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Biomedical subjects

M Grau

Publications and source records attributed to M Grau.

At least 19 recordsLinked to original sources

Elastoderma.

Elastoderma is an exceedingly rare condition that is characterized clinically as an acquired localized laxity of skin resembling cutis laxa and histologically as an excessive accumulation of pleomorphic elastic structures within the dermis. We report the case of a 27-year-old white man with a 2-year history of lax, extensible, wrinkled skin with areas of protrusion and ulceration localized to the anterior aspect and back of the neck. Histologic examination of specimens from the affected area revealed increased masses of intertwined thin, elastic fibers without calcification in the papillary and upper reticular dermis. Transmission and scanning electron microscopy demonstrated irregular deposition of elastic material at the periphery of elastic tissue fibers, with grapelike globular structures. To our knowledge, this is the second reported case of elastoderma.

Adult

Relationship between epidermal growth factor in mouse submandibular glands, plasma, and bile: effects of catecholamines and fasting.

The epidermal growth factor (EGF) concentration in bile is high (approximately 150 fold higher than that in plasma), but little is known about its physiological control. Acute administration of the alpha 1-adrenergic agonist phenylephrine (1.7 mg/kg, iv) to male mice produced a rapid increase in the EGF concentration in bile. We suggest that this EGF originates in submandibular glands and not in the liver. The bases for this are: 1) this increase was parallel to the increase in plasma, and the EGF content of the submandibular glands decreased after phenylephrine injection; and 2) the EGF concentrations in plasma and bile did not increase after phenylephrine administration to sialoadenalectomized mice. The concentration of EGF in bile is not only under pharmacological control, but is also regulated physiologically. Thus, the EGF concentrations in plasma, bile, and submandibular glands increased in fasted mice. All of these changes were reversed by refeeding. As 1) [125I]EGF binding to liver membranes decreased only after 2 days of fasting, but the level of circulating EGF was already increased in 1-day fasted mice, and 2) EGF secretion by submandibular glands from 1-day fasted mice incubated in vitro increased, we suggest that the increase in EGF concentrations in plasma and bile is the consequence of increased endocrine secretion by submandibular glands. Taken together, our results suggest that there is a flux of EGF from submandibular glands to bile in mice, which is under physiological control.

Animals

N-substituted pyrazino[2,3-c][1,2,6]thiadiazine 2,2-dioxides. A new class of diuretics.

The synthesis and evaluation of a new class of diuretic agents derived from the pyrazino[2,3-c][1,2,6]thiadiazine 2,2-dioxide ring system are described. Preliminary structure-activity relationships indicate that the nature and location of the substituents at different positions of the heterocycle are crucial for activity. Thus, a novel synthetic methodology has been developed to selectively introduce the desired substituents at different positions. From the study of the pharmacological properties (dose-response curves, duration of action, and acute toxicity) of the most active compounds, 4-amino-1,7-diethyl-6-methylpyrazino[2,3-c][1,2,6]thiadiazine++ + 2,2-dioxide (9) was selected for further investigation. Compound 9 (C10H15N5O2S) crystallizes in space group P21/a with unit cell dimensions a = 16.482 (1), b = 9.3484 (3), c = 8.333 (3) A, beta = 103.003 (3) degrees, Z = 4.

Animals

Impaired response to recombinant hepatitis B vaccine in HIV-infected persons.

We studied the immunogenicity of the standard schedule of recombinant hepatitis B vaccine (20 micrograms per dose at months 0, 1, and 6) in 21 anti-human immunodeficiency virus (HIV)-positive persons. Relatively low titers of anti-HBs developed in only five subjects (23.8%) 1 month after the third dose; all five had T4 cell counts greater than 700 cells/mm and none of the 11 subjects with a T4 cell count below this value responded. Five of the 16 nonresponders to the vaccine later had acquired immunodeficiency syndrome (AIDS)-related complex (two) and AIDS (three), while none of the responders did. Our results show that anti-HIV-positive persons are poor responders to the recombinant hepatitis B vaccine, and that the absence of a response is an indicator of a more severe immune deficiency and of a poor prognosis. An optimal regimen of hepatitis B vaccination in HIV-infected persons is still to be established.

Follow-Up Studies

Neisseria meningitidis with reduced sensitivity to penicillin: observations in 10 children.

10/84 strains (11.9%) of Neisseria meningitidis isolated from blood and/or cerebrospinal fluid in children 1986-1987 had reduced sensitivity to benzylpenicillin (MICs 0.1-0.4 mg/l). Group C meningococci predominated among these strains. The clinical course was satisfactory in all cases regardless of the antibiotic treatment used, although the time to abatement of fever was prolonged compared to that of children infected with susceptible strains.

Adolescent

Pharmacology of the potent new non-steroidal anti-inflammatory agent aceclofenac.

Aceclofenac (2-[(2,6-dichlorophenyl) amine]phenylacetoxyacetic acid; CAS 89796-99-6) is a new orally effective non-steroidal anti-inflammatory agent of the phenylacetic acid group which showed remarkable anti-inflammatory, analgesic, and antipyretic properties. Hence, aceclofenac possesses a potent inhibitory activity in several models of acute and chronic inflammation in rodents, and resembles indometacin and diclofenac in its pharmacodynamic profile, being superior to naproxen and phenylbutazone. In addition, aceclofenac was found to be highly active against sodium urate-induced synovitis in dogs and adjuvant-induced polyarthritis in rats, both prophylactically and therapeutically. The analgesic effect of aceclofenac on the pain elicited by chemical and mechanical stimuli was nearly equal to or slightly better than that of indometacin and diclofenac. Fever induced by brewer's yeast injection in rats was also markedly suppressed by aceclofenac. In contrast, the acute gastric ulcerogenic activity of aceclofenac was about 2, 4 and 7-fold lesser than that of naproxen, diclofenac, or indometacin, respectively. As a consequence of its high anti-inflammatory activity and lower potential for gastric damage aceclofenac exhibited the most favourable therapeutic ratio in comparison with indometacin, diclofenac, naproxen, and phenylbutazone. These data indicate that aceclofenac could be a potent anti-inflammatory and analgesic agent with a wide margin of safety in clinical practice.

Animals

Pharmaco-toxicological effects of acetaminophen in rodents. Battery of tests to screen potential analgesic acetaminophen derivatives.

The pharmacological effects of acute oral administration of acetaminophen have been extensively evaluated in rodents. Using this drug as reference compound we have also standardized several pharmaco-toxociological tests in order to select new analgesic-antipyretic acetaminophen derivatives. According to the results obtained in this work, the following battery of assays is proposed to screen these compounds: a) pharmacological: antipyretic activity against Brewer's yeast-induced pyresis in rats; analgesic activity against chemical-induced writhings in mice and paw pressure test in rats; b) toxicological: oral acute toxicity in mice with and without phenobarbital pretreatment; determination of SGOT and SGPT activities as well as total bilirubin in mice. The usefulness of this procedure in the evaluation of drug effects is also considered.

Acetaminophen

[Oral hairy leukoplakia. A study of 5 cases].

Oral hairy leukoplakia (HL) is a newly described lesion (1984) in human immunodeficiency virus infected patients. Patients with HL show a high probability of developing an acquired immunodeficiency syndrome (AIDS). The results of histopathological, microbiological, immunological and ultrastructural studies in five patients with HL and AIDS are reported. The histopathological exam revealed in all cases acanthosis, parakeratosis, koilocytosis and keratin projections on the surface. Dermis was normal. Herpes type virus were seen in four cases and in one of them papilloma virus was also present in electron microscopic examination. There was immunocytochemical evidence of papilloma virus in one lesion. Candida albicans was found in 5 lesions by culture but only in two ones by periodic acid Schiff stain. Virus cultures for herpes virus were negative. Immunocytochemical search of Langerhans cells (S-100, HLA-DR, OKT4, OKT6) showed nearly absence of these cells in HL lesions. These results favour the viral etiology hypothesis of hairy leukoplakia.

Acquired Immunodeficiency Syndrome

Abnormal scintigraphic evolution in AA hepatic amyloidosis.

A patient with AA amyloidosis secondary to ankylosing spondylitis showed intense liver uptake of Tc-99m MDP on bone imaging. The biopsy showed hepatic amyloid deposition. A repeat bone scan with Tc-99m MDP 1 year later was negative, although the clinical signs and liver function tests of the patient had not changed. A mechanism might exist, other than the affinity of amyloid to calcium, which would explain the extraosseous uptake of pyrophosphates and diphosphonates in organs and soft tissues affected by systemic amyloidosis.

Amyloidosis

Bone scan in systemic amyloidosis.

Thirty patients diagnosed as having systemic amyloidosis (six with primary amyloidosis and 24 with secondary amyloidosis) were given bone scans with 99Tcm-methylene diphosphonate in order to evaluate the skeletal and extra-osseous uptake and their clinical-scintigraphic correlation. Extra-osseous uptake appeared in nine instances, more frequently in primary (5/6) than in secondary (4/24) amyloidosis. Fourteen patients had clinical and echocardiographic suspicion of cardiac amyloidosis but only one showed cardiac uptake. Six patients had probable hepatic involvement but in only two cases was hepatic uptake seen. The extra-osseous uptake suggests the presence of amyloid deposits in the organs and soft tissues which take up the bone tracer. The absence of any uptake does not rule out amyloid infiltration.

Adult

Effect of Piracetam on electrocorticogram and local cerebral glucose utilization in the rat.

The effect of Piracetam on hypoxia-induced alterations of cerebral cortex electrogenesis is studied. The results showed protection. As this anti-hypoxidotic property could be linked to Piracetam influence on energy-metabolic processes in the brain, we studied the effect of this nootropic drug on local cerebral glucose utilization (LCGU) by means of a variant of the Sokoloff's technique. Our results showed that Piracetam enhances LCGU. We suggest that both effects, the functional and the metabolic one, are related.

Animals

Nicardipine: protection against brain hypoxia.

Nicardipine, a new vasodilator and calcium antagonist, was tested for antihypoxic activity on the central nervous system. Two methods were used: hypobaric hypoxia and alteration of the electrocorticogram by asphyxic anoxia. Both survival time and the impaired electrical signal were improved by nicardipine. These results suggest brain protection by increased cerebral blood supply.

Animals

Protective effects of "cerebroactive drugs" in a model of acute hypoxia.

A systematic study of the hypobaric hypoxia method was carried out, using a wide range of vasodilators and metabolic modifiers. In general cerebral metabolic modifiers have a more effective antihypoxic action than cerebral vasodilators. After a discussion, the conclusion is that hypobaric hypoxia is useful as an initial screening procedure.

Animals