Current experience and attitudes to biomedical scientist cut-up: results of an online survey of UK consultant histopathologists.

AIMS: To assess the current utilisation of biomedical scientist (BMS) surgical specimen cut-up in the UK and attitudes of consultant histopathologists to the practice. METHODS: Email invitations were sent to all UK consultant histopathologists to participate in an online survey (SurveyMonkey) assessing attitudes to and utilisation of BMS surgical specimen cut-up. RESULTS: 463 individual replies were received (35% response rate) from 1320 invitations to participate, covering 181 UK histopathology departments. A majority of the respondents were either fully in favour of BMS cut-up (52.7%), or in favour but with some reservation (46.2%). Only five respondents (1.1%) were completely opposed to BMS cut-up. 267 (57.7%) respondents reported that their BMS staff loaded biopsies only. 148 (32%) reported BMS cut-up of more complex benign specimens, and 83 (17.9%) reported BMS handling of orientated skin specimens. Only 39 (8.4%) reported that BMS staff in their departments currently cut-up larger cancer resections. CONCLUSIONS: This survey is representative of current BMS cut-up practice in the UK. The majority of UK consultant histopathologists replying to this survey support BMS cut-up to some degree, but utilisation of BMS cut-up is rather limited and patchy at present. Cost, staffing constraints, perceived quality issues and individual consultant preferences are cited as reasons for limited uptake currently. Recognised benefits of promoting BMS cut-up include better use of consultant time, enhanced team working, BMS job satisfaction and career progression, and better adherence to standard operating procedures.

Use of an isolated joint model to detect early changes induced by intra-articular injection of paclitaxel-impregnated polymeric microspheres.

Paclitaxel is a chemotherapeutic agent that suppresses cellular proliferation and angiogenesis and has been effective in suppressing proliferative synovitis in animal models. Local joint delivery ofpaclitaxel is being pursued as a treatment for rheumatoid arthritis in humans, to avoid systematic toxicity of the drug. We used an extracorporeal, isolated metacarpophalangeal joint preparation that uniquely permitted the simultaneous evaluation of codependent hemodynamic, microvascular, and transsynovial flow responses of a joint. Specifically in this study, the isolated joint preparation provided quantitative assessment of vascular flow, transsynovial flow, and morphologic changes in response to intraarticular injection of paclitaxel (50 ng) in poly-(DL)-lactide co-glycolide 50:50 microspheres (50 microm diameter) to assess initial intra-articular biocompatibility. Control joints were isolated but not injected. Serial hemodynamic measurements, transsynovial fluid forces, synovial fluid analysis, synovial and capillary permeability, and oxygen metabolism were measured every 30 min during a subsequent 3-h isolation period. At termination, synovium and cartilage were harvested from bilateral metacarpophalangeal joints for histopathologic assessment. Intra-articular injection of this formulation of paclitaxel did not significantly affect hemodynamic parameters in the joint during this short-term study, and early joint inflammatory reaction was minimal. However, transsynovial fluid forces were significantly greater in treated joints as evidenced by greater synovial fluid flow, intra-articular pressure, transitional microvascular pressure, and permeability to fluid transport. Gross and histologic morphology of synovium and articular cartilage were normal in all isolated joints. In conclusion, this extracorporeal in vivo isolated joint model permitted investigation of the early changes in joint physiology induced by this microsphere formulation and dose ofpaclitaxel in joints and could provide a more physiologic and dynamic model for study of the pharmacokinetics of drug absorption following intra-articular administration. Due to the minimal inflammation and lack of evidence of gross or histologic change in the joint, this formulation of paclitaxel should be adequately biocompatible for use in an in vivo animal model for further study of its feasibility for human use.

Effect of long-term administration of an injectable enrofloxacin solution on physical and musculoskeletal variables in adult horses.

OBJECTIVE: To evaluate clinical safety of administration of injectable enrofloxacin. DESIGN: Randomized controlled clinical trial. ANIMALS: 24 adult horses. PROCEDURES: Healthy horses were randomly allocated into 4 equal groups that received placebo injections (control) or IV administration of enrofloxacin (5 mg/kg [2.3 mg/lb], 15 mg/kg [6.8 mg/lb], or 25 mg/kg [11.4 mg/lb] of body weight, q 24 h) for 21 days. Joint angles, cross-sectional area of superficial and deep digital flexor and calcaneal tendons, carpal or tarsal osteophytes or lucency, and midcarpal and tarsocrural articular cartilage lesions were measured. Physical and lameness examinations were performed daily. Measurements were repeated after day 21, and articular cartilage and bone biopsy specimens were examined. RESULTS: Enrofloxacin did not induce changes in most variables during administration or for 7 days after administration. One horse (dosage, 15 mg/kg) developed lameness and cellulitis around the tarsal plantar ligament during the last week of administration. One horse (dosage, 15 mg/kg) developed mild superficial digital flexor tendinitis, and 1 horse (dosage, 25 mg/kg) developed tarsal sheath effusion without lameness 3 days after the last administration. High doses of enrofloxacin (15 and 25 mg/kg) administered by bolus injection intermittently induced transient neurologic signs that completely resolved within 10 minutes without long-term effects. Slower injection and dilution of the dose ameliorated the neurologic signs. Adverse reactions were not detected with a 5 mg/kg dose administered IV as a bolus. CONCLUSIONS AND CLINICAL RELEVANCE: Enrofloxacin administered IV once daily at the rate of 5 mg/kg for 3 weeks is safe in adult horses.

Nitric oxide synthase activity in healthy and interleukin 1beta-exposed equine synovial membrane.

OBJECTIVE: To quantitate nitric oxide synthase (NOS) activity in healthy and interleukin 1beta (IL-1beta)-exposed equine synovial membrane. ANIMALS: 6 healthy horses, 2 to 8 years old. PROCEDURE: Recombinant human IL-1beta (0.35 ng/kg of body weight) was injected intra-articularly into 1 metacarpophalangeal joint of each horse. The contralateral joint served as an unexposed control. All horses were euthanatized 6 hours after injection of IL-1beta, and synovial membrane specimens were assayed for NOS activity by measuring conversion of arginine to citrulline. Severity of inflammation was semiquantitated by analysis of synovial fluids and histologic examination of synovial membrane. RESULTS: Equine synovial membrane had minimal NOS activity. A significant difference was not detected in NOS activity between control and IL-1beta-exposed specimens. Histologic examination revealed a neutrophilic infiltrate in synovial membrane exposed to IL-1beta. Synovial fluid from IL-1beta-exposed joints had a moderate inflammatory response and significantly greater concentrations of IL-1beta and interleukin-6 than fluid from healthy joints. CONCLUSION: Healthy equine synovial membrane had low NOS activity that was not affected by exposure to IL-1beta.

Instability-induced osteoarthritis in the metacarpophalangeal joint of horses.

OBJECTIVE: To establish an instability model of osteoarthritis (OA) that mimics the early changes of naturally acquired OA. ANIMALS: 6 mature radiographically normal horses. Procedure-The collateral and lateral collateral sesamoidean ligaments were transected in a metacarpophalangeal (MCP) joint in each horse. Lameness examinations were performed every 7 days after surgery for 8 weeks. Radiographs were taken immediately before and after desmotomy and 8 weeks after surgery. Eight weeks after surgery, bilateral MCP joints were grossly evaluated, specimens of articular cartilage were harvested for histologic examination and tissue culture, and synovial membrane was harvested for histologic examination. RESULTS: Lameness scores significantly increased over time (mean score of 1.6 for the 8-week study period). Joint circumference was significantly greater and range of motion significantly less in OA joints, compared with contralateral joints. Number and size of osteophytes were significantly greater in OA joints. Amount of newly synthesized proteoglycan (PG) was significantly greater at 18 and 72 hours of cartilage explant culture for OA joints, compared with contralateral joints. Total PG content and PG degradation did not differ between OA and contralateral joints. IMPLICATIONS FOR HUMAN MEDICINE: This instability model in horses may be useful in the study of OA in humans. CONCLUSION: Desmotomy of the lateral collateral and lateral collateral sesamoidean ligaments induced instability similar to that of naturally acquired OA in horses, as documented by lameness, clinical signs of OA, osteophyte formation, and erosions of articular cartilage surfaces and score lines in OA joints.

Anti-inflammatory effects of topically applied dimethyl sulfoxide gel on endotoxin-induced synovitis in horses.

OBJECTIVE: To evaluate the effect of topically applied dimethylsulfoxide (DMSO) on lipopolysaccharide (LPS)-induced synovitis in the mid-carpal joint. ANIMALS: 6 sound, healthy, adult horses (12 carpi). PROCEDURE: In a double-blinded, crossover, paired study with a 1-week washout period, mid-carpal joints were allocated to group 1 (DMSO, n = 6) or group 2 (control, n = 6). Each joint was injected with 1.3 ml (0.0125 ng/dl) of LPS to induce synovitis. For group-1 joints, DMSO gel (15 g; 90%) was applied after injection of LPS and at 12-hour intervals for 60 hours. Joints of group 2 received LPS, but not DMSO gel. All horses were evaluated by serial lameness examinations and synovial fluid analyses (total and differential WBC count and total protein concentration) at 12-hour intervals for 60 hours after LPS injection. Plasma and synovial fluid were obtained at baseline and 36 hours to document presence of DMSO. RESULTS: Mean WBC concentration was significantly (P < 0.05) lower in group-1, compared with group-2 joints, at 24 hours and had a trend to be lower at 36 hours. Mean total neutrophil count was significantly lower in group-1, compared with group-2 joints at 24 hours. In group-1 joints, DMSO was detected by use of gas chromatography in the synovial fluid of 5 of 6 joints and in plasma from 1 of 6 horses. CONCLUSION: Topically applied DMSO penetrated into synovial fluid in sufficient quantities to be detected and to decrease joint inflammation.

Vascular and transsynovial forces of the isolated stationary equine joint.

OBJECTIVE: To provide quantitative assessment of forces affecting filtration of synovial fluid in response to incremental changes in arterial and venous hemodynamics. ANIMALS: 7 clinically normal adult horses. PROCEDURE: Using a stationary, isolated metacarpophalangeal joint preparation, blood flow (Qa[cir]), tissue perfusion, arterial pressure (Pa[cir]), venous pressure (Pv[cir]), transsynovial fluid flow, total vascular resistance, vascular compliance, and tissue compliance were evaluated before and after arterial and venous pressure manipulations. At isogravimetric conditions, pre- and postcapillary resistance and ratios, osmotic reflection coefficient (sigma[d]), capillary pressure, net filtration pressure, and transitional microvascular pressure were determined. RESULTS: Synovial tissue blood flow was similar before, immediately after, and 3.5 hours after joint isolation. The sigma(d) for the joint was low, owing to the high oncotic pressure of synovial fluid at filtration-independent states. Transsynovial flow occurred in preference to lymph flow because of the high permeability of synovial tissue (low sigma[d]). Synovial fluid production and transfluid flow (synovium weight gain) increased at Pa(cir) > 200 mm of Hg, indicating a threshold phenomenon for synovial filtration. Net filtration pressure > 6 mm of Hg is needed to effect an increase in synovial fluid flow, and pressure of approximately 11 mm of Hg is necessary to increase lymphatic flow. Vascular compliance in the joint was low, but increased markedly with Pv(cir). Vascular and tissue compliance increased with increased Pa(cir). Vascular compliance changes caused by increased arterial pressure were minimal, compared with those caused by increased venous pressure owing to the greater elastance of arteries and the larger muscular arterial wall. CONCLUSION: This isolated joint preparation permitted evaluation of codependent hemodynamic, microvascular, and transsynovial flow responses to hemodynamic manipulations. Synovial tissue permeability was markedly affected by increased vascular forces altering filtration pressures toward synovial fluid production.

Evaluation of horizontal and vertical tracheotomy healing after short-duration tracheostomy in dogs.

PURPOSE: The purpose of the study was to assess healing of horizontal and vertical tracheotomy after short-duration tracheostomy in dogs using clinical, radiographic, endoscopic, and histologic methods. MATERIALS AND METHODS: Horizontal tracheotomy (n = 6) between the third and fourth tracheal rings or vertical tracheotomy (n = 6) across tracheal rings three through five was performed for airway management during laryngoplasty. Tracheostomy tubes were maintained for 6 hours with low-pressure cuff inflation time limited to the first 1.5 hours. Cervical radiographs and tracheoscopy were performed preoperatively and at postoperative weeks 2, 4, 8, and 12. Ten of the 12 dogs were killed 12 weeks after tracheostomy. RESULTS: There was no significant difference in preoperative and postoperative tracheal diameter or change in endoscopic tracheal circumference at the tracheostomy site when dogs were compared based on type of tracheotomy. Three dogs with horizontal tracheotomies had evidence of scar (web) within the tracheal lumen 12 weeks after surgery. All vertical tracheotomies had a mild, ventral, triangular deformity. Histologic examination of vertical tracheotomy sites showed complete restoration of the pseudostratified columnar epithelium. Horizontal tracheotomies healed with a single layer of columnar epithelium. Intraluminal scar was composed primarily of loose connective tissue. CONCLUSION: Based on the results of this study, vertical tracheotomy shows more consistent healing compared with horizontal tracheotomy after short-duration tracheostomy. No evidence was found to support the preferential recommendation of horizontal tracheotomy for short-duration tracheostomy airway management.