Comparison of the efficacy of macrocyclic lactone anthelmintics, either singly or in combination with other anthelmintic(s), in nine beef herds in southern NSW.

Anthelmintic resistance (AR) is a well-recognized challenge in farmed ruminants. The use of anthelmintics in combination is one of the strategies recommended to slow the rate of AR development. Two studies were undertaken in 2017 and 2019 to assess the efficacy of single-dose macrocyclic lactone (ML) anthelmintic and ML combination drenches. In total, 11 Faecal Egg Count Reduction Trials (FECRTs) were set up in 10 different beef herds, with results available from 10 of those FECRTs (9 herds). AR to a single ML anthelmintic was detected in all 9 herds, with resistance to Cooperia and Haemonchus spp on 9 farms, and resistance to Ostertagia and Trichostrongylus spp on 2 farms. In contrast, for the ML combination anthelmintics, all FECRTs resulted in efficacies of 99%-100%. The results suggest that cattle producers should strongly consider using combination drenches in their herds in preference to single actives.

Lung cancer physicians' referral practices for palliative care consultation.

BACKGROUND: Integration of palliative care with standard oncologic care improves quality of life and survival of lung cancer patients. We surveyed physicians to identify factors influencing their decisions for referral to palliative care. METHODS: We provided a self-administered questionnaire to physicians caring for lung cancer patients at five medical centers. The questionnaire asked about practices and views with respect to palliative care referral. We used multiple regression analysis to identify predictors of low referral rates (<25%). RESULTS: Of 155 physicians who returned survey responses, 75 (48%) reported referring <25% of patients for palliative care consultation. Multivariate analysis, controlling for provider characteristics, found that low referral rates were associated with physicians' concerns that palliative care referral would alarm patients and families [odds ratio (OR) 0.45, 95% confidence interval (CI) 0.21-0.98], while the belief that palliative care specialists have more time to discuss complex issues (OR 3.07, 95% CI 1.56-6.02) was associated with higher rates of referral. CONCLUSIONS: Although palliative care consultation is increasingly available and recommended throughout the trajectory of lung cancer, our data indicate it is underutilized. Understanding factors influencing decisions to refer can be used to improve integration of palliative care as part of lung cancer management.

Increased parenchymal damage and steatohepatitis in Caucasian non-alcoholic fatty liver disease patients with common IL1B and IL6 polymorphisms.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a complex, multifactorial disease affected by diet, lifestyle and genetics. Proinflammatory cytokines like IL-1ß and IL-6 have been shown to be elevated in non-alcoholic steatohepatitis (NASH). AIM: To investigate the relationship between IL1B and IL6 gene polymorphisms and histological features of NAFLD in the NASH CRN cohort. METHODS: A total of 604 adult (≥18 years) non-Hispanic Caucasians with biopsy-proven NAFLD were genotyped for the following SNPs: IL1B, rs16944, rs1143634; IL6, rs1800795, rs10499563. Logistic regression was used to examine the relationship between genotype and a definitive diagnosis and advanced histological features of NASH after controlling for the following variables selected a priori: age, sex, diabetes, obesity and HOMA-IR level. RESULTS: The IL6 rs10499563 C allele was independently associated with the presence of definitive NASH, and increased ballooning and Mallory bodies. The IL1B rs1143634 TT genotype was associated with advanced fibrosis and increased Mallory bodies. The IL6 rs1800795 C allele was associated with not only increased risk for severe steatosis, >66% but also decreased risk for advanced fibrosis and lobular inflammation and Mallory body formation. CONCLUSIONS: These results suggest that common variants in the IL6 and IL1B genes may increase susceptibility for NASH and confer a higher risk of hepatic parenchymal damage including increased ballooning, increased Mallory bodies, and bridging fibrosis or cirrhosis. In contrast, the IL6 rs1800795 C allele may confer a higher risk for steatosis, but less parenchymal damage. Our findings support the development of therapeutics aimed at IL-1ß and IL-6 suppression.

A double-blind comparison of clomipramine, desipramine, and placebo in the treatment of autistic disorder.

OBJECTIVE: To determine whether clomipramine hydrochloride, a serotonin reuptake blocker with unique anti-obsessional properties, is differentially effective for obsessive-compulsive and stereotyped motor behaviors in autistic disorder compared with placebo and with the noradrenergic tricyclic antidepressant agent, desipramine hydrochloride. DESIGN: Following a 2-week, single-blind placebo washout phase, 12 autistic subjects completed a 10-week, double-blind, crossover comparison of clomipramine and placebo, and 12 different subjects completed a similar comparison of clomipramine and desipramine. SETTING: Outpatient clinic. PATIENTS: A referral sample of 30 male and female autistic patients were enrolled, and 24 completed the study. MEASURES: Key outcome measures were the Autism Relevant Subscale of the Children's Psychiatric Rating Scale, the Modified Comprehensive Psychopathological Rating Scale-Obsessive-Compulsive Disorder Subscale, and the Clinical Global Impressions Scale. RESULTS: Clomipramine was superior to both placebo and desipramine on ratings of autistic symptoms (including stereotypies), anger, and compulsive, ritualized behaviors (P < .05), with no differences between desipramine and placebo. Clomipramine was equal to desipramine and both tricyclic agents were superior to placebo for amelioration of hyperactivity. CONCLUSION: Biological links between compulsions and stereotyped, repetitive behaviors in autistic disorder should be explored.

Screening for adult phenylketonuria in state psychiatric hospitals.

The authors report the results of screening patients admitted to a state psychiatric hospital for unrecognized adult phenylketonuria. The results suggest that unrecognized adult phenylketonuria is very uncommon in these patients.

Association of binge eating disorder and psychiatric comorbidity in obese subjects.

OBJECTIVE: The authors determined the prevalence of binge eating disorder in a self-referred study group of moderately and severely obese subjects and investigated whether binge eating disorder was associated with psychiatric disorders, a history of psychotherapy, a family history of psychiatric illness, or a history of sexual abuse. METHOD: They interviewed 89 obese women and 39 obese men (body mass index > 30 kg/m2) who were not currently in weight loss treatment, using the Binge Eating Disorder Clinical Interview, the Structured Clinical Interview for DSM-III-R, and the Structured Clinical Interview for DSM-III-R Personality Disorders. RESULTS: Forty-three (34%) of the subjects met criteria for binge eating disorder--33 women and 10 men. Black and white subjects had similar rates of binge eating disorder. Subjects with binge eating disorder were significantly more likely than those without the disorder to have a lifetime prevalence of a DSM-III-R axis I or axis II diagnosis and to have undergone psychotherapy or counseling. The lifetime rates of major depression, panic disorder, bulimia nervosa, borderline personality disorder, and avoidant personality disorder were all significantly higher in subjects with binge eating disorder. The rate of reported sexual abuse was not higher among subjects with binge eating disorder; however, they were significantly more likely to have a family history of substance abuse. The relative risks for psychiatric disorders were higher in both moderately and severely obese subjects with binge eating disorder than in those without the disorder. CONCLUSIONS: Among both moderately and severely obese subjects, binge eating disorder is associated with higher rates of axis I and axis II psychiatric disorders.

Childhood-onset psychotic disorders: magnetic resonance imaging of volumetric differences in brain structure.

OBJECTIVE: Although childhood-onset schizophrenia is rare, children with brief psychotic symptoms and prominent emotional disturbances commonly present diagnostic and treatment problems. Quantitative anatomic brain magnetic resonance images (MRIs) of a subgroup of children with psychotic disorder not otherwise specified were compared with those of children with childhood-onset schizophrenia and healthy comparison subjects. METHOD: Anatomic MRIs were obtained for 71 patients (44 with childhood-onset schizophrenia and 27 with psychotic disorder not otherwise specified) and 106 healthy volunteers. Most patients had been treated with neuroleptics. Volumetric measurements for the cerebrum, anterior frontal region, lateral ventricles, corpus callosum, caudate, putamen, globus pallidus, and midsagittal thalamic area were obtained. RESULTS: Patients had a smaller total cerebral volume than healthy comparison subjects. Analysis of covariance for total cerebral volume and age found that lateral ventricles were larger in both patient groups than in healthy comparison subjects and that schizophrenia patients had a smaller midsagittal thalamic area than both subjects with psychotic disorder not otherwise specified and healthy comparison subjects. CONCLUSIONS: Pediatric patients with psychotic disorder not otherwise specified showed a pattern of brain volumes similar to those found in childhood-onset schizophrenia. Neither group showed a decrease in volumes of temporal lobe structures. Prospective longitudinal magnetic resonance imaging and clinical follow-up studies of both groups are currently underway to further validate the distinction between these two disorders.

Auditory forebrain organization of an Australian marsupial, the northern native cat (Dasyurus hallucatus).

Structures and connections of auditory forebrain regions of the Northern native cat, a member of one of the most primitive families among Australian marsupials, have been examined anatomically by using anterograde and retrograde tracing techniques with wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) after defining the acoustically responsive neocortical area physiologically. The structure of the medial geniculate body (MG) was similar to that described in other species. The results obtained from a case with a WGA-HRP injection into the MG showed that the MG strongly projects to the lateral amygdaloid nucleus (LAmy) and the putamen as well as the auditory neocortex (ACx). Results obtained from other cases with WGA-HRP injections into the physiologically defined ACx show also that the ACx is connected not only with the ipsilateral MG and the contralateral ACx but also with the LAmy both bilaterally and reciprocally. The regions within the LAmy in which the MG-LAmy projection fibers terminate largely overlap with those in which the ACx-LAmy fibers terminate and the LAmy-ACx pathway originates. The connectional relationships revealed in the present study--that the LAmy receives auditory information from the MG and reciprocates auditory information with the ACx bilaterally--strongly suggest that, in some primitive mammals with small neocortical areas, a specific portion of noncortical telencephalon functions as an auditory center and occupies a relatively large volume of space in the forebrain. It is possible that the auditory sector of noncortical telencephalon in some primitive mammals such as the American Didelphidae and the Australian Dasyuridae is homologous with part of the auditory sector of the dorsal ventricular ridge (DVR) in reptiles and birds and also may have functions shared with the auditory primary and association neocortex in advanced mammals such as the domestic cat and the monkey (Kudo et al., '86a).

Hearing, vocalization and the external ear of a marsupial, the northern Quoll, Dasyurus hallucatus.

As part of a continuing study of the development of the marsupial auditory system, auditory brainstem responses (ABR) were recorded and an ABR audiogram was constructed for five female Northern Quolls (Dasyurus hallucatus), which are nocturnal carnivores. The best frequency for hearing lies between 8 and 10 kHz, and at 50 dB SPL there is a range from about 0.5 to 40 kHz. Vocalizations of adult quolls and pouch-young were recorded with a digital audio tape recorder, and the power spectra of representative calls were compared with the ABR audiogram. The common adult vocalizations have most energy at the lower end of the hearing range, whereas frequencies that are dominant in the isolation calls of the pouch-young lie close to the best frequency of hearing. Samples of nocturnal sounds of the habitat of the quoll were also recorded and analyzed. Power spectra have peak energy at frequencies between 2 and 5 kHz, with a smaller contribution above 10 kHz. The spectrum contains relatively little power at the best frequency of hearing. Measurements of the sound pressure level at the external ear canal as a function of stimulus frequency and location in space suggest that the directional amplifying properties of the pinna will operate most effectively on sound frequencies at the upper end of the quoll's hearing range, a region that may be important in prey detection. Comparisons are made with other mammalian nocturnal carnivores and with other marsupials. We speculate that, for nocturnal carnivores, one role of the low-frequency part of the hearing range concerns the recognition of adult conspecifics, the mid-frequency range is important for the detection of pouch-young, and the upper range may be particularly concerned with prey/predator detection.

Frequency representation in auditory cortex of the common marmoset (Callithrix jacchus jacchus).

The location and characteristics of the primary auditory cortex of the common marmoset, Callithrix jacchus jacchus, were determined in five anesthetized male adult animals by mapping the responses of cortical units and unit clusters to pure tone stimuli presented to the contralateral ear. The primary auditory cortex lies largely ventral to the lateral sulcus, the only major fissure on the lateral cortex of this smooth-brained primate, but in some animals it may extend significantly down the ventral bank of this sulcus. Responses are distributed such that low best frequencies are found rostroventrally whereas high best frequencies occur caudally. The disposition of frequency-band contours is fan-shaped, with contours separating low-frequency octaves nearly parallel to the lateral sulcus and high-frequency (greater than 8 kHz) contours perpendicular to that sulcus. Best frequencies range from 0.6 to 30 kHz across the primary field, but there is a disproportionate representation of the three octaves between 2 and 16 kHz. The most sensitive thresholds (as low as -2 dB SPL) are found between 7 and 9 kHz. The primary auditory cortex is similar in cytoarchitecture to that reported for the cat, showing a blurring of lamination in the middle layers (II-IV) and a preponderance of small cells in these merged layers, giving a highly granular appearance. The accessibility of the cochlear representation on the gyral surface makes the marmoset an attractive animal for studies of primate auditory cortex.

Hemoptysis in HIV-infected patients.

STUDY OBJECTIVE: To define the causes and clinical features of hemoptysis in HIV-infected patients. DESIGN: Retrospective analysis of inpatient medical records for patients with HIV infection and hemoptysis. SETTING: A large New York City teaching hospital and tertiary referral center. PATIENTS: Fifty HIV-infected adult patients with 51 episodes of hemoptysis. RESULTS: The incidence of hemoptysis was 1.9%. A definite or presumptive etiology was identified for most (78%) episodes, with infection being the leading cause (80% of episodes with identified etiology). Hemoptysis was most often (40% of episodes with a definite or presumptive etiology) attributed to bacterial pneumonia. Mycobacterium tuberculosis was infrequently the cause of hemoptysis (6%). Mortality attributed to hemoptysis was 8%. In most patients, hemoptysis was mild (77%) and resolved (78%) without specific treatment. CONCLUSIONS: Our retrospective series of HIV-infected patients hospitalized for short-term care in New York City suggests that hemoptysis in this group has diverse causes but usually is infectious in etiology and most often due to bacterial pneumonia. Bleeding is typically mild and resolves without specific treatment, but can occasionally be fatal. Differential diagnosis should be approached with specific reference to this patient population and its unique features.

Magnesium sulfate potentiates several cardiovascular and metabolic actions of terbutaline.

beta-Adrenergic agonists are useful for the emergency treatment of asthma. Recently, magnesium sulfate (MgSO4) has also been shown to be efficacious in this situation. beta-Agonists have unwanted cardiovascular and metabolic actions: increased systolic blood pressure, corrected QT interval (QTc), serum glucose and insulin, and decreased RR interval, diastolic blood pressure, serum potassium, phosphate, and calcium. As beta-agonists and MgSO4 quite possibly will be used in combination, we sought to determine how MgSO4 would affect these actions. Healthy young male adults were administered two doses of terbutaline sulfate, 0.25 mg subcutaneously, 30 min apart on two separate occasions, in a randomized, double-blind fashion. On one occasion, 4 g of MgSO4 was administered intravenously over the same 30-min period. On the other, normal saline solution was given as a placebo. Cardiovascular and metabolic variables were measured sequentially for 2 h. Data at 60 min with p values given for a summation of all time points are as follows: MgSO4 increased terbutaline's effects on the RR interval by 0.09 s, p < 0.0001; QTc interval by 0.01 s, p < 0.0007; diastolic blood pressure by 8 mm Hg, p = 0.0001; serum calcium by 0.13 mg/dl, p = 0.01; and glucose by 9 mg/dl, p < 0.0001. MgSO4 also mitigated the systolic blood pressure elevating the effect of terbutaline by 5 mm Hg (p = 0.007). The magnitude of the response potentiations was modest. We conclude that combining terbutaline and MgSO4 is unlikely to result in serious short-term adverse events, if used acutely in patients with relatively normal cardiac and metabolic function. MgSO4 may act by potentiating the effect of beta-agonists on magnesium requiring enzymes such as adenyl cyclase.

Coordinate expression of the PRM1, PRM2, and TNP2 multigene locus in human testis.

Maintenance of the transcriptionally inert state of the mature human spermatozoon requires the expression of the various members of the human protamine gene cluster prior to the final stages of spermatogenesis. During this process, known as spermiogenesis, round spermatids morphologically differentiate into mature spermatozoa. The expression of the PRM1, PRM2, and TNP2 genes facilitates the compaction and condensation of the genetic material within the developing spermatid. To understand better the coordinate control governing this transformation, we have examined the localization and distribution of the human protamines PRM1 and PRM2 and transition protein TNP2 transcripts during human spermatogenesis. The stage-specific expression of these transcripts was determined by in situ hybridization analysis using [alpha-35S]-labeled cRNA probes. PRM1, PRM2, and TNP2 transcripts were abundant in association with round and elongating spermatids, located in the adluminal region of the seminiferous epithelium. They were not observed in association with spermatogonia, spermatocytes, Sertoli cells, or interstitial cells. These data indicate that the human PRM1, PRM2, and TNP2 transcripts are expressed postmeiotically in round and elongating spermatids. The quantitative evaluation of each transcript was determined as a function of the relative optical density per unit area. In all cases examined, the relative level of each transcript was consistent with the following pattern, PRM2 > PRM1 congruent to TNP2.

Visual acuity of the northern native cat (Dasyurus hallucatus)--behavioural and anatomical estimates.

Behavioural estimates of the visual acuity of the Northern Native Cat (or Northern Quoll)--Dasyurus hallucatus--were made using the Mitchell jumping stand technique. A value of 2.3-2.8 cycles per degree was obtained. This functional acuity compared well with predictions based on the peak ganglion cell density (2600 cells/mm2) determined from the retinal ganglion cell density map.

Afferent input for target survival in marsupial visual development.

The influence of afferent input on the survival of target neurons in mammals has been examined by the removal of one eye of pouch young of the marsupial native cat (Dasyurus hallucatus). The ages at eye removal spanned the period of neurogenesis of the ascending visual pathway, and were earlier than the time of maximal axon number in the optic nerve. Autoradiography following the injection of tritiated proline into the intact eye of adult animals shows that the lateral geniculate nucleus contralateral to the injected eye of the earliest enucleates retains its laminated structure, despite the total absence of binocular competition throughout development. However, we find a dramatic, age-related reduction in the volume of those parts of the lateral geniculate nucleus and superior colliculus which would normally receive a contralateral-only projection from the enucleated eye. The effects of the enucleation are not restricted to the primary termination sites of the optic axons but ramify throughout a large part of the neo- and archicortex.

Assay of stable isotope labelled urea in biological fluids by selected ion monitoring.

A selected ion-monitoring method, incorporating an internal standard, was developed to allow the direct and simultaneous measurement of stable isotope-labelled urea and unlabelled urea concentrations in biological specimens. After cyclization of urea with malonaldehyde bis(dimethylacetal) to form 2-hydroxypyrimidine, the volatile heptafluorobutyryl derivative was made in a two-step process utilizing a trimethylsilyl intermediate. The internal standard, 4-methyl-2-hydroxypyrimidine, was found to be stable under the cyclization conditions. The structures of the internal standard and urea derivatives were confirmed by electron impact and chemical ionization mass spectrometry. This method was applied to the measurement of [15N2]urea concentrations in dog plasma.

Inverse association of prostate cancer and non-steroidal anti-inflammatory drugs (NSAIDs): results of a case-control study.

We examined the association of prostate cancer and non-steroidal anti-inflammatory drugs (NSAIDs) in a case control study of 417 prostate cancer patients and 420 group-matched control subjects. Regular daily use of over the counter NSAIDs, ibuprofen or aspirin, was associated with a 66% reduction in prostate cancer risk (odds ratio = 0.34, 95% confidence interval = 0.23-0.58, p<0.01). The risk of prostate cancer was also significantly reduced in men who reported taking prescription NSAIDs (odds ratio = 0.35, 95% confidence interval = 0.15-0.84, p<0.05). These results suggest that NSAIDs may have value in the chemoprevention of prostate cancer.

Sarcoidosis presenting as heart disease.

It is unusual for sarcoidosis to present with isolated cardiac involvement. We report 3 patients in whom conduction disturbances preceded other clinical or radiographic evidence of sarcoidosis, in 2 cases by several years. The literature of sarcoidosis manifesting solely with cardiac disease is reviewed. Our report is intended to emphasize consideration of sarcoidosis in the diagnostic evaluation of cardiac disease without another obvious cause, particularly in young patients with conduction disturbances, arrhythmias, or cardiomyopathy. We suggest diagnostic strategies and a therapeutic approach.

Do big-brained animals play more? Comparative analyses of play and relative brain size in mammals.

It has been hypothesized that play is more likely to be present in larger brained species. We tested this hypothesis in mammals using independent contrasts, a method that controls for phylogenetic relatedness. Comparisons across 15 orders revealed that the prevalence and complexity of play was significantly correlated with brain size, with larger brained orders having more playful species. Three orders, Rodentia, Marsupialia, and Primates, were used for within-order comparisons among species and, where possible, among families. The comparisons were not significant for rodents or primates, and those for marsupials yielded inconsistent results. Therefore, although a strong relationship is present at the highest taxonomic level of comparison, it diminishes or evaporates at lower level comparisons.

Developmental staging in a marsupial Dasyurus hallucatus.

In a marsupial, Dasyurus hallucatus, pouch-young of various ages from newborn to 55 days were embedded in wax and serially sectioned. On the basis of the relative development of external and internal characteristics, they were placed in the Carnegie staging system developed by Streeter and elaborated by O'Rahilly and associates. Birth occurred at stage 15, and the end of embryogenesis (stage 23) was reached about day 33. Whereas stage 23 is characterised in all eutherians by the closure of the secondary palate, this occurs before stage 15 in D. hallucatus. Since most other characters of the newborn are at a stage 15 level of development, there has been a relative acceleration of development of the secondary palate (and forelimb) in D. hallucatus that allows it to suckle and breathe at the same time. Between D. hallucatus and eutherians, there is general agreement in the sequence of development and in the relative degree of most structures at each stage. Further marsupials should be examined to see if the minor differences noted are peculiar to D. hallucatus or apply to marsupials generally.