Biomedical subjects

M R Harrison

Publications and source records attributed to M R Harrison.

At least 91 records · Page 5Linked to original sources

PubMed1997

Fetendo-clip: a fetal endoscopic tracheal clip procedure in a human fetus.

Fetal tracheal occlusion accelerates lung growth and corrects the often fatal pulmonary hypoplasia seen in fetuses with congenital diaphragmatic hernia. Fetoscopy presents a unique opportunity to glimpse into the world of the fetus, but its use, until recently, has been limited to diagnostic and simple procedures. Using fetoscopic techniques ("Fetendo"), we now report successful tracheal occlusion in a 30-week-old fetus for the treatment of congenital diaphragmatic hernia.

Adult↗

PubMed1997

In utero hematopoietic stem cell transplants prolong survival of postnatal kidney transplantation in monkeys.

The authors hypothesized that in utero transplantation of T-cell-depleted paternal marrow into rhesus monkey fetuses would induce tolerance to postnatal kidney grafts from the marrow donor. T-cell-depleted paternal bone marrow was transplanted intraperitoneally into two female fetal rhesus monkeys at 61 +/- 1 days' gestation. Chimeric monkeys (n = 2) received kidney transplants from paternal donors. Control monkeys (n = 2) underwent kidney transplants without prior in utero stem cell transplants. Both chimeric monkeys demonstrated low level (<0.1% donor cells) engraftment in the bone marrow and peripheral blood using the polymerase chain reaction assay for the Y chromosome. The mixed lymphocyte reaction demonstrated hyporeactivity to the donor. Control animals demonstrated severe acute rejection and graft failure 1 week posttransplant. The first chimeric monkey had no significant clinical or sonographic evidence of renal failure until 7 weeks after the transplant. Biopsy findings showed mild rejection 1 week postoperatively, but rejection did not significantly progress until 5 weeks later. The second chimeric monkey had no significant clinical or sonographic changes for 4 weeks, but evidence of moderate rejection was seen on biopsy results. This monkey was given a 10-week course of immunosuppression, and had no clinical or sonographic renal deterioration, although biopsy results showed chronic rejection that was confirmed when electively euthanized 8 months later. Our data suggest that in utero transplantation of hematopoietic stem cells can increase the survival of a kidney allograft in the rhesus monkey.

Animals↗

PubMed1997

Prenatal therapy for pericardial teratomas.

Although the majority of reported pericardial teratomas have been excised successfully in the postnatal period, the outcome of prenatally diagnosed pericardial teratomas remains less favorable. Two recent cases of prenatally diagnosed pericardial teratomas and a review of previously reported cases suggest a new management algorithm for those pericardial teratomas discovered in utero. Fetuses in whom hydrops does not develop may be safely followed up and treated postnatally. However, if hydrops develops, the fetus requires treatment with either aspiration of the pericardial effusion, or fetal surgery and resection.

Decision Trees↗

PubMed1997

Prospective analysis of lung-to-head ratio predicts survival for patients with prenatally diagnosed congenital diaphragmatic hernia.

BACKGROUND: Accurate prenatal prediction of outcome for fetuses who have congenital diaphragmatic hernia (CDH) is very difficult. The authors previously reported a retrospective analysis of risk factors for fetal CDH and proposed a new index of severity: the lung-to-head ratio (LHR). The authors now report a prospective study to test whether this new index predicts neonatal outcome. METHODS: Fifteen patients who had left-sided CDH were sonographically evaluated at the University of California, San Francisco (UCSF) and followed prenatally and postnatally. LHR was measured at 24 to 26 weeks' gestation. Outcome variables included survival and the need for extracorporeal membrane oxygenation (ECMO). RESULTS: Overall survival was 47%. LHR ranged from 0.62 to 1.86. No patient with an LHR of less than 1.0 (n = 3) survived despite ECMO, whereas all patients with an LHR greater than 1.4 survived (n = 4), one requiring ECMO. LHR values between 1.0 to 1.4 were associated with 38% survival (n = 8), 75% requiring ECMO. Overall, survivors had a mean LHR of 1.4 +/- 0.33 and nonsurvivors, 1.05 +/- 0.3 (P < .05). CONCLUSION: The LHR is a useful index to help predict neonatal outcome in patients who have left-sided CDH.

California↗

PubMed1997

Correction of congenital diaphragmatic hernia in utero VII: a prospective trial.

BACKGROUND: Congenital diaphragmatic hernia (CDH) remains an unsolved problem. Despite optimal postnatal care, up to 60% of CDH babies die. Experimental evidence and clinical experience have shown that in utero repair of CDH is feasible and can reverse pulmonary hypoplasia, but only in fetuses without liver herniation. For this subgroup, the safety and efficacy of repair before birth has not been compared with standard care after birth. METHODS: Four fetuses in whom CDH without liver herniation was diagnosed underwent open fetal surgery for repair of the CDH. Seven comparison fetuses were treated conventionally. Neonatal mortality was the principle outcome variable. Secondary outcome variables included death of all causes until 2 years of age, number of days of ventilatory support, length of hospital stay, requirement for extracorporeal membrane oxygenation (ECMO), and total hospital charges. RESULTS: There was no difference in survival between the fetal surgery group and the postnatally treated comparison group (75% v 86%). Fetal surgery patients were born more prematurely than the comparison group (32 weeks v 38 weeks' gestation). Length of ventilatory support and requirement for ECMO were equivalent in the fetal surgery group and the postnatally treated comparison group. Length of hospital stay and hospital charges did not differ between the groups. CONCLUSIONS: Open fetal surgery is physiologically sound and technically feasible, but does not improve survival over standard postnatal treatment in the subgroup of CDH fetuses without liver herniation, primarily because overall survival in this subgroup is favorable with or without prenatal intervention. These data suggest that fetuses who have prenatally diagnosed CDH and without evidence of liver herniation should be treated postnatally.

California↗

PubMed1997

The spinal cord lesion in human fetuses with myelomeningocele: implications for fetal surgery.

Recently produced experimental evidence suggests that secondary traumatic injury and degenerative changes, acquired in utero, to the openly exposed neural tissue may be primarily responsible for the massive neurological deficit associated with myelomeningocele (MMC). The goal of this study was to examine the morphology of human fetuses with MMC to determine if acquired trauma to the spinal cord could be identified. The MMC lesions with surrounding tissues from 10 human fetuses ranging in gestational age between 19 and 23 weeks were prepared with serial histological sections. The MMC lesions were characterized by an open vertebral arch, an open dura mater fused laterally to the dermis, and an open pia mater fused laterally to the epidermis. The spinal cord was exposed, without any meningeal, bony, or cutaneous covering, and was resting on the dorsal aspect of the abnormal arachnoid sac created by the fusion of the meninges to the cutaneous tissues. The exposed neural tissue had undergone varying degrees of recent traumatic injury as a result of its exposed position, ranging from nearly complete preservation of neural elements in four cases to nearly complete loss in two cases. The neural tissue remaining in the MMC with partial loss contained hemorrhages and abrasions from recent injury, suggesting that injury occurred during passage through the birth canal. The presence of dorsal and ventral parts of the cord with nerve roots and ganglia demonstrated that these structures had formed during development and that the loss of tissue by injury was a secondary change. The results support the concept that performing in utero surgery could protect the exposed but initially well-developed and uninjured cord, prevent secondary neural injury, and preserve neural function in the human fetus with myelomeningocele.

Brain Damage, Chronic↗

PubMed1997

Latissimus dorsi flap procedures to cover myelomeningocele in utero: a feasibility study in human fetuses.

There is experimental and clinical evidence that in utero repair of myelomeningocele (MMC) may preserve neurological function. In five aborted human fetuses (gestational age, 18 to 29 weeks), the authors tested whether proximally and distally based latissimus dorsi flaps (LDF) can be used to cover MMC lesions. Fetal soft tissues were developed enough to allow surgical handling, preparation of both flap types was technically easy, and the vascular pedicles could be preserved. The proximally pedicled LDF was suitable to cover the upper spine from lower cervical to lower thoracic levels, whereas the distally pedicled LDF was suitable to cover the spine between lower thoracic and lower sacral levels. These results suggest that various LDF procedures are technically feasible in early gestational human fetuses and could be used for in utero repair of MMC.

Back↗

PubMed1997

Estimate of methane emissions from the U.S. natural gas industry.

Global methane emissions from the fossil fuel industries have been poorly quantified and, in many cases, emissions are not well-known even at the country level. Historically, methane emissions from the U.S. gas industry have been based on sparse data, incorrect assumptions, or both. As a result, the estimate of the contribution these emissions make to the global methane inventory could be inaccurate. For this reason the assertion that global warming could be reduced by replacing coal and oil fuels with natural gas could not be defended. A recently completed, multi year study conducted by the U.S. Environmental Protection Agency's Office of Research and Development and the Gas Research Institute had the objective of determining methane emissions from the U.S. gas industry with an accuracy of +/-0.5% of production. The study concluded that, in the 1992 base year, methane emissions from the industry were 314 +/- 105 Bscf or 6.04 +/- 2.01 Tg (all conversions to international units are made at 15.56 degrees C and 101.325 kPa).

Air Pollutants, Occupational↗

PubMed1997

The human homeobox genes MSX-1, MSX-2, and MOX-1 are differentially expressed in the dermis and epidermis in fetal and adult skin.

In order to identify homeobox genes which may regulate skin development and possibly mediate scarless fetal wound healing we have screened amplified human fetal skin cDNAs by polymerase chain reaction (PCR) using degenerate oligonucleotide primers designed against highly conserved regions within the homeobox. We identified three non-HOX homeobox genes, MSX-1, MSX-2, and MOX-1, which were differentially expressed in fetal and adult human skin. MSX-1 and MSX-2 were detected in the epidermis, hair follicles, and fibroblasts of the developing fetal skin by in situ hybridization. In contrast, MSX-1 and MSX-2 expression in adult skin was confined to epithelially derived structures. Immunohistochemical analysis of these two genes suggested that their respective homeoproteins may be differentially regulated. While Msx-1 was detected in the cell nucleus of both fetal and adult skin; Msx-2 was detected as a diffuse cytoplasmic signal in fetal epidermis and portions of the hair follicle and dermis, but was localized to the nucleus in adult epidermis. MOX-1 was expressed in a pattern similar to MSX early in gestation but then was restricted exclusively to follicular cells in the innermost layer of the outer root sheath by 21 weeks of development. Furthermore, MOX-1 expression was completely absent in adult cutaneous tissue. These data imply that each of these homeobox genes plays a specific role in skin development.

DNA-Binding Proteins↗

PubMed1997

Fetal congenital cystic adenomatoid malformations of the lung: a clinicopathologic study of eleven cases.

We describe the pathological examination of 11 cases of fetal congenital cystic adenomatoid malformation of the lung. All patients were treated in utero between 21 and 27 weeks of gestation with either lobectomy or placement of a thoracoamniotic shunt. Ten cases involved a single lobe, and one case involved two lobes. The lesions contained both solid and cystic areas. On the basis of microscopic appearances, we separated the malformations into two distinct types. The first type consisted of seven cases showing scattered bronchiole-like dilated spaces lined by pseudostratified ciliated epithelium with intervening tightly packed small tubules lined by columnar cells with subnuclear vacuoles. This pattern superficially resembled the pseudoglandular period of lung development. The remaining four cases were of the other histologic type. They contained scattered bronchiole-like structures with intervening irregularly branching glands lined by cuboidal epithelium within loose mesenchymal stroma. This pattern superficially resembled the canalicular period of lung development. We observed that the malformations contained cysts of various sizes and that cyst size varied widely within a single lesion. Moreover, predominantly cystic and predominantly solid lesions could not be separated histologically. Thus, we identify two patterns of fetal congenital cystic adenomatoid malformations, pseudoglandular and canalicular, the clinical significance of which is yet to be determined.

Adult↗

PubMed1997

A new in vivo model for the study of fetal wound healing.

We have developed a new in vivo model for the study of fetal wound healing. Fetal ICR mice (total gestation, 21 days) received a full-thickness incisional wound in the hind limb at gestational day 14 (N = 100). The wound was made with a 28.5-gauge needle that was passed transplacentally into the amniotic cavity. The wounds were analyzed histologically on postoperative days 0, 1, 3, and 5 by hematoxylin-eosin and Mallory's trichrome stains. Once the wounding technique was mastered, the overall mortality rate for this model was 20% by postwounding day 5. Each fetus healed their wound without scar by postwounding day 3. In 3 animals, 5 microliters of human transforming growth factor beta 1 (25 micrograms per microliter) was injected into the wound site, resulting in scar and an inflammatory cell infiltrate, indicating that the 14-day-gestation fetal mouse can be manipulated if necessary. This model offers the advantages of an in vivo system that can be studied at an early gestational age. Furthermore, it is inexpensive, easy to manipulate, and can be studied with commercially available murine probes.

Animals↗

PubMed1997

A new in utero model for lateral facial clefts.

The etiopathogenesis behind the formation of atypical craniofacial facial clefts remains unknown. To test the hypothesis that physical restricting forces such as amniotic bands can lead to the formation of these unusual clefts in the postorganogenesis period, we have modified a previously reported fetal lamb model of amniotic band syndrome to examine the effects of these bands on craniofacial development. Five 70-day gestation fetal lambs (term, 140 days) were exposed via a maternal hysterotomy. In each animal, an attempt was made to create a lateral craniofacial cleft by applying a 2-0 nylon suture as a constriction band to the growing face. The sutures were attached to either the zygomatic arch or the infraorbital rim externally and then looped circumferentially into the oral commissure. Each suture was positioned so as to create either a Tessier type 5 or a Tessier type 7 cleft. Four of five fetal lambs survived to term. Both types of lateral facial clefts were effectively produced using this model. In each group, the presence of an intraoral constriction band led to the formation of macrostomia, with an average 7.4-mm lateral displacement of the oral commissure. In addition to these soft tissue changes, each animal also had partial bony clefting (i.e., a bony groove) induced by the pressure of the restriction band across the growing facial skeleton. In the two lambs with the Tessier type 7 cleft, incomplete bony clefts developed across the zygomatic arch. In three animals with bands placed across the medial infraorbital rim, significant infraorbital and malar bony clefts formed similar to a classic Tessier type 5 facial cleft. No evidence of tissue necrosis, maceration, or ulceration was noted in any animal. These data present, for the first time, evidence that the constriction of craniofacial growth by external forces such as a swallowed amnionic band can lead to the development of lateral facial clefting involving both soft tissue and bony elements. These malformations are likely due to a combination of directly tethering normal tissue migration and an increase in local pressure, which produces cellular ischemia and apoptosis. Furthermore, our data demonstrate that these clefts can occur later in fetal development during a period of facial growth rather than during the period of primary facial morphogenesis.

Amniotic Band Syndrome↗

PubMed1997

Midgestational sciatic nerve transection in fetal sheep results in absent nerve regeneration and neurogenic muscle atrophy.

In order to test whether fetal nerve healing and regeneration result in complete functional recovery, we transected the sciatic nerve at trunk level in 13 midgestational sheep fetuses. In 10 fetuses immediate microsurgical nerve coaptation was performed. The neonatal lambs were evaluated clinically, electrophysiologically, and histologically. On the transected side, the 10 surviving lambs showed a sensorimotor sciatic nerve paralysis and atrophy of the muscles innervated by the sciatic nerve. Somatosensory evoked potentials were weakly present in 5 animals and absent in 5 animals. Histologically, minimal signs of axonal regeneration, massive degeneration of the entire nerve, and a marked neurogenic muscle atrophy were found. These unexpected results differ from the findings after peripheral nerve transections in late gestational sheep fetuses and also from the classic wallerian degeneration-regeneration pattern that follows adult nerve injury. We speculate that the almost absent regenerative potential at midgestation is related to axotomy-induced neurotrophic factor deprivation during a developmental phase where the neurons are critically dependent on growth factor for survival.

Animals↗

PubMed1996

Experimental fetal transesophageal and intracardiac echocardiography utilizing intravascular ultrasound technology.

Fetal transesophageal and intracardiac echocardiography by utilizing ultrasound technology permits accurate definition of cardiac anatomy in fetal sheep. Because fetal transesophageal echocardiography is less invasive than intracardiac echocardiography, it has the potential to serve as a monitoring tool for currently developed open and fetoscopic fetal cardiac interventions.

Animals↗

PubMed1996

Laparoscopic adrenalectomy. Comparison of the lateral and posterior approaches.

OBJECTIVE: To compare the lateral transabdominal and posterior retroperitoneal laparoscopic methods for performing adrenalectomy. DESIGN: Nonrandomized. SETTING: Hospitals affiliated with the University of California, San Francisco. PATIENTS: Thirty-six patients (15 men and 21 women), aged 5 to 78 years (mean age, 49 years), were treated for the following conditions: aldosteronoma, 18 patients; pheochromocytoma, 4 patients; Cushing syndrome, 6 patients; androgen-secreting tumor, 1 patient; nonfunctioning adenoma, 3 patients; adrenal hemorrhage, 1 patient; metastatic neoplasm, 2 patients; and myelolipoma, 1 patient. INTERVENTIONS: Twenty-three lateral and 14 posterior laparoscopic adrenalectomies. MAIN OUTCOME MEASURES: Success rate, operating time, complications, and length of hospital stay. RESULTS: The tumors, which ranged in size from 1 to 13 cm (mean, 4.2 cm; median, 2.5 cm), were all successfully resected laparoscopically. All 8 tumors larger than 6 cm were resected by the lateral approach. One critically ill patient died. No patient required blood transfusions or conversion to laparotomy. Mean operating time was 3.8 hours vs 3.4 hours (median, 3.5 hours vs 3 hours) and mean hospital stay was 2.2 days vs 1.5 days (median, 2 days vs 1 day) for the lateral and posterior approaches, respectively. All patients without concomitant procedures were ready to be discharged within 48 hours. CONCLUSIONS: Both approaches were effective and safe. We prefer the lateral approach for tumors larger than 6 cm and the posterior approach for bilateral tumors.

Adolescent↗

PubMed1996

Transesophageal echocardiography in fetal sheep. A monitoring tool for open and fetoscopic cardiac procedures.

BACKGROUND: Cardiac procedures in exteriorized fetuses or assisted by fetoscopy require monitoring capabilities not attended by conventional maternal transabdominal echocardiography. METHODS: We, therefore, assessed the potential of fetal transesophageal echocardiography (TEE) utilizing an intravascular ultrasound catheter (IVUC) for fetal cardiac monitoring. We inserted a 10-F-10-MHz IVUC into the esophagus in 12 exteriorized fetal sheep and by a fetoscopic approach in 4 fetal sheep. Cardiac events were observed. Heart rate, cardiac rhythm, patency of the foramen ovale and ductus arteriosus, and the width of the branch pulmonary arteries could be assessed in all fetuses. Ventricular contractility could be assessed only in fetuses weighing less than 2.5 kg. Larger fetuses did not allow adequate imaging of the apical portion of the ventricles because of limited tissue penetration of the IVUC. Fetal TEE permitted placing small guide wires in the cardiac atria and left ventricle. Short-lived premature beats following intracardiac manipulations of these wires could be observed by fetal TEE in all cases. RESULTS: At autopsy, no complications from IVUC insertion were observed in the exteriorized fetuses. Fetoscopic placement of the IVUC resulted in minor perioral skin erosion in two nonexteriorized fetuses. CONCLUSIONS: In conclusion, fetal TEE can be achieved with minor fetal injury and may provide useful information during open and fetoscopic cardiac procedures. Further improvements in IVUC design will permit the application of this technique to monitor human fetal cardiac procedures.

Animals↗

PubMed1996

Fetal surgery.

Although most fetal defects are best managed after birth, a few with predictable, life-threatening developmental consequences have been successfully corrected in utero. Many technical problems have been solved, but preterm labor remains a significant risk to mother and fetus. Less invasive interventional techniques and fetal stem cell transplantation promise to extend the indications for intervention.

Female↗

PubMed1996

Gastroschisis increases small bowel nitric oxide synthase activity.

In gastroschisis, the eviscerated fetal bowel frequently is damaged and this results in hypoperistalsis and malabsorption. The mechanistic link that ties gastroschisis-induced intestinal damage to dysfunction may be nitric oxide (NO) and the enzyme responsible for producing it, NO synthase. Using a fetal rabbit model, the authors investigated the hypothesis that the hypoperistalsis and malabsorption associated with gastroschisis may be attributable to abnormal small bowel NO synthase activity. Using the 3H-arginine-to-3H-citrulline conversion assay, they measured NO synthase activity in the small bowel of full-term fetal rabbits with and without gastroschisis. The mean total small bowel NO synthase activity of fetal rabbits with gastroschisis was 2.5 times greater than that of control littermates without gastroschisis (n = 6; 5,726 +/- 834 v 2,208 +/- 537 mean pmol/mg protein/min; P = .004). This increased NO synthase activity also was studied by measuring the individual isoforms of NO synthase, and the site of increased NO synthase activity was localized to the small bowel epithelium and neurons. After detecting and localizing the gastroschisis-induced increase in NO synthase activity, the authors explored the mechanism of this increase using NADPH-diaphorase staining. With this histological staining technique, no quantitative increase was found in the small bowel NO synthase of the rabbits with gastroschisis. This suggests that the increased NO synthase activity found in these rabbits is the result of accelerated enzyme kinetics. These findings suggest that the increased NO synthase activity caused by gastroschisis may contribute to the common clinical sequelae of malabsorption and intestinal dysmotility.

Animals↗