Profound hypoglycemia with the addition of a tricyclic antidepressant to maintenance sulfonylurea therapy.

Cases of profound hypoglycemia after the initiation of tricyclic antidepressant therapy in two patients taking sulfonylureas are described. To the authors' knowledge, this is the first report of a potential drug interaction between tricyclic antidepressants and sulfonylureas.

Decreased specific antibody synthesis in old adults: decreased potency of antigen-specific B cells with aging.

The rise in rates of infection in adults over the age of 60 is accompanied by a decreased ability of older adults to make specific immune responses after immunization with a variety of specific antigens (Ag). This investigation delineates age-related changes in Ag-specific humoral immunity, comparing adults over age 60 to young adults aged 18-40, using tetanus toxoid (TT) as an immunologic probe. A culture system which does not require TT booster immunizations of study subjects was used to induce in vitro specific antibody responses. The amount of anti-TT antibody (Ab) produced in serum and in culture was measured by a TT-specific enzyme-linked immunosorbent assay (ELISA). The numbers of anti-TT Ab-secreting B cells were measured by a TT-specific ELISA-plaque assay. The TT-specific responses of old subjects were significantly less than that seen for young control subjects in the following measures: (1) serum anti-TT Ab titers (mean +/- S.E. log 2 titer = 3.3 +/- 1.1 vs. 9.5 +/- 1.4, P less than 0.01); (2) anti-TT Ab produced by peripheral blood lymphocytes (PBL) in cultures stimulated with TT (6 +/- 2.1 ng/ml vs. 22 +/- 8.4 ng/ml, P less than 0.01); (3) numbers of anti-TT Ab secreting B cells per million cells cultured (6.7 +/- 3.4 vs. 26.6 +/- 7.6, P less than 0.001) and (4) mean ng Ab secreted per anti-TT Ab-secreting B cell (0.6 +/- 0.4 ng vs. 12.7 +/- 7.8 ng, P less than 0.01). This study shows that both decreased numbers of Ag-specific immune B cells and decreased potency on a per cell basis contribute to the impaired immune responses to immunizations in older adults.

Familial occurrence of hypersensitivity to phenytoin.

PURPOSE: Therapy with anticonvulsants such as phenytoin, phenobarbital, and carbamazepine can be complicated by severe hypersensitivity reactions. Previous work has suggested that the predisposition to such reactions is based on an inherited abnormality in the detoxification of reactive metabolites of the drugs. However, there are no reports of familial occurrence of the reactions in the literature. In the current study, we examined a family in which three siblings developed hypersensitivity reactions to phenytoin, confirming the inheritance of a predisposition to the reactions. Detoxification of reactive metabolites of the anticonvulsants was studied in cells from the patients and their siblings. PATIENTS AND METHODS: Three siblings from a family of 12 siblings developed hypersensitivity reactions to phenytoin characterized by fever, rash, lymphadenopathy, and anicteric hepatitis. All recovered completely after discontinuation of treatment. One sibling tolerated phenobarbital without toxic sequelae. Peripheral blood mononuclear cells from the three patients and five additional siblings who had never taken anticonvulsants were exposed to oxidative metabolites of phenytoin, phenobarbital, and carbamazepine generated by a hepatic microsomal drug-metabolizing system in vitro. The toxicity of metabolites in the cells from the siblings was compared with that in cells from control subjects. RESULTS: Cells from each of the patients who had experienced a hypersensitivity reaction exhibited increased toxicity from metabolites of phenytoin and carbamazepine, while the cellular response to metabolites of phenobarbital was within normal limits. Cells from four of the other siblings showed an abnormal response to phenytoin metabolites, while cells from the final sibling detoxified phenytoin metabolites normally. CONCLUSION: Our observations on the patients confirm the inherited nature of phenytoin hypersensitivity reactions in vivo. In vitro studies demonstrated abnormal metabolite detoxification in the patients and several of their siblings. The detoxification defect included metabolites of phenytoin and carbamazepine but not of phenobarbital. A family history of a drug hypersensitivity reaction should alert physicians to the probability of a markedly increased risk of an adverse reaction in family members. In vitro assays to confirm adverse reaction risks may ultimately be able to provide individualized risk assessment for patients who must take anticonvulsants.

Sibling grief in reaction to sudden infant death syndrome.

Much of the literature that exists regarding psychologic outcomes of sudden infant death syndrome (SIDS) has focused on parental grief or family response; at least two studies suggest that a SIDS death also affected siblings. It is believed that children who experience the death of a sibling due to SIDS do grieve. Factors related to bereavement are the child's age at the time of the sibling's death, special circumstances of the SIDS death, and explanations and grieving response of the parents. However, no information currently exists that characterizes the course of the grief response of these children. Studies have indicated that about 1 year is a normal grieving period for adults. This study was conducted to evaluate the time frame of children's grief response to the death of a sibling from SIDS. A questionnaire was designed that incorporated child grieving behaviors from several sources; 151 questionnaires were distributed to families in which a SIDS death had occurred in the past 16 years in Iowa and Illinois. Information was obtained from 43 families for 50 children who were older than 2 years of age at the time of the sibling's death. With respect to the length of children's grief response, 54% were reported to have grieved longer than 1 year and only 40% were reported to have grieved less than 6 months. Thus, it appears that the length of the grieving response for these children is similar to that described for adults.

Cardiopulmonary resuscitation policies in long-term care facilities.

OBJECTIVES: To describe CPR policies and the procedures for discussing CPR policies of Wisconsin long-term care facilities. DESIGN: Mail survey and telephone interview. MEASUREMENTS: Information about CPR policy, how policy is disclosed to residents and by whom, emergency medical technician team (EMT) response time, and number of CPR attempts during 1993. RESULTS: The 1994 survey response rate was 85% (346/ 404 facilities). Four percent of responding facilities maintain a policy of never initiating CPR. Another 23% never initiate CPR but would call an EMT. Lack of efficacy was the usual basis for policies never initiating CPR. About 15% of facilities would initiate CPR only on residents who had previously indicated a preference. On individuals who had not made an advanced directive decision, 57% of facilities would initiate CPR in the event of an arrest. Almost 30% of facilities offering CPR would initiate CPR on unwitnessed arrests. Approximately 51% of all facilities assigned a social worker alone to discuss CPR policy and preference, whereas 12.5% assigned a physician alone or as part of a team. During 1993, an estimated 118 attempts at CPR were reported for 172 facilities with a total of 19,596 licensed beds, for a frequency of one CPR attempt per 166 beds per year. CONCLUSIONS: Poor efficacy in this population was the main reason given for policies of never initiating CPR. Specific factors relating to CPR efficacy, such as EMT response time and ease of maintaining trained staff, were not major influences. Almost 30% of facilities offering CPR would perform it in unwitnessed situations, despite unlikely success. Many decisions about CPR may not be fully informed as nurses and physicians are not often assigned to discuss advance directives with residents or surrogates. Utilization of CPR in nursing homes offering resuscitation is low.

Minimal trauma fractures in older nursing home residents: the interaction of functional status, trauma, and site of fracture.

OBJECTIVE: This study was conducted to determine the incidence of long bone fractures in institutionalized older persons and to describe preceding traumatic events and the functional status of individuals sustaining fractures. DESIGN: A 1-year, prospective, cumulative incidence survey. SETTING: Eleven skilled nursing care facilities in the state of Wisconsin. PATIENTS: All residents of the 11 facilities. MEASUREMENTS: All incident reports of long bone fractures, description of events preceding the fractures, and functional status of the fracture cases. In addition, demographic and medical information was collected on fracture cases and the general nursing home population. MAIN RESULTS: Overall long bone fracture incidence was 3.52 per 100 subjects per year. Minimal trauma fracture incidence was 0.84 per 100 subjects per year. Fracture location was significantly related to type of trauma. Functional status was significantly related to fracture location and to the type of trauma preceding the fracture. Minimal trauma fractures occurred in individuals who were less mobile and more likely to be bed-bound, and the location was more likely to be the lower extremity below the hip. CONCLUSION: This is the first prospective survey of long bone and spontaneous fracture incidence rates in multiple nursing home facilities. Minimal trauma fractures are common in the nursing home, and most have no clear precipitating factors other than severely impaired mobility.

Mandibular and palatal tori, bone mineral density, and salivary cortisol in community-dwelling elderly men and women.

BACKGROUND: This investigation evaluated the relationship between the presence of tori and bone mineral density (BMD) and salivary cortisol levels. METHODS: A total of 230 healthy, community-dwelling elderly men (n = 129) and women (n = 101) aged 60 and older participated in this study. Forty-three women were on hormone replacement therapy (HRT). This was a component of a 5-year longitudinal study measuring subjects' body composition, hormone levels, physical activity, and diet every 6 months. Subjects were examined for the presence of tori by visual inspection and digital palpation. BMD at six sites was measured by dual-energy X-ray absorptiometry. Salivary cortisol levels were measured by radioimmunoassay. RESULTS: Twenty-three percent of all subjects had mandibular tori, 13% had palatal tori, and 12% had both mandibular and palatal tori. Mandibular tori were more common in men, and palatal tori were more common in women. The presence of mandibular tori was significantly correlated with BMD of the lumbar spine, femoral neck, trochanter, and Ward's triangle for all subjects, and with the femoral neck and trochanter of women not on HRT. Men with palatal tori had lower levels of salivary cortisol in the evening. CONCLUSIONS: This study documented the high prevalence of mandibular and palatal tori in a group of 230 elderly, community-dwelling subjects. Women not on HRT and all subjects taken as a group with mandibular tori had higher BMD. The presence of tori at young adulthood may be a marker of higher BMD in the future and of a lower risk for developing osteoporosis.

Immunodeficiency of aging.

Aging is associated with declines in multiple areas of immune function, but to date no single mechanism has emerged as being responsible for all the observed changes. Many changes occur at different rates within individuals as well as between individuals. With advancing age there is a concomitant increase in the incidence of many infections and cancers. It is being increasingly acknowledged that autoimmune processes play a proinflammatory role in the development of many pathological conditions, such as atherosclerosis. However, direct causal relationships between specific changes in immunity and the occurrence of specific diseases are rare. There is accumulating epidemiological, in vivo and in vitro evidence to support many such direct relationships in both animals and humans. It is likely that the mechanisms underlying age-related changes in immunity are multifactorial, with both genetic and environmental factors playing a significant role. Despite the current lack of unifying theories, much active and exciting work is proceeding in the area of immune stimulation. Studies describing age-related changes in immunity, as well as the testing of interventions to reverse these changes, will continue to fill the gaps in our knowledge, leading to a more comprehensive understanding of immunosenescence.

Effects of aging on immune function.

A variety of changes are observed in the immune system in both animals and humans with increasing age. There is a decline in the functional capacity of the cell populations that mount generalized and focused immune responses, and decreasing production and response of these cells to regulatory signals and proteins. These changes translate into less effective innate and adaptive immune responses, increased reactivity against self-antigens in vivo, and an increased incidence of infection. There may also be an increased risk of mortality. The mechanisms underlying age-related changes in immune function are not fully understood, but are likely to be multifactorial, including environmental and behavioral factors that affect over-all immune function from the molecular level to that of the entire organism.

Relationships between attitudes and use of adult-learning teaching activities by medical faculty.

This study examined teaching behaviors of medical faculty and their attitudes toward adult learners. A number of studies have examined characteristics of adult learners and found that certain teaching activities produce more effective learning in adults. Adult learners tend to be more self-directed and bring a variety of experiences to the educational setting; they also profit more from collaborative curriculum planning, learning activities, and evaluation of progress.

Patient care telephone calls received in family practice offices.

The majority of patients care calls referred to practitioners at each of two family practice office study sites were related to medications. However, there were significant differences in the proportion of patient care calls managed by staff physicians, family practice residents, and clinical pharmacists which involved discussion of medication. There were also significant differences in the callers and types of medication related calls managed by each practitioner group. Calls initiated by patients and those classified as refill requests accounted for the largest proportion of calls managed by staff physicians, residents, and clinical pharmacists. The majority of calls received by each practitioner group were managed without consultation. A follow-up office visit was recommended in approximately one half of all medication related calls. The findings of this study may be useful in determining the personnel required to manage medication related telephone calls and in identifying potential areas for education and training of personnel in family practice.

A study of the use of adult learning theory in medical instruction.

This study examined relationships between the attitudes of medical faculty toward specific aspects of adult learning theory as well as the degree to which behaviors were actually used to build upon those beliefs. A questionnaire was developed to assess attitudes toward adult learning theory and returned by 269 of the medical faculty at the University of Iowa College of Medicine (58.5%). Several significant relationships were noted between faculty beliefs and the teaching methods they reported using. First, the six components of adult learning theory studied were independent of one another, suggesting a lack of consistent attitudes toward these components. Second, faculty who had taken teaching courses or workshops on teaching showed attitudes different than their peers, and used different types of teaching activities. This finding suggests that educational experiences can in fact affect the attitudes and teaching practices used by medical faculty, at least with respect to principles of adult learning theory.

Routine pertussis immunization.

The benefits and risks of both the vaccine for pertussis and the disease itself are reviewed in this article. Unlike with the smallpox vaccine, it seems unlikely that a vaccine will be developed to eradicate pertussis completely, since most confer only a short-term immunity. A longitudinal study was undertaken to compare the mortality and morbidity rates of pertussis with the adverse reaction rate of the vaccination program. Risks of the vaccination, such as erythema, drowsiness, and vomiting are well known. However, the issue of neurologic difficulties has surfaced and disagreement exists. Some association does seem to exist between the vaccine and neurologic problems; however, the morbidity and mortality of whooping cough is of a greater health consequence than these rare neurologic reactions.

Aging, immunity, and cancer.

BACKGROUND: The prime function of the immune system is to protect the entire organism from a variety of insults and illnesses, including the development of cancer. The question of how age-related declines in immune function contribute to an increasing incidence of malignancies continues to be a focus of discussion and speculation. METHODS: The recent literature from the National Library of Medicine database (1990 through the present) was searched for articles using the medical subject headings (MeSH terms) of aging, immunity, cancer, senescence, and apoptosis. Bibliographies of articles retrieved were also scanned. RESULTS: Data from in vitro and in vivo animal and human studies demonstrate clear age-related alterations in both the cellular and humoral components of the immune system, but there is little evidence supporting direct causal links between immune senescence and most malignancies. CONCLUSIONS: Senescent decline in immune surveillance leads to the accumulation of cellular and DNA mutations that could be a significant factor in the development of malignancy and programmed cell death or apoptosis observed in the elderly.

Lymphocyte proliferation response to baker's yeast in Crohn's disease.

The etiology of Crohn's disease is still unknown. The present study served to test the hypothesis that baker's yeast (Saccharomyces cerevisiae) plays a role in Crohn's disease. Blood samples were obtained from 12 patients and 15 healthy controls. Peripheral blood leukocytes were isolated and incubated alone or with different concentrations of baker's yeast. After 3 days, the cultures were pulsed with tritiated thymidine. None of the lymphocyte cultures from healthy controls, including 3 bakers, proliferated in response to yeast. In striking contrast, all 9 patients with Crohn's disease in remission, on no medication, showed a threefold increase in their lymphocyte proliferation rate. Lymphocytes from 3 patients on 1.5 g of olsalazine maintenance therapy failed to respond. These results are consistent with previous findings that showed increased titers of IgG and IgA antibodies to baker's yeast in patients with Crohn's disease as compared to healthy controls. They confirm the suspicion that baker's yeast itself or a related antigen play a role in Crohn's disease and suggest that anti-inflammatory agents may act, in part, by inhibiting lymphocyte proliferation.

Stressful life events and depressive symptomatology in obstetric patients: a pilot study in a family practice setting.

Several studies have found the presence of stressful life events to be associated with the appearance of postpartum depression. However, many of these previous studies have been conducted in obstetric clinics; relatively little research in this area has been done in a family practice setting. The first objective of this study was to note the prevalence of depressive symptomatology in a family practice clinic's pregnant patients. The second purpose was to evaluate the relationship between stressful life events and depressive symptomatology during pregnancy and the postpartum period. Each subject (n = 27) was given a Beck Depression Inventory (BDI) at three times: second trimester, third trimester, and three weeks postpartum. Each subject also completed a life events scale for obstetric patients after delivery; both weighted and unweighted life events scores were calculated. The correlation between the weighted and unweighted life events scores was 0.85. Postpartum BDI scores were significantly related to life events scores: 0.47 (n = 27, p = .0133) for unweighted scores and 0.58 (n = 27, p = .0015) for weighted scores. Weighted life events scores were more highly correlated with BDI scores at each of the three administration. Finally, 19% of these subjects showed BDI scores consistent with mild depression after delivery. Each of these results is consistent with findings from studies done in other settings.

Review of the etiology and treatment of premenstrual syndrome.

Premenstrual syndrome (PMS) is a diagnostic enigma that causes significant morbidity in many woman. Numerous theories have been proposed in an attempt to explain the varied symptoms that occur cyclically in women with PMS. Suggested etiologic theories of PMS include psychological abnormalities, nutritional deficiencies, aberrations in the renin-angiotensin-aldosterone axis, altered prostaglandin activity, hormonal imbalances, and changes in endogenous opioid peptide activity. Because of the lack of standardized diagnostic criteria, clinical drug trials for PMS have been severely compromised. For every proposed cause of PMS, there exists a drug or drug class that has been investigated for treatment of the associated symptoms. Many clinical studies are uncontrolled, a significant deficiency in study design for a disorder that is associated with a high placebo response rate. At the present time, no definitive treatment for PMS exists and therapy must be individualized according to clinical response. This review article defines PMS, describes one of the current approaches to the diagnostic work-up, discusses the proposed etiologies of PMS, and reviews the various proposed treatment modalities.

Specific humoral immunity in the elderly: in vivo and in vitro response to vaccination.

Vaccinations are often unsuccessful in preventing infection among elderly populations because of generally poor humoral immune responses. We have used tetanus toxoid (TT) antigen to stimulate in vitro anti-tetanus toxoid antibody (anti-TT) synthesis and have found that lymphocytes from many healthy elderly individuals have a reduced production of anti-TT in vitro compared to young adults. This is associated with decreased numbers of B cells secreting anti-TT IgG and a decrease in the mean amount of anti-TT IgG produced per TT-specific B cell. In the present study we report that immunization results in a significant increase in serum titers in young adults for up to one year, whereas levels in old adults fall to baseline by 6 months. The number of B cells that secrete anti-TT IgG increases after immunizations in both young and old subjects, although the number in old subjects is significantly lower than in young subjects at all times except 6 months after. The mean amount of anti-TT produced per B cell (B-cell potency) is significantly lower for the old adults both before and at 6 and 12 months after booster. Immunization does not significantly change the mean amount of anti-TT produced per B cell for either age group. The decreased response to immunization with aging is associated with decreased numbers of specific Ab-secreting B cells and usually decreased potency of those B cells.

Effects of interleukin-4 on antigen-specific antibody synthesis by lymphocytes from old and young adults.

The current series of experiments were designed to explore the role of the B cell growth factor, interleukin-4 (IL-4), in the age-related decrease in production of antitetanus toxoid antibody in vitro. Exogenous recombinant IL-4 led to significant suppression of antitetanus toxoid antibody synthesis and numbers of antitetanus toxoid antibody-secreting B cells in cultures from healthy old subjects and healthy young subjects. These effects were most pronounced when IL-4 was present during the early phase of culture. Lymphocytes from old subjects were less sensitive to these effects and produced significantly less IL-4 than did lymphocytes from young controls. The addition of exogenous IL-4 may be inhibiting early activation signals that normally stimulate proliferation of B cells. A decreased sensitivity to the growth-promoting effects of IL-4 may be one of the mechanisms underlying defective specific antibody synthesis in aging.