Replication by silicone impression materials in crown and bridge construction.
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Crowns↗
Biomedical subjects
J M Hoffman
Publications and source records attributed to J M Hoffman.
Pancreatic islet arachidonic acid turnover and metabolism and insulin release in response to delta-9-tetrahydrocannabinol.
Isolated pancreatic islets from the rat secrete insulin in response to glucose or delta-9-tetrahydrocannabinol (THC). THC stimulated the basal release of insulin and also potentiated the secretory response to glucose. The exposure of control or glucose-stimulated islets to THC inhibited the incorporation of [14C]arachidonic acid (AA) into phospholipids. However, in islets prelabeled with [14C]AA, THC enhanced the glucose-induced loss of AA from phospholipids. The enhanced AA release from islet phospholipids in response to glucose and THC was accompanied by increased synthesis of 12-L-[5,6,8,9,11,12,14,15-3H(N)]-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) and prostaglandin E2. The lipoxygenase inhibitor 3-amino-1-(3-trifluoromethylphenyl)-2-pyrazoline hydrochloride (BW755C) inhibited 12-HETE synthesis and insulin release in glucose and THC-challenged islets; nordihydroguaiaretic acid also inhibited insulin release in THC-treated islets. In contrast, the cyclooxygenase inhibitor, indomethacin, stimulated insulin release. In homogenized islet preparations, THC inhibited acyl-CoA acyltransferase, while it stimulated phospholipase A2 activity. The stimulatory effects of THC on islet cell AA hydrolysis from phospholipids, lipoxygenase product formation, and secretion suggests that these biochemical sequelae in cell activation are important modulators of insulin release.
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
Utilization of a polyethylene enclosure for nerve tracing studies in the rat ovary.
A commonly used technique for mapping neuronal connections in the peripheral nervous system involves the injection of a tracer substance into a peripheral organ. The tracer is taken up by nerve terminals at the injection site and transported retrogradely to motor or sensory perikarya where it can be visualized. One of the pitfalls of this technique is that tracer may leak from the injection site, enter nerve terminals adjacent to the injection area and thus cause erroneous interpretations. Similarly, some tracers may enter blood vessels and be taken up by nerve cell bodies indiscriminately. In order to circumvent these potential problems in studies on the innervation of the rat ovary, a polyethylene enclosure for the organ was fabricated from a BEEM capsule. The retrograde tracer, True blue, was then applied topically on the ovarian surface inside the enclosure. In chronic experiments, specifically labeled ovarian nerve cell bodies were identified in dorsal root and preaortic ganglia. Utilization of this simple and effective enclosure eliminates the false-positive and non-specific labeling of perikarya due to diffusion and blood-borne transport of the tracer from the injection area.
Animals↗
Hypoxia mediated binding of misonidazole in non-malignant tissue.
Binding of 3H-misonidazole in hypoxic nonmalignant tissue was investigated in the gerbil stroke model. Cerebral infarcts were produced in male Mongolian gerbils by ligating the right common carotid artery and the severity of the lesions was quantified by scoring the animals' symptoms. The uptake of [H-3]misonidazole in the right cerebral hemisphere and the ratios of right:left hemispheral uptake correlated positively with the severity of the stroke when measured 6 to 10 hours after carotid ligation. Autoradiographs of the gerbil brains with severe infarcts showed heavy label, which was uniformly distributed, on the affected side. We conclude that the gerbil stroke model is useful for studying hypoxia in vivo. There is variability between animals that closely correlates with stroke index, but more importantly the hypoxia may be more homogeneous over regions of the brain within one animal. A reliable model of homogeneous induced hypoxia in vivo will be useful for evaluating radiolabeled drugs which may be used for quantitation of hypoxia in tumors by nuclear imaging.
Animals↗
Structure-activity, theoretical, and X-ray studies on the intramolecular interactions in a series of novel histamine H2 receptor antagonists.
The furan ring of the histamine H2 receptor antagonist 3-amino-4-[[2-[[[5-[(dimethylamino)methyl]-2-furanyl]-methyl] thio]ethyl]amino]-1,2,5-thiadiazole 1-oxide (1a) was replaced by thiophene, pyridine, benzene, and pyrrole. The relative receptor affinities of these analogues were estimated by in vitro and in vivo techniques. A theoretical model for the stacking interaction, observed by single crystal X-ray analysis of 1a, was developed, and the ability to enter into this type of interaction was estimated. The X-ray analysis of the pyridine analogue of 1a revealed no intramolecular stacking interaction. The theoretical studies were evaluated in light of the observed receptor affinities, and the relevance of the solid-state geometry of 1a to the receptor-bound geometry was assessed. It is suggested that the stacked geometry found in the X-ray structure of 1a does not represent a conformation that is relevant to that bound at the histamine H2 receptor.
Animals↗
Quantitative determination of plasma fibrinolytic activity in patients with ruptured intracranial aneurysms who are receiving epsilon-aminocaproic acid: relationship of possible complications of therapy to the degree of fibrinolytic inhibition.
Fifty-two patients were each given a constant infusion of 1.5 g of epsilon-aminocaproic acid (EACA) per hour after subarachnoid hemorrhage (SAH) from an intracranial aneurysm. Each patient's available plasminogen activity (APA), a measure of plasma fibrinolytic activity, was determined by fluorometric assay before and during EACA treatment. Five categories of potential EACA complications were identified: rebleeding, cerebral vasospasm, hydrocephalus, thrombosis, and miscellaneous (bleeding time prolongation, thrombocytopenia). The APA of the 37 patients with complications was significantly higher than that of the 15 without complications. Four patients suffered rebleeding episodes and had significantly higher APA levels during EACA therapy when compared to all other patients, i.e., those with and without other complications. Patients with vasospasm, hydrocephalus, and thrombotic complications also had significantly higher APA levels during EACA therapy compared to patients without complications. The latter may be simply a reflection of the activation of fibrinolytic activity that occurs after SAH. It is apparent from these studies that, after the initiation of EACA treatment, a maximal steady state inhibition of fibrinolytic activity is not achieved for 2 days and, after the cessation of EACA therapy, normal fibrinolytic activity is not restored for a period of 3 to 4 days. In addition, patients with thrombotic events may show persistently low serum plasminogen activity after discontinuance of EACA therapy, probably due to continuing thrombosis and consumption of plasminogen. These results indicate that patients with recurrent preoperative aneurysmal hemorrhage while on EACA therapy may have inadequate fibrinolytic inactivation, and this may be an important factor contributing to rebleeding episodes.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Conformational requirements for histamine H2-receptor inhibitors: a structure-activity study of phenylene analogues related to cimetidine and tiotidine.
Two series of compounds related to cimetidine and tiotidine were synthesized as part of a study to evaluate the importance of conformational parameters in binding at histamine H2 receptors. The flexible methylthioethyl connecting chain was replaced by a conformationally restricting phenylene unit. These compounds were evaluated for antagonism of the dimaprit-stimulated chronotropic response in the guinea pig atrium and inhibition of histamine stimulated secretion of gastric acid in the dog. In both series, biological activity is markedly dependent on the m-phenylene regioisomers. Histamine H2-receptor activity is retained in both series; however, in the tiotidine series, gastric antisecretory activity is significantly improved. Regardless of the end group, N-cyanoguanidine 1,1-diamino-2-nitroethene or 3,4-diamino-1,2,5-thiadiazole 1-oxide, each 3 3-(2-guanidino-4-thiazolyl)phenyl analogue was ca. 8 and 90 times more potent intravenously than tiotidine and cimetidine, respectively. The electronic influences of the phenylene unit on biological activity were also evaluated. It was concluded that the geometric constraints imposed by the m-phenylene connecting element were more important than electronic factors in binding events at the histamine H2 receptor.
Animals↗
Inhibitors of gastric acid secretion: antisecretory 2-pyridylurea derivatives.
A series of aminoalkyl-substituted pyridylureas has been prepared and evaluated as inhibitors of gastric acid secretion. N,N-Dimethyl-N'-[2-(diisopropylamino)ethyl]-N'-(4,6-dimethyl-2-pyridyl)urea (8g) was the most potent example of the class. Comparison of this compound with cimetidine showed it to be equipotent in dogs stimulated with gastrin tetrapeptide but approximately half as potent in dogs stimulated with histamine. Inhibition of secretion does not appear to result from antagonism of the histamine H2 receptor, since the compounds show only weak inhibition of the H2 receptor in vitro.
Animals↗
A deuterium isotope effect on the inhibition of gastric secretion by N,N-dimethyl-N'-[2-(diisopropylamino)ethyl]-N'-(4,6-dimethyl-2-pyridyl)urea. Synthesis of metabolites.
The use of isotopic substitution to retard the oxidative metabolism of the gastric antisecretory agent N,N-dimethyl-N'-[2-(diisopropylamino)ethyl]-N'-(4,6-dimethyl-2-pyridyl)urea (1) and improve its antisecretory potency was examined. The pyridine ring methyl hydrogens of 1 were replaced with either deuterium or fluorine. The hexadeuterated analogue (12) was found to be approximately 2.1 times more potent than the protio form (1) as an inhibitor of gastric acid secretion stimulated by gastrin tetrapeptide. The hexafluoro analogue (11) was 0.4 times as potent as 1. A useful pyridine ring synthesis was developed to prepare the metabolites of 1, 10a (4-hydroxymethyl) and 10b (6-hydroxymethyl), and the hexafluoro analogue 11. These syntheses involved the condensation of 1,3-diketones with an appropriately N-substituted amidinoacetate.
Animals↗
Inhibition of gastric acid secretion by 1,8-naphthyridin-2(1H)-ones.
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Animals↗
Age estimations from diaphyseal lengths: two months to twelve years.
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Age Determination by Skeleton↗
A prehistoric achondroplastic dwarf from California: a preliminary note.
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History of Medicine↗
Pilot study of positron emission tomography in patients with advanced head and neck cancer receiving radiotherapy and chemotherapy.
BACKGROUND: Positron emission tomography (PET) provides a noninvasive modality for evaluating the biochemical processes of normal and pathologic tissue. Preliminary reports of F-18 fluorodeoxyglucose (FDG) PET indicate its potential usefulness in evaluating head and neck tumors. The current study was performed to explore the relationship between changes in tumor FDG metabolism and local control in patients receiving hyperfractionated radiotherapy and concurrent chemotherapy. METHODS: The study group consisted of six patients with locally advanced, nonmetastatic squamous cell carcinoma of the head and neck. FDG studies were performed prior to, during, and 24 months post-therapy. Ratios of tumor to nontumor FDG uptake in regions of interest (ROI) were compared. RESULTS: All pretherapy studies demonstrated a focal hypermetabolic abnormality corresponding to the known tumor. The pretherapy tumor to nontumor FDG ratios declined significantly during therapy (p < 0.05) with a similar continued trend post-therapy (p < 0.07). CONCLUSION: The treatment-induced decrease in tumor hypermetabolism as seen on serial FDG PET parallels the clinical response in squamous carcinoma of the head and neck. Two-year follow-up scans also suggest that continued low tumor to nontumor ratios reflect eradication of local disease. Because of its high cost, a study of larger numbers of patients is necessary to better define the role of PET in the management of head and neck cancer.
Adult↗
Prevalence of hypertension in patients with type II diabetes in referral versus primary care clinics.
We compared the prevalence of hypertension in patients with non-insulin-dependent diabetes mellitus (NIDDM) in referral and primary care practices using definitions of The Fifth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC-V), while controlling for other risk factors such as hypertension, obesity, smoking, and age. Patients (n = 1443) were enrolled consecutively from a large referral practice at the Jackson Diabetes Center and four primary care clinics in the vicinity. Blood pressures were measured at three clinic visits after a 5-min rest in a sitting position using a standard clinical sphygmomanometer. Charts were reviewed to determine diabetes duration, insulin usage, height, weight, smoking history, use of antihypertensive and oral hypoglycemic medications, socioeconomic status, and race. Patients were classified as hypertensive based on JNC-V definitions or if they were on antihypertensive medication. Hypertension was termed uncontrolled if blood pressure was JNC-V Stage 2 or higher while on antihypertensive medication. Seventy-eight percent of referral clinic and 55% of primary care clinic patients had either JNC-V State 1 or higher hypertension or were on antihypertensive medication. Actual blood pressures indicated that more patients had JNC-V Stage 1 (mild) or higher hypertension in referral compared to primary care clinics (62% versus 48% p = 0.01) but fewer had JNC-V Stage 2 or higher (moderate-severe) hypertension (12% versus 19% p = 0.002). Patients seen in the referral clinic were significantly more likely to have greater age, greater duration of diabetes, higher insulin dosage, longer smoking history, antihypertensive medication, and live outside the metropolitan area. By logistic regression, the odds of hypertension were significantly increased with age (OR 1.51/decade), BMI greater than 27 (OR 2.17), diabetes duration (OR 1.04/year), and insulin dosage (OR 1.74/U/kg). Current smoking and attending a referral clinic were not significantly related. The odds of moderate-severe hypertension were significantly increased with age (OR 1.23/ decade), decreased by attending a referral clinic (OR 0.45), and not significantly related to other confounders in the model. The prevalence of hypertension among patients with NIDDM was higher in referral than primary care clinics. The higher prevalence in the referral practice can be accounted for by the greater severity of associated risk factors in the referral practice patients; however, most patients will be diagnosed and treated for hypertension prior to referral. More patients in the referral practice were on hypertensive medication, which lowered the stage or severity of hypertension but still not to the normal range. The results suggest that the primary detection of hypertension in patients with type II diabetes resides with the primary care physician. Management of hypertension will require both a delineation and acceptance of responsibilities between the primary care physician and diabetes specialists.
Blood Pressure↗
FDG-PET in the selection of brain lesions for biopsy.
The CT-guided stereotaxic needle biopsy has become a widely used procedure in the diagnostic evaluation of intracranial lesions including tumors. Conventional CT or MR frequently defines the anatomic regions of abnormality, which may be multiple lesions or a single lesion that is heterogeneous in cellular composition owing to the topographic variation of cellular constituency or the combination of active disease, nonspecific inflammation, necrosis, and/or edema. In these cases, selection of the most appropriate site for a successful diagnostic needle biopsy can be difficult. In three patients, we have used [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) to determine the site most likely to provide a diagnostic biopsy result. In the first patient, who presented with confusion, multiple biopsies from the temporal lobe, based on MR abnormalities, revealed only reactive gliosis and edema. Repeat biopsy directed by PET revealed an anaplastic astrocytoma. In a second patient, PET allowed us to differentiate radiation effect from active metastatic breast cancer. In the third patient, who presented with a grand mal seizure, biopsy of a CT-defined hypodense region demonstrated lymphocytosis. Metabolism of FDG was normal or increased in areas of Aspergillus encephalitis at autopsy. These preliminary studies suggest a complementary role for FDG-PET and CT or MR in selected patients for defining the intracranial site most likely to yield a positive biopsy result.
Adenocarcinoma↗
FDG-PET in pediatric posterior fossa brain tumors.
Seventeen pediatric patients with posterior fossa brain tumors were studied with 2-[18F]fluoro-2-deoxy-D-glucose (FDG) and positron emission tomography (PET). The FDG uptake was ranked by two observers, and the results were correlated with tumor histology. Increased FDG uptake was associated with more malignant and aggressive tumor types. Heterogeneity of FDG uptake was associated with previous therapy, including radiation therapy and chemotherapy. 2-[18F]Fluoro-2-deoxy-D-glucose PET will likely be an important adjunct in the management of pediatric posterior fossa tumors, much as in adult patients with brain tumors.
Adolescent↗
Serial FDG-PET studies in the prediction of survival in patients with primary brain tumors.
OBJECTIVE: This study examines the changes in tumor [18F]fluoro-2-deoxyglucose (FDG) uptake on serial FDG-PET studies and the ability of serial FDG-PET studies to predict survival in patients with treated and untreated primary brain tumors. MATERIALS AND METHODS: The study population included 20 patients with primary brain tumors. Changes in FDG uptake over time were visually assessed and correlated with clinical course and survival. RESULTS: Although little change in FDG uptake was noted for individual patients, high average FDG uptake (greater than or equal to gray matter) on serial studies was associated with shorter survival. Patients with persistently low FDG uptake (less than gray matter) survived significantly longer than patients with persistently high FDG uptake (p = 0.007). CONCLUSION: Serial evaluation of metabolic activity with PET may provide more accurate prognostic information than a single FDG uptake determination in patients with primary brain tumors.
Adult↗
Accuracy of surface fit registration for PET and MR brain images using full and incomplete brain surfaces.
OBJECTIVE: The accuracy of a surface-fitting image registration technique has been investigated for matching [18F]fluorodeoxyglucose (FDG) and [15O]H2O PET brain images with MR images. Use of partial-brain surfaces (a single hemisphere or a limited number of slices) was investigated to simulate cases in which severe brain defects or limited axial field of view would preclude using the entire brain surface. MATERIALS AND METHODS: Three FDG and three H2O scans were performed on five volunteers, in addition to volume MR studies. Fiducial markers were placed on the subjects' scalps to provide references for registration accuracy. The registration procedure was applied to each PET-MR set, using the surfaces defined by locating the brain edge in multiple slices for each set. RESULTS: The surfaces fit well, with only 1% scaling necessary for the best fit. Errors in fiducial marker positions between MRI and transformed PET were < 2 mm in the transverse directions and < 4.5 mm in the axial direction. Fits based on the partial surfaces worked well and gave results very similar to the full-brain fits. CONCLUSION: The surface-fitting technique is accurate for FDG and H2O PET studies, even when part of the brain surface cannot be used.
Algorithms↗