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Biomedical subjects

A Martin

Publications and source records attributed to A Martin.

At least 721 records · Page 40Linked to original sources

On the nature of the verbal memory deficit in Alzheimer's disease.

Verbal memory was investigated in patients with Alzheimer's disease (AD) with previously documented deficits in word production and comprehension. Procedures were employed to evaluate word recall and recognition within the context of both "multistore" and "levels of processing" models of memory. In addition, memory abilities were evaluated with respect to performance on measures of verbal fluency and language comprehension. As expected, the AD patients performed significantly worse than normal individuals on all tasks. However, in each experiment their pattern of recall across conditions was found to be qualitatively similar to that produced by normal subjects. It was argued that the memory impairment associated with Alzheimer's disease may be largely due to an inability to encode a sufficient number of stimulus features or attributes. Furthermore, this encoding deficit includes, but is not limited to, semantic attributes. Similarities between the performance of the AD patients and reported findings with Korsakoff patients and normal subjects with "weak" memory were discussed.

Aged↗

Diminution of circulating polymorphonuclear leucocytes by administration of a monoclonal antibody reacting with granulocytes and monocytes.

The monoclonal antibody 3A35 which binds mouse polymorphonuclear leucocytes (PMN) and monocytes was injected intravenously (i.v.) into normal mice. A great diminution of circulating PMN was observed. The percentage of PMN passed through a minimum (2.5%) 20 min after antibody injection and returned to normal value (18.3%) within 24 h. After repeated daily injections, the ability of the antibody to induce granulopenia attenuated. Moreover, mice bearing the 3A35-producing hybridoma as an ascitic tumor had a normal percentage of blood PMN and a normal granulopoiesis as judged from bone marrow cytological examination. Thus, the monoclonal antibody produced a transitory diminution of PMN but could not induce a lasting granulopenia.

Animals↗

Clinical trial of 252Cf neutron brachytherapy vs. conventional radiotherapy for advanced cervical cancer.

252Cf, a neutron emitting radioactive transplutonium isotope, was tested for its efficacy against advanced bulky Stage III-IV cancers of the cervix in a clinical trial at the University of Kentucky Medical Center. Eighty-two patients were treated during 1976-1979 and followed for 5-year survival and tumor control. Three different treatment methods went on sequentially and concurrently, that is, (a) conventional whole pelvis photon with delayed 137Cs implants, (b) conventional photon therapy with delayed 252Cf implants, and (c) 252Cf implants ("early") preceding photon therapy. There were 12% 5-year survival for Stage IIIB cancers by conventional therapy, and 15% by delayed 252Cf implant therapy. For early 252Cf implant therapy there were 54% 5-year survivals with 4% complications and 65% 5-year local control, but distant metastases became a prominent delayed failure pattern.

Adult↗

Cardiac pacing in an elderly population with a satellite clinic in a district general hospital.

It has been suggested that in the United Kingdom the rate of implantation of cardiac pacemakers is too low. One possible reason for this may be the inadequate availability or usage of ambulatory ECG monitoring services for elderly patients. Since the introduction of such a service in Crawley, West Sussex, pacemaker implantation has increased from less than five to more than 20 per annum. Ninety-five of the 102 pacemakers (93%) implanted in that time were in patients over the age of 65 years and 68 of them were over 70 years. This rate of implantation is equivalent over the nation as a whole to at least 8000 new pacemakers per year. This represents a 14-23% increase over the present implantation rate. Since all patients were symptomatically improved and survived on average more than 30 months, despite their advanced ages, pacemaker implantation was certainly justified. The establishment of a local pacemaker surveillance service reduced the need for elderly patients to travel long distances for pacemaker checks.

Aged↗

A qualitative limitation on visual transfer via the anterior commissure. Evidence from a case of callosal agenesis.

Interhemispheric transfer of visual information was investigated in a patient with agenesis of the corpus callosum. CT scanning, pneumoencephalography, and neuropsychological evaluation failed to reveal any evidence of extracallosal cortical damage. The patient's performance was within normal limits both in the left and right visual fields on tasks requiring identification of briefly presented material. In contrast, his performance was abnormally poor when required simply to detect or localize a dot presented to the right of fixation. Performance with presentations in the left visual field was normal. These findings suggested that the absence of the corpus callosum may result in a selective impairment of visuospatial, but not identification, processes for material initially presented to the left hemisphere. To document this possibility further, the patient was tested on tasks designed to assess these processes simultaneously by requiring him both to identify and judge the exact location of each stimulus presented. Performance was normal in both lateral fields for identification accuracy, but significantly worse in the right visual field for location judgements. A similar pattern of results was found on a task requiring the identification of a stimulus and specification of its spatial orientation. These findings suggest a qualitative limitation on the type of information which may be transferred via the anterior commissure, possibly due to the inability of temporal lobe neurons to encode spatially organized information. Furthermore, the findings suggest that in the normal brain the right hemisphere may be crucially involved in visual attention and spatial functions, regardless of the field of presentation.

Adult↗

Ultrastructural changes in Sertoli cells in ageing humans.

Ultrastructural study of seminiferous tubules in ageing men revealed a varying degree of spermatogenetic arrest associated with changes in the Sertoli cells. Approximately half of the Sertoli cells showed a normal mature nuclear appearance although the cytoplasm was altered morphologically. These cells were classified as containing abundant lipid droplets (30%), containing large cytoplasmic vacuoles filled with an amorphous material similar to that in the tubule lumen and surrounded by junctional specializations (8%), multinucleated Sertoli cells (4%), or Sertoli cells with numerous mitochondria displaying tubular cristae (2%). The remaining 7% of Sertoli cells had an immature nuclear appearance and sparse development of the cytoplasmic organelles; these cells probably represent dedifferentiated Sertoli cells. Although individual differences were marked, a correlation between the increase in gonadotrophin levels and changes in both germ cell development and Sertoli cell structure was observed.

Adult↗

Metoprolol in the aged hypertensive: a comparison of two dosage schedules.

Thirty-one patients aged 65 y or over suffering from moderate hypertension were studied for 16 weeks using a cross-over design in which metoprolol 100 mg daily and metoprolol 200 mg daily were compared. Both treatment regimes were effective in controlling hypertension and no difference was found between the two with regard to efficacy. The 100 mg regime was, however, better tolerated and we propose this as the preferred metoprolol dose for the aged hypertensive.

Aged↗

Relationship between maternal and fetal fuels and placental glucose transfer in rats with maternal diabetes of varying severity.

Gestational diabetes mellitus (GDM) is a nonhomogeneous entity known to affect fetal development in different ways in both rats and human beings. The degree of severity of diabetes could affect the maternal-fetal transfer of metabolic fuels and consequently influence fetal development. To study this hypothesis, pregnant rats were made diabetic by streptozocin (STZ) treatment (45 mg/kg) at day 7 of gestation and were treated with different daily doses of insulin until the 20th day of gestation, when they were killed and examined. Differences in plasma glucose levels in the groups studied were not accompanied by differences in plasma glycerol, beta-hydroxybutyrate (beta-OHB), or total amino acid levels in mothers or their fetuses. Fetal/maternal ratios of these circulating fuels were not modified by maternal diabetes, whereas the glucose level was enhanced in diabetic rats not treated with insulin. Placental glucose transfer was studied directly with a recently reported in situ experimental design and was found to increase linearly with maternal glycemia, independently of whether this was modified by insulin treatment or by acute intravenous (i.v.) infusion of glucose in normal animals. Lactate production by the fetal/placental unit decreased in proportion to the glucose level in the maternal circulation. The present data indicate that the diabetic condition of the mother rat does not modify the mechanisms of placental transfer of metabolic fuels to the fetus, and that the actual transfer is mainly dependent on the concentrations of these fuels in the maternal circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗

Modulation of expression of mouse macrophage surface antigens by monoclonal antibodies.

Mouse macrophages from peritoneal cavity were exposed to monoclonal antibodies (MAbs) directed against cell surface antigens and the effect on antigen expression was investigated. The two Mabs used, 3A33 and 3A35, were produced by cell fusion between a mouse plasmacytoma and rat lymphocytes immunized against mouse macrophages. The binding of the MAbs to cell surface was measured by immunofluorescence and flow cytometry or by a radioimmunological technique. When injected i.p. the MAbs diminished the expression of the corresponding antigens but did not alter it when added to cultures of adherent macrophages. Antigenic modulation, however, could be produced in vitro either by inhibiting macrophage adherence during incubation with MAbs or by using a second antibody layer. MAb 3A33 (IgG2a) was more effective than 3A35 (IgM) in provoking modulation. The appearance of re-synthesized antigens on cell surface was not affected by macrophage adherence. The modulated antigens were found to internalize into cytoplasmic vacuoles.

Animals↗

[Etiologic and epidemiologic questions posed by erythema chronicum migrans and Lyme disease. Apropos of 4 cases at the Regional Hospital Center, Rennes].

The authors give 4 observations, made in Rennes (France), of 3 cases contracted in France and 1 in Canada, cases they think to be related, for 3 at least, to the infectious entity described by American authors under the name of Lyme disease. If 1 of these cases was limited to an erythema chronicum migrans, the 3 others showed a beginning evolution towards a classical Lyme disease. In 2 of these 3 last cases, the infection was perhaps cut short by a quickly applied therapy by antibiotics. They discuss the different hypotheses about the negative Borrelia serologic reactions in 3 of the 4 cases. A possible arboviral aetiology is evocked. In only one of the 4 cases, a tick-bite can be asserted, the role in the the transmission of this kind of arthropods being strictly excluded in 2 of the 3 other cases (transmission likely by a mosquito and by a biting fly (tabanid?)). The authors put the question of the possibility of transmission, for erythema chronicum migrans and Lyme disease, by arthropods other than ticks.

Adult↗

Can phosphorylation of phosphatidate phosphohydrolase by a cyclic AMP-dependent mechanism regulate its activity and subcellular distribution and control hepatic glycerolipid synthesis?

Incubating the particle-free supernatant of rat liver with alkaline phosphatase decreased the activity of phosphatidate phosphohydrolase by 21-29%. When the particle-free supernatant was incubated with various combinations of Mg2+, ATP, cyclic AMP and cyclic AMP-dependent protein kinase this failed to alter significantly phosphatidate phosphohydrolase activity under the conditions employed. The incubation of hepatocytes in monolayer culture with 0.5 mM-8-(4-chlorophenylthio)adenosine 3',5'-monophosphate increased the total activity of phosphatidate phosphohydrolase as measured in vitro. This also decreased the proportion of the phosphohydrolase that was associated with the membrane fraction of the cells and increased that in the cytosolic fraction. Adding 1 mM-oleate to the hepatocytes promoted the translocation of phosphatidate phosphohydrolase from the cytosol to the membrane-associated compartment. Oleate overcame the effect of the cyclic AMP analogue in favouring the cytosolic distribution of the phosphohydrolase. These results are discussed in relation to the interaction of hormonal balance and substrate supply in controlling the synthesis of phosphatidylcholine and triacylglycerol in the liver in stress and in diabetes. It is proposed that the cytosolic phosphatidate phosphohydrolase activity represents a reservoir of potential activity that becomes expressed when the enzyme translocates to the membranes on which the synthesis of glycerolipids occurs.

Adenosine Triphosphate↗

Differential perceptual-spatial impairment in Huntington's and Alzheimer's dementias.

Because the severity of memory disorders exhibited by neuropsychiatric patients overshadows other cognitive deficiencies, we explored the visuoperceptual and constructive abilities of patients with Alzheimer's (AD) or Huntington's (HD) disease. The tasks assessed directional sense with reference to egocentric space, as well as visuodiscriminative and constructive skills of patients and matched controls. A double dissociation was found: the performance of patients with AD was found to be significantly impaired on tasks involving extrapersonal perception and construction but not on the test of egocentric space. In contrast, visuoconstructive performance by patients with HD was not significantly impaired, while salient deficits were apparent when manipulation of personal space was required. These differential patterns of defects may have been aligned with neuropathologic changes in different cortical and subcortical structures, respectively, in patients with AD and HD.

Adult↗

SAV 1, a temperate u.v.-inducible DNA virus-like particle from the archaebacterium Sulfolobus acidocaldarius isolate B12.

Sulfolobus acidocaldarius, strain B12, which harbours a double-stranded DNA species both as a plasmid and in a linear form, which is integrated at a specific site of the chromosome, produces virus-like particles upon u.v. irradiation. These particles contain the same circular DNA and a number of coat proteins and are probably surrounded by a lipid membrane. They are lemon shaped, 100 x 60 nm in size and carry tail structures at one pole. The host cell recovers and remains lysogenic after virus production. Though a large fraction of liberated particles is found attached to structures derived from the cells, neither adsorption nor infection of a number of Sulfolobus isolates has so far been observed.

Journal Article↗

Evaluation of the bioavailability of sarpicillin, the methoxymethyl ester of hetacillin, in humans.

The relative bioavailability of sarpicillin (the methoxymethyl ester of hetacillin) from three different oral dosage forms was compared in humans employing a three-way crossover study design. Each unit dose contained 250 mg of sarpicillin in terms of anhydrous ampicillin activity. The comparative bioavailability of a tablet containing added buffer, a liquid-filled capsule, and a standard powder-filled capsule was determined. The bioavailability parameters were Cmax, tmax, and AUC of intact plasma sarpicillin levels and saliva ampicillin levels. Significant correlation was found between plasma sarpicillin levels and saliva ampicillin levels following the administration of sarpicillin. All three formulations yielded statistically similar Cmax and AUC values with respect to plasma sarpicillin and saliva ampicillin levels. However, a more rapid absorption of intact sarpicillin was observed with the buffered tablet formulation, as reflected by significantly smaller tmax for both plasma sarpicillin and saliva ampicillin levels. The faster absorption from the tablet formulation gave more precise absorption among subjects.

Adult↗

Expanded solubility parameter approach. I: Naphthalene and benzoic acid in individual solvents.

An expanded solubility parameter system was tested in conjunction with the extended Hansen solubility approach and the UNIFAC method to calculate the solubilities of naphthalene and benzoic acid in polar and nonpolar solvents. The expanded parameter system is characterized by delta d for the dispersion force, delta p for dipolar forces, a basic or electron-donor parameter, delta b, and an acidic or electron-acceptor parameter delta a. The correlation between the calculated and observed solubilities of benzoic acid was increased by use of the four-parameter system. An indicator variable was required to bring the solubilities into line in strongly dipolar solvents such as N,N-dimethylformamide. For naphthalene, use of the four-parameter approach proved not to be an improvement over the three-parameter extended Hansen solubility approach. The UNIFAC method was not successful in calculating solubilities of benzoic acid in the 40 polar and nonpolar solvents. A triangular plot of the three Hansen parameters for benzoic acid, p-hydroxybenzoic acid, and methyl p-hydroxybenzoate illustrated the contributions of dispersion, dipolar, and Lewis acid-base (hydrogen bonding) interaction forces among the three benzoic acid compounds and the various classes of solvents. A multiple regression procedure for calculating the four partial solubility parameters of drug solutes was developed.

Benzoates↗

Expanded solubility parameter approach. II: p-Hydroxybenzoic acid and methyl p-hydroxybenzoate in individual solvents.

The recently introduced four-parameter extended Hansen approach was used to study the solubility of p-hydroxybenzoic acid and methyl p-hydroxybenzoate in 32 and 35 individual solvents, respectively. The results are compared with those for benzoic acid in 40 solvents. Seventeen of the thirty-two or 53% of the calculated solubilities of p-hydroxybenzoic acid were within the established solubility criterion (i.e., less than 30% error from the experimental value). Twenty-two of thirty-six or 61% of the calculated solubility values for methyl p-hydroxybenzoate met the solubility criterion. Experimental excess free energies of solution for p-hydroxybenzoic acid and methyl p-hydroxybenzoate were plotted against theoretical values using the expanded four-parameter solubility regression equations. From such results, adjustments may be made in the partial solubility parameters to bring the calculated solubilities in line with experimental results. Multiple regression analyses were used to estimate the total solubility parameter and the four partial solubility parameters of the two benzoic acid derivatives. Satisfactory results were obtained for methyl p-hydroxybenzoate, but poor agreement was found for p-hydroxybenzoic acid for the total parameter when compared with the Fedors group contribution method. Both the multiple regression and group contribution methods may yield inaccurate solubility parameters for relatively polar solid solutes. Factor analysis was used to test the adequacy of three- and four-parameter approaches in the evaluation of drug solubility. A principal factor method without iteration and orthogonal factor rotation were used to compare the two expanded solubility parameter approaches.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemical Phenomena↗

Membrane solubility parameter and in situ release of theophylline.

The solubility of theophylline in polyethylene glycol 400-water binary mixtures was analyzed in terms of solute-solvent interaction using the solubility parameter principle of Hildebrand. Preliminary in situ (rat gut permeation) studies with the solvent mixtures having varying polarity as expressed by the solubility parameter showed that (a) the more alike the solubility parameter of theophylline (delta 2 = 14, as obtained from solubility studies) and the solubility parameter of the solvent mixture, the greater was the attraction of solvent for the drug (b) sufficient similarity must exist between the solubility parameter of theophylline and that of the intestinal mucosa to promote bioabsorption, and (c) from the above, it follows that there exists a competition between solvent and rat gut membrane for the drug. The solubility parameter of the solvent vehicle must be such that it does not impede absorption of the molecules into the intestinal mucosa.

Animals↗