Therapeutic monitoring of mycophenolic acid. A consensus panel report.
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Drug Monitoring↗
Biomedical subjects
M Hale
Publications and source records attributed to M Hale.
Phenomenology and the meaning of aging for young and old adults.
Qualitative methods were used to examine the similarities and differences in the meaning of aging for young and old adults. Nineteen young adults and seventeen older adults were asked to describe in detail a specific event or time in their lives that suggested to them that they were aging. Their responses were reduced to significant statements by two independent coders, until a thematic structure became apparent. Younger adults associated aging with major events in their lives, and even though these events tended to be positive, aging had a negative meaning for them. Young adults tended to associate aging with increased responsibility and lost freedom. By contrast, older adults associated aging with everyday events or no specific events at all, and they perceived aging positively. Both young and old adults mentioned themes of times, the body, and others.
Adult↗
Adenoid cystic carcinoma of the salivary glands: a review of 10 years.
A retrospective analysis was performed of 50 patients with adenoid cystic carcinoma who were seen in the Department of Radiation Oncology, University of Witwatersrand, Johannesburg, South Africa, in the past 10 years. There were 25 men and 25 women with a mean age of 52 years (age range, 21 to 88 years). Five patients had metastatic disease, and 17 had neural invasion. Thirty-four patients had surgery (11, complete; 23, microscopic residual). Sixteen patients had radiotherapy as initial management. The disease-free survival was 26%, overall survival was 29%, and local control was 30% at 10 years. Most recurrences occurred in the first 3 years. Nine patients had metastasis following treatment. The mean survival after metastasis was 15 months. Seven prognostic variables were analyzed using the log-rank test. There was no impact of age, site, type of salivary gland (major vs. minor), tumor stage, node positivity, or neural invasion on disease-free survival, overall survival, or local control. Extent of surgical resection (complete vs. microscopic residual) had a significant impact on disease-free survival and local control (P < 0.05) but no impact on overall survival (P > 0.05) because of the slow-growing nature of these tumors. Similarly, patients who had microscopic residual after surgery and were treated with radiotherapy did better than those who had biopsy and radiotherapy, although this was not significant statistically (P > 0.05). Thus, whenever possible, every attempt must be made to remove all microscopic tumor by surgery. Addition of postoperative radiotherapy with high-energy photons did not improve the locoregional control or survival in our series. There is a place for neutrons in the treatment of adenoid cystic carcinomas in advanced cases of inoperable or recurrent tumors, as a review of literature shows.
Adult↗
Pharmacokinetics and bioavailability of mycophenolate mofetil in healthy subjects after single-dose oral and intravenous administration.
A randomized, crossover study of 12 healthy volunteers was conducted with single, 1.5-g doses of mycophenolate mofetil (MMF), a prodrug of mycophenolic acid (MPA), after oral and intravenous administration. During the intravenous infusion, phase systemic plasma clearance of MMF was approximately 10 L/min and the half-life (t1/2) was a few minutes. After oral administration, however, plasma MMF was below quantitation limits at all times. The plasma MPA profile of oral MMF showed a sharp peak at approximately 1 hour and a secondary peak at 8 to 12 hours. Mean apparent plasma t1/2 of MPA was similar for both routes (approximately 17 hours). The area under the concentration-time curve (AUC) from time 0 to 24 hours was statistically higher for intravenous than for oral administration, but total AUC showed statistical equivalence (80-120 rule), with mean bioavailability of MPA from oral administration of MMF estimated as 94.1% relative to the intravenous route. Total plasma AUC of mycophenolic acid glucuronide (MPAG), the sole metabolite of MPA, was four- to five-fold higher than MPA. Total 48-hour MPAG recovery in urine was statistically equivalent for the two routes and represented a mean of 70% of administered drug; corresponding MPA recovery was less than 1%. Renal clearance (ClR) values required transport mechanisms for MPAG, but not for MPA. The ClR of MPAG was statistically higher after intravenous administration than oral administration. MMF administered orally undergoes rapid, complete absorption and essentially complete presystemic deesterification. There was presystemic removal of MPA, but enterohepatic circulation compensated for the first pass loss. Renal metabolism of MPA also may have occurred.
Administration, Oral↗
Pharmacokinetics of oral mycophenolate mofetil in volunteer subjects with varying degrees of hepatic oxidative impairment.
Eighteen patients with compensated alcoholic cirrhosis participated in a single-dose pharmacokinetic study of oral mycophenolate mofetil (MMF). Participants were divided into groups of 6 patients each with mild, moderate, or severe hepatic oxidative impairment as defined by the aminopyrine breath test (APBT). Clinically, hepatic disease was of mild or moderate severity. Six healthy volunteers were included as control subjects. Plasma and urine samples were collected over 96 hours and assayed for the active metabolite mycophenolic aced (MPA) and the glucuronide conjugate, MPAG. Plasma protein binding of MPA also was determined in 6 unrelated patients with cirrhosis. Cirrhosis did not grossly affect plasma pharmacokinetics or plasma binding of MPA. Maximum plasma concentrations (C(max)) and area under the curve (AUC) of MPA and MPAG consistently decreased, increased, and then decreased as oxidative impairment declined from normal to severe. Patients with cirrhosis had comparable or greater recovery of administered drug substance in urine than controls, showing that cirrhosis did not affect the extent of MMF absorption. Urine clearance of MPAG was two times higher in the group with severe impairment than in the other groups. Creatinine clearance was similar in all groups. These results suggest progressive impairment of hepatic glucuronidation of MPA and induction of renal glucuronidation in patients with severe hepatic oxidative impairment.
Administration, Oral↗
Functions of fish skin: flexural stiffness and steady swimming of longnose gar, Lepisosteus osseus
The functions of fish skin during swimming remain enigmatic. Does skin stiffen the body and alter the propagation of the axial undulatory wave? To address this question, we measured the skin's in situ flexural stiffness and in vivo mechanical role in the longnose gar Lepisosteus osseus. To measure flexural stiffness, dead gar were gripped and bent in a device that measured applied bending moment (N m) and the resulting midline curvature (m-1). From these values, the flexural stiffness of the body (EI in N m2) was calculated before and after sequential alterations of skin structure. Cutting of the dermis between two caudal scale rows significantly reduced the flexural stiffness of the body and increased the neutral zone of curvature, a region of bending without detectable stiffness. Neither bending property was significantly altered by the removal of a caudal scale row. These alterations in skin structure were also made in live gar and the kinematics of steady swimming was measured before and after each treatment. Cutting of the dermis between two caudal scale rows, performed under anesthesia, changed the swimming kinematics of the fish: tailbeat frequency (Hz) and propulsive wave speed (body lengths per second, L s-1) decreased, while the depth (in L) of the trailing edge of the tail increased. The decreases in tailbeat frequency and wave speed are consistent with predictions of the theory of forced, harmonic vibrations; wave speed, if equated with resonance frequency, is proportional to the square root of a structure's stiffness. While it did not significantly reduce the body's flexural stiffness, surgical removal of a caudal scale row resulted in increased tailbeat amplitude and the relative total hydrodynamic power. In an attempt to understand the specific function of the scale row, we propose a model in which a scale row resists medio-lateral force applied by a single myomere, thus functioning to enhance mechanical advantage for bending. Finally, surgical removal of a precaudal scale row did not significantly alter any of the kinematic variables. This lack of effect is associated with a lower midline curvature of the precaudal region during swimming compared with that of the caudal region. Overall, these results demonstrate a causal relationship between skin, the passive flexural stiffness it imparts to the body and the influence of body stiffness on the undulatory wave speed and cycle frequency at which gar choose to swim.
Journal Article↗
Pharmacokinetics of mycophenolate mofetil (RS61443): a short review.
Overall, the PK of MMF is reasonably straightforward and relatively unaffected by the complex pathophysiological changes involved in the management of renal transplant recipients. The ability to relate plasma MPA concentrations to efficacy through the PK/PD correlation implies that, unlike for many other drugs, plasma PK has direct relevance to the clinical outcome. These features should not only greatly help the exploration of immunosuppressive regiments using MMF but also the development of clinical use of MMF in situations other than renal transplantation.
Body Weight↗
Co-amplification of MYCN and a DEAD box gene (DDX1) in primary neuroblastoma.
DEAD box proteins are putative RNA helicases that have been implicated in cellular processes involving alteration of RNA secondary structure, such as translation initiation and splicing. These proteins share eight conserved amino acid motifs, including Asp(D)-Glu-(E)-Ala(A)-Asp(D) which is part of a more extended motif. Recently, we have shown that the novel DDX1 gene containing a DEAD box motif maps to the same chromosome band as MYCN at 2p24 and is co-amplified with MYCN in retinoblastoma cell lines. Here, we show that the DDX1 gene is co-amplified with the MYCN gene in 2 of three neuroblastoma cell lines and that DDX1 RNA levels correlate with DDX1 gene copy number. Since amplification of MYCN is an indicator of poor prognosis in neuroblastoma, it was of interest to determine whether co-amplification with DDX1 occurred in clinical samples of neuroblastoma and whether such a finding carried any additional prognostic significance. We determined the gene copy number of DDX1 in 32 neuroblastoma patient samples (representative of all stages): 13 were MYCN amplified and 19 had normal copy numbers of the MYCN gene. Of the 13 neuroblastomas that were MYCN amplified, seven were also DDX1 amplified. Of the 19 that were not MYCN amplified, none were DDX1 amplified. This is the first example of a gene that is co-amplified with MYCN at a high frequency in neuroblastoma. While there was a trend towards a worse clinical outcome with co-amplification, the numbers were too small to reach significance.
Child↗
Dramatic decrease in tuberculin skin test conversion rate among employees at a hospital in New York City.
BACKGROUND: The Centers for Disease Control and Prevention recently issued updated guidelines for preventing the transmission of tuberculosis in health care facilities. Many recommendations, including the use of high-efficiency particulate air filter respirators, are expensive to implement and of unproven efficacy. We therefore reviewed the tuberculin skin test conversion rate among our employees from 1991 to 1993, before introduction of high-efficiency particulate air filter respirators. During this period, several other improvements in tuberculosis control were implemented. METHODS: Employee tuberculin test conversion rates were reviewed by 6-month interval from 1991 to 1993. RESULTS: Throughout the study period, several tuberculosis control measures were implemented, including early isolation of patients with suspected cases of tuberculosis in rooms with negative-pressure ventilation, placement of germicidal UV light fixtures into patient rooms and common areas, and use of Technol shields (Technol, Inc., Fort Worth, Texas) (1991), particulate respirators (1992), and dust-mist-fume respirators (1993). With these improvements, the conversion rate among employees fell from 20.7% in the first 6 months of 1991 to 5.8% in the latter half of 1993. CONCLUSIONS: The rate of skin test conversion among our employees decreased before introduction of high-efficiency particulate air filter respirators. This suggests that nosocomial spread of tuberculosis can be decreased by means of previously established, less costly methods.
Cross Infection↗
A human DEAD box protein with partial homology to heterogeneous nuclear ribonucleoprotein U.
In a previous report, we showed that a novel DEAD box protein-encoding gene, DDX1, was amplified in two retinoblastoma (RB) cell lines. In addition to the eight conserved motifs that characterize all DEAD box proteins, the deduced amino acid sequence of DDX1 contains a subregion with considerable homology to heterogeneous nuclear ribonucleoprotein U.
Amino Acid Sequence↗
Lymphocyte-specific genetic instability and cancer.
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Ataxia Telangiectasia↗
Patients' perception of the hysterosalpingogram: the initial stages of the audit cycle.
A prospective study of 98 consecutive hysterosalpingogram examinations was undertaken to evaluate patients' understanding of the examination, to assess their anxiety levels and to identify any factors where improvements might alleviate this anxiety. This was achieved by employing three simple questionnaires, two being completed by the patient (before and after the examination), the third being completed by the radiologist who recorded clinical and technical details. In this study the majority of patients knew why the examination was being performed, although only 50% had received an explanation of the technique prior to their arrival in the department. Anxiety levels associated with the examination were high. The importance of a sympathetic approach by the radiologist prior to the examination was highlighted, and it was found that time delays contributed to the anxiety level.
Adolescent↗
Case report: accessory lobe of the liver mimicking lesser omental lymphadenopathy.
An accessory lobe of the liver is an uncommon occurrence and often an incidental finding. We present the case of a middle-aged man whose upper abdominal pain was relieved following removal of an accessory lobe. His preoperative imaging had led us to believe that he had lesser omental lymphadenopathy. We draw attention to the fact that this congenital abnormality can cause diagnostic confusion.
Diagnosis, Differential↗
Mary Hale: serving her community. Interview by Cynthia Q Barger.
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Emergency Nursing↗
High or low osmolar contrast media?
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Contrast Media↗
A trial to assess the effectiveness of bowel preparation prior to intravenous urography.
A randomized prospective trial was undertaken to compare the relative effectiveness of two commonly used bowel preparations (senna tablets and sodium picosulphate powder) administered to patients before they underwent out-patient intravenous urography. Their 'control' films were compared with plain 'kidneys, ureters, and bladder' (KUB) radiographs of patients who had had no bowel preparation. The results show no significant difference in the degree of faecal shadowing between those receiving a bowel preparation and the unprepared patients. Nor is there any difference between the two laxatives. We conclude that the routine administration of a bowel preparation is unlikely to improve the diagnostic quality of out-patient intravenous urograms. In addition, 40% of the urogram patients found the effects of the laxatives to be unpleasant or very unpleasant.
Adolescent↗
Maintaining professional relationships in your office setting.
How do plastic surgical nurses in private offices maintain the balance between personal and professional relationships with their physicians and their families while also adhering to professional nursing standards? In this interview, ASPRSN National Secretary Catherine Salisbury and ASPRSN Board Seat West Margaret Hale, both of whom work in private office settings, discuss these issues and how to maintain longevity in the field.
Humans↗
Depression and chronic fatigue. Indications for psychiatric consultation.
Symptoms of fatigue and the fatigue syndrome itself are familiar complaints heard by nonpsychiatric physicians in the general hospital. The nature of these complaints is often diffuse and frequently conceals atypical psychiatric disorders. In the general hospital setting, consultation psychiatry, which functions as the interface between psychiatry and these medical practitioners, is ideally situated to assist in the assessment and management of these patients. This article reviews the methods of approach that psychiatric consultants can use to assist their nonpsychiatric colleagues in identification and referral for problems involving fatigue. In addition, a brief review of diagnosis, management, and treatment of such patients is given.
Adult↗