Oral complications in the treatment of cancer patients.

While treatment for cancer in terms of chemotherapy and radiation therapy have evolved significantly since their inception, both of these cancer treatment modalities, especially if used in combination (e.g., as with head and neck cancers), have a very real potential to result in painful and debilitating adverse effects that clearly decrease quality of life and, potentially, increase mortality due to cancer. Herein, we discuss the prevalence and etiology of three broad categories of oral complications found during the treatment of cancer patients: mucositis, dysgeusia, and infectious disease. Lastly, we present therapeutic options that may be helpful in ameliorating these uncomfortable and, sometimes, life-threatening oral complications.

Genetic influences on bone loss in the San Antonio Family Osteoporosis study.

UNLABELLED: The genetic contribution to age-related bone loss is not well understood. We estimated that genes accounted for 25-45% of variation in 5-year change in bone mineral density in men and women. An autosome-wide linkage scan yielded no significant evidence for chromosomal regions implicated in bone loss. INTRODUCTION: The contribution of genetics to acquisition of peak bone mass is well documented, but little is known about the influence of genes on subsequent bone loss with age. We therefore measured 5-year change in bone mineral density (BMD) in 300 Mexican Americans (>45 years of age) from the San Antonio Family Osteoporosis Study to identify genetic factors influencing bone loss. METHODS: Annualized change in BMD was calculated from measurements taken 5.5 years apart. Heritability (h(2)) of BMD change was estimated using variance components methods and autosome-wide linkage analysis was carried out using 460 microsatellite markers at a mean 7.6 cM interval density. RESULTS: Rate of BMD change was heritable at the forearm (h(2) = 0.31, p = 0.021), hip (h(2) = 0.44, p = 0.017), spine (h(2) = 0.42, p = 0.005), but not whole body (h(2) = 0.18, p = 0.123). Covariates associated with rapid bone loss (advanced age, baseline BMD, female sex, low baseline weight, postmenopausal status, and interim weight loss) accounted for 10% to 28% of trait variation. No significant evidence of linkage was observed at any skeletal site. CONCLUSIONS: This is one of the first studies to report significant heritability of BMD change for weight-bearing and non-weight-bearing bones in an unselected population and the first linkage scan for change in BMD.

Low risk of vertebral fracture in Mexican American women.

Ethnicity is important in assessing risk for osteoporotic fractures, and should be considered in decision-making about the use of prophylactic treatments. Few data are available, however, on fracture risks among Hispanic patients. To assess the risk of vertebral fracture in Mexican Americans, we determined the prevalence of vertebral fracture among 822 patients, aged 15 to 86 years, who underwent spinal roentgenography in a study of low-back pain. After adjusting for age, use of steroids, drug or alcohol abuse, and recent trauma, the odds ratio for Mexican American women compared with non-Hispanic whites was 0.55 (95% confidence interval, 0.32 to 0.95), indicating a substantially lower risk. These results are concordant with earlier data documenting a reduced risk of hip fracture among Mexican American women. Thus, recommendations for prophylactic treatments for osteoporosis may be different for Mexican Americans than for non-Hispanic whites.

Medication compliance in non-insulin-dependent diabetes: a randomized comparison of chlorpropamide and insulin.

Medication compliance may be a problem in the management of patients with diabetes. Some physicians initially treat patients having non-insulin-dependent diabetes with oral sulfonylureas because they fear greater compliance problems with insulin therapy. We compared compliance with insulin and chlorpropamide in patients newly beginning medication for NIDDM. Seventy-seven adults with hyperglycemia despite diet therapy were randomly assigned to chlorpropamide or insulin. Compliance was measured four times over 24 wk. Patients then crossed over to the other medication and were followed for 24 additional weeks. Overall, there were no differences in compliance with the two medications in terms of percent of prescription used, proportion taking at least 80% of prescribed medication, self-report of medication or diet compliance, or protocol dropout rates. However, treatment satisfaction was higher with chlorpropamide, and most patients preferred chlorpropamide to insulin (P less than 0.0001). While such differences in satisfaction may affect long-term compliance, physicians should not assume that their patients will be less compliant with insulin than with oral sulfonylureas.

Genes influencing variation in serum osteocalcin concentrations are linked to markers on chromosomes 16q and 20q.

Osteocalcin (OC) is an important constituent of bone that is synthesized by osteoblasts. Serum levels of OC have been used as a biochemical marker of bone turnover. To identify the genes influencing variation in serum OC levels, we conducted a genome-wide scan in 429 individuals comprising 10 large multigenerational families. OC levels were measured by immunoassay, and genetic markers were typed at approximately 10-cM intervals across the genome. Quantitative trait linkage was tested using a multipoint analysis based on variance component methodology, adjusting for the effects of age, sex, and oral contraceptive use. Significance levels for linkage were obtained empirically, by Monte Carlo simulation. The heritability of OC levels in this population was 62 +/- 8%. We detected significant evidence for linkage between a quantitative trait locus influencing serum OC levels and markers on chromosome 16q, and suggestive evidence for linkage of OC levels with markers on chromosome 20q. The multipoint lod scores peaked at 3.35 on chromosome 16 and 2.78 on chromosome 20, corresponding to P values of 0.00004 and 0.00017, respectively. A potential candidate gene for bone formation in the linked region on chromosome 20 is CDMP1, which encodes cartilage-derived morphogenetic protein 1. Future studies should evaluate whether variation in CDMP1 or in other genes in the linked regions on chromosomes 16 and 20 influence the rate of bone turnover.

Impact of legal liability, family wishes, and other "external factors" on physicians' life-support decisions.

PURPOSE: The purpose of this study was to determine the impact of external factors on physicians' life-support decisions. "External factors" are those factors that promote the interests of people other than the patient. Examples of external factors include physician legal liability and family wishes about patient care. SUBJECTS AND METHODS: A nationwide sample consisted of 300 randomly selected physician-members from the American Society of Law and Medicine (ASLM) and 300 from the Society for Critical Care Medicine (SCCM); 179 ASLM physicians (60%) and 165 SCCM physicians (55%) responded. A mailed questionnaire presented three cases, each requiring the physician to make a life-support decision. For each case, the physician chose one of several life-support options and rated the importance to his or her decision of specific "decision factors," including some external factors. We assumed the physician would choose the management option supported by the decision factors that the physician considered most important. For this reason, we used discriminant analysis to identify the factors whose importance ratings best predicted management choices. RESULTS: In the first case, 46% of ASLM respondents and 55% of SCCM respondents chose to stop the ventilator of a chronically comatose patient with unknown preferences about life support. Thirty-one percent of ASLM and 27% of SCCM respondents chose to continue the ventilator, and 21% of ASLM and 14% of SCCM respondents chose to apply for a judicial decision. Importance ratings for the external factor, physician legal liability, best predicted management choices. In the second case, 95% of ASLM and 94% of SCCM respondents chose to resuscitate a cancer patient at the patient's request; 3% of ASLM and 4% of SCCM respondents chose no resuscitation. Importance ratings for patient preferences best predicted management choices. In the third case, 38% of ASLM and 35% of SCCM respondents honored a stroke patient's previous refusal of tube feedings, but 59% of ASLM and 62% of SCCM respondents authorized tube feedings in order to secure nursing home placement. Importance ratings for patient preferences best predicted management choices in this case. External factors impacted management choices considerably in the first case and more modestly in the second and third cases. CONCLUSION: External factors impact the life-support decisions of physicians. Physician legal liability may have an especially great impact on these decisions when patients' preferences are not known.

Area variation in mortality from diseases amenable to medical intervention: the contribution of differences in morbidity.

Several conditions, whose timely and appropriate therapy should decrease case fatality, have been proposed as indicators of medical care quality for the National Health Service. Mortality rates for these diseases vary widely within the UK. To evaluate the contribution of varying incidence rates to these mortality differences, routinely collected morbidity and mortality data for 1974-1978 were analysed for 98 Area Health Authorities (AHAs) in England and Wales. Although differences in morbidity (as measured by hospital discharge and disease registration rates) and socioeconomic factors account for some of the area variation in mortality, significant heterogeneity persists after these factors are taken into account. This finding suggests that morbidity and socioeconomic factors are not the only determinants of mortality variation among areas for these particular diseases. Variation in quality of medical care may account for this result, although regional diagnostic and reporting differences and variation in disease severity among areas must also be considered.

PIP: This study is concerned with variations in mortality from diseases amenable to medical intervention in England and Wales. The focus is on the extent to which these variations can be used to evaluate the quality of medical care provided by the National Health Service. The data concern 98 Area Health Authorities and are for the period 1974-1978. The results suggest that differences in morbidity and socioeconomic factors are not the only determinants of mortality and that variations in the quality of health care may also be relevant factors.

The association of obesity and glucose and insulin concentrations with bone density in premenopausal and postmenopausal women.

Obese subjects have increased bone density relative to non-obese subjects, yet this relationship is not fully understood. We examined whether alterations in glucose or insulin concentrations might explain the effect of obesity on bone density in 317 women from the San Antonio Heart Study, a population-based study of diabetes. We measured fasting and 2-hour plasma glucose and fasting and 2-hour serum insulin levels. Bone density was assessed by a Hologic dual-photon absorptiometer. Lumbar spine and femoral neck density were positively correlated with body mass index (BMI). Femoral neck density also was positively correlated with fasting insulin level in younger women after adjustment for age (r = .214, P < .01). After further adjustment for BMI, femoral neck density was not significantly correlated with fasting insulin level (P = .08). The magnitude of the estimated femoral neck density difference for a 32.2-microU/mL decrease in fasting insulin level (the difference in insulin concentrations between nondiabetics and diabetics) was 0.13 g/cm2. Adjustment for glucose and insulin concentrations does not explain the association between bone density and obesity.

The effect of an ambulatory internal medicine rotation on students' career choices.

PURPOSE: To assess the effect of an ambulatory care experience on medical students' perceptions of internal medicine and their choices of careers (as measured by residency selections). METHOD: In 1990-91, the 196 third-year students enrolled in the 12-week internal medicine clerkship at the University of Texas Medical School at San Antonio were randomized to a curriculum that included a three-week ambulatory care component or to a traditional, exclusively inpatient curriculum. The ambulatory curriculum included the evaluation of walk-in-patients, exposure to community internists, and a lecture series. The students' perceptions of internal medicine were surveyed before and after the clerkship. Their career choices were determined by their residency selections at graduation. Data analysis employed chi-square tests, t-tests, and logistic regression. RESULTS: Of the 196 students, 184 (76 in the ambulatory and 108 in the traditional curricula) provided complete data. The ambulatory care students were somewhat more likely to enter an internal medicine residency (odds ratio = 1.49; 95% CI, 0.72 to 3.09) than were the traditional students. The ambulatory care students' perceptions of internal medicine did not change significantly from before to after the clerkship. CONCLUSION: The ambulatory curriculum had a modest but favorable effect on the students' selections of careers in internal medicine, but was not associated with changes in their perceptions of internal medicine.

Traffic accidents and minor tranquilizers: a review.

Minor tranquilizers, including the benzodiazepines, have been found to impair driving skills such as hand-eye coordination and reaction time. Several studies have also demonstrated an association between minor tranquilizer use and traffic accidents; however, the association may be due entirely to more frequent alcohol use or to the underlying anxiety found in users of minor tranquilizers. Whichever the case, patients taking minor tranquilizers do have higher accident rates. It is recommended that physicians emphasize the possible risks of driving while using these medicines, particularly if used with alcohol.

Office techniques to maintain the health of aging patients.

The fecal occult blood test is safe and inexpensive; however, diet, medications, desiccation of the sample, and delay in developing the specimen may affect results. If the test is used, six separate samples, two from each of three consecutive bowel movements, should be examined to obtain optimum results. Serum cholesterol need not be assessed routinely in geriatric patients. Dietary restriction of fats is a necessity only in the context of a weight reduction diet.

Ethnic differences in hip fracture: a reduced incidence in Mexican Americans.

To confirm a previous report of lower risks of hip fracture in Mexican Americans, we calculated the incidence of hip fractures among Hispanics, blacks, and non-Hispanic whites residing in Bexar County, Texas, during 1980. A total of 576 residents with hip fracture not due to severe trauma were identified. The 1980 census data were used to calculate ethnic-specific incidence rates which were age-adjusted using the entire 1980 US population as the standard. Hip fractures were more common among non-Hispanic white women (139 per 100,000; 95% confidence interval (CI) = 124-153) than among Mexican-American (67 per 100,000; 95% CI = 51-82) or black (55 per 100,000; 95% CI = 27-83) women. Thus, Mexican Americans and blacks are relatively protected from hip fractures, and they may benefit less than whites from prophylactic therapies for osteoporosis.

Excess androgenicity only partially explains the relationship between obesity and bone density in premenopausal women.

Obese subjects have increased bone density relative to non-obese subjects yet this relationship is not fully understood. We examined whether alterations in sex hormones or binding proteins might explain the effect of obesity on osteoporosis in 83 premenopausal women from the San Antonio Heart Study, a population-based study of diabetes. We measured total testosterone, oestradiol, oestrone, sex hormone binding globulin (SHBG), and serum dehydroepiandrosterone sulphate (DHEA-SO4). Bone density was assessed by a Hologic dual photon absorptometer. Lumbar spine and femoral neck density were positively correlated with body mass index (BMI). In addition, femoral neck density was positively correlated with DHEA-SO4. BMI was negatively correlated with SHBG. After adjustment for sex hormones by multiple linear regression a positive association between bone density and obesity still exists suggesting that the association between obesity and bone density is at least partially independent of sex steroids in premenopausal women.

United Kingdom Heart Disease Prevention Project: 12-year follow-up of risk factors.

Ten of the original 24 factories from the United Kingdom Heart Disease Prevention Project were resurveyed in 1983 to assess the long-term (12-year) effects of an education program on diet, smoking, and exercise. These 10 factories had previously been grouped into five pairs matched for size, location, and nature of industry, with one of each pair randomly chosen for intervention. Men in intervention factories were given advice on reduction of cholesterol in diet, stopping smoking, weight reduction, and regular exercise. High-risk workers (13%) received personal counseling in addition to the factory-wide education program. A total of 1,204 workers randomly selected from those still employed in 1978 were surveyed. There were significant differences observed in cigarette consumption, butter use, and several other dietary behaviors; however, the differences were small and insignificant for the proportion smoking and leisure-time exercise. The largest effects were in the high-risk group who had received personal counseling. This education program appears to have some lasting effects on behavior associated with coronary disease risk factors. Similarly designed programs may serve as models for community-wide coronary disease prevention programs.

Spinal bone density and tooth loss in a cohort of postmenopausal women.

Osteoporosis has been suggested to contribute to the edentulous condition. However, studies specifically designed to examine the relationship between tooth loss and osteoporosis are scarce, and reported results have been mixed. This study investigated the correlation between tooth loss and spinal bone density in a nonHispanic white female population. Forty-four subjects were recruited and divided into high and low spinal bone density groups based on whether the bone density was higher or lower than the age-adjusted population mean bone density. Missing teeth and periodontal status in these groups were assessed and analyzed. Tooth loss was not significantly different between subjects with low spinal bone density (4.90 +/- 0.89 teeth) and high spinal bone density (3.81 +/- 0.90 teeth). Tooth loss did not differ after age and periodontal adjustment. However, the loss of attachment levels (relative to the cementoenamel junction) was greater in the low spinal bone density subjects (3.42 +/- 0.30 mm) than in the high spinal bone density subjects (2.37 +/- 0.26 mm) (P < .05). The difference may have resulted from gingival recession (P < .05), because the gingival pocket depths were not significantly different between the two groups. In this study, total tooth loss was not directly associated with systemic bone density. However, periodontal disease was negatively associated with spinal bone density. Whether periodontal disease will ultimately lead to greater tooth loss in low spinal bone density group merits further investigation.

Ductal carcinoma in situ-associated nipple discharge: a clinical marker for locally extensive disease.

BACKGROUND: This study evaluates the diagnosis and treatment of women with pathologic nipple discharge caused by ductal carcinoma in situ (DCIS). METHODS: Women with unilateral spontaneous bloody, serous, or brown nipple discharge who presented between January 1, 1988 and August 1, 1996 were identified by retrospective chart review. Women with nonspontaneous, physiologic discharge were excluded. RESULTS: Two hundred seventy-seven women with a mean age of 59.5 years (range, 24 to 88 years) underwent duct exploration and biopsy for pathologic discharge, with 43 (15.5%) found to have DCIS. The discharge was bloody in 29, clear in eight, and brown in six women. Seven of 12 (58%) women with an associated breast mass were found to have a microinvasive component with the DCIS. Discharge cytology showed malignant cells in only two of 12 (16%) women examined. A ductogram was performed on 20 women, with filling defects seen in 10, ectasia in 3, narrowing in 4, and normal ducts in 3. The DCIS included 17 (40%) specimens with cribriform pattern, 17 (40%) micropapillary, 8 (18%) comedo, and 2 (2%) solid. Twelve microinvasive cancers were found in combination with DCIS. After duct exploration, 37 (86%) patients were found to have extensive or multifocal DCIS to the margin, or both, with 32 (74%) patients requiring mastectomy to achieve free surgical margins. There was residual disease in 27 of 32 (84%) mastectomy specimens after initial biopsy. Breast conservation was possible in only 11 (26%) women. Forty of 43 (93%) are disease-free with a median follow-up of 37 months. CONCLUSION: Women presenting with pathologic nipple discharge require duct exploration regardless of cytologic or radiologic findings. When discharge is the result of DCIS, extensiveness of disease in relation to central location and intraductal spread may preclude breast conservation in as many as 27 of 43 (63%) cases.

Private physicians in ambulatory care training in U.S. medical schools.

The contribution of private physicians to medical student education in ambulatory care was determined by a questionnaire directed to departments of family practice, internal medicine, and pediatrics in 124 U.S. medical schools and their branch campuses. The response rate was 84 percent. Of the responding departments, 82 percent offered an ambulatory care course in curricular years three and/or four, and 56 percent utilized private physicians in their courses. Departments of internal medicine were least likely to offer such a course, and their courses less frequently included teaching by private physicians (p less than 0.0001). When offered, internal medicine courses in ambulatory care were least likely to be required for graduation and involved the fewer students. Departments of family practice were most likely to offer ambulatory care courses and were most likely to utilize private physicians in their courses.

Correlates of medication compliance in non-insulin-dependent diabetes mellitus.

Maintaining compliance with medications is important in the management of patients with non-insulin-dependent diabetes mellitus. We examined correlates of medication compliance in 77 patients followed up prospectively for 24 weeks. Of the demographic, socioeconomic, and clinical variables examined, only older age and greater education were related to compliance. While statistically significant, the differences observed were small and unlikely to be useful to clinicians. Factors reflecting the process of care, including frequency of appointments, minutes spent with the provider, and patient satisfaction were not related to compliance. Symptoms associated with poor glucose control and fasting glucose levels were also not significantly related. The patient's report of his own compliance, however, was strongly associated with our independent measures of medication taking. We conclude that rather than attempting to predict compliance from sociodemographic characteristics, symptoms, or glucose values, the physician should directly inquire about medication taking in a nonthreatening manner.

Lobular carcinoma in situ with microinvasion.

Six patients with lobular carcinoma in situ with microinvasion were described in this report. Lobular carcinoma in situ is not known to progress to microinvasive disease. Although this feature is rare, the current under standing that lobular carcinoma in situ is a marker needs to be revised.