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Biomedical subjects

J Buxbaum

Publications and source records attributed to J Buxbaum.

At least 19 recordsLinked to original sources

Comparison of 0.25% ropivacaine and bupivacaine for epidural analgesia for labor and vaginal delivery.

STUDY OBJECTIVE: Part 1: To measure ropivacaine levels in the mother and infant at delivery after continuous lumbar epidural infusion. Part 2: To compare epidural ropivacaine to epidural bupivacaine for labor analgesia in regard to effectiveness, motor blockade, and maternal and neonatal effects. DESIGN: Part 1: Open-labelled, non-blind study. Part 2: Randomized, double-blind study. SETTING: Labor and delivery units of two academic hospitals. PATIENTS: Part 1: 20 ASA physical status I and II parturients in active labor. Part 2: 81 ASA physical status I and II parturients in active labor. INTERVENTIONS: For Part 1, 8 to 12 ml of 0.25% ropivacaine was administered through a lumbar epidural catheter to achieve a T10 dermatomal sensory level. An infusion of 0.25% ropivacaine, 8 to 10 ml/hr, maintained this sensory level. Maternal and umbilical cord blood samples obtained at delivery were analyzed for ropivacaine concentration. For Part 2, anesthetic management was similar to that previously described except patients were randomized to receive either 0.25% ropivacaine or 0.25% bupivacaine. Onset, regression, maximal spread of sensory block, and onset and degree of motor blockade were measured. Contraction pain as assessed using a visual analog scale (VAS), maternal blood pressure, and heart rate were determined every 5 minutes until a stable VAS-contraction score was achieved, and every 30 minutes thereafter. Neonatal assessment included Apgar scores and neurologic and adaptive capacity scores (NACS) at 15 minutes, 2 hours, and 24 hours. MEASUREMENTS AND MAIN RESULTS: For Part 1, the total and free maternal arterial concentrations of ropivacaine at delivery were 0.64 +/- 0.14 microgram/ml and 0.10 +/- .02 microgram/ml, respectively; the umbilical venous total and free concentrations were 0.19 +/- 0.03 microgram/ml and 0.12 +/- 0.07 microgram/ml, respectively (n = 12). The umbilical arterial and venous concentrations did not differ for both the free and total concentrations. For Part 2, there was no difference between ropivacaine and bupivacaine in the variables measured. Umbilical cord gases and Apgar scores were not different between the two groups; NACS were higher at 15 minutes and 2 hours in the ropivacaine group (p < 0.05) than the bupivacaine group. CONCLUSION: Both ropivacaine and bupivacaine produced excellent analgesia for labor with no major adverse effect on the mother or neonate.

Adult

Comparison of sulfasalazine and placebo in the treatment of ankylosing spondylitis. A Department of Veterans Affairs Cooperative Study.

OBJECTIVE: To determine whether sulfasalazine (SSZ) at a dosage of 2,000 mg/day is effective for the treatment of active ankylosing spondylitis (AS) that is not controlled with nonsteroidal antiinflammatory drug therapy. METHODS: Two hundred sixty-four patients with AS were recruited from 15 clinics, randomized (double-blind) to SSZ or placebo treatment, and followed up for 36 weeks. Treatment response was based on morning stiffness, back pain, and physician and patient global assessments. RESULTS: While longitudinal analysis revealed a trend favoring SSZ in the middle of treatment, no difference was seen at the end of treatment. Response rates were 38.2% for SSZ and 36.1% for placebo (P = 0.73). The Westergren erythrocyte sedimentation rate declined more with SSZ treatment than with placebo (P < 0.0001). AS patients with associated peripheral arthritis showed improvement that favored SSZ (P = 0.02). Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints. CONCLUSION: SSZ at a dosage of 2,000 mg/day does not seem to be more effective than placebo in the treatment of AS patients with chronic, longstanding disease. SSZ is well tolerated and may be more effective than placebo in the treatment of AS patients with peripheral joint involvement. This effect is more pronounced in treatment of the peripheral arthritis in this subgroup of AS patients.

Adult

Comparison of sulfasalazine and placebo in the treatment of reactive arthritis (Reiter's syndrome). A Department of Veterans Affairs Cooperative Study.

OBJECTIVE: To determine whether sulfasalazine (SSZ) at a dosage of 2,000 mg/day is effective in the treatment of reactive arthritis (ReA) that has been unresponsive to nonsteroidal antiinflammatory drug (NSAID) therapy. METHODS: One hundred thirty-four patients with ReA who had failed to respond to NSAIDs were recruited from 19 clinics, randomized (double-blind) to receive either SSZ or placebo, and followed up for 36 weeks. The definition of treatment response was based on joint pain/tenderness and swelling scores and physician and patient global assessments. RESULTS: Longitudinal analysis revealed improvement in the patients taking SSZ compared with those taking placebo, which appeared at 4 weeks and continued through the trial (P = 0.02). At the end of treatment, response rates were 62.3% for SSZ treatment compared with 47.7% for placebo treatment. The Westergren erythrocyte sedimentation rate declined more with SSZ treatment than with placebo (P < 0.0001). Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints. CONCLUSION: SSZ at a dosage of 2,000 mg/day is well tolerated and effective in patients with chronically active ReA.

Adult

Surface EMG reliability using spectral analysis.

Several papers have recently appeared in the literature questioning the usefulness of surface EMG in the management of temporomandibular dysfunction (TMD) patients. One of the concerns is the stability of EMG over time in any one patient. This study was undertaken on normal subjects to determine the level of surface EMG stability over time using a variety of spectral analysis parameters. Four male and seven female subjects, ranging from 24 to 38 years of age, were selected for the study. All subjects had class I occlusions, intact dentition and no history of TMD. Oral and perioral hard and soft tissues were within normal limits. EMG data from the bilateral masseter muscles were obtained during four states of jaw activity: rest, right-sided chewing, left-sided chewing, and 50% maximal clench. Three sets of recordings were obtained in each study session. Three 10-min study sessions were obtained for each subject. Six measures, which included SP-50, central frequency, band width, effective band width, zero crossings and power spectrum, were analysed to assess their reliability and sensitivity over time during the several states of jaw activity. The conclusion of the study was that bilateral masseter EMG band width, effective band width, and power spectrum in normal humans are all reliable enough to be stable over a 6 week period, and sensitive enough to differentiate among jaw rest, right chewing, left chewing and 50% clench; power spectra being the most sensitive.

Adult

The effects of the menstrual cycle on the incidence of emesis and efficacy of ondansetron.

Postoperative nausea and vomiting after general anesthesia remains a complex and perturbing phenomenon associated with several factors. In women, the phase of the menstrual cycle as a factor in postoperative nausea and emesis is controversial. This retrospective study was performed to assess the effects of the menstrual cycle and efficacy of the antiemetic ondansetron on postoperative emesis. A total of 1169 ASA grade I-II patients from two double-blind, placebo-controlled studies were enrolled in 18 centers. Patients with irregular cycles or taking estrogens or progesterones were excluded from the analysis, leaving 873 patients eligible for this study. The patients were stratified on the basis of their last menses into four groups: 1) 1-8, 2) 9-16, 3) 17-28, and 4) 29-35 days. All patients received a general anesthetic with endotracheal intubation. Patients received either 1, 4, or 8 mg ondansetron or placebo given intravenously before induction of anesthesia. All patients were studied for a 24-h period. Emesis rates were compared with respect to the phase of the menstrual cycle and between menstruating and nonmenstruating patients. There was no relationship (P = 0.100) between the incidence of emesis and the phase of the menstrual cycle in the group receiving the placebo. There was, however, a significant reduction (P < 0.001) in emesis for the ondansetron-treated patients regardless of the phase of the menstrual cycle. In addition, ondansetron had a similar dose-response curve in both menstruating and nonmenstruating women.

Adult

The amyloidoses.

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Black or African American

Therapy for the seronegative spondyloarthropathies.

Rheumatologists have recently become more circumspect and have begun to demand biologic as well as statistical meaning from the data obtained in therapeutic trials. The same may be applied to therapy for the seronegative spondyloarthropathies. In some respects, the spondyloarthropathies present an even greater problem, because the axial skeleton is even more difficult to evaluate. The studies reviewed here represent the current state of the art, and with the exception of those examining the effects of antimicrobial treatment in reactive arthritis occurring after specific infections, are subject to the same uncertainties. Nonetheless, they represent our immediate point of departure.

Anti-Inflammatory Agents, Non-Steroidal

Mechanisms of disease: monoclonal immunoglobulin deposition. Amyloidosis, light chain deposition disease, and light and heavy chain deposition disease.

All forms of MIDD are related to the presence of an expanded clone of B-cell origin that is producing an Ig product, usually, but not exclusively an L-chain, which is predisposed to deposit in tissues, with or without some degree of processing. The nature of the processing is currently unclear, although limited proteolysis is likely to play a major role in most, but not all, patients. Diagnosis is made by the identification, using immunohistochemical techniques, of the monoclonal Ig nature of the deposited material, which may be fibrillar and Congo red-positive (AL and AH), or more amorphous and Congo red-negative (LCDD and LCHDD). Present modalities of therapy are similar or identical to those employed in multiple myeloma, attempting to eliminate the monoclonal cell population responsible for the production of the precursor of the deposited protein. A variety of ancillary therapeutic measures may be employed to treat problems associated with the failure of specific organs produced by the deposition. The details of how the uniformly soluble precursor molecule is converted to an essentially insoluble aggregate that compromises the function of the tissue in which it is formed are not yet known. It is still not possible to construct a potential "unified field theory" governing the deposition of intact Igs or their fragments. It is likely, as appears to be the case in other forms of amyloid unrelated to Ig, that many proteins contain, within their sequence, peptides that are capable of forming insoluble beta sheet-like structures. When these peptides are isolated from their surrounding molecular environment--either by proteolysis in the test tube, by a mutational change that predisposes them to limited proteolysis; or by a point mutation, deletion, or some other structural modification (as glycosylation), which alters their molecular context without proteolysis--and are present in sufficient concentration, they become less soluble under physiologic conditions. It is likely that the site of deposition depends upon the site of synthesis, but to a lesser extent than the protease profile and the physicochemical make-up of the affected tissues. Better understanding of the latter factors is necessary for the development of better modes of treatment.

Amyloidosis

Needs and recommendations for behavior research in the prevention and early detection of cancer.

Because life-style patterns affect many cancer risks, research on health-risk behavior and behavior change is critical to cancer prevention. This report recommends priorities for the next decade of psychosocial research on cancer prevention and detection. The leading priority for future research is to fill gaps in basic knowledge left by the rush to intervention and outcome studies. Such research must be theoretically driven and should aim to develop broad principles applicable to diverse health behaviors. Studies that include relevant process data on various stages of behavior change are considered more desirable than simple outcome studies. Epidemiologic investigations should be expanded to include measures of relevant behaviors, so that their impact on clinical outcomes might be established. More research is needed on lay perception of health risks and on individual and health-system barriers to effective cancer prevention and detection. Studies that address the needs of minority and underprivileged populations are crucial. Funding agencies' narrow categorical mandates impede interdisciplinary research on multiple risk factors and their interactions; these boundaries must be relaxed to promote such approaches. Funding agencies should also consider basic research as a long-term investment towards the development of effective interventions.

Health Behavior

Immunoglobulin heavy chain constant-region gene polymorphism in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is associated with immunoglobulin allotypes in several ethnic groups. In this study, we investigated the association of a Bst EII immunoglobulin heavy chain constant-region gene restriction fragment length polymorphism with SLE in patients from the US and Mexico. A 3-kb restriction fragment was observed with significantly decreased frequency in randomly selected Mexican SLE patients and in Mexican SLE patients in multiplex families. However, no such association was observed in SLE patients from the US. Thus, the absence of a 3.0-kb Bst EII restriction fragment from immunoglobulin heavy chain constant-region genes provides a marker for SLE in Mexican individuals.

Blotting, Southern

A diffuse infiltrative CD8 lymphocytosis syndrome in human immunodeficiency virus (HIV) infection: a host immune response associated with HLA-DR5.

STUDY OBJECTIVE: To describe the clinical, immunologic, and immunogenetic features of a diffuse infiltrative lymphocytic disorder resembling Sjögren syndrome in persons infected with human immunodeficiency virus (HIV). DESIGN: Clinical case study. SETTING: University-affiliated hospitals and outpatient clinics. PATIENTS: Consecutive sample of 17 patients. MEASUREMENTS AND MAIN RESULTS: All of the 17 patients had bilateral parotid gland enlargement; 14 had xerostomia and 6 had xerophthalmia. Of the 17 patients, 14 had generalized lymphadenopathy, 10 had histologically proved lymphocytic interstitial pneumonitis, 4 had neurologic involvement, and 3 had lymphocytic infiltration of the gastrointestinal tract. Gallium scanning in all of 11 tested patients showed abnormal salivary gland uptake. Minor salivary gland biopsies showed more than 2 lymphocytic foci per 4 mm2 tissue in all of 11 tested patients, the infiltrate consisting predominantly of CD8 cells. Fifteen patients had circulating CD8 lymphocytosis; the principal phenotype of these cells was CD8+ CD29+. Rheumatoid factor and antinuclear antibodies were infrequent, and none of the patients had anti-Ro/SS-A or anti-La/SS-B antibodies. HLA-DR5 was significantly more frequent in the black patients (10 of 12) compared with controls (13 of 45). Only one patient developed an opportunistic infection during 544 patient-months of study, and none has died of AIDS. CONCLUSIONS: A distinct syndrome primarily characterized by parotid gland enlargement, sicca symptoms, and pulmonary involvement occurs in HIV infection. This disorder is associated with CD8 lymphocytosis and the presence of HLA-DR5, and appears to be a genetically determined host immune response to HIV.

Adult

The spectrum of monoclonal immunoglobulin deposition disease associated with immunocytic dyscrasias.

Immunocytic dyscrasias may be manifested by MIDD often presenting with renal manifestations. The diagnosis is established when deposits are shown by immunopathologic methods to contain a single light-chain isotype in patients who have a monoclonal Ig in the serum or urine, altered kappa:lambda ratio in bone marrow, and/or abnormal biosynthesis of Igs in bone marrow cell cultures. The morphologic expressions of deposits are varied: fibrillar in AL, granular and punctate in LCDD, granular or crystalline in LHCDD, and crystalline in type I cryoglobulinemia.

Amyloidosis

A double monoclonal IgG1 kappa and IgG2 kappa in a single myeloma patient. Variation in clonal products and therapeutic responses.

Two electrophoretically homogeneous immunoglobulins were detected in the serum of a patient with multiple myeloma. The heavy chains were of different classes (gamma 1 and gamma 2). The light chains of both were kappa, but had different electrophoretic mobilities on polyacrylamide gels. Amino acid sequence analysis, carbohydrate determinations, and biosynthetic experiments indicated that the difference seen in their electrophoretic mobility was due to the glycosylation of one but not the other kappa-chain. The primary structure of both chains demonstrated that they both used a V kappa 1 and a J kappa 2 gene segment and the same C kappa allele, Km(1,2), and that both contained the same junctional three amino acid deletion. However, they varied by 19 amino acids in the first 94 amino terminal residues encoded for by the V kappa gene, with some of the substitutions requiring two base changes in the appropriate codons. Moreover, the malignant "clones" producing the two proteins differed in their responses to chemotherapy. These data indicate that, although the two clones producing the serum proteins were different at the time of study, they may have arisen from the same precursor clone.

Amino Acid Sequence

Gamma heavy chain disease in man. Genomic sequence reveals two noncontiguous deletions in a single gene.

A genomic clone was isolated from a human lymphoid cell line which synthesized an NH2-terminally deleted gamma 3 heavy chain disease protein. Nucleotide sequence analysis revealed a normal sequence from 310 bp 5' to the initiator ATG through the codon for VH amino acid 14. Amino acid 15 was derived from the codon for the last J4 amino acid. Thus, the clone contained a deletion of the codons for the VH region beyond amino acid 14, as well as those for the entire D region and most of the J coding region. Some sequence abnormalities were observed in the 400 bp after the deletion. Beyond this, there was excellent homology to published J and intervening sequences, including those containing the enhancer elements. The 1,200-bp switch region was abruptly interrupted by a sequence corresponding to the 3' one-third of CH1. Thus, a second deletion eliminated the acceptor splice site at the 5' end of CH1. When splicing of the primary RNA transcript occurred, the truncated VH region was joined via the J4 donor splice site to the next available acceptor site 5' to the first hinge exon. Hence, the aberrant serum protein was the product of two deletions and a splice correction as well as postsynthetic NH2-terminal proteolysis.

Amino Acid Sequence

Nonamyloidotic monoclonal immunoglobulin deposits lack amyloid P component.

Deposits in tissues from 13 patients with amyloid, 8 with monoclonal light chain or light and heavy chain deposition disease, and 2 with both amyloid and nonamyloidotic light chain deposits of the same isotype were examined in parallel for the presence of amyloid P component by immunofluorescence and/or immunoperoxidase methods. Amyloid P component was detected in the amyloid but not the nonamyloid deposits, even in the 2 individuals in whom both types of deposits were present, indicating a specific relationship between the amyloid P component and the amyloid fibrils.

Amyloidosis