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Biomedical subjects

W F Hoffman

Publications and source records attributed to W F Hoffman.

At least 37 records · Page 2Linked to original sources
PubMed1986

3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. 3. 7-(3,5-Disubstituted [1,1'-biphenyl]-2-yl)-3,5-dihydroxy-6-heptenoic acids and their lactone derivatives.

The syntheses of a series of 7-(3,5-disubstituted [1,1'-bephenyl]-2-yl)-3,5-dihydroxy-6-heptenoic acids and their lactones are reported. Intrinsic 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitory activity is enhanced markedly when the biphenyl moiety is substituted by chloro or methyl groups at positions 3 and 5 and a fluoro group at position 4'. These substitutions, followed by resolution, provided compounds 100(+) and 110(+) with 2.8 times the intrinsic inhibitory activity of compactin. Compound 100(+) was shown to possess the same chirality in the lactone ring as compactin by single-crystal X-ray crystallography.

Animals↗
PubMed1986

3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. 4. Side chain ester derivatives of mevinolin.

Modification of the 2(S)-methylbutyryl moiety of mevinolin led to a series of side chain ester derivatives. A systematic exploration of the structure-activity relationships showed that the introduction of an additional aliphatic group on the carbon alpha to the carbonyl group increased potency. This observation led to the synthesis of compound 16, which has about 2.5 times the intrinsic inhibitory activity of mevinolin.

Hydroxymethylglutaryl-CoA Reductase Inhibitors↗
PubMed1985

3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. 1. Structural modification of 5-substituted 3,5-dihydroxypentanoic acids and their lactone derivatives.

A series of 5-substituted 3,5-dihydroxypentanoic acids and their derivatives have been prepared and tested for inhibition of HMG-CoA reductase in vitro. In general, unless a carboxylate anion can be formed and the hydroxy groups remain unsubstituted in an erythro relationship, inhibitory activity is greatly reduced. Furthermore, only one enantiomer of the ring-opened form of lactone 6a(+/-) possesses the activity displayed by the racemate. Insertion of a bridging unit other than ethyl or (E)-ethenyl between the 5-carbinol moiety and an appropriate lipophilic moiety (e.g., 2,4-dichlorophenyl) attenuates activity.

Glycols↗
PubMed1985

Comparison of pregnancy diagnosis by milk progesterone on day 21 and day 24 postbreeding: field study in dairy cattle.

Milk samples collected at 21 and 24 d after breeding were used to diagnose cows as pregnant, questionable, or not pregnant with high, intermediate, or low progesterone in the milk. Total agreement of pregnancy diagnosis in cows by milk progesterone at 21 d postbreeding and diagnosis by return to estrus or palpation of reproductive organs was 85.8% (77.4% on pregnant progesterone diagnosis and 97.2% on not pregnant progesterone diagnosis). Total agreement of diagnosis by progesterone at 24 d postbreeding and diagnosis by estrus or palpation was 88.4% (83.5% on pregnant progesterone diagnosis and 95.3% on not pregnant progesterone diagnosis). Although total accuracy of cows diagnosed both pregnant and not pregnant by milk progesterone on d 24 postbreeding was greater than diagnosis on d 21 postbreeding when cows in estrus by d 24 were deleted from the data, other comparisons for effect of day on accuracy of diagnosis were not different. Total accuracy of diagnosis on d 24 was not increased by using milk progesterone on both d 21 and 24. Samples collected on the day of breeding indicated that 18 of 960 (1.9%) had intermediate or high progesterone. Fourteen (1.5%) additional cows had progesterone above levels expected for a cow in estrus.

Animals↗
PubMed1983

Efficacy of gonadotropin-releasing hormone administered at the time of artificial insemination of heifers and postpartum and repeat breeder dairy cows.

The efficacy of gonadotropin releasing hormone (GnRH) on the fertility of dairy heifers and postpartum cows was studied. In one study, 300 cows were assigned randomly to 1 treatment from a 2 X 2 design, and 2 ml of 0.15M saline solution or 100 micrograms of GnRH was given IM on postpartum day (PPD) 14 and at the time of 1st postpartum breeding. In a 2nd study, repeat breeder cows (n = 346) were given saline solution or GnRH at the time of the 3rd breeding. In a 3rd study, heifers (n = 185) were given saline solution or GnRH at 1st breeding. Animals were observed for repeat estrus, and pregnancy diagnoses were made by rectal palpation 45 to 60 days after breeding. Conception rates were 15% to 18% higher for cows given GnRH, whether at PPD 14 or at the first postpartum breeding. When GnRH was given at the first breeding, conception rates were significantly higher (P less than 0.05). Conception rates for repeat breeder cows given GnRH were 25% higher than those in controls (P less than 0.005). Conception rates for heifers did not differ between treatments.

Animals↗
PubMed1982

Milk progesterone for pregnancy diagnosis in dairy goats.

Factors affecting progesterone concentration in milk of lactating dairy goats and use of this milk for pregnancy diagnosis were studied. Radioimmunoassay was used to assay progesterone in milk. Mean milk progesterone (ng/ml) +/- standard errors of 6 pregnant does for first, composite, and last milk were 9.9 +/- 2.0, 18.2 +/- 3.5, and 21.7 +/- 4.1. Correlation between milk fat and progesterone in composite milk was low (.11). Composite milk samples from 4 nonpregnant does were obtained daily throughout the estrous cycle. Milk progesterone (ng/ml) was 1 to 2 at estrus, rose to 5 to 12 within 2 to 5 days, reached a plateau at 15 to 25 in the middle of the estrous cycle, and then dropped to low concentrations again at 3 to 5 days before the next estrus. Milk progesterone also was used to diagnose pregnancy in 72 does. Forty-two does were diagnosed pregnant by high progesterone; 36 of these does later produced kids, and 5 other does aborted in various stages of pregnancy. Of 21 does diagnosed not pregnant with low progesterone, 19 does were not pregnant by either return to estrus or lack of parturition in the spring. All three incorrectly diagnosed does were problem breeders. Nine does with intermediate milk progesterone were classified questionable. Milk progesterone can be used to provide an early indication of the pregnancy status of does.

Animals↗
PubMed1981

(Acylaryloxy)acetic acid diuretics. 3. 2,3-Dihydro-5-acyl-2-benzofurancarboxylic acids, a new class of uricosuric diuretics.

The discovery that dihydroethacrynic acid and other (4-acylphenoxy)acetic acids possessed modest but significant uricosuric and diuretic activity prompted our investigation of the related 2,3-dihydro-5-acyl-2-bensofurancarboxylic acids. Synthetic routes to a number of these compounds are presented along with the structure-activity relationships generated from studies in rats, dogs, and chimpanzee. Examination of the enantiomers of 6,7-dichloro-2,3-dihydro-5-(2-thienylcarbonyl)-2-benzofurancarboxylic acid (10c) in the chimpanzee revealed that all diuretic and saluretic activity is due to the (+) enantiomer 10d, while the (-) enantiomer 10e is responsible for all of the uricosuric activity. X-ray analysis showed that the (-) enantiomer 10e possesses the 2R configuration.

Animals↗
PubMed1980

Prognostic significance of the pretreatment CT scan on time to progression for patients with malignant gliomas.

Case histories of 61 patients receiving multimodality therapy for primary malignant brain tumors were reviewed for factors visible on the computerized tomography (CT) scan that correlated with the interval of time from diagnosis and pretherapy evaluation to the time of documented tumor progression. The initial pretreatment CT scan of each patient was reviewed. Midline shift, peritumor low density (edema), the greatest diameter of tumor enhancement, and the greatest diameter of the intratumor low-density area were measured prior to radiation therapy and chemotherapy. Using a Weibull survival probability model, time to tumor progression was most satisfactorily fitted using two covariates, the volume of enhancing tumor (for instance, contrast-enhancing tumor less intratumor low density), and the presence of a peritumor low-density area. Patients who exhibited a small amount of contrast-enhancing tumor with peritumor low density tended to have a longer time to progression than patients with large contrast-enhancing tumor volume and no peritumor low density. Midline shift was not as important a variable as the extent of tumor contrast enhancement or peritumor low density.

Brain Neoplasms↗
PubMed1979

Recurrent transient ischemic attacks secondary to an embolizing saccular middle cerebral artery aneurysm. Case report.

Over a 1-year period, a 60-year-old woman had nine episodes of transient weakness, clumsiness, and hypesthesia of the right upper extremity. Angiography revealed normal extracranial vessels and a left middle cerebral artery aneurysm. The aneurysmal sac, removed at operation, had an organized thrombus, which was believed to be the cause of the transient ischemic attacks. Postoperatively, the patient has remained free of neurological symptoms.

Female↗
PubMed1978

BCNU-5-fluorouracil combination therapy for recurrent malignant brain tumors.

Twenty-nine patients with recurrent malignant brain tumors were evaluated. BCNU (180 mg/m2) was administered iv on Day 1 and 5-fluorouracil (1 g/m2/day) was given by continuous infusion on Days 15--17. Courses were repeated every 6 weeks until tumor progression occurred. Before each course, a neurologic examination and radionuclide and computerized tomographic scans were performed. Response and progression were defined as improvement or deterioration, respectively, in at least two of the three tests. Nine of 29 patients (31%) responded to therapy, five of 29 (17%) showed progression, and 15 of 29 (52%) had disease stability. The estimated median time to progression was 27 weeks for all patients, 34 weeks for the response group, and 25 weeks for the stable group. Of all 29 patients, 24 (83%) had tumor progression arrested; 40% with response and 6% with stable disease were continuing therapy after 1 year. The stable disease group was larger and the duration of stability was longer than that seen in previous studies. Evaluated by time to progression, a BCNU-5-fluorouracil combination is superior to either BCNU alone or a BCNU-procarbazine combination.

Astrocytoma↗
PubMed1977

Photoinduced size change of membrane vesicles from bovine retinal rod outer segment.

Quasielastic light-scattering measurements were made on isolated, osmotically swollen, bovine rod outer segment (ROS) disk membranes in aqueous Ficoll. The translational diffusion coefficients determined were (1.66 +/- 0.21) X 10(-9) and (2.31 +/- 0.14) X 10(-9) cm2/s at 25 degrees C for the unbleached and bleached membranes in 5% Ficoll, respectively, yielding the Stokes radii of 0.53 +/- 0.07 micronm for the former and 0.38 +/- 0.02 micronm for the latter. This photoinduced size decrease, which corresponds to a 60% decrease in the intravesicular volume, is far more pronounced than thos reported by others for ROS fragments.

Animals↗
PubMed1976

Intact photoreceptor membrane from bovine rod outer segment: size and shape in bleached state.

Photoreceptor disk membranes isolated from bovine rod outer segments are suspended in dilute aqueous sucrose (4.36 X 10(-3%)) and bleached, and their size and shape are determined with quasielastic and elastic light scattering. They are found to be extremely homogeneous spherical vesicles with a radius of 0.49 +/- 0.07 mum which appear to have derived from the native disk shape by osmotic swelling.

Animals↗
PubMedDate not supplied

Computed tomographic evaluation of patients with tardive dyskinesia.

X ray computed tomography has been used since its introduction to evaluate patients with tardive dyskinesia (TD). A critical review of the 18 reports which have appeared since 1976 suggests that TD may be associated with neuroanatomical abnormalities. In particular, a meta-analysis of the reports of ventricular brain ratio found a trend for patients with TD to have larger lateral ventricles than unaffected patients. The magnitude of the difference appears to be small, however, and several well conducted studies have reported negative results. A careful analysis revealed that low statistical power, concurrent neuroleptic treatment, insensitive measures of ventricular dilatation, and variable diagnostic criteria for TD may have led to negative findings in most of the investigations. The possible significance of these results and suggestions for further research are discussed.

Age Factors↗