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Biomedical subjects

L Jacobs

Publications and source records attributed to L Jacobs.

At least 91 records · Page 5Linked to original sources

Clinical and magnetic resonance imaging in optic neuritis.

We found 23 of 48 patients (48%) with isolated monosymptomatic optic neuritis (ON) to have 1 to several brain lesions by MRI. All the brain lesions were clinically silent and had characteristics consistent with multiple sclerosis (MS). During 4 years of follow-up, 9 patients (19%) developed definite MS on clinical grounds. Six of the converting patients had abnormal MRIs; the other 3 had MRIs that were normal both initially (when they had ON only) and when repeated after they had developed MS. The other 17 patients with abnormal MRIs have not developed symptoms or signs of MS during follow-up. Thus, an abnormal MRI does not auger development of clinical MS within a mean of 4 years, nor does a normal MRI protect against development of disseminated disease. It is not prudent to give a patient with isolated monosymptomatic ON the diagnosis of MS (probable or definite) because of an abnormal MRI (with or without other laboratory abnormalities).

Adolescent↗

A randomized trial of replacement antioxidant vitamin therapy for neutrophil locomotory dysfunction in blunt trauma.

Studies in patients with serious trauma indicate that the observed neutrophil (PMN) locomotory dysfunction is partly the result of auto-oxidation as shown by evidence of preactivation, diminished reducing capacity, and low serum and cellular ascorbic acid and alpha-tocopherol. To investigate whether replacement of the antioxidant vitamins ascorbic acid and alpha-tocopherol can improve the PMN locomotory defect, ascorbic acid, alpha-tocopherol, ascorbic acid and alpha-tocopherol, or placebo was administered to a total of 46 victims of blunt trauma. PMN locomotion was quantitated using a micropore filter assay. Locomotion data were analyzed by repeated measures analysis with a split plot design and data for days 2-6 after injury were compared. Compared with placebo, the antioxidants improved PMN locomotion. The mean differences in distance migrated (treated minus placebo) were ascorbic acid and alpha-tocopherol = 11.3 +/- 3.0 microns (one-tailed p = 0.001) (mean +/- SE); ascorbic acid = 4.7 +/- 3.4 microns (p = 0.19); and alpha-tocopherol = 3.3 +/- 2.9 microns (p = 0.27). Although both antioxidants given together produced the best results, a plot of the 95% confidence intervals indicates that ascorbic acid and alpha-tocopherol, either given alone, were also better than placebo. We conclude that antioxidant replacement therapy significantly improves the PMN locomotory abnormality in blunt trauma.

Adult↗

A baboon model for in vivo assessment of mucociliary lung clearance.

A suitable baboon model (Papio ursinus) for assessing inhibitory effects on mucociliary lung clearance was required. Clearance of various dimensions of nebulized particles (99mTc-labelled) was monitored with the animals (n = 6) under either ketamine or pentobarbitone anaesthesia. The best prospect of substantial and reproducible clearance in spite of the inhibition by the anaesthesia were obtained with pentobarbitone, and using nebulized radiolabelled particles of diameter range between 10 and 45 microns, thus avoiding trapping in the non-ciliary alveoli.

Aerosols↗

Extracellular microfibrils are increased in localized and systemic scleroderma skin.

Extracellular microfibrils, about 10 nm thick with a hollow core have been found in most organs as free bundles or in association with elastic fibrils. Histochemistry of the dermis of 4 patients with localized and 6 with systemic scleroderma revealed numerous fine elastic fibrils in areas of fibrosis. Immunofluorescence and immunoelectron microscopy were performed with antibodies against fibrillin and amorphous elastin. The lower dermis revealed an increase in 10-nm microfibrils interspersed between collagen fibrils. These microfibrils stained for fibrillin but not for amorphous elastin. Fibrosis in localized and systemic scleroderma involves the deposition of collagen fibrils and microfibrils.

Extracellular Space↗

The construct validity of an aftereffect-based subtyping system for alcoholics.

In an earlier project, we identified five alcohol-consumption aftereffect factors, which were named Hangover, Euphoria, Flushing, Seizures, and Sleepiness. In this study (N = 100) we assessed the construct validities of the five, using 47 MMPI, self-report, and recidivism criteria. The number of significant relationships between the factors and the criteria substantially exceeded chance. The Hangover factor related to social maladjustment and to the MMPI Psychopathic Deviate, Paranoia, Psychasthenia, Hypomania, and Masculinity-Femininity scales. The Euphoria factor was associated with a high number of job losses, but a low incidence of certain physical sequelae. The Flushing factor was associated with high consumption, late development of alcoholism, many physical complaints, and older age. The Seizure factor correlated with high consumption, facial puffiness, tremors, and lack of defensiveness on the MMPI. The Sleepiness factor was associated with a good prognosis and several mild MMPI elevations. These findings suggest that the factors may provide the basis for a useful alcoholism subtyping system and that additional research on them should prove fruitful.

Adult↗

Investigation by scintigraphic methods of neutrophil kinetics under normal and septic shock conditions in the experimental baboon model.

The purpose of this study was the correlation of neutrophil kinetics with the pathogenic course of septic shock in the baboon model. Radioactively labelled neutrophils were traced in vivo in normal baboons (n = 6) and in Escherichia coli-infected baboons, which were reinjected with labelled autologous neutrophils either 2 h after the onset of the E. coli infusion (procedure A) (n = 3) or simultaneously with the infusion (procedure B) (n = 3). Cell isolation was done according to a method developed in this laboratory. The cells were labelled with tropolonate In 111, resuspended in 1-2 ml plasma and reinjected. One-minute images were taken every 5th min and then hourly for 4 h with a gamma camera and analysed with a data processor. Time-activity curves were obtained for neutrophil washout from the lungs and neutrophil accumulation in the liver and spleen. These curves were compared for normal baboons and for those treated according to procedures A and B. A significant retention of neutrophils in the lungs of baboons with E. coli-induced septic shock was noted as well as an abnormally slow rate of accumulation in the liver and spleen. It also seems that any lung injury which could be attributed to changes in neutrophil behaviour should be traced back to events during the early exposure of neutrophils to bacterial infection.

Animals↗

Additional evidence of autoxidation as a possible mechanism of neutrophil locomotory dysfunction in blunt trauma.

Previous studies in victims of blunt injury suggest that the observed neutrophil (PMN) locomotory dysfunction is, in part, due to autoxidation. To further clarify the occurrence and significance of autoxidation, we studied changes in levels of glutathione in PMN and of ascorbic acid and alpha-tocopherol in serum and blood cells of postsurgical and blunt trauma patients. Levels of total, reduced, and oxidized glutathione in PMN from trauma patients were similar to normal controls. Serum and cellular ascorbic acid and alpha-tocopherol levels dropped significantly after injury and remained below normal control levels during the 7 to 8-day study period. Low serum alpha-tocopherol was partially explainable on the basis of changes in serum lipids. When serum samples of trauma patients were thawed unprotected without pyrogallol, there was significant loss of recoverable alpha-tocopherol, whereas no significant losses occurred with unprotected thawed normal sera. Less total reducing capacity was observed in PMN of trauma patients compared with normal controls. These findings indicate that synthesis and regeneration capacity of glutathione are intact but that the levels of the consumable antioxidants, ascorbic acid, and alpha-tocopherol are compromised after injury. These results add further support to the hypothesis that autoxidation occurs in trauma.

Adolescent↗

Epitope analysis of glycoprotein I of pseudorabies virus.

A panel of 11 monoclonal antibodies (MAbs) raised against pseudorabies virus (PRV) was used to map epitopes on the virus glycoprotein I (gI). We employed three approaches to map epitopes on gI. By a competition binding assay, six groups of MAbs were defined as reacting with distinct antigenic domains on gI. To identify regions along the gI polypeptide chain encompassing the domains recognized by these MAbs, DNA fragments derived from the gI-coding region were cloned into pEX expression plasmids. The antigenic reactivity of the fusion proteins expressed in Escherichia coli was analysed by immunoblotting. Five antigenic domains were mapped within the first 238 amino acids of gI: domains A, B and D were mapped between amino acids 52 and 123 and domains C and E between amino acids 78 and 238. One MAb, representing domain F, did not react with the expressed fusion proteins. To assess the precise location and amino acid sequences of the epitopes, overlapping nonapeptides covering the amino acid sequence 52 to 238 were synthesized. The antibody-binding activity of these peptides was tested by an ELISA (Pepscan-method). Three antigenic domains were mapped: domain A was localized to amino acids 64 to 73 and 75 to 84, domain B to amino acids 52 to 67 and domain D to amino acids 68 to 82. Four MAbs representing antigenic domains C, E and F did not react in the Pepscan. Finally, sera from pigs infected experimentally with PRV reacted with the fusion protein of plasmid ps 1 (amino acids 52 to 238).

Amino Acid Sequence↗

Investigation by scintigraphic methods of platelet kinetics under normal and septic shock conditions in the experimental baboon model.

This study concerned the correlation of platelet kinetics with the pathogenic course of septic shock and adult respiratory distress syndrome (ARDS) in the anesthetised baboon model. 111In-tropolonate platelets were traced in vivo in normal baboons (n = 7) and in Escherichia coli-infected baboons, which were reinjected with the labeled autologous platelets either 2 hr after the onset of the E. coli infusion (procedure A: n = 4) or simultaneously with the infusion (procedure B; n = 3). One minute images were taken hourly for 5 hr, using a gamma camera and data processor. Time-activity curves were obtained for platelet clearance from the blood and the lungs and for platelet accumulation in the liver and spleen. A significant retention of platelets in the lungs of baboons with E. coli-induced septic shock was noted, as well as an accelerated clearance from the circulation. Platelets were distributed mainly to the spleen after induction of bacteremia, later substantially moved to the liver, and even later moved back to the spleen.

Animals↗

Preparation and biokinetic evaluation of various halogenated iminodiacetic acid-type compounds labeled with technetium-99m for hepatobiliary scintigraphy in the baboon (Papio ursinus) model.

In an evaluation of various 99mTc-labeled halogenated (F, Cl, Br, I) iminodiacetic acid (IDA) derivatives for hepatobiliary scintigraphy, it was found that, in the baboon model, none of these compounds performed as well as did disida. F-IDA was least effective, with the lowest biliary excretion and highest renal participation, but multihalogen substitution as in penta-F-IDA increased the biliary specificity and reduced urinary excretion to the extent that penta-F-IDA scored second to disida and even above I-IDA, with its high molecular weight. Surprising also was the relatively good performance of Cl-IDA compared to Br-IDA and I-IDA.

Animals↗

Using the "integral spleen" method of radiorenogram analysis and a baboon model to compare the diagnostic usefulness of technetium-99m-diethylenetriamine pentaacetic acid to that of various technetium-99m-mercaptoacetyltriglycene formulations and iodine-123-hippuran.

In light of the high price of commercially available mercaptoacetyltriglycene (MAG3) it was decided to attempt a local MAG3-formation and to test this against diethylenetriamine pentaacetic acid (DTPA), 123I-Hippuran, and commercial MAG3 for diagnostic radiorenographic capabilities also in conjunction with furosemide and captopril. A baboon model (n = 6) was used, and the parameters evaluated were obtained by the "integral spleen" method of radiorenogram analysis. Although the images and parameters pointed to 123I-Hippuran and commercial MAG3 as the ideal renal scanning agents and to DTPA as the least so, with the local product an acceptable alternative, the differences were not significant enough to warrant either the purchase of the commercial product or the extensive development of the local product. Inexpensive 99mTc-DTPA in conjunction with modern computer techniques will probably supply most of the answers.

Animals↗

Left ventricular volume and function changes during beta-blockade and accompanying atrial pacing.

Radionuclide ventriculography was performed at rest and during transoesophageal pacing on nine anaesthetized baboons (Papio ursinus), alternatively with and without administration of a beta-blocker. Left ventricular volumes, cardiac output, and ejection fraction were determined at each heart rate. A gradual decrease in end-diastolic, end-systolic, and stroke volume followed with increasing heart rate, significantly more pronounced under beta-blockade. Cardiac output and ejection fraction showed no significant changes, although tendencies to increase were observed without beta-blockade. Comparisons of these parameter changes were drawn to those previously observed during the first 5 h of septic shock (E. coli). We conclude that the tachycardia present during this phase of shock is not the only contributory factor to cardiac function changes but that other depressant influences prevail as the added effect of the beta-blocker seems to suggest.

Adrenergic beta-Antagonists↗

Changes in phase analysis patterns of radionuclide ventriculograms obtained from baboons during atrial pacing, septic shock, and induced myocardial infarction.

Changes in intraventricular phase delays, phase angle histograms, amplitude images, and electrocardiograms (ECG) were investigated during oesophageal pacing with and without beta-blockade, after induced myocardial infarction, and during septic shock in the anaesthetized baboon model. Unavoidable triggering from the pacemaker spike and to a lesser extent increased heart rate were responsible for parameter changes during pacing. Myocardial infarction changed contraction patterns, which did not always correlate with conduction changes from the ECG's. Cardiac volume changes during septic shock could be responsible for the abnormal trends in phase angle spread and electrocardiographic data.

Animals↗

The comparative recidivism rates of voluntary- and coerced-admission male alcoholics.

The outcomes of inpatient alcoholics who reported that they had been coerced into treatment by commitment or pressure from others were compared in a follow-up study to those of alcoholics who described themselves as voluntary admissions. Ten assessments of control over drinking, number of drinking days in the past week, and intoxication since previous appraisal were made by collaterals between 2 weeks and 18 months after treatment. Even though the data were analyzed in several ways, the number of significant differences did not exceed chance expectations. This suggests that the prognoses of alcoholics who present for treatment under court order or interpersonal pressure were not substantially different from those of men who claim to have entered without coercion. However, the differences between the groups' Control over Drinking ratings, even though not statistically significant, consistently favored the coerced admissions, which raises the possibility that their outcomes may have been slightly better than those of the voluntary admissions.

Adult↗

Neuropsychological improvement following endarterectomy as a function of outcome measure and reconstructed vessel.

30 patient receiving right or left carotid reconstruction and 15 medically matched controls were compared pre- and post-surgically on measures of motor speed, sustained vigilance, verbal memory and verbal and nonverbal intellectual function. The group receiving right sided vessel reconstruction demonstrated the largest post-operative improvement in intellectual function in any of the groups. The findings suggest that increased blood perfusion following right sided endarterectomy facilitates the right hemisphere's exclusive control of bilateral attention/arousal responses. In addition, findings suggest that detection of post-endarterectomy improvement may be dependent on the specific task dimension sampled, e.g., speed vs. cognitive ability and verbal-graphic vs. nonverbal symbol manipulation.

Carotid Arteries↗

Scintigraphic phase analysis of abnormal A-V conduction in a baboon.

During an interventional cardiac investigation on an anaesthetised baboon (Papio ursinus) the animal developed A-V block. Scintigraphic phase analysis leading to quantified intraventricular delays and histogram characteristics pointed to abnormalities which persisted even after A-V block was replaced by nodal tachycardia as was reflected by the electrocardiogram. This indicated towards an increased diagnostic sensitivity with the use of phase analytical methods.

Animals↗