Biomedical subjects
T Baker
Publications and source records attributed to T Baker.
Cost-effectiveness of the clinical practice recommendations in the AHCPR guideline for smoking cessation. Agency for Health Care Policy and Research.
CONTEXT: The Agency for Health Care Policy and Research (AHCPR) published the Smoking Cessation: Clinical Practice Guideline in 1996. Based on the results of meta-analyses and expert opinion, the guideline identifies efficacious interventions for primary care clinicians and smoking cessation specialty providers. OBJECTIVE: To determine the cost-effectiveness of clinical recommendations in AHCPR's guideline. DESIGN: The guideline's 15 recommended smoking cessation interventions were analyzed to determine their relative cost-effectiveness. Then, using decision probabilities, the interventions were combined into a global model of the guideline's overall cost-effectiveness. PATIENTS: The analysis assumes that primary care clinicians screen all presenting adults for smoking status and advise and motivate all smokers to quit during the course of a routine office visit or hospitalization. Smoking cessation interventions are provided to 75% of US smokers 18 years and older who are assumed to be willing to make a quit attempt during a year's time. INTERVENTION: Three counseling interventions for primary care clinicians and 2 counseling interventions for smoking cessation specialists were modeled with and without transdermal nicotine and nicotine gum. MAIN OUTCOME MEASURE: Cost (1995 dollars) per life-year or quality-adjusted life-year (QALY) saved, at a discount of 3%. RESULTS: The guideline would cost $6.3 billion to implement in its first year. As a result, society could expect to gain 1.7 million new quitters at an average cost of $3779 per quitter, $2587 per life-year saved, and $1915 for every QALY saved. Costs per QALY saved ranged from $1108 to $4542, with more intensive interventions being more cost-effective. Group intensive cessation counseling exhibited the lowest cost per QALY saved, but only 5% of smokers appear willing to undertake this type of intervention. CONCLUSIONS: Compared with other preventive interventions, smoking cessation is extremely cost-effective. The more intensive the intervention, the lower the cost per QALY saved, which suggests that greater spending on interventions yields more net benefit. While all these clinically delivered interventions seem a reasonable societal investment, those involving more intensive counseling and the nicotine patch as adjuvant therapy are particularly meritorious.
Comparison of the biological properties of two anti-mucin-1 antibodies prepared for imaging and therapy.
A comparison was made between the murine anti-MUC1 antibody BC2 (which reacts with the peptide epitope APDTR) and the "humanised" antibody hCTMO1 from CellTech, which reacts with the MUC1 epitope RPAP. Preliminary studies demonstrated that hCTMO1 was a "good" antibody whereas BC2 was not. Various parameters were determined and conclusions reached. (a) Affinity: the affinity of hCTMO1 was 2.60 x 10(7) M(-1) and that of BC2 was 1.36 x 10(7) M(-1); we did not consider these numbers to be substantially different, although hCTMO1 was clearly of higher affinity than BC2. (b) On/off rate at 4 degrees C: both antibodies bound effectively to the MUC-1 transfectant MOR5-CF2; the association rate for hCTMO1 was 3.8 times that of BC2 and the dissociation rate for BC2 was twice as fast as that of hCTMO1. (c) On/off rates at 37 degrees C: at 37 degrees C the association rate for hCTMO1 was greater than that of BC2. (d) Internalization: hCTMO1 was also more efficient at internalising bound antibody; 70% of bound hCTMO1 was internalised, whilst 6% of bound BC2 was internalised. From these studies it was clear that, while hCTMO1 was of similar affinity to BC2, the faster uptake and internalisation and lower off rate indicated that it was likely to be a superior antibody; this was proven in vivo. (e) Localisation: hCTMO1 bound much better in vivo than BC2 (68% compared to 28%). (f) Therapeutic experiments: BC2-idarubicin conjugates were essentially ineffective in eradicating tumours in mice whereas hCTMO1-idarubicin had a dramatic effect on breast cancer tumour cells growing in mice. We conclude that the simple measurements on/off rates and internalisation at 37 degrees C are the most important parameters to use to determine antibody effectiveness, prior to embarking on clinical studies.
Hospital communication threats and intervention.
1. Threats are indirect acts of criminal behavior designed to weaken or injure individuals, institutions, or property. 2. All threats should be analyzed and investigated quickly and with high priority. 3. An interdisciplinary hospital team should conduct periodic reviews of threats received, threat management, and case outcome.
Challenges to identifying actual diabetes case-mix complexity and total treatment charges.
Patient management programs are being used to improve the quality of care and decrease charges for both high-cost and potential high-cost claimants. Adequate information is key to program development, planning, and implementation. Claims-based data are a ready source of valuable information, but without proper processing, true case-mix complexity and total charges for patients will not be identified.
An effect of magnesium on neuromuscular function in parturients.
STUDY OBJECTIVE: To determine the effects of magnesium sulfate on neuromuscular transmission in parturients. DESIGN: Open-label, clinical study. SETTING: Preeclamptic patients at a university-affiliated hospital. PATIENTS: 12 pregnant patients, ages 18 to 40 years, with preeclampsia or entering preterm labor. INTERVENTIONS: Patients were treated with magnesium sulfate. Train-of-four (TOF) recordings of the adductor pollicis muscle were obtained before and 30 minutes after the magnesium sulfate infusion. MEASUREMENTS AND MAIN RESULTS: Each contractile response in the control TOF showed an increase in the tension developed in response to supramaximal stimulation. The TOF responses after magnesium sulfate did not demonstrate this phenomenon, but rather developed fade. The T4/T1 ratios ranged from 0.72 to 0.92. CONCLUSIONS: In this patient population, clinically relevant infusions of magnesium sulfate produced significant changes in neuromuscular transmission as manifested by loss of treppe phenomenon and diminished TOF response to ulnar nerve stimulation.
Familial myeloid leukemia associated with loss of the long arm of chromosome 5.
A 24-member kindred is described in which four cases of acute myeloid leukemia (AML), and one case of myelodysplastic syndrome (MDS) occurred over three generations. The proband was diagnosed with AML at age 47; within 6 months, her sister, age 41, was diagnosed with MDS. The proband's father, grandfather and a paternal uncle all died of AML, preceded by a pre-leukemic phase. The five cases had several clinical features in common. In the two sisters and their paternal uncle, cytogenetic analyses of bone marrow cells revealed a common abnormality characterized by loss of the long arm of chromosome 5, del(5q). No constitutional cytogenetic abnormality was detected in mitogen-stimulated peripheral blood lymphocytes from the proband. In addition, there was no history of common environmental or occupational exposure in the family. The occurrence of AML and MDS in three generations of this family most likely resulted from a single gene defect with an autosomal dominant pattern of inheritance. The association with the somatic loss of 5q material in the leukemia cells of affected members suggests that a germline mutation of a leukemia suppressor gene located on 5q might be the primary event responsible for hereditary susceptibility to leukemia in this family.
Parents' perceptions of their children's recovery 5 to 10 years following day-care abuse.
A follow-up study of 19 parents whose children had been physically, sexually and psychologically abused in day care 5 to 10 years previously, suggests that as perceived by the parent, over one third of the children remain clinically symptomatic, one third are in the normal symptomatic range, and one third are asymptomatic. Also, parents themselves were still distressed by the event and expressed concern as to their child's future interpersonal relationships. It is recommended that nurses provide brief counseling sessions to parents for management of their children's posttrauma symptoms.
Matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 expression and synthetic matrix metalloproteinase-2 inhibitor binding in ovarian carcinomas and tumor cell lines.
Enhanced matrix metalloproteinase-2 (MMP-2/72-kd type IV collagenase) action correlates with invasion in neoplasia. MMP-2 is inhibited in vivo by tissue inhibitors of metalloproteinases (TIMPs)-TIMP-1 and, especially, TIMP-2. A synthetic, biotinylated inhibitor specific for activated MMP-2 in solution phase, and immunohistochemistry were used to detect MMP-2 and TIMP-2 expression in cell lines and ovarian tumors and to analyze the surface-binding capacity of the inhibitors, which are potential therapeutic agents. Characterization of novel monoclonal antibodies to MMP-2 and TIMP-2 is described together with immunocytochemical staining of 83 paraffin-embedded ovarian tumors (67 malignant, 7 borderline, 9 benign) and 9 cell lines. Synthetic MMP-2 inhibitor binding under controlled conditions was visualized by immunofluorescence and avidin-biotin complex immunoperoxidase methods in cell lines and cryostat sections of ovarian tumors. MMP-2 and TIMP-2 showed heterogenous immunoreactivity, with enhanced staining on high-grade tumors, specifically at the invasive front and in vascular invasion. TIMP-2 immunoreactivity was maximal in malignant cell cytoplasm and less intense in desmoplastic fibroblasts. One monoclonal antibody to MMP-2 showed membrane immunoreactivity, apically polarized in benign and low-grade tumors but depolarized and strong in 37 of 44 cases of high-grade invasive tumors. Eleven of eighteen ovarian carcinomas and six of nine cell lines showed membrane localization of the synthetic inhibitor. Maximal binding occurred in the ovarian cell line OVCA 432 and the breast cell lines MCF 7 and MDA MB 435, all of which were immunoreactive for MMP-2. Cell lines propagated on type I collagen showed no enhancement in inhibitor binding. This study demonstrates cell surface binding of a synthetic MMP-2 inhibitor and provides new evidence of MMP-2 and TIMP-2 immunoreactivity in ovarian carcinomas and cell lines.
Cardiac enzymes in patients undergoing caesarean section.
Some of the changes reported in the ECG of parturients undergoing Caesarean section are suggestive of myocardial ischaemia. This study determined serum CK total and the isoenzyme CK-MB levels in 21 patients during and after Caesarean section under epidural anaesthesia. Twenty patients complained of chest pain, discomfort and pressure, while 12 had ST segmental depression. Although the total CK activity in ten patients was elevated, CK-MB activity in all patients was negative. The electrocardiographic changes were rate-related and occurred at the time pressure was placed upon the upper abdomen and lower thoracic cage by the surgeon to facilitate Caesarean delivery. The data from this study demonstrate that no myocardial injury as measured by CK-MB activity occurs in parturients undergoing Caesarean delivery despite the complaint of chest pain, discomfort and pressure, and ST changes in the ECG.
Speed and ease of tracheal intubation: priming with mivacurium compared with succinylcholine.
This study examined the efficacy of mivacurium priming (0.015 mg.kg-1) with five minutes between the priming and intubating doses by comparing the effects of one, two and three times the ED95 dose (0.075 mg.kg-1) of mivacurium after priming (Groups 1, 2 and 3, respectively), with a saline prime and 2 x ED95 mivacurium (Group 4) or 1 mg.kg-1 dose of succinylcholine (Group 5). The time from the intubating dose injection to intubation was measured and intubating conditions were rated on a five-point scale with 4 being optimal and 0 being failure. Mean times (+/- SEM) in seconds between the administration of the intubating dose and tracheal intubation were: 106.4 +/- 5.1, 89.6 +/- 6.7, 81.9 +/- 2.7, 169.9 +/- 7.8 and 82.9 +/- 3.5 for Groups 1-5 respectively. The times for Group 2 (2 x ED95 with priming), Group 3 (3 x ED95 with priming) and Group 5 (succinylcholine with saline) were shorter than the times of Groups 1 (1 x ED95 with priming) and 4 (2 x ED95 with saline) P < 0.05. Mean intubating condition scores (+/- SD) for the five groups respectively were 3.1 +/- 0.6, 3.4 +/- 0.6, 3.5 +/- 0.5, 3.2 +/- 0.6 and 3.8 +/- 0.4. Scores for Groups 2, 3 and 5 were higher than those of Group 1 (P < 0.05). The data demonstrated that (1) priming with mivacurium shortens the intubation time and is accompanied by good intubating conditions with doses 2x and 3x ED95, and (2) intubating times and conditions similar to those achieved with succinylcholine can be obtained using mivacurium 2x (total dose 0.150 mg.kg-1) or 3 x ED95 (total dose 0.215 mg.kg-1) with a five-minute priming interval. Priming provides an alternative technique in those clinical circumstances where succinylcholine is contraindicated.
The minor issue of electroconvulsive therapy.
ECT can be life-saving for patients with certain mental illnesses, such as severe depression, but that is no reason to allow ECT without informed consent. Nor is there general medical justification for the use of ECT on children, a practice in the United Kingdom that is out of control.
Probable succinylcholine-induced rhabdomyolysis in a male athlete.
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Structural and functional analyses of the transcription-translation proteins NusB and NusE.
The NusB and NusE (ribosomal protein S10) proteins function in transcription and translation. The two proteins form a complex that binds to the boxA sequence found in the leader RNA of rrn operons; boxA is required for transcription antitermination in rrn operons. Although binding of these two proteins to the boxA RNA of the bacteriophage lambda nut site has not been observed, both NusB and NusE as well as the RNA boxA sequence are required for lambda N-mediated antitermination. Studies identifying the amino acid changes caused by mutations in nusB and nusE and relating these changes to altered function are reported. It is concluded that boxA is essential for an effective NusB contribution to N-mediated antitermination and that by mutation NusB may be changed to allow more-effective binding to boxA variants.
Memory presentations of childhood sexual abuse.
Questions are continually raised about the accuracy and validity of very young children's memories of traumatic events. Out of 19 children, where the median age was 2 1/2 at time of disclosure, 11 had full verbal memory, five had fragmented verbal memory traces, and three had no memory 5 to 10 years following day care sexual abuse. Data from this clinical study suggest the nature of children's memory is four-dimensional: somatic, behavioral, verbal, and visual. Efforts need to continue to document the nonverbal components for assessment and treatment purposes.
Health problems of Maryland's migrant farm laborers.
The health problems of Maryland's agricultural migrant labor force are presented for the information of Maryland's health care providers. Maryland's problems are placed in the context of U.S. and worldwide migrant labor practices.
Bacteriophage lambda N-dependent transcription antitermination. Competition for an RNA site may regulate antitermination.
Bacteriophage lambda controls the expression of its early genes in a temporal manner by a series of transcription termination and antitermination events. This antitermination requires the lambda N protein as well as host proteins called Nus, and cis-acting sites called nut. Following transcription of the nut site, N and Nus proteins bind to the nut RNA and modify the transcription complex to a termination-resistant form. The nut site is a composite of at least two components; one is the boxB hairpin structure which interacts with N. The other is boxA, a nine-nucleotide sequence upstream of boxB. To understand more about the formation of the antitermination complex, we have characterized the effect of point mutations in and deletions of boxA on antitermination. Point mutations in boxA were found to either enhance or reduce N-mediated antitermination. Several boxA deletions, on the other hand, had little effect on antitermination other than to eliminate the requirement for the NusB host protein. To explain these observations, we propose that at least two factors compete to interact with boxA, NusB and an inhibitor of the antitermination reaction. In addition, we propose that NusB is required to prevent the inhibitor from binding at boxA. The results with various nusB and boxA mutations can be explained by this model of competition between NusB and an inhibitor for boxA RNA.