Predictors of psychosocial adaptation in children with CHD.

Survival of CHD has significantly improved, but children with CHD remain susceptible to neurodevelopmental and psychosocial impairments. Our goal was to investigate the association between socio-demographic factors and psychosocial adaptation for future intervention. A retrospective cross-sectional study of an independent children's hospital's records was conducted. Psychosocial adaptation was measured by the Pediatric Cardiac Quality of Life Inventory Psychosocial Impact score (range 0-50, higher score indicates greater psychosocial adaptation). Bivariate and regression analyses were performed to estimate relationships between Psychosocial Impact score and socio-demographic variables including Child Opportunity Index, family support, financial support, academic support, and extracurricular activities. A total of 159 patients were included. Compared to patients in high opportunity neighbourhoods, patients in low opportunity neighbourhoods had a 9.27 (95% confidence interval [-17.15, -1.40], p = 0.021) point lower Psychosocial Impact score, whereas patients in moderate opportunity neighbourhoods had a 15.30 (95% confidence interval [-25.38, -5.22], p = 0.003) point lower Psychosocial Impact score. Compared to patients with adequate family support, those with limited support had a 6.23 point (95% confidence interval [-11.82, -0.643], p = 0.029) lower Psychosocial Impact score. Patients in moderate opportunity neighbourhoods had a higher Psychosocial Impact score by 11.80 (95% confidence interval [1.68, 21.91], p = 0.022) when they also had adequate family support compared to those with limited family support. Our findings indicate that among children with CHD, psychosocial adaptation is significantly impacted by neighbourhood resources and family support structures. These findings identify possible modifiable and protective factors to improve psychosocial adaptation in this vulnerable population.

Phenomenological Constraints on the Transport Properties of QCD Matter with Data-Driven Model Averaging.

Using combined data from the Relativistic Heavy Ion and Large Hadron Colliders, we constrain the shear and bulk viscosities of quark-gluon plasma (QGP) at temperatures of ∼150-350 MeV. We use Bayesian inference to translate experimental and theoretical uncertainties into probabilistic constraints for the viscosities. With Bayesian model averaging we propagate an estimate of the model uncertainty generated by the transition from hydrodynamics to hadron transport in the plasma's final evolution stage, providing the most reliable phenomenological constraints to date on the QGP viscosities.

Current status of scoliosis school screening: targeted screening of underserved populations may be the solution.

OBJECTIVES: The growing body of evidence documenting the effectiveness of brace treatment for scoliosis has renewed interest in potential benefits of early detection through school screening. We aimed to assess the prevalence and identify barriers of screening. We hypothesized that school screening is more frequent in schools that have a nurse on staff compared to schools without nurse on staff. STUDY DESIGN: A questionnaire survey. METHODS: All schools located in four counties in Louisiana, United States of America comprising the New Orleans metropolitan area between September 2015 and January 2016 were contacted by phone to assess rates of scoliosis screening, report the availability of a school nurse, and specify barriers if screening was not performed. RESULTS: Two hundred and ninety-one schools responded to the survey including 152 public, 30 charter, and 109 private schools (101 had religious affiliation). A staff nurse was available in 180 schools (61.8%). Only 21 schools (7.2%) performed scoliosis screening. The majority were charter schools (11 schools), while six were private and four were public (P < 0.0001). Of these 21 schools, 16 (76.2%) had a nurse on staff while five schools did not (P = 0.16). Lack of a referral pathway in the event of a positive screen was the most common barrier to performing scoliosis screening. CONCLUSION: Scoliosis screening is infrequent in the examined school districts. Efforts to support school screening can facilitate clear referral pathways for schools in the event of a positive screen. These findings suggest a potential need for different pathway of scoliosis screening. Pediatricians and family physicians can assist with scoliosis screening during the annual visit. While universal screening is overburdensome and likely unnecessary, targeted screening of underserved populations may prove to be beneficial. Further investigation should include assessment of the economic viability of targeted screening programs. LEVEL OF EVIDENCE: IV.

Efficacy and safety of open-label ixekizumab treatment in Japanese patients with moderate-to-severe plaque psoriasis, erythrodermic psoriasis and generalized pustular psoriasis.

BACKGROUND: Ixekizumab, an anti-IL-17A monoclonal antibody, demonstrated a high level of efficacy in moderate-to-severe plaque psoriasis (PP) patients. OBJECTIVE: To evaluate the efficacy and safety of open-label ixekizumab in Japanese patients with moderate-to-severe PP, erythrodermic psoriasis (EP) and generalized pustular psoriasis (GPP). METHODS: Patients received 160-mg subcutaneous ixekizumab injection at Week 0, 80-mg every 2 weeks through Week 12 and 80-mg every 4 weeks through Week 24. Efficacy and safety are reported through 24 weeks; additional safety data are available for some patients. RESULTS: A total of 78 patients with PP, 8 with EP and 5 with GPP enrolled. In PP patients, PASI75 and PASI90 response rates were 98.7% (77/78) and 83.3% (65/78) at Week 12 respectively. In EP patients, PASI75 and PASI90 were 100.0% (8/8) and 62.5% (5/8) and in GPP patients were 80.0% (4/5) and 60.0% (3/5). Overall, 84.0% (76/91) had a treatment-emergent AE through ≥24 weeks. There were no serious AEs, deaths, cases of tuberculosis or invasive fungal infections. LIMITATIONS: No control group and small sample sizes, especially for EP and GPP. CONCLUSION: By Week 12, nearly all patients with PP, EP and GPP achieved PASI75. The safety profile was consistent with reported results and no unexpected safety signals were observed.

Improvement of scalp and nail lesions with ixekizumab in a phase 2 trial in patients with chronic plaque psoriasis.

BACKGROUND: Scalp and nail psoriasis have a major impact on quality of life and are traditionally resistant to therapy. Ixekizumab is a monoclonal antibody that targets IL-17A, a key cytokine in psoriasis pathogenesis. OBJECTIVE: Changes in nail and scalp psoriasis associated with ixekizumab treatment were evaluated in a post hoc analysis of a phase 2 study comprising a 20-week randomized, placebo-controlled (RCT) period and 48 weeks of an open-label extension (OLE) period. METHODS: There were 142 patients with moderate-to-severe plaque psoriasis at baseline of the RCT. Patients were randomized to receive placebo, 10, 25, 75 or 150 mg of ixekizumab injected subcutaneously at weeks 0, 2, 4, 8, 12 and 16. In the OLE, all patients received 120 mg ixekizumab every 4 weeks. Nail Psoriasis Severity Index (NAPSI) and Psoriasis Scalp Severity Index (PSSI) were used to evaluate nail and scalp psoriasis respectively. Fifty-eight (41.0%) patients had nail psoriasis (NAPSI > 0) and 105 (74.0%) had scalp psoriasis (PSSI > 0) at baseline; these cases were evaluated for the present analyses. RESULTS: At RCT week 20, patients with scalp psoriasis in the 25-, 75- and 150-mg groups had significant mean change and percent improvement from baseline PSSI of -16.3 (75.3%; P = 0.001), -11.6 (83.7%; P = 0.001) and -18.2 (82.2%; P < 0.001) respectively compared to -6.0 (18.8%) in placebo. Patients with nail psoriasis in the 75- and 150-mg groups had significant improvements from baseline NAPSI of -26.3 (63.8%; P = 0.003) and -23.1 (52.6%; P = 0.009) respectively compared to 0.4 (-1.7%) in placebo. By OLE week 48, 78.0% of patients with scalp psoriasis and 51.0% of patients with nail psoriasis experienced complete resolution of lesions (PSSI = 0 or NAPSI = 0). CONCLUSIONS: Ixekizumab monotherapy improved scalp psoriasis quickly with maintenance of clinical response and complete resolution of plaques in the majority of patients. Additionally, over 50.0% of patients with nail psoriasis experienced complete resolution of nail lesions by OLE week 48.

Dimensions of the paediatric femur: anatomical limitations of flexible intramedullary nailing.

PURPOSE: Although spica casting remains the benchmark for treating diaphyseal femur fractures in preschool children, some authors advocate using flexible intramedullary nails in certain situations. The aim of the current study was to evaluate the anatomic feasibility of flexible nailing in young children. METHODS: Consecutive patients between the ages of zero and ten years with normal femurs who received femur radiographs at a tertiary paediatric hospital over a two-year period were included. Anteroposterior femur radiographs were evaluated for length and isthmus width measurements. Each femur was templated for flexible nail size. The proportions of each age group capable of accommodating two flexible nails up to 4.0 mm in size were determined and compared. RESULTS: A total of 381 full-length femur radiographs were reviewed. There was a strong, direct linear relationship between age and femoral length (R2 = 0.896) and a moderate correlation between age and femoral isthmus width (R2 = 0.417). Although the percentage of femurs able to accommodate flexible nails continued to increase with age, this increase did not represent a significant difference when comparing preschool-aged children with older age groups. CONCLUSIONS: Age and femoral length demonstrated a strong, positive correlation while age and isthmus width had weaker correlation. The ability of femurs to accommodate flexible nails increased with age with most children age two years and older able to accommodate two flexible nails of at least 2.5 mm in size. LEVEL OF EVIDENCE: III.

Fluoroscopic imaging overestimates the screw tip to subchondral bone distance in a cadaveric model of slipped capital femoral epiphysis.

PURPOSE: Intra-operative imaging plays a key role in screw placement for slipped capital femoral epiphysis (SCFE). Complications have been associated with inadequate screw position. The purpose of this study was to evaluate computed tomography (CT) (3D fluoroscopy) and standard fluoroscopy (C-arm) images as compared with direct anatomic measurement to determine final screw position in a cadaveric SCFE model. METHODS: Osteotomy with pinning was performed at the physeal scar in ten cadaveric hips. A standardised approach-withdrawal technique was performed with C-arm images taken at 15° increments. We also obtained a CT (3D fluoroscopy) scan of each hip. The screw tip-subchondral bone (STSB) distance was measured on digital imaging software and also with a digital calliper directly when the femoral head was cut in plane to expose the STSB distance anatomically. Statistical analysis included t-tests and Fisher's exact test. RESULTS: Moderate SCFE osteotomies were achieved with a mean Southwick angle (39.5° ± 7°). The 60° fluoroscopic image was found to be the most representative image (41% of the time) compared with both anteroposterior (AP) and lateral images (8% and 21%). Both fluoroscopy (2.7 ± 0.8 mm, p < 0.001) and CT (1.6 ± 0.7 mm, p = 0.03) overestimated the STSB distance compared with direct measurement (0.94 ±  0.51 mm). Two-thirds (67%) of CT measurements were within 1 mm of the cadaveric measurement, while only 20% of C-arm measurements fulfilled this criterion (p = 0.04). CONCLUSIONS: Both standard fluoroscopy and CT overestimated the STSB distance when compared with direct measurement in a cadaveric model of SCFE. Surgeons should be aware of the limitations of intra-operative imaging to determine the STSB distance. We suggest that using the known pitch of a screw (2.9 mm in a 7.3-mm cannulated screw) as an intra-operative tool to help guide screw placement.

Molecular characterization of P2B/LAMP-1, a major protein target of a metastasis-associated oligosaccharide structure.

Sialylated and GlcNAc beta 1-6Man alpha 1-6Man beta 1 (beta 1-6 branched) complex-type oligosaccharides linked to asparagine residues of membrane glycoproteins in metastatic murine tumor cells have been associated with efficient tumor cell metastasis. A large proportion of these oligosaccharide structures, in several unrelated malignant cell lines, have been shown to be associated with a glycoprotein termed P2B, with a molecular weight of 130,000. This glycoprotein has recently been purified from the metastatic MDAY-D2 cell line and shown to be biochemically similar to a lysosomal associated membrane glycoprotein (LAMP-1). We report here the details of a 2147 nucleotide complementary DNA encoding the entire murine P2B polypeptide which was immunoselected from a lambda gt11 expression library and sequenced. The sequence is similar to a complementary DNA coding for mouse LAMP-1 with the exception of a 5' untranslated region, a leader signal-sequence, and various insertions, deletions, and substitutions in the 3' untranslated domain. An open reading frame of 405 amino acids encodes a mature polypeptide of 382 residues with a predicted molecular weight of 42,000. P2B/LAMP-1 possesses 20 asparagine-linked glycosylation sites separated into equal halves by a central, putative hinge region and is anchored by a carboxy, membrane-spanning, domain. Topological considerations dictate that cell surface expression of P2B/LAMP-1 exposes the bulk of the glycoprotein into the extracellular compartment. Immunofluorescent staining of fibroblast cells indicated that P2B/LAMP-1 was associated with lysosomal membranes and, to a lesser degree, select surfaces of plasma membrane. An amino acid comparison of the murine sequence with its recently cloned rat, human, and chicken counterparts shows a conservation of 17 of 20 asparagine-linked glycosylation consensus sites, eight of eight cysteine residues, and other selected protein domains. The interspecies conservation of these domains suggests that they are important for the structure and function of the P2B/LAMP-1 glycoprotein. Northern analysis revealed that P2B/LAMP-1 is widely expressed in normal murine tissues and tumor cell lines. However, in two experimental models of metastasis, where changes in branching of oligosaccharides on P2B/LAMP-1 have been shown to occur, comparable levels of P2B/LAMP-1 mRNA were found in both metastatic and nonmetastatic cell lines.

Pamidronate reduces skeletal morbidity in women with advanced breast cancer and lytic bone lesions: a randomized, placebo-controlled trial. Protocol 18 Aredia Breast Cancer Study Group.

PURPOSE: To assess whether pamidronate can reduce the frequency of skeletal morbidity in women with lytic bone metastases from breast cancer treated with hormone therapy. PATIENTS AND METHODS: Three hundred seventy-two women with breast cancer who had at least one lytic bone lesion and who were receiving hormonal therapy were randomized to receive 90 mg of pamidronate or placebo as a 2-hour intravenous infusion given in double-blind fashion every 4 weeks for 24 cycles. Patients were evaluated for skeletal complications: pathologic fractures, spinal cord compression, irradiation of or surgery on bone, or hypercalcemia. The skeletal morbidity rate (the ratio of the number of skeletal complications to the time on trial) was the primary efficacy variable. Bone pain, use of analgesics, quality of life, performance status, bone tumor response, and biochemical parameters were also evaluated. RESULTS: One hundred eighty-two patients who received pamidronate and 189 who received placebo were assessable. The skeletal morbidity rate was significantly reduced at 12, 18, and 24 cycles in patients treated with 90 mg of pamidronate (P = .028, .023, and .008, respectively). At 24 cycles, the proportion of patients having had any skeletal complication was 56% in the pamidronate group and 67% in the placebo group (P = .027). The time to the first skeletal complication was longer for patients receiving pamidronate than for those given placebo (P = .049). There was no statistical difference in survival or in objective bone response rate. Pamidronate was well tolerated. CONCLUSION: Treatment with 90 mg of pamidronate as a 2-hour intravenous infusion every 4 weeks in addition to hormonal therapy significantly reduces skeletal morbidity from osteolytic metastases.

Long-term prevention of skeletal complications of metastatic breast cancer with pamidronate. Protocol 19 Aredia Breast Cancer Study Group.

PURPOSE: Pamidronate, an aminobisphosphonate, has been shown to lower the risk of skeletal complications associated with lytic bone lesions for up to 1 year in women with stage IV breast cancer who received chemotherapy. We studied the long-term effectiveness and safety of continued treatment with intravenous pamidronate infusions for up to 2 years. PATIENTS AND METHODS: Three hundred eighty-two women with metastatic breast cancer and lytic bone lesions who received chemotherapy were randomly assigned to receive either 90 mg of pamidronate or placebo intravenously every 3 to 4 weeks in this double-blind, multicenter, parallel-group trial. Patients were evaluated monthly for 2 years for skeletal complications, which included pathologic fractures, need for radiation or surgery to treat bone complications, spinal cord compression, and hypercalcemia. Bone pain, analgesic use, bone biochemical markers, performance status, quality of life, radiologic response in bone, and survival were also evaluated. RESULTS: As in the first year of treatment, the proportion of patients with any skeletal complication was significantly less for the pamidronate than the placebo group at 15, 18, 21, and 24 months (P < .001). The proportions of patients with any pathologic fracture (i.e., vertebral and nonvertebral fractures), need for radiation or surgery to treat bone complications, and hypercalcemia were also statistically less for the pamidronate than the placebo group. The median time to the first skeletal complication was 13.9 months in the pamidronate-treated women and 7.0 months in the placebo group (P < .001). Long-term treatment did not result in any unexpected adverse events. Survival did not differ between the two groups. CONCLUSION: The risk for osteolytic bone lesion complications in metastatic breast cancer was significantly decreased with monthly infusions of 90 mg of pamidronate, and this effect was maintained for at least 2 years. Pamidronate is a useful adjunct to standard chemotherapy in the palliative treatment of metastatic breast cancer.

Long-term pamidronate treatment of advanced multiple myeloma patients reduces skeletal events. Myeloma Aredia Study Group.

PURPOSE: To determine the efficacy and safety of 21 monthly cycles of pamidronate therapy in patients with advanced multiple myeloma. PATIENTS AND METHODS: Patients with stage III myeloma and at least one lytic lesion received either placebo or pamidronate 90 mg intravenously administered as a 4-hour infusion monthly for 21 cycles. At study entry, the patients were stratified according to whether they were to receive first-line (stratum 1) or second-line (stratum 2) antimyeloma chemotherapy. Skeletal events (pathologic fracture, radiation or surgery to bone, and spinal cord compression) and hypercalcemia were assessed monthly. RESULTS: The results of the first nine previously reported cycles are extended to 21 cycles. Of the 392 randomized patients, efficacy could be evaluated in 198 who received pamidronate and 179 who received placebo. After 21 cycles, the proportion of patients who developed any skeletal event was lower in the pamidronate-group (P = .015). The mean number of skeletal events per year was less in the pamidronate-group (1.3) than in placebo-treated patients (2.2; P = .008). Although survival was not different between the pamidronate-treated group and placebo patients overall, stratum 2 patients who received pamidronate lived longer than those who received placebo (14 v 21 months, P = .041). Pamidronate was safe and well tolerated during the 21 cycles of therapy. CONCLUSION: Long-term monthly infusions of pamidronate as an adjunct to chemotherapy are superior to chemotherapy alone in reducing skeletal events in stage III multiple myeloma patients, and may improve the survival of patients on salvage therapy.

Treatment of cancer-associated hypercalcemia. Double-blind comparison of rapid and slow intravenous infusion regimens of pamidronate disodium and saline alone.

BACKGROUND: We assessed the effects of 60-mg single doses of pamidronate disodium compared with saline alone in the treatment of cancer-associated hypercalcemia. METHODS: After pretreatment hydration, patients with corrected serum calcium concentrations of 3.0 mmol/L (12 mg/dL) or greater secondary to cancer were randomized to double-blind treatment with a single infusion of pamidronate disodium, 60 mg, over either 4 or 24 hours or continued infusions of 0.9% saline alone (n = 23 per group). Corrected serum calcium levels were measured daily for 7 days of inpatient evaluation. RESULTS: Response rates for both of the pamidronate regimens were significantly (P < .05) higher than that for saline alone. A complete response to treatment (corrected serum calcium concentration normalized) was observed for five (22%), 18 (78%), and 14 (61%) patients, respectively, who received saline alone, 4-hour infusion of pamidronate, and 24-hour infusion of pamidronate. There were no significant differences between the two pamidronate regimens. Median durations of complete response were 6, 6, and 11 days, respectively, and median times to relapse (includes complete plus partial responders and nonresponders) were 0, 7, and 7 days, respectively. Pamidronate was well tolerated as assessed by all clinical and laboratory measures, regardless of the time of infusion. CONCLUSIONS: A 4-hour infusion of pamidronate disodium, 60 mg, was as safe and effective as a 24-hour infusion, and both were superior to saline alone in lowering corrected serum calcium concentrations in patients with cancer-associated hypercalcemia.

The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta(3)-AR knock-out mice.

Both human GH (hGH) and a lipolytic fragment (AOD9604) synthesized from its C-terminus are capable of inducing weight loss and increasing lipolytic sensitivity following long-term treatment in mice. One mechanism by which this may occur is through an interaction with the beta-adrenergic pathway, particularly with the beta(3)-adrenergic receptors (beta(3)-AR). Here we describe how hGH and AOD9604 can reduce body weight and body fat in obese mice following 14 d of chronic ip administration. These results correlate with increases in the level of expression of beta(3)-AR RNA, the major lipolytic receptor found in fat cells. Importantly, both hGH and AOD9604 are capable of increasing the repressed levels of beta(3)-AR RNA in obese mice to levels comparable with those in lean mice. The importance of beta(3)-AR was verified when long-term treatment with hGH and AOD9604 in beta(3)-AR knock-out mice failed to produce the change in body weight and increase in lipolysis that was observed in wild-type control mice. However, in an acute experiment, AOD9604 was capable of increasing energy expenditure and fat oxidation in the beta(3)-AR knock-out mice. In conclusion, this study demonstrates that the lipolytic actions of both hGH and AOD9604 are not mediated directly through the beta(3)-AR although both compounds increase beta(3)-AR expression, which may subsequently contribute to enhanced lipolytic sensitivity.

Short-term effects of recombinant human insulin-like growth factor I on metabolic control of patients with type II diabetes mellitus.

Recombinant human insulin-like growth factor I (rhIGF-I) lowers blood glucose, serum insulin, C-peptide, and lipid levels in healthy and diabetic animals and humans. We hypothesized that rhIGF-I might control blood glucose levels and concomitantly reduce pancreatic insulin secretion in patients with type II diabetes. If true, rhIGF-I might serve as a therapeutic agent that could mitigate some of the detrimental effects of hyperinsulinemia secondary to insulin resistance in these patients. In this study, we treated 12 patients with type II diabetes mellitus twice daily for 5 days with sc rhIGF-I in doses of 90, 120, or 160 micrograms/kg body weight. Metabolic parameters in the fasting and postprandial states were assessed during a 3-day baseline period, the rhIGF-I treatment period, and a 3-day follow-up period, respectively. Administration of rhIGF-I significantly reduced mean (+/- SD) concentrations of fasting blood glucose (12.3 +/- 4.5 to 9.1 +/- 2.6 mmol/L), serum insulin (98 +/- 52 to 56 +/- 27 pmol/L), and C-peptide (993 +/- 298 to 728 +/- 232 pmol/L). It also decreased postprandial (area under the curve) blood glucose (32.5 +/- 12.7 to 23.9 +/- 8.1 mmol/L.h), serum insulin (1102 +/- 707 to 467 +/- 332 pmol/L.h), and C-peptide (5958 +/- 2747 to 3442 +/- 1523 pmol/L.h). The administration of rhIGF-I was also associated with a small but significant reduction in serum triglycerides (6.76 +/- 3.45 to 5.32 +/- 2.59 mmol/L) and total cholesterol (6.13 +/- 1.25 to 5.66 +/- 1.20 mmol/L), 24-h creatinine clearance increased significantly (85 +/- 30 to 133 +/- 51 mL/min), and microalbuminuria was unchanged. Although rhIGF-I was reasonably well tolerated, side effects included low-grade edema, mild and mainly asymptomatic orthostatic hypotension, and bilateral temporomandibular tenderness. We conclude that short-term treatment of type II diabetic patients with rhIGF-I favorably affects metabolic control and enhances kidney function. An assessment of the risk/benefit ratio of rhIGF-I administration to this group of patients awaits extended experiments.

Thiol proteases released in vitro by Fasciola hepatica.

Immature Fasciola hepatica release 11 distinct proteases when cultured in vitro for 16 h as revealed by gelatin-substrate sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Six of these proteases are active in the pH range 4.5 to 8.0. Five are acid proteases, being most active in the pH range 3.0 to 4.5. The majority of proteases released in vitro by immature flukes are also released by mature flukes; however, a 40-kDa protease released by immature flukes is a very minor protease released by mature flukes. The activity of all proteases is inhibited by leupeptin, L-trans-epoxysuccinyl-leucylamido(4-guanidino)butane, phenylmethylsulfonyl fluoride and iodoacetamide and enhanced or stabilized by the reducing agents cysteine and dithiothreitol. Therefore, all F. hepatica in vitro-released proteases identified by gelatin-substrate SDS-PAGE are thiol proteases.

Fasciola hepatica: a secreted cathepsin L-like proteinase cleaves host immunoglobulin.

Adult Fasciola hepatica secrete a cysteine proteinase capable of cleaving host IgG close to the papain cleaving site. The proteinase was separated by size permeation chromatography. Gelatin-substrate polyacrylamide gel electrophoresis analysis revealed that the proteinase migrates as 6 proteolytic bands in the apparent molecular size range 60-90 kDa. Based on pH profiles of activity, inhibition studies using diethylpyrocarbonate and the diazomethylketone Z-phe-ala-CHN2, and characterising the substrate specificity of the enzymes using fluorogenic peptide substrates we have shown that the 60-90-kDa proteinases are cathepsin L-like proteinases.

Antinuclear antibodies in dermatology.

Antinuclear antibodies are used in the diagnosis and evaluation of patients with connective tissue diseases. The study of antinuclear antibodies has also fundamentally expanded our understanding of nuclear anatomy and function. This article reviews the clinically relevant antinuclear antibodies and their disease associations. Developing an understanding of the utilities and limitations of antinuclear antibodies is essential to providing the expert diagnoses prognoses, and care expected of a dermatologist.

Alpha-glutathione s-transferase (alpha-GST) release, an early indicator of carbon tetrachloride hepatotoxicity in the rat.

1. The use of the cytoplasmic enzyme, alpha glutathione s-transferase (alpha-GST) as an early index of carbon tetrachloride (CCl4) toxicity in the rat was investigated and compared with a standard enzyme, marker, aspartate aminotransferase (AST). The hepatotoxic effects of CCl4 in the rat were determined in a time and dose-response study. 2. Following CCl4 exposure, alpha-GST release was shown to be an earlier and more sensitive biomarker of hepatotoxicity than AST. 3. Significant increases in alpha-GST were detected 2 h after CCl4 exposure. Using the enzyme marker AST, this early hepatotoxic injury went undetected. At 6 and 16 h, alpha-GST was also a more sensitive indicator of hepatotoxicity than AST. 4. alpha-GST release was significantly increased at a dose of 5 microliters/kg, the lowest concentration of CCl4 administered and clearly responded in a dose-dependent manner with increasing doses of CCl4. In contrast, release of AST did not reach statistical significance until a dose of 25 microliters/kg. 5. Thus, these findings indicate that alpha-GST is a more sensitive and more accurate reflector of CCl4 induced hepatotoxicity than AST.

Incidence of cryptorchidism in dogs and cats.

Over a period of 54 months, 3518 dogs and 3806 cats were castrated; 240 of the dogs and 50 of the cats were cryptorchid. Pedigree dogs, in particular the German shepherd dog, boxer and chihuahua were over-represented. Among the dogs, right-sided inguinal cryptorchidism was the most common form, followed by right-sided abdominal cryptorchidism. The location of the affected testicle(s) was most variable in the boxer. Among the cats, left- or right-sided inguinal cryptorchidism were the most common forms of the condition.