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Biomedical subjects

J Baker

Publications and source records attributed to J Baker.

At least 127 records · Page 7Linked to original sources
PubMed1996

Contraceptive efficacy, pharmacokinetics, and safety of Annuelle biodegradable norethindrone pellet implants.

OBJECTIVE: To evaluate the contraceptive efficacy, pharmacokinetics, and safety of two formulations of Annuelle (Endocon, Inc., South Walpole, MA) biodegradable norethindrone (NET) SC pellet implants. DESIGN: Prospective observational study. SETTING: Two clinical sites in the United States. PATIENT(S): Thirty-nine healthy, fertile, sexually active women. INTERVENTION(S): Nineteen women received a four-pellet system containing 174 mg NET; 20 women received a five-pellet system containing 266.5 mg NET. MAIN OUTCOME MEASURE(S): Contraceptive efficacy, median serum NET levels, adverse events. RESULT(S): No pregnancies were observed in 293 woman-months in the four-pellet group or in 375 woman-months in the five-pellet group. An initial burst in median serum NET levels occurred in the first 24 hours postinsertion followed by a steady decline over the next 3 years. Norethindrone levels varied considerably among women. The main side effect was bleeding abnormalities, which persisted in half the participants for up to 2 years. No serious adverse events were reported that were related to the pellets. Pellet insertion and removal generally were uncomplicated. CONCLUSION(S): Annuelle shows potential as an effective, safe contraceptive with distinct advantages over other long-acting agents, because it is biodegradable but can be removed if problems arise or if fertility is desired.

Adolescent↗
PubMed1996

Association of pain with radiological changes in different compartments and views of the knee joint.

The aim of this study was to examine the association between radiological patellofemoral and tibiofemoral osteoarthritis and knee symptoms in a population-based survey. Two hundred and fifty unrelated, normal individuals (500 knees) were included in the study. Anteroposterior (AP), lateral and skyline radiographs on each individual were graded for joint space narrowing and osteophytes using a standard atlas. Radiographic features were assessed on their ability to predict knee pain for 15 or more days in the last month, the last year or pain "ever'. The presence of osteophytes had the strongest association with knee pain "ever' with an odds ratio (95% Cl) for skyline osteophytes of 7.56 (3.84-14.81) and anteroposterior osteophytes of 5.00 (2.40-10.43). The presence or absence of joint space narrowing in all the radiological views (AP, lateral and skyline) was not significantly associated with knee pain, but there was a trend for an association with severity of narrowing in the lateral and skyline views. The presence of osteophytes in all knee views (AP, lateral or skyline) was best at predicting knee pain in the last year. Osteophytes predict pain more accurately than narrowing on all knee radiographic views (AP, lateral or skyline). Pain in the last year (defined as two or more episodes of pain, each lasting for at least 15 days and not related to recent trauma) is predicted more accurately than pain in the last month or ever having had an episode of knee pain and is a useful symptom for inclusion in population studies.

Arthralgia↗
PubMed1996

Medicaid claims history of Florida long-term care facility residents hospitalized for pressure ulcers.

The purpose of this study was to identify patterns of admission, discharge, and readmission between hospital and long-term care facility among a group of Florida long-term care facility residents with pressure ulcers whose care was paid for by Medicaid. A patient-specific, longitudinal claims history database was constructed from data provided by the Florida Department of Health and Rehabilitative Services. This database was used to determine and analyze hospital admissions for pressure ulcer care among Medicaid recipients cared for in a long-term care facility. Analysis of the data determined that more than half of the Medicaid-covered long-term care facility residents who formed the target study group (54.57%) had multiple hospital admissions associated with pressure ulcers. Pressure ulcer hospital admissions amounted to a program cost of $9.9 million.

Florida↗
PubMed1996

Intracellular expression of human immunodeficiency virus type 1 (HIV-1) protease variants inhibits replication of wild-type and protease inhibitor-resistant HIV-1 strains in human T-cell lines.

The enzymatic activity of the human immunodeficiency type 1 (HIV-1) protease (PR) is crucial to render HIV-1 virions mature and infectious. Hence, genetic intervention strategies based on trans-dominant (td) variants of the HIV-1 PR might be an alternative to current pharmacological and gene therapy regimens for AIDS. CD4-positive human CEM-SS T-cell lines were generated which constitutively expressed HIV-1 td PR variants. HIV-1 infection experiments demonstrated severely reduced HIV-1 replication in these td PR CEM-SS cell lines compared with control T cells expressing wild-type PR. Furthermore, replication of an HIV-1 isolate bearing a PR inhibitor-resistant PR was blocked, showing that genetic intervention strategies based on td PRs can be effective against HIV-1 isolates containing PR inhibitor-resistant mutants.

CD4-Positive T-Lymphocytes↗
PubMed1996

Intracellular expression of RNA transcripts complementary to the human immunodeficiency virus type 1 gag gene inhibits viral replication in human CD4+ lymphocytes.

Intracellular expression of antisense transcripts was evaluated for its potential to interfere with human immunodeficiency virus type 1 (HIV-1) replication. Retroviral vectors encoding HIV-1 psi-gag complementary sequences downstream of a selectable gene (neo, puromycin gene, or Lyt2 gene) were stable and yielded high titers. Human CEMSS T cells were transduced with amphotropic retroviral vectors to express RNA complementary to the psi-gag sequence of HIV-1. Replication of laboratory-adapted HIV-1 strains was inhibited by more than 1 order of magnitude (log10) in these transduced cells even at high inoculation doses (4 x 10(4) 50% tissue culture infective doses). Antisense-mediated anti-HIV efficacy was further demonstrated by survival of CD4+ cells in these cultures relative to controls. The level of anti-HIV-1 activity of the psi-gag antisense sequence correlated with the length of the antisense transcript. Maximal anti-HIV efficacy was observed with complementary sequence more than 1,000 nucleotides long, whereas transcripts less than 400 nucleotides long failed to inhibit HIV-1 replication. Expression of psi-gag antisense RNA also reduced HIV-1 JR-CSF replication 10-fold in primary CD4+ lymphocytes. These results obtained with a T-cell line and primary peripheral blood lymphocytes indicate the potential of long antisense RNAs as an efficient anti-HIV-1 therapeutic agent for gene therapy.

Anti-HIV Agents↗
PubMed1996

Choosing the best method for radiological assessment of patellofemoral osteoarthritis.

OBJECTIVE: To assess the reproducibility of different methods of radiological assessment of patellofemoral osteoarthritis (OA) and to determine which is the best view as a research tool in epidemiological studies of knee OA requiring explicit diagnostic criteria to classify the disease in the general population. METHODS: A population based study of 252 unrelated, normal individuals (504 knees) was performed. Lateral and skyline radiographs from each individual were graded for joint space narrowing and osteophytes using a standard atlas. Reproducibility was assessed by two observers on 50 knees. Radiographic features were assessed on their ability to predict knee pain. RESULTS: The skyline views performed better than the lateral views in the assessment of patellofemoral joint OA. The reproducibility for osteophytes was high (kappa > 0.8) and that for joint space narrowing moderate (kappa > 0.6) for both lateral and skyline views. Although the specificity for detecting knee pain was similar in both views, the sensitivity of skyline views in the assessment of knee pain was greater (52.8% versus 30%). The odds ratio for skyline osteophytes as a predictor of knee pain was 7.66 (95% confidence interval (CI) 3.68 to 15.90); that for osteophytes seen on lateral view was 1.83 (95% CI 0.96 to 3.49). Narrowing on both views was a poor predictor of pain. There was frequent disagreement between the lateral and skyline views for detecting osteophytes. CONCLUSION: In a community based study, skyline views performed better than lateral views in terms of reproducibility and for identifying symptomatic patellofemoral joint OA. Skyline radiographs should be the preferred method for examining the patellofemoral joint in such studies.

Female↗
PubMed1996

Effects of an Igf1 gene null mutation on mouse reproduction.

Both sexes of adult mice homozygous for a targeted mutation of the Igf1 gene, encoding insulin-like growth factor 1, are infertile dwarfs (approximately 30% of normal size). The testes are reduced in size less than expected from the degree of dwarfism but sustain spermatogenesis only at 18% of the normal level. The epididymides are overall nearly allometric to the reduced body weight, but the distal regions of the duct, vas deferens, seminal vesicles, and prostate are vestigial. Despite the mutational impact on the epididymis, capacitated sperm are able to fertilize wild type eggs in vitro. It is hypothesized that the infertility of male mutants is caused by failure of androgenization resulting in absence of mating behavior, due to drastically reduced levels of serum testosterone (18% of normal). This hormonal deficiency was correlated with an ultrastructural analysis of mutant Leydig cells revealing a significant developmental delay, while assays in organ culture showed that the basal and LH-stimulated production of testosterone by testicular parenchyma is reduced in comparison with wild type controls. The female mutants fail to ovulate even after administration of gonadotropins, which is apparently the primary cause of their infertility, and possess an infantile uterus that exhibits a dramatic hypoplasia especially in the myometrium. The phenotypic manifestations of the mutation were correlated with the localization of transcripts for insulin-like growth factor I and its cognate receptor in wild type reproductive tissues by in situ hybridization.

Animals↗
PubMed1996

Psychogenic vomiting complicated by marijuana abuse and spontaneous pneumomediastinum.

OBJECTIVE: This case illustrates an unusual physical sequel of psychogenic vomiting. CLINICAL PICTURE: A 22-year-old man with a picture of psychogenic vomiting and marijuana use developed the complications of a pneumomediastinum and subcutaneous emphysema. TREATMENT: Therapy included gradual exposure to anxiety provoking stimuli, psychotropics to reduce vomiting and psychotherapeutic exploration of family relationships. OUTCOME: The patient's vomiting and physical state resolved without complication. Follow-up at 12 months revealed continued improvement with occasional less severe vomiting. CONCLUSIONS: Psychogenic vomiting as a manifestation of anxiety can result in serious physical and psychological sequelae. This patient's desperate attempts to control such vomiting complicated the picture. Successful short term intervention included the use of several treatment modalities.

Adult↗
PubMed1996

Medication use review process and information systems utilized for oncology chemotherapy quality improvement.

Fatal chemotherapy overdoses at prestigious institutions have prompted extensive reviews of policies and procedures in medical centers throughout the country. Improving medication use systems for chemotherapy requires a comprehensive multidisciplinary approach. A process to develop a medical center policy on chemotherapy based on the medication use model adopted by the Joint Commission on Accreditation of Healthcare Organizations will be discussed. This will include the prescribing, preparing, dispensing, administering, and monitoring process as well as quality improvement systems. Pharmacy information systems enhancements that safeguard patients are also discussed including maximum dose checks and specific dosing algorithms for bone marrow transplant patients.

Antineoplastic Agents↗
PubMed1996

Phase I clinical trial of the flavonoid quercetin: pharmacokinetics and evidence for in vivo tyrosine kinase inhibition.

We have performed a Phase I clinical trial with the naturally occurring flavonoid quercetin (3,3',4',5,7-pentahydroxyflavone). Quercetin has antiproliferative activity in vitro and is known to inhibit signal transduction targets including tyrosine kinases, protein kinase C, and phosphatidyl inositol-3 kinase. Quercetin was administered by short i.v. infusion at escalating doses initially at 3-week intervals. The first dose level was 60 mg/m2; at the 10th dose level of 1700 mg/m2, dose-limiting nephrotoxicity was encountered, but no myelosuppression. At the preceding dose level of 1400 mg/m2, five patients were treated at 3-week intervals, and another eight patients were treated on a once-weekly schedule; overall, 2 of 10 evaluable patients had renal toxicity, 1 at grade 2 and 1 at grade 4. We therefore treated other patients at 945 mg/m2 (eight at 3-week intervals and six at weekly intervals); 3 of 14 patients had clinically significant renal toxicity, 2 patients with grade 2 and 1 patient with grade 3. Patients treated on the weekly schedule did not have cumulative renal impairment but did have a fall in the glomerular filtration rate of 19 +/- 8% in the 24 h after drug administration. We recommend 1400 mg/m2 as the bolus dose, which may be given either in 3-week or weekly intervals, for Phase II trials. Quercetin pharmacokinetics were described by a first-order two-compartment model with a median t(1/2)alpha of 6 min and median t(1/2)beta of 43 min. The median estimated clearance was 0.28 liter/min/m2, and median volume of distribution at steady state was 3.7 liter/m2. In 9 of 11 patients, lymphocyte protein tyrosine phosphorylation was inhibited following administration of quercetin at 1 h, which persisted to 16 h. In one patient with ovarian cancer refractory to cisplatin, following two courses of quercetin (420 mg/m2), the CA 125 had fallen from 295 to 55 units/ml, and in another patient with hepatoma, the serum alpha-fetoprotein fell. In conclusion, quercetin can be safely administered by i.v. bolus at a dose injection. The plasma levels achieved inhibited lymphocyte tyrosine kinase activity, and evidence of antitumor activity was seen.

Adult↗
PubMed1995

Secondary organ allografting after a primary "bridging" xenotransplant.

It remains uncertain whether xenotransplantation can sensitize the recipient to alloantigens, rendering subsequent allotransplantation unsuccessful. This is of considerable importance if a xenograft is to be used as a "bridge" to support the patient until a suitable allograft becomes available. When sera from 9 baboons that had received pig or African green monkey heart or liver xenografts were tested against a panel of lymphocytes from 5 or 6 potential donor baboons, positivity was seen in only 1 baboon (and then to only 2 of the potential 5 donors). In 4 baboons that had undergone previous xenotransplants (1 from this series of 9 baboons and 3 others), subsequent organ allografting was not followed by hyperacute, antibody-mediated, or accelerated cellular rejection. We conclude that organ xenotransplantation using discordant or concordant donor species does not prohibit subsequent allotransplantation.

Animals↗
PubMed1995

Evidence that productive rearrangements of TCR gamma genes influence the commitment of progenitor cells to differentiate into alpha beta or gamma delta T cells.

Two models have been considered to account for the differentiation of gamma delta and alpha beta T cells from a common hematopoietic progenitor cell. In one model, progenitor cells commit to a lineage before T cell receptor (TCR) rearrangement occurs. In the other model, progenitor cells first undergo rearrangement of TCR gamma, delta, or both genes, and cells that succeed in generating a functional receptor commit to the gamma delta lineage, while those that do not proceed to attempt complete beta and subsequently alpha gene rearrangements. A prediction of the latter model is that TCR gamma rearrangements present in alpha beta T cells will be nonproductive. We tested this hypothesis by examining V gamma 2-J gamma 1C gamma 1 rearrangements, which are commonly found in alpha beta T cells. The results indicate that V gamma 2-J gamma 1C gamma 1 rearrangements in purified alpha beta T cell populations are almost all nonproductive. The low frequency of productive rearrangements of V gamma 2 in alpha beta T cells is apparently not due to a property of the rearrangement machinery, because a transgenic rearrangement substrate, in which the V gamma 2 gene harbored a frame-shift mutation that prevents expression at the protein level, was often rearranged in a productive configuration in alpha beta T cells. The results suggest that progenitor cells which undergo productive rearrangement of their endogenous V gamma 2 gene are selectively excluded from the alpha beta T cell lineage.

Animals↗