Patricia A. Martin

Predicting Quality of Well-being Scores from the SF-36: Results from the Beaver Dam Health Outcomes Study

Background. The SF-36 and the Quality of Well-being index (QWB) both quantify health status, yet have very different methodologic etiologies. The authors sought to develop an empirical equation allowing prediction of the QWB from the SF-36. Data. They used empirical observations of SF-36 profiles and QWB scores collected in in terviews of 1,430 persons during the Beaver Dam Health Outcomes Study, a com munity-based population study of health status, and 57 persons from a renal dialysis clinic. Method. The eight scales of the SF-36, their squares, and all pairwise cross- products, were used as candidate variables in stepwise and best-subsets regressions to predict QWB scores using 1,356 interviews reported in a previous paper. The re sulting equation was cross-validated on the remaining 74 cases and using the renal dialysis patients. Results. A six-variable regression equation drawing on five of the SF- 36 components predicted 56.9% of the observed QWB variance. The equation achieved an R2 of 49.5% on cross-validation using Beaver Dam participants and an R2 of 58.7% with the renal dialysis patients. An approximation for computing confidence intervals for predicted QWB mean scores is given. Conclusion. SF-36 data may be used to predict mean QWB scores for groups of patients, and thus may be useful to modelers who are secondary users of health status profile data. The equation may also be used to provide an overall health utility summary score to represent SF-36 profile data so long as the profiles are not severely limited by floor or ceiling effects of the SF-36 scales. The results of this study provide a quantitative link between two important measures of health status. Key words: health status; SF-36; Quality of Well- being index; quality of life; health-state utility; population study. (Med Decis Making 1997;17:1-9

Health status and hypertension: A population-based study

We describe the relation between self-reported hypertension and measures of health-related quality of life (HRQOL) in a community-dwelling population. In a cross-sectional study, 1430 randomly selected adults, aged 45 to 89 years, were interviewed to obtain a medical history and health status measures, including the SF-36 questionnaire, the Quality of Well Being (QWB) index, and time trade-off (TTO) assessments. A total of 519 participants reported being affected by hypertension (HTN group). The HTN group, compared to the No HTN group, had significantly lower age-adjusted health status scores measured by the General Health scale of the SF-36 and by TTO, with differences between groups for each measure comprising approximately 5% of the total scale. HTNs also had a significant decline in general health status measures associated with increasing numbers of antihypertensive medications but not with specific classes of medications. We conclude that hypertension and hypertension drug therapy are associated with clinically meaningful decreases in reported health status.

Modulation of ventilatory control during exercise

The control of ventilatory responses to mild or moderate dynamic exercise has been the subject of considerable debate for over a century. The prevailing view has been that the ventilatory response to exercise is stereotypical and rather unmalleable. However, paradigms involving novel associations of stimulus inputs have been shown to modulate breathing in short and longer time scales. The scope of this review includes examples of modified ventilatory responses to exercise which have been investigated in terms of neural mechanisms. An attempt to synthesise the available data into a model of neuromodulation is presented.

Potentiation of differential hyperthermic sensitivity of AKR leukemia and normal bone marrow cells by lidocaine or thiopental.

Previous work has utilized spleen colony formation to evaluate the fractional survival of AKR leukemia and normal bone marrow cells after in vitro heat exposure. An inherently greater sensitivity of neoplastic cells to thermal killing, as compared to normal syngeneic stem cells, has been established both at 41.8°C and 42.5°C. Normal bone marrow colony‐forming units were assayed in lethally irradiated (750 cGy) mice. Leukemic colony‐forming units were assayed in nonirradiated mice. Using this methodology, the authors demonstrated that the differential effect of hyperthermia on AKR murine leukemia and AKR bone marrow cells can be further enhanced by the addition of lidocaine or thiopental to incubation mixtures. These findings may have application to autologous bone marrow transplantation in humans.

Temperature distribution during radiant heat whole-body hyperthermia: experimental studies in the dog.

A radiant heat system for whole-body hyperthermia (WBH) has been safely and effectively used in mice, pigs and humans. This report details our adaptation of this methodology to dogs. Mongrel dogs were used to study different anaesthesia methods including spontaneous ventilation with or without intubation, as well as mechanical ventilation. Temperature distribution was studied during 42 degrees C WBH; intraabdominal, liver, bone marrow, brain, rectal, lung, oesophageal and skin temperatures were monitored. When a target temperature of 42 degrees C was achieved, temperature gradients between organs were minimal with the possible exception of bone marrow. Results obtained are consistent with the concept that the liver is a major source of metabolic heat production. The establishment of a dog model for WBH allows for physiological and pharmacological studies. The existence of spontaneous neoplasms should promote the use of this species for trials combining hyperthermia with other modalities.

A hyperthermia study of differential sensitivity and thermotolerance in AKR murine leukemia and normal bone marrow cells

It has been previously demonstrated that AKR leukemia (lymphoma) cells are more sensitive than normal bone marrow cells to hyperthermic killing at 41.8 degrees C and 42.5 degrees C in vitro. This differential heat sensitivity might be explained by a greater ability to induce thermotolerance (TT) in normal versus neoplastic hematopoetic cells. We tested this hypothesis using the spleen colony methodology in the AKR murine model. A greater heat sensitivity of leukemia in comparison to normal bone marrow cells was observed at 42.5 degrees C; this observation agrees with previous reports. However, using a preincubation temperature of 40.0 degrees C for 120 min did not result in the induction of TT in either normal bone marrow (AKR) cells or AKR leukemia cells. The rationale for the choice of preincubation temperatures and times, as well as the clinical implications of these results are discussed.

Neuroendocrine changes in patients undergoing whole body hyperthermia

A phase I study of whole body hyperthermia (WBH) (52 treatments/12 patients) utilizing a radiant heat device has been completed. This study incorporated a temperature escalation scheme from 39.5 to 41.8 degrees C for up to 150 min. Pain relief or a sense of well being was observed post-WBH in the first three patients entered in this study. We postulated that WBH might result in increases in the opiate peptide beta-endorphin. Therefore we elected to study prospectively the next six patients entered in this study to test the hypothesis that WBH stimulates the neuroendocrine axis. Results are reported which show thermal-induced increases in plasma levels of beta-endorphin as well as prolactin, ACTH and cortisol.

Whole body hyperthermia (41-42 degrees C): a simple technique for unanesthetized mice.

A technique for accomplishing 41-42 degrees C whole body hyperthermia (WBH) in unrestrained, unanesthetized mice using a simple apparatus is reported. This method combines a radiant heat technology with monitoring of individual rectal temperatures at 10-min intervals. In 66 heating sessions, involving 116 AKR mice and a total of 619 WBH treatments, the mortality rate was less than 1%. Treatment at 41-42 degrees C for periods of up to 120 min were accomplished. Relationships of several variables of mouse temperature-time profiles were studied including (1) initial core temperature, (2) rate of heating, (3) whole body irradiation, and (4) the presence of tumor (transplanted AKR leukemia). Sham treatments produce a consistent temperature-time profile showing about a 1 degree C rise. Between-mouse variability, as well as between-treatment variability in individual animals was estimated. Thermal mapping of the device demonstrates a range from 32-38 degrees C of the air temperature in the zone with the mice to a high of 47 degrees C near to the radiant heating surface at the top of the apparatus.

HYPOXIC EXERCISE DOES NOT ELICIT LONGTERM MODULATION OF THE NORMOXIC EXERCISE VENTILATORY RESPONSE IN GOATS

Ventilation typically increases during exercise to an extent whereby PaCO2 is maintained at or below resting levels (4).Traditionally, attempts to describe the neural mechanisms responsible for the exercise hyperpnoea have invoked a combination of feed-forward and feedback signals (5,8).

Beta-blockade during whole-body hyperthermia: A toxicity study in the dog

A radiant heat device (RHD) for whole-body hyperthermia (WBH) has been safely and effectively used with a dog model. The cardiovascular changes which occur in the dog during WBH--including heart rate, blood pressure, cardiac output, stroke volume and ejection fraction--agree qualitatively and quantitatively with changes observed in previous WBH-RHD studies done in pigs and humans. We elected to study the effect of propanolol in dogs during WBH in order to evaluate this drugs potential use in human cancer patients who are ineligible for WBH because of coronary artery disease. This report details cardiovascular changes which occur with beta-blockade during 42 degrees C WBH in the dog. Our results show that the level of beta-blockade needed to control heart rate during WBH produces acute cardiovascular decompensation.