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Biomedical subjects

C L Smith

Publications and source records attributed to C L Smith.

409 records · Page 23Linked to original sources

The role of pharmacy in the management of patients with temporomandibular disorders and orofacial pain.

OBJECTIVE: To provide information regarding the current understanding of the etiology and treatment, both nonpharmacologic and pharmacologic, of orofacial pain conditions including temporomandibular disorders (TMDs). This review briefly discusses the etiology and pathophysiology underlying the development of TMDs, generally accepted nonpharmacologic methods of treatment, and the most common current pharmacologic management approaches. DATA SOURCES: Current medical literature and the authors' clinical experiences. DATA SYNTHESIS: TMDs encompass a number of diagnostic subgroups that involve the masticatory musculature, the temporomandibular joint(s), and associated structures. More than 10 million individuals in the United States are affected by TMDs. Most current pharmacologic management approaches in the treatment of orofacial pain conditions, including TMDs, involve the use of antidepressants, anticonvulsants, muscle relaxants, corticosteroids, and nonsteroidal anti-inflammatory drugs. CONCLUSION: Inclusion of pharmacists who are knowledgeable in the nonpharmacologic and pharmacologic treatment approaches on the TMD management team would improve therapeutic monitoring, follow-up, and outcomes in these patients.

Anticonvulsants↗

Recombinant metallothionein-conjugated streptavidin labeled with 188Re and 99mTc.

Consideration is now being given to the use of avidin (or streptavidin) and biotin for radiotherapy of tumor. Accordingly, the goal of this study was to radiolabel a mouse metallothionein-streptavidin fusion protein with 188Re and to compare its properties to those of the same fusion protein radiolabeled with 99mTc. A recombinant metallothionein-streptavidin fusion protein was radiolabeled by transchelation with 99mTc- and 188Re-glucoheptonate. Labeling efficiency, which was not optimized for either radionuclide, was approximately 60% for 99mTc and 20% for 188Re. Radiochemical purity was demonstrated by size exclusion HPLC both by nearly quantitative shifts of the 188Re label to higher molecular weight upon the addition of biotinylated antibody and by the absence of a shift with biotinsaturated 188Re-metallothionein-streptavidin. Stability of the labels in 37 degrees C serum was evaluated by comparing the HPLC radiochromatograms of serum samples both before and after the addition of biotinylated antibody. The 188Re label behaved like 99mTc in that the same peaks were evident, including one prominent peak due to labeled cysteine. Recoveries during HPLC analysis of serum samples showed that oxidation rates to perrhenate and pertechnetate were identical. However, instability to cysteine challenge was greater for 188Re; for example, the loss of label to cysteine after 24 h under one set of conditions was 41% for 188Re and 22% with 99mTc. Analysis by HPLC of liver and kidney homogenates from mice administered the labeled antibodies were qualitatively and, in large measure, quantitatively independent of label. Biodistributions at 5 h in normal mice were statistically identical between the two labels in blood and in most tissues. In conclusion, streptavidin may be radiolabeled with radiorhenium using recombinant mouse metallothionein as a bifunctional chelator, and under one set of labeling conditions at least, 188Re showed similar in vitro and in vivo behavior to that of 99mTc labeled to the same fusion protein.

Animals↗

In vitro evaluation of the effect of dimethyl sulfoxide on equine articular cartilage matrix metabolism.

OBJECTIVE: To evaluate the effects of dimethyl sulfoxide (DMSO) on equine articular cartilage matrix metabolism. STUDY DESIGN: Using a cartilage explant culture system, proteoglycan (PG) synthesis, PG release, lactate metabolism, chondrocyte viability, and metabolism recovery were determined after cartilage exposure to DMSO. SAMPLE POPULATION: Cartilage harvested from metacarpophalangeal and metatarsophalangeal joints of 12 horses (age range, 1 to 10 years). METHODS: Explants were exposed to concentrations of DMSO (1% to 20%) for variable times (3 to 72 hours). PG synthesis and release were determined by a radiolabel incorporation assay and dimethylmethylene blue (DMMB) dye assay, respectively. Lactate released into culture media was measured, and chondrocyte viability was assessed using the Formizan Conversion Assay and a paravital staining protocol. Metabolism recovery was assessed in explants that were allowed to recover in maintenance media after exposure to DMSO. RESULTS: PG synthesis and lactate metabolism were inhibited in a dose- and time-dependent manner after exposure to DMSO concentrations > or = 5%; there was no significant alteration in PG release. No change in chondrocyte viability was detected after incubation with DMSO. PG synthesis and lactate metabolism returned to baseline rates when allowed a recovery period after exposure to DMSO. CONCLUSIONS: DMSO concentrations > or = 5% suppress equine articular cartilage matrix metabolism. Suppression of PG synthesis and lactate metabolism is reversible and does not appear to be the result of chondrocyte death. CLINICAL RELEVANCE: Equine clinicians adding DMSO to intraarticular lavage solutions should be aware that DMSO may have deleterious effects on equine articular cartilage matrix metabolism.

Analgesics, Non-Narcotic↗

Use of 5-nitroindole-2'-deoxyribose-5'-triphosphate for labelling and detection of oligonucleotides.

The 5'-triphosphate of 5-nitroindole-2'-deoxyriboside has been shown to be a good substrate for terminal deoxynucleotidyl transferase (TdT). An antibody has been prepared for the detection of 5-nitroindole and has been used for the detection of 5-nitroindole tailed DNA both in single-stranded form and after hybridisation to a template. This is therefore a new method for the detection of nucleic acid probes.

Antibodies↗

Synthesis and incorporation of pyrrole carboxamide nucleoside triphosphates by DNA polymerases.

We have synthesised and examined the enzymatic incorporation properties of the 5'-triphosphates of 2'-deoxyribosyl pyrrole 3-monocarboxamide (dMTP) and 2'-deoxyribosyl pyrrole 3,4-dicarboxamide (dDTP). These analogues we had hoped would behave as ambivalent base analogues in that they can present two alternative hydrogen-bonding faces either by rotation about the carboxamide group or about the glycosidic bond. The two pyrrole derivatives, dMTP and dDTP, exhibit a preference for incorporation with Klenow polymerase. They are preferentially incorporated as either A or C.

Base Sequence↗

Synthesis and study of the fluorescein conjugate of the nucleotide dPTP.

The synthesis of a fluorescein conjugate on the non-natural base P is described. The ability of the newly synthesised fluorescein--dPTP and of a fluorescein-11-dUTP to compete with the natural nucleotide TTP was also studied. Overall the efficiency of labelling a nucleic acid with a fluorescein moiety was found to be approximately equal.

Binding, Competitive↗

The molecular biology of rabies viruses.

Comparative nucleotide and deduced amino acid sequence analyses of the RNA and proteins of several fixed rabies virus strains have allowed detailed characterization of structural-functional relations of individual virus components. Several unique features of rabies viruses have been deduced from the complete nucleotide sequences of four of the five genes and the four intergenic regions of the genome. The most extensively analyzed rabies virus gene has been that of the surface glycoprotein. Direct comparisons between the deduced amino acid sequences of glycoprotein variants have led to the location of specific sites on the glycoprotein that bind virus-neutralizing antibodies and to the identification of an epitope correlating with viral pathogenicity. Structural requirements for immunogenic activity within the glycoprotein have also been investigated. This article presents an overview of the molecular biology of rabies viruses and describes the current state of knowledge of immunobiologic characteristics of different rabies virus components.

Amino Acid Sequence↗

Hyperphosphatemia in a burn patient.

Hypophosphatemia has been observed in severely burned patients and has been associated with increased mortality. Hyperphosphatemia has rarely been described in this population. We present a burn patient with hyperphosphatemia, hypercalciuria, and suppressed parathyroid hormone level 5 months after the initial burn. The patient's presentation is most consistent with the effect of immobilization on bone and calcium metabolism.

Adult↗

Prevention of relapse in reflux esophagitis: a placebo controlled study of ranitidine 150 mg bid and 300 mg bid.

OBJECTIVE: To compare the efficacy and safety of long term use of ranitidine 150 mg bid, 300 mg bid and placebo in prevention of endoscopic and symptomatic relapse of reflux esophagitis in an international, double-blind, placebo controlled, parallel group study. PATIENTS AND METHODS: A total of 279 patients at least 18 years old from hospital out-patient departments with healed esophagitis (grade 0) with no or mild symptoms entered the study. Patients were randomly allocated to receive ranitidine 150 mg, 300 mg placebo twice daily for 48 weeks. Patients returned for symptom assessments at eight-week intervals and for re-endoscopy every 16 weeks. RESULTS: Both ranitidine regimens were significantly more effective than placebo in preventing endoscopic and symptomatic relapse of reflux esphagitis (p = 0.003 for ranitidine 150 mg bid; P < 0.001 for ranitidine 300 mg bid). No statistically significant differences were observed in relapse rates between the two ranitidine regiments. The percentage of patients with endoscopic relapse (grade 2) after 48 weeks were 60%, 37% and 27% for placebo, ranitidine 150 mg bid and ranitidine 300 mg bid, respectively (P = 0.002 for ranitidine 150 mg bid versus placebo; P < 0.001 for ranitidine 300 mg bid versus placebo). Ranitidine was well tolerated. CONCLUSIONS: Ranitidine 150 mg bid and 300 mg bid are safe and effective treatments in the prevention of reflux esophagitis relapse.

Adolescent↗

Autoimmune neutropenia in early infancy: a review.

Fourteen infants with autoimmune neutropenia reported in the literature have been reviewed. Autoantibodies directed against their own neutrophils were demonstrated in the sera of these infants by agglutination, complement-dependent cytotoxicity, and immunofluorescence techniques. These antibodies were highly specific and were directed against antigens present on neutrophils. Among the currently known neutrophil antigens (NA1, NA2, NB1, NC1, NE1, ND1, 9A), antibodies reacting with either NA1 or NA2 have been identified frequently in the sera of infants with autoimmune neutropenia. Good correlation was demonstrated between the presence or absence of autoantibodies and the episodes of neutropenia in many cases. Antibodies from the patients also reacted with neutrophils from their parents and from normal unrelated volunteers when they shared the neutrophil-specific antigen against which the antibody was directed. Antibodies demonstrable by complement-dependent cytotoxicity appeared to detect different antigens which may also cause autoimmune neutropenia. Infants with this disorder were healthy at birth and for a few months afterwards, then became chronically ill with such symptoms as intermittent fever, diarrhea, and infections. Their hemoglobin levels, lymphocyte and platelet counts, and other immunological studies were normal except for severe to moderate neutropenia.

Adrenal Cortex Hormones↗

Clinical and medicoeconomic impact of the cyclosporine-diltiazem interaction in renal transplant recipients.

The effect of the diltiazem-cyclosporine interaction on cyclosporine pharmacokinetics, pharmacodynamics, and pharmacoeconomics was studied in 10 recipients of renal allografts. Each subject was studied while receiving diltiazem 60 mg twice/day and while not taking the drug. After achieving steady-state conditions, cyclosporine and metabolite concentrations were determined in whole blood from samples drawn after the morning cyclosporine dose. After pharmacokinetic analysis, all patients were followed for 6 months during treatment with cyclosporine plus diltiazem or cyclosporine alone. Cyclosporine blood clearance decreased significantly after treatment with diltiazem (18.0-11.0 ml/min.kg; p = 0.008). The apparent volume of cyclosporine distribution also decreased significantly (4.26-2.62 L/kg; p < 0.05). After 6 months, diltiazem had no effect on renal function indexes, and no apparent effect on immunosuppression. Alterations in cyclosporine clearance and apparent volume of distribution secondary to diltiazem result in dosage reduction and potential cost savings in transplant pharmacotherapy. The mean decrease in cyclosporine dosage requirements would produce a cost saving of $1520 or 28% per patient per year.

Adolescent↗

Faculty have few incentives for becoming board certified in pharmacotherapy.

A telephone survey of all colleges of pharmacy in the United States (including Puerto Rico) and Canada was conducted to assess the incentives offered for pharmacy practice faculty to become board-certified pharmacotherapy specialists (BCPS). Board certification is not a requirement for employment at any college of pharmacy; however, it plays a part in promotion, tenure, and merit salary increases at several schools. Fewer than half of the schools provide at least partial reimbursement of examination-related expenses. Sixteen have initiated BCPS study groups. We perceive that faculty must have more incentives to take the examination. It may be difficult to change institutional policies regarding merit increases or promotion and tenure, but colleges of pharmacy can do more to decrease the cost burden and to promote study groups within the department.

Canada↗

Does BcgI, a unique restriction endonuclease, require two recognition sites for cleavage?

BcgI is a multi-subunit restriction-modification (R-M) complex. BcgI prefers pBR322 DNA over pUC19 in a DNA cleavage reaction. Linearized pBR322 contains two BcgI recognition sites and pUC19 has only one site. To test whether two target sites are required for BcgI cleavage, one of the two sites in pBR322 was deleted, and as a result pBR322-1 became a poor substrate for BcgI. Conversely, adding a BcgI site to pUC19 makes it a much better substrate for BcgI cleavage. In addition, the BcgI (R-M) complex forms a heterohexamer in solution that is capable of interacting with two recognition sites. Our results suggest that BcgI requires two recognition sites for cleavage.

Binding Sites↗