Neil H. Willits

Large Diurnal Temperature Fluctuations Negatively Influence Aedes aegypti (Diptera: Culicidae) Life-History Traits

ABSTRACT Seasonal variation in dengue virus transmission in northwestern Thailand is inversely related to the magnitude of diurnal temperature fluctuations, although mean temperature does not vary significantly across seasons. We tested the hypothesis that diurnal temperature fluctuations negatively influence epidemiologically important life-history traits of the primary dengue vector, Aedes aegypti (L.), compared with a constant 26°C temperature. A large diurnal temperature range (DTR) (≈18°C daily swing) extended immature development time (>1 d), lowered larval survival (≈6%), and reduced adult female reproductive output by 25% 14 d after blood feeding, relative to the constant 26°C temperature. A small DTR (≈8°C daily swing) led to a negligible or slightly positive effect on the life history traits tested. Our results indicate that there is a negative impact of large DTR on mosquito biology and are consistent with the hypothesis that, in at least some locations, large temperature fluctuations contribute to seasonal reduction in dengue virus transmission.

Neutering Dogs: Effects on Joint Disorders and Cancers in Golden Retrievers

In contrast to European countries, the overwhelming majority of dogs in the U.S. are neutered (including spaying), usually done before one year of age. Given the importance of gonadal hormones in growth and development, this cultural contrast invites an analysis of the multiple organ systems that may be adversely affected by neutering. Using a single breed-specific dataset, the objective was to examine the variables of gender and age at the time of neutering versus leaving dogs gonadally intact, on all diseases occurring with sufficient frequency for statistical analyses. Given its popularity and vulnerability to various cancers and joint disorders, the Golden Retriever was chosen for this study. Veterinary hospital records of 759 client-owned, intact and neutered female and male dogs, 1–8 years old, were examined for diagnoses of hip dysplasia (HD), cranial cruciate ligament tear (CCL), lymphosarcoma (LSA), hemangiosarcoma (HSA), and mast cell tumor (MCT). Patients were classified as intact, or neutered early (<12 mo) or late (≥12 mo). Statistical analyses involved survival analyses and incidence rate comparisons. Outcomes at the 5 percent level of significance are reported. Of early-neutered males, 10 percent were diagnosed with HD, double the occurrence in intact males. There were no cases of CCL diagnosed in intact males or females, but in early-neutered males and females the occurrences were 5 percent and 8 percent, respectively. Almost 10 percent of early-neutered males were diagnosed with LSA, 3 times more than intact males. The percentage of HSA cases in late-neutered females (about 8 percent) was 4 times more than intact and early-neutered females. There were no cases of MCT in intact females, but the occurrence was nearly 6 percent in late-neutered females. The results have health implications for Golden Retriever companion and service dogs, and for oncologists using dogs as models of cancers that occur in humans.

APACHE II scoring in the injured patient

The purpose of this study was to measure the predictive power of Acute Physiology and Chronic Health Evaluation (APACHE II) with respect to mortality in a group of seriously injured patients and to compare this predictive power with that of the Trauma Score (TS) and the Injury Severity Score (ISS). Six hundred ninety-one helicopter-transported patients were studied. Individual logistic regressions demonstrated that all three scores had significant predictive power when considered individually (TS chi 2 = 136, p less than .0001; APACHE II chi 2 = 171, p less than .0001; ISS chi 2 = 109, p less than .0001). In addition, each severity score added significantly to the predictive power in a stepwise logistic regression (TS chi 2 = 15, p less than .0001; APACHE II chi 2 = 45, p less than .0001; ISS chi 2 = 15, p less than .0001). Areas under the receiver operating curves for the three scores were not significantly different (TS 0.8116, SD 0.0245; APACHE II 0.8515, SD 0.0204; ISS 0.7967; SD 0.0223). APACHE II is a good predictor of mortality, and its predictive power is complemented by TS and ISS.

Practical Considerations for the Use of the Pedobarograph

The pedobarograph functions as a device for the dynamic, quantitative measurement of pedal pressures. To date, little attention has been paid to various practical questions concerning its operation. For example, the number and timing of trials sufficient to provide meaningful information upon which to reliably base investigational or management decisions has yet to be addressed. Twenty volunteers were used for the measurement of pedal pressures for 15 trials during three separate sessions. Statistical analysis for the determination of MIVQUE(0) estimates and maximum likelihood estimates were used to determine the individual variability, the variability of the specific area of the foot, the daily variability, and the trial-to-trial variability. This analysis indicated that for the assessment of pedal pressures in a clinical setting, the variance factors were sufficiently minimized by obtaining multiple measurements. The improvement in the estimate of error by obtaining trials on different days was overshadowed by the potential benefit of doing extra trials on a single day. Three trials on 1 day should sufficiently reduce estimates of error for both clinical and investigational purposes.

Quantification of midline shift as a predictor of poor outcome following head injury

A retrospective study of patient outcome, based on admission computed tomography, was carried out in 75 consecutive patients with head injury. Computed tomography data collected included the type and extent of intracranial hemorrhage, the extent of midline shift, and the ratio of midline shift compared with the extent of intracranial hemorrhage. Midline shift was considered to be out of proportion to intracranial hemorrhage when the midline shift of the septum pellucidum exceeded the extent of the hemorrhage as measured radially from the inner table of the skull. When computed tomography data were analyzed by logistic regression, significant predictive factors for poor outcome were intracranial hemorrhage (34%), intracranial hemorrhage with midline shift (61%), and midline shift out of proportion to the extent of intracranial hemorrhage (88%). When patient outcome and mortality rates are considered, our study indicates that midline shift out of proportion to the extent of intracranial hemorrhage is a highly useful predictor of poor patient outcome following head injury.

Dopamine use is an indicator for the development of threshold retinopathy of prematurity

AIM To assess whether treatment of premature infants with dopamine is a risk factor for development of retinopathy of prematurity (ROP). METHODS A retrospective case series analysis of two groups was utilised with a minimum follow up of 6 months. Clinical profiles and patient risk factors were identified along with an evaluation of ROP progression and an analysis of clinical outcome. All infants were seen in a single community neonatal intensive care unit (NICU). 41 consecutive high risk infants were identified during a 36 month period whose birth weight was less than 1000 grams and who remained in the NICU without transfer until at least 28 days of age. Dilated indirect ophthalmoscopy fundus examinations were performed on all infants to identify the degree of and progression to threshold ROP. RESULTS 18 of 41 infants were treated with dopamine for hypotension. The group of infants requiring dopamine differed statistically from the non-dopamine treated group by having a slightly higher birth weight, a greater incidence of hypotension and colloid treatment, and in manifesting more advanced respiratory disease. Within the dopamine treated group, 12 of 18 infants (67%) reached prethreshold ROP and seven infants (39%) reached threshold ROP requiring laser treatment. In contrast, only three of the infants (13%) who did not require dopamine for hypotension progressed to prethreshold (p=0.001) and only one of these infants (4%) progressed to threshold ROP (p = 0.02). Logistic regression analysis among other variables demonstrated that dopamine use and gestational age are important factors in this low birthweight population for predicting the development of threshold ROP (dopamine use: adjusted odds ratio = 119.88, p = 0.0061; gestational age: adjusted odds ratio = 0.061, p = 0.0043). CONCLUSIONS Dopamine use in low birthweight infants may therefore be a risk factor for the development of threshold ROP. More vigilant screening of high risk infants requiring dopamine therapy for systemic hypotension may be warranted.

Long-Term Health Effects of Neutering Dogs: Comparison of Labrador Retrievers with Golden Retrievers

Our recent study on the effects of neutering (including spaying) in Golden Retrievers in markedly increasing the incidence of two joint disorders and three cancers prompted this study and a comparison of Golden and Labrador Retrievers. Veterinary hospital records were examined over a 13-year period for the effects of neutering during specified age ranges: before 6 mo., and during 6–11 mo., year 1 or years 2 through 8. The joint disorders examined were hip dysplasia, cranial cruciate ligament tear and elbow dysplasia. The cancers examined were lymphosarcoma, hemangiosarcoma, mast cell tumor, and mammary cancer. The results for the Golden Retriever were similar to the previous study, but there were notable differences between breeds. In Labrador Retrievers, where about 5 percent of gonadally intact males and females had one or more joint disorders, neutering at <6 mo. doubled the incidence of one or more joint disorders in both sexes. In male and female Golden Retrievers, with the same 5 percent rate of joint disorders in intact dogs, neutering at <6 mo. increased the incidence of a joint disorder to 4–5 times that of intact dogs. The incidence of one or more cancers in female Labrador Retrievers increased slightly above the 3 percent level of intact females with neutering. In contrast, in female Golden Retrievers, with the same 3 percent rate of one or more cancers in intact females, neutering at all periods through 8 years of age increased the rate of at least one of the cancers by 3–4 times. In male Golden and Labrador Retrievers neutering had relatively minor effects in increasing the occurrence of cancers. Comparisons of cancers in the two breeds suggest that the occurrence of cancers in female Golden Retrievers is a reflection of particular vulnerability to gonadal hormone removal.

Synovial fluid growth factor and cytokine concentrations after intra-articular injection of a platelet-rich product in horses.

Platelet-rich plasma (PRP) products may be useful for treatment of joint disease in horses, but may contain undesirable pro-inflammatory cytokines in addition to growth factors. This study investigated whether autologous PRP increases synovial fluid growth factor and cytokine concentrations when injected into normal equine metacarpophalangeal and metatarsophalangeal (fetlock) joints. Fetlock joints of seven healthy horses received one of four treatments: saline, resting PRP, CaCl2-activated PRP or thrombin-activated PRP. Synovial fluid was sampled prior to injection and at 6, 24, 48 and 96 h post-injection. Platelet-derived growth factor (PDGF-BB), transforming growth factor β1 (TGFβ1), interleukin (IL)-6 and tumor necrosis factor α (TNFα) concentrations in synovial fluid and PRP were measured by ELISA. Synovial fluid PDGF-BB, TGFβ1, IL-6, TNFα and IL-1 concentrations were also measured in vitro after incubation for 6h with resting PRP only. Growth factor concentrations, but not cytokine concentrations, were significantly higher in activated PRP than in resting PRP samples. After intra-articular injection with resting or thrombin-activated PRP, synovial TGFβ1 increased significantly compared to baseline levels. TNFα and IL-6 were significantly increased in synovial fluid after thrombin-activated PRP injection. In vitro, growth factor concentrations increased significantly in synovial fluid after mixing with PRP, indicating that exogenous activation of PRP for intra-articular injection may be unnecessary, whereas cytokine levels did not. In conclusion, thrombin-activated PRP induced an inflammatory cytokine response in joints, whereas resting or CaCl2-activated PRP did not. Synovial growth factor levels were low overall; the reported benefits of intra-articular PRP may not be attributable to changes in local PDGF or TGFβ1 concentrations.

Evaluation of thermal antinociceptive effects after intramuscular administration of hydromorphone hydrochloride to American kestrels (Falco sparverius)

OBJECTIVE To evaluate the antinociceptive and sedative effects and duration of action of hydromorphone hydrochloride after IM administration to American kestrels (Falco sparverius). ANIMALS 11 healthy 2-year-old American kestrels. PROCEDURES Hydromorphone (0.1, 0.3, and 0.6 mg/kg) and an equivalent volume of saline (0.9% NaCl) solution (control treatment) were administered IM to kestrels in a masked randomized complete crossover study design. Foot withdrawal response to a thermal stimulus was determined 30 to 60 minutes before (baseline) and 0.5, 1.5, 3, and 6 hours after treatment administration. Agitation-sedation scores were determined 3 to 5 minutes before each thermal test. RESULTS Hydromorphone at 0.6 mg/kg, IM, significantly increased the thermal foot withdrawal threshold, compared with the response after administration of saline solution, for up to 3 hours, and hydromorphone at 0.1, 0.3, and 0.6 mg/kg, IM, significantly increased withdrawal responses for up to 6 hours, compared with baseline values. No significant differences in mean sedation-agitation scores were detected between hydromorphone and saline solution treatments; however, appreciable sedation was detected in 4 birds when administered 0.6 mg of hydromorphone/kg. CONCLUSIONS AND CLINICAL RELEVANCE Hydromorphone at the doses evaluated significantly increased the thermal nociception threshold for American kestrels for 3 to 6 hours. Additional studies with other types of stimulation, formulations, dosages, routes of administration, and testing times are needed to fully evaluate the analgesic and adverse effects of hydromorphone in kestrels and other avian species and the use of hydromorphone in clinical settings.

Rapid acute physiology scoring in transport systems.

A multi-institutional study was undertaken to define the predictive power for mortality of the Rapid Acute Physiology Score (RAPS) in a large and diverse group of transported patients. RAPS is a truncated version of the Acute Physiology and Chronic Health Evaluation (APACHE II) score that uses definitions and weighting consistent with APACHE II, but is modified to provide a consistent score just before transport, just after transport, and to use the most deranged (worst) physiologic values during the initial 4 h after arrival at the receiving hospital. During an 8-month period, 1,927 patients transported by six helicopter emergency medical service programs were studied. Over 97% (1,881) of the patients had RAPS obtained before and after transport to the receiving hospital and 92.6% (1,785) had APACHE II scoring completed after hospital admission. Receiver operating curves demonstrate similar predictive power for RAPS and APACHE II (both based on the most deranged physiologic values during the initial 24 h after admission). Before- and after-transport RAPS were also highly predictive of mortality. RAPS appears to be a reliable and highly predictive measure of patient severity/physiologic stability before and after transport to critical care.