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Biomedical subjects

J D Jacobson

Publications and source records attributed to J D Jacobson.

At least 37 records · Page 2Linked to original sources

Chylothorax associated with constrictive pericarditis in a dog.

Chylothorax was associated with constrictive pericarditis in a 6-year-old mixed-breed dog. Clinical signs included hepatomegaly, bilateral jugular pulses, muffled heart sounds, and dyspnea. Pleural effusion was identified on thoracic radiographs. Thoracentesis yielded 3 L of chylous effusion, confirmed by the cholesterol/triglyceride ratio (0.14). Echocardiography revealed a thickened pericardium, with numerous fibrin tags, which was suggestive of constrictive pericarditis. Central venous, right atrial, and right ventricular pressures were high and on right ventricular diastolic pressure tracings, the square-root sign, which is indicative of constrictive pericarditis, was evident. Exploratory thoracotomy and pericardiectomy were performed. Histopathologic findings were consistent with chronic non-suppurative pericarditis. The dog's condition improved after surgery. On reevaluation 11 months later, central venous pressure and results of physical examination and thoracic radiography were normal. On the basis of these findings, we concluded that chylothorax was caused by constrictive pericarditis in this dog. Chylothorax is often associated with disorders that have a poor prognosis, but if constrictive pericarditis can be identified as the cause of the chylothorax, exploratory thoracotomy and pericardiectomy can provide a cure.

Animals↗

White blood cells in semen affect hyperactivation but not sperm membrane integrity in the head and tail regions.

The presence of high numbers of peroxidase-positive PML in ejaculated semen significantly reduced sperm HA, an important step leading to sperm capacitation. Sperm membranes at both the head and tail regions, as assessed by the hypo-osmotic viability parameter and the hypo-osmotic sperm swelling test, respectively, were not affected by peroxidase-containing leukocytes. Sperm motility was not affected, but sperm curvilinear and straight line velocity parameters were reduced in the presence of high concentrations of leukocytes in the ejaculate. The results suggested that the effect of leukocytes on sperm was through a reduction in sperm hyperactive motility but not through alterations in the sperm head and tail membranes.

Cell Membrane↗

Modulation of the expression of murine lupus by gonadotropin-releasing hormone analogs.

Recent studies have suggested that hypothalamic and pituitary hormones may directly influence the immune system. One such hormone with immunomodulatory properties is GnRH. We hypothesized that GnRH and/or the gonadotropins might alter the severity of autoimmune disease through mechanisms distinct from their effects on gonadal hormones. This possibility was tested in a murine model of lupus. We assessed disease severity over time in intact and castrated, male and female, lupus-prone (SWR x NZB) F1 hybrid mice during treatment with GnRH agonist, GnRH antagonist, or vehicle. Compared to vehicle administration, GnRH antagonist administration significantly decreased total serum immunoglobulin G and anti-DNA antibodies in castrated male and female mice and significantly improved survival. In contrast, GnRH agonist administration exerted reciprocal effects in castrated mice, leading to early increases in serum anti-DNA and total immunoglobulin G levels. We conclude that GnRH and/or the gonadotropins can modify the expression of murine lupus independently of their regulation of gonadal steroid secretion.

Animals↗

Cardiorespiratory effects of glycopyrrolate-butorphanol-xylazine combination, with and without nasal administration of oxygen in dogs.

Cardiopulmonary consequences of IV administered glycopyrrolate (0.01 mg/kg of body weight), followed in 11 +/- 2 minutes by butorphanol (0.2 mg/kg) and xylazine (0.5 mg/kg), were evaluated in 6 dogs, with and without nasal administration of oxygen (100 ml/kg/min). Glycopyrrolate caused significant (P < 0.05) increases in heart rate and cardiac index and significant (P < 0.05) decreases in stroke index. Subsequent administration of butorphanol and xylazine was associated with significant (P < 0.05) increases in systemic vascular resistance, mean arterial blood pressure, mean pulmonary artery pressure, central venous pressure, pulmonary capillary wedge pressure, PaCO2, venous admixture, oxygen extraction ratio, and hemoglobin concentration. It caused significant (P < 0.05) decreases in cardiac index, stroke index, breathing rate, minute volume index, oxygen delivery, and oxygen consumption. Mean arterial blood pressure, pulmonary vascular resistance, tidal volume index, and minute volume index were significantly (P < 0.05) higher when dogs were breathing room air. The arterial and venous PO2 and PCO2, and venous oxygen content were significantly (P < 0.05) higher, and the arterial and venous pH, and oxygen consumption were significantly (P < 0.05) lower when oxygen was administered. Pulsus alternans and S-T segment depression were observed in dogs of both groups. Ventricular premature contractions were observed in 1 dog breathing room air. All dogs were intubated briefly 15 minutes after administration of butorphanol and xylazine. Time to first spontaneous movement was 45 minutes. All dogs remained in lateral recumbency without physical restraint for 60 minutes.

Animals↗

Cardiorespiratory effects of induction and maintenance of anesthesia with ketamine-midazolam combination, with and without prior administration of butorphanol or oxymorphone.

Cardiorespiratory effects of an IV administered bolus of ketamine (7.5 mg/kg of body weight) and midazolam (0.375 mg/kg) followed by IV infusion of ketamine (200 micrograms/kg/min) and midazolam (10 micrograms/kg/min) for 60 minutes was determined in 6 dogs. Ketamine-midazolam combination was administered to dogs on 3 occasions to determine effects of prior administration of IV administered saline solution (1 ml), butorphanol (0.2 mg/kg), or oxymorphone (0.1 mg/kg). The infusion rate of ketamine and midazolam was decreased by 25% for anesthetic maintenance after opioid administration. There were no significant differences in cardiorespiratory variables after saline solution or butorphanol administration; however, oxymorphone caused significant (P < 0.05) increases in mean arterial blood pressure, systemic vascular resistance, and breathing rate. Bolus administration of ketamine-midazolam combination after saline solution caused significant (P < 0.05) increases in heart rate, mean arterial blood pressure, cardiac index, mean pulmonary blood pressure, venous admixture, and significant decreases in stroke index, pulmonary capillary wedge pressure, arterial and mixed venous oxygen tension, arterial oxygen content, and alveolar-arterial oxygen gradient. Opioid administration was associated with significantly (P < 0.05) lower values than was saline administration for heart rate, mean arterial blood pressure, and arterial and mixed venous pH and with higher values for stroke index, pulmonary capillary wedge pressure, and arterial and mixed venous carbon dioxide tension. Prior oxymorphone administration resulted in the highest (P < 0.05) values for mean pulmonary blood pressure, venous admixture, and arterial and mixed venous carbon dioxide tension, and the lowest values for arterial oxygen tension, and arterial and mixed venous pH. Each treatment provided otherwise uncomplicated anesthetic induction, maintenance, and recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Intravenous↗

Pharmacokinetics of midazolam administered concurrently with ketamine after intravenous bolus or infusion in dogs.

Midazolam, a water-soluble benzodiazepine tranquilizer, has been considered by some veterinary anaesthesiologists to be suitable as a combination anaesthetic agent when administered concurrently with ketamine because of its water solubility and miscibility with ketamine. However, the pharmacokinetics of midazolam have not been extensively described in the dog. Twelve clinically healthy mixed breed dogs (22.2-33.4 kg) were divided into two groups at random and were administered ketamine (10 mg/kg) and midazolam (0.5 mg/kg) either as an intravenous bolus over 30 s (group 1) or as an i.v. infusion in 0.9% NaCl (2 ml/kg) over 15 min. Blood samples were obtained immediately before the drugs were injected and periodically for 6 h afterwards. Serum concentrations were determined using gas chromatography with electron-capture detection. Serum concentrations were best described using a two-compartment open model and indicated a t1/2-alpha of 1.8 min and t1/2-beta of 27.8 min after i.v. bolus, and t1/2-alpha of 1.35 min and t1/2-beta of 31.6 min after i.v. infusion. The calculated pharmacokinetic coefficient B was significantly smaller after i.v. infusion (429 +/- 244 ng/ml) than after i.v. bolus (888 +/- 130 ng/ml, P = 0.004). Furthermore, AUC was significantly smaller after i.v. infusion (29,800 +/- 6120 ng/h/ml) than after i.v. bolus (42,500 +/- 8460 ng/h/ml, P < 0.05), resulting in a larger ClB after i.v. infusion (17.4 +/- 4.00 ml/min/kg than after i.v. bolus (12.1 +/- 2.24 ml/min/kg, P < 0.05). No other pharmacokinetic value was significantly affected by rate of intravenous administration.

Anesthesia↗

Increased expression of human leukocyte antigen-DR on pulmonary macrophages in bronchopulmonary dysplasia.

We used an immunoperoxidase method to examine the expression of the immune activation marker HLA-DR on pulmonary tissue obtained at autopsy from 14 patients dying of bronchopulmonary dysplasia. Controls consisted of 16 age-matched, sex-matched children dying of noncardiac, nonrespiratory, noninfectious illnesses or as a result of motor vehicle accidents. We did not observe aberrant expression of HLA-DR on pulmonary endothelial cells. Positive staining appeared exclusively on macrophages. We quantitated the expression of antigen by counting the number of positive macrophages and total macrophages/monocytes per high power field. Bronchopulmonary dysplasia patients displayed significantly greater numbers of both positive and total macrophages compared with the control group (p < 0.05). The percent positive macrophages also was significantly higher in the bronchopulmonary dysplasia patients (p < 0.005). We also examined a group of patients dying with infant respiratory distress syndrome. There was no significant difference in number of total macrophages in this group compared with age-matched controls.

Bronchopulmonary Dysplasia↗

Cardiorespiratory effects of intravenous bolus administration and infusion of ketamine-midazolam in dogs.

Twelve healthy dogs were used to determine the cardiorespiratory effects of i.v. administered ketamine (10 mg/kg of body weight) and midazolam (0.5 mg/kg). Half the dogs received a ketamine-midazolam combination (K-M) as a bolus over 30 seconds and the other half received the K-M as an infusion over 15 minutes. Induction of anesthesia by use of K-M was good in all dogs. Ketamine-midazolam combination as a bolus or infusion induced minimal cardiorespiratory effects, except for significant (P < 0.05) increases in mean heart rate and rate-pressure product. The increase in heart rate was greater in dogs of the infusion group. Mild and transient respiratory depression was observed in dogs of both groups immediately after administration of K-M, but was greater in dogs of the bolus group than in dogs of the infusion group. Duration of action of K-M for chemical restraint was short. Salivation and defecation were observed in a few dogs. Extreme muscular tone developed in 1 dog after K-M bolus administration.

Administration, Oral↗

Cardiovascular effects of intravenous bolus administration and infusion of ketamine-midazolam in isoflurane-anesthetized dogs.

Cardiovascular effects of IV administered ketamine (10 mg/kg) and midazolam (0.5 mg/kg) were determined in 12 healthy isoflurane-anesthetized (1.7% end-tidal concentration) dogs. Six dogs received a ketamine-midazolam combination (K-M) as a bolus over 30 seconds and 6 dogs received K-M as an infusion over 15 minutes. Ketamine-midazolam combination as a bolus and an infusion caused early significant (P < 0.05) reductions in mean systemic blood pressure, cardiac index, and stroke index, which returned to baseline values near the end of the study. Heart rate decreased significantly (P < 0.05) in dogs of the infusion group and returned to the baseline value near the end of the study. One dog died after K-M bolus administration. Mean maximal decreases from baseline for systemic blood pressure, cardiac index, and stroke index were significantly (P < 0.05) greater in dogs of the bolus group than in dogs of the infusion group; therefore, cardiovascular effects of K-M after infusion were less severe than those after bolus. Base excess and pHa decreased significantly (P < 0.05) in the infusion group, although similar changes occurred in both groups. Four dogs were maintained with 1.7% end-tidal isoflurane to determine temporal effects of isoflurane; these dogs did not receive K-M. Increases in heart rate, cardiac index, stroke index, and left and right ventricular stroke work indexes were significant (P < 0.05) at various sample collection intervals, particularly during the later stages of the study. Isoflurane anesthesia effectively blocked the cardiostimulatory properties of K-M.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Comparison of Telazol, Telazol-ketamine, Telazol-xylazine, and Telazol-ketamine-xylazine as chemical restraint and anesthetic induction combination in swine.

The use of Telazol (T, tiletamine and zolazepam, 4.4 mg T/kg) alone, Telazol-ketamine (TK, 4.4 mg T/kg and 2.2 mg K/kg), Telazol-xylazine (TX, 4.4 mg T/kg, 2.2 mg X/kg), and Telazol-ketamine-xylazine (TKX, 4.4 mg T/kg, 2.2 mg K/kg, and 2.2 mg X/kg) as chemical restraint and anesthetic induction combination was compared in pigs. Forty mixed-breed healthy pigs (24.4 +/- 5.6 kg, mean +/- SD) were randomly assigned to the four treatment groups (T, TK, TX, TKX) with 10 pigs in each group. All the anesthetics were premixed by adding sterile water, ketamine, xylazine, or xylazine and ketamine directly into the Telazol vial and given as a single intramuscular injection. All four anesthetic combinations induced a rapid onset of sternal recumbency within 1.76 +/- 1.0 minutes and lateral recumbency within 3.02 +/- 2.2 minutes in pigs after intramuscular injection; there was no significant difference among treatments. The combinations TX and TKX induced analgesia (as evident by a lack of response to needle prick in the middle portion of the pinna and flank regions) duration of 29.0 +/- 11.0 and 36.0 +/- 12.2 minutes, respectively, and ability to tolerate tracheal intubation (as evident by lack of coughing and chewing response to a laryngoscope) for a period of 34.0 +/- 8.4 and 39.0 +/- 9.9 minutes, respectively. The combinations T and TK did not induce analgesia nor conditions suitable for intubation. Duration of lateral recumbency was 29.9 +/- 10, 33.1 +/- 6.9, 52.2 +/- 6.9, and 61.5 +/- 10.7 minutes in T-, TK-, TX-, and TKX-treated pigs, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia Recovery Period↗

Effects of a 44-day administration of phenobarbital on disposition of clorazepate in dogs.

The disposition of clorazepate, a benzodiazepine anticonvulsant, was determined in dogs after administration of a single oral dose of clorazepate (2 mg/kg of body weight) and after oral administration of clorazepate (2 mg/kg, q 12 h) concurrently with phenobarbital (5 mg/kg, q 12 h) for 44 consecutive days. Serum concentrations of nordiazepam, the active metabolite of clorazepate, were measured. After a single oral dose of clorazepate, maximal nordiazepam concentrations ranged from 569.6 to 1,387.9 ng/ml (mean, 880.2 +/- 248.9 ng/ml) and were detected 16.8 to 131.4 minutes (mean, 85.2 +/- 36 minutes) after dosing. After administration of phenobarbital for 44 consecutive days, maximal nordiazepam concentrations were significantly (P < 0.01) lower, ranging from 209.6 to 698.5 ng/ml (mean, 399.3 +/- 155.6 ng/ml) at 68.4 to 145.8 minutes (mean, 93 +/- 25.8 minutes) after dosing. Mean area under the curve (AUC) on day 1 (mean, 3.37 +/- 0.598 ng.min/ml) was significantly (P < 0.001) greater than AUC on day 44 (1.66 +/- 0.308 ng.min/ml). Oral clearance was significantly (P < 0.01) greater on day 44 (12.44 +/- 2.55 ml/min/kg), compared with that on day 1 (6.16 +/- 1.35 ml/min/kg). Values for area under the first moment curve, oral volume of distribution, mean residence time, and elimination half-life were not significantly altered by concurrent administration of phenobarbital. Administration of phenobarbital altered the disposition of clorazepate such that the amount of nordiazepam in circulation during each dose interval was significantly reduced. Adequate control of seizures in epileptic dogs, therefore, may require higher dosages of clorazepate when it is coadministered with phenobarbital.

Administration, Oral↗

Evaluation of accuracy of pulse oximetry in dogs.

The accuracy of a pulse oximeter was evaluated over a wide range of arterial oxygen and carbon dioxide tensions, using 2 probes (finger probe and ear probe) and 2 monitoring sites (tongue and tail) in anesthetized dogs. The arterial oxygen saturation of hemoglobin (SaO2) measured directly with a multiwavelength spectrophotometer was compared with saturation estimated by pulse oximetry (SpO2). Linear regression analysis of the pooled data from 399 simultaneous measurements of SpO2 and SaO2 indicated a highly significant correlation of SpO2 with SaO2 (r = 0.97; P less than or equal to 0.0001). Although the mean difference (+/- SD) between SpO2 and SaO2 for pooled data was small (-0.06 +/- 6.8%), SpO2 tended to underestimate high SaO2 values (greater than or equal to 70%) and to overestimate low SaO2 values (less than 70%). When SaO2 values were greater than or equal to 70%, the ear probe applied to the tail was less accurate (produced a significantly greater SpO2-SaO2 difference) than the ear probe on the tongue, or the finger probe at either site. When SaO2 values were less than or equal to 50%, the finger probe applied at the tail was more accurate (produced significantly smaller SpO2-SaO2 differences) than the ear probe at either site. When SaO2 values were less than or equal to 70%, high arterial carbon dioxide tension (greater than or equal to 60 mm of Hg) was associated with greater overestimation of SaO2.

Animals↗

A comparison of end-tidal halothane concentrations measured at proximal and distal ends of the endotracheal tube in the horse.

Measurements (n = 126) of end-tidal halothane concentrations were taken from 21 horses anesthetized for routine and emergency surgery. One hundred five paired values allowed comparison of gas samples taken near the oral end of the endotracheal tube (Y1) to samples obtained at the cuffed end of the endotracheal tube (Y2). Twenty-one paired readings were assessed to compare samples taken 25 cm beyond the cuffed end of the tube (Y3) to samples from Y1. Measurements were made at all locations at 15-minute intervals starting 30 minutes after beginning halothane. All measurements were made in triplicate at end-expiration, and both sites were sampled within 1 minute of each other. Halothane concentration was measured by rapid infrared analysis with a gas sampling rate of 150 ml/min and displayed as a digital reading. Calibration of the machine was checked regularly. The difference between readings (Y1-Y2 or Y1-Y3 = Sdif) was tested using general linear models and a significance level of p less than 0.05 was used. The variable Sdif was analyzed with respect to time, mode of ventilation, and type of recumbency; no effects of these variables were detected. The mean values (+/- SD) of 105 readings for Y1 and Y2 were 2.41 vol% (+/- 0.49) and 2.39 vol% (+/- 0.49) respectively, and the Pearson's correlation coefficient (Y1 vs Y2) was 0.96. The mean values (+/- SD) of 21 measurements for Y1 and Y3 were 2.31 vol% (+/- 0.27) and 2.32 vol% (+/- 0.28) respectively and the Pearson's correlation coefficient (Y1 vs Y3) was 0.98.

Anesthesia, Inhalation↗

Anesthesia for head and neck surgery.

Anesthesia in patients for surgery of the head and neck should begin with evaluation of the animal's medical history, laboratory data, and physical examination. This information plus knowledge of the physiologic changes induced by abnormalities and surgery of the head and neck provide the basis for selection of anesthetic regimens and techniques. The regimen should include drugs that produce minimal impact on organ systems, especially those systems lacking physiologic reserve because of disease. Establishment of a patent airway, protection of the airway, and control of ventilation should receive primary attention. Monitoring and support of cardiopulmonary function and maintenance of fluid volume and renal function are essential. The patient should be observed until protective reflexes return and recovery is complete. Postoperative pain should be managed with analgesics.

Anesthesia↗

Real-time microcomputer-based analysis of spontaneous and augmented labor.

In an attempt to develop a reproducible, objective measure of adequate uterine activity in labor, real-time measurements of intrauterine pressure amplitude and contraction frequency, interval, duration, and integral were made in 54 patients, 11 of whom received oxytocin augmentation. We determined the active pressure integral required per centimeter of cervical dilatation, expressed in kPa seconds, and the mean active pressure, expressed in kPa. The augmented group had a significantly higher mean active pressure integral per centimeter than those in normal labor (P less than .01). There was a trend, which did not reach statistical significance, for subjects who required oxytocin augmentation of labor to develop a higher mean active pressure than those in normal labor. However, the correlation of any uterine contractility index (Montevideo units, Alexandria units, mean active pressure) with progress in labor was poor. We conclude that women with dysfunctional labor require more uterine activity for progress in labor than women with normally progressing labor, and that the computer-derived "area under the curve" is not a better predictor of labor progress than Montevideo units.

Adult↗

A population-based study of maternal and perinatal outcome in patients with gestational diabetes.

A prospective population-based study of gestational diabetes mellitus was done with 2272 patients to determine perinatal and maternal outcomes. A large data base was collected on all patients. Patients with gestational diabetes mellitus were older, shorter, heavier, and had more children than did the control group. The higher cesarean section rate in the patients with gestational diabetes mellitus was explained by their increased rate of repeat cesarean section compared with control patients. This was associated with increased infectious complications. Other maternal complication rates were similar in the two groups. Acceptable glucose control did not normalize birth weight percentiles in patients with gestational diabetes mellitus. Maternal weight at delivery was the only significant predictor of birth weight percentile in the group with gestational diabetes mellitus. Plasma glucose levels were a poor predictor of birth weight percentile. Factors associated with maternal obesity in well-controlled gestational diabetes mellitus may be more significant than glucose control in the development of large-for-gestational-age infants.

Adult↗

Modulation of the major histocompatibility complex antigen and the immunogenicity of islet allografts.

Modulation of major histocompatibility complex (MHC) antigen by parenchymal cells and "passenger leukocytes" is a common feature of allograft rejection. To assess its significance we have examined the fate of antigen-presenting cell (APC)-depleted pancreatic islet allografts subsequent to increasing their expression of MHC antigens by in vitro exposure to the lymphokine interferon-gamma (gIFN). While most untreated grafts survived indefinitely, gIFN-exposed grafts were acutely rejected. Using in vitro islet cell-lymphocyte coculture assays, we attempted to dissect the underlying mechanism of enhanced islet cell immunogenicity resulting from gIFN treatment. We determined that gIFN exposure did not affect the capacity of islet cells to serve as APC for T lymphocytes, however islet cell exposure to gIFN was associated with enhanced vulnerability to allogeneic cytotoxic T lymphocyte (CTL) lysis in vitro by an CD5+ (OX-19+), CD8+ (OX-8+), CD4- (W3/25-), class I-restricted CTL. On the basis of these findings, we conclude that antigenic modulation can be a decisive factor in the survival of engrafted tissues by augmenting the interaction of the graft antigens with cytolytic effector T lymphocytes.

Animals↗

Prevention of recurrent diabetes in BB rats after islet transplantation by monoclonal antibody therapy.

Two immune responses imperil pancreatic islet allografts transplanted into subjects afflicted with autoimmune diabetes: 1) the well-described allograft response that is mounted against tissues bearing foreign transplantation antigens and 2) a recurrence of the beta-cell-specific autoimmune process responsible for the primary disease. To define the role of autoimmune response to transplanted islets, the possibility of a rejection response must be prevented. To accomplish this in spontaneously diabetic BB rats, we induced neonatal tolerance. We found that recurrent autoimmunity in tolerant BB rats can be prevented by treatment of recipients with the monoclonal antibody OX8 (specific for cytotoxic T-lymphocytes) but not W3/25 (specific for helper T-lymphocytes). These findings provide direct evidence for the role of OX8-bearing lymphocytes in autoimmune diabetogenesis.

Animals↗