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Biomedical subjects

Michael R Harrison

Publications and source records attributed to Michael R Harrison.

At least 19 recordsLinked to original sources

Magnetic Mini-Mover Procedure for pectus excavatum: I. Development, design, and simulations for feasibility and safety.

BACKGROUND/PURPOSE: Correction of pectus excavatum (PE) results in measurable improvement in lung capacity and cardiac performance as well as improved appearance and self-image. The Nuss and modified Ravitch approaches attempt to correct the chest wall deformity by forcing the sternum forward in 1 step and holding it in place using a metal strut. The initial operation requires extensive manipulation under general anesthesia and results in postoperative pain, requiring hospitalization and regional anesthesia. Pain and disability may last for weeks. Both procedures are expensive. A better principle would be a gradual bit-by-bit repair via small increments of pressure applied over many months. We developed the Magnetic Mini-Mover Procedure and applied this strategy to correct PE. METHODS: The Magnetic Mini-Mover Procedure uses magnetic force to pull the sternum forward. An internal magnet implanted on the sternum and an external magnet in a nonobtrusive custom-fitted anterior chest wall orthosis produce an adjustable outward force on the sternum. Outward force is maintained until the abnormal costal cartilages are remodeled and the pectus deformity is corrected. RESULTS: We implanted a magnet in human skeletons and measured the force applied to the sternum when the distance between the internal and external magnets was varied in increments. With the 2 magnets 1 cm apart, the outward force was adequate to move the sternum at least 1 cm. We also mapped the magnetic field in the two-magnet configuration and found that maximum field strengths at the surface of the heart and at the outer surface of the orthosis were at safe levels. CONCLUSIONS: The Magnetic Mini-Mover Procedure allows correction of PE by applying magnetic force over a period of months. Crucial questions raised during our design, redesign, and simulation testing have been satisfactorily answered, and we have received a Food and Drug Administration Investigation Device Exemption (G050196/A002) to proceed with a phase I to II clinical trial.

Feasibility Studies↗

Fetal intervention for mass lesions and hydrops improves outcome: a 15-year experience.

PURPOSE: The natural history of certain prenatally diagnosed masses is well known. Large thoracic mass lesions can evolve one of 2 ways, either to regress and cause minimal morbidity, or to progress and enlarge, often resulting in hydropic changes in the fetus. This nonimmune hydrops carries a dismal prognosis, with nearly all fetuses expiring before or shortly after birth. However, hydrops associated with fetal mass lesions can be halted and even reversed with fetal intervention and treatment of the underlying defect. We examined our patients with fetal mass lesions to evaluate survival after intervention. METHODS: Institutional approval was obtained by the Committee on Human Research. A retrospective review was performed of 294 fetuses evaluated over 15 years with large mass lesions. All patients were evaluated for evidence of fetal hydrops using ultrasound criteria. Patients were divided according to type of intervention. Primary outcome measure was 30-day survival after birth. RESULTS: (1) Patients without fetal hydrops did not undergo fetal intervention and survived to 30 days after birth (167/172, 97%). (2) Patients with fetal mass lesions that developed hydrops fared poorly with no intervention (1/33 survival, 3%), whereas fetuses undergoing prenatal intervention fared much better (15/30 open, 50%; 3/10 percutaneous, 30%). (3) Four patients with hydropic congenital cystic adenomatoid malformation (n = 3) or pulmonary sequestration (n = 1) received steroids in preparation for surgery but underwent no intervention, and the patients survived the neonatal period. CONCLUSION: Fetuses with prenatal diagnoses of masses not associated with hydrops have excellent prognosis with survival higher than 95%. Nonimmune hydrops associated with prenatal diagnosis of a fetal mass is a devastating complication with less than 5% survival. Open resection of a mass causing hydrops resulted in 50% survival, with reversal of hydrops in a group with near-uniform fatality. Further investigation is warranted regarding the use of minimally invasive prenatal therapies including steroid administration for hydropic fetuses.

Edema↗

Maternal morbidity after maternal-fetal surgery.

OBJECTIVE: There is a paucity of published data on the maternal risks of fetal surgical interventions. We analyzed maternal morbidity and mortality that were associated with different types of fetal intervention (open hysterotomy, various endoscopic procedures and percutaneous techniques) to quantify this risk. STUDY DESIGN: We performed a retrospective evaluation of a continuous series of 187 cases that had been performed between July 1989 and May 2003 at the Fetal Treatment Center, a highly specialized interdisciplinary center for fetal surgery at the University of California, San Francisco. The primary outcome was the frequency of maternal morbidity for open, endoscopic, and percutaneous procedures to access the fetus. RESULTS: There were 187 pregnant women with confirmed major fetal malformations who were candidates for intrauterine fetal intervention. Maternal-fetal surgery was performed in 87 cases by open hysterotomy, in 69 cases by endoscopic procedures, and in 31 cases by percutaneous techniques. There were no maternal deaths, but significant short-term morbidity was observed. There were no significant differences in the incidence of premature rupture of membranes, pulmonary edema, placental abruption, postoperative vaginal bleeding, preterm delivery, or interval from maternal-fetal surgery to delivery between endoscopic procedures and open surgery. Complications were significantly less in the percutaneous ultrasound-guided procedures. Endoscopic procedures, even with a laparotomy, showed statistically significantly less morbidity compared with the open hysterotomy group regarding cesarean delivery as delivery mode (94.8% vs 58.8%; P < .001), requirement for intensive care unit stay (1.4% vs 26.4%; P < .001), length of hospital stay (7.9 vs 11.9 days; P = .001), and requirement for blood transfusions (2.9% vs 12.6%; P = .022). Chorion-amnion membrane separation (64.7% vs 20.3%; P < .001) was seen more often in the endoscopy group. CONCLUSION: Short-term morbidities include increased rates of cesarean birth, treatment in intensive care, prolonged hospitalization, and blood transfusion, all of which were more common with hysterotomy compared with other techniques. Maternal-fetal surgery can be performed without maternal death. Results from this study provide helpful data for counseling prospective patients.

Female↗

Prosthetic patches for congenital diaphragmatic hernia repair: Surgisis vs Gore-Tex.

PURPOSE: The sequelae of congenital diaphragmatic hernia (CDH) continue well beyond the perinatal period. Up to 50% of these patients have subsequent recurrent herniation or small bowel obstruction (SBO). A recent trend has been toward the use of bioactive prosthetic materials. We reviewed different patch closure techniques used for CDH repair at our institution and their association with these sequelae. METHODS: A retrospective review was performed of 152 records for patients with CDH. Newborns that underwent patch repair for CDH and survived for at least 30 days were included in the analysis. Primary outcomes evaluated were recurrent herniation and SBO. Two types of prostheses were examined, Gore-Tex, an artificial material, and Surgisis, a bioactive material. RESULTS: Twelve (44%) of 27 patients who had Surgisis repair had recurrent herniation. Seventeen (38%) of 45 patients who had a Gore-Tex repair had recurrent herniation. Two additional patients in each group presented with SBO. No significant difference in recurrent herniation rates was observed (P > .5). The time to recurrence was similar in both groups (log-rank, P = .75), with most recurrences (92% Surgisis, 76% Gore-Tex) occurring in the first year. CONCLUSION: The rates of recurrent herniation and SBO after neonatal prosthetic patch repair of CDH were similar regardless of the prosthetic material used (Surgisis or Gore-Tex).

Biocompatible Materials↗

Long-term follow-up after thymectomy for myasthenia gravis: thoracoscopic vs open.

PURPOSE: The aim of this study was to determine if patients are in remission or weaning off medication after thymectomy for myasthenia gravis (MG) and to examine the thoracoscopic versus open approaches. METHODS: A retrospective review of all patients who underwent thymectomy for MG at a tertiary referral center between 1992 and 2004 (N = 14). Six patients (42.9%) underwent thoracoscopic resection. Eight patients underwent open resection; 5 (35.7%) had median sternotomy and 3 (21.4%) by transcervical approaches. Follow-up was obtained in 12 (85.7%) of 14 patients by both chart review and telephone. The mean follow-up was 43.0 months (range, 4-111 months). Statistical significance was determined by Student's t test or Fisher's Exact Test. RESULTS: The thoracoscopic group had a mean operating time of 138.8 minutes compared with 139.8 minutes in the open group (P = .9). The thoracoscopic group had a mean estimated blood loss of 7.5 mL compared with 52.5 mL in the open group (P = .02). The mean length of stay for the thoracoscopic group was 1.5 days (range, 1-2 days) and was 10.6 days (range, 3-41 days) in the open group (P = .13). Three (60%) of 5 patients were entirely off medication in the thoracoscopic group at the time of follow-up compared with 3 (50%) of 6 patients in the open group (P = 1.0). In the thoracoscopic group, 5 (83.3%) of 6 were in class 1 to 3 of the DeFilippi classification (complete remission or improved with decreased medication requirements). One patient had no change in symptoms (class 4). In the open group, 5 (83.3%) of 6 were classified as DeFilippi 1 to 3 at the time of follow-up, and one patient had worsening symptoms (class 5). CONCLUSIONS: Both thoracoscopic and open approaches to thymectomy in patients with MG are effective, with more than 80% of patients in both groups in remission or with improvement at the time of follow-up. The thoracoscopic group has the added benefits of decreased estimated blood loss, decreased length of hospital stay, and improved cosmesis. We advocate the thoracoscopic approach for thymectomy in the treatment of juvenile MG.

Adolescent↗

Residual congenital cystic adenomatoid malformation and thoracic scar deformation after fetal surgery: a case report.

Fetal surgery is a treatment option for fetuses with congenital cystic adenomatoid malformation (CCAM) of the lung who develop hydrops before 32 weeks of gestation. We report on a fetus with CCAM and hydrops who underwent subtotal resection of a huge right, lower lobe CCAM at 20 weeks of gestation. Postnatally, the infant developed a thoracic scar deformation and was suspected to have residual CCAM. The residual CCAM was resected and the chest wall deformity was corrected at 3 1/2 years of age.

Adult↗

Monochorionic twin gestation complicated by a sacrococcygeal teratoma with hydrops--optimal timing of delivery allows for survival of the unaffected twin.

Sacrococcygeal teratomas are the most common tumors found in newborns and have a favorable outcome when diagnosed late in gestation. Solid, highly vascularized tumors diagnosed early in gestation have a higher incidence of hydrops fetalis and fetal demise. The following is a case report of a monochorionic twin gestation complicated by a solid highly vascular sacrococcygeal teratoma and the development of hydrops in the affected twin. In this case, serial ultrasound evaluations and timing of delivery optimized the outcome of the unaffected twin.

Adult↗

Pulmonary endocrine cells in hypoplastic lungs due to foetal urinary tract obstruction: a microscopic immunohistochemical study.

METHODS: We performed a urinary tract obstruction (UTO) surgical procedure at 93-107 days' gestation in lambs to investigate the relationship between pulmonary hypoplasia and the appearance of pulmonary endocrine cells by quantitative analysis of respiratory tract cells using light microscopic immunohistochemistry. RESULTS: UTO produced a significant reduction in lung weight, lung/body weight ratio, air capacity, air capacity/body weight ratio (p < 0.01) and radial alveolar count (p < 0.05), which indicated the presence of lung hypoplasia. These foetuses also showed a significant increase in the number of neuron-specific enolase (NSE)-positive pulmonary endocrine cells, expressed as the number of NSE-positive cells per bronchus (p < 0.01) or bronchiole (p < 0.05), the number of NSE-positive cells per unit perimeter of bronchus or bronchiole (p < 0.01), and the number of NSE-positive cells per unit bronchial or bronchiolar surface area (p < 0.01). CONCLUSION: These results suggest that UTO significantly retards and modifies the structural growth and functional development of pulmonary endocrine cells in NSE expression. We speculate that pulmonary endocrine cells and their mediators may play a role in the problems associated with UTO during intrauterine life.

Animals↗

Thoracoscopic resection of foregut duplication cysts.

BACKGROUND: Foregut duplications are rare entities that include both esophageal and bronchogenic cysts. The diagnosis of foregut duplication cyst is made most often from an incidental finding on chest radiograph, or due to respiratory compromise due to mass effect or infection. Treatment consists of complete resection. Recurrences are associated with incomplete resection. Six cases of foregut duplication cysts are presented that were resected thoracoscopically. MATERIALS AND METHODS: From May 1998 to April 2003, six patients underwent thoracoscopy for resection of foregut duplication cyst. One patient required conversion to open thoracotomy due to esophageal perforation. The distribution of cysts was 4 on the left and 2 on the right; all procedures were performed with three or four ports. Single lung ventilation was used in three patients. The masses were removed via a port site after intrathoracic decompression. Chest tubes were placed in all patients, and most were removed within 12 hours. RESULTS: Five of six cases underwent successful thoracoscopic resection. Pathology demonstrated esophageal duplication cyst in three patients and bronchogenic cyst in the other three patients. Average hospital stay was 5.5 days. Complications included aspiration pneumonia and chest tube dislodgment. There were no deaths, and no recurrences. CONCLUSION: Thoracoscopic resection is a safe and effective method of treating foregut duplications. Outcomes have been good with little short-term morbidity and no mortality. Morbidity and cosmesis are improved by avoiding thoracotomy. Thoracoscopic resection should be considered the first-line therapy for these benign masses.

Adolescent↗

Spontaneous rupture of fetal sacrococcygeal teratoma.

With recent advances in technology, fetal sacrococcygeal teratoma is being diagnosed increasingly during the early prenatal period by ultrasound examination. In addition, early detection of tumor related complications such as polyhydramnios, congestive heart failure, hydrops, hemorrhage, urinary tract or bowel obstruction can be followed closely in utero. Active prenatal management can improve fetal perinatal outcome by allowing planned delivery for neonatal surgery [Chisholm, C.A. et al.: Am J Perinatol 1999;16:47-50] or in some cases, fetal intervention. Additionally, families can be counseled appropriately regarding the range of outcomes. We report a case of fetal sacrococcygeal teratoma Type I diagnosed at 20 weeks with a prominent vessel supplying the tumor mass. At 23 weeks, there was a sudden appearance of an additional lobular mass, consistent with intrauterine spontaneous ruptured of a sacrococcygeal teratoma mass.

Adult↗

Myelomeningocele: characterization of a surgically induced sheep model and its central nervous system similarities and differences to the human disease.

OBJECTIVE: The purpose of this study was to determine how closely the surgically induced sheep myelomeningocele (MMC) model resembles the central nervous system derangements seen in human disease, and identify which aspects of MMC are the result of the early neuronal developmental defect, and which are secondary to the cerebrospinal fluid (CSF) drainage. STUDY DESIGN: An MMC-like lesion was created surgically in 16 fetal sheep at 75 days' gestation: 5 died in utero, 7 underwent no fetal repair, 4 were repaired (2-layer closure or biological glue) at 100 days' gestation. MMC sheep were delivered at term and allowed to survive up to 17 days for analysis of behavioral status and feeding behavior. Animals not repaired in utero were repaired at birth. All lambs were sacrificed and analyzed for hindbrain herniation, hydrocephalus, and other CNS derangements. RESULTS: Hindbrain herniation was observed in 43% of animals not repaired in utero, and in 1 lamb repaired with Bioglue. No animal developed hydrocephalus or other CNS derangements. CONCLUSION: Although this sheep MMC-like model reproduces the CSF leak, but not the developmental defect seen in humans, it suggests CSF leak contributes to hindbrain herniation seen in humans. This model may be useful to develop new minimally invasive techniques to halt CSF leak in utero.

Animals↗

Pre-emptive placement of a presealant for amniotic access.

OBJECTIVE: Amniotic access for fetal diagnosis and therapy can lead to membrane leaks, separation, and preterm premature rupture of membranes. Morbidity limits the beneficial effects of fetal intervention. We propose to examine a novel preventive "presealant" membrane puncture technique and evaluate it in vitro. STUDY DESIGN: Fetal membranes from normal term deliveries were fastened to a pressure controlled pump and punctured after presealant placement. Distinct bioadhesives were then compared for sealing efficacy by the measurement of leak pressures. Membranes were also evaluated for changes in tensile rupture strength after treatment. RESULTS: Preemptive sealing by 2 of the presealants achieved significantly higher leak pressures compared with control membranes (85 and 78, respectively, vs 27 cm of water; P < .05). One of the presealants worked effectively in a membrane-sealant-membrane interface (62 vs 30 cm of water; P < .05). All treated membranes, however, demonstrated diminished tensile rupture forces compared with control membranes (124 vs 170 g/cm2; P > .05). CONCLUSION: The application of a presealant is effective for the prevention of iatrogenic rupture in an in vitro model and may be beneficial for clinical application. Further studies with different bioadhesives are needed, given the limitations of the glues that are described in this study.

Cyanoacrylates↗

Survival of severe congenital diaphragmatic hernia has morbid consequences.

BACKGROUND/PURPOSE: Fetal tracheal occlusion (TO) was developed in an attempt to enhance prenatal lung growth and improve survival in fetuses with severe congenital diaphragmatic hernia (CDH). We conducted a randomized, controlled clinical trial in 24 fetuses with severe left CDH (liver herniated into the thorax and low lung-to-head ratio) to compare survival after endoscopic fetal TO vs standard perinatal care (control) and prospectively followed up the 16 survivors (9 control, 7 TO) to compare neurodevelopmental, respiratory, surgical, growth, and nutritional outcomes. METHODS: At 1 and 2 years old, subjects underwent evaluation consisting of medical and neurological history and physical, developmental testing, nutritional assessment, oxygen saturation and pulmonary function testing, chest radiograph, and echocardiogram. Growth and developmental measures were corrected for prematurity. Data were analyzed by Mann-Whitney rank sum test, Fisher's Exact test, and logistic and linear regression. RESULTS: Infants with TO were significantly more premature at birth (control vs TO, 37.4 +/- 1.0 vs 31.1 +/- 1.7 weeks; P < .01). Growth failure ( z score for weight <2 SDs below mean) was severe in both groups at 1 year of age (control vs TO, 56% vs 86%; P = .31). There was considerable catch-up growth by age 2 years (growth failure: control vs TO, 22% vs 33%; P = .19). There were no differences in other growth parameters. There were also no differences in neurodevelopmental outcome at 1 and 2 years. Supplemental oxygen at hospital discharge was a significant predictor of worse neurodevelopmental outcome at 1 and 2 years old (P = .05 and P = .02, respectively). Hearing loss requiring amplification has been diagnosed in 44% of the group (control vs TO, 44% vs 43%; P = 1.0). CONCLUSIONS: In this group of infants with severe CDH, there were no differences in outcome at 2 years old despite significant prematurity in the TO group. Oxygen supplementation at hospital discharge identified the most vulnerable group with respect to neurodevelopmental outcome, but all infants had significant growth failure, and hearing impairment is a substantial problem in this population. Severe CDH carries significant risk of chronic morbidity.

Female↗

Subcutaneous endoscopically assisted ligation (SEAL) of the internal ring for repair of inguinal hernias in children: a novel technique.

Subcutaneous endoscopically assisted ligation (SEAL) is a technique for high ligation of the patent processus at the internal ring without a groin incision or dissection of the vas and vessels. Under endoscopic visualization through a single umbilical port, a suture is guided extraperitoneally around the internal ring, avoiding the vas and vessels. The safety, efficacy (recurrence risk), and cost-effectiveness of this unproven procedure must be tested against standard open repair in a trial.

Cost-Benefit Analysis↗

Congenital teratoma: a clinicopathologic study of 22 fetal and neonatal tumors.

Extragonadal teratoma is the most common congenital tumor. The prognostic significance of the grade of immaturity and the presence of small foci of conventional yolk sac tumor (YST) in fetal and neonatal teratomas have not been determined. We report detailed histologic studies of 22 congenital teratomas, including eight tumors resected in utero for developing hydrops, and correlate the histologic features with initial serum alpha-fetoprotein (AFP) levels and clinical outcome. All fetal tumors that required in utero intervention were grade 3 immature teratomas, with admixed conventional YST in 44%. Among tumors resected postnatally, those presenting in utero were more commonly immature (71% vs. 50%). All initial post-surgical serum AFP levels were high, as expected in a neonate. No correlation was found between AFP elevation above the mean for gestational age and the presence of YST, hepatic differentiation, or immature endodermal glands in the tumor. Among 15 survivors with follow-up, 5 patients had malignant mixed germ cell tumors (immature teratoma with foci of conventional YST) and 5 had immature teratomas with foci of hepatic differentiation or immature endodermal glands with subnuclear vacuoles (so-called "well-differentiated YST"). No patient has developed recurrent or metastatic disease after treatment by complete surgical excision alone (mean follow-up, 37.6 months). The clinical behavior of congenital teratomas is determined predominantly by whether or not the tumor can be completely resected and in our study did not correlate with the grade of the teratoma or with the presence or absence of foci of hepatic tissue, immature intestinal glands, or foci of conventional YST.

Adult↗

Infant pulmonary function in a randomized trial of fetal tracheal occlusion for severe congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) carries a high mortality risk secondary to pulmonary hypoplasia and respiratory failure. In experimental animals, fetal tracheal occlusion (TO) induces lung growth and morphologic maturation. We measured indicators of pulmonary function in 20 infants who were enrolled in a randomized trial of fetal TO as treatment for severe CDH [nine with conventional treatment (controls); 11 with TO]. We hypothesized that TO would improve lung function. At birth, the TO group had a lower mean gestational age (30.8 +/- 2.0 versus 37.4 +/- 1.0 wk; p=0.0002). All infants required assisted ventilation. Mortality did not differ between groups (64 versus 78%, TO and control, respectively; p=0.64). We measured respiratory mechanics at four study points: 1) first 24 h, 2) before CDH operative repair (5.9 +/- 2.2 d), 3) immediately after repair (7.0 +/- 2.2 d), and 4) before elective extubation (32.5 +/- 16.1 d). We calculated perioperative oxygenation index and alveolar-arterial oxygen difference to assess efficiency of pulmonary gas exchange. Data were analyzed by univariate and repeated measures techniques. Respiratory system compliance (Crs) was low. The rate of increase in Crs over the four study points was greater in the TO group than in control subjects. Crs in the TO group was significantly greater at study 2 (0.28 +/- 0.12 versus 0.17 +/- 0.04 mL.cm H2O(-1).kg(-1); p=0.02) and study 4 (0.93 +/- 0.45 versus 0.51 +/- 0.16 mL.cmH2O(-1).kg(-1); p=0.02). oxygenation index did not differ between groups, but alveolar-arterial oxygen difference was lower in the TO infants. We conclude that fetal TO for severe CDH results in modest improvements in neonatal pulmonary function that are of questionable clinical significance.

Administration, Inhalation↗

The ex utero intrapartum treatment procedure: Looking back at the EXIT.

PURPOSE: The ex utero intrapartum treatment (EXIT) procedure was developed originally for management of airway obstruction after fetal surgery, and indications have continued to expand for a variety of fetal anomalies. The authors review their single-institution experience with EXIT. METHODS: Retrospective review of all patients who underwent an EXIT procedure from 1993 to 2003 (n = 52) was performed. Variables evaluated include indication for EXIT, gender, gestational age at EXIT, birth weight, maternal blood loss, operative complications, operative time, and survival rate. Technique, personnel, and anesthesic management were reviewed. RESULTS: Long-term follow-up was available for all patients. Fifty-one of 52 patients were born alive; currently, 27 of 52 patients (52%) are alive. All deaths have been in patients with congenital diaphragmatic hernia. Forty-five patients underwent EXIT for reversal of tracheal occlusion for congenital diaphragmatic hernia. Of these patients, 30 underwent tracheal clip removal. Two patients had repair of tracheal injury from clipping at EXIT. Fifteen patients underwent bronchoscopy and tracheal balloon removal. Five patients underwent EXIT procedure for neck masses. Tracheostomy was performed in 3 of these patients. One patient was intubated successfully, and 1 patient underwent resection of the neck mass while on placental support. Two patients underwent EXIT procedure and tracheostomy for congenital high-airway obstruction syndrome. Average gestational age at delivery was 31.95 +/- 2.55 weeks. Average birth weight was 1,895 +/- 653 g. Average maternal blood loss was 970 +/- 510 mL. Average operating time on placental support was 45 +/- 25 minutes with a maximum of 150 minutes. CONCLUSIONS: EXIT procedures can be performed with minimal maternal morbidity and with good outcomes. It is an excellent strategy for establishing an airway in a controlled manner, avoiding "crash" intubation or tracheostomy. Longer procedures on placental support allowing for definitive management of neck masses and airway obstruction have been realized. EXIT procedures have evolved from an adjunct to fetal surgery to a potentially life-saving procedure in fetuses with airway compromise at birth.

Airway Obstruction↗