic IGF-I mRNA was detected within 2 h of GH treatment, with peak values of more than 15-fold above untreated animals by 4 h, and a decline by 16 h. A coordinate increase was seen in all IGF-I mRNA splicing and polyadenylation variants, indicating that neither alternative RNA processing nor differential poly A addition were altered by GH. Transcription run-on experiments using isolated hepatic nuclei and direct analysis of nuclear RNA demonstrated a rise in nascent IGF-I mRNA within 30 min of GH treatment, with peak levels reaching more than 10-fold above background by 2 h and declining by 6 h. As determined by RNase protection assays, transcripts directed by each promoter were coordinately and equivalently activated after GH. A single GH-responsive DNase I hypersensitive site was mapped in chromatin to the second IGF-I intron. This site exhibited rapid kinetics of induction which mirrored the pattern of transcriptional stimulation after GH treatment. These experiments show that GH enhances IGF-I expression in vivo by predominantly transcriptional mechanisms. The rapid kinetics of IGF-I gene activation and the temporally associated chromatin changes demonstrate a direct link between a GH-dependent signal transduction pathway and nuclear events.

Animals↗
PubMed1986

Characterization of alpha-actinin from Acanthamoeba.

Characterization of a protein from Acanthamoeba that was originally called gelation protein [T.D. Pollard, J. Biol. Chem. 256:7666-7670, 1981] has shown that it resembles the actin filament cross-linking protein, alpha-actinin, found in other cells. It comprises about 1.5% of the total amoeba protein and can be purified by chromatography with a yield of 13%. The native protein has a molecular weight of 180,000 and consists of two polypeptides of 90,000 Da. The Stokes' radius is 8.5 nm, the intrinsic viscosity is 0.35 dl/dm, and the extinction coefficient at 280 mm is 1.8 X 10(5)M-1 X cm-1. Electron micrographs of shadowed specimens show that the molecule is a rod 48 nm long and 7 nm wide with globular domains at both ends and in the middle of the shaft. On gel electrophoresis in sodium dodecylsulfate the pure protein can run as bands with apparent molecular weights of 60,000, 90,000, 95,000, or 134,000 depending on the method of sample preparation. Rabbit antibodies to electrophoretically purified Acanthamoeba alpha-actinin polypeptides react with all of these electrophoretic variants in samples of purified protein and cell extracts. By indirect fluorescent antibody staining of fixed amoebas, alpha-actinin is distributed throughout the cytoplasmic matrix and concentrated in the hyaline cytoplasm of the cortex. The protein cross-links actin filaments in the presence and absence of Ca++. It inhibits slightly the time course of the spontaneous polymerization of actin monomers but has no effect on the critical concentration for actin polymerization even though it increases the apparent rate of elongation to a small extent. Like some other cross-linking proteins, amoeba alpha-actinin inhibits the actin-activated ATPase of muscle myosin subfragment-1. Although Acanthamoeba alpha-actinin resembles the alpha-actinin from other cells in shape and ability to cross-link actin filaments, antibodies to amoeba and smooth muscle alpha-actinins do not cross react and there are substantial differences in the amino acid compositions and molecular dimensions.

Actinin↗