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Biomedical subjects

M Jacobs

Publications and source records attributed to M Jacobs.

At least 217 records · Page 12Linked to original sources

In vitro activity of amiloride combined with tobramycin against Pseudomonas isolates from patients with cystic fibrosis.

The diuretic amiloride has been under recent investigation as adjunctive therapy for pulmonary disease in children with cystic fibrosis (CF). In preliminary studies, the antimicrobial activity of this agent alone or combined with beta-lactam agents against reference strains of Pseudomonas aeruginosa and P. cepacia was poor; however, amiloride was markedly synergistic with tobramycin against P. cepacia. The purpose of this study was to determine the extent of amiloride-tobramycin synergy against CF respiratory isolates of P. aeruginosa, P. cepacia, and P. maltophilia. The MICs of tobramycin and amiloride alone against the Pseudomonas test strains were determined by agar dilution. Synergy was determined by combining each of four subinhibitory concentrations of amiloride (at least fourfold below the MIC) with doubling dilutions of tobramycin and comparing the MIC of tobramycin alone and in combination for each strain. At the highest concentration tested, the drug combination synergistically inhibited 50% of the P. cepacia strains tested; the combination was synergistic against fewer isolates of P. aeruginosa and P. maltophilia. Only P. cepacia was inhibited by tobramycin combined with amiloride at achievable airway concentrations. We conclude that the combination of tobramycin and amiloride may be potentially useful in the treatment of P. cepacia infections in children with CF.

Amiloride↗

Progressive myoclonus epilepsy treated with zonisamide.

Two patients with progressive myoclonus epilepsy of the Unverricht-Lundborg type and with intractable seizures in spite of standard anticonvulsant regimens were treated with zonisamide. After zonisamide therapy was initiated, both had a marked decrease in seizure frequency and significant improvement of functioning. Serum zonisamide concentrations were 43 and 27 micrograms/ml, respectively, with doses of 8.8 and 10.5 mg/kg/d. Both patients also continue to receive valproic acid and a benzodiazepine.

Adult↗

Consultation among peers in general practice; from no consultation to peer review.

The present study concerned several aspects of peer consultation by general practitioners, investigated in a group of 184 doctors (response rate: 83%) who had their vocational training in the department of general practice of the University of Utrecht and practised for at least three years at the time of the study. Questionnaire responses indicated that consultation during and outside surgery hours and participation in case-discussion groups generally extended over more than two years, occurred frequently, and usually pertained to diverse problems associated with diagnosis and treatment. Participation in study and peer review groups extended usually over a shorter time (1 to 1 1/2 years) and the problems dealt with were predominantly the same as for individual consultation. One-third of the general practitioners consulted colleagues frequently and continued to do so for long periods, dealing systematically with a variety of problems; one-third did so infrequently or unsystematically, and one-third did little or not at all. A relationship was found between the setting of the practice and consulting behaviour: 20% of those who practised alone never consulted peers, whereas those in group practices and health centres were accustomed to do so regularly.

Family Practice↗

Cross-clamping the thoracic aorta. Effect on intracranial pressure.

A clinical case is reported indicating that intracranial pressure (ICP) rises with cross-clamping of the thoracic aorta (CCTA) in humans and does not fall if arterial blood pressure (BP) is lowered by nitroprusside. Hantler and Knight (Anesthesiology 1982;56:146-147) also reported a similar case. We investigated this phenomenon prospectively, measuring ICP, aortic arch BP, and right atrial pressure in 10 halothane-anesthetized New Zealand White rabbits ventilated to pH 7.45-7.55. When CCTA was applied, BP and ICP rose significantly (by paired t test, p less than or equal to 0.01), although right atrial pressure did not change. After removal of the cross-clamp and a period of stabilization, BP was elevated to the same level as that attained with CCTA with phenylephrine. Although phenylephrine induced BP elevation, neither ICP nor CVP changed significantly from control or recovery measurements. In six animals, after applying CCTA, BP was lowered to control levels with nitroprusside (in combination with CCTA). Nitroprusside was effective in lowering BP to control level, but ICP remained elevated as long as the cross-clamping continued. With no rise in central venous pressure, venous engorgement is an unlikely mechanism for ICP elevation. Time constants of ICP change are too short to invoke increased cerebral spinal fluid production or decreased absorption. BP does not rise above the expected range for autoregulation, but recruitment of either arterial capacitance vessels or of a neuroreflex arc, or the effects of cord ischemia disrupting cerebral autoregulation may be the cause of an acute increase in cerebral blood volume.

Animals↗

Rates of protein synthesis in brain and other organs.

We previously found a decrease in protein synthesis in brain during development, which was much greater as measured in brain slices than in brain in vivo. In the present work such changes in brain were compared to those in other organs. With measurement of incorporation of flooding doses of [14C]valine into proteins of organs, the highest synthesis rate in the adult animal in vivo was found in liver (2.2%) followed by kidney (1.8%), spleen (1.6%), lung (1.0%), heart (0.7%), brain (0.6%) and muscle (0.5%). In immature animals the synthesis rate was highest in spleen (2.6%) followed by liver (2.4%), kidney (1.7%), lung (1.6%), brain (1.5%), heart (1.1%), and muscle (0.9%). Protein synthesis in slices from each tissue proceeded at lower rates than in vivo, especially in adults. The tissue affected the most by the preparation of the slices was muscle.

Aging↗

The superiority of cold oxygenated dilute blood cardioplegia.

It has been clearly shown, both in a laboratory model and in humans, that oxygenation of crystalloid cardioplegic solutions markedly enhances myocardial preservation. The addition of a small volume of red cells to a crystalloid perfusate improves capillary perfusion. Based on these results, we have changed our cardioplegic solution from cold crystalloid to cold oxygenated dilute blood. In the present study we retrospectively evaluate the results of 400 operative procedures to determine whether the addition of oxygenation and a small volume of blood to the cardioplegic solution enhances myocardial protection in the clinical setting. Two hundred consecutive patients who underwent operation with cardioplegic arrest using a cold crystalloid cardioplegic solution (group 1) were compared with a subsequent 200 patients who underwent operation with cold oxygenated dilute blood cardioplegia (group 2). Patients in group 2, who received cold oxygenated dilute blood cardioplegia, had a significantly reduced need for postoperative intraaortic balloon pump counterpulsation and for atrioventricular pacing. Also, patients in group 2 had a lower incidence of perioperative myocardial infarction and had improved early outcome. None of the 200 patients in group 2 had electrocardiographic evidence of perioperative infarction. We conclude that cold oxygenated dilute blood cardioplegia provides better preservation than does a nonoxygenated crystalloid solution during elective ischemic arrest, because a cold crystalloid solution is able to deliver oxygen and the red cells are able to enhance capillary perfusion.

Blood↗

Percutaneous balloon valvotomy for patients with severe mitral stenosis.

Thirty-five patients with severe mitral stenosis underwent percutaneous mitral valvotomy (PMV). There were 29 female and six male patients (mean age 49 +/- 3 years, range 13 to 87). After transseptal left heart catheterization, PMV was performed with either a single- (20 patients) or double- (14 patients) balloon dilating catheter. Hemodynamic and left ventriculographic findings were evaluated before and after PMV. There was one death. Mitral regurgitation developed or increased in severity in 15 patients (43%). One patient developed complete heart block requiring a permanent pacemaker. PMV resulted in a significant decrease in mitral gradient from 18 +/- 1 to 7 +/- 1 mm Hg (p less than .0001) and a significant increase in both cardiac output from 3.9 +/- 0.2 to 4.6 +/- 0.2 liters/min (p less than .001) and in mitral valve area from 0.8 +/- 0.1 to 1.7 +/- 0.2 cm2 (p less than .0001) Effective balloon dilating diameter per square meter of body surface area correlated significantly with the decrease in mitral gradient but did not correlate with the degree of mitral regurgitation. There was no correlation of age, prior mitral commissurotomy or mitral calcification with hemodynamic results. PMV is an effective nonsurgical procedure for patients with mitral stenosis, including those with pliable valves, those with previous commissurotomy, and even those with mitral calcification.

Adolescent↗

A controlled study of progabide in partial seizures: methodology and results.

The results of a multicenter, double-blind, placebo-controlled clinical trial of the efficacy and safety of progabide (PGB) in the treatment of partial seizures are presented. This study was performed with a number of rigorous controls not usually present in clinical trials. These included uniform co-medication in which all patients received only phenytoin and carbamazepine; concentrations of these two drugs were maintained within narrow, predefined concentration ranges. There was no statistically significant difference between PGB and placebo in seizure frequency and seizure duration for most of the analyses performed. One patient was withdrawn from the study because of hepatotoxicity. PGB was associated with a significant inhibition of phenytoin but not carbamazepine clearance. The results of this study indicate that PGB was not a potent antiepileptic drug in this population of persons with intractable epilepsy.

Adolescent↗

Comparison of alprazolam and imipramine for treatment of outpatient depression.

A 6-week double-blind comparison of the therapeutic efficacy of alprazolam and imipramine in 90 depressed psychiatric outpatients revealed a significantly superior response to alprazolam in the first 2 weeks of treatment as measured by total scores on the Hamilton Rating Scale for Depression and the Brief Psychiatric Rating Scale. Further analyses revealed that all significant differences could be accounted for by the superior effect of alprazolam on sleep disturbance. By the end of Weeks 4 and 6, no significant differences in therapeutic response between the two treatment groups were noted, with patients in both groups evidencing improvement on all measures. A differentially high dropout rate among patients in the imipramine treatment group posed a problem for interpretation of results in the latter weeks of treatment.

Adolescent↗

Rates of amino acid incorporation into particulate proteins in vivo and in slices of young and adult brain.

Incorporation of a flooding dose of valine into brain proteins was measured in vivo and in brain slices, according to subcellular fraction and to solubility. In particulate fractions in vivo in the immature brain, soluble cytosol proteins had the highest synthesis rates (2.0% per hr), followed by microsomes (1.7%), mitochondria, nuclei (1.4%), and synaptosomes (0.85%). In adult, the rates were about half of those of immature animals except for microsomes, which were the same. In young, rates of incorporation into particles in brain slices were about 80% of in vivo rates, and adult rates were 10-20% of the in vivo rates. When brain proteins were fractionated into four groups--isotonic soluble, hypotonic soluble, Triton X-100 soluble, and the remainder solubilized in 0.2% SDS--in both young and adult brain in vivo, the isotonic fraction had the highest rate of protein synthesis, followed by the Triton-soluble fraction, the SDS-soluble fraction, and the hypotonic fraction. Also, with this method of separation in vitro rates for immature brain were 10-20% lower than in vivo rates, while in vitro adult rates were 80-90% lower. The results indicate that the most proteins are synthesized at a higher rate in the immature brain, and that the difference between in vivo and brain slice protein synthesis is not as great in the immature as in the mature brain in all the fractions examined.

Amino Acids↗

Amino acid incorporation in relation to molecular weight of proteins in young and adult brain.

Rates of protein synthesis were studied in immature and adult rat brain tissue. After an amino acid incorporation period, in vivo or in incubated slices from brain, the soluble protein was fractionated according to molecular weight by column chromatography. In examining soluble whole proteins, no direct correlation between molecular weights and synthesis rates could be established; the highest synthesis rates were found in fractions around 70,000 MW and below 10,000. Incorporation into the subunits after fractionation by SDS gel electrophoresis was proportional to subunit molecular weight, with rates of incorporation into the largest subunits being the highest. The results suggest a relationship between turnover rate and structure of subunits of brain proteins.

Aging↗

Basal and forskolin-stimulated cyclic adenosine monophosphate in intact human platelets during the menstrual cycle.

In previous studies we observed modifications of cyclic adenosine monophosphate and adenylate cyclase activity in human endometrium during the menstrual cycle. In the present study our intension was to verify whether these modifications occur in isolated intact platelets. The results demonstrate that in nine normal women platelet cyclic adenosine monophosphate content varies during the menstrual cycle both in basal and in stimulated conditions (in vitro addition of forskolin). In fact, significantly higher levels of cyclic adenosine monophosphate were consistently observed during the proliferative phase. These findings provide evidence that platelet cyclic adenosine monophosphate metabolism normally varies during the menstrual cycle, which suggests a possible involvement of this system in some important clinical events.

Adolescent↗

Regional and cellular differences in rat brain protein synthesis in vivo and in slices during development.

We compared the rate of protein synthesis in immature and adult rat brain in vivo to that in brain slices. After the incorporation of a flooding dose of [14C]valine, in vivo and in brain slices, the label in proteins was measured in CNS regions and in neuron- and glia-enriched fractions. In regions in vivo in the adult, incorporation rates in corpus callosum were lower than in other regions, which were similar; in the young, cerebellum showed the highest rates and hypothalamus and cord the lowest. Since hypothalamus and cord were low in the young, there was no change during development in these two areas; in other areas incorporation rates in young were 2-3 times higher than in adult brain proteins. Incorporation rates in slices were lower than in vivo. In the young, cerebellum, olfactory bulb, and cord were close to in vivo, and other areas in slices from young incorporated at 60-90% of in vivo rates. In adult slices incorporation was 5-15% of that in vivo except in olfactory bulb, where it was 30%. In the cellular fractions, incorporation in vivo in young was close in the neuronal and glial fractions; in adults incorporation rates in neurons were higher, as the decrease in development was less in neurons than astrocytes. In slices in young, astrocytes incorporated amino acids at 100% of the in vivo rates, neurons at 60%; in adult slices, incorporation was at only 4-7% of the in vivo rate. The results show that developmental changes in protein metabolism occur in all brain areas and brain cells, with metabolic rates in young 2-3 times that in adult.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Characteristics of psychiatric patients who engage in assaultive or other fear-inducing behaviors.

The hospital records of 1687 psychiatric patients were rated for the presence of assaultive or other fear-inducing behaviors associated with the reasons for their hospital admissions. Data analyses indicated that significant associations existed between these behaviors and sex, race/ethnicity, diagnosis, previous admissions, referral source for hospitalization, legal status at admission, and legal status at discharge. No associations were found for age, education, marital status, employment status, number of days hospitalized during the index hospitalization, and referral at discharge. A comparison of these results with the results of studies by other investigators led to the conclusion that clinical variables appear to have a more consistent relation to violent behavior than demographic variables. Future research examining for the correlates of violent behavior in psychiatric patients may be more productive by focusing on the type and degree of patients' psychopathologies rather than on patients' demographic characteristics.

Adolescent↗

Serum CA 125 in ovarian pathology and its variation in ovarian carcinoma after integrated therapy.

Serum CA 125 was detected by RIA in a total of 66 patients with various ovarian pathologies (16 malignant and 50 benign). Six patients with ovarian carcinoma were monitored during the 1st week after surgery (2 patients underwent only explorative laparatomy) and during chemotherapy for a total of 150 days of treatment. We observed that CA 125 serum level is consistently above the normal range (greater than 35 U/ml) in all malignant diseases. In benign pathology, levels above the normal were found to be represented almost exclusively by ovarian endometriosis. Furthermore, the results demonstrate that the chemotherapeutic regime alone is capable of lowering CA 125 serum levels.

Antigens, Neoplasm↗

Cloning, sequencing and expression of subtilisin Carlsberg from Bacillus licheniformis.

The gene encoding subtilisin Carlsberg from Bacillus licheniformis has been isolated by molecular cloning using a mixture of synthetic oligonucleotides. The entire nucleotide sequence of the coding sequence as well as 5' and 3' flanking sequences have been determined. The deduced amino acid sequence reveals an N-terminal signal peptide consisting of 29 residues, a pro-peptide of 76 residues followed by the mature protein comprising 274 residues. The ATG initiator codon is preceded by two putative overlapping ribosomal binding sequences. A palindromic sequence typical for transcription termination is found downstream from the TAA stop codon. Structural comparisons between different known subtilisin genes reveal extensive homology, particularly in the parts coding for the pro-region and the mature protein. Expression studies in Bacillus subtilis show that the cloned fragment produces a functional enzyme when inserted after a B. subtilis promoter.

Amino Acid Sequence↗