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Biomedical subjects

J Upton

Publications and source records attributed to J Upton.

At least 19 recordsLinked to original sources
PubMed2000

The TIGR gene indices: reconstruction and representation of expressed gene sequences.

Expressed sequence tags (ESTs) have provided a first glimpse of the collection of transcribed sequences in a variety of organisms. However, a careful analysis of this sequence data can provide significant additional functional, structural and evolutionary information. Our analysis of the public EST sequences, available through the TIGR Gene Indices (TGI; http://www.tigr.org/tdb/tdb.html ), is an attempt to identify the genes represented by that data and to provide additional information regarding those genes. Gene Indices are constructed for selected organisms by first clustering, then assembling EST and annotated gene sequences from GenBank. This process produces a set of unique, high-fidelity virtual transcripts, or tentative consensus (TC) sequences. The TC sequences can be used to provide putative genes with functional annotation, to link the transcripts to mapping and genomic sequence data, and to provide links between orthologous and paralogous genes.

Base Sequence↗
PubMed2000

Experimental use of fibrin glue to induce site-directed osteogenesis from cultured periosteal cells.

The purpose of this study was to determine whether a combination of fibrin glue and cultured periosteal cells will result in new bone formation at heterotopic sites in nude mice. Growing cells and developing matrices surrounding periosteal explants from the diaphyses of radii of newborn calves were minced and mixed with fibrin glue in a syringe. The cell/matrix-fibrin glue admixture was then injected into the subcutaneous space on the dorsum of athymic nude mice. After 12 weeks of implantation, gross morphology and histologic investigations showed newly formed bone structures in all cell/matrix-fibrin glue admixtures, but none in fibrin glue injected alone and used as control samples. Osteopontin, a protein important in bone development, was identified by a Western blot assay of the cell/matrix-fibrin glue composite. This study supports the feasibility of initiating site-directed formation of bone structures at heterotopic tissue sites by means of injection of cultured periosteal cells and matrix in a fibrin glue carrier.

Animals↗
PubMed2000

Soft-tissue augmentation with injectable alginate and syngeneic fibroblasts.

Tissue engineering, a field that combines polymer scaffolds with isolated cell populations to create new tissue, may be applied to soft-tissue augmentation-an area in which polymers and cell populations have been injected independently. We have developed an inbred rat model in which the subcutaneous injection of a hydrogel, a form of polymer, under vacuum permits direct comparison of different materials in terms of both histologic behavior and their ability to maintain the specific shape and volume of a construct. Using this model, we compared three forms of calcium alginate, a synthetic hydrogel, over an 8-week period-standard alginate that was gelled following injection into animals (alginate post-gel), standard alginate that was gelled before injection into animals (alginate pre-gel) and alginate-RGD, to which the cell adhesion tripeptide RGD was linked covalently (RGD post-gel). Parallel groups that included cultured syngeneic fibroblasts suspended within each of these three gels were also evaluated (alginate post-gel plus cells, alginate pre-gel plus cells, and RGD post-gel plus cells). The study used 54 inbred Lewis rats (n = 9 for each of the six groups). Construct geometry was optimally maintained in the alginate post-gel group in which 58 percent of the original volume was preserved at 8 weeks and increased to 88 percent at 8 weeks when syngeneic fibroblasts were included within the gel. Volume was not as well preserved in the RGD post-gel group (25 percent of original volume at 8 weeks), but again increased when syngeneic fibroblasts were included (41 percent of original volume at 8 weeks). Maintenance of volume was poorest in the alginate pre-gel group (31 percent of original volume at 8 weeks) and failed to be augmented by the addition of fibroblasts (19 percent of original volume at 8 weeks). Histologically, the gel remained a uniform sheet surrounded by a fibrous capsule in the alginate post-gel groups. In the alginate pre-gel and RGD post-gel groups, there was significant ingrowth of a fibrovascular stroma into the gel with fragmentation of the construct. In constructs in which syngeneic fibroblasts were included, cells were visualized throughout the gel but did not extend processes or appear to contribute to new tissue formation. Material compression testing indicated that the alginate and RGD post-gel constructs became stiffer over a 12-week period, particularly in the cell-containing groups. Our results suggest that calcium alginate could be a suitable agent for soft-tissue augmentation when gelled subcutaneously following injection. The addition of syngeneic fibroblasts enhanced the ability of the gel to maintain the volume of a construct; this seems to be mediated by increased gel stiffness rather than by de novo tissue formation. Our animal model, in combination with material testing data, permits rigorous comparison of different materials used for soft-tissue augmentation.

Alginates↗
PubMed2000

Particle films for suppression of the codling moth (Lepidoptera: Tortricidae) in apple and pear orchards.

Studies were conducted in 1997 and 1998 to evaluate the effects of three particle film formulations consisting of kaolin and adjuvants on neonate larvae, ovipositing adult females, and eggs of the codling moth, Cydia pomonella (L.). Neonate larval walking speed, fruit discovery rate, and fruit penetration rate on apple host plants coated with particle films were significantly lower than on host plants without particle films in laboratory assays. Females oviposited less on host plants covered with a particle film residue than on untreated plants in laboratory choice and no-choice tests. Hatch rate of codling moth neonate larvae was unaffected by particle films sprayed on host plants either before or after oviposition. Fruit infestation rates were significantly reduced on particle film-treated trees compared with untreated trees for both first- and second-generation codling moth in field trials in both apple and pear orchards. Particle films appear to be a promising supplemental control approach for codling moth in orchards where moth density is high, and may represent a stand-alone method where moth densities are lower.

Animals↗
PubMed1999

Vascular malformations of the upper limb: a review of 270 patients.

Vascular malformations of the upper limb were once thought to be impossible to properly diagnose and treat. We reviewed our experience with these malformations of the upper limb in 270 patients seen over a 28-year period. These anomalies were slightly more common in females than males (ratio, 1.5:1.0). The malformations were categorized as either slow flow (venous, n = 125; lymphatic, n = 47; capillary, n = 32; combined, n = 33) or fast flow (arterial, n = 33). Three categories of fast-flow malformations were identified and designated as types A, B, and C. Over 90% of these lesions could be properly diagnosed by their appearance and growth pattern within the first 2 years of life. Additional radiographic studies were used to confirm this diagnosis and to define specific characteristics. Magnetic resonance imaging with and without contrast best demonstrated site, size, flow characteristics, and involvement of contiguous structures for all types of malformations. Algorithms for treatment of both slow-flow and fast-flow anomalies are presented. Two hundred sixty surgical resections were performed in 141 patients, including 24 of 33 fast-flow anomalies. Preoperative angiographic assessment, with magnified views, was an important preoperative adjunct before any well-planned resection of fast-flow arteriovenous malformations. The surgical strategy in all groups was to thoroughly extirpate the malformation, with preservation of nerves, tendons, joints, and uninvolved muscle, and microvascular revascularization and skin replacement as required. Resections were always restricted to well-defined regions and often completed in stages. Symptomatic slow-flow malformations and types A and B fast-flow anomalies were resected without major sequelae. Type C arterial anomalies, diffuse, pulsating lesions with distal vascular steal, and involvement of all tissues, including bone, progressed clinically and resulted in amputation in 10 of 14 patients. The complication rate was 22% for slow-flow lesions and 28% for fast-flow lesions.

Adolescent↗
PubMed1999

Formation of phalanges and small joints by tissue-engineering.

BACKGROUND: This report describes the formation of small phalanges and whole joints from three types of bovine-cell sources transplanted onto biodegradable polymer matrices. The resulting structures had the shape and composition of human phalanges with joints. METHODS: Fresh bovine periosteum was wrapped around a copolymer of polyglycolic and poly-L-lactic acid. Separate sheets of polyglycolic acid polymer were then seeded with chondrocytes and tenocytes isolated from the shoulders of freshly killed calves. The gross form of a composite tissue structure was constituted in vitro by assembling the parts and suturing them to create models of a distal phalanx, a middle phalanx, and a distal interphalangeal joint. RESULTS: Subcutaneous implantation of the sutured composite tissues into athymic mice resulted in the formation, after twenty weeks, of new tissue with the shape and dimensions of human phalanges with joints. Histological examination revealed mature articular cartilage and subchondral bone with a tenocapsule that had a structure similar to that of human phalanges and joints. There was continuous cell differentiation at the ectopic site even after extended periods. CONCLUSIONS: These findings suggest that the formation of phalanges and small joints is possible with the selective placement of periosteum, chondrocytes, and tenocytes into a biodegradable synthetic polymer scaffold.

Animals↗
PubMed1998

Transplantation of cells in matrices for tissue regeneration.

Tissue engineering is a field that has truly emerged in the last decade. It has brought together diverse technologies, e.g. cell culture, polymer chemistry and transplantation. The creation of matrices to guide tissue regeneration allows manipulation at several levels, i.e. the cells employed, the choice of polymer and the design of construct assembly methods. We present experience using such constructs to guide regeneration of diverse tissues, e.g. liver, intestine, urologic tissue, skin, cartilage, bone and cardiovascular structures. Emerging concepts in using cell/polymer constructs include the need for appropriate modeling of the micromechanical environments of different tissues, as well as the necessity of finding new strategies to achieve vascularization of tissues for transplant. Finally, the concept of applying tissue-engineered structures to non-native sites is discussed.

Journal Article↗
PubMed1998

Low-dose diuretic and/or dietary sodium restriction when blood pressure is resistant to ACE inhibitor.

AIM: To compare the efficacy of indapamide (1.25 mg daily) and low-salt diet (<100 mmol/day) separately and in combination in essential hypertensive patients with inadequate BP response to perindopril. DESIGN AND METHODS: Randomized double-blind, double-dummy, crossover design. The randomized treatments were indapamide 1.25 mg daily, sodium chloride 80 mmol daily, the combination of indapamide and sodium chloride and placebo. All patients received perindopril 4 mg daily and maintained a low-sodium diet. RESULTS: 19 patients entered and 17 completed the study. Prior to randomization, average clinic sitting blood pressure was 162/101 mm Hg and average 24-h urine sodium excretion was 157 mmol/day. Compared to the phase in which patients received perindopril with sodium repletion, clinic and ambulatory BPs were significantly reduced (p<0.01) in all the other phases. Indapamide had a greater effect on BP than dietary sodium restriction, and in combination their effects were additive. The effect of indapamide on ambulatory BP persisted throughout 24 h, but the effect of the low-salt diet was predominantly observed during waking hours. CONCLUSIONS: In hypertensives with BP resistant to the angiotensin converting enzyme (ACE) inhibitor perindopril, the diuretic indapamide had greater additional efficacy and longer duration of action than dietary sodium restriction. In combination they had additive effects on BP.

Adolescent↗
PubMed1998

Plantar verrucous carcinoma following transmetatarsal amputation and renal transplantation.

Verrucous carcinoma is a rare, low-grade, well-differentiated squamous cell carcinoma that may occur anywhere on the skin. It is slow growing, enlarges relentlessly, and invades locally. Most cutaneous verrucous carcinomas are found on the plantar surface of the foot, and share many gross and histological characteristics common to the ubiquitous verruca vulgaris. It is not uncommon for verrucous carcinoma of the sole to be mistaken for the more common verruca plantaris. The case of a 53-year-old white male with plantar verrucous carcinoma following cadaveric renal transplantation, right popliteal-tibial bypass, and a right transmetatarsal amputation is presented. Treatment included reamputation followed by reconstruction with a free radial forearm fasciocutaneous flap. Verrucous carcinoma is a slow-growing but relentlessly invading tumor that is easily misdiagnosed. The extent of early resection is often inadequate. We must be aware that certain persistent "warts" may represent a form of cancer that is treated differently from common verrucae or other squamous carcinomas.

Amputation, Surgical↗
PubMed1998

Microsurgical replantation of the lip: a multi-institutional experience.

Traumatic amputation of the lip is a rare yet devastating event affecting both form and function. Considering the available methods for reconstruction, replantation may offer a reasonable solution. We sought to characterize the variables associated with lip replantation and to assess the outcome in a retrospective review of 13 lip replantations performed in 12 institutions utilizing a form database and clinical and photographic analysis. Lip replantation was successful in all 13 patients; partial flap loss occurred in one patient owing to iatrogenic injury. Follow-up averaged 3.1 years. Average patient age at the time of injury was 21.1 years. There were six male and seven female patients. Injuries in two patients were the result of a human bite, the remaining injuries resulted from dog bites. One patient had significant associated injuries. Average length of hospital stay was 11.9 days. Ten patients suffered amputations of the upper lip, and three suffered amputations of the lower lip. Average defect size was 10.6 cm2. Operative time averaged 5.7 hours (range 2.5 to 12 hours). Warm ischemia time averaged 2.9 hours, and cold ischemia time averaged 2.7 hours. Donor and recipient veins were often scarce; all patients had at least one arterial anastomosis, whereas no vein was available in 7 of 13 patients; vein grafts were required in one patient. Leech therapy was employed in 11 of 13 patients. Anticoagulant therapy was administered in the majority of patients. Systemic heparin was utilized in 10 of 13 patients, low molecular weight dextran was used in 7 of 13 patients, and aspirin was given to 7 of 13 patients. One bleeding complication was incurred. An average of 6.2 units of packed red blood cells was administered to 12 of 13 patients (adjusted to 250 cc/unit). Antispasmodic therapy was employed in six of eight patients intraoperatively and in two of eight patients postoperatively. Intraoperative complications included difficulty identifying veins in 7 of 13 patients, arterial spasm in 1 of 13 patients, and vessel diameter < 0.5 mm in 4 patients. Postoperatively, one patient suffered vein thrombosis requiring anastomotic revision. Broad spectrum antibiotics were administered to all patients, and there were no infections. Nearly one-third (4 of 13) patients suffered prolonged edema lasting > 4 months. Color match of the replanted lip segment was rated excellent in all cases. Hypertrophic scarring occurred in 6 of 13 patients. A total of 12 revision procedures was performed in six patients. Interestingly, leech therapy resulted in permanent visible scarring as a result of the leech bite in 6 of 11 patients treated. Ten patients demonstrated active orbicularis muscle contraction in the replanted lip segment. Stomal continence was present in all lips. Sensibility return in the replanted lip segment was quite good with 12 of 13 patients demonstrating at least protective moving two-point sensibility (> or = 10 mm). Partial replant necrosis in one patient resulted in significant scar and contraction that compromised the aesthetic appearance. Overall, however, all patients were uniformly pleased with their final results. This clinical study is one of the largest of its kind on lip replantation. Although this represents a multi-institutional experience, the data are remarkably consistent. Re-establishment of venous outflow seems to be the most problematic technical challenge. By incorporating the adjuncts of anticoagulation, leech therapy, and antispasmodics, a successful outcome can be expected despite the paucity of vessels and small vessel size. The risks of blood transfusion, lengthy operative time, and hospital stay must be weighed against the functional benefits.

Adolescent↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗