Eighty-three per cent of elite athletes return to preinjury sport after anterior cruciate ligament reconstruction: a systematic review with meta-analysis of return to sport rates, graft rupture rates and performance outcomes.

OBJECTIVES: The primary objective was to calculate the rate of return to sport (RTS) following anterior cruciate ligament (ACL) reconstruction in elite athletes. Secondary objectives were to estimate the time taken to RTS, calculate rates of ACL graft rupture, evaluate postsurgical athletic performance and identify determinants of RTS. DESIGN: Pooled RTS and graft rupture rates were calculated using random effects proportion meta-analysis. Time to RTS, performance data and determinants of RTS were synthesised descriptively. DATA SOURCES: MEDLINE, EMBASE, AMED, CINAHL, AMI, PEDro, SPORTDiscus and The Cochrane Library were searched from inception to 19 January 2016. Hand searching of 10 sports medicine journals and reference checking were also performed. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies were included if they reported the ratio of elite athletes who returned to their preinjury level of sport following ACL reconstruction. Twenty-four studies were included. RESULTS: The pooled RTS rate was 83% (95% CI 77% to 88%). The mean time to RTS ranged from 6 to 13 months. The pooled graft rupture rate was 5.2% (95% CI 2.8% to 8.3%). Six out of nine studies that included a noninjured control group found no significant deterioration in athletic performance following ACL reconstruction. Indicators of greater athletic skill or value to the team were associated with RTS. SUMMARY AND CONCLUSIONS: Eighty-three per cent of elite athletes returned to sport following ACL reconstruction, while 5.2% sustained a graft rupture. Most athletes who returned to sport performed comparably with matched, uninjured controls. This information may assist in guiding expectations of athletes and clinicians following ACL reconstruction.

Patellofemoral osteoarthritis is prevalent and associated with worse symptoms and function after hamstring tendon autograft ACL reconstruction.

OBJECTIVES: To evaluate the compartmental distribution of knee osteoarthritis (OA) after anterior cruciate ligament reconstruction (ACLR), to determine if patellofemoral or tibiofemoral OA is more strongly associated with knee symptoms and function, and to evaluate the contribution of associated injuries and surgical delay to the development of OA. METHODS: This cross-sectional study recruited 70 participants who underwent hamstring tendon (HT) ACLR 5-10 years previously. Radiographic OA was assessed according to the Osteoarthritis Research Society International (OARSI) criteria. Knee symptoms were assessed with the Knee Injury and Osteoarthritis Outcome Score (KOOS) and Anterior Knee Pain Scale (AKPS), while function was assessed with three lower limb tasks (hop-for-distance, one-leg rise and side-hop). Multivariate and binary logistic regression analyses were performed to assess the relationship between OA and symptomatic/functional outcomes and associated injuries/surgical delay, respectively. RESULTS: Radiographic OA was observed in the patellofemoral (47%) and tibiofemoral joints (31%). Pain, symptoms and quality of life on the KOOS and the AKPS were associated with severity of patellofemoral OA (standardised regression coefficient (ß)=-0.3 to -0.5, p=0.001-0.042), whereas only the KOOS-pain subscale was associated with tibiofemoral OA (ß=-0.3, p=0.037). For each functional task, greater patellofemoral OA severity was associated with worse performance, independent of tibiofemoral OA severity (ß=-0.3 to -0.4, p=0.001-0.026). Medial meniscal and patellofemoral chondral lesions at surgery were associated with tibiofemoral and patellofemoral OA development at follow-up, respectively, while a longer surgery delay was associated with patellofemoral OA. CONCLUSIONS: Patellofemoral OA is common following HT ACLR and is associated with worse knee-related symptoms, including anterior knee pain, and decreased functional performance.

Effects of dehydroepiandrosterone sulphate (DHEAS) replacement on insulin action and quality of life in hypopituitary females: a double-blind, placebo-controlled study.

OBJECTIVE: Addition of dehydroepiandrosterone sulphate (DHEAS) to standard pituitary replacement may improve quality of life and glucose metabolism. Conflicting results from the previous work probably relate to differences in populations studied and assessment techniques used. We examined the effects of DHEAS on insulin action and the quality of life in female patients with hypopituitary hypoadrenalism. DESIGN: Randomized, double-blind, placebo-controlled, crossover design was used. Patients received either DHEAS 50 mg daily or placebo for 12 weeks. PATIENTS: Fourteen hypopituitary females on stable standard replacement therapy and with low DHEAS were enrolled. MEASUREMENTS: Insulin action by euglycaemic hyperinsulinaemic clamp and extensive quality of life parameters were assessed after each treatment. RESULTS: Serum DHEAS (DHEAS 5·4 ± 0·8 vs placebo <0·8 ± 0·0 µm; P < 0·001) and androstenedione (DHEAS 4·1 ± 0·8 vs placebo 1·3 ± 0·2 nm; P < 0·05) rose to within the normal range after DHEAS 50 mg daily. There were no differences between treatments in testosterone, sex hormone-binding globulin (SHBG) or IGF-1. Quality of life measures were unchanged after DHEAS. There were no differences between treatments in fasting glucose, serum insulin, HbA1c or in insulin action (glucose infusion rates required to maintain euglycaemia; DHEAS 21·9 ± 2·5 vs placebo 24·5 ± 2·1 µmol/kg/min; P = 0·4). Triglyceride concentrations were lower following DHEAS (DHEAS 1·24 ± 0·18 vs placebo 1·41 ± 0·19 mm; P < 0·05) but other lipid parameters remained unchanged. CONCLUSION: There were no differences compared with placebo in quality of life or insulin action after DHEAS replacement therapy for 12 weeks. These results do not provide evidence for the addition of DHEAS to standard hypopituitary replacement therapy.

Mechanisms of human insulin resistance and thiazolidinedione-mediated insulin sensitization.

Cellular and tissue defects associated with insulin resistance are coincident with transcriptional abnormalities and are improved after insulin sensitization with thiazolidinedione (TZD) PPARgamma ligands. We characterized 72 human subjects by relating their clinical phenotypes with functional pathway alterations. We transcriptionally profiled 364 biopsies harvested before and after hyperinsulinemic-euglycemic clamp studies, at baseline and after 3-month TZD treatment. We have identified molecular and functional characteristics of insulin resistant subjects and distinctions between TZD treatment responder and nonresponder subjects. Insulin resistant subjects exhibited alterations in skeletal muscle (e.g., glycolytic flux and intramuscular adipocytes) and adipose tissue (e.g., mitochondrial metabolism and inflammation) that improved relative to TZD-induced insulin sensitization. Pre-TZD treatment expression of MLXIP in muscle and HLA-DRB1 in adipose tissue from insulin resistant subjects was linearly predictive of post-TZD insulin sensitization. We have uniquely characterized coordinated cellular and tissue functional pathways that are characteristic of insulin resistance, TZD-induced insulin sensitization, and potential TZD responsiveness.

Joint British Diabetes Societies guideline for the management of diabetic ketoacidosis.

The Joint British Diabetes Societies guidelines for the management of diabetic ketoacidosis (these do not cover Hyperosmolar Hyperglycaemic Syndrome) are available in full at: (i) http://www.diabetes.org.uk/About_us/Our_Views/Care_recommendations/The-Management-of-Diabetic-Ketoacidosis-in-Adults; (ii) http://www.diabetes.nhs.uk/publications_and_resources/reports_and_guidance; (iii) http://www.diabetologists-abcd.org.uk/JBDS_DKA_Management.pdf. This article summarizes the main changes from previous guidelines and discusses the rationale for the new recommendations. The key points are: Monitoring of the response to treatment (i) The method of choice for monitoring the response to treatment is bedside measurement of capillary blood ketones using a ketone meter. (ii) If blood ketone measurement is not available, venous pH and bicarbonate should be used in conjunction with bedside blood glucose monitoring to assess treatment response. (iii) Venous blood should be used rather than arterial (unless respiratory problems dictate otherwise) in blood gas analysers. (iv) Intermittent laboratory confirmation of pH, bicarbonate and electrolytes only. Insulin administration (i) Insulin should be infused intravenously at a weight-based fixed rate until the ketosis has resolved. (ii) When the blood glucose falls below 14 mmol/l, 10% glucose should be added to allow the fixed-rate insulin to be continued. (iii) If already taking, long-acting insulin analogues such as insulin glargine (Lantus(®), Sanofi Aventis, Guildford, Surry, UK) or insulin detemir (Levemir(®), Novo Nordisk, Crawley, West Sussex, UK.) should be continued in usual doses. Delivery of care (i) The diabetes specialist team should be involved as soon as possible. (ii) Patients should be nursed in areas where staff are experienced in the management of ketoacidosis.

Diabetes and Covid-19: Clinical implications and novel management strategies.

From the outset of the Covid-19 pandemic, diabetes has been identified as attracting higher rates of severe infection and associated mortality. Our understanding of the mechanisms behind these observations continue to develop but it is clear that the comorbidities associated with diabetes play a key role. Here we provide a brief overview of the clinical implications relevant to Covid-19 infection in diabetes and outline the changes we have instituted to adapt the management of both acute hyperglycaemic emergencies and routine diabetes care during the current pandemic.

Playing Performance After Anterior Cruciate Ligament Reconstruction Among Australian Football League Players From 1999 to 2013.

BACKGROUND: Achieving preinjury levels of athletic performance has been challenging for elite athletes after anterior cruciate ligament (ACL) reconstruction. Although a recent study found that 77% of Australian Football League (AFL) players who underwent ACL reconstruction from 1999 to 2013 returned to play at the highest level, the study did not indicate how consistently or well they were able to play. PURPOSE: To identify the number of AFL players who returned to play consistently over 2 seasons after ACL reconstruction, compare their playing performance in these seasons with preinjury performance, and evaluate factors associated with returning to preinjury levels of performance. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Analysis included 104 AFL players who underwent ACL reconstruction between 1999 and 2013. All had played at least 10 AFL matches in 1 season before ACL injury. Ranking points, as devised by AFL statisticians, were used to measure individual playing performance. RESULTS: Of the 104 players who played at least 10 matches in 1 season before ACL injury, 53 (51%) returned to play at least 10 matches in 2 seasons after surgery. Of these 53 players, 36 (68%) returned to their preinjury levels of performance. The 17 remaining players who did not return to their preinjury performance still performed comparably to the AFL average level after surgery. Players <25 years old (odds ratio = 2.9, P = .01) or <90 kg (odds ratio = 2.7, P = .03) had greater odds of returning to their preinjury levels of performance. CONCLUSION: Returning to play on a consistent basis was a substantial challenge for AFL players after ACL reconstruction. However, among players who did return to play consistently over 2 seasons, their postsurgery average performance was comparable with the AFL average level of performance, and two-thirds returned to their preinjury levels of performance. Younger and lighter players were more likely to return to their preinjury levels of performance, possibly given the nature of AFL club playing list management decisions.

Fifteen-Year Audit of Anterior Cruciate Ligament Reconstructions in the Australian Football League From 1999 to 2013: Return to Play and Subsequent ACL Injury.

BACKGROUND: Anterior cruciate ligament (ACL) injury has been a major cause of missed game time among Australian Football League (AFL) players. Return to play after ACL reconstruction is not always achieved, even among elite athletes. The rate of subsequent ACL injury in the AFL from 1990 to 2000 was high as compared with that of other elite sports. PURPOSE: To determine the rates of return to play and subsequent ACL injury after ACL reconstruction among AFL players from 1999 to 2013 and to explore factors associated with differing rates of return to play and subsequent ACL injury. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A total of 158 AFL players who underwent ACL reconstruction were identified from a prospectively maintained registry of AFL player injuries. Further data were gathered from official playing statistics, surgical records, and structured phone interviews. RESULTS: The rate of return to play after an initial ACL injury was 77% (121 of 158 players). Greater preinjury playing experience and earlier selection in the AFL draft were associated with higher rates of return to play. The rate of subsequent ACL injury to either knee was 30% (48 of 158 players) and was especially high among players aged <21 years (23 of 46 players, 50%). After subsequent ACL injury, 34 of 48 players (71%) returned to play. In primary ACL reconstruction, the use of Ligament Augmentation and Reconstruction System grafts resulted in a faster return to play ( P = .001) but had a higher risk of subsequent revision reconstruction (risk ratio = 2.8, P = .048). Family history of ACL injury was associated with an increased risk of subsequent contralateral ACL injury (risk ratio = 3.8, P = .002). CONCLUSION: Most AFL players who underwent ACL reconstruction returned to play at least 1 AFL match. The high rate of subsequent ACL injury among AFL players demonstrates the highly demanding nature of Australian football, particularly at the elite level. The risk factors for subsequent ACL injury should be considered carefully when treatment and rehabilitation decisions are made for these high-demand athletes.

Exogenous T3 toxicosis following consumption of a contaminated weight loss supplement.

A 42-year-old male presented with a one-week history of palpitations and sweating episodes. The only significant history was of longstanding idiopathic dilated cardiomyopathy. Initial ECG demonstrated a sinus tachycardia. Thyroid function testing, undertaken as part of the diagnostic workup, revealed an un-measureable thyroid-stimulating hormone (TSH) and free thyroxine (T4). Upon questioning the patient reported classical thyrotoxic symptoms over the preceding weeks. Given the persistence of symptoms free tri-iodothyronine (T3) was measured and found to be markedly elevated at 48.9 pmol/L (normal range: 3.1-6.8 pmol/L). No goitre or nodular disease was palpable in the neck. Historically there had never been any amiodarone usage. Radionucleotide thyroid uptake imaging (123I) demonstrated significantly reduced tracer uptake in the thyroid. Upon further questioning the patient reported purchasing a weight loss product online from India which supposedly contained sibutramine. He provided one of the tablets and laboratory analysis confirmed the presence of T3 in the tablet. Full symptomatic resolution and normalised thyroid function ensued upon discontinuation of the supplement. LEARNING POINTS: Free tri-iodothyronine (T3) measurement may be useful in the presence of symptoms suggestive of thyrotoxicosis with discordant thyroid function tests.Thyroid uptake scanning can be a useful aid to differentiating exogenous hormone exposure from endogenous hyperthyroidism.Ingestion of thyroid hormone may be inadvertent in cases of exogenous thyrotoxicosis.Medicines and supplements sourced online for weight loss may contain thyroxine (T4) or T3 and should be considered as a cause of unexplained exogenous hyperthyroidism.

Host movement and the genetic structure of populations of parasitic nematodes.

Mitochondrial DNA (mtDNA) sequence data were used to compare the population genetic structures of five species of parasitic nematodes from three different hosts: Ostertagia ostertagi and Haemonchus placei from cattle, H. contortus and Teladorsagia circumcincta from sheep, and Mazamastrongylus odocoilei from white-tailed deer. The parasites of sheep and cattle showed a pattern consistent with high gene flow among populations. The parasite of deer showed a pattern of substantial population subdivision and isolation by distance. It appears that host movement is an important determinant of population genetic structure in these nematodes. High gene flow in the parasites of livestock also indicates great opportunity for the spread of rare alleles that confer resistance to anthelmintic drugs. All species, including the parasite of deer, had unusually high within-population diversities (averages of 0.019-0.027 substitutions per site between pairs of individuals from the same population). Large effective population sizes (Ne), perhaps in combination with rapid mtDNA evolution, appear to be the most likely explanation for these high within-population diversities.

Laboratory and clinical experience in 55 patients with macroprolactinemia identified by a simple polyethylene glycol precipitation method.

PRL exists in different forms in human serum. The predominant form is little PRL (molecular mass 23 kDa) with smaller amounts of big PRL (molecular mass 50--60 kDa) and at times big big or macroprolactin (molecular mass 150--170 kDa). The frequency and clinical consequences of macroprolactinemia have not been clearly established, mainly because of difficulty in identifying these patients biochemically. This previously required the use of gel filtration chromatography, which could not be used routinely. Recently, a screening test using polyethylene glycol (PEG) has been used to identify macroprolactin in serum. Consequently, this study was designed to examine the use of PEG precipitation in the identification of patients with a predominance of macroprolactin and to establish the clinical characteristics of such a cohort. Over 12 months, 18,258 requests for serum PRL were received and of these 1225 patients had a serum PRL more than 700 mU/L. A total of 322 of these patients (26%) had a percentage recovery after PEG precipitation of less than 40%, thus indicating the presence of a predominance of macroprolactin. Fifty-five of these patients were referred for detailed clinical assessment. Symptoms typical of hyperprolactinemia were not common in this cohort. None had sustained amenorrhea and eight have had oligomenorrhea at age less than 40 yr. One had galactorrhea. All had pituitary imaging, and four had a microadenoma with none having a macroadenoma. PEG precipitation allows easy identification of macroprolactin in routine clinical practice. As the clinical consequences of this entity at this stage seem relatively benign, referral and intensive investigation of these patients may not be necessary. However, follow-up of a large cohort is required to ensure that the long-term outlook is likewise benign. This would have important implications for both patients and healthcare systems.

Cloning and characterization of the ribosomal RNA gene repeat from Ostertagia ostertagi.

Clones of the rRNA genes of Ostertagia ostertagi were selected from a library prepared from the genomic DNA of adult worms of strain LA-2. A 13.4-kb insert in a clone, lambda OOR78, is comprised of one complete 7.5-kb rDNA unit and portions of two adjacent units. The rDNA unit is directly repeated in a head-to-tail fashion and represents approximately 0.9% of the total genomic DNA. This repeating unit appears to be the only long tandemly repeated sequence in the genome. Restriction enzyme recognition sites in the rDNAs of four strains of O. ostertagi were fully conserved with the exception of one PstI site present in the large rRNA gene which was absent from a proportion of the genes of the LA-2 strain. The rDNA of O. ostertagi is more similar to that of Caenorhabditis elegans in unit length and arrangement than to parasitic helminths previously examined.

Seasonal transmission of Fasciola hepatica in north central Florida (U.S.A.).

To assess seasonal transmission of Fasciola hepatica 37 groups of fluke-free tracer sheep, one group of four sheep each month in succession, grazed an infected pasture in north central Florida (U.S.A.) from June 1984 to June 1987. At the end of each month, tracers were moved to a fluke-free barn for 2 months, then necropsied and flukes counted. Fluke transmission mostly occurred during the first half of the year, with peak transmission from February to April. No transmission occurred during the warm summer months, having ceased in either May or June of each year to begin again in late autumn or early winter (November-January).

The development of an enzyme-linked immunosorbent assay for Trypanosoma vivax and its use in a seroepidemiological survey of the Eastern Caribbean Basin.

An enzyme-linked immunosorbent assay (ELISA) for IgG antibodies against a South American (New World) strain of Trypanosoma vivax was developed and used for mass screening of cattle from 20 islands in the Eastern Caribbean Basin. The sensitivity and specificity of antigens prepared from a bovine-derived field strain and a murine-adapted laboratory strain of T. vivax, both of New World origin, were compared using an indirect fluorescent antibody (IFA) test, and an antigen prepared from the murine-adapted strain was subsequently used to develop an ELISA test. The results of the ELISA test were then compared with the results of a concurrently run IFA test. There was no cross-reactivity with either test using serum from a Trypanosoma theileri-infected cow. Both tests were weakly cross-reactive with sera from a T. brucei-infected steer, and the IFA test was moderately cross-reactive with several serum samples from a T. evansi-infected steer. For bovine sera collected from herds on islands in the Eastern Caribbean region, only five of 640 tested positive with the ELISA test. Thirty five of 653 sera tested were positive by IFA although the fluorescence elicited was weak as compared to that elicited by sera from known infected animals. Sera collected from 27 cattle in a region known to be free of T. vivax (OH, U.S.A) were negative with the ELISA test, whereas seven of 30 sera from a herd in French Guiana known to be infected with T. vivax were positive.(ABSTRACT TRUNCATED AT 250 WORDS)

The prevalence of Fasciola hepatica in its snail intermediate host determined by DNA probe assay.

Accurate snail intermediate host infection prevalence data have the potential to be extremely useful in determining seasonal transmission dynamics of Fasciola hepatica. Because the microscopic techniques currently used lack the sensitivity and specificity necessary to obtain meaningful infection prevalence data, we developed a highly accurate and efficient DNA probe assay. The assay has a sensitivity of 100%, a specificity of > 99%, easily detects a single miracidia and does not cross-hybridize with DNA of Fascioloides magna, Paramphistomum liorchis or Heterobilharzia americana, trematodes that share the same intermediate host and enzootic range as Fasciola hepatica. Using this assay, we determined the prevalence of F. hepatica in its snail intermediate host, Fossaria cubensis, during the second year of a 2-year study on the epizootiology of Fasciola hepatica in Florida. The overall infection prevalence of snails assayed in this study (n = 5246) was 1.5% and ranged from 0.1% to 3.1% for individual cattle ranches. Additionally, infection prevalence differed significantly for successive size groupings of snails, varying from 0% for 1-mm snails to 18.5% for 9- and 10-mm snails. The accuracy and efficiency of the DNA probe assay reported here for determining snail infection prevalence offers an inexpensive alternative to tracer animal studies for determining the epizootiology of F. hepatica.

Haemonchus placei and Haemonchus contortus are distinct species based on mtDNA evidence.

Debates continue over the extent to which the parasitic trichostrongylids Haemonchus placei and Haemonchus contortus hybridise in nature, and whether they deserve species status. Mitochondrial ND4 gene sequences from individuals of each putative species collected from populations around the United States indicate that the two species are highly differentiated at the mtDNA level. Furthermore, there was no evidence of introgressive hybridisation occurring in wild populations.

A repetitive DNA probe for the sensitive detection of Fasciola hepatica infected snails.

Epizootiologic studies on F. hepatica frequently use microscopic techniques for the detection of infected snails, however, the poor efficiency, sensitivity, and specificity associated with these techniques limit their usefulness. A DNA-based test for the identification of snails infected with larval stages of F. hepatica would solve these problems and enable a level of detection accuracy previously unavailable. We have cloned and sequenced a 124 bp fragment of repetitive DNA from F. hepatica which hybridizes specifically with DNA of F. hepatica but not with DNA of its snail intermediate hosts Fossaria cubensis and Pseudosuccinea columella, or with DNA of Fascioloides magna and Paramphistomum liorchis, ruminant trematodes which share the same intermediate host and same enzootic range as F. hepatica. Using this 124 bp fragment as a probe, infection in snails was detected immediately following miracidial penetration, thus a sensitivity equivalent to the minimum biologic unit of the parasite was achieved. This 124 bp repeated sequence belongs to a large family of 124 bp repeats that share a high level of sequence identity and constitute approximately 15% of the F. hepatica genome. We also report here the development of a quick and inexpensive DNA extraction protocol for use in field-collected snails. Thus, we have developed both a highly sensitive and specific DNA probe and a means to use the probe in a large epizootiologic study of F. hepatica where thousands of field-collected snails need to be assayed for infection.

Comparison of the priming effects of pulsatile and continuous insulin delivery on insulin action in man.

Insulin is normally secreted in man in regular pulses every 5 to 15 minutes. Disordered pulsation has been demonstrated in several insulin-resistant states and it is unclear whether this represents a primary beta-cell defect contributing to impairment of peripheral insulin action or rather is a consequence of insulin resistance. Basal or near basal insulin administration by pulsatile infusion augments hypoglycemic effect and improves insulin-mediated glucose uptake compared with insulin by continuous infusion. To date no study has examined whether normal basal insulin pulsatility is required to preserve subsequent insulin sensitivity during hyperinsulinemia. We studied the effect of overnight pulsatile versus continuous basal insulin on a subsequent hyperinsulinemic euglycemic clamp. Nineteen normal volunteers (male:female ratio, 17:2; mean age +/- SEM, 26.1 +/- 2.3 years) were studied on 2 occasions each. Endogenous insulin secretion was inhibited by octreotide (0.43 microg kg(-1). h(-1)) and replaced overnight at 5.4 mU kg(-1). h(-1) either by continuous infusion or in 2-minute pulses every 13 minutes (n = 10) or every 7 minutes (n = 9). Glucagon was replaced at physiological concentration by continuous infusion (30 ng. kg(-1). h(-1)). Venous plasma glucose overnight was not significantly different between the pulsatile and continuous protocols. After discontinuing the overnight insulin infusion, insulin action was assessed during a hyperinsulinemic euglycemic clamp (1 mU kg(-1). h(-1)). Glucose infusion rates at steady-state during the hyperinsulinemic clamp were similar between continuous and both frequencies of pulsatile infusion (continuous 44.6 +/- 4.3 micromol. kg(-1). min(-1) v 13-minute pulsatile 41.7 +/- 5.9 micromol. kg(-1). min(-1), P =.27; continuous 34.6 +/- 2.5 micromol. kg(-1) min(-1) v 7-minute pulsatile 41.4 +/- 3.2 micromol. kg(-1). min(-1), P =.08). We conclude that overnight pulsatile compared with continuous insulin administration has no different effect on subsequent peripheral insulin-mediated glucose uptake. A priming effect cannot therefore explain the previously demonstrated association between endogenous insulin pulse frequency and peripheral insulin action.

Seasonal transmission of equine cyathostomes in warm climates.

Few studies investigating the seasonal transmission of equine cyathostomes have been done in warm climates. Two Australian studies used experimentally-infected plots to determine hatching, development and survival of free living stages of equine cyathostomes. Four studies in the southern United States used pasture larval counts, and in some instances tracer animals, to determine seasonal availability of infective cyathostome larvae on naturally-infected pastures. With the exception of the dry Australian tropics, a general pattern of peak transmission of cyathostomes during the cooler seasons of the year and minimal transmission during the warmest seasons was observed. Infective larvae and developing stages survived poorly in hot weather, although the rate of development was most rapid during that time. In contrast, infective larvae and developing stages survived well in cool weather, although the rate of development was slower. Adequate moisture was crucial to cyathostome transmission in warm climates, thus hot, dry weather effectively sterilized a pasture, whereas cool, moist weather was optimum for transmission. These data suggest that suppression of cyathostome egg output in feces of horses beginning shortly before the onset of cooler and/or more moist weather, and continued through the favorable period for development and survival of larvae on pasture - usually the autumn and winter should provide adequate control of these parasites. However, the efficacy of such seasonal control programs has yet to be adequately tested against that of traditional year round treatments.

Relationship between microfilaria count and sensitivity of the direct smear for diagnosis of canine dirofilariosis.

Direct blood smear examination (using 0.05 ml of whole blood) detected 168 (80.9%) of 204 microfilaremic canine blood samples as determined by the modified Knott test for microfilariae (mff) of Dirofilaria immitis (using 1 ml of whole blood). Direct smear examination detected all of 134 microfilaremias greater than 50 mff ml(-1), but only 31 of 70 (44.3%) microfilaremias having less than 50 mff ml(-1). In a separate retrospective query of a database of 963 dogs with necropsy-confirmed heartworm infections, 834 (86.6%) were positive by the DiroCHEK heartworm antigen test, and 504 (52.3%) were microfilaremic by the modified Knott test. Only 2 (0.4%) of the microfilaremic dogs were DiroCHEK negative and another 18 (3.6%) were very weak positives. Although these microfilaremic dogs were not tested by direct smear, only one of the two DiroCHEK-negative and six of 18 weakly DiroCHEK-positive dogs had microfilaremias so low that a direct smear may have given a false negative result. Significant adverse reactions to either diethylcarbamazine or the macrolide endectocides have not been reported for microfilaremias less than 500 mff ml(-1), thus substitution of the direct smear for a concentration test for mff, such as the modified Knott test or membrane filtration, does not appear to increase the risk of an unexpected adverse reaction to heartworm prophylactic drugs. Such a substitution results in only a very slight decrease (on the order of 0.1%) in the overall sensitivity of heartworm screening, provided a test for mff is run concurrently with an antigen test. If a test for mff is the only screening test used, then substitution of a direct smear for a concentration test may decrease the sensitivity of heartworm screening by nearly 20%, depending on the prevalence of low level microfilaremias in the population of dogs tested.