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Biomedical subjects

W Briner

Publications and source records attributed to W Briner.

At least 19 recordsLinked to original sources

The effect of GABA receptor ligands in experimental spina bifida occulta.

BACKGROUND: The pathophysiology behind spina bifida and other neural tube defects (NTDs) is unclear. Folic acid is one variable, but other factors remain. Studies suggest that substances active at the GABA receptor may produce NTDs. To test this hypothesis pregnant rats were exposed to either the GABA a agonist muscimol (1, 2 or 4 mg/kg), the GABA a antagonist bicuculline (.5, 1, or 2 mg/kg), the GABA b agonist baclofen (15, 30, 60 mg/kg), or the GABA b antagonist hydroxysaclofen (1, 3, or 5 mg/kg) during neural tube formation. Normal saline was used as a control and valproic acid (600 mg/kg) as a positive control. The embryos were analyzed for the presence of a spina bifida like NTD. RESULTS: After drug administration the pregnancies were allowed to proceed to the 21st day of gestation. Then embryos were removed and skeletons staining and cleared. Vertebral arch closure was measured. Results indicate that the GABAa receptor agonist muscimol, the GABAa receptor antagonist bicuculline, and the GABAb agonist baclofen produced NTDs characterized by widening of the vertebral arch. Oppositely the GABAb antagonist hydroxysaclofen produced narrowing of the vertebral arches. CONCLUSIONS: The findings indicate that GABA a or b ligands are capable of altering neural formation. GABA may play a greater than appreciated role in neural tube formation and may be important in NTDs. The narrowing of the vertebral arch produced by the GABA b antagonist hydroxysalcofen suggests that GABA b receptor may play an undefined role in neural tube closure that differs from the GABA a receptor.

Animals↗

Corticosteroid injection therapy for overuse injuries.

Local corticosteroid injection therapy may be considered for many conditions commonly treated by the primary care physician. Chronic overuse and flawed biomechanics may lead to inflammation in areas easily accessible to injected local corticosteroids, including bursae, tendon sheaths and joints. It is generally preferable to mix the steroid preparation with an anesthetic agent to minimize the injection pain, provide immediate symptom relief and confirm the diagnosis. Local complications of corticosteroid injection include tendon and ligament weakening, bacterial infections of joints and related structures, and subcutaneous tissue atrophy. Systemic complications are rare but reportedly include hyperglycemia and adrenal axis suppression.

Adrenal Cortex Hormones↗

Arnold-Chiari-like malformation associated with a valproate model of spina bifida in the rat.

The brains of rat fetuses exposed to saline and valproic acid (VA: 600 mg/kg or 1,200 mg/kg) at 10 days of gestation were examined for structural changes similar to that seen for the Arnold-Chiari malformation (ACM) in humans. Only fetuses exposed to the 1,200-mg/kg level VA demonstrated spina bifida (SB) type widening of the vertebral arch when compared to saline treated animals. When compared to controls, both 600-and 1,200-mg/kg VA animals demonstrated microencephaly. The brains of treated animals demonstrated alterations in their angular morphology such that the cerebellum was displaced toward the foramen magnum in a manner akin to human ACM. These findings indicate that valproate-induced SB in the rat more closely approximates SB in humans than was previously appreciated and provides a model for experimental study of both SB and ACM.

Animals↗

A behavioral nosology for tinnitus.

Studies of the physiological and psychological characteristics of tinnitus and its treatment have yielded a variety of conclusions. The variation in results may reflect heterogeneous patient populations. Although the sources of variation are many, one may be derived from combining patients of several severities of tinnitus into a single group. A nosology is proposed for tinnitus severity to be classified by the patient's behavioral responses. Classifying patients allows direction to specific treatment modalities and will facilitate research. The concept of phantom auditory pain and a rational basis for the use of antidepressant therapy are discussed.

Activities of Daily Living↗

A scanning electron microscope study of the human cervical lymph node.

Arterial casts of human cervical lymph nodes were studied using scanning electron microscopy. Human cervical lymph nodes appear to be much more complex and dense than their animal counterparts. Human lymph nodes have a separate medulla arising from the hilar artery complex and cortical structure derived from capillaries. Also present is a previously unknown rosette formation of blood vessels. The possible implications of these findings for inflammatory and neoplastic diseases are discussed.

Arteries↗

Reduction of oral microbes by a single chlorhexidine rinse.

Because of the continued threat of human immunodeficiency virus and hepatitis B infection, as well as the possibility of cross-infection from microbes, such as the herpesviruses and staphylococci, infection control remains a critical issue in dentistry. A traditional response to the infection-control issue is the use of barrier protection by the practitioner and staff. Little attention has been paid to reducing the number of potential pathogens in the oral cavity before dental procedures as a means of minimizing the potential spread of contagion between patients and treatment providers. A study to determine the effectiveness and duration of a single rinse with 0.12% chlorhexidine gluconate oral antiseptic in reducing the number of microorganisms in the oral cavity is presented.

Bacteria, Aerobic↗

Synthetic prostaglandin E1 misoprostol as a treatment for tinnitus.

OBJECTIVE: A pilot study to determine if the synthetic prostaglandin E1 misoprostol is effective in treating severe tinnitus, to test the hypothesis that tinnitus production is related to prostaglandin metabolism. DESIGN: Blinded, placebo controlled, hemicrossover. SETTING: House Ear Clinic, Los Angeles, Calif. PATIENTS: A volunteer and convenience sample of 24 subjects complaining of severe tinnitus was recruited from mailings, telephone calls, and the clinic population. The patients were not preselected except to be in otherwise good health. INTERVENTION: Subjects were started on a regimen of placebo or 200 micrograms/d of misoprostol. The dosage was increased every 5 days by 200 micrograms until a total of 800 micrograms/d was achieved. After 1 month of drug administration, the placebo group was crossed over to the active drug phase. MAIN OUTCOME MEASURES: Outcome was measured in terms of subjective reports of tinnitus severity, sleep patterns, and ability to concentrate. RESULTS: Eight (33%) of the 24 patients reported improvement during the active drug phase. There were no placebo responders. Responders reported improvement in tinnitus severity, sleep, and concentration. CONCLUSIONS: Findings support the contention that prostaglandins may be useful in the treatment of tinnitus. Further studies with larger samples are needed before widespread use of this intervention can be recommended.

Adult↗

Evaluation of amino-oxyacetic acid as a palliative in tinnitus.

Amino-oxyacetic acid (AOAA) was evaluated as a palliative in tinnitus. Sixty-six patients with tinnitus presumed to be of cochlear origin were given either a placebo or 75 mg of AOAA four times a day for 1 week. Response was evaluated by both audiometric measurement of tinnitus loudness and subjective rating by patients of change or no change in tinnitus severity. Because loudness measurements and self-rating have not been shown to be independent, and since the aim of clinical treatment of tinnitus is the alleviation of subjective distress, greater weight was given to the patient's self-rating. A total of 21% of all patients reported a subjective decrease in tinnitus severity, usually within 3 to 4 days after the start of AOAA use. Patients with tinnitus caused by presbycusis or Meniere's disease were the most likely to respond to AOAA treatment with a reduction in tinnitus severity, whereas those with drug-induced tinnitus were the least likely to respond. Nausea and dysequilibrium were the most common side effects of AOAA use. Of the 21% of patients who responded to AOAA, 71% developed some type of side effect. Amino-oxyacetic acid produces a reduction in the severity of tinnitus in about 20% of patients; however, the incidence of side effects makes the drug unacceptable for clinical use.

Acetates↗

In vitro virucidal effectiveness of a 0.12%-chlorhexidine gluconate mouthrinse.

The purpose of this work was to assess the in vitro antiviral effectiveness of a mouthrinse (Peridex) containing 0.12% chlorhexidine gluconate (CH) on several viruses that are associated with the oral cavity. These included herpes simplex virus (HSV), cytomegalovirus (CMV), influenza A, parainfluenza, polio, and hepatitis B (HBV). Virucidal assays in tissue cultures were performed on all viruses except HBV. The virucidal effect on HBV was assessed by inactivation of the DNA polymerase contained within the Dane particle of HBV. The CH mouthrinse had virucidal activity against all of the viruses, except polio, in as little as 30 s. The virucidal activity increased with time. However, there were differences in the responses of these viruses to the challenge of the CH mouthrinse, probably due to subtle differences in the physical/chemical structures of the virus envelopes. Results on DNA polymerase of the HBV virus were similar to those on the other viruses, except polio, suggesting a common mechanism. With respect to this mechanism, it was proposed that CH exerted its antiviral effect on the envelopes of these viruses, and that the absence of an envelope on polio precluded effectiveness against this virus.

Animals↗

Use of the Million Clinical Multiaxial Inventory in evaluating patients with severe tinnitus.

The Million Clinical Multiaxial Inventory (MCMI) was evaluated as a diagnostic tool for personality disorder among 41 patients with severe tinnitus. Nearly 70 percent of the subjects demonstrated a personality disorder. Nearly half of the patients fell into one of two categories; dependent/submissive or the narcissistic category. Other important features include a high incidence (24%) of severe anxiety. One-third of the patients had a complaint tendency but 50 percent had a denial problem. We have found the MCMI to be easy to administer and evaluate and it provides the clinician with useful information. We believe that more routine use of this or similar instruments would improve the treatment outcome of tinnitus sufferers by bringing into focus the important psychological factors found in each patient.

Auditory Perceptual Disorders↗

Behavioral correlates of renal damage and cardiac changes.

The locomotor activity (determined by open-field test) and analgesic response (measured by tail-flick latency) of rats were evaluated during exposure to novel stimuli and again after exposure to shock. The effects of shock stress on hearts and kidneys were evaluated. This study has found that the more active an animal is when exposed to a novel stimuli the more likely it is to develop renal damage or cardiac changes after shock. Shock stress was found to produce changes in locomotor activity and analgesic state, but shock did not correlate as well with cardiac changes as did the animal's response to novel stimuli. A novel system of evaluating renal damage, which correlated to behavioral changes and organ damage, is described.

Animals↗

The superiority of the Goodwin procedure over the traditional procedure in measuring the loudness level of tinnitus.

The results of two procedures for measuring the loudness level of tinnitus will be presented. The traditional procedure yielded significantly smaller loudness matches, when expressed in decibel sensation level (i.e., dB SL), than did the Goodwin procedure. The Goodwin procedure is more sensitive to pharmacologically induced changes in tinnitus loudness than is the traditional procedure. The Goodwin method correlates well with changes in patient's subjective rating of tinnitus severity. The Goodwin match has a larger reliability coefficient. Nonlinear correlation also indicates that the Goodwin procedure is superior to the traditional method.

Aminooxyacetic Acid↗

Psychosocial enhancement of immunocompetence in a geriatric population.

This study assessed the enhancement of immunocompetence by relaxation and social contact in 45 geriatric residents of independent-living facilities. Subjects were randomly assigned to one of three protocols: relaxation training, social contact, or no contact. Subjects in the relaxation and social-contact conditions were seen individually three times a week for a month. Blood samples and self-report data were obtained at baseline, at the end of the intervention, and at a 1-month follow-up. At the end of the intervention, the relaxation group showed a significant increase in natural killer cell activity, and significant decreases in antibody titers to Herpes simplex virus and self-rated distress; the other two groups showed nonsignificant changes. There was a general increase in the T-lymphocyte response to phytohemagglutinin stimulation at the end of the intervention, with greater change at lower mitogen concentrations. These data suggest that cellular immunocompetence may be enhanced by psychosocial interventions.

Aged↗

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) as a potent and persistent thyroxine agonist: a mechanistic model for toxicity based on molecular reactivity.

TCDD and thyroxine have common molecular reactivity properties which enable them to present a planar face and lateral halogens in interactions with proteins. These molecular properties are consistent with the structure-toxicity relationship for TCDD and related compounds. Biological evidence is discussed including preliminary studies on the effects of TCDD exposure on tadpole growth and development which is consistent with the possible thyroxine-like activity of TCDD. The work suggests the possibility that toxicity is at least in part the expression of potent and persistent thyroid hormone activity (responses induced by TCDD which qualitatively correspond to those mediated by thyroid hormones). A mechanism for toxicity is proposed which involves receptor proteins; the planar aromatic system controls binding to cytosolic proteins and halogen substituents regulate binding to nuclear proteins. This simple model based on molecular reactivity sheds light on the diversified effects of TCDD and related compound toxicity and on certain thyroid hormone action. The model also permits predictions to be made with regard to the toxicity and thyroid hormone activity of untested compounds. In addition, the model suggests a general mechanism for hormone action based on metabolically regulated differential and cooperative protein receptor binding events in cellular compartments which can explain agonism, antagonism and potentiation within the framework of receptor occupancy theory.

Animals↗

Immunodiagnosis of tumors in vivo using radiolabeled monoclonal antibody A2B5.

Recently a murine monoclonal antibody (A2B5) has been described that reacts with a membrane associated GQ ganglioside common to peptide secreting normal cells and tumors. In vitro binding data demonstrated the presence of this ganglioside on neurons, adrenal medulla, and pancreatic islets, along with neuroendocrine tumors such as insulinomas, pheochromocytomas, melanomas and neuroblastomas. Negative binding has previously been shown for tissue sections from liver, kidney, colon, lung, stomach, and tumors not derived from the neural crest. Because of the specificity at A2B5 in vitro, this monoclonal antibody was labeled with 131I for in vivo tumor localization studies. Daily radionuclear scans were obtained in 5 KX rats bearing the radiation induced rat insulinoma with disappearance of the label from the blood pool and concentration in the tumor so that by the fourth day, the only activity present by scan was in the insulinoma. Tissue-counting data showed tumor/blood ratios (av +/- SE, 1.29 +/- 0.25) of A2B5 activity two to ten times the average activity found in other organs (0.28 +/- 0.05). No tumor concentration of the control nonspecific monoclonal antibody P3X63 was evident (0.27 +/- 0.04). In addition A2B5 also localized to five different human melanoma cells lines grown in nude mice with high tumor/blood levels (1.04 +/- 0.27) compared to normal tissues (0.32 +/- 0.05) (P = .0005), while no localization is seen in nudes carrying osteosarcomas, colon, bladder, and renal cell carcinomas. In addition antibody A2B5 did not concentrate in any normal tissue though the antigen is present on several. The finding that A2B5 reacts across species lines (mouse, rat, man) lends itself to obvious diagnostic and therapeutic possibilities.

Adenoma, Islet Cell↗

In vivo and in vitro binding of iodinated monoclonal antibody A2B5 to RIN insulinoma cells.

Monoclonal antibody A2B5 reacts with the cell surface of a series of amine precursor uptake decarboxylation (APUD) cells and their tumors in many vertebrate species including chicken, rat, mouse, and man. We have studied the in vivo and in vitro binding of iodinated monoclonal antibody A2B5 to rat insulinoma cells. In vitro, radiolabeled A2B5 binds specifically to RINm5F insulinoma cells and the binding of 125I-A2B5 is inhibited by unlabeled A2B5 or a ganglioside extract of RINm5F cells. In vivo, scintigrams taken Day 0 to Day 5 after injection of 131I-labeled A2B5 showed a striking localization of 131I-A2B5 in transplanted RIN tumors grown in syngeneic rats. Other control radiolabeled monoclonal antibodies did not concentrate in the tumors. 131I-labeled A2B5 did not concentrate in other transplantable tumors (colon adenocarcinoma, osteosarcoma, renal cell carcinoma, and bladder transitional cell carcinoma) grown in nude mice. The tumor/blood ratio detected 5 days after antibody injection, was approximately two to 12 times higher in the insulinoma compared to other organs and only in the insulinoma did 131I-A2B5 show a higher concentration than control antibody 125I-P3X63.

Adenoma, Islet Cell↗

Lymphoscintigraphy for malignant melanoma. Surgical considerations.

Lymphoscintigraphy using technetium-99m atimony sulfur colloid was performed in 22 patients with melanoma referred to Duke University Comprehensive Cancer Center in an attempt to identify patterns of regional lymphatic drainage. Scans from six patients revealed lower extremity lesions with three located below the knee, one in the popliteal space, and two others proximal to the knee joint. Despite the location of the primary, all scans but one showed initial drainage to the inguinal nodes bypassing the popliteal lymph node group. Of the three patients who had primary melanoma of the posterior scalp, the lymphatic drainage was directed to the posterior cervical nodes. No drainage to the parotid nodes or anterior neck nodes was visualized. The knowledge gained from lymphoscintigraphy resulted in posterior neck dissections instead of the standard anterior neck dissection and superficial parotidectomy. In areas of ambiguous lymphatic drainage from the trunk, radiocolloid scanning can identify areas at risk for developing metastatic disease. Six lesions within 5 cm of the midline demonstrated bilateral axillary or groin drainage in 83 per cent of the patients. For two lesions near Sappey's line colloidal uptake to the ipsilateral axilla and groin was the rule. After a 3-year follow-up, during which time 70 to 90 per cent of lymph node metastases are predicted to occur, no nodal metastases were ever documented in areas that did not show colloidal uptake. No correlation was found between amount of radiolabel in positive compared to negative nodes, although those nodes that were completely replaced by tumor contained no 99mTc activity and were negative on scanning.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of aspirin and dipyridamole on platelet function, hematology, and blood chemistry of saturation divers.

Twenty-four young male divers were assigned randomly to 4 treatment groups: Group I received aspirin (325 mg) three times daily; II received dipyridamole (75 mg) three times daily; III received both drug regimens; and IV received matching placebo. Double-blind procedures were followed. Treatment began 24 h prior to a 48-h saturation dive (inclusive of 17 h decompression) at a simulated depth of 18.3 m and continued throughout and for 3 days after the dive. A post-dive reduction in circulating platelet count was observed in all groups, except the group that received aspirin only. Platelet survival was shortened in all treatment groups. Five cases of Type I decompression sickness occurred and were treated by recompression, two in the aspirin plus dipyridamole group, two in the dipyridamole group, and one in the placebo group. Blood chemistry and hematology profiles showed that divers with decompression sickness had more elevated GOT, GPT, CPK, cholesterol and triglyceride levels, and greater reductions in platelet count, Platelet Factor 4 and Thrombin Clotting Time than most other subjects. Subjects receiving either aspirin or aspirin plus dipyridamole had fewer changes in these parameters. Failure of aspirin to potentiate, or add to, dipyridamole may be due to other actions of aspirin such as inhibition of prostacyclin synthesis. Further studies of the role of antiplatelet drugs in decompression sickness are warranted.

Adult↗