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Biomedical subjects

J Upton

Publications and source records attributed to J Upton.

At least 37 records · Page 2Linked to original sources

Congenital fibrosarcoma of the upper extremity.

Congenital or infantile fibrosarcoma is a rare soft-tissue neoplasm that should be considered in the differential diagnosis of a large extremity mass presenting at birth. These tumors are notoriously misdiagnosed at birth as either hemangiomas or lymphatic malformations. Definitive diagnosis is made by physical examination, special radiologic studies, and biopsy. Although histologically similar to fibrosarcomas occurring in adults, the congenital lesions differ in their clinical behavior; metastases are rare, local recurrence is common, and the prognosis is good with wide local excision combined with chemotherapy. Amputation should be reserved for chemoresistant patients in whom the involvement of neurovascular structures by the tumor make a limb-sparing aggressive excision impossible.

Adult↗

Muscle stapling technique for free muscle transfer to the face.

Free muscle transfer for facial reanimation can be facilitated by the use of a linear gastrointestinal stapler. This technique not only offers reliable muscle insertion at the recipient site but also helps to provide an adequate motor unit by facilitating safe muscle debulking, splitting, and tailoring.

Adult↗

Direct visualization of arterial anatomy during toe harvest dissections: clinical and radiological correlations.

The arterial patterns seen during 57 clinical dissections during toe transfers were divided into four types: (1) type A: a large first dorsal metatarsal artery and present plantar vessel (27 patients, 47 percent); (2) type B: a smaller first dorsal metatarsal artery within the interosseous muscle and an equal-sized plantar vessel (17 patients, 30 percent); (3) type C: a small, interosseous first dorsal metatarsal artery and dominant plantar vessel (8 patients, 14 percent); and (4) type D: an absent first dorsal metatarsal artery (5 patients, 9 percent). A modified and more expeditious toe harvest used the early identification of the vascular pattern through the first webspace followed by a retrograde dissection. The use of a meticulous surgical technique and multiple arterial anastomoses is advocated. Preoperative angiography of the foot is no longer routine and is now used selectively for trauma, cold injuries, or congenital anomalies. All 57 toe transfers (single or multiple) were successful; three were reexplored successfully for arterial insufficiency. A clinical correlation of arterial patterns was made between the angiograms obtained on 33 of these 57 patients and on 65 adult and pediatric patients without intrinsic vascular disease of the lower limb. Contrast reached the foot and toes faster through the posterior tibial artery and plantar arch in the majority of feet studied. Like the ulnar artery in the forearm and hand, the posterior tibial artery is the dominant conduit to the foot and ankle and, through the plantar arch, the major arterial system to the toes.

Adult↗

Synpolydactyly phenotypes correlate with size of expansions in HOXD13 polyalanine tract.

Synpolydactyly (SPD) is a dominantly inherited congenital limb malformation. Typical cases have 3/4 finger and 4/5 toe syndactyly, with a duplicated digit in the syndactylous web, but incomplete penetrance and variable expressivity are common. The condition has recently been shown to be caused by expansions of an imperfect trinucleotide repeat sequence encoding a 15-residue polyalanine tract in HOXD13. We have studied 16 new and 4 previously published SPD families, with between 7 and 14 extra residues in the tract, to analyze the molecular basis for the observed variation in phenotype. Although there is no evidence of change in expansion size within families, even over six generations, there is a highly significant increase in the penetrance and severity of phenotype with increasing expansion size, affecting both hands (P = 0.012) and feet (P < 0. 00005). Affected individuals from a family with a 14-alanine expansion, the largest so far reported, all have a strikingly similar and unusually severe limb phenotype, involving the first digits and distal carpals. Affected males from this family also have hypospadias, not previously described in SPD, but consistent with HOXD13 expression in the developing genital tubercle. The remarkable correlation between phenotype and expansion size suggests that expansion of the tract leads to a specific gain of function in the mutant HOXD13 protein, and has interesting implications for the role of polyalanine tracts in the control of transcription.

Base Sequence↗

Esophageal replacement in children who have caustic pharyngoesophageal strictures.

Caustic injury to the upper aerodigestive system with scarring of the pharynx, hypopharynx, and esophagus is a challenging reconstructive problem. The authors report on seven patients who required total esophageal replacement from the pharynx to the stomach. Injury occurred from alkali in six and acid in one. Age at injury ranged from 14 months to 14 years (mean, 4.5 years.) in five boys and two girls. Time from injury to esophageal replacement was 6 months to 10 years (mean, 3.5 years). Two required pharyngeal reconstruction before and one after esophageal replacement. Six patients had an isoperistaltic right or transverse colon interposition. One who had gastric necrosis had an ileo-right colonic substernal interposition with creation of a jejunal reservoir. Results of barium swallows showed intact anastomoses in all patients. There were no leaks. Most had some degree of mild to moderate aspiration, and one who had left vocal cord paralysis had initially massive aspiration. Three patients currently eat regular diets; four eat but still require supplemental tube feeds. The authors conclude that children who have hypopharyngeal scarring and obliterated esophageal inlet can undergo a successful colonic esophageal replacement with high proximal pharyngocolic anastomosis.

Adolescent↗

Tissue expansion in children: a retrospective study of complications.

We retrospectively reviewed 105 consecutive children in whom 191 tissue expanders were placed by the Plastic Surgical Service at The Children's Hospital from 1987 to 1995. The age range was 1 month to 28 years. The series included 68 females and 37 males. The indications for tissue expansion were congenital pigmented nevus (N = 55), craniofacial anomaly (N = 13), aplasia cutis congenita (N = 7), meningomyelocele (N = 7), posttumor resection (N = 5), unstable scar (N = 4), burn scar (N = 3), and miscellaneous disorders. The expanders were located in the scalp (N = 59), cervicofacial area (N = 23), back (N = 18), chest (N = 6), and extremities (N = 6). A single expander was used in 47 patients and the mean number of expanders per patient was 1.8. All patients were given preoperative intravenous antibiotics. There were 25 complications in 20 patients (19%), which comprised 13% of all expanders. The most common complications were infection (6%, N = 11), deflation (3%, N = 6), and exposure (2%, N = 5). These complication rates were not related to either the gender, site of implantation, number of expanders, use of closed suction drains, or the indication for expansion. The complications were related to age, being higher in children (age 1-12 years) compared with infants and adolescents. Tissue expanders can be successfully used in children to construct and reconstruct a variety of cutaneous defects, but there is an irreducible minimum for the three major complications.

Adolescent↗

Lacidipine, hydrochlorothiazide and their combination in systolic hypertension in the elderly.

OBJECTIVE: To compare with placebo the efficacies of once-daily administrations of lacidipine and hydrochlorothiazide separately and in combination to elderly patients with systolic hypertension. DESIGN AND METHODS: Nineteen elderly subjects (five men and 14 women, median age 71 years, range 62-79 years) participated in the study, which had a randomized double-blind crossover design. For each subject there were four treatment phases, each of duration 4 weeks. The initial treatments in each phase were 2 mg lacidipine once a day and 25 mg hydrochlorothiazide once a day, separately and in combination, and placebo. Doses of each agent could be doubled after 2 weeks in each phase if the patient's goal systolic blood pressure had not been achieved. The numbers of subjects administered the higher dose of each treatment were 13 for placebo, 14 for lacidipine, 11 for hydrochlorothiazide and eight for lacidipine plus hydrochlorothiazide. RESULTS: End-of-phase mean clinic blood pressures were 164/85 mmHg with placebo, 159/82 mmHg with lacidipine, 157/84 mmHg with hydrochlorothiazide and 152/82 mmHg with lacidipine plus hydrochlorothiazide. Systolic blood pressure was significantly reduced during all active treatment phases compared with placebo and that for the lacidipine plus hydrochlorothiazide phase was also significantly less than those for both of the other active treatment phases. There was no difference between sitting and standing blood pressure for any phase. Factorial analysis of the main effects of treatment indicated that the effects of lacidipine and hydrochlorothiazide on clinic blood pressure were additive and also that heart rate was higher when hydrochlorothiazide had been administered. Ambulatory blood pressure monitoring confirmed the pattern of the responses of blood pressure and showed that administration of hydrochlorothiazide had a significantly greater effect on systolic blood pressure and a longer duration of action than did administration of lacidipine. There was no difference in the frequency of adverse effects among any of the phases. CONCLUSIONS: In treating elderly systolic hypertensives the diuretic hydrochlorothiazide is a more effective antihypertensive agent with a longer duration of action than is the calcium channel antagonist lacidipine. In combination the effects of these two drugs on blood pressure are additive.

Aged↗

An investigation of lymphatic function following free-tissue transfer.

Despite microsurgical advances in the repair of severed arteries, veins, and nerves, disrupted lymphatics are not usually identified or reconnected during replantation. Although temporary swelling of a replanted part is attributed to lymphedema, this condition resolves without microsurgical intervention. Spontaneous regeneration or reconnection of lymphatics is thought to occur in such situations. Microsurgical free-flap transfer is clinically analogous to replantation in that it also results in a complete division of all lymphatic channels exiting the flap. The ability of lymphatics to regenerate after flap reconstruction, either pedicled or free, has received little attention because safe and accurate techniques for visualization and evaluation of the status of these structures have not been available. As a result of recent advances in radiocolloid lymphoscintigraphic imaging techniques, it is possible to demonstrate lymphatic flow in a physiologic, anatomic, and noninvasive manner. These methods can be applied to free-flap models to document lymphatic function after surgical treatment and determine when and to what extent such a process of growth occurs. We studied 10 consecutive patients having free-flap reconstruction. These flaps were performed for chronic osteomyelitis (6) and unstable wound coverage (4). Microvascular flaps used were latissimus dorsi, scapular-parascapular fasciocutaneous, lateral arm, rectus abdominis, temporoparietal, and free toe. Radiocolloid lymphoscintigraphy with technetium-99m-antimony trisulfide colloid (Sb2S3) was done on all patients by injection directly into the free-flap dermis. All patients were studied between 8 and 44 days (mean 23.6) after free-flap transfer. Following injection into each flap, rapid egress of the radiotracer along lymphatic pathways with progression to locoregional nodes was observed in all patients. Reestablishment of lymphatic pathways following microvascular free-tissue transfer was demonstrated by radionuclide lymphoscintigraphic techniques in 10 consecutive patients who had reconstruction for extremity wounds.

Adolescent↗

Transplantation of chondrocytes utilizing a polymer-cell construct to produce tissue-engineered cartilage in the shape of a human ear.

This study evaluates the feasibility of growing tissue-engineered cartilage in the shape of a human ear using chondrocytes seeded onto a synthetic biodegradable polymer fashioned in the shape of a 3-year-old child's auricle. A polymer template was formed in the shape of a human auricle using a nonwoven mesh of polyglycolic acid molded after being immersed in a 1% solution of polylactic acid. Each polyglycolic acid-polylactic acid template was seeded with chondrocytes isolated from bovine articular cartilage and then implanted into subcutaneous pockets on the dorsa of 10 athymic mice. The three-dimensional structure was well maintained after removal of an external stent that had been applied for 4 weeks. Specimens harvested 12 weeks after implantation and subjected to gross morphologic and histologic analysis demonstrated new cartilage formation. The overall geometry of the experimental specimens closely resembled the complex structure of the child's auricle. These findings demonstrate that polyglycolic acid-polylactic acid constructs can be fabricated in a very intricate configuration and seeded with chondrocytes to generate new cartilage that would be useful in plastic and reconstructive surgery.

Animals↗

Free flap coverage of the hand.

Microvascular free tissue transfer has been a major advancement in the treatment of soft-tissue defects of the hand. Free tissue transfers have expanded our options and have altered our approach to hand defects. It is no longer satisfactory to cover hand wounds with unsightly, bulky flaps of tissue. Microsurgical free tissue transfers have given us the tools for more refinement in hand soft-tissue reconstruction and have changed the standards for a successful outcome.

Hand↗

Altered growth and branching patterns in synpolydactyly caused by mutations in HOXD13.

Hox genes regulate patterning during limb development. It is believed that they function in the determination of the timing and extent of local growth rates. Here, it is demonstrated that synpolydactyly, an inherited human abnormality of the hands and feet, is caused by expansions of a polyalanine stretch in the amino-terminal region of HOXD13. The homozygous phenotype includes the transformation of metacarpal and metatarsal bones to short carpal- and tarsal-like bones. The mutations identify the polyalanine stretch outside of the DNA binding domain of HOXD13 as a region necessary for proper protein function.

Amino Acid Sequence↗

Use of forearm flaps for the severely contracted first web space in children with congenital malformations.

Eighteen forearm flaps were used in 12 patients with congenital anomalies following release of severe first web-space contractures. Radial forearm axial pattern flaps were preferred in 10 children, and the dorsal interosseous system was used in 2 patients with incomplete palmar arches and those who had previous surgery. Ten of the flaps were transferred in children younger than 2 years of age. The results were excellent both esthetically and functionally. Superficial skin loss occurred in one patient. These local vascular island flaps are an excellent alternative for coverage in situations where a large tissue deficiency exists after an adequate release.

Child↗

Free flaps as flow-through vascular conduits for simultaneous coverage and revascularization of the hand or digit.

In complex extremity injuries, which include volar skin loss and ischemic digits, simultaneous coverage and revascularization are required. In this series of 12 patients, free-tissue transfers were utilized to provide both soft tissue coverage and a flow-through arterial conduit for revascularization. Eleven cases involved the hand or digits, and one case involved the great toe. Six cases were performed for acute ischemia associated with traumatic soft-tissue loss. The remaining six flaps were utilized to lengthen contracted vascular pedicles and provide vascularized soft-tissue coverage during reconstruction of severe hand and foot contractures. Nine temporoparietal fascia free flaps were used for hand or digit revascularization. Two fillet flaps were created, one from a nonreplantable foot and another from an isolated index amputation. The distal end of the axial artery of the flap was anastomosed to a digital artery to restore circulation. Fascial flaps were covered with full-thickness skin grafts. Primary wound healing was achieved in all patients. There were no flap losses or other complications. All the distal parts were revascularized adequately by the axial arteries of the flaps, and functional recovery was good. In this technique, the flap satisfied the need for both coverage and revascularization. Vein grafts were not needed. This series further describes the utility of flow-through flaps in the revascularization of digits.

Adolescent↗

Reconstruction following resection of malignancies of the upper extremity.

A multidisciplinary approach using advances in diagnosis, staging, adjuvant therapy, surgical resection, and especially reconstruction has made limb salvage a viable option in the treatment of most upper extremity malignancies. Although adequate surgical resection never should be compromised by reconstructive considerations, the reconstructive surgeon's input into preoperative planning may be crucial to the best possible functional and aesthetic outcome. Emphasis should be placed on a thorough evaluation by all members of the treatment team so that the best possible result is not compromised. A broad spectrum of techniques currently available for both salvage and restoration of function includes local soft-tissue flaps, regional pedicled and vascular island flaps, free tissue transfers, bone autografts and allografts (Fig. 17), endoprostheses, skin expansion, skeletal lengthening techniques, tendon transfers, and nerve and arterial grafts. This article reviews both new and well-established reconstructive options after resection of upper extremity malignancies in children and adults and provides illustrative case examples.

Amputation, Surgical↗

Urinary catecholamines and plasma hormones predict mood state in rapid cycling bipolar affective disorder.

Over the course of 1 year, a patient with a rapid cycling bipolar affective disorder was followed at weekly intervals to examine whether plasma hormones and urinary catecholamines could predict current or future mood. Higher cortisol levels were found to predict depressed mood 3 days after blood sampling, higher urinary dopamine predicted a manic mood 3 days after blood sampling, urinary norepinephrine was associated with severity of current mood and prolactin was lower with concurrent depressed mood. In multivariate analyses of mood against cortisol, prolactin and three urinary catecholamines, > 50% of the variance in mood state in 3 days was explained by combinations of these biologic measures, especially cortisol and urinary dopamine, while all five biologic variables contributed to explaining 50% of the variance in current mood state. Based on the interrelationships between urinary dopamine, norepinephrine and mood, we postulate the existence of an overcompensating mechanism which is reflected in opposing correlations between urinary dopamine and norepinephrine with mood, despite the two urinary catecholamines being positively correlated.

Adult↗

Bone marrow-derived murine mast cells migrate, but do not degranulate, in response to chemokines.

We have determined that several chemokines induce mast cell migration in vitro. This directed migration is dependent on the presence of particular extracellular matrix proteins and the activation status of the cells. Mast cell haptotactic responses were observed in response to various chemokines on vitronectin-, laminin-, and fibronectin-coated filters. Unstimulated mast cells were chemoattracted only by monocyte chemotactic protein-1 and RANTES on vitronectin-coated and, to a lesser extent, laminin-coated filters, whereas IgE-activated mast cells migrated in response to monocyte chemotactic protein-1, regulated on activation normal T expressed and secreted, platelet factor-4, and macrophage inflammatory protein-1 alpha on all three matrix proteins. No significant migration was observed on collagen type IV-coated or uncoated filters. Mast cell migration in response to chemokines on extracellular matrices and its enhancement by IgE-dependent activation provide a mechanism by which cells may be drawn to sites of inflammation. Chemokine-induced mast cell recruitment may be particularly relevant in host defense responses to parasitic infections, allergic reactions, Jones-Mote reactions, and in wound healing.

Animals↗

Infantile digital fibromas.

A series of 15 digital lesions in 8 pediatric patients is presented. All infantile digital fibromas appear early in life at the distal or proximal interphalangeal joint level, characteristically involve the ulnar three digits, may be multicentric, and undergo rapid growth within a short time. Histology reveals deep dermal origin and intracytoplasmic inclusion bodies not observed in any other fibrous proliferative disorders. A viral etiology has never been proved. The lesions may recur despite wide excision followed by resurfacing with a flap or graft. This distinctive lesion has no adult counterpart and should be considered in the differential diagnosis of hard, immobile distal digital masses in children.

Child↗