Biomedical subjects

W Hoffman

Publications and source records attributed to W Hoffman.

At least 19 recordsLinked to original sources

PubMed2003

Reversed latissimus dorsi muscle flap for repair of recurrent congenital diaphragmatic hernia.

BACKGROUND/PURPOSE: Neonates with large congenital diaphragmatic hernias (CDH) require prosthetic patch closure of the defect because of the paucity of native diaphragmatic tissue. As the child grows, patch separation can occur necessitating reoperation. Use of vascularized autologous tissue may decrease the incidence of reherniation as tissue incorporation and growth may be improved. The authors report our early experience using a local muscle advancement flap with microneural anastomosis for those children in whom reherniation develops after prosthetic patch placement. METHODS: Seven patients with CDH (6 left and 1 right) whose synthetic diaphragmatic patch separated from the chest wall resulting in a clinically significant recurrent hernia were followed up with prospectively. After dissecting the ipsilateral latissimus dorsi off the chest wall and dividing the thoracodorsal neurovascular bundle (based on its lumbar blood supply), the synthetic patch was removed via an eighth intercostal incision. The muscle flap was placed into the hemithorax through the bed of the tenth rib and sutured in place over a Vicryl mesh scaffold. The thoracodorsal nerve was anastomosed to the phrenic nerve. Functional analysis of the flap was performed in 4 patients. RESULTS: Age at placement of the muscle graft ranged from 2 months to 48 months (median, 24 months). There has been no evidence of reherniation after placement of the muscle graft. Long-term outcome and functional analysis of the flap was available in 4 patients (mean, 19 months). Two infants had fluoroscopic and sonographic evidence of nonparadoxical neodiaphragmatic motion. In one of these, electromyographic evidence of function was documented with a phrenic nerve conduction velocity of 22 meters per second. The third infant showed no evidence of neodiaphragmatic motion, and the fourth infant had paradoxical motion. CONCLUSIONS: This is the first direct documentation of phrenic nerve function in an infant with CDH. An innervated reversed latissimus dorsi (RLD) flap reconstruction for recurrent CDH provides an alternative to prosthetic patch repair. This technique offers the advantages of autologous vascularized tissue with potential phrenic nerve innervation and physiologic neodiaphragmatic motion.

Female↗

PubMed2001

Reconstruction with rectus abdominis myocutaneous free flap after orbital exenteration in children.

OBJECTIVE: To present a 1-stage technique for orbital reconstruction after exenteration with the use of myocutaneous rectus abdominis free flap in children. SURGICAL TECHNIQUE: After orbital exenteration, a myocutaneous rectus abdominis free flap with long vascular pedicle is harvested from the abdomen. The flap is transferred to the orbit and the vascular pedicle is passed through an opening made in the lateral orbital wall, where it is anastomosed to superficial temporal vessels. The skin of the flap is trimmed to correspond to the eyelid defect and the incisions are closed. METHODS: After informed consent was obtained, 2 children, 3 and 8 years old, underwent orbital reconstruction with a rectus abdominis free flap after exenteration for orbital rhabdomyosarcoma and orbital osteosarcoma in the setting of retinoblastoma. RESULTS: This technique allowed easy postoperative wound care. Viability of the flap was excellent. The technique provided sufficient volume to fill the orbit, with improved aesthetic results and minimal donor site deformity. CONCLUSIONS: The postoperative care and aesthetic outcome in patients with rectus abdominis free flap after exenteration are much improved over those provided with traditional surgical techniques. This primary reconstruction is recommended for any patient requiring orbital exenteration, but particularly for pediatric patients who tolerate debridement of traditional exenteration sites poorly.

Child↗

PubMed2001

Regulation of p53 by hypoxia: dissociation of transcriptional repression and apoptosis from p53-dependent transactivation.

Hypoxic stress, like DNA damage, induces p53 protein accumulation and p53-dependent apoptosis in oncogenically transformed cells. Unlike DNA damage, hypoxia does not induce p53-dependent cell cycle arrest, suggesting that p53 activity is differentially regulated by these two stresses. Here we report that hypoxia induces p53 protein accumulation, but in contrast to DNA damage, hypoxia fails to induce endogenous downstream p53 effector mRNAs and proteins. Hypoxia does not inhibit the induction of p53 target genes by ionizing radiation, indicating that p53-dependent transactivation requires a DNA damage-inducible signal that is lacking under hypoxic treatment alone. At the molecular level, DNA damage induces the interaction of p53 with the transcriptional activator p300 as well as with the transcriptional corepressor mSin3A. In contrast, hypoxia primarily induces an interaction of p53 with mSin3A, but not with p300. Pretreatment of cells with an inhibitor of histone deacetylases that relieves transcriptional repression resulted in a significant reduction of p53-dependent transrepression and hypoxia-induced apoptosis. These results led us to propose a model in which different cellular pools of p53 can modulate transcriptional activity through interactions with transcriptional coactivators or corepressors. Genotoxic stress induces both kinds of interactions, whereas stresses that lack a DNA damage component as exemplified by hypoxia primarily induce interaction with corepressors. However, inhibition of either type of interaction can result in diminished apoptotic activity.

Acetylation↗

PubMed1999

Distal internal carotid artery pseudoaneurysms: technique and pitfalls of surgical management: two technical case reports.

OBJECTIVE AND IMPORTANCE: Small, irregular aneurysms of the internal carotid artery (ICA) that are not related to arterial divisions are rare and have characteristics similar to pseudoaneurysms: they do not appear to have well-formed sacs, they are surrounded by clot, and they avulse readily. We report two patients whose treatment demonstrates the surgical technique and important points concerning the management of distal ICA pseudoaneurysms. CLINICAL PRESENTATION: Both patients presented with diffuse subarachnoid hemorrhage. The initial angiographic results were unremarkable in each case. A week after presentation, however, a growing outpouching in the distal ICA was seen. INTERVENTION: At surgery, the aneurysms were found to be on the medial wall of the ICA and were not related to arterial divisions. Quantitative blood flow measurements of the efferent vessels at risk (ICA, M1 and A1 segments) were obtained using a perivascular microflowprobe before and after clipping. In each patient, the aneurysm avulsed entirely during clip application, despite careful placement of the clip parallel to the parent vessel. An encircling clip was then used. Pathological sectioning of the aneurysms revealed loose connective tissue and/or clot with no defined aneurysmal sac. CONCLUSION: Aneurysms of the distal ICA that are not related to arterial divisions are difficult to visualize on angiograms immediately after subarachnoid hemorrhage. They are frail, avulse easily, and may be pseudoaneurysms, necessitating the use of encircling clips. The base of the aneurysm or clot must be trimmed to prevent it from buckling inside the clip sleeve and compromising the ICA lumen. Measuring distal blood flow quantitatively provides valuable information about the patency of the ICA inside the metallic sleeve, since this segment cannot be demonstrated with angiography.

Aneurysm, False↗

PubMed1999

A long-term, controlled-outcome analysis of in utero versus neonatal cleft lip repair using an ovine model.

Successful open repair of a cleft lip in utero has the advantage of scarless wound healing in the fetus. Unfortunately, no long-term outcome studies have been performed to evaluate the efficacy of these repairs. Moreover, no study to date has compared the long-term results of an in utero cleft lip repair to a similar, control-matched, newborn cleft repair. This study was performed to evaluate the 9-month outcome of in utero cleft lip surgery compared with an identical cleft lip repair performed on infant lambs. In utero epithelialized cleft lips were created through an open hysterotomy in sixteen 65-day-old fetal lambs (term = 140 days) using methods described by Longaker et al. Eight of 16 animals underwent subsequent in utero repair of these clefts at 90 days gestational age. The repair of the remaining eight animals was delayed until 1 week postpartum. At 9 months, the animals were analyzed for changes in lip contour and for the degree of scarring by hematoxylin and eosin and Masson's trichrome collagen staining. Two animals in each group died from preterm labor. Of the animals that survived to term, all repaired lips had some degree of abnormality postoperatively. One of six lips repaired in utero dehisced before delivery. Three of six neonatal repairs dehisced in the first postoperative month. In the remaining animals with intact lip repairs, the vertical lip height on the repaired side was an average of 9 to 12 mm shorter than the normal lip in both the in utero and neonatally repaired animals. Phenotypically, the postnatally repaired animals had more lip distortion and visible notching. Histologically, the in utero repair was scarless and the neonatal repairs had scar throughout the entire vertical height of the lip with an associated loss of hair in this region. Maxillary growth was also evaluated. There was no inhibition of maxillary growth in the animals that underwent in utero cleft lip repair. However, in the neonatal repair group, significant maxillary retrusion was evident. Compared with the cleft side of the maxilla, horizontal growth was decreased by 11 percent (p = 0.01). Compared with the intrauterine repair group, there was a 17-percent decrease in horizontal maxillary width (p = 0.01). Straight-line in utero repair of a cleft lip produces a better long-term result in terms of maxillary growth than a similar repair performed postnatally in the ovine model. There was no diminution in maxillary growth in the animals treated in utero. Histologically, in utero repair of clefts was indeed scarless. However, both lip repairs produced lips that were significantly shorter than their contralateral noncleft sides. This degree of lip shortening would require a secondary lip revision, thereby defeating the purpose of performing an intrauterine repair. Comparisons now need to be made between in utero and neonatal repairs using a Millard-type rotation advancement technique before intrauterine treatment can be considered to be more beneficial than our current treatment modalities.

Animals↗

PubMed1998

Intracranial migration of microplates versus wires in neonatal pigs after frontal advancement.

Several case reports have demonstrated that microplates migrate intracranially when used in the reconstruction of the neonatal craniofacial skeleton. We conducted a study to analyze the validity of this finding, to calculate the rate of intracranial plate migration, and to compare the migration of microplates to standard surgical wire. We hypothesized that, because of constant bone generation and resorption in the developing cranial skeleton, both microplates and wires would migrate and resorption in the developing cranial skeleton, both microplates and wires would migrate intracranially. Bilateral supraorbital osteotomies were performed in five 6-week-old Yucatan minipigs. The right side was repaired by fixating the bone segment with 32-gauge stainless steel wire. The left side was fixed with two microplates (Leibinger Corp, Dallas, TX). The pigs were monitored for 6 months. During this time each pig was injected with a fluorescent bone dye on the first day of each month. One pig was killed at 3 months and used for midpoint comparison. We found that both microplates and wires migrated intracranially in these neonatal pigs. None of the plates or wires penetrated the dura, but several pieces of hardware from each group migrated far enough to rest directly on the dural surface. The rate of plate and wire migration also varied slightly among animals, but the mean rate remained relatively constant at 0.91 mm/month. Computed tomographic scans and morphometric analysis revealed no significant difference between the fracture healing and facial growth of the microplate and wire sides. We conclude that the biology of bone deposition in the calvarium causes any stationary foreign body on the surface of the skull to migrate intracranially in the neonate.

Animals↗

PubMed1998

The in utero repair of Tessier number 7 lateral facial clefts created by amniotic band-like compression.

The purpose of this study was to determine the effectiveness of intrauterine reconstruction of lateral facial clefts caused by surgically simulated amniotic band compression. The authors hypothesized that intrauterine lysis of these bands could: 1) prevent the progression of cleft formation; 2) normalize facial development; and 3) allow for the scarless repair of these lateral atypical facial clefts. In a prospective randomized trial, eight 65-day gestational fetal lambs (term, 140 days) were exposed via a maternal hysterotomy. A Tessier 7 facial cleft was made by applying a 2.0 nylon suture as a constriction band to the growing face. The sutures were attached to the zygomatic arch and looped circumferentially into the oral commissure. Two weeks after surgery, four of eight animals were re-exposed. All four animals developed phenotypic changes consistent with Tessier 7 lateral facial clefts. These animals were treated in utero by 1) excising the synthetic constricting band, and 2) opening the epithelialized edges of the lateral facial clefts and performing a primary repair. At birth, the bands on the four untreated animals were cut. The lambs developed to 3 months of age, at which time they were evaluated anthropomorphically for changes in soft tissue measurements, and histologically using hematoxylin and eosin and Mason trichrome stain for the degree of scar at the repair site. Tessier 7 lateral facial clefts were produced in all the untreated animals. Each developed macrostomia with an average 2.3-cm lateral displacement of the oral commissure and partial maxillary clefting induced by the pressure of the restriction band. No evidence of tissue necrosis, maceration, or ulceration was noted. In contrast, animals treated in utero were phenotypically normal. There was no evidence of macrostomia and all anthropomorphic measurements were symmetrical. No bony clefts were seen on gross examination. Histologically, there was no evidence of scar formation at the site of the cleft repair. These findings suggest that like the standard cleft lip, atypical lateral facial clefts can be repaired successfully in utero without scarring. Furthermore, lysis of a restriction band in utero can prevent the progression of this facial deformity, leading to normal development of the face.

Amniotic Band Syndrome↗

PubMed1998

Outcome after hemorrhagic shock in trauma patients.

BACKGROUND: It is essential to identify patients at high risk of death and complications for future studies of interventions to decrease reperfusion injury. METHODS: We conducted an inception cohort study at a Level I trauma center to determine the rates and predictors of death, organ failure, and infection in trauma patients with systolic blood pressure < or = 90 mm Hg in the field or in the emergency department. RESULTS: Among the 208 patients with hemorrhagic shock (blood pressure < or = 90 mm Hg), 31% died within 2 hours of emergency department arrival, 12% died between 2 and 24 hours, 11% died after 24 hours, and 46% survived. Among those who survived > or = 24 hours, 39% developed infection and 24% developed organ failure. Increasing volume of crystalloid in the first 24 hours was strongly associated with increased mortality (p = 0.00001). CONCLUSION: Hemorrhage-induced hypotension in trauma patients is predictive of high mortality (54%) and morbidity. The requirement for large volumes of crystalloid was associated with increased mortality.

Adolescent↗

PubMed1998

Abnormal spinal fluid in hypertensive encephalopathy.

A 44-year-old white male presented with marked hypertension and encephalopathy. His spinal fluid showed a neutrophilic pleocytosis in the absence of infection. While cases of hypertensive encephalopathy with concomitant minor lymphocytic pleocytosis have been occasionally described, it is distinctly abnormal to have a neutrophilic pleocytosis in this setting.

Adult↗

PubMed1997

Immune response to the filaria Litomosoides sigmodontis in susceptible and resistant mice.

Comparisons were made between the immune responses evoked during the course of chronic and patient infections of Litomosoides sigmodontis in susceptible BALB/c mice and non-patent infections in resistant B10.D2 mice. Early antigen specific responses of spleen cells were weak in both mouse strains. However, by day 58 post infection a strong Th2 response, as determined by production of IL-4, IL-5 and IL-10, was observed in BALB/c mice but not in B10.D2 mice. Antibody responses seemed to appear sooner in B10.D2 than in BALB/c mice, and these differentially recognised two antigens of 15 kD and 80 kD.

Animals↗

PubMed1997

Nd:YAG laser irradiation in conjunction with cryogen spray cooling induces deep and spatially selective photocoagulation in animal models.

Successful laser treatment of haemangiomas requires selective photocoagulation of subsurface targeted blood vessels without thermal damage to the overlying epidermis. We present an in vivo experimental procedure, using a chicken comb animal model, and an infrared feedback system to deliver repetitive cryogen spurts (of the order of milliseconds) during continuous Nd:YAG laser irradiation. Gross and histologic observations show deep-tissue photocoagulation is achieved, while superficial structures are protected from thermal injury due to cryogen spray cooling. Experimental observation of epidermis protection in chicken comb animal models suggests selective photocoagulation of subsurface targeted blood vessels for successful treatment of haemangiomas can be achieved by repetitive applications of a cryogen spurt during continuous Nd:YAG laser irradiation.

Animals↗

PubMed1995