Atypical Chronic Inflammatory ANCA-Positive Deforming Arthritis After Cocaine-Levamisole Exposure.

BACKGROUND/OBJECTIVE: Immunostimulatory drugs including immune checkpoint inhibitors and levamisole can induce inflammatory disease including vasculitis, rashes, tissue necrosis, and arthritis. METHODS: This prospective cohort study determined the 5-year outcomes of cocaine-levamisole-induced inflammatory disease as to outcomes and survival. Thirty-one consecutive cocaine-levamisole autoimmune patients and 45 primary vasculitis patients were characterized as to clinical differentiating features, antineutrophil cytoplasmic antibody (ANCA) status, treatment, the presence of acute and chronic arthritis, and 5-year outcome. RESULTS: Seventy-one percent (22/31) of cocaine-levamisole vasculopathy cases were ANCA positive (86% p-ANCA and 14% c-ANCA), whereas 53% (23/45) of the primary vasculitis were ANCA positive (p = 0.04). The ANCA-positive cocaine-levamisole cohort at onset were characterized by younger age (45 ± 12 vs 53 ± 14 years, p = 0.04), superficial skin necrosis (82% vs 54%, p = 0.036), depressed complement C3 (27% vs 4%, p = 0.33), antiphospholipid antibodies (50% vs 4%, p < 0.001), neutropenia (18% vs 0%, p = 0.044), and elevated antimyeloperoxidase (MPO) antibody levels (100% vs 67%, p < 0.001). Chronic cocaine-levamisole disease was characterized by severe cicatrical deformities of the face and extremities (45.5% vs 8.3%, p = 0.005). Arthralgias (71% vs 82%, p = 0.19) and acute arthritis (33% vs 32%, p = 0.25) were similar between the 2 groups. However, a substantial proportion cocaine-levamisole-induced autoimmune patients (18% vs 0%, p = 0.045) developed a chronic deforming inflammatory arthritis that was rheumatoid factor, anti-cyclic-citrillinated antibody antibody, and HLA-B27 negative, but p-ANCA-and MPO antibody positive. CONCLUSIONS: Patients exposed to cocaine-levamisole may develop serious chronic sequelae including cicatrical cutaneous and facial deformities and an atypical seronegative, p-ANCA and MPO antibody-positive, HLA-B27-negative chronic deforming inflammatory arthritis.

HLA-B27 spondyloarthritis and spotted fever rickettsiosis: case-based review.

Rickettsia rickettsii, a tick borne disease, is the pathogen responsible for inducing Rocky Mountain Spotted Fever (RMSF), an illness that can progress to fulminant multiorgan failure and death. We present a case where R. rickettsii, acquired on a camping trip, precipitated a flare of peripheral arthritis and episcleritis in an HLA-B27 positive patient. Although Yersinia, Salmonella, Mycobacteria, Chlamydia, Shigella, Campylobacter, and Brucella have been previously associated with HLA-B27 spondyloarthritis, this unusual case demonstrates that obligate intracellular rickettsial organisms, and specifically, R. rickettsii, can also induce flares of HLA-B27 spondyloarthritis. Rickettsial infections in general can rapidly become fatal in both healthy and immunosuppressed patients, and thus, prompt diagnosis and therapy are required.

Outcomes and cost-effectiveness of ultrasound-guided injection of the trochanteric bursa.

We hypothesized that ultrasound (US) guidance improves outcomes of corticosteroid injection of trochanteric bursitis. 40 patients with greater trochanteric pain syndrome defined by pain to palpation over the trochanteric bursa were randomized to injection with 5 ml of 1% lidocaine and 80 mg of methylprednisolone using (1) conventional anatomic landmark palpation guidance or (2) US guidance. Procedural pain (Visual Analogue Pain Scale), pain at outcome (2 weeks and 6 months), therapeutic duration, time-to-next intervention, and costs were determined. There were no complications in either group. Ultrasonography demonstrated that at least a 2-in (50.8 mm) needle was required to consistently reach the trochanteric bursa. Pain scores were similar at 2 weeks: US: 1.3 ± 1.9 cm; landmark: 2.2 ± 2.5 cm, 95% CI of difference: - 0.7 < 0.9 < 2.5, p = 0.14. At 6 months, US was superior: US: 3.9 ± 2.0 cm; landmark: 5.5 ± 2.6 cm, 95% CI of difference: 0.8 < 1.6 < 2.4, p = 0.036. However, therapeutic duration (US 4.7 ± 1.4 months; landmark 4.1 ± 2.9 months, 95% CI of difference - 2.2 < - 0.6 < 1.0, p = 0.48), and time-to-next intervention (US 8.7 ± 2.9 months; landmark 8.3 ± 3.8 months, 95% CI of difference - 2.8 < - 0.4 < 2.0, p = 0.62) were similar. Costs/patient/year was 43% greater with US (US $297 ± 99, landmark $207 ± 95; p = 0.017). US-guided and anatomic landmark injection of the trochanteric bursa have similar 2-week and 6-month outcomes; however, US guidance is considerably more expensive and less cost-effective. Anatomic landmark-guided injection remains the method of choice, but should be routinely performed using a sufficiently long needle [at least a 2 in (50.8 mm)]. US guidance should be reserved for extreme obesity or injection failure.

Can Diagnostic and Therapeutic Arthrocentesis Be Successfully Performed in the Flexed Knee?

BACKGROUND/OBJECTIVE: The objective of this study was to determine whether the extended or flexed knee positioning was superior for arthrocentesis and whether the flexed knee positioning could be improved by mechanical compression. METHODS: Fifty-five clinically effusive knees underwent arthrocentesis in a quality improvement intervention: 20 consecutive knees in the extended knee position using the superolateral approach, followed by 35 consecutive knees in the flexed knee position with and without an external compression brace placed on the suprapatellar bursa. Arthrocentesis success and fluid yield in milliliters were measured. RESULTS: Fluid yield for the extended knee was greater (191% greater) than the flexed knee (extended knee, 16.9 ± 15.7 mL; flexed knee, 5.8 ± 6.3 mL; P < 0.007). Successful diagnostic arthrocentesis (≥2 mL) was 95% (19/20) in the extended knee and 77% (27/35) in the flexed knee (P = 0.08). After mechanical compression was applied to the suprapatellar bursa and patellofemoral joint of the flexed knee, fluid yields were essentially identical (extended knee, 16.9 ± 15.7 mL; flexed knee, 16.7 ± 11.3 mL; P = 0.73), as were successful diagnostic arthrocentesis (≥2 mL) (extended knee 95% vs. flexed knee 100%, P = 0.12). CONCLUSIONS: The extended knee superolateral approach is superior to the flexed knee for conventional arthrocentesis; however, the extended knee positioning and flexed knee positioning have identical arthrocentesis success when mechanical compression is applied to the superior knee. This new flexed knee technique for arthrocentesis is a useful alternative for patients who are in wheelchairs, have flexion contractures, cannot be supine, or cannot otherwise extend their knee.

The outcomes and cost-effectiveness of intraarticular injection of the rheumatoid knee.

Although intraarticular injections are important to the management of rheumatoid arthritis, there are few studies regarding the cost-effectiveness of alternative injection techniques. This randomized controlled study addressed the cost-effectiveness of two different low-cost, anatomic landmark palpation-directed intraarticular injection techniques. Ninety-six symptomatic rheumatoid knees were randomized to two different low-cost, palpation-guided intraarticular injection techniques utilizing (1) a conventional syringe or (2) a mechanical syringe, the RPD (the reciprocating procedure device). Three milliliters of 1% lidocaine were used to anesthetize the synovial membrane, followed by arthrocentesis and hydrodissection, and injection of 80 mg of triamcinolone acetonide utilizing the one-needle two-syringe technique. Baseline pain, procedural pain, aspirated fluid volume, pain at outcome (2 weeks and 6 months), responders, reinjection rates, cost/patient/year, and cost/responder/year were determined. Pain was measured with the 10 cm Visual Analogue Pain Scale (VAS). Both techniques significantly reduced pain scores at outcome from baseline (P < 0.001). The mechanical syringe technique resulted in a greater volume of aspirated fluid (P < 0.01), a 38% reduction in procedural pain (P < 0.001), a 24% reduction in pain scores at outcome (P < 0.03), an increase in the responder rate (P < 0.025), 33% increase in the time to next injection (P < 0.001), 23% ($35 US) reduction in cost/patient/year for a patient treated in a physician office (P < 0.001), 24% reduction ($26 US) in cost/patient/year for a hospital outpatient (P < 0.001), and 51% ($151 US) reduction in cost/responder/year (P < 0.001). The outcomes and cost-effectiveness of intraarticular injection of the rheumatoid knee can be improved significantly with low-cost alternations in technique.

The histopathologic associates of neurometabolite abnormalities in fatal neuropsychiatric systemic lupus erythematosus.

OBJECTIVE: To determine the histopathologic basis of altered brain neurometabolites in neuropsychiatric systemic lupus erythematosus (NPSLE). METHODS: Brain neurometabolite concentrations in a 20-voxel area of the brain were determined premortem by magnetic resonance spectroscopy (MRS) in 7 individuals with NPSLE. Absolute concentrations of neurometabolite for N-acetylaspartate (NAA), choline, creatine, and lactate were measured. After the death of the patients, histopathologic changes were determined at autopsy of the brain and were matched voxel-by-voxel with the neurometabolites. RESULTS: The mean +/- SD absolute concentrations of NAA (9.15 +/- 1.78 mM in patients versus 12.2 +/- 0.8 mM in controls; P < 0.01) and creatine (6.43 +/- 0.16 mM in patients versus 6.90 +/- 0.60 mM in controls; P < 0.003) were significantly reduced and the concentration of choline (2.51 +/- 0.42 mM in patients versus 1.92 +/- 0.32 mM in controls; P < 0.04) was significantly elevated in NPSLE patients as compared with controls. Widespread heterogeneous changes in the histologic features of the brain were present, including microinfarcts, microhemorrhages, bland angiopathy, thrombotic angiopathy with platelet and fibrin thrombi, neuronal necrosis in various states of resolution, reduced numbers of axons and neurons, vacuole and space formation among the fibers, reduced numbers of oligodendrocytes, reactive microglia and astrocytes, lipid-laden macrophages, and cyst formation. Neurometabolite abnormalities were closely associated with underlying histopathologic changes in the brain: 1) elevated choline levels were independently associated with gliosis, vasculopathy, and edema (r = 0.75, P < 0.004 in the multivariate model); 2) reduced creatine levels with reduced neuronal-axonal density and gliosis (r = 0.72, P < 0.002 in the multivariate model); 3) reduced NAA levels with reduced neuronal-axonal density (r = 0.66, P < 0.001 in the multivariate model); and 4) the presence of lactate with necrosis, microhemorrhages, and edema (r = 0.996, P < 0.0001 in the multivariate model). CONCLUSION: Altered neurometabolites in NPSLE patients, as determined by MRS, are a grave prognostic sign, indicating serious underlying histologic brain injury.

Nerve blocks at the wrist for painful injections of the palm.

PURPOSE: Injections into the palmar hand for trigger finger, palmar flexor tenosynovitis, and Dupuytren contracture can be very painful. This randomized, controlled study evaluated nerve block anesthesia at the wrist for prevention of procedural pain associated with painful injection of the palmar hand. METHODS: Forty-seven corticosteroid injections for trigger fingers in 19 individuals were randomized to (1) anesthesia consisting of median and ulnar nerve block with 1% lidocaine anesthesia followed by standard injection or (2) standard injection alone using the 1-needle 2-syringe technique consisting of transthecal dilation of the synovial sheath with 0.5 mL 1% lidocaine with a mechanical syringe, the reciprocating procedure device, followed by injection with 20 mg triamcinolone acetonide. Baseline pain, needle insertion/sheath dilation pain, corticosteroid injection pain, resolution of trigger finger, and pain at outcome (2 weeks) were determined. RESULTS: Standard injection for trigger finger was associated with significant pain in 100% of subjects. Nerve blocks at the wrist provided effective anesthesia, resulting in a 56% reduction in injection pain compared with direct injection (P < 0.01). There was 100% resolution of trigger finger in both treatment groups. Pain at the 2-week outcome, reduction in pain from baseline, responders, and nonresponders were not statistically different (P > 0.3 for all). Eighty-eight percent of subjects preferred nerve block anesthesia to direct injection (P < 0.0001). CONCLUSIONS: Nerve block anesthesia at the wrist before palmar injection is preferred by patients and is highly effective in preventing pain associated with injection of the palmar hand for trigger finger and other painful hand procedures.

A randomized controlled trial evaluating the cost-effectiveness of sonographic guidance for intra-articular injection of the osteoarthritic knee.

OBJECTIVE: The present randomized controlled study investigated whether sonographic needle guidance affected the outcomes of intra-articular injection for osteoarthritis of the knee. METHODS: Ninety-four noneffusive knees with osteoarthritis were randomized to injection by conventional palpation-guided anatomic landmark injection or sonographic image-guided injection enhanced with a 1-handed mechanical (the reciprocating procedure device) syringe. After intra-articular placement and synovial space dilation were confirmed by sonography, a syringe exchange was performed, and 80 mg of triamcinolone acetonide was injected with the second syringe through the indwelling intra-articular needle. Baseline pain, procedural pain, pain at outcome (2 weeks and 6 months), responders, therapeutic duration, reinjection rates, total cost, and cost per responder were determined. RESULTS: Relative to conventional palpation-guided anatomic landmark methods, sonographic guidance for injection of the knee resulted in 48% reduction in procedural pain (P < 0.001), a 42% reduction in pain scores at outcome (P < 0.03), 107% increase in the responder rate (P < 0.001), 52% reduction in the nonresponder rate (P < 0.001), a 36% increase in therapeutic duration (P = 0.01), a 13% reduction ($17) in cost per patient per year, and a 58% ($224) reduction in cost per responder per year for a hospital outpatient (P < 0.001). CONCLUSIONS: Sonographic needle guidance reduced procedural pain and improved the clinical outcomes and cost-effectiveness of intra-articular injections of the osteoarthritic knee.

Integration of new safety technologies for needle aspiration of breast cysts.

INTRODUCTION: National and international regulatory agencies and professional societies mandate systematic improvements in both the safety of patients and heath care workers (HCW), including the integration of safety technologies into the procedures of obstetrics and gynecology (Ob-Gyn). MATERIALS AND METHODS: Using national resources for patient safety and literature review, these safety technologies were identified: (1) a safety needle to reduce needle sticks to HCW, and (2) the reciprocating procedure device (RPD) to reduce injuries to patients. These technologies were introduced in a trial fashion into routine breast cyst aspiration, and physician responses were determined. RESULTS: The safety needle presented a number of difficulties associated with the safety sheath, but could be used efficiently for breast cyst aspiration. The RPD safety device functioned well for breast aspiration procedures and was well accepted by physicians. CONCLUSIONS: New safety technologies can be successfully evaluated and introduced into the clinic to improve patient and HCW safety during outpatient breast procedures. Since these technologies have been demonstrated to decrease injuries to patients and HCW by 60-70%, serious efforts should be undertaken to systematically integrate safety technologies into the routine practice, including aspiration of breast cysts.

Syringe size: does it matter in physician-performed procedures?

PURPOSE: We hypothesized that the size of syringe influenced needle control in physician-performed procedures. MATERIALS AND METHODS: Operators were tested for their ability to control a 1-, 3-, 5-, 10-, and 20-mL syringe and equivalent sizes of the new safety device, the reciprocating procedure device (RPD), using the quantitative needle-based displacement method. Three hundred twenty clinical syringe procedures were then randomized to either a 3- or 10-mL conventional syringe or to a 3- or 10-mL RPD. Patient pain was measured with the Visual Analog Pain Scale (VAPS). RESULTS: Increasing syringe size was associated with the undesirable characteristic of unintended forward penetration (loss of control of the needle in the forward direction) (r(2) = 0.97, slope = 2.14, 95% CI: 1.54-2.76, P < 0.002), and unintended retraction (loss of control of the needle in the reverse direction) (r(2) = 0.97, slope 2.15, 95% CI: 1.54-2.76, P < 0.002). In addition, 2-handed operation of a syringe resulted in greater control than 1-handed operation of a syringe (P < 0.001). When 1-handed operation was required, the RPD control syringe reduced unintended penetration by 52.3% (P >or= 0.001), unintended retraction by 56.8% (P >or= 0.001), and patient pain by 54.7% (P >or= 0.001) at each device size. CONCLUSIONS: For greater safety and control when operating the conventional syringe, smaller syringe sizes and 2 hands instead of 1 hand should be used whenever possible. If 1-handed operation of a syringe is necessary, a safety technology like the RPD control syringe should be used.

Kaposi Sarcoma as a Cutaneous Vasculitis Mimic: Diagnosis and Treatment.

Painful, palpable purpura usually indicate underlying vasculitis. We report a case of systemic vasculitis treated with immunosuppression that developed painful, vasculitis-like purpuric lesions that progressed rapidly to fulminant Kaposi sarcoma (KS). These purpuric, tumorous lesions resolved completely following the suspension of immunosuppression; however, without immunosuppression, the underlying autoimmunity recurred. This case highlights the potential for early KS to present as a vasculitis mimic or pseudovasculitis that clinicians should keep in mind when purpuric, vasculitis-like lesions develop in an immunosuppressed patient with vasculitis. It is important to recognize these pseudovasculitis lesions as KS rather than recurrent vasculitis so that immunosuppression can be withdrawn.

Characteristics of Behcet's Disease in the American Southwest.

OBJECTIVE: The goal of this study was to determine the characteristics of Behçet's disease (BD) in the American Southwest. MATERIAL AND METHODS: This was a cross-sectional study of BD patients clinically encountered during a 2-year period. All subjects fulfilled the International Study Group criteria (ISG) or International Criteria for Behcet's Disease (ICBD). Age, gender, clinical characteristics, substance use, and HLA-B51 status were determined. RESULTS: 63 patients (female: male ratio: 4.7:1) fulfilled ISG criteria and 76 the ICBD criteria (estimated prevalence of 8.9-10.6 per 100,000). 84.1% (53/63) were initially diagnosed with non-BD primary diagnoses including inflammatory arthritis (15.9%), fibromyalgia (7.9%), vasculitis (7.9%), or systemic lupus erythematosus (7.9%). Common BD manifestations were oral aphthous ulcers (100%), acneiform lesions (69.8%), genital aphthous ulcers (61.9%), papulopustular lesions (52.4%), pseudofolliculitis (42.9%), inflammatory arthritis (41.3%), anterior uveitis (23.8%), posterior uveitis (15.9%), pathergy (15.9%), deep vein thrombosis (14.3%), non-ocular vasculitis (11.1%), erythema nodosum (7.9%), arterial thrombosis (6.3%), and retinal vasculitis (1.6%). BD ethnic proportions were 49.2% Hispanic American (HA), 31.7% European-American (EA), 14.3% Native American (NA), and 1.7% Silk Road. HLA-B51 was present more in NA (89.0%, p = 0.02) and HA (74.2%, p = 0.02) compared to EA (42.1%). Therapy of BD was conventional, except for the frequent use of hydroxychloroquine. CONCLUSIONS: BD is common in the American Southwest with a prevalence of 8.9-10.6 cases per 100,000. BD patients are commonly initially diagnosed with alternative primary conditions. Hydroxychloroquine may be an effective alternative therapy for BD. This is one of the first reports of BD in HA and NA populations.

Extractable synovial fluid in inflammatory and non-inflammatory arthritis of the knee.

INTRODUCTION/OBJECTIVES: We hypothesized that mechanical compression of the knee in rheumatoid arthritis (RA) would mobilize occult extractable fluid and improve arthrocentesis success. METHODS: Sixty-seven consecutive knees with RA and 186 knees with OA and were included. Conventional arthrocentesis was performed and success and volume (milliliters) determined; the needle was left intraarticularly, and mechanical compression was applied with an elastomeric knee brace. Arthrocentesis was then resumed until fluid return ceased. Fluid was characterized as to volume and cell counts. RESULTS: In the RA, knee mechanical compression decreased failed diagnostic arthrocentesis from 56.7% (38/67) to 26.9% (18/67) (- 47.4%, p = 0.003) and increased absolute arthrocentesis yield from 4.7 ± 10.3 ml to 9.8 ± 9.8 ml (108% increase, 95% CI - 8.5 < - 5.1 < - 1.7 p = 0.0038). Total extractable fluid yield was 96% greater in RA (9.8 ± 9.8 ml) than OA (5.0 ± 9.4 ml, p = 0.0008), and occult extractable fluid was 77% greater in RA than OA (RA 5.3 ± 8.7 ml, OA 3.0 ± 5.5 ml, p = 0.046). Large effusions versus small effusions in RA demonstrated increased neutrophils in synovial fluid (p = 0.04) but no difference in radiologic arthritis grade (p = 0.87). In contrast, large effusions versus small effusions in OA demonstrated no difference in neutrophils in synovial fluid (p = 0.87) but significant different radiologic arthritis grade (p = 0.04). CONCLUSION: Mechanical compression improves the success of diagnostic and therapeutic knee arthrocentesis in both RA and OA. Large effusions in RA are associated with increased neutrophil counts but not arthritis grade; in contrast, large effusions in OA are associated with more severe arthritis grades but not increased neutrophil counts. Key points• Mechanical compression of the painful knee improves arthrocentesis success and fluid yield in both rheumatoid arthritis and osteoarthritis.• The painful rheumatoid knee contains approximately 100% more fluid than the osteoarthritic knee.• Large effusions in the osteoarthritic knee are characterized by higher grades of mechanical destruction but not increased neutrophil counts.• In contrast, large effusions in the rheumatoid knee are characterized by higher synovial fluid neutrophil counts but not the grade of mechanical destruction, indicating different mechanisms of effusion formation in rheumatoid arthritis versus osteoarthritis.

A randomized, controlled trial of the reciprocating procedure device for local anesthesia.

The purpose of this study was to determine whether the new reciprocating procedure device (RPD) is superior to the conventional syringe for the administration of local anesthesia. There were 209 local lidocaine anesthesia procedures randomized between the RDP and the conventional syringe. Outcome measures included administration time, anesthesia pain, procedure pain, and operator satisfaction. The RPD significantly reduced anesthesia administration time by 49% (RPD: 0.68 +/- 0.59 min, Syringe: 1.32 +/- 1.01 min, p < 0.001, 95% confidence interval [CI] for % reduction: 36%-60%), reduced anesthesia pain by 27% (RPD visual analog pain scale score: 4.05 +/- 2.64; Syringe: 5.55 +/- 3.00; p < 0.001, 95% CI 14%-38%), reduced significant procedure pain by 74% (p < 0.001, 95% CI 60%-87%), and improved physician satisfaction by 63% (p < 0.001, 95% CI 53%-74%). The RPD markedly reduces the pain associated with lidocaine anesthesia administration, reduces administration time, and maintains the effectiveness of local anesthesia. The RPD is superior to and significantly more effective than the conventional syringe for the administration of local lidocaine anesthesia.

Improvement in diagnostic and therapeutic arthrocentesis via constant compression.

We hypothesized that constant compression of the knee would mobilize residual synovial fluid and promote successful arthrocentesis. Two hundred and ten knees with grade II-III osteoarthritis were included in this paired design study: (1) conventional arthrocentesis was performed with manual compression and success and volume (milliliters) determined; and (2) the intra-articular needle was left in place, and a circumferential elastomeric brace was tightened on the knee to provide constant compression. Arthrocentesis was attempted again and additional fluid volume was determined. Diagnostic procedural cost-effectiveness was determined using 2017 US Medicare costs. No serious adverse events were noted in 210 subjects. In the 158 noneffusive (dry) knees, sufficient synovial fluid for diagnostic purposes (≥ 2 ml) was obtained in 5.0% (8/158) without compression and 22.8% (36/158) with compression (p = 0.0001, z for 95% CI = 1.96), and the absolute volume of arthrocentesis fluid obtained without compression was 0.28 ± 0.79 versus 1.10 ± 1.81 ml with compression (293% increase, p = 0.0001). In the 52 effusive knees, diagnostic synovial fluid (≥ 2 ml) was obtained in 75% (39/52) without compression and 100% (52/52) with compression (p = 0.0001, z for 95% CI = 1.96), and the absolute volume of arthrocentesis without compression was 14.7 ± 13.8 versus 25.3 ± 15.5 ml with compression (72.1% increase, p = 0.0002). Diagnostic procedural cost-effectiveness was $655/sample without compression and $387/sample with compression. The new technique of constant compression via circumferential mechanical compression mobilizes residual synovial fluid beyond manual compression improving the success, cost-effectiveness, and yield of diagnostic and therapeutic arthrocentesis in both the effusive and noneffusive knee.

Dibutyltin exposure decreases granzyme B and perforin in human natural killer cells.

Natural killer (NK) cells are a subset of lymphocytes that are capable of killing tumor and virally-infected cells. Dibutyltin (DBT) is a catalyst in the production of PVC plastics and a breakdown product of tributyltin (TBT). DBT is a significant environmental contaminant. This study investigates the mechanism by which DBT exposure decreases the immune function of human NK cells. NK cells destroy their target cells by releasing cytotoxic proteins, perforin, and granzyme B. We examined the effect of DBT exposures on the levels of cytotoxic proteins and their mRNAs. Exposure of NK cells to DBT for 1h caused significant decreases in the mRNAs for granzyme B and perforin but not in protein levels. A 24h exposure to DBT decreased mRNAs as well as protein levels for both granzyme B and perforin. Exposure to DBT for 1h followed by either a 24 or 48h period in DBT-free media, decreased levels of granzyme B and perforin. The results indicate that decreases in granzyme B and perforin levels in NK cells are consequences of DBT exposure. Additionally, DBT causes rapid decreases in mRNAs for perforin and granzyme B, suggesting decreases in transcription and/or increases in mRNA degradation.

Tributyltin exposure causes decreased granzyme B and perforin levels in human natural killer cells.

Natural Killer (NK) cells are a subset of lymphocytes that are capable of killing tumor cells, virally infected cells and antibody coated cells. Tributyltin (TBT) is a toxic chemical used for various industrial purposes such as: slime control in paper mills, disinfection of circulating industrial cooling waters, anti-fouling agents in shower curtains and the preservation of wood. TBT can be found in edible items such as dairy products and fish. This study investigates the mechanism by which TBT exposure decreases the immune function of human NK cells, in vitro. Cytotoxic function, the expression of the cytotoxic proteins (granzyme B and perforin), and cAMP response element binding protein (CREB) phosphorylation were examined. NK cells exposed to 300 nM TBT for 1 h showed no significant decrease in cytotoxic function, levels of granzyme B and perforin, or phosphorylation of CREB. However, mRNA levels for the cytotoxic proteins were significantly decreased. A 24 h exposure to 200 nM TBT caused significant decreases in cytotoxic function, levels of granzyme B and perforin, and levels of granzyme B and perforin mRNA. When NK cells were exposed to 300 nM TBT for 1h followed by a 24 h period in TBT-free media, again there were significant decreases in NK cell cytotoxic function, levels of granzyme B and perforin and their mRNA. A 1h exposure to 300 nM TBT followed by a 48 h period in TBT-free media showed similar changes in cytotoxic function and levels of granzyme B and perforin as seen after 24 h in TBT-free media. Additionally, both of these exposures showed significant decreases in phosphorylation of CREB. These results indicate that TBT exposures can disrupt the transcription of granzyme B and perforin and that this disruption cannot be entirely accounted for by a decrease in phosphorylated CREB (phosphoCREB) levels.

Outcomes and cost-effectiveness of carpal tunnel injections using sonographic needle guidance.

This randomized controlled study addressed whether sonographic needle guidance affected the outcomes of corticosteroid injection for symptomatic carpal tunnel syndrome. Seventy-seven symptomatic carpal tunnels were randomized to injection by either (1) conventional anatomic landmark palpation-guided injection or (2) sonographic image-guided injection, each using a two-step technique where 3 ml of 1% lidocaine was first injected to hydrodissect and hydrodisplace critical intra-carpal tunnel structures followed by injection with 80 mg of triamcinolone acetonide (2 ml). Baseline pain, procedural pain, pain at outcome (2 weeks and 6 months), responders, therapeutic duration, total cost, and cost per responder were determined. There were no complications in either treatment group. Relative to conventional anatomic landmark palpation-guided methods, sonographic guidance for injection of the carpal tunnel resulted in 77.1% reduction in injection pain (p<0.01), a 63.3% reduction in pain scores at outcome (p<0.014), 93.5% increase in the responder rate (p<0.001), 84.6% reduction in the non-responder rate (p<0.001), a 71.0% increase in therapeutic duration (p<0.001), and a 59.3% ($150) reduction in cost/responder/year for a hospital outpatient (p<0.001). However, despite improved outcomes, cost per patient per year was significantly increased for an outpatient in a physician's office and was neutral for a hospital outpatient. Sonographic needle guidance significantly improves the performance and clinical outcomes of injection of the carpal tunnel and is cost-effective for a hospital-based practice, but based on current reimbursements, it significantly increases overall costs for medical care delivered in a non-hospital-based physician practice.