Isolated Osseous Excision in the Adult Carpus: A Narrative Review.

Various pathologies of the adult carpus result in clinical scenarios where excision can be considered and even recommended. In the appropriate patient population, isolated carpal excision can alleviate pain and improve mobility. Excisions of the pisiform, trapezium, and trapezoid have abundant literature evidence to support positive long-term functional outcomes. In contrast, isolated excision of the capitate, hamate, and triquetrum has limited support in the literature secondary to compromise of carpal mechanics and lead to recurrent pain. Additionally, isolated scaphoid and lunate excision are best avoided secondary to carpal collapse and should be paired with concomitant stabilizing procedures in the carpus. This article provides a comprehensive literature review of isolated excision of each osseous carpal bone, their indications, and previously assessed outcomes.

The "Standing Peanut" Scaphoid View: A Semi-supinated Radiographic View for Intraoperative Evaluation of Screw Placement in Scaphoid Waist Fractures.

Scaphoid waist fractures are the most common fracture of the scaphoid. Operative management is indicated with unstable fractures and often for nondisplaced waist fractures to decrease time to union and return to work/sport. Screw placement within the central axis of the scaphoid is paramount and correlates with outcomes. Assessment of intrascaphoid screw placement is classically done via intraoperative fluoroscopy. An additional fluoroscopic view is presented to assist in confirming implant positioning. Along with the standard anterioposterior, lateral, pronated oblique, and "scaphoid" view we obtain a "standing peanut" view for assessment of central screw placement. This view also allows for further evaluation of center/center positioning and better assessment of fixation crossing the fracture into the proximal pole. The "standing peanut" view is best obtained in a sequential manner beginning with the forearm in neutral rotation. First, the forearm is then supinated 30 degrees; next, the wrist is placed at 45 degrees of ulnar deviation. Then finally, 10 degrees of wrist extension. We utilize this additional intraoperative view in conjunction with the standard fluoroscopic views for assessing and ensuring center-center implant positioning, particularly within the proximal pole. When ensuring center-center positioning, we prefer this view as an adjunct view to the standard fluoroscopic views intraoperatively. It provides a beneficial view of the proximal pole delineating the number of screw threads that have obtained proximal pole purchase. We have found it particularly useful in the setting of scaphoid waist fracture nonunion with the classic 'humpback' deformity after correction with volar interposition grafting. Standard radiographic views may be misinterpreted regarding implant positioning if there remains any residual flexion. The view requires little in the way of training to obtain once appreciated and exposes the patient to minimal additional radiation.

Developmental toxicity of di-(C(7)-C(9) alkyl) phthalate and di-(C(9)-C(11) alkyl) phthalate in the rat.

Two phthalate esters, di-(C(7)-C(9) alkyl) phthalate (D79P) and di-(C(9)-C(11) alkyl) phthalate (D911P), have been assessed for their potential to cause developmental toxicity in the rat. Groups of 22 timed-mated Sprague-Dawley rats were administered 250, 500, or 1000 mg/kg D79P or D911P daily by oral gavage (5 ml/kg) between gestation days (GD) 1 and 19. Control animals received the vehicle (olive oil) alone. On GD20, the animals were sacrificed and the fetuses examined. Treatment resulted in no signs of maternal toxicity, as assessed by adjusted maternal bodyweight gain throughout gestation and clinical examinations, and no effects upon litter size, fetal survival or bodyweight. Pups of the high dose D79P and intermediate and high dose D911P groups showed increased incidences of supernumerary lumbar ribs. There was a significant increase in dilated renal pelves in pups of the low dose D79P and high dose D911P groups, but only for D911P was there a significant trend. Consequently, the no observed adverse effect level (NOAEL) for maternal toxicity for both D79P and D911P is 1000 mg/kg/day. The NOAEL values for developmental toxicity are 500 mg/kg/day D79P and 250 mg/kg/day D911P.

Two-generation reproduction toxicity studies of di-(C(7)-C(9) alkyl) phthalate and di-(C(9)-C(11) alkyl) phthalate in the rat.

Di-(C(7)-C(9) alkyl) phthalate (D79P) and di-(C(9)-C(11) alkyl) phthalate (D911P), based on high-normality linear oxo-alcohols, have been assessed for their impact upon reproductive performance in Sprague-Dawley rats. Rats were continuously exposed to either D79P or D911P at dietary levels of 0%, 0.1%, 0.5%, or 1.0% over two generations. Selected F(0) offspring (F(1) generation) were exposed to the same dietary concentration of D79P or D911P as the respective F(0) animals, and were mated to produce F(1) offspring. Both D79P and D911P markedly reduced body weight gain in F(0) and F(1) adult males at the highest dose, but females were affected to a lesser extent. There was no impairment of fertility, fecundity, or development in either generation, but body weights of offspring in the 1.0% D79P and 1.0% D911P groups were slightly and transiently reduced over the weaning period. Although decreases in the weight of several organs were accounted for by depressed body weight, ovary weights were reduced in both generations exposed to 1.0% D79P, and epididymidal weights were slightly reduced in adults of both generations exposed to 1.0% D911P. However, ovarian function-assessed by the oestrus cycle and mating behaviour-and epididymidal sperm concentration, motility, and morphology were unaffected by either substance. Treatment resulted in liver changes, particularly in males, characterised by increased liver weight in young animals, histopathologic changes and reduced organ weight in mature animals, and an increase in palmitoyl CoA oxidase activity. In conclusion, neither D79P nor D911P impaired reproductive function in rats when administered in the diet at levels that induce systemic toxicity, and the NOAEL for effects on reproduction in the rat is 0.5% for both D79P and D911P.

Corneal subepithelial nodular scarring treated with phototherapeutic keratectomy in a child with Rothmund-Thomson syndrome.

PURPOSE: To report the use of excimer laser phototherapeutic keratectomy (PTK) in the treatment of corneal subepithelial nodular scarring in a child with Rothmund-Thomson syndrome (RTS), a form of ectodermal dysplasia. METHODS: A case report and review of the literature. RESULTS: Excimer laser PTK successfully treated the recurrent anterior stromal fibrosis and irregular astigmatism, facilitating visual development. The use of excimer laser PTK prevented the development of dense amblyopia in this child. CONCLUSION: This case demonstrates an indication for excimer laser PTK in the pediatric population.

The effect of transdermal nicotine on digital perfusion in reformed habitual smokers.

The effects of transdermal nicotine-assisted smoking cessation on digital perfusion and health-related quality of life were assessed in 10 chronic smokers. Components of digital blood flow were evaluated by digital temperature and laser Doppler fluxmetry before, during, and after a standardized cold challenge. Nutritional flow was measured by vital capillaroscopy; a quantitative perfusion profile was obtained by laser Doppler perfusion imaging. A battery of validated measures were used to evaluate health-related quality of life. The microvascular response of smokers was evaluated before smoking cessation and at 2 and 7 days after smoking cessation and was compared with the response of nonsmoking controls. Results demonstrated that a (1) cutaneous microvascular perfusion was lower in smokers than nonsmokers, (2) the acute administration of transdermal nicotine did not decrease cutaneous perfusion, (3) smoking cessation and transdermal nicotine normalized digital microvascular perfusion by 7 days, and (4) transdermal nicotine and smoking cessation did not negatively impact health-related quality of life.

Upper-extremity tendinitis and overuse syndromes in the athlete.

Overuse injuries are the result of repetitive microtrauma to the musculotendinous unit. Treatment protocols are based on the stage of the inflammatory process that is active at the time of diagnosis. Control of the inflammatory response with rest, elevation, and ice is the treatment objective during the inflammatory stage. Prevention of further injury is the primary treatment goal throughout the proliferative phase. Once the inflammatory process has reached the maturation stage, rehabilitation can begin with flexibility exercises, isometric contractions, and a slow return to strength training. Surgical decompression is frequently necessary if chronic inflammation causes fibrosis of the fibro-osseous tendon sheaths. Anomalous muscle bellies and tendinous interconnections can be contributing factors to overuse syndromes. Properly structured training programs and rehabilitation regimens can prevent tendinitis and overuse syndromes.

The role of operative arthroscopy for the diagnosis and treatment of lesions about the distal ulna.

Operative arthroscopy of the wrist compliments the physical examination and radiographic imaging to improve diagnosis and treatment of lesions about the distal ulna. This article reviews the relevant anatomy, biomechanics, and classification of acute and degenerative lesions of the triangular fibrocartilage complex (TFCC). Minimally invasive diagnostic and management techniques for TFCC tears are described in detail.

The catalytic activity of cytochrome P450cam towards styrene oxidation is increased by site-specific mutagenesis.

The styrene oxidation activity of cytochrome P450cam, has been greatly improved by rational protein engineering. Compared to the wild-type enzyme, the active-site mutants Y96A and Y96F bound styrene more tightly, consumed NADH more rapidly, and were more efficient at utilising reducing equivalents for product formation. Styrene oxide formation rates were enhanced 9-fold in the Y96A mutant relative to wild-type, and 25-fold in the Y96F mutant, thus demonstrating the effectiveness of active-site redesign in improving the activity of a haem monooxygenase towards an unnatural substrate.

Inhibition of proliferating lens epithelium with antitransferrin receptor immunotoxin.

We investigated the effect of an antitransferrin receptor immunotoxin (454A12-rRA) on proliferating human and baboon lens epithelium in vitro. Human and baboon lens epithelial cells grown in modified TC-199 medium at 35 degrees Celsius in 7% CO2 were seeded in 24 well plates at a density of 17,500 cells/ml to 40,000 cells/ml. The cells were exposed to various concentrations of 454A12-rRA for seven days. The sensitivity of proliferating human lens epithelium to 454A12-rRA was dependent on the dose, with a 60% to 70% reduction in cell counts at immunotoxin concentrations of 100 ng/ml and above. The immunotoxin had no significant effect on baboon lens epithelium in vitro, which suggests that it is specific for human tissue. By preventing the proliferation of human lens epithelial cells, immunotoxin 454A12-rRA may be useful in the management of posterior capsule opacification after planned extracapsular cataract surgery.

Suppression of human corneal epithelial proliferation with breast carcinoma immunotoxin.

We examined the effects of the immunotoxin 260F9 Mab-recombinant ricin A (developed against human breast carcinoma) on proliferating and confluent human corneal epithelium (HCE) cells in vitro. HCE cells derived from explants of discarded human donor corneoscleral rims were established as proliferating and confluent cell cultures, and were exposed continuously for 7 days to immunotoxin. Final cell counts at day 7, and thymidine uptake measured at days 1 and 7 postexposure, showed > 95% suppression of proliferating cells at an immunotoxin concentration of 10 ng/ml, with confluent HCE cells relatively unaffected. This immunotoxin may prove useful in treatment of proliferative ocular epithelial diseases such as epithelial downgrowth or squamous cell carcinoma of the ocular surface.

Inhibition of human corneal epithelium with immunotoxin 454A12-rRA.

We examined the effects of the immunotoxin 454A12-rRa on proliferating and confluent human corneal epithelium (HCE) in vitro. Proliferating HCE was sensitive to 454A12-rRA in a dose-dependent fashion. At immunotoxin concentrations of 1,000 ng/ml for 7 days we observed an 86% reduction in cell counts. Confluent HCE was not sensitive to 454A12-rRA at equivalent concentrations of immunotoxin. These data confirm previous observations regarding selective sensitivity of proliferating ocular tissue to immunotoxin, but suggest that HCE is less sensitive to 454A12-rRA than other ocular cell types.

Inhibition of human subconjunctival fibroblast proliferation by immunotoxin.

The ability to target proliferating cells is important for agents used to modulate wound healing by decreasing the growth of fibroblasts. Proliferating cells are known to express increased numbers of transferrin receptors and have increased receptor turnover. 454A12 Mab-rRA, an immunotoxin containing anti-human transferrin receptor monoclonal antibody conjugated to recombinant ricin A chain, was shown to inhibit the proliferation of human subconjunctival fibroblasts in vitro. A dose-related reduction of cell counts was observed in proliferating cells. More than 90% inhibition was achieved with an immunotoxin concentration of 10 ng/ml per 20,000 cells plated. In contrast, confluent fibroblasts were markedly less sensitive to the immunotoxin at equivalent concentrations. Comparative experiments demonstrated that 5-fluorouracil has less specificity for proliferating cells, with significant death of confluent fibroblasts at high drug concentrations.

Antitransferrin receptor immunotoxin inhibits proliferating human retinal pigment epithelial cells.

Cultured human retinal pigment epithelial cells were exposed to an immunotoxin composed of a monoclonal antibody, 454A12, directed against transferrin receptors conjugated to a toxin, recombinant ricin A chain. Exposure of proliferating human retinal pigment epithelial cells to the immunotoxin (0.1 to 10,000 ng/mL) caused a statistically significant (P less than .0001) decrease in the number of cells. This inhibitory effect was induced after an exposure to the immunotoxin as short as 5 minutes and was maximal after 24 hours of exposure. The diminution in cell number was dose dependent over the range from 0.1 to 100 ng/mL. Monoclonal antibody alone, recombinant ricin A chain alone, or an irrelevant immunotoxin, MOP21C monoclonal antibody-recombinant ricin A, did not diminish the number of cells. There was a marked decrease in DNA synthesis measured by nuclear tritiated thymidine incorporation that accompanied the immunotoxin-mediated decrease in cell number. Viable cells remaining after exposure to the immunotoxin (0.1 to 10,000 ng/mL) were morphologically abnormal; typically the cells had elongated spindle-shaped processes and had lost their normal cuboidal appearance. In contrast, cell number was not decreased in confluent human retinal pigment epithelial cells after treatment with maximal doses of immunotoxin. Morphologic changes similar to those seen in proliferating cells were observed in confluent cells exposed to more than 100 ng/mL of immunotoxin. The effect of the immunotoxin was species specific because large doses of immunotoxin did not reduce the number of viable cells in proliferating or confluent pig retinal pigment epithelial cells or cause observable morphologic changes in this cell type. Our results indicate that the immunotoxin selectively inhibited proliferating retinal pigment epithelial cells by receptor-mediated internalization of the antitransferrin receptor monoclonal antibody-recombinant ricin A chain conjugate.

Long-term inhibition of cellular proliferation by immunotoxins.

The proliferation and fibrous metaplasia of retinal glial and pigment epithelial cells cause proliferative vitreoretinopathy. The immunotoxin 454A12 MAB-rRA is composed of a murine monoclonal antibody, specific for the human transferrin receptor, and is chemically linked to recombinant ricin A chain, a cellular toxin. The rapidly proliferating cells take up the immunotoxin, but non-proliferating cells do not. Using a collagen-gel medium to simulate the vitreous, we have studied the effect of the immunotoxin on fibroblast proliferation in vitro. Exposure of the fibroblasts to 1000 ng of immunotoxin per milliliter of the collagen gel medium for 10 minutes kills 96% or more of the cells for 20 days. These in vitro data indicate that the immunotoxin is effective in an environment similar to the vitreous; however, in vivo studies will be necessary to prove if it is a suitable agent for the long-term prevention of cell proliferation in the human eye.

Use of immunotoxin to inhibit proliferating human corneal endothelium.

Transferrin plays a central role in cellular proliferation and proliferating cells have been shown to express transferrin receptors with increased density. We examined the effect of an immunotoxin consisting of anti-transferrin receptor monoclonal antibody (454A12) conjugated to recombinant ricin A chain (rRTA) on the proliferation of human corneal endothelium (HCE) in vitro. In proliferating cultures an immunotoxin (454A12-rRTA) concentration of 50 ng/mL reduced cell counts at day 7 by at least 89%, with no effect observed at 0.01 ng/ml. In contrast, cell counts were only minimally reduced in confluent cultures, even after 7 days' exposure to high concentrations of immunotoxin. These data suggest that 454A12-rRTA may be used to prevent growth of human corneal endothelium in pathological conditions such as the iridocorneal endothelial (ICE) syndrome.

A computerized recall system for clinical trials.

A major difficulty facing investigators involved in clinical studies is ensuring the timely follow-up of patients involved in the investigations. Two microcomputer programs are described that create a follow-up calendar for each subject, list patients due to appear for any given month, and generate printouts of subjects who have missed key follow-up appointments. These programs were formulated using dBASE II (Ashton Tate, California), a widely used data base management package suitable for International Business Machines-compatible microcomputers. The programming concept used in formulating these programs can be adapted to most other data base management software systems. These programs are currently enhancing the follow-up of patients enrolled in a prospective ophthalmic surgical protocol and are potentially useful to any investigator involved in prospective studies who has access to a microcomputer.

Selective inhibition of the growth of human erythroid bursts by monoclonal antibodies against transferrin or the transferrin receptor.

The relative requirements of colonies derived from erythroid (BFU-E) and myeloid (CFU-c) progenitors for transferrin were examined using monoclonal antibodies directed against the transferrin molecule (TF-6) or its cell surface receptor (TFR-A12, TFR1-2B). Growth of erythroid bursts was profoundly reduced at concentrations of all three antibodies that had no effect on CFU-c-derived colonies. When TFR1-2B was layered over cultures established one to seven days previously, further burst development was inhibited, and degeneration of early erythroid colonies was observed. Addition of erythropoietin augmented transferrin receptor expression on cells harvested after 1 to 2 weeks in culture and analyzed by flow cytometry. Recombinant human erythropoietin gave results comparable to those obtained in experiments using human urinary erythropoietin. Analysis of erythroblasts plucked directly from culture plates confirmed the presence of transferrin receptors on BFU-E-derived colonies. Thymidine incorporation was maximal early in the second week of culture and coincided with high transferrin receptor expression. These data demonstrate that transferrin must be available into the second week of culture to support the growth and differentiation of BFU-E-derived erythroid bursts, that the generation of erythroid colonies from BFU-E is more dependent on transferrin than myeloid colony formation from CFU-c, and that erythropoietin modulates the expression of transferrin receptors on growing bursts.