New frontiers in applied veterinary point‐of‐capture diagnostics: Toward early detection and control of zoonotic influenza

Among the chief limitations in achieving early detection and control of animal‐origin influenza of pandemic potential in high‐risk livestock populations is the existing lag time between sample collection and diagnostic result. Advances in molecular diagnostics are permitting deployment of affordable, rapid, highly sensitive, and specific point‐of‐capture assays, providing opportunities for targeted surveillance driving containment strategies with potentially compelling returns on investment. Interrupting disease transmission at source holds promise of disrupting cycles of animal‐origin influenza incursion to endemicity and limiting impact on animal production, food security, and public health. Adoption of new point‐of‐capture diagnostics should be undertaken in the context of promoting robust veterinary services systems and parallel support for operationalizing pre‐authorized plans and communication strategies that will ensure that the full potential of these new platforms is realized.     

Both alpha- and beta-adrenoreceptors contribute to the central depressor effect of catecholamines

We compared the effects of alpha 2- and beta-adrenoreceptor blockade on the central actions of catecholamines and metabolites of alpha-methyldihydroxyphenylalanine, epinephrine, alpha-methylnorepinephrine, and alpha-methylepinephrine were studied. I.c.v. and nucleus tractus solitarii (NTS) injections were carried out under anesthesia. Following i.c.v. injection, both epinephrine and methylepinephrine rapidly reduced blood pressure and heart rate, but the effects of methylnorepinephrine occurred somewhat later. Following microinjection into the nucleus of the solitary tract, epinephrine, methylepinephrine, and methylnorepinephrine all caused hypotension and bradycardia. The hypotensive effects of all 3 amines in the NTS were attenuated in additive fashion by yohimbine, an alpha 2 adrenoreceptor antagonist, and timolol, a beta-adrenoreceptor antagonist, whereas only yohimbine attenuated the bradycardia. The combination of yohimbine and timolol abolished the effects of the amines. These data suggest that in the NTS both alpha 2 and beta adrenoreceptor stimulation contribute to the hypotensive effects of these amines, but that only alpha 2 adrenoreceptors are principally involved in the heart rate response.     

Therapy of human cervical carcinoma with monoclonal antibody-Pseudomonas exotoxin conjugates.

Pseudomonas exotoxin A (PE) linked to the F(ab')2 fragment of 1H10, a murine monoclonal antibody recognizing a carbohydrate epitope of a glycoconjugate expressed on the surface of human cervical carcinoma tumor cells, was evaluated for in vitro and in vivo activity. PE can kill cells by ADP-ribosylating elongation factor 2 thus inhibiting protein synthesis. Disulfide- as well as thioether-linked immunotoxins (1H10-PE) killed cervical carcinoma cells in vitro and were 20-160 times more inhibitory to target than to control cells. Cell killing was antibody mediated as demonstrated by the reduction of 1H10-PE growth inhibition to target CaSki cells by free 1H10 F(ab')2. In addition, a control antibody immunotoxin was nontoxic to CaSki cells. Thioether-linked 1H10-PE administered either i.v. or i.p. suppressed the growth of established solid s.c. cervical carcinoma tumors xenografted in nude mice for over 30 days. Treatment with antibody alone or a control immunotoxin had no significant effect on tumor growth. Administration of immunotoxin i.p. was associated with less toxicity than administration i.v., but i.v. injections were more effective at suppressing the growth of established solid tumors.     

OVERHEATING IN BED AS AN IMPORTANT FACTOR IN MANY COMMON DERMATOSES

Background. Extensive questioning of patients with a wide variety of skin disorders led to the impression that nocturnal overheating was probably an important factor in the initiation and the perpetuation of many skin disorders. Methods. In order to test the hypothesis, 12 “clean-skinned” subjects (6M/6F) aged 18 to 45 years were monitored electronically every 30 seconds during an 8 hour sleep period (2300 to 0700 hours), sleeping under a standard 10 tog duvet. Results. All the subjects were too hot by 3 to 4°C. All showed changes in their EEG patterns with reduced REM sleep, increased awakenings, and all showed changes in their sleep stage patterns. In addition, they all showed evidence of increased sweating in the “heat-sink” area. Conclusions. The mechanisms where by such changes could be implicated in the precipitation and perpetuation of skin disease are discussed. “Lifestyle” modification as a very effective, noninvasive, therapeutic regime is recommended. Further research along these lines would probably be very valuable and instructive.     

Inducible nitric oxide expression in equine articular chondrocytes: effects of antiinflammatory compounds.

OBJECTIVE: To determine the effects of recombinant equine IL-1beta and a number of antiinflammatory compounds on the expression and activity of inducible nitric oxide synthase (iNOS) in cultured equine chondrocytes. DESIGN: RT-PCR methods were used to amplify a portion of the equine iNOS message to prepare an RNA probe. Northern blot analysis was used to quantify the expression of iNOS in first passage cultures of equine articular chondrocytes propagated in the presence or absence of recombinant equine interleukin-1beta (reIL-1beta), dexamethasone (DEX), polysulfated glycosaminoglycan (PSGAG), hyaluronan (HA), and phenylbutazone (PBZ), each at concentrations of 10 and 100 microg/ml. Nitrite concentrations in conditioned media of similarly treated cells were used to quantify iNOS activity. RESULTS: Recombinant equine IL-1beta increased the expression of iNOS in a dose-dependent manner. This result was paralleled by an increased concentration of nitrite in the culture media of reIL-1beta-treated cells. DEX and PSGAG significantly reduced iNOS gene expression and media supernatant nitrite concentrations in cytokine-stimulated cultures. HA and PBZ had no consistent effect on the expression of iNOS and did not significantly influence nitrite content of conditioned media. CONCLUSIONS: NO is considered an important mediator in the pathophysiologic processes of arthritis and an inducible NOS is expressed by equine chondrocytes. Pre-translational regulation of the iNOS gene by DEX and PSGAG appears to contribute to the cartilage-sparing properties of these compounds.     

Tyramine-Induced cardiac arrhythmias

Five out of 12 physically healthy patients with depression undergoing a tyramine pressor test developed cardiac arrhythmias. These arrhythmias occurred in drug-free patients in three out of 12 infusions following as little as 0.03 mg/kg of tyramine and after moclobemide, a reversible inhibitor of monoamine oxidase-A, in four out of 14 tyramine infusions with as little as 0.04 mg/kg of tyramine. The arrhythmias seen were independent of patient's age and occurred both before and after 30 mmHg elevations in systolic blood pressure. Electrocardiographic abnormalities and arrhythmias seen were a loss of p waves, sinus tachycardia, frequent atrial ectopic beats, atrial premature beats, Wenckebach phenomenon, junctional rhythm, ventricular ectopics, varying QRS configurations, and ventricular bigeminy. Tyramine, both oral and intravenous, caused similar reproducible changes in dogs, though not in rats, mice or guinea pigs. Practical implications are that tyramine pressor testing in humans should be performed cautiously and only with adequate cardiac monitoring and resuscitation facilities at hand. These findings suggest that a normal dietary component can induce serious cardiac arrhythmias, and that a low-tyramine diet may be of value for patients who are susceptible to cardiac arrhythmias.     

Preoperative Clinic Visits Reduce Operating Room Cancellations and Delays

Background: Anesthesiologist-directed preoperative medicine clinics are used to prepare patients for the administration of anesthesia and surgery. Studies have shown that such a clinic reduces preoperative testing and consults, but few studies have examined the impact of the clinic on the day of surgery. The authors tested whether a visit to an anesthesia preoperative medicine clinic (APMC) would reduce day-of-surgery case cancellations and/or case delays.

Methods: The authors conducted a retrospective chart review of all surgical cases during a 6-month period at the University of Chicago Hospitals. Case cancellations and rates of first-start case delay over the 6-month period were cross-referenced with a database of APMC attendees in both the general operating rooms and the same-day surgery suite. The impact of a clinic visit on case cancellation and delay in both sites were analyzed separately.

Results: A total of 6,524 eligible cases were included. In the same-day surgery suite, 98 of 1,164 (8.4%) APMC-evaluated patients were cancelled, as compared with 366 of 2,252 (16.2%) in the non-APMC group (P < 0.001). In the general operating rooms, 87 of 1,631 (5.3%) APMC-evaluated patients were cancelled, as compared with 192 of 1,477 (13.0%) patients without a clinic visit (P < 0.001). For both operating areas, APMC patients had a significantly earlier room entry time than patients not evaluated in the APMC.     

Dose-rate scaling factor estimation of THOR BNCT test beam.

In 1998, an epithermal neutron test beam was designed and constructed at the Tsing Hua Open-Pool Reactor (THOR) for the purpose of preliminary dosimetric experiments in boron neutron capture therapy (BNCT). A new epithermal neutron beam was designed at this facility, and is currently under construction, with clinical trials targeted in late 2004. Depth dose-rate distributions for the THOR BNCT test beam have been measured by means of activation foil and dual ion chamber techniques. Neutron and structure-induced gamma spectra measured at the test beam exit were configured into a source function for the Monte Carlo-based treatment planning code NCTPlan. Dose-rate scaling factors (DRSFs) were determined to normalize computationally derived dose-rate distributions with experimental measurements in corresponding mathematical and physical phantoms, and to thus enable accurate treatment planning using the NCTPlan code. A similar approach will be implemented in characterizing the new THOR epithermal beam in preparation for clinical studies. This paper reports the in-phantom calculated and experimental dosimetry comparisons and derived DRSFs obtained with the THOR test beam.