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C B Cuono

Publications and source records attributed to C B Cuono.

At least 19 recordsLinked to original sources
PubMed1998

Critical role of phosphagens in the energy cascade of cutaneous ischemia and protective action of phosphocreatine analogues in skin flap survival.

A general understanding of the pivotal role of phosphocreatine (PCr) as the principal determinant of skin flap survival is now emerging. Definitive metabolic investigations using phosphorus (31P) and proton (1H) magnetic resonance spectroscopy (MRS) have established that the inability to replenish metabolically exhausted PCr reserves predictably correlates with skin flap necrosis. Furthermore, postoperative parenteral administration of PCr has been shown to augment effectively skin flap survival. We hypothesized that creatine kinase, the enzyme controlling the utilization of the high-energy phosphate component of PCr, is a critical determinant of the tolerance of a skin flap to ischemic insult. In other words, if the rate of utilization of PCr is too rapid, PCr stores will rapidly deplete, and the flap will not be able to withstand a period of ischemia. Alternatively, if the rate of dephosphorylation of PCr is reduced, survival of skin flaps during periods of ischemia could be extended. To test this hypothesis, we investigated the metabolic distribution and fate of cyclocreatine (cCr), a competent creatine analogue with a lower affinity for the creatine kinase enzyme. When administered as 1.5 percent (w/w) of the normal diet of laboratory rats, cCr accumulates in skin as the competent phosphagen, phosphocyclocreatine (PcCr). Cutaneous flaps elevated in these animals, and studied by 31P and 1H MRS, demonstrate that once depletion of PCr has occurred, PcCr continues to sustain ATP levels. This results in significant enhancement of skin flap survival (p < 0.005). These observations confirm the importance of the creatine kinase enzyme in cutaneous flap ischemia and suggest new approaches to augment skin flap survival.

Adenosine Triphosphate↗
PubMed1995

The carpal boss. A 20-year review of operative management.

Between 1969 and 1989, 116 patients were evaluated and treated surgically for symptomatic carpal boss. Their mean age was 32 years and male and female patients were equally affected. 28 patients gave a history of previous injury. Surgical treatment consisted of excision of the localized bony abnormality and the associated degenerative arthritic process to the level of normal articular surfaces and normal adjacent cancellous bone. The mean follow-up period for the patients in this study was 42 months. Complete symptomatic relief was observed in 94% of the patients undergoing surgical treatment. Recurrence or persistence of symptoms developed in seven surgical patients. Six had a second operation with more extensive removal of sclerotic bone and degenerate cartilage, and all patients had relief of symptoms.

Adolescent↗
PubMed1994

Localized in vivo 31P NMR spectroscopy of skin flap metabolism.

We have used a rectangular surface coil and chemical shift imaging to conduct in vivo localized 31P NMR metabolic studies in a rat dorsal skin flap model. This approach permits regional comparisons without manipulation of either coil position or subject within the magnet bore. Both the PCr:Pi ratio (reflecting ischemia insult) and the PCr:ATP ratio (reflecting phosphagen reserves) decreased as functions of time and distance from the vascular pedicle. The maximum change was nearly 6-fold for the PCr:Pi ratio, and 3-fold for the PCr:ATP ratio. Signal contamination from subjacent muscle is constant and does not interfere with the metabolic evaluations of skin flaps. This technique may facilitate a better understanding of cutaneous metabolic derangements, such as burns and skin flaps used in reconstructive surgery, as well as studies of pharmacologic regimens developed for their treatment. It also holds potential for application in the study of congenital and neoplastic metabolic disorders of skin.

Adenosine Triphosphate↗
PubMed1993

Chemiluminescent restriction fragment length polymorphism analysis (DNA fingerprinting) to identify keratinocytes from two donors in co-culture.

The transplantation of allogeneic cells such as pancreatic islet cells, bone marrow, and keratinocytes for skin replacement is in growing use clinically. Present techniques which are used to distinguish transplanted allogeneic cells from phenotypically identical host cells in chimeric tissue have serious limitations. This study assesses the feasibility of using chemiluminescent restriction fragment length polymorphism (RFLP) analysis to distinguish between keratinocyte cell lines from 2 different donors grown in co-culture. We evaluated the sensitivity of this technique in tissue cultured cells in order to define its usefulness in clinical situations. RFLP analysis readily detects heterologous DNA comprising only 10% of a 5 micrograms sample. This was a detection threshold of 500 ng of high molecular weight DNA. With standard extraction methods, this represents the DNA obtained from 4000 cells. This new chemiluminescent technique is as sensitive as older techniques which employ radioactive probes, but avoids the hazards of handling radioactive material. Using this RFLP analysis, the presence of transplanted allogeneic cells can be readily detected in small biopsy specimens. This technique has wide potential application in allogeneic cellular transplantation investigations.

Cell Line↗
PubMed1991

Amelioration of renal ischemic injury by phosphocreatine.

Phosphocreatine (PCr) is a critical intracellular energy reservoir used in the regeneration of ATP. The aim of this study was to determine the efficacy of exogenously added PCr on preservation of renal function in an in vitro model. The renal artery and ureter of a rat were cannulated and the kidney was subjected to 45 min of normothermic in vivo ischemia. The kidneys were then perfused ex vivo with either a Krebs-bicarbonate solution (Krebs) or a Krebs solution containing 3 mM PCr or an osmotically balanced solution containing 3 mM PCr. Our results indicate that the perfusion of kidneys subjected to 45 min of warm ischemia with solutions containing PCr resulted in significant improvements in GFR, RPF, and V, FRNa and FRH2O compared to KREBS alone. This suggests that the important factor in preservation of kidney function after an initial ischemic insult may be the addition of PCr rather that the electrolyte solution used.

Absorption↗
PubMed1991

In vitro reconstitution of skin: fibroblasts facilitate keratinocyte growth and differentiation on acellular reticular dermis.

Extensive full-thickness burns require replacement of both epidermis and dermis. We have described a method in which allogeneic dermis from engrafted cryopreserved cadaver skin was combined with cultured autologous keratinocytes. In the present study we combined human keratinocytes and fibroblasts, and acellular human dermis in vitro and transplanted this "reconstituted skin" into athymic mice. Both human papillary dermis in which the basement membrane zone has been retained and human reticular dermis that has been repopulated with human dermal fibroblasts are good substrates for keratinocyte attachment, stratification, growth, and differentiation. Both of these dermal preparations can be lyophilized and stored at room temperature without losing their ability to support keratinocyte growth. In contrast, human papillary dermis that has been treated with trypsin lacks laminin and collagen type IV in the BMZ and supports keratinocyte attachment and differentiation less well.

Animals↗
PubMed1990

Double-Z rhombic technique for reconstruction of facial wounds.

The double-Z rhombic technique of repair of excisional defects is characterized by borrowing the required tissue from two nonadjacent opposite sides of the defect. Most other flaps borrow the required tissue from a single adjacent region or all adjacent directions. The "sharing" of tissue from two opposite regions minimizes tension in that direction, while not borrowing from the remaining regions prevents the distortion of anatomic landmarks located along that direction. The orientation of the final scar and direction of tissue tension can be controlled by rotating the rhombic defect about its central axis. This study was undertaken to assess the utility of the double-Z rhombic technique in terms of cosmesis and avoidance of displacement of mobile anatomic landmarks such as eyelids, eyebrows, nasal alae, and lips. Excisional defects resulting from removal of skin neoplasms in 30 patients in whom primary closure or reconstruction with direct tissue advancement was not feasible and displacement of facial landmarks was undesirable were reconstructed using the double-Z rhombic technique. No considerable asymmetry or facial anatomic landmark deformity was observed in any of the 30 patients. Our results are presented along with representative illustrations.

Basal Cell Carcinoma↗
PubMed1989

Upper extremity entrapment neuropathy and tourniquet use in patients undergoing hemodialysis.

Patients with end-stage renal disease, undergoing hemodialysis, have been shown to have an increased prevalence of carpal tunnel syndrome. From mid-1981 through 1986, 21 patients undergoing hemodialysis were operated on for 33 cases of clinically diagnosed entrapment of the median and/or ulnar nerves, including 14 extremities with functioning vascular access. All patients report improvement in symptoms and function in the affected extremity. Preoperative tourniquet use did not have a permanent adverse effect on any access site. Electrophysiologic studies were not reliable predictors of clinically resolvable nerve entrapment.

Adult↗
PubMed1988

Nuclear magnetic resonance spectroscopy of skin: predictive correlates for clinical application.

The first application of phosphorous 31 (31P) and proton (1H) nuclear magnetic resonance (NMR) spectroscopy to the analysis of the metabolic profiles of skin flaps in a rat model and of human skin grafts is presented. Resonances of adenosine triphosphate (ATP), phosphocreatine (PCr), and inorganic phosphate (Pi) were identified in 31P nuclear magnetic resonance spectra. Resonances of phosphocreatine, creatine (Cr), and lactate (Lac) were identified in 1H nuclear magnetic resonance spectra. The most significant finding was the substantial presence of phosphocreatine as the major high-energy phosphometabolite in mammalian skin, a finding which heretofore has not been widely recognized. An energy shuttle between phosphocreatine and ATP is operative in skin to buffer the fall in ATP during ischemic (anaerobic) insult. Inability to replenish exhausted phosphocreatine reserves predictively correlates with eventual flap necrosis. We have defined and analyzed temporal fluxes in the phosphocreatine-creatine and phosphocreatine plus creatine-lactate ratios by proton nuclear magnetic resonance. Both are sensitive, accurate, and unambiguous early prognostic indices of eventual flap outcome. These findings support the concept that the fate of a flap may be established as early as 3 hours after elevation and have laid the groundwork for development and application of noninvasive in vivo nuclear magnetic resonance spectroscopy to the study of skin flaps in animals and humans.

Adenosine Triphosphate↗
PubMed1988

Reconstitution of structure and cell function in human skin grafts derived from cryopreserved allogeneic dermis and autologous cultured keratinocytes.

Grafts of allogeneic dermis plus autologous epidermal cell cultures were used to replace extensively burned skin. Cryopreserved split-thickness cadaveric skin was grafted onto debrided burn wound, and autologous keratinocytes were cultured from uninjured donor sites. Several weeks later, allograft epidermis was abraded and replaced with the keratinocyte cultures. The final grafts were thus composites of autologous cultured epidermis and allogeneic dermis. In a case with 28 months follow-up, reconstitution of the dermal-epidermal (BMZ.1) and microvascular (BMZ.2) basement membrane zones was studied immunohistochemically and ultrastructurally. Immediately before grafting, thawed cryopreserved skin reacted with antibodies against laminin and type IV collagen in normal patterns. Twenty-nine days after grafting, BMZ.1 reacted weakly with both antibodies, and anticollagen type IV reactivity was absent from BMZ.2. Antilaminin reactivity of BMZ.2, however, was moderately intense, consistent with recent neovascularization. On day 29, the allograft epidermis was replaced with autologous keratinocyte cultures. Twenty-five days later (54 d after allografting), staining of both BMZs was intense with both antibodies. Ultrastructurally, at day 76 (47 d after culture placement) BMZ.1 revealed only small hemidesmosomes, few incipient anchoring fibrils, and a discontinuous lamina densa. BMZ.2, however, was fully reconstituted. By 124 d, both BMZs appeared normal. Observations in the dermis at 76 d included the presence of lymphocytes, organellar debris, and hyperactive collagen fibrillogenesis, all indicative of dermal remodelling. The microvasculature was well differentiated, but no elastic fibers or nerves were found. In the epidermis, melanocytes and evidence of melanosome transfer were seen at 5, 47, and 95 d after grafting of keratinocyte cultures. We conclude that the composite procedure reconstitutes skin with excellent textural and histologic qualities.

Basement Membrane↗
PubMed1987

Composite autologous-allogeneic skin replacement: development and clinical application.

A major unsolved problem in skin restoration in severe burns is replacement of lost dermis. We report the development and clinical application of a composite grafting technique in which allogeneic skin is the source of dermis, and cultured autologous keratinocytes generate epidermis. Excised burn wounds are resurfaced with unmatched allograft. Immunosuppression from the burn and reduced immunoreactivity of the allograft permit successful allograft engraftment. Keratinocyte cultures are initiated from the patient. Allogeneic epidermis is removed, and the dermal bed is resurfaced with keratinocyte cultures. The allogeneic dermis promotes rapid (less than 7 days) stratification, maturation, and integration of the cultures and the synthesis of anchoring fibrils. One case followed 11 months has shown no evidence of rejection. We reason that removal of the epidermis from allograft eliminates the majority of cells constitutively expressing alloclass II antigens, leaving behind a viable allogeneic dermal bed that serves as an ideal substrate for engraftment and integration of keratinocyte cultures but does not initiate rejection.

Adult↗
PubMed1987

Augmentation of experimental skin flap survival via postoperative phosphocreatine replacement.

Despite improvements in our understanding of cutaneous vascular territories, clinical skin flap necrosis resulting from ischemic compromise is still a reality. Therapy with vasodilators has been generally unsuccessful, but replacement of high-energy phosphometabolites through the use of ATP-MgCl2 and fructose 1,6-diphosphate has been effective. Recently we reported that phosphocreatine is the major high-energy phosphometabolite in mammalian skin and that ATP levels and cellular well-being in skin flaps are dependent on adequate supply of this phosphometabolite. We report herein the successful augmentation of survival of ischemically compromised skin flaps through postoperative phosphocreatine infusion. This metabolite effectively circumvents the nonfunctioning mitochondrial creatine-phosphocreatine energy shuttle without disturbing the delicate [ATP]/[ADP] balance in the cytosol. In addition, phosphocreatine may favorably redistribute blood flow from muscle to the ischemically compromised skin.

Animals↗
PubMed1987

Burn injury.

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Burns↗
PubMed1986

Demonstration of cutaneous doxorubicin extravasation by rhodamine-filtered fluorescence microscopy.

Accidental extravasation of the widely used antineoplastic anthracycline doxorubicin (adriamycin) is capable of causing serious and on-going skin and soft tissue necrosis leading to loss of limb function. The only effective cure has been the complete surgical excision of drug-contaminated tissue. Surgical excisions preparatory to skin grafting have often underestimated the extent of drug infiltration into tissue. Using an experimental technique utilizing the drug's natural property of red fluorescence, we were able to effect complete surgical excision by rhodamine fluorescence microscopy in frozen sections of resected skin.

Child, Preschool↗
PubMed1986

Free radial forearm flap versatility for the head and neck and lower extremity.

Microsurgical techniques have developed numerous territories suitable for free tissue transfer. However, the demand for thin cutaneous resurfacing limits the choice of flaps available to the reconstructive microsurgeon. The radial forearm flap is a thin, axial, fasciocutaneous flap, offering pliable cutaneous resurfacing, with or without sensation. We have used 15 flaps to reconstruct defects in the head and neck and lower extremity resulting from burns, blunt and avulsive trauma, radiation necrosis, and tumor ablation. Two flaps (15 percent) developed venous congestion and were salvaged by reoperation. One retrograde flap (7.5 percent) developed partial necrosis from arterial insufficiency. Neural re-innervation was successful in two out of three patients in whom it was attempted. Two patients (15 percent) sustained minor donor site skin graft loss that healed secondarily. In our series of predominantly older patients the donor sites have been relatively inconspicuous at one year follow-up. A functional restoration was achieved in all patients.

Adult↗