Outcomes of posterior sheath supplementation with Vicryl mesh in TAR-a single-center study.

INTRODUCTION: In the Transversus Abdominis Release (TAR) procedure, ideally, the posterior sheath is completely reapproximated to establish an interface isolating the polypropylene mesh from visceral contents. When primary closure of the posterior sheath is unachievable, Vicryl mesh is commonly used to supplement the posterior sheath closure and an uncoated polypropylene mesh is placed superficial to the Vicryl mesh. The long-term implications of utilizing Vicryl mesh as an antiadhesive barrier are poorly understood. In this study, we aimed to assess our outcomes when utilizing Vicryl mesh to supplement the posterior sheath defects when placed underneath polypropylene mesh in patients undergoing posterior component separation. METHODS: Adult patients who underwent VHR with concurrent TAR procedure with a permanent synthetic mesh and posterior sheath supplementation with Vicryl mesh in the Cleveland Clinic Center for Abdominal Core Health between January 2014 and December 2022 were queried retrospectively from a prospectively collected database in the Abdominal Core Health Quality Collaborative. We evaluated 30-day wound morbidity, perioperative complications, long-term mesh-related complications, and pragmatic hernia recurrence. RESULTS: 53 patients who underwent TAR procedure with posterior sheath supplementation using Vicryl mesh and had a minimum 12-month follow-up were identified. Of the 53 patients, 94.3% presented with recurrent hernias, 73.6% had a midline hernia, 7.5% had a flank hernia, and 18.9% had concurrent parastomal hernia. The mean hernia width was 24.9 cm (± 8.8 cm). No Vicryl mesh-related operative complications were identified in our study, with no instances of mesh erosion, fistulas, or interventions for small bowel obstruction. Skin necrosis requiring reoperations was observed in three patients (5.7%), leading to permanent mesh excision in two cases (3.8%) without intraabdominal visceral involvement. Throughout the 12-month follow-up, 23 incidences (43.4%) of surgical site occurrences (SSOs) and surgical site occurrences requiring procedural intervention (SSOPI) were documented. CONCLUSIONS: Our findings suggest that posterior sheath supplementation with Vicryl mesh is a feasible approach to achieve posterior sheath closure in challenging abdominal wall reconstruction cases. Given the absence of notable mesh-related complications and a similar hernia recurrence rate to cases without posterior sheath supplementation, Vicryl mesh can be used to safely achieve posterior sheath closure in complex reconstructions with insufficient native tissue.

The impact of smoking on inguinal hernia repair outcomes: a meta-analysis of multivariable-adjusted studies.

PURPOSE: While the detrimental effects of smoking on postoperative outcomes are recognized, the extent of its risk for inguinal hernia repair remains unclear. Our study aims to assess the influence of smoking on patients who undergo inguinal hernia repair. METHODS: We systematically reviewed PubMed, Embase, and Cochrane databases. Our goal was to identify studies that compared postoperative outcomes in smoking and non-smoking patients after inguinal hernia repair, and which employed a multivariate analysis to reduce possible confounding factors. Outcomes were recurrence, postoperative complications, and surgical site infection. Odds ratios (ORs) with 95% confidence intervals (CIs) were computed with the use of a random-effects model. Heterogeneity was examined with I2 statistics. This review was prospectively registered in PROSPERO (CRD42023445513). RESULTS: Our analysis encompassed 11 studies, involving a total of 577,901 patients. Of these, 77,226 (or 13.4%) identified as smokers, with males constituting 90% of the cohort. In terms of surgical approaches, 58% underwent laparoscopic procedures were most common at 58%, followed by open surgeries at 41%, and 1% used robotic techniques. All included studies had a low risk of bias. Smoking was associated with a higher incidence of hernia recurrence (OR 2.95; 95% CI 2.08 to 4.18; p < 0.001; I2 = 0%). No differences were found in postoperative complication (OR 1.15; 95% CI 1.00 to 1.32; p = 0.05; I2 = 56%) or surgical site infection (OR 2.94; 95% CI 0.80 to 10.88; p = 0.11; I2 = 79%). CONCLUSION: Smoking was associated with a three-fold increase in recurrence. Further studies are needed to evaluate the impact of preoperative smoking cessation on reducing recurrence.

Can surgeons accurately identify mesh type when interpreting computed tomography scans after ventral hernia repair?

BACKGROUND: Recurrent ventral hernia repair can be challenging due to scarred tissue planes and the increasing complexity of disease related to multiple recurrences. Given the challenges of acquiring complete and accurate prior operative reports, surgeons often rely on computed tomography (CT) scans to obtain information and plan for re-operation. Still, the contribution of CT scans and the ability of surgeons to interpret them is controversial. Previously, we examined the ability of surgeons to determine prior operative techniques based on CT scans. Here, we assessed the accuracy of expert abdominal wall reconstruction (AWR) surgeons in identifying the type of prior mesh using CT imaging. METHODS: A total of 22 highly experienced AWR surgeons were asked to evaluate 21 CT scans of patients who had undergone open ventral hernia repair with bilateral transversus abdominis release utilizing mesh. The surgeons were required to identify the mesh type from a multiple-choice selection. Additionally, negative controls (patients without a history of prior laparotomy) and positive controls (patients with laparotomy but no ventral hernia repair) were incorporated. The accuracy of the surgeons and interrater reliability was calculated. RESULTS: The accuracy rate of the surgeons in correctly identifying the mesh type was 46%, with heavy-weight synthetic mesh (HWSM) being identified only 35.4% of the time, Strattice mesh and medium-weight synthetic mesh (MWSM) were identified at 46.3%, and 51.8%, respectively. The interrater reliability analysis found a moderate level of agreement 0.428 (95% CI 0.356-0.503), and the repeatability measure was poor-0.053 (95% CI 0-0.119); this indicates that surgeons cannot reliably replicate the identification process. CONCLUSIONS: Surgeons' ability to accurately identify the type of previous mesh using CT scans is poor. This study underscores the importance of documenting the type of mesh used in the operative report and the need for standardized operative notes to improve the accuracy and consistency of documentation.

Outcomes of complex abdominal wall reconstruction in patients with connective tissue disorders: a single center experience.

INTRODUCTION: Individuals diagnosed with connective tissue disorders (CTD) are known to be predisposed to incisional hernia formation. However, there is a scarcity of data on outcomes for these patients undergoing hernia repair. We sought to describe our outcomes in performing abdominal wall reconstructions in these complex patients. METHODS: Adult patients with CTD undergoing open, elective, posterior component separation with permanent synthetic mesh at our institution from January 2018 to October 2022 were queried from a prospectively collected database in the Abdominal Core Health Quality Collaborative. We evaluated 30-day wound morbidity, perioperative complications, long-term hernia recurrence, and patient-reported quality of life. RESULTS: Twelve patients were identified. Connective tissue disorders included Marfan's n = 7 (58.3%), Loeys-Dietz syndrome n = 2 (16.7%), Systemic Lupus Erythematosus n = 2 (16.7%), and Scleroderma n = 1 (8.3%). Prior incisions included three midline laparotomies and nine thoracoabdominal, mean hernia width measured 14 cm, and 9 were recurrent hernias. Surgical site occurrences (SSOs) were observed in 25% of cases, and 16.7% necessitated procedural intervention. All twelve patients were available for long-term follow-up, with a mean of 34 (12-62) months. There were no instances of reoperation or mesh excision related to the TAR procedure. One patient developed a recurrence after having his mesh violated for repair of a new visceral aneurysm. Mean HerQLes scores at 1 year were 70 and 89 at ≥ 2 years; Mean scaled PROMIS scores were 30.7 at 1 year and 36.3 at ≥ 2 years. CONCLUSION: Ventral hernia repair with TAR is feasible in patients with connective tissue disorder and can be a suitable alternative in patients with large complex hernias.

Analysis of retromuscular drain output and postoperative outcomes for heavyweight versus mediumweight polypropylene mesh following open ventral hernia repair.

PURPOSE: Heavyweight polypropylene (HWPP) mesh is thought to increase inflammatory response and delay tissue integration compared to mediumweight (MWPP). Reactive fluid volume (i.e., drain output) may be a reasonable surrogate for integration. We hypothesized that daily drain output is higher with HWPP compared to MWPP in open retromuscular ventral hernia repair (VHR). METHODS: This is a post-hoc analysis of a multicenter, randomized clinical trial conducted March 2017-April 2019 comparing MWPP and HWPP for VHR. Retromuscular drain output in milliliters was measured at 24-h intervals up to postoperative day seven. Univariate analyses compared differences in daily drain output and time to drain removal. Multivariable analyses compared total drain output and wound morbidity within 30 days and hernia recurrence at 1 year. RESULTS: 288 patients were included; 140 (48.6%) HWPP and 148 (51.4%) MWPP. Daily drain output for days 1-3 was higher for HWPP vs. MWPP (total volume: 837.8 mL vs. 656.5 mL) (p < 0.001), but similar on days 4-7 (p > 0.05). Median drain removal time was 5 days for both groups. Total drain output was not predictive of 30-day wound morbidity (p > 0.05) or hernia recurrence at 1 year (OR 1, p = 0.29). CONCLUSION: While HWPP mesh initially had higher drain outputs, it rapidly returned to levels similar to MWPP by postoperative day three and there was no difference in clinical outcomes. We believe that drains placed around HWPP mesh can be managed similarly to MWPP mesh.

Cannabis smoking and abdominal wall reconstruction outcomes: a propensity score-matched analysis.

PURPOSE: Despite increasing use of cannabis, literature on perioperative effects is lagging. We compared active cannabis-smokers versus non-smokers and postoperative wound morbidity and reoperations following open abdominal wall reconstruction (AWR). METHODS: Patients who underwent open, clean, AWR with transversus abdominis release and retromuscular synthetic mesh placement at our institution between January 2014 and May 2022 were identified using the Abdominal Core Health Quality Collaborative database. Active cannabis-smokers were 1:3 propensity matched to non-smokers based on demographics and comorbidities. Wound complications, 30 day morbidity, pain (PROMIS 3a-Pain Intensity), and hernia-specific quality of life (HerQles) were compared. RESULTS: Seventy-two cannabis-smokers were matched to 216 non-smokers. SSO (18% vs 17% p = 0.86), SSI (11.1% vs 9.3%, p = 0.65), SSOPI (12% vs 12%, p = 0.92), and all postoperative complications (46% vs 43%, p = 0.63) were similar between cannabis-smokers and non-smokers. Reoperations were more common in the cannabis-smoker group (8.3% vs 2.8%, p = 0.041), driven by major wound complications (6.9% vs 3.2%, p = 0.004). No mesh excisions occurred. HerQles scores were similar at baseline (22 [11, 41] vs 35 [14, 55], p = 0.06), and were worse for cannabis-smokers compared to non-smokers at 30 days (30 [12, 50] vs 38 [20, 67], p = 0.032), but not significantly different at 1 year postoperatively (72 [53, 90] vs 78 [57, 92], p = 0.39). Pain scores were worse for cannabis-smokers compared to non-smokers at 30 days postoperatively (52 [46, 58] vs 49 [44, 54], p = 0.01), but there were no differences at 6 months or 1 year postoperatively (p > 0.05 for all). CONCLUSION: Cannabis smokers will likely experience similar complication rates after clean, open AWR, but should be counseled that despite similar wound complication rates, the severity of their wound complications may be greater than non-smokers.

Abdominal wall mass resections: single-center closure practices and outcomes following oncologic resections of abdominal wall fascia.

PURPOSE: Radical resections for abdominal wall tumors are rare, thus yielding limited data on reconstruction of defects. We describe surgical management and long-term outcomes following radical tumor resection. METHODS: This was a single-center retrospective review of patients between January 2010 and December 2022. Variables included operative characteristics, wound complications, hernia development, tumor recurrence, and reoperation. A multivariable analysis compared wound morbidity for suture and mesh repairs while adjusting for defect width, fascial closure, and CDC wound class. RESULTS: 120 patients were identified. Mean follow-up was 3.9 ± 3.4 years. Seventy-five (62.5%) of the masses were primary; most commonly desmoid (n = 25) and endometrioma (n = 27). Forty-five masses were metastases. Mean tumor width was 6.2 ± 3.4 cm; mean defect width was 8.1 ± 4.1 cm. Sixty-one patients (50.8%) had mesh placed, with variation in technique. Postoperative CT scans were available for 88 (73.3%) patients. Forty SSOs (33.3%), 11 SSIs (9.2%), and 18 (15%) SSOPIs occurred within 30 days. On multivariable analysis, increased defect width was associated with SSOPI (OR 1.17, p = 0.041) and CDC wound class II-III was associated with SSI (OR 8.38 and 49.1, p < 0.05) and SSOPI (OR 5.77 and 17.4, p < 0.05); mesh was not associated with these outcomes. Seven patients (5.8%) underwent 30-day reoperations and 35 (20.8%) required additional operations after 30 days. Thirteen percent developed abdominal wall (n = 8) or intra-abdominal tumor recurrence (n = 8) requiring reoperation. Twenty-seven (22.5%) patients developed hernias with a mean fascial defect width of 9.8 ± 7.2 cm. CONCLUSION: Abdominal wall mass resections are morbid, often contaminated cases with high postoperative complication rates. Risks and benefits of mesh implantation should be tailored on an individual basis.

Clinical assessment of blood glucose homeostasis in horses: comparison of a continuous glucose monitoring system with a combined intravenous glucose and insulin test protocol.

BACKGROUND: The combined glucose-insulin test (CGIT) is helpful for evaluating insulin sensitivity. A continuous glucose monitoring system (CGMS) reports changes in interstitial glucose concentrations as they occur in the blood. Use of the CGMS minimizes animal contact and may be useful when performing a CGIT. HYPOTHESIS: Results obtained using a CGMS are useful for the evaluation of glucose responses during the evaluation of insulin sensitivity in equids. ANIMALS: Seven mature, obese ponies. METHODS: Ponies were equipped with CGMS for determination of interstitial glucose concentrations. Glucose (150 mg/kg, i.v.) and insulin (0.1 U/kg, i.v.) were administered and blood glucose concentrations determined at (minutes after time zero) 1, 5, 15, 25, 35, 45, 60, 75, 90, 105, and 120 with a hand-held glucometer. Blood chemistry results were compared with simultaneously obtained results using CGMS. RESULTS: Concordance coefficients determined for comparison of blood glucose concentrations determined by a hand-held glucometer and those determined by CGMS after the zero time point were 0.623, 0.764, 0.834, 0.854, and 0.818 (for delays of 0, 5, 10, 15, and 20 minutes, respectively). CONCLUSIONS AND CLINICAL IMPORTANCE: Interstitial glucose concentrations obtained by the CGMS compared favorably to blood glucose concentrations. CGMS may be useful for assessment of glucose dynamics in the CGIT.

Laminar leukocyte accumulation in horses with carbohydrate overload-induced laminitis.

BACKGROUND: While there is evidence of laminar leukocyte infiltration in black walnut extract (BWE)-induced laminitis, there is no such evidence for carbohydrate overload (CHO) laminitis. OBJECTIVE: To assess presence of leukocytes and signs of epidermal stress/injury in the laminar tissue from horses with CHO-induced laminitis. ANIMALS: Twenty-four adult horses. METHODS: Immunohistochemistry for myeloid cell markers calprotectin (CP) and monocyte-specific marker (CD163) was performed on laminar sections obtained from 2 groups of horses in the CHO model: the developmental time point (DTP) group (n = 6) and the onset of lameness (LAM) group (n = 6), and a control (CON) group (n = 8). RESULTS: DTP was characterized by an increase in CP(+) leukocytes (7.8-fold increase versus CON, P < .001), and LAM time point was characterized by a more marked increase in laminar CP(+) (108.5-fold, P < .001) and mild increase in CD163(+) (1.9-fold, P = .007) cell counts. Increased CP epidermal signal (indicating epidermal stress or injury) occurred consistently at the LAM time point, although histological evidence of basement membrane (BM) detachment was minor, only being present in 3/6 horses. CONCLUSIONS AND CLINICAL RELEVANCE: Maximal laminar leukocyte infiltration and epithelial stress occurred at the onset of lameness in the CHO model showing a different temporal pattern from the BWE model, where maximal leukocyte infiltration clearly precedes epithelial stress. Leukocyte infiltration before major histological changes in the CHO model indicates that leukocyte infiltration can be a cause of and not a reaction to BM degradation and structural failure.

Seasonal and pulsatile dynamics of thyrotropin and leptin in mares maintained under a constant energy balance.

The objective of this study was to determine if seasonal and/or pulsatile variations occur in plasma concentrations of thyrotropin (TSH) and leptin in mares while maintaining a constant energy balance. Blood samples were collected every 20 min during a 24h period in winter and again in summer from six Quarter Horse type mares. Plasma concentrations of TSH, leptin, and T(4) were determined by radioimmunoassay. No differences were observed in body weight between winter (388.1+/-12.5 kg) and summer (406.2+/-12.5 kg; P=0.11). Plasma concentrations of TSH were greater in the summer (2.80+/-0.07 ng/ml) when compared to winter (0.97+/-0.07 ng/ml; P<0.001). Pulse frequency of TSH was not different between winter (6.17+/-0.78 pulses/24h) and summer (5.33+/-0.78 pulses/24h; P=0.49). Mean TSH pulse amplitude, pulse area, and area under the curve were all greater in summer compared to winter (3.11+/-0.10 ng/ml versus 1.20+/-0.10 ng/ml, 24.86+/-0.10 ng/ml min versus 13.46+/-1.90 ng/ml min, 3936+/-72.93 ng/ml versus 1284+/-72.93 ng/ml, respectively; P<0.01). Mean concentrations of leptin were greater in summer (2.48+/-0.17 ng/ml) compared to winter (0.65+/-0.17 ng/ml; P<0.001). Pulsatile secretion patterns of leptin were not observed in any horses during experimentation. Mean concentrations of T(4) were greater in winter (20.3+/-0.4 ng/ml) compared to summer (18.2+/-0.4 ng/ml; P<0.001). These seasonal differences between winter and summer provide evidence of possible seasonal regulation of TSH and leptin.

Professional-patient relationships and informed consent.

Four theoretical ethical perspectives on professional-patient relationships-autonomy, justice, virtue ethics, and the ethic of care-are surveyed, and some of their implications for the informed consent requirement in health care are sketched out. The practical issues of competence to consent, adequate information, and voluntariness are reviewed, and examples are given of the ways in which the theoretical perspectives outlined earlier might inform practice in areas such as these. Finally, the situation of patients not competent to consent is considered in the light of the same theoretical perspectives.

Tissue-specific dysregulation of cortisol metabolism in equine laminitis.

REASONS FOR PERFORMING STUDY: The role of glucocorticoids (GCs) in the pathogenesis of laminitis is incompletely understood. Local tissue activity of GC is regulated by the steroid converting enzyme, 11beta-hydroxysteroid dehydrogenase-1 (11beta-HSD-1). Changes in integumentary (skin and hoof lamellar) 11beta-HSD activity occurring during laminitis could affect the extent to which GCs are involved in its development. HYPOTHESIS: That changes in integumentary 11beta-HSD-1 activity associated with the laminitic condition would lead to elevated local tissue levels of GCs, which could subsequently contribute, through paracrine and autocrine mechanisms, to the further development of laminitis; and that similar changes in 11beta-HSD-1 activity would be evident in both skin and hoof lamellar tissue. METHODS: Activity of 11beta-HSD-1 was determined in skin and hoof lamellar tissue specimens obtained from normal and laminitic horses using a radiometric assay. Skin samples were obtained from 10 normal horses and from 10 horses before and after induction of acute laminitis following administration of starch via nasogastric tube. Hoof lamellar samples were obtained from 10 normal horses, 10 horses following induction of acute laminitis and 4 chronically-foundered horses. Bidirectional 11beta-HSD-1 activity was measured in both skin and lamellar tissues. RESULTS: 11-ketoreductase activity exceeded 11beta-dehydrogenase activity in both skin and lamellar tissues. Cutaneous activity was higher than lamellar 11beta-HSD-1 activity in all groups. Both ketoreductase and dehydrogenase activity increased in skin and lamellae following experimental induction of acute laminitis, but the increase in ketoreductase activity was substantially greater than that for dehydrogenase in the lamellae. Induction of acute laminitis was attended by increases of 227 and 220% in cutaneous dehydrogenase and ketoreductase activity, respectively, and 173 and 398% in lamellar dehydrogenase and ketoreductase activity, respectively (P<0.05). CONCLUSIONS: The 11-ketoreductase moiety of 11beta-HSD-1 plays a role in equine skin and hoof lamellae regarding the regulation of local glucocorticoid activity. Increased 11-ketoreductase activity will lead to increased local tissue GC activity by virtue of conversion of cortisone to cortisol. POTENTIAL RELEVANCE: The laminitic condition is attended by integumentary biochemical changes that enhance the local concentration of cortisol, especially in the hoof lamellar interface. Through multiple and diverse actions, increased local GC activity contributes to the pathogenesis and morbidity associated with laminitis. Pharmacological manipulation of 11beta-HSD-1 deserves further investigation regarding the prevention and treatment of laminitis.

Detection of spinal ataxia in horses using fuzzy clustering of body position uncertainty.

REASONS FOR PERFORMING STUDY: Subjective neurological evaluation in horses is prone to bias. An objective method of spinal ataxia detection is not subject to these limitations and could be of use in equine practice and research. HYPOTHESIS: Kinematic data in the walking horse can differentiate normal and spinal ataxic horses. METHODS: Twelve normal and 12 spinal ataxic horses were evaluated by kinematic analysis walking on a treadmill. Each body position signal was reduced to a scalar measure of uncertainty then fuzzy clustered into normal or ataxic groups. Correct classification percentage (CCP) was then calculated using membership values of each horse in the 2 groups. Subsequently, a guided search for measure combinations with high CCP was performed. RESULTS: Eight measures of body position resulted in CCP > or = 70%. Several combinations of 4-5 measures resulted in 100% CCP. All combinations with 100% CCP could be obtained with one body marker on the back measuring vertical and horizontal movement and one body marker each on the right fore- and hindlimb measuring vertical movement. CONCLUSIONS AND POTENTIAL RELEVANCE: Kinematic gait analysis using simple body marker combinations can be used objectively to detect spinal ataxia in horses.

Effects of propylthiouracil and bromocryptine on serum concentrations of thyrotrophin and thyroid hormones in normal female horses.

REASONS FOR PERFORMING STUDY: There exists a need for better diagnostic tests to characterise thyroid disease in horses. Currently available diagnostic tests fail to differentiate between thyroid gland disorders and thyroid abnormalities resulting from pituitary or hypothalamic problems. OBJECTIVES: To evaluate the effects of treatment with propylthiouracil (PTU) and bromocryptine (BROM) on serum concentrations of triiodothyronine (T3), thyroxine (T4), reverse T3 (rT3) and equine thyroid-stimulating hormone (e-TSH, thyrotrophin) in mature horses. METHODS: Healthy mature horses were treated using either PTU or BROM for 28 days. The effect of treatment on the thyroid axis was assessed by measuring T3, T4, rT3 and e-TSH before and at +14 and +28 days. The effect of PTU and BROM on the response of T3, T4, rT3 and e-TSH to thyrotrophin-release hormone (TRH) administration was also assessed before and at +14 and +28 days of treatment. RESULTS: Treatment with PTU led to a significant reduction in serum concentrations of T3, T4 and rT3 on Day 28 and increase of e-TSH on Day 28 (P < 0.05). Treatment with BROM did not cause any measurable effect on serum concentrations of T3, T4, rT3 or e-TSH. The percentage increment by which serum concentration of T4, T3 and e-TSH increased following stimulation with TRH was decreased by treatment with PTU for 28 days (P < 0.05) but were not affected by treatment with BROM for 28 days. CONCLUSIONS: These results suggest that 1) treatment with PTU may be used in horses as a model of primary hypothyroidism; 2) the use of BROM as a model of secondary hypothyroidism in horses is not supported; and 3) e-TSH assay deserves further investigation for the clinical diagnosis of thyroid axis dysfunction in horses. POTENTIAL RELEVANCE: Propylthiouracil effectively causes primary hypothyroidism. There is substantial variability between horses with respect to their sensitivity to this substance when administered orally. Further studies pertaining to the characterisation of equine thyroid disorders are warranted and the use of both PTU for the experimental induction of primary hypothyroidism and e-TSH for the diagnostic characterisation of thyroid disorders in horses should be considered.

Serum markers of lamellar basement membrane degradation and lamellar histopathological changes in horses affected with laminitis.

In order better to evaluate the extent to which degradation of the lamellar basement membrane (LBM) by matrix metalloproteinases (MMP) occurs in equine laminitis, we determined the concentration of type IV collagen and laminin in normal and laminitic horses, using specific immunoassays. Blood samples were obtained from both the jugular and the cephalic veins of horses (n = 10) before and after the induction of acute alimentary laminitis by carbohydrate overload. Jugular and cephalic venous blood samples were also obtained from horses affected with naturally occurring laminitis (n = 16) and nonlaminitic controls (n = 8). The serum collagen IV concentration was not changed following the induction of laminitis in the experimental group. Serum collagen IV concentration was increased in jugular venous blood obtained from cases of naturally occurring laminitis (mean +/- s.e. 218.04 +/- 18.59 ng/ml) compared with nonlaminitic controls (157.50 +/- 10.93 ng/ml) (P<0.05). Serum collagen IV concentration was also increased in jugular venous blood obtained from severely laminitic horses (219.50 +/- 18.18 ng/ml) compared with nonlaminitic controls (157.50 +/- 10.93 ng/ml) (P<0.05). A difference in serum concentration of collagen IV was not identified based on chronicity of naturally occurring laminitis. Serum laminin concentration did not differ between laminitic and nonlaminitic horses. Differences in serum laminin concentration were not identified based on sampling location (jugular or cephalic vein), severity of laminitic pain, or chronicity of spontaneous laminitis. In conclusion, the circulating concentration of collagen IV was increased in horses affected with naturally occurring laminitis. The potential role for serum collagen IV assay for characterisation of equine laminitis warrants further investigation.

The nature of the metabolic signal that triggers onset of puberty in female rats.

These experiments examined the effects of different refeeding stimuli on reproductive activity as measured by the onset of first estrus in prepubertal, food-restricted female rats. Such rats were placed on a restricted food intake until day 50 of age to maintain a weight of 80-90 g, and to suppress onset of puberty (normal time of puberty: 37 +/- 1.4 days of age). In Experiment 1, rats were refed at different daily caloric intakes from day 50 through day 62. First estrus was observed in all rats, with highest caloric intake after 5.7 +/- 0.6 days of refeeding. Progressively fewer rats achieved first estrus, and the time to first estrus increased as the caloric intake per day decreased. These results suggest that the highest caloric intake most closely resembles an ad lib diet in such realimented rats. The second experiment determined the duration of an ad lib food stimulus needed to initiate first estrus. Similarly growth-restricted rats were refed (on Day 50 of age) ad lib meals of 67.2 +/- 0.1 kcal, presented for periods of 12, 24, 48, or 72 h. The majority of rats (6 of 7) achieved first estrus when the ad lib meals were presented for 72 h, but progressively fewer rats achieved first estrus when such meals were presented for less time. These data indicate that an extended ad lib food stimulus (72 h) is necessary to cause onset of cycling in the majority of food-restricted, prepubertal female rats.

Expression of endothelin in equine laminitis.

Biosynthesis of endothelin-1 (ET-1), the most potent endogenous vasoconstrictor yet identified, is increased following myocardial infarction (MI) in man. Pathological events which occur in the connective tissues of the equine hoof during laminitis are similar in some respects, to changes occurring in the myocardial connective tissues following MI in man. The objective of this study was to determine whether ET-1 expression in connective tissues obtained from the hoof of laminitic horses is increased compared with tissues obtained from healthy horses. Expression of ET-1 in connective tissues of the equine hoof was measured following tissue extraction from 3 groups of horses: horses in which acute laminitis had been induced by the administration of starch; chronically foundered horses; nonlaminitic horses. The concentration of ET-1 in laminar connective tissues obtained from all laminitic horses (1573.0 +/- 392.8 pg/g of tissue; n = 10) was increased when compared with tissues obtained from nonlaminitic horses (392.5 +/- 117.4 pg/g of tissue; n = 5) (P<0.05). The concentration of ET-1 in laminar connective tissues obtained from the experimentally induced, acute laminitic horses (1043.6 +/- 254.4 pg/g of tissue; n = 7) and from the spontaneously affected, chronic laminitic horses (2808.3 +/- 878.6 pg/g of tissue; n = 3) was increased compared with the control group (P<0.05, P<0.01, respectively). The concentration of ET-1 in laminar connective tissues obtained from the chronic laminitic horses was greater than that of the experimentally induced, acute laminitic group (P<0.05). It is suggested that the data provide a strong argument that increased ET-1 expression in the connective tissues of the equine hoof represent a potentially important and hitherto unrecognised component of the pathophysiology of equine laminitis. Further studies are needed to determine whether inhibitors of ET-1 converting enzyme or antagonists of ET-1 receptors might be useful in the treatment and prevention of laminitis in horses.

Activation of extracellular matrix metalloproteinases in equine laminitis.

Samples of connective tissue obtained from the hoof of six laminitic and eight non-laminitic adult horses were analysed zymographically to investigate whether connective tissue matrix metalloproteinases are activated or induced during laminitis. The activity or matrix metalloproteinases was substantially greater in the tissues from the laminitic horses than in the tissues from the non-laminitic horses. A comparison of the collagenolytic activity in the laminitic and control tissues showed that collagenolytic activities corresponding to the 92 kDa (P < 0.001), 72 kDa (P < 0.01) and 66 kDa (P < 0.01) bands were induced in the laminitic tissues.

Congenital defects in newborn foals of mares treated for equine protozoal myeloencephalitis during pregnancy.

Three weak, recumbent neonatal foals with skin lesions, including a thin wooly coat, were born to mares being treated for equine protozoal myeloencephalitis. Mares received sulfadiazine or sulfamethoxazole-trimethoprim, pyrimethamine, folic acid, and vitamin E orally. Foals were anemic, leukopenic, azotemic, hyponatremic, and hyperkalemic. Serum folate concentrations in the 3 foals and 2 mares were lower than those reported in the literature for clinically normal brood mares. Treatment was unsuccessful. For each foal, necropsy revealed lobulated kidneys with thin cortices and a pale medulla, and the spleen and thymus were small. Histologic examination revealed marked epidermal necrosis without inflammatory cells, thin renal cortices, renal tubular nephrosis, lymphoid aplasia, and bone marrow aplasia and hypoplasia. These observations indicate that oral administration of sulfonamides, 2,4-diaminopyrimidines (pyrimethamine with or without trimethoprim), and folic acid to mares during pregnancy is related to congenital defects in newborn foals.