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Biomedical subjects

M Parker

Publications and source records attributed to M Parker.

At least 181 records · Page 10Linked to original sources

Amiodarone in patients with previous drug-mediated torsade de pointes. Long-term safety and efficacy.

The safety and efficacy of long-term amiodarone therapy were examined in 12 patients who had previously developed torsade de pointes as a complication of previous antiarrhythmic therapy. The QTc intervals were determined at the time of torsade de pointes (570 +/- 40 ms), after 7 days of amiodarone loading (490 +/- 70 ms), and after 3 months of chronic amiodarone administration (580 +/- 80 ms). Compared to a drug-free control period, QTc was significantly prolonged (P less than 0.05) at the time of torsade de pointes, after amiodarone loading, and after 3 months of amiodarone therapy. The QTc intervals at the time of torsade de pointes and after chronic amiodarone treatment were not significantly different. At 16 +/- 7 months of follow-up, all patients remained free of subsequent torsade de pointes, syncope, or sudden death. In addition, 5 of 6 patients with a history of sustained ventricular tachycardia remained free from arrhythmic recurrence despite persistence of inducible ventricular tachycardia during programmed stimulation studies done before discharge. We conclude that amiodarone can often be used safely and effectively in patients who have previously had an episode of drug-mediated torsade de pointes. Amiodarone-induced QTc prolongation, even when marked, does not predict recurrent torsade de pointes. These observations also suggest that the propensity for a drug to produce this arrhythmia is dependent on other electrophysiologic effects in addition to its ability to simply lengthen repolarization.

Adult↗

Evidence for positive and negative regulatory elements in the 5'-flanking sequence of the mouse sparc (osteonectin) gene.

We have investigated the role of 5'-flanking DNA sequences in regulating the expression of the murine Sparc (osteonectin) gene in parietal endoderm cells and in F9 embryonal carcinoma cells induced to differentiate into parietal endoderm with retinoic acid and cyclic AMP. Varying lengths of flanking sequences extending up to 3.0 kilobase pairs 5' of the transcription initiation site were linked to the bacterial chloramphenicol transacetylase gene in the Bluescript M13- vector. The constructs were tested in transient assays, using a beta-galactosidase plasmid as a transfection control. Sequences between 78 and 169 base pairs upstream of the cap site are the minimum required for cell-type specific promoter activity; this region is dominated by two oligopurine/oligopyrimidine stretches or "GAGA" boxes and is highly conserved between the mouse and bovine genes. Addition of the sequence between -169 and -449, which includes part or all of a third GAGA box, results in increased parietal endoderm specific transcription, up to a maximum of 6.3-fold higher than in undifferentiated F9 cells. Further addition of sequences between -449 and -638 markedly reduces promoter activity in both cell types but parietal endoderm-specific activity is restored in constructs containing 2.2 and 3.0 kilobase pairs of flanking DNA. In addition, we have identified sequences related to the consensus sequence for steroid response elements, one of which is able to confer progesterone-enhanced transcription when tested with a heterologous promoter in steroid responsive cells. These results suggest that negative and positive elements normally interact to regulate the temporal and tissue-specific patterns of Sparc gene transcription seen in vivo.

Animals↗

Improved diagnostic performance of exercise thallium-201 single photon emission computed tomography over planar imaging in the diagnosis of coronary artery disease: a receiver operating characteristic analysis.

Qualitative interpretation of tomographic and planar scintigrams, a five point rating scale and receiver operating characteristic analysis were utilized to compare single photon emission computed tomography and conventional planar imaging of myocardial thallium-201 uptake in the accuracy of the diagnosis of coronary artery disease and individual vessel involvement. One hundred twelve patients undergoing cardiac catheterization and 23 normal volunteers performed symptom-limited treadmill exercise, followed by stress and redistribution imaging by both tomographic and planar techniques, with the order determined randomly. Paired receiver operating characteristic curves revealed that single photon emission computed tomography was more accurate than planar imaging over the entire range of decision thresholds for the overall detection and exclusion of coronary artery disease and involvement of the left anterior descending and left circumflex coronary arteries. Tomography offered relatively greater advantages in male patients and in patients with milder forms of coronary artery disease, who had no prior myocardial infarction, only single vessel involvement or no lesion greater than or equal to 50 to 69%. Tomography did not appear to provide improved diagnosis in women or in detection of disease in the right coronary artery. Although overall detection of coronary artery disease was not improved in patients with prior myocardial infarction, tomography provided improved identification of normal and abnormal vascular regions, particularly of the left anterior descending and circumflex artery regions. These results indicate that single photon emission computed tomography provides improved diagnostic performance compared with planar imaging in many clinical subgroups, and suggest that it represents the diagnostic imaging procedure of choice in exercise thallium-201 perfusion studies.

Adrenergic beta-Antagonists↗

The independent long extensor tendon of the fifth toe as a source of tendon grafts for the hand.

The anatomical relationships of the extensor of the fifth toe to the long extensor of the other toes have been studied in 78 cadaver specimens. 50% of the specimens had an independent extensor to the fifth toe without interconnections to the other long toe extensors or the peroneus tertius. The independent fifth toe extensor was consistently of good quality and adequate length for use as a tendon graft, for which purpose it has been successfully used in five patients, with transfer of the adjacent long extensor from the fourth toe to maintain extension of the fifth metatarso-phalangeal joint.

Hand↗

Renal vascular effects of antihypertensive therapy in uninephrectomized SHR.

Serial determinations of protein excretion rate and systolic blood pressure (SBP) were made in spontaneously hypertensive rats (SHR) uninephrectomized (UNX) at six weeks of age and given tap water (CON), or water with hydrochlorthiazide, hydralazine and reserpine (HHR), captopril (CAP) or enalapril (ENP). Compared to CON, significant hypertension was prevented, kidney weight was lower and there was less proteinuria in HHR, CAP and ENP rats followed for 30 weeks after UNX. Morphologic studies of these four groups revealed that antihypertensive therapy reduced the incidence of glomerular sclerosis in UNX SHR by 50%. Despite complete absence of systemic hypertension, there was striking medial thickening of lobular arteries and arterioles of rats given the angiotensin converting enzyme (ACE) inhibitor, captopril. These vascular abnormalities were present to a lesser degree in rats given ENP, but were entirely absent in untreated animals or in those ingesting the HHR combination. Micropuncture studies performed five weeks after UNX in four additional groups of CON, HHR, CAP and ENP rats revealed that glomerular capillary pressure was elevated in CON and reduced by all three drug regimens. These studies support the hypothesis that glomerular capillary hypertension and/or nephron hypertrophy predispose to glomerular injury in this model of hypertension and reduced renal mass. ACE inhibitors and HHR are equivalent in their ability to prevent glomerular hypertension and damage in these rats, but the former, and in particular captopril, produce abnormalities of cortical vessels via a mechanism not dependent on the presence of systemic hypertension.

Animals↗

Metastatic carcinoma of unknown primary: complete response to second-line treatment with plicamycin.

In selected groups of patients, metastatic carcinoma of unknown primary (MCUP) is highly responsive to cisplatin-based combination chemotherapy. These therapeutic responses usually are partial and shortlived. The authors report the case of a 41-year-old man whose MCUP relapsed after responding to cisplatin, bleomycin, and etoposide. Alternate-day treatment with plicamycin induced a second complete remission (CR) in this patient with minimal hematologic and metabolic toxicity. Plicamycin may prove effective in enhancing CR rate, prolonging CR duration, and salvaging cisplatin failures in MCUP.

Adult↗

Malignant hyperthermia crisis.

Clearly the malignant hyperthermia crisis offers a significant challenge in the well cosmetic surgical patient. Aggressive early treatment is mandatory in these cases. Any delay can be disastrous. At times, the crisis may be aborted due to such therapy, leaving some doubt as to the current diagnosis. With such a disease entity, this is the hopeful scenario.

Adult↗

The provision of home health care services through health maintenance organizations.

The vast majority of the HMOs responding to the survey in this study use home health care as a substitute for acute inpatient hospitalization, contract out for services with community-based home health agencies, reimburse on a discounted fee-for-service basis, and use prior authorization and concurrent review as the primary methods to control the use of home health care. These findings suggest that HMO home health care services mirror the inadequacies of Medicare home health care in that they are acute care-focused and not intended to fill the supportive and maintenance care needs of the chronically ill elderly. HMOs, however, are typically more flexible in their service provision than is Medicare. Need for home health care is determined primarily on prospective, case-by-case evaluations of cost effectiveness, not on retrospective determinations based on strict, and sometimes arbitrary, guidelines and limitations. This, however, does raise some important issues for access and quality and for the relationship between HMOs and home health agencies. Is cost containment the only legitimate reason for providing home health care? Should home health care be used solely as a substitute for acute inpatient hospitalization? Where does the locus of authority lie for deciding coverage of home health care services? This study uncovered several issues related to the provision of home health care in HMOs that created conflict and uncertainty for all parties. These issues included: conflicting roles for HMOs, whether to provide services internally or externally, contracting between HMOs and home health agencies, the locus of authority for utilization review, the role of physicians, quality assurance, and perceived problems with the Health Care Financing Administration. HMOs are often perceived as failing to do an adequate job of providing home health care services because of the difficulty in satisfying conflicting considerations in three key areas: whether home health care should be focused on cost containment or meeting unmet needs, whether home health care should be focused on acute or long term care, and the unrealistic expectations patients and providers have of HMOs. HMOs primarily provide home health care in an effort to contain costs, particularly by using home health care to substitute for inpatient hospitalization. While HMO representatives acknowledge the importance of home health care in improving the patient's and family's quality of life by providing supportive or chronic maintenance care, the use of home health care for this purpose is generally not allowed by HMOs.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗

Characterization of response elements for androgens, glucocorticoids and progestins in mouse mammary tumour virus.

We have characterized steroid response elements in mouse mammary tumour virus (MMTV) by transient transfection. Four partial inverted repeats of the sequence TGTTCT function as response elements for androgen, as well as for glucocorticoid and progestins, although the relative hormone inductions mediated by each oligonucleotide were different. Mutational analysis of the left half of the palindrome showed that a perfect dyad symmetry is not required for optimum activity as a steroid response element. To investigate potential interactions between steroid receptors and transcription factors we have analysed the minimum sequence requirements for a hormone response. Interestingly, a single 15 bp steroid response element and a TATA box are sufficient for steroid inductions. When the distance between the two elements was increased by up to two turns of the helix the hormone induction initially increased and then gradually declined with no obvious periodicity.

Animals↗

Assignment of estradiol receptor gene to mouse chromosome 10.

Differences in restriction fragment lengths were detected with murine estrogen receptor cDNA (clone MOR-100) between Chinese hamster and mouse. These were used to determine the chromosomal location of the estrogen receptor in the mouse by Southern blot analysis of DNAs obtained from a panel of mouse-Chinese hamster somatic cell hybrids. The mouse estrogen receptor gene was localized on mouse chromosome 10.

Animals↗

Private geriatric case management: current trends and future directions.

Private geriatric case management is a means of meeting the complex service needs of older persons who do not qualify for publicly funded programs or who seek services that the public sector does not provide. InterStudy surveyed 117 private case management firms and compiled a profile of service providers and their clients, types of services offered, fees charged, and other information. The study raises issues about access to and the quality of case management and other services for the elderly.

Aged↗

The use of epinephrine in the treatment of older adult asthmatics.

Three subcutaneous doses of 0.3 mL 1:1,000 epinephrine were given 20 minutes apart to 95 adult asthmatics 15 to 96 years old during 108 asthma exacerbations. Patients with a history of recent myocardial infarction or of angina were excluded from our study. Heart rhythm and rate, blood pressure, respiratory rate, and clinical response were prospectively evaluated before, during, and after the administration of epinephrine. There was no significant difference in the occurrence of ventricular arrhythmias between patients less than 40 and more than 40 years old. The mean systolic and diastolic blood pressures, mean heart rate, and mean respiratory rate decreased with treatment in the older population. Our results suggest that epinephrine is safe to use in acute asthmatics of any age.

Acute Disease↗