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Biomedical subjects

A L Aronson

Publications and source records attributed to A L Aronson.

At least 19 recordsLinked to original sources

Opitz syndrome is genetically heterogeneous, with one locus on Xp22, and a second locus on 22q11.2.

Opitz syndrome (OS, McKusick 145410) is a well described genetic syndrome affecting multiple organ systems whose cardinal manifestations include widely spaced eyes and hypospadias (Fig. 1). It was first reported as two separate entities, BBB syndrome, and G syndrome. However, subsequent reports of families in which the BBB and G syndrome segregated within a single kindred suggested that they were a single clinical entity. Although the original pedigrees were consistent with X-linked and autosomal dominant inheritance, male-to-male transmission in subsequent reports suggested that OS was inherited as an autosomal dominant trait. Here we report that OS is a heterogeneous disorder, with an X-linked and an autosomal locus. Three families were linked to DXS987 in Xp22, with a lod score of 3.53 at zero recombination. Five families were linked to D22S345 from chromosome 22q11.2, with a lod score of 3.53 at zero recombination. This represents the first classic multiple congenital anomaly syndrome with an X-linked and an autosomal form.

Abnormalities, Multiple

Determination of ceftiofur and its metabolite desfuroylceftiofur in bovine serum and milk by ion-paired liquid chromatography.

A simple and sensitive liquid chromatographic method has been developed for the simultaneous determination of ceftiofur and its metabolite desfuroylceftiofur in bovine serum and milk. The method involved an ultrafiltration of diluted serum/milk with an equal volume of 50% acetonitrile through a 10,000 dalton molecular mass cut-off filter. Separation of ceftiofur and desfuroylceftiofur from the other serum/milk components was performed by ion-paired (octane and dodecanesulfonate) liquid chromatography using a reversed-phase column eluted with acetonitrile-water solution. The ultraviolet-visible absorbance of the column effluent was monitored in 200-350 nm range of a photodiode-array detector or at lambda max 289.6 nm for ceftiofur, lambda max 265.8 nm for desfuroylceftiofur and lambda max 271.4 nm for dimer of desfuroylceftiofur. Recoveries of ceftiofur from bovine milk spiked with 1 and 10 micrograms/ml were 95.9 and 97.0% with coefficients of variation of 3.69 and 2.51%, respectively. Recovery of ceftiofur from bovine serum spiked with 10 micrograms/ml was 90.4% with a coefficient of variation of 5.29%. A correlation coefficient of 0.9992 occurred with ceftiofur in aqueous solutions (n = 5, in duplicates). The limit of detection was estimated to be approximately 50 ppb (ng/ml). Additionally, this paper documents the presence of a ceftiofur metabolite in bovine serum under in vitro and in vivo conditions. The metabolite was identified as desfuroylceftiofur together with its dimer 3,3'-desfuroylceftiofur disulfide by thermospray liquid chromatography-mass spectrometry.

Animals

Development of analytical methods for some penicillins in bovine milk by ion-paired chromatography and confirmation by thermospray mass spectrometry.

Analytical methods for the determination of cloxacillin, ampicillin/hetacillin, and amoxicillin in bovine milk were developed. The methods involved ultrafiltration of milk diluted with methanol, acetonitrile, and water on a 10,000-dalton cut-off filter. Separation of penicillins from other milk components was accomplished by ion-paired chromatography using a microbore column. The penicillins were detected using ultraviolet photodiode array (UV-PDA) detection and confirmed by thermospray liquid chromatography-mass spectrometry (LC-MS). The thermospray spectra of these compounds exhibited [M + H]+ and [M + Na]+ ions along with several fragment ions. The limits of detection for these antibiotics were estimated to be 50 to 100 ppb for LC with UV-PDA detection and 100-200 ppb for thermospray LC-MS detection.

Animals

Development of an analytical method for cephapirin and its metabolite in bovine milk and serum by liquid chromatography with UV-VIS detection and confirmation by thermospray mass spectometry.

Metabolites of the cephapirin beta-lactam antibiotic have not previously been reported in bovine milk. The principal metabolite was tentatively identified as desacetylcephapirin by liquid chromatography with UV-VIS photodiode array (LC/UV-VIS PDA), and liquid-chromatography-mass-spectrometric (LC-MS) detection. Synthetic desacetylcephapirin was prepared by incubation of cephapirin in bovine milk and serum at 37 degrees C. Also, a method for determining cephapirin in bovine milk and serum was developed. The detection limits for cephapirin and desacetylcephapirin were estimated to be 10 and 50 micrograms/kg, respectively, for LC/UV-VIS PDA, and 100 and 500 micrograms/kg for LC-MS.

Animals

High-performance liquid chromatographic method for the simultaneous determination of enrofloxacin and its primary metabolite ciprofloxacin in canine serum and prostatic tissue.

A simple and sensitive high-performance liquid chromatographic method was developed for the determination of enrofloxacin and ciprofloxacin in canine serum and prostatic tissue. Sample preparation consisted of mixing canine serum with a 1:1 dilution of acetonitrile and 0.1 M sodium hydroxide followed by ultrafiltration through a 10,000 molecular mass cut-off filter. Prostatic tissue was sonicated with the same solution prior to ultrafiltration. Separation of these two quinolones in the ultrafiltrate was accomplished by ion-paired liquid chromatography using a reversed-phase analytical column eluted with an acetonitrile-methanol-water solution. Enrofloxacin and ciprofloxacin were detected by a photometric ultraviolet-visible detector set at 278.6 nm and confirmed by a photodiode array detector operating from 230 to 360 nm. The limits of detection for enrofloxacin and ciprofloxacin were 4 and 2 ng/ml, respectively.

Animals

Development of an analytical method for penicillin G in bovine milk by liquid chromatography with ultraviolet-visible detection and confirmation by mass spectrometric detection.

A liquid chromatographic (LC) method with ultraviolet-visible photodiode array (UV-VIS PDA) detection was developed to measure penicillin G in bovine milk. A liquid chromatographic-mass spectrometric (LC-MS) procedure was divised to confirm the LC method. The method involved diluting milk with a drug-releasing solvent consisting of acetonitrile-methanol-water and ultrafiltration through a 10,000 dalton cutoff filter. Penicillin G was separated from other components in the ultrafiltrate by ion-paired LC using a reversed-phase microbore column eluted with a 25% acetonitrile solution. The LC method was confirmed by thermospray LC-MS. The detection limit for penicillin G determination in milk was estimated to be 10 ppb for LC with UV-VIS PDA and 100 ppb for LC-MS.

Animals

Analysis of cephalexin from canine skin biopsy by liquid chromatography with ultraviolet-visible photodiode-array detection.

A sensitive and selective ion-paired liquid chromatographic method with UV-VIS photodiode-array detection was developed to measure cephalexin in skin biopsy samples. The method involved a sonication of minced canine skin with ethanol-acetonitrile-water (30:20:50, v/v/v) and ultrafiltration of received extract through 10,000 daltons. Separation of cephalexin from other components was by liquid chromatography using a reversed-phase column which was eluted with an ion-paired acetonitrile-water solution. Detection was achieved with a UV-VIS photodiode-array detector scanning from 230 to 320 nm. Cephalexin in the eluate was quantitated at its wavelength maximum of 260 nm. The evaluation of chromatographic peak homogeneity was performed by absorbance ratios, contour maps, first-derivative spectra and a three-dimensional spectrochromatogram. Additionally, the cephalexin peak identity was confirmed by liquid chromatography-mass spectrometry.

Cephalexin

Simple LC method for determination of chloramphenicol in equine, canine, and feline serum.

A simple and sensitive high-performance liquid chromatographic (HPLC) method is developed for the determination of chloramphenicol (CAP) concentrations in equine, canine, and feline serum. Serum samples are diluted, then ultrafiltered using a microconcentrator with a 30,000 MW cutoff filter. CAP is separated and quantitated directly from the ultrafiltrate on a reversed-phase column using a buffered methanol mobile phase and a variable wavelength UV detector set at 278 nm. The recovery of CAP from 5 micrograms/mL spiked serum samples is determined using 10 serum samples from each of the three species. This method of sample preparation yields recoveries of 99.8%, 92.0%, and 88.6% with coefficients of variation of 1.2%, 1.3%, and 1.0% in equine, canine, and feline sera, respectively. Concentrations of CAP between 0.5 and 400 micrograms/mL as determined by peak area are found to have a linear relationship (correlation coefficient = 0.99997, n = 10), although amounts as low as 0.025 microgram/mL can be detected.

Animals

Teratogenic effect of calcium edetate (CaEDTA) in rats and the protective effect of zinc.

The calcium chelate of EDTA (CaEDTA) currently is the drug of choice in the treatment of lead intoxication. This study investigated the teratogenic potential of CaEDTA, administered parenterally during periods of organogenesis and determined if incorporating zinc into EDTA would protect against teratogenic effects. Four doses (2, 4, 6, and 8 mmol/m2/day) of CaEDTA, two concentrations (8 and 20 mmol/m2/day) of ZnEDTA and ZnCaEDTA (molar ratio 0.5:0.5:1) were used, and a saline control (0.9% NaCl). Timed-pregnant Long-Evans rats were assigned at random to the treatment groups, 20 per dose for each chelate and 30 to the saline control. Rats were injected with the chelate or saline solution sc, twice daily during the 11th through 15th days of gestation. Pups removed by cesarean section on the 21st day were processed for osseous and visceral examination. Additional animals per treatment group were used for maternal plasma and liver and fetal zinc determinations. Results showed increases in several abnormalities (submucous cleft, cleft palate, adactyly-syndactyly, curly tail, abnormal rib and vertebrae) with increasing amounts of CaEDTA. No malformations were seen with ZnEDTA at either dose or with ZnCaEDTA at 8 mmol/m2/day. However, submucous cleft was seen in 6 of 20 litters from the dams receiving the higher dose of ZnCaEDTA. It was concluded that CaEDTA is teratogenic in rats at concentrations which, except for decreased weight gain, produce no discernible toxicity to the dam, and which are comparable to the recommended therapeutic dosage in humans (1500 mg/m2/day corresponding to 4 mmol/m2/day). Protection is afforded by incorporating zinc in the chelate.

Abnormalities, Drug-Induced

Choice of the optimum pulse duration for precordial cardiac pacing: a theoretical study.

In precordial pacing with skin-surface electrodes, the goal is to excite the ventricles with minimal stimulation of overlying tissues. A theoretical analysis is presented to identify the relevant factors; the two most important are electrode location and pulse duration. Using the basic law of stimulation, we developed a model which indicates that the optimum pulse duration for the closed-chest pacing pulse is one that is long with respect to the membrane time constant of cardiac muscle. Current-versus-duration curves are presented for pacing and pain, based on experimentally obtained data. For pacing with minimum pain, the optimum stimulus duration was found to be about 10 ms.

Adult

Comparative effects of Ca-ethylenediaminetetraacetic acid (EDTA), ZnEDTA, and ZnCaEDTA in mobilizing lead.

Male Long-Evans rats weighing approximately 240 g were given (Pb) at 14 mg/kg as the acetate by slow iv infusion 17 days prior to chelate treatment. The chelating agents were administered by continuous iv infusion at either 1 mmol/kg over 6 hr or 6 mmol/kg over 24 hr or at 0.16 mmol/kg/day by sc injections. ZnEDTA was 60% and ZnCaEDTA 76% as effective as CaEDTA in promoting urinary Pb excretion at 1 mmol/kg over 6 hr, iv. At 6 mmol/kg/24 hr, iv, ZnEDTA was 76% and ZnCaEDTA 98% as effective as CaEDTA. Mean urinary Pb excretion for each chelate via the sc route and the lowest iv route of administration was the same. Blood delta-aminolaevulinic acid dehydratase (ALAD) activity (an indicator of Pb toxicity) was enhanced approximately twofold by CaEDTA, two and one-half-fold by ZnCaEDTA, and fivefold by ZnEDTA treatment. It is suggested that the safety of EDTA can be markedly enhanced if administered as a ZnCaEDTA chelate without appreciably diminishing its efficacy in promoting urinary Pb excretion.

Animals

External non-invasive cardiac pacing: a comparative hemodynamic study of two techniques with conventional endocardial pacing.

Out-of-hospital therapy for cardiac arrest due to bradyarrhythmias or asystole is pharmacologic and the outcome is uniformly dismal. Optimal therapy for the latter disturbances may be artificial cardiac pacing, but conventional invasive pacing techniques are not employed or are of limited value in the out-of-hospital and emergency department setting. This investigation compared the hemodynamic effects of two techniques of non-invasive external pacing: 1) transcutaneous transthoracic pacing (TTP) and 2) tongue-to-epigastrium pacing (TEP), with conventional transvenous right ventricular endocardial pacing (RVEP) in a closed-chest, chronic heart block canine model. All techniques significantly increased (p less than .001) cardiac output (CO). However, CO and mean arterial pressure (MAP) measured during external pacing with either non-invasive technique were significantly greater than that during RVEP (p less than .001). TEP produced vigorous skeletal muscle stimulation and, in the canine model, it produced contraction resulting in impaired ventilation, hypoxemia, and a decrease in systemic vascular resistance. TTP in this model resulted in improved MAP and CO when compared with control and RVEP values and did not affect arterial or mixed venous blood gas values. Thus, this study demonstrates that noninvasive TTP is comparable to RVEP in its hemodynamic effects. TTP may offer definitive non-invasive therapy for a subset of victims of out-of-hospital cardiac arrest.

Animals

Use of an automated external defibrillator-pacemaker by ambulance staff.

A new portable external device detects ventricular fibrillation and profound bradycardia or asystole by analysis of wave forms; it automatically delivers a defibrillating shock or repetitive pacing stimuli. Ambulance crews used the device on 27 cardiac-arrest patients. The initial group (16) was restricted to patients prejudged as probably beyond successful resuscitation, and none survived. The subsequent group (11) was not restricted. 5 were discharged alive from the hospital. The device is simple to use, and its application by modestly trained technicians and lay people may be feasible. Widespread use of the device as an adjunct to conventional cardiopulmonary resuscitation could reduce mortality from out-of-hospital cardiac arrest. The capability for external cardiac pacing enhances the efficacy of treatment.

Ambulances

Pharmacotherapeutics of the newer tetracyclines.

The newer tetracyclines are defined as those tetracyclines available in the United States but not approved for veterinary use. These include demeclocycline, methacycline, doxycycline, and minocycline. Of these, doxycycline and minocycline appear to offer advantages that would render them useful in certain situations in veterinary medicine. Their major advantage lies in their greater lipid solubility relative to other tetracyclines. This characteristic probably accounts for their enhanced antimicrobial effectiveness for some organisms, more efficient absorption after oral administration, and enhanced distribution in the body. The principal excretory organ for doxycycline is the intestine, where the drug diffuses through the intestinal mucosa into the intestinal tract. This unique characteristic makes this drug useful in cases of preexisting renal dysfunction and may render this drug superior to other tetracyclines in the treatment of intestinal infections. Doxycycline is used in other countries for respiratory tract and intestinal tract diseases of poultry. The usefulness of doxycycline and minocycline in food-producing animals may be limited because of persistent drug residues. Minocycline has, in large doses, been used with streptomycin in the elimination of the carrier state of canine brucellosis. The superiority of doxycycline and minocycline, relative to other tetracyclines, in their distribution to areas of he body such as the eye, brain, cerebrospinal fluid, and prostate gland suggests that trials of their efficacy in tetracycline-sensitive infections of these areas are indicated. Pharmacokinetic studies designed to determine optimal dosage schedules have not been made for domestic animals. These determinations are necessary to evaluate most effectively the usefulness of the newer tetracyclines in veterinary medicine.

Absorption

The bacteriological culture of equine uterine contents, in-vitro sensitivity of organisms isolated and interpretation.

A total of 19 pathogenic bacterial species was isolated from uterine swabs of 498 out of 1539 mares over 4 years. The swabs were taken by 5 veterinary clinicians using 2 different techniques. Bacterial contamination during swabbing was minimized by scrupulous attention to cleansing of the external genitalia and the perineal area, and in the handling of the culture specimen. The most prevalent organisms isolated were beta-haemolytic streptococcus (39%), Escherichia coli (27%) and Klebsiella pneumoniae (7%). Interpretation of microbiological findings correlated well with clinical findings when number of organisms isolated and endometrial cytology were considered. The use of a bacterial transport medium combined with sophisticated culture methods reflects a more accurate picture of the uterine microflora than can be obtained by previous techniques. Streptococci isolated were uniformly sensitive to penicillins. The sensitivity of E. coli and K. pneumoniae towards chloramphenicol, gentamicin and polymyxin was nearly 100%. The selection of an appropriate antibacterial agent depends upon sensitivity, pharmacological action, genital tract status and cost. This study shows that a Gram stain of uterine cytology can be used to diagnose quickly and select an appropriate antibiotic for treatment prior to culture results if sufficient numbers of organisms are present.

Animals