Biomedical subjects
Publications and source records attributed to H Laurent.
The synthesis of the new progestogen, 17 alpha-ethinyl-17 beta-hydroxy-18-methyl-4,15-estradien-3-one (gestodene, 6), starting from 18-methyl-4-estren-3,17-dione (1) can be accomplished by several methods. The oral progestational activity of gestodene is greater than that of levonorgestrel. Gestodene, in combination with ethinylestradiol, is contained in a recently developed oral contraceptive.
Several derivatives of the highly active aldosterone antagonists dihydrospirorenone (2) and spirorenone (3) were synthesized. The purpose of these efforts was to prepare compounds exhibiting reduced endocrinological properties with the same or better aldosterone antagonistic activity than that of spirorenone. The 1 alpha,2 alpha-methylene derivative 20 has a similar aldosterone antagonistic potency compared to that of spirorenone but does not show decreased endocrinological side effects. Other substituents as in compounds 4-11, 15-19, and 21 sharply decreased the aldosterone antagonistic activity of 2 or 3, respectively.
A study was undertaken to evaluate the use of self-administered medication in 895 patients with rheumatologic disorders by all of the 18 rheumatologists practicing in one region (the southern portion of the Loire Department and all of the Haute-Loire Department) over a six-day period. It was noted that 445 out of 895 patients (49.72 percent) reported taking one or several medications other than those prescribed during the previous 3 month period before their office visit. Self-administered medications were taken at least weekly in 53.5 percent of cases and at least monthly in 83,7 percent. Most often one or two medications were involved (60.9 and 25.6 percent respectively). Age, profession, the presence or absence of psychiatric disturbances, the duration of the doctor-patient relationship, as well as the patient's specific rheumatologic problem seemed to be influencing factors. Aspirin or other analgesics comprised 53.1 percent of the medication taken, whereas other non-steroidal antiinflammatory agents comprised only 2.3 percent. No steroids were self-administered. There are multiple potential side effects with self-administered drugs: therapy can be poorly suited for the illness in question, it may delay diagnosis and the beginning of effective therapy, there can be increased iatrogenic risk due to inadequate therapy, and unnecessary expense. Drugs used as self-administered medications originate most often from previous medical prescriptions which may or may not have been prescribed for the patient's same medical problem (34.4 percent), and most medication used was bought without needing a prescription (52.4 percent). Prevention, therefore, requires that potential consumers of self-administered drugs be educated concerning these problems, as well as health professionals, the pharmaceutical industry, and concerned government agencies.
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The authors report the results of more than twelve years' personal research on the value of anti-alphahemolysin (AASTL) and antigammahemolysin (AGSTL) assays for the diagnosis of staphylococcal infections, and particularly of osteoarthritis. Among 574 controls, AASTL levels exceeded 2 IU in only 14 subjects (11 of these, levels were between 2 and 3 IU). Levels less than, or equal to, 2 IU were therefore considered normal. This is consistent with previously published data. In 144 staphylococcal infections, confirmed by bacteriology, an increase in AASTL was found in 95 of all cases (65.9%) and in 54 of the 76 osteoarthritis' (71%). Similarly, AGSTL titres, which were under 1/160 (upper normal limit) in 138 controls, were increased in 35 patients with unequivocal staphylococcal infections (61.4%), and in 25 of 36 patients with osteoarthritis (69.4%). These results show that AASTL assay is reliable and often abnormal. However, assay of both hemolysins yields even better results. This dual assay was performed in 57 patients with staphylococcal infection. One hemolysin at least was increased in 47 patients (82.4%). This represents additional positivity in 15.7% of patients when compared to AASTL assay alone, and in 21% when compared to AGSTL assay alone. The high level of positive results with dual assay is even more striking when only staphylococcal osteoarthritis is considered: one or both hemolysins were increased in 91.1% of these patients (31/34).
Using their own personal series of 19 cases of leprosy complicated by massive osteolysis (AO), along with a comparison of these cases with data from previously published reports, the authors review the principal clinical and radiological findings of these manifestations which are not observed except in cases of leprosy where neuropathy is present, even though other factors (perforating plantar ulcers, poor hygiene, traumatisms) may play a contributing role independent of possible interference from non specific osteoarthritis or Hansen's bacilla, itself. After reviewing other causes of massive osteolysis and discussing the pathogeny of these manifestations during leprosy, the authors refer to the various therapies which can prevent or stabilize osteolysis or aid the patient to better tolerate its manifestations.
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The effects of the intravenous or intracerebroventricular injection of the stereoisomers, and the racemic mixture, of allylglycine (2-amino-pent-4-enoic acid) have been studied in baboons, Papio papio, with photosensitive epilepsy. Enhancement of the natural syndrome of photosensitivy epilepsy is seen 1-12 h (maximally at 3-8 h) after L-allyglycine, 100 mg/kg, intravenously, or D,L-allyglycine, 200 mg/kg, intravenously. Such enhancement is seen with a slower onset, and to a lesser, and more variable, extent after D-allyglycine, 500-750 mg/kg, intravenously. Brief focal or generalised seizures occurred (in the absence of intermittent photic stimulation) after L-allyglycine, 150-200 mg/kg, intravenously. This effect is similar to that previously observed after D,L-allyglycine, 300-400 mg/kg. D-Allyglycine, 780 mg/kg, intravenously produced episodes of vertical nystagmus with increased extensor motor tone, but no 'spontaneous' seizures. Intracerebroventricular injection of L-allylglycine, D-allyglycine or D,L-allyglycine, 100 mg in 1 ml saline, did not modify the natural syndrome of photosensitive epilepsy. D-Allylglycine, or D,L-allyglycine, 100 mg intracerebroventricularly, after 1-2 h gave rise to a syndrome with vomiting, sustained vertical nystagmus, and intermittent extensor spasms. The results are interpreted in terms of regional differences in the metabolism of the two isomers to active compounds that can inhibit glutamic acid decarboxylase. D-Allylglycine is active only at the brain stem and cerebellum because D-amino acid oxidase is largely confined to these brain areas.
Among the metabolites of fluocortolone (1) there was found the alpha-keto acid 4a. This acid, as well as the esters 4b--4k were synthesized and the butyl ester 4c was chosen for local anti-inflammatory therapy.
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