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Biomedical subjects

D Wilkins

Publications and source records attributed to D Wilkins.

At least 19 recordsLinked to original sources

Failure of autoresuscitation in weanling mice: significance of cardiac glycogen and heart rate regulation.

"Autoresuscitation" (AR) is the spontaneous recovery from hypoxic apnea by gasping. We examined aspects of heart function in two situations: 1) the maturationally acquired failure of AR that is characteristic of SWR, but not BALB/c, weanling mice and 2) AR failure in BALB/c mice induced by repeated exposures to anoxia. We determined maturational changes in heart and liver glycogen. Unlike liver glycogen levels, heart glycogen levels in SWR mice differed from those in BALB/c mice. They were consistently much lower throughout maturation and reached a nadir during the brief period when SWR weanling mice are vulnerable to AR failure. Also, rate of cardiac glycogen utilization in vulnerable SWR mice was lower than that of same-aged BALB/c mice and was nil during the latter one-half of the gasping stage when heart function is critical for AR success. Therefore, because glycogen utilization reflects cardiac work, heart failure could explain AR failure in SWR weanlings. Additionally, the increase in hypoxic heart rate that occurs with maturation is developmentally delayed in SWR mice, and this may contribute to their AR failure. Cardiac glycogen was not fully depleted in BALB/c mice during repeated anoxic exposures, indicating other reasons for AR failure. We view these findings as a potential model for the age-related peak in incidence of sudden infant death syndrome.

Age Factors

A dose-controlled study of 153Sm-ethylenediaminetetramethylenephosphonate (EDTMP) in the treatment of patients with painful bone metastases.

One hundred and fourteen patients with painful bone metastases participated in this randomised, dose-controlled study of the efficacy and safety of 153Sm-ethylenediaminetetramethylenephosphonate (EDTMP), a systemically administered radiopharmaceutical. Fifty-five patients received single doses of 0.5 mCi/kg and 59 patients received single doses of 1.0 mCi/kg. Treatment with 153-Sm-EDTMP produced improvement from baseline in all patient-rated efficacy assessments, including degree of pain, level of daytime discomfort, quality of sleep and pain relief. During the first 4 weeks after dose administration, when the patients evaluated efficacy daily, there were statistically significant changes from baseline with the 1.0 mCi/kg dose but not with the 0.5 mCi/kg dose. The difference between doses in visual analogue pain scores was statistically significant at week 4 (P = 0.0476). Among subsets of patients examined, female patients with breast cancer receiving 1.0 mCi/kg had the most noticeable improvement. The physicians judged that approximately half of the patients in each dose group were experiencing some degree of pain relief by week 2. This value increased to 55% for the 0.5 mCi/kg group and 70% for the 1.0 mCi/kg group at week 4. More patients in the higher dose group (54%) than in the lower dose group (44%) completed the 16-week study. A predictable level of dose-related marrow suppression was the only toxicity associated with 153Sm-EDTMP treatment. Values for platelets and WBCs reached nadirs at 3 or 4 weeks with both doses and recovered by 8 weeks. Even at their lowest point, the values were generally higher than those associated with infectious or haemorrhagic complications. Myelotoxicity was no greater in female patients than in male patients. Long-term follow-up revealed longer survival among breast cancer patients who had received the higher dose than among those who had received the lower dose. The results suggest that the 1.0 mCi/kg dose of 153Sm-EDTMP is safe and effective for the treatment of painful bone metastases.

Adult

The effect of dose rate dependence of p-type silicon detectors on linac relative dosimetry.

Cumulative radiation damage to silicon semiconductor diode detectors can induce dose rate dependent sensitivity, a concern in the pulsed beam of a linac. Two p-Si diode photon detectors were used in this study, diodes A and B. Both were preirradiated by the supplier to 5 kGy, with diode A receiving an estimated 8 kGy from measurements, and diode B, 25 kGy. At 6 MV, the PDD measured with diode B was lower (by 4.4% at a depth of 25 cm) than diode A. Using SSD to vary the dose per pulse from 0.02 to 0.64 mGy/pulse, diode A was dose rate independent (within 2%), while the sensitivity of diode B changed by 13%. Silicon diode detectors should be checked regularly against ionization chambers in the pulsed beam of a linac, especially older high-resistivity diodes that have accumulated dose from high-energy photon beams.

Biophysical Phenomena

Simulators for anesthesia.

Two commercially available complete anesthetic simulators were studied in the United States. Although there are some differences between the two systems, each consists of an adult manikin allowing some direct anesthetic interventions, a system of producing physiologic signals to any commercial monitoring system, and the ability to interface with an anesthetic machine and ventilator. In addition, both simulators model the responses to a variety of drugs used by anesthetists. With their associated computer controls, it is possible to mimic a number of recognized anesthetic critical situations and to record the responses made by the anesthetist and determine the effects on the "patient." In use, one system is devoted principally to teaching crisis resource management to anesthetists. The other system is used more generally to teach anesthetists how to approach a variety of problems. In our opinion, each system could be used in either of these ways. Both systems are capable of development into valuable teaching tools for anesthetists and for others involved in critical care. There is potential for the training of paramedics or nurses involved in anesthetic and recovery room care and intensive care. Other options include the investigation of critical events and the development and subsequent testing of clinical management protocols. Anesthetists are familiar with the use of manikins in the teaching of airway management and basic and advanced life support. Newer manikins can be used to practice skills in intravascular cannulation; some can be used with monitoring equipment and defibrillators to provide more realistic teaching. Computer programs, especially those for personal computers (PCs), can also be used to simulate the pharmacophysiologic behavior of patients in a variety of states. Now available are combined systems using manikins controlled by computer, with interfaces to anesthetic machines, ventilators, and monitoring equipment. Two systems are commercially available in the United States. In this report, we briefly describe their technical specifications and how we saw them being used.

Adult

Quantitative determination of codeine and its major metabolites in human hair by gas chromatography-positive ion chemical ionization mass spectrometry: a clinical application.

A highly sensitive method was developed for the quantitative analysis of codeine and morphine in human hair. After addition of deuterated internal standards, hair samples were digested overnight in 1N NaOH at 37 degrees C. Hydrolysis was performed on certain digests by addition of 1 mL 6N HCl. Digest solutions were extracted using a solid-phase procedure with Bond Elut Certify extraction columns. Derivatized extracts were analyzed on a Finnigan ion trap mass spectrometer (Magnum) in the positive ion chemical ionization mode using acetone as the reagent gas, helium as the carrier gas, and a DB-5 MS (30 m x 0.25-mm i.d.) capillary column. The assay was linear to 75 ng/mg (r = 0.99) and was capable of detecting 10 pg of codeine and morphine on-column. Intra-assay precision ranged from 8 to 20%. The method was used to quantitate codeine in human hair obtained from two male volunteers with dark brown to black hair after a single oral dose of 120 mg codeine phosphate liquid. Hair samples were plucked from the scalp for 28 days and then cut at the scalp. Codeine was detectable in 1-cm long hair (containing the bulb) at 12 h following the dose and remained detectable in the hair shaft for at least 8 weeks. Codeine metabolites were not detected in the hair of these two subjects. The method is currently being used in dose-response disposition studies to quantitate codeine and its major metabolites in human subjects.

Administration, Oral

Quantitative analysis of THC, 11-OH-THC, and THCCOOH in human hair by negative ion chemical ionization mass spectrometry.

A sensitive and specific method was developed for the quantitative analysis of delta9-tetrahydrocannabinol (THC), 11 -hydroxy-THC (11-OH-THC), and 11-nor-9-carboxy-THC (THCCOOH) in human hair. Deuterated internal standards were added to hair samples, and samples were digested overnight in 1 N NaOH at 37 degrees C. Digest solutions were extracted with a liquid-liquid extraction procedure, which was previously developed in our laboratory for the analysis of plasma and whole blood. Derivatized extracts were analyzed on a Finnigan 4500" mass spectrometer in negative ion chemical ionization mode using methane as the reagent gas, hydrogen as the carrier gas, and a Restek Rtx 200-15M-0.25-microm capillary column. The assay was linear up to 50 ng/mg hair (r, 0.99) for all three compounds and was capable of detecting 10 pg THC and THCCOOH and 100 pg 11-OH-THC on column. The intra-assay precision ranged from 2.1 to 11.2% for the three analytes; the interassay precision ranged from 4.4 to 13.0%. The method was used to detect and quantitate the presence of THC, 11-OH-THC, and THCCOOH in human hair obtained from eight regular users of cannabis. THC, but not 11-OH-THC or THCCOOH, was detectable in the hair shaft above the assay limit of quantitation. Four laboratory wash procedures were also evaluated for their effect on the measured concentration of THC in hair. in seven of eight subjects, a methylene chloride wash procedure substantially reduced the measured THC concentration by up to 50%. The gas chromatographic-mass spectrometric assay is currently being used to support pharmacokinetic studies of drug disposition into the hair of humans and animals.

Boranes

Tuberculosis: medical students at risk.

In 1979 an outbreak of tuberculosis occurred in medical students at the University of Sydney. Eight of 35 Mantoux-negative students who attended the autopsy of an immunosuppressed patient with unsuspected active tuberculosis became infected and one developed clinical disease. A report of the incident was prepared for publication because it supported the then controversial University policy of recommending BCG vaccination to medical and dental students in a country where the reported prevalence of tuberculosis is very low. The report was never published, mainly in order to protect the privacy of the individual students involved, but also because it was felt by the administration of the time that it might undermine confidence in infection control procedures in the autopsy room. The original report, updated and reproduced here, suggested that tuberculosis might be an emerging nosocomial problem. This has been all too clearly realised since its re-emergence as an opportunistic infection in AIDS patients. Worldwide, the problem of antibiotic resistance in Mycobacterium tuberculosis provides an added risk of a return to the situation which prevailed early this century when tuberculosis was a major occupational risk for young health care workers. Infection often restricted career choices, even in those whose disease was relatively benign. Our purpose in bringing this incident to light after so many years is to point out the relevance of the extensive studies of the problem which were conducted in the 1930s and 1940s to the current situation and to suggest that health care students are vulnerable to airborne infections as well as those spread by inoculation injuries. In retrospect, our 1979 conclusions about prospects for preventing nosocomial tuberculosis appear optimistic.

Autopsy

A comparison of laparoscopically assisted vaginal hysterectomy vs traditional total abdominal and vaginal hysterectomies.

The objective of this work was to compare laparoscopically assisted vaginal hysterectomy to traditional total abdominal and vaginal hysterectomies in seven critical areas: anesthesia time, surgery time, hospital stay, operative blood loss, total analgesic use, time required to return to work, and total cost of each of these procedures. The first 25 unscreened, consecutive laparoscopically assisted vaginal hysterectomies performed by the senior author were compared with 25 randomly selected traditional total abdominal and 25 randomly selected vaginal hysterectomies performed by the senior author's professional corporation. Laparoscopically assisted vaginal hysterectomy compared favorably to abdominal and vaginal hysterectomy in three areas and was superior to both total abdominal hysterectomy and vaginal hysterectomy in the remaining four areas. Although the use of the endoscopic stapling device and laser made the laparoscopically assisted vaginal hysterectomy a more expensive procedure than traditional vaginal hysterectomy, the expense was not significant and was justified by the decreased surgery time. The results of this comparative study suggest that laparoscopically assisted vaginal hysterectomy is superior or comparable to total abdominal hysterectomy and vaginal hysterectomy, especially for patients who may not have been candidates for vaginal hysterectomy. This procedure has allowed the gynecologic endoscopic surgeon to convert abdominal to vaginal procedures. Laparoscopically assisted vaginal hysterectomy provides an overall cost savings to the patient, has a low complication rate, adapts well to the outpatient setting, causes less patient discomfort, and allows the patient to return rapidly to home and workplace.

Adult

Primary writing tremor and myoclonic writer's cramp.

Four patients with primary writing tremor had a focal, task-specific tremor that responded to anticholinergic drugs. Physiologic features included EMG activity alternating in antagonist muscles, 5- to 20-microV cerebral potentials evoked by stretch of pronator teres, and no C-reflexes. Another patient had myoclonic jerks of the forearm on attempts to write ("myoclonic writer's cramp") that also responded to anticholinergic drugs; EMG activity appeared synchronously or alternating in antagonist muscles. These disorders have features of dystonia and enlarge the spectrum of writer's cramp.

Adult

Prediction of energy requirements of obese patients after massive weight loss.

A regression analysis was made of resting metabolic rate on weight and body composition in 140 women with varying degrees of obesity. In 19 severely obese women before weight loss, average resting metabolic rate was 290 ml O2/min, or 4 per cent higher than predicted from the regression equation. After losing 30 kg in one year the average metabolic rate of this group was 234 ml O2/min, 1 per cent higher than that predicted for their reduced weight. Women whose metabolic rate was high or low relative to prediction before weight loss tended to maintain this status after weight loss (P less than 0.05). There is a close relation between resting metabolic rate and total energy expenditure. We conclude that there is a reduction in energy requirements for weight maintenance after massive weight loss, but the requirements of obese patients after weight loss are similar to those of people of comparable weight who have not reduced.

Adolescent