Retinocoroiditis asociada a tatuaje / Tattoo associated retinochoroiditis

CASO CLÍNICO: Una joven mujer fue referida por compromiso de la agudeza visual después de recibir un tercer tatuaje en su brazo. Se realizó evaluación sistémica y de laboratorio para excluir agentes infecciosos o enfermedad inflamatoria. Una lesión amarillenta yuxtafoveal junto con disrupción de la retina externa de tipo placoide y defectos pigmentarios focales fueron evaluados con imágenes multimodales. DISCUSIÓN: Los oftalmólogos que tratan uveítis deben considerar esta asociación poco común y preguntar a sus pacientes acerca de tatuajes e inflamación de estos, dado el número creciente de sujetos con tatuajes artísticos

CLINICAL CASE: A young woman was referred to our offices with impairment of visual acuity after she received a third tattoo on her arm. Systemic medical and laboratory work-up were performed in order to exclude an infectious agent or inflammatory disease. A yellowish juxtafoveal lesion in left eye along with a plaque-like outer retinal disruption and focal pigmentary defects was assessed using multi-modal diagnostic imaging. DISCUSSION: Ophthalmologists treating uveitis should consider this uncommon association and question patients regarding tattoos and tattoo inflammation given the rise of subjects undergoing artistic tattooing

Tattoo associated retinochoroiditis. / Retinocoroiditis asociada a tatuaje.

CLINICAL CASE: A young woman was referred to our offices with impairment of visual acuity after she received a third tattoo on her arm. Systemic medical and laboratory work-up were performed in order to exclude an infectious agent or inflammatory disease. A yellowish juxtafoveal lesion in left eye along with a plaque-like outer retinal disruption and focal pigmentary defects was assessed using multi-modal diagnostic imaging. DISCUSSION: Ophthalmologists treating uveitis should consider this uncommon association and question patients regarding tattoos and tattoo inflammation given the rise of subjects undergoing artistic tattooing.

Moment arms of the digital flexor tendons at the wrist: role of differential loading in stability of carpal tunnel tendons.

When a flexor digitorum superficialis tendon crossing a flexed or extended wrist has a load applied to it in excess of that applied to adjacent tendons, that tendon may translate across the carpal tunnel. In 6 cadaver specimens, each of the 9 carpal tunnel tendons was loaded with a baseline tension of 85 g and the moment arms of the flexor pollicis longus and the 4 flexor digitorum superficialis tendons were determined. Applying a higher 540-g load to individual flexor digitorum superficialis tendons and the flexor pollicis longus while loading the remaining tendons with the baseline 85-g tension significantly changed the moment arms from those measured under baseline load. The results demonstrated that tendons with applied differential loads in the carpal tunnel shift their positions, as revealed by their changing moment arms.

The chronic lymphocytic leukemia antigen (cCLLa) as immunotherapy target: pharmacokinetics and biodistribution of two divalent, ricin-based immunotoxins in xenografted athymic mice.

The chronic lymphocytic leukemia (CLL) antigen (cCLLa) is potentially suitable for targeted immunotherapy given its restriction to clonal CLL cells and lack of expression by normal lymphocytes. In order to assess the pharmacokinetics and biodistribution of two potent anti-cCLLa immunotoxins (ITs) were examined in the mouse model. The IgG fraction of anti-cCLLa monoclonal antibody CLL2m was conjugated with 125I-labeled intact (RTA) or deglycosylated (dgA) ricin chain A, injected intravenously into athymic mice engrafted with cCLLa-expressing human tumors, and monitored over 120 hours. Blood concentrations of CLL2m/125I-RTA and CLL2m/125I-dgA were best fit to biexponential equations but the latter exhibited a lower alphaT1/2 and betaT1/2 (4.1 and 102 min vs 5.9 and 126 min), a smaller volume of distribution (5.1 g vs 9.7 g), and a lower blood clearance (2.2 g/hr vs 4.6 g/hr). Both ITs exhibited preferential tumor uptake that followed distinct kinetics: rising tumor uptake for 2 hrs post-injection (while tissue uptake decreased), reaching tumor/non-tumoral tissue uptake ratios up to 16.9; and slower dissociation rates of tumor- vs tissue-bound ITs (>45% vs <20% remaining tissue-bound 6 hrs post-injection, respectively). Non-specific liver uptake was not prominent for either IT. In vivo IT deconjugation reached 50% approximately 12 hours pos-injection. The pharmacokinetics and biodistribution data in the mouse model suggest that ricin-based anti-cCLLa ITs are suitable for use in human trials.

The chronic lymphocytic leukemia antigen (cCLLa) as immunotherapy target: assessment of LD50 and MTD of four ricin-based anti-cCLLa immunotoxins (ITs) in Balb/c mice.

The chronic lymphocytic leukemia (CLL) antigen (cCLLa) is a promising immunotherapy target given its disease-restricted expression, its highest prevalence among CLL surface antigens, and its lack of expression by normal T- and B-lymphocytes. The objectives of this study were to assess the 50% lethal dose (LD50) and the maximum tolerated dose (MTD) in Balb/c mice of four anti-cCLLa immunotoxins (ITs) derived from the intact monoclonal antibody (MoAb) or its Fab fraction, each conjugated to either ricin chain-A (RTA) or its deglycosylated derivative (dgA). The IgG fraction of anti-cCLLa monoclonal antibody CLL2m and its Fab fraction were conjugated to RTA or dgA to generate four ITs: IgG/RTA, IgG/dgA, Fab/RTA and Fab/dgA. Progressive concentrations of each IT (ranging between 2.60 mg/kg and 100.00 mg/kg) were injected intravenously into groups of 5 mice each. After injection, mice were monitored daily for 10 days for survival. Observed mortality data in each group were matched to those in Weil's tables for estimating LD50 (mg/kg) from the moving average interpolation method. Estimated LD50 (in mg/kg) were: IgG/RTA, 13.33; Fab/RTA, 25.53; IgG/dgA, 55.33; Fab/dgA, 55.33. Their respective MTD (mg/kg), defined as the highest dose level survived by all mice, were 8.78, 13.17, 29.63 and 29.63. Depending on the animal-to-human extrapolation method used, the calculated LD50 and MTD in humans ranged from 1.2 mg/kg and 0.8 mg/kg (IgG/RTA), to 55.6 mg/kg and 36.9 mg/kg (IgG/dgA and Fab/dgA), respectively. The following conclusions are drawn. 1. Antibody valence exerted little influence on either the LD50 or the MTD; 2. The LD50 to MTD ratios were approximately 2:1; 3. dgA-derived ITs were approximately one half as toxic as their RTA-derived counterparts; and 4. Extrapolation of LD50 and MTD mouse data to humans resulted in dose levels comparable to or exceeding those reported in most IT human trials. These data suggest the suitability of anti-cCLLa ITs for clinical immunotherapy trials.

Carpal tunnel syndrome: unusual contraindications to endoscopic release.

Endoscopic carpal tunnel release has become an increasingly popular method of surgical treatment of carpal tunnel syndrome. Consequently, the contraindications to this technically challenging procedure continue to evolve. We describe two patients with carpal tunnel syndrome and unusual anomalies and pathology of the hook of the hamate that we believe represent relative or absolute contraindications to endoscopic carpal tunnel release.

Endoscopic carpal tunnel release: a prospective study of complications and surgical experience.

A 63-center prospective study of endoscopic carpal tunnel release using the Agee Carpal Tunnel Release System was conducted in 1049 procedures in 988 patients. Prior experience with endoscopic release varied significantly among surgeon participants. Surgeons evaluated the newly redesigned system for blade visibility, blade height, and mechanical function. Data on patient complications were collected at the time of surgery and 3-4 weeks postoperative. The results indicated minimal complications and no confirmed injuries to vessels or nerves; the symptoms from one possible digital nerve injury eventually resolved completely. Surgeons were able to observe the point of entry of the blade into the transverse carpal ligament in 97.5% of procedures. Introduction of the blade assembly into the carpal tunnel was rated easy or adequate in 90.6% of procedures, and blade height was rated adequate in 97.4% of procedures.

Treatment of comminuted distal radius fractures: an approach based on pathomechanics.

Following dorsally displaced fractures of the distal radius, the classic position of immobilization is with the wrist flexed and in ulnar deviation. This is not the position of function and entails morbidity in the form of finger stiffness, which may require prolonged rehabilitation. We treated 20 consecutive, comminuted, intraarticular distal radial fractures using a new external fixation system with the wrist in a neutral to extended position, thereby promoting metacarpophalangeal joint flexion by relatively relaxing the finger extensor tendons. Supplemental pin fixation was used in eight cases. Most patients were performing active digital motion on the day of surgery and 95% maintained functional finger motion during treatment. All fractures healed uneventfully. Palmar tilt was restored in 55% of patients in spite of a wrist neutral or extended position. This method of fixing distal radial fractures allows restoration of anatomy while avoiding hand stiffness.

Endoscopic carpal tunnel release using the single proximal incision technique.

The goal of the single incision endoscopic technique is to avoid an incision on the palmar surface of the hand. As compared with open release and the two-portal endoscopic technique for release of the carpal tunnel, this single incision technique permits the patient to return earlier to work and activities of daily living as a result of less tenderness and earlier return of strength. Safe performance of the technique requires that the surgeon have both a thorough knowledge of the anatomy of the hand and a commitment to master the technical details of the surgical approach. Because the technique is of value strictly to view and divide the TCL, patient selection requires careful preoperative evaluation to exclude those carpal tunnels with pathology that requires direct inspection or surgical treatment. In a prospective study with the redesigned point of entry blade assembly that allows a view of the blade's entry into the ligament, no device-related complications occurred. In considering a surgical approach for endoscopic carpal tunnel release, the authors feel that it is important to recognize the value of an "open" proximal surgical incision designed to directly view the plane between the finger flexor synovium and the deep surface of the TCL. Stab wound "portals" that are widely used in arthroscopic surgery are inadequate for endoscopic carpal tunnel releases. The device and the procedure are designed to obtain an unobstructed view of the underside of the TCL and divide it completely. Additional long-term prospective studies are needed to define the comparative recurrence rates of open versus single incision endoscopic carpal tunnel release surgeries.

Distal radius fractures. Multiplanar ligamentotaxis.

Ligamentotaxis is the principle of molding fracture fragments into alignment as a result of tension applied across a fracture by the surrounding intact soft tissues. Uniplanar ligamentotaxis obtained by longitudinal traction does not always restore palmar tilt to the distal radius. Multiplanar ligamentotaxis extends the principle of uniplanar ligamentotaxis to include translation of the hand in the dorsal-palmar and the radial-ulnar planes to effect appositional and tilting alignment of the distal fragment(s) of a fractured radius. Use of an external fixator that allows adjustments in multiple planes helps restore anatomic alignment and maintain fracture reduction during healing.

The Sauve-Kapandji procedure for reconstruction of the rheumatoid distal radioulnar joint.

Our experience with the Sauve-Kapandji procedure for reconstruction of the rheumatoid distal radioulnar joint is reported. Twenty-one wrists in 17 patients were followed for an average of 39 months postoperatively. Average range of motion at follow-up evaluation was pronation to 78 degrees and supination to 86 degrees. X-ray films demonstrated that significant ulnarward and palmarward translocation of the carpus was prevented. The Sauve-Kapandji procedure provides a stable ulnar side support in the rheumatoid wrist with distal radioulnar degeneration.

A simple technique for the rapid enrichment of class and subclass hybridoma switch variants. A 1000-fold enrichment in half the time, for half the cost.

Switching parental hybrids in vitro to downstream switch variant clones producing more desirable monoclonal antibodies (MoAbs) requires either labor intensive and time consuming subcloning techniques, or fluorescence activated sorting of the desired clones. We tested the hypothesis that enrichment of downstream switch variant clones might be achieved by selective lysis of upstream hybridoma cells followed by expansion of the enriched downstream clone. Using a parental hybridoma with surface and secretory IgM, we attempted to enrich downstream switch variant clones producing class (IgG) and subclass (IgG1 or IgG2a) MoAbs. Enrichment of downstream IgG, IgG1 and IgG2a MoAb-producing switch variants was achieved by single or repeated antibody-dependent, complement-mediated lysis of the upstream IgM-bearing parental hybridoma cells followed by limited subcloning. Two exposures of parental hybridoma cells to lysis followed by plating at 100 cells/well enriched the frequency of switch variants up to 1235-fold, enabling the development of IgG1 or IgG2a-producing subclones exhibiting high yield antibody production. Using this protocol, production time and costs were reduced by > 50% when compared to the standard technique. This novel technique for the rapid isolation and expansion of switch variant clones should be ideal for most laboratories, particularly those without access to cell sorting capabilities.

Four ricin chain A-based immunotoxins directed against the common chronic lymphocytic leukemia antigen: in vitro characterization.

The common B-chronic lymphocytic leukemia (B-CLL) antigen (cCLLa) appears to be ideal for targeted immunotherapy in that it is the most prevalent and disease-restricted marker in B-CLL. To assess this potential, we developed four immunotoxins (ITs) of anti-cCLLa monoclonal antibody CLL2m (an IgG2a kappa), using ricin chain A (RTA) or its deglycosylated derivative (dgA), each conjugated to either the whole IgG molecule or its Fab' fragment. Each IT was tested in vitro for specificity and cytotoxic activity (assessed by protein synthesis inhibition [PSI] and by cell kill [CK] in the clonogenic assay) against B-CLL cells. RTA-based anti-CD5 ITs and enriched normal B and T lymphocytes were used as controls. Each IT exhibited antigen-specific, dose-dependent activity. Thus, whereas B-CLL cells exhibited dose-dependent PSI and CK (whether the B-CLL clone was CD5+ or CD5-), normal B (cCLLa-/CD5-) and T lymphocytes (cCLLa-/CD5+) remained unaffected. IT potency was independent of toxin glycosylation, but was slightly influenced by antibody valence; divalent ITs were twice as potent as monovalent ITs (IC50, 2.3 v 7.1 x 10(-11) mol/L; CK, 2.6- v 2.0-log reached with 524 v 1,072 IT molecules bound/cell, respectively). In the presence of ammonium chloride or Verapamil, IT-induced CK was enhanced 10- to 80-fold. These data suggest that the cCLLa is a promising target for IT-based immunotherapy of B-CLL in vivo and ex vivo.

External fixation. Technical advances based upon multiplanar ligamentotaxis.

The principle of ligamentotaxis obtained by longitudinal traction is useful in restoring skeletal length to distal radial fractures. Using external skeletal fixation to translate the hand in radial-ulnar and dorsal-palmar directions, ligamentotaxis in two additional planes aligns and tilts the distal radial fragment and its articular surface. Following restoration of palmar tilt by palmar translation, wrist position can be adjusted into neutral or extension to help avoid finger stiffness and carpal tunnel syndrome without compromising fracture reduction.

Endoscopic release of the carpal tunnel: a randomized prospective multicenter study.

A 10-center randomized prospective multicenter study of endoscopic release of the carpal tunnel was carried out. Surgery was performed with a new device for transecting the transverse carpal ligament while control hands were treated with conventional open surgery. There were 122 patients in the study; 25 had carpal tunnel surgery on both hands and 97 had surgery on one hand. Of the surgical procedures, 65 were in the control group and 82 were in the device group. The endoscopic device was coupled to a fiberoptic light and a video camera. A trigger-activated blade was used to incise the transverse carpal ligament. After surgery, the best predictors of return to work and to activities of daily living were strength and tenderness variables. For patients in the device group with one affected hand, the median time for return to work was 21 1/2 days less than that for the control group. Two patients treated with the endoscopic device required reoperation by open surgical decompression; only one of these had incomplete release with the device. Two patients in the device group experienced transient ulnar neurapraxia.

CD20 and CD5 expression in B-chronic lymphocytic leukemia.

In order to quantitate a previously noted decrease in CD20 fluorescence intensity (FI) on B-CLL lymphocytes, binding capacities [BC x 10(3) +/- 1SD = number of antibodies bound per cell] were calculated. The mean (N = 5) BC x 10(3) +/- 1SD of CD20 reagents for normal B-PBL and B-CLL lymphocytes confirmed this observation. B-PBL and B-CLL were 56 +/- 11 and 61 +/- 14, and 19 +/- 15 and 18 +/- 16, respectively, for Leu 16 and B1. Although adequate compensation standards for the determination of CD5 and CD20 coexpression are not available, qualitatively, the density of CD5 on both normal B-PBL and B-CLL is less compared to the expression of CD5 by normal T cells. CD5 expression on B-CLL seems to be linked to the lower levels of CD20, whereas CD5 expression may appear to be absent on CLL lymphocytes expressing normal levels of CD20. Levels of CD20 in B-CLL suggest involvement of one or two genes (alleles) whose decreased expression may be linked to CD5 expression.