Introduction of a Simple Second Tier Screening Test for C5 Isobars in Dried Blood Spots: Reducing the False Positive Rate for Isovaleric Acidaemia in Expanded Newborn Screening.

In 2015 the English Newborn Screening programme expanded to include Isovaleric Acidaemia (IVA). Screening is performed by flow injection analysis tandem mass spectrometry of isovalerylcarnitine. Isovalerylcarnitine is isobaric with pivaloylcarnitine which can be present in blood due to the use of pivalic ester pro-drugs or pivalic acid derivatives used as emollients in some nipple creams; the potential for false positives (FP) is well documented. A pilot study in England screened 438,164 babies, 18 had presumptive positive results but only 4 were confirmed as true positives (TP). We developed a simple test to separate the isobaric compounds and investigate these samples further.We studied newborn screening blood spots from 122 randomised controls and 34 infants with an initial raised C5 result. Dried blood spots were eluted with 30% acetonitrile (150 µL) and injected into a Waters Acquity UPLC coupled to a Waters Premier XE tandem mass spectrometer operating in positive ion mode. Isocratic separation of isovalerylcarnitine, pivaloylcarnitine, valerylcarnitine and 2-methylbutyrylcarnitine was achieved within 8 min. Assay performance characteristics were acceptable and non-parametric reference ranges (n = 122) were determined for each analyte.If this method had been used as a second tier test for the 34 presumptive positive samples, the number of FP's would have reduced from 24 to 8 and the positive predictive value of the screening test would have increased from 29 to 56%. Introduction of this test into the screening protocol has the potential to significantly reduce FP results for IVA and prevent unnecessary anxiety.

Economic evaluation of neonatal health protection programs for cattle.

OBJECTIVE: To develop an economic tool that can be used to help cattle producers evaluate benefits of neonatal health programs. DESIGN: Computer simulation of a multiple-year spreadsheet model, using economic and production variables. SAMPLE POPULATION: Records for a university research farm beef herd. PROCEDURE: Data from the university research farm beef herd for each year from 1990 to 1995 were evaluated to determine economic benefits for the cow-calf enterprise that would result from a decrease in morbidity and mortality. A baseline economic evaluation of returns to variable costs was performed, using actual production and marketing information. Actual economic performance was contrasted with a projected simulation in which morbidity and mortality were decreased. Sensitivity analysis for the simulation model assessment of a neonatal health program was also performed. RESULTS: Mean-per-cow increase in net income for the herd during the 6-year period for morbidity and mortality reductions of 20, 40, and 60% was $7.44, $14.93, and $22.42, respectively. Sensitivity analysis revealed that net income per cow was not sensitive to errors in projections of morbidity and mortality. CLINICAL IMPLICATIONS: Identifying potential economic benefits for implementing a neonatal health plan and quantifying the costs to implement each component of the plan can be used by veterinarians and their clients when formulating a proactive strategy to provide the greatest potential for economic reward.

Epidemiologic evaluation of encephalitic listeriosis in goats.

OBJECTIVE: To evaluate host and environmental factors associated with the development of encephalitic listeriosis in goats. DESIGN: Retrospective analysis of diagnostic laboratory records and survey of veterinarians and goat producers. SAMPLE POPULATION: 355 goat herds accessible through laboratory records; 38 veterinarians who treated goats and 76 goat producers. PROCEDURE: Data regarding breed and use for goats affected with encephalitic listeriosis were obtained from surveys and case follow-up information. Listeria monocytogenes isolates from the brains of 7 affected goats were serotyped and subjected to DNA restriction analysis. RESULTS: Odds ratio for the development of encephalitis listeriosis in Angora (mohair-producing) goats was 22.9 by use of diagnostic laboratory records. Survey also revealed a high prevalence in herds of Angora and other breeds that subsisted on woody browse, although Angora goats feeding predominantly on hay or pasture were not affected. Listeria monocytogenes isolates from 4 Angora goats in 3 herds differed in DNA restriction patterns, although the pattern was identical in 3 other goats from another herd. CLINICAL IMPLICATIONS: Encephalitic listeriosis can be observed in all goat breeds, but a lifestyle of heavy browse consumption seems important to the development of disease in some herds.

Production medicine considerations for enhanced reproductive performance in beef herds.

The purpose of this article is to provide considerations that must be included in a production medicine program. Although no two programs are the same, each of these areas must be addressed to be effective. Use of current knowledge and technology as well as emerging knowledge and technology to provide input into management practices for enhancing performance is the underlying goal of any production medicine program. The veterinary practitioner can serve as a participant in establishing and maintaining such a program as part of the complete management team.

Vestibular-ocular accommodation reflex in man.

Stimulation of the vestibular system by angular acceleration produces widespread sensory and motor effects. The present study was designed to study a motor effect which has not been reported in the literature, i.e., the influence of rotary acceleration of the body on ocular accommodation. The accommodation of 10 young men was recorded before and after a high-level deceleration to zero velocity following 30 s of rotation. Accommodation was recorded continuously on an infrared optometer for 110 s under two conditions; while the subjects observed a target set at the far point, and while they viewed the same target through a 0.3-mm pinhole. Stimulation by high-level rotary deceleration produced positive accommodation or a pseudomyopia under both conditions, but the positive accommodation was substantially greater and lasted much longer during fixation through the pinhole. It is hypothesized that this increase in accommodation is a result of a vestibular-ocular accommodation reflex.

Diurnal rhythms of visual accommodation and blink responses: implication for flight-deck visual standards.

The major purpose of this study was to determine whether 24-h variations in accommodation responses occur and, if they do, whether they should be considered in setting visual standards for flight-deck tasks. A recently developed servo-controlled optometer and focus stimulator were used to obtain monocular accommodation response data on four college-age subjects. No 24-h rhythm in accommodation was shown. Heart rate and blink rate also were measured and periodicity analysis showed a mean 24-h rhythm for both; however, blink rate periodograms were significant (p less than or equal to 0.003) for only two of the four subjects. Thus, with the qualifications that college students were tested instead of pilots and that they performed monocular laboratory tasks imstead of binocular flight-deck task, it is concluded that 24-h rhythms in accommodation responses need not be considered in setting visual standards for flight-deck task.

Responses of myopes to volitional control training of accommodation.

Twelve young, low myopes were trained to control volitionally their accommodation responses and to achieve clear focus on visual targets moved progressively outward in optical distance. The trainees participated in from 15 to 40 daily training sessions (mean = 28 sessions). All demonstrated volitional control with varying degrees of control authority. Though three of the trainees were unsuccessful, the group achieved a statistically reliable extension of their far points. Post-training optometric examinations were reliably improved over pre-training examinations, but did not appear to be commensurate with the large gains in far-point extension. It was hypothesized that the learned skill may have been 'instrument-specific', i.e. it might not fully generalize to significantly improved post-training binocular performance unless it were accompanied by clinical assistance to transfer the training.

Metal-on-metal articulation in total hip arthroplasty: preliminary results in 57 cases.

BACKGROUND: Aseptic loosening of hip prostheses may lead to implant failure and necessitate revision surgery. Metal-on-metal hip articulation has characteristics that may minimize prosthesis loosening when compared with other forms of hip articulation. The purpose of the present prospective study was to identify early problems that may contraindicate the use of the 'prosthesis femorale modulaire' (PFM) metal-on-metal prosthesis. METHODS: The preliminary results of 57 metal-on-metal total hip arthroplasties performed by one surgeon (RR) from 1994 to 1996 in Lismore, New South Wales, are presented here. Data were obtained using patient questionnaires, physical examination and by examination of radiographs. RESULTS: A total of 87.6% of patients had an excellent or good outcome, according to the Harris rating system, at the latest review. The two patients with poor results had obvious alternative causes for their continuing symptoms. There was no radiological evidence of bone or prosthesis failure during the period of follow-up. CONCLUSIONS: The preliminary results are comparable with those of other authors who have examined the early results of metal-on-metal total hip arthroplasty.

Effect of a concurrent counting task on dynamic visual accommodation.

The visual accommodation of four male subjects was selectively recorded over a 3-day period using an objective, continuously recording, infrared optometer to determine the effects of a concurrent counting task on their ability to accommodate to a sinusoidally changing focus stimulus ranging from 0.0 to 3.0 D. There was an increase in their steady-state errors in the direction of negative accommodation of from 0.25 to 0.50 D, but the magnitude of the steady-state error induced by the concurrent task did not change over the three sine wave frequencies used (0.1, 0.2 and 0.4 Hz). The results are discussed in terms of an accommodative "lag" model of sympathetic-parasympathetic arousal induced by superimposing an extraneous mental task.

Growth hormone secretion, serum, and cerebral spinal fluid insulin and insulin-like growth factor-I concentrations in pigs with streptozotocin-induced diabetes mellitus.

Diabetes mellitus was induced using streptozotocin in five gilts between 8 and 12 weeks of age. Gilts were maintained with exogenous insulin (INS) except during experimental periods. Four litter-mate gilts served as controls. At 9 months of age, all gilts were ovariectomized, and 30 days after ovariectomy, Experiment (Exp) 1 was conducted. Jugular vein catheters were inserted and blood samples were collected every 10 min for 8 hr. Experiment 2 was conducted when gilts were 11 months of age. Venous blood and cerebrospinal fluid (CSF) samples were collected in the absence (Phase I) or presence (Phase II) of INS therapy. In Experiment 1, plasma glucose concentrations were greater (P < 0.05) in diabetic (465 +/- 17 mg/100 ml) than in control (82 mg +/- 17 mg/100 ml) gilts, whereas serum INS was lower (P < 0.0001) in diabetic gilts (0.3 +/- 0.02 vs 0.9 +/- 0.05 ng/ml) and insulin-like growth factor-I was similar in diabetic and control gilts (32 +/- 3 vs 43 +/- 4 ng/ml, respectively). Mean serum GH concentration was 2-fold greater (P < 0.02) in diabetics (2.8 +/- 0.4 ng/ml) than in control gilts (1.2 +/- 0.2 ng/ml). Diabetic gilts exhibited a greater (P < 0.05) number of GH pulses than control gilts (3.2 +/- 0.4 vs 1.5 +/- 0.3/8 hr, respectively). In addition, GH pulse magnitude was markedly elevated (P < 0.02) in diabetic (5.8 +/- 0.4 ng/ml) compared with control gilts (3.3 +/- 0.6 ng/ml). Mean basal serum GH concentrations were greater (P < 0.07) in diabetic (2.2 +/- 0.5 ng/ml) compared with control gilts (1.0 +/- .1 ng/ml). In Experiment 2, CSF concentrations of insulin-like growth factor-I, INS, GH, and protein were similar for diabetic and control gilts in both phases. Serum GH levels were similar for diabetics and controls in Phase I, but were greater (P < 0.05) in diabetics than in controls in Phase II. CSF glucose levels were greater in diabetic than in control gilts in both the presence (P < 0.003) and absence (P < 0.0002) of INS therapy, whereas plasma glucose was greater (P < 0.003) in diabetic than in control gilts in the absence of INS, but returned to control concentrations in the presence of INS. However, serum GH levels were unchanged after INS therapy in the diabetic gilts. In conclusion, altered GH secretion in the diabetic gilt may, in part, be due to elevated CSF glucose concentrations, which may alter GH-releasing hormone and/or somatostatin secretion from the hypothalamus.