Drug intolerance in patients with idiopathic environmental intolerance syndrome.

The increasing rate of the idiopathic environmental intolerance (IEI) has been observed for the last decade. The aim of this report was to analyse the allergic component of the disease in particular relation to drug intolerance. Six patients with diagnosed IEI showed a positive skin test reaction to several commonly used antibiotics, nonsteroidal anti-inflammatory drugs, myorelaxants, verapamil, etc. In three cases, the thorough diagnosis of sensitivity to anaesthetic agents enabled to perform necessary surgical treatment, in others - facilitated the proper treatment of headaches and hypertension. Symptoms related to allergy contributed to the deterioration of IEI. Thus, a consultation of IEI patients by an allergologist seems to be of a substantial importance.

A classification of drug substances according to their mechanism of action.

Different classification systems for therapeutic agents exist. The most commonly used one is the ATC Code (ATC: Anatomy, Therapeutic properties, Chemical, pharmacological properties). Here, an alternative classification system (TCAT: Target-Chemistry-Anatomy-Therapy) is proposed which refers to the molecular mechanism of action or rather, target. The main subgroups of targets are: enzymes; substrates, metabolies, proteins; receptors; ion channels; transporter molecules and systems; nucleic acids, ribosomes; physicochemical mechanisms; antigen-antibody reactions; unknown targets. This target-oriented approach may be particularly useful in teaching advanced medicinal chemistry.

Structural effects of framework mutations on a humanized anti-lysozyme antibody.

A humanized version of the mouse anti-lysozyme Ab D1.3 was previously constructed as an Fv fragment and its structure was crystallographically determined in the free form and in complex with lysozyme. Here we report five new crystal structures of single-amino acid substitution mutants of the humanized Fv fragment, four of which were determined as Fv-lysozyme complexes. The crystals were isomorphous with the parent forms, and were refined to free R values of 28-31% at resolutions of 2.7-2.9 A. Residue 27 in other Abs has been implicated in stabilizing the conformation of the first complementarity-determining region (CDR) of the H chain, residues 31-35. We find that a Phe-to-Ser mutation at 27 alters the conformation of immediately adjacent residues, but this change is only weakly transmitted to Ag binding residues in the nearby CDR. Residue 71 of the H chain has been proposed to control the relative disposition of H chain CDRs 1 and 2, based on the bulk of its side chain. However, in structures we determined with Val, Ala, or Arg substituted in place of Lys at position 71, no significant change in the conformation of CDRs 1 and 2 was observed.

Endogenous digoxin-like immunoreactive factor (DLIF) serum concentrations are decreased in manic bipolar patients compared to normal controls.

BACKGROUND: A decrease in sodium pump activity in erythrocytes has been associated with manic episodes of bipolar illness relative to euthymic moods. Since red blood cells are long-lived and lack a nucleus, it is likely that a plasma factor is responsible for the observed decrease in sodium pump activity. METHODS: Utilizing a radioimmunoassay, we examined the serum concentrations of the digoxin-like immunoreactive factor (DLIF) in ill and well bipolar patients and compared the values to those of normal controls. RESULTS: DLIF was significantly decreased in manic individuals as compared to normal controls (143.6+/-S.E.M. 20.94 vs. 296.6+/-12.76 pg digoxin equivalents/ml, respectively, F = 4.77, P<0.05), but not compared to euthymic bipolar subjects 213.8+/-86.92, P = 0.77). There were no significant differences in DLIF concentrations between manic and euthymic bipolar individuals (P = 0.8). Since relapse in bipolar patients appears to display a seasonal pattern, we also measured the plasma concentration of this factor over a 12-months period. Normal controls exhibited a seasonal pattern of change in serum DLIF concentrations with a nadir in the winter months. Plasma concentrations of DLIF in bipolar patients did not show a seasonal pattern and maintained low levels throughout the year. LIMITATIONS: Due to the nonspecificity of our antibody, we could measure only total DLIF. Furthermore, it is unclear what the role of circulating DLIF, if any, may be on brain function. CONCLUSION: DLIF may be involved in the pathophysiology of mania.

Conformational correction mechanisms aiding antigen recognition by a humanized antibody.

The crystal structure of the complex between hen egg lysozyme and the Fv fragment of a humanized antilysozyme antibody was determined to 2.7-A resolution. The structure of the antigen combining site in the complex is nearly identical to that of the complexed form of the parent mouse antibody, D1.3. In contrast, the combining sites of the unliganded mouse and humanized antilysozymes show moderate conformational differences. This disparity suggests that a conformational readjustment process linked to antigen binding reverses adverse conformations in the complementarity determining regions that had been introduced by engineering these segments next to human framework regions in the humanized antibody.

PCASSO: a secure architecture for access to clinical data via the Internet.

Patient Centered Access to Secure Systems Online (PCASSO) is a National Information Infrastructure research project funded by the US National Library of Medicine (NLM). PCASSO is specifically designed to address the problem of enabling secure access to health information over the Internet, not just for healthcare providers and medical researchers, but also for patients to view their own medical records. The project is using familiar Web technologies to support the search and retrieval of information, including patient demographics, medications, lab tests, and transcription reports. State-of-the-art security technologies protect patient privacy and the integrity of patient information. This paper describes the security architecture of the PCASSO system.

Worry about health status among the elderly: patient management and health policy implications.

Health care reform depends on reducing inappropriate utilization and improving access. Elderly people, major consumers of primary care, are a place to begin reforms, but progress has been slow. We combined primary care screening questions for objective (medical condition as wellness) and subjective (perception of health as worry) health in a study of 767 elderly people in Youngstown, Ohio. The worried well (31.2%), a group likely to consume medical care inappropriately, and unconcerned ill (4.4%), a group likely to avoid seeking necessary medical care, account for more than one-third of the elderly. The unconcerned well (57.0%) and worried ill (6.9%) pose fewer problems. Family physicians can predict utilization and access problems for targeted groups (older people, minorities, and women), along with health beliefs and other indicators of health status. Although findings in this study are preliminary, they do point to positive uses in health policy and patient management. Extensive usage of the sure would require financial reimbursement to health care providers.

Concurrent use of cocaine and alcohol by patients treated in the emergency department.

STUDY OBJECTIVE: To compare the demographics, presenting signs and symptoms, morbidity, and mortality of emergency department patients with drug screen results positive for benzoylecgonine ester (BE; a cocaine metabolite) and those positive for BE and alcohol. METHODS: We carried out a retrospective cohort study, in a university-affiliated community hospital, of 190 patients positive for BE alone and 125 patients positive for BE and alcohol. RESULTS: Patients positive for BE and alcohol were more often male and single. They were more likely to have been intubated, admitted to an ICU, and involved in violent trauma and to have demonstrated altered mental status than patients who tested positive for BE alone. These patients had higher mean heart rate and blood pressure values than patients positive for BE alone, and the two patients with myocardial infarction were positive for BE and alcohol. The incidence of rhabdomyolysis and the mean blood urea nitrogen value were lower in the patients positive for BE and alcohol. The two deaths in our study were patients in the BE-and-alcohol group, but these were due to trauma and not to the toxic effects of cocaine or alcohol. CONCLUSION: Cocaine use was associated with a low incidence of morbidity and mortality, but patients who combined it with alcohol had decreased mental status and required a higher intensity of care.

Lymphoblastoid transmembrane potential in bipolar patients, their siblings, and unrelated healthy comparison subjects.

Bipolar illness appears to be characterized by alterations in ionic homeostasis that are related to mood state. This is reflected by reports of altered intracellular sodium and calcium concentrations, altered sodium pump (Na+,K+-adenosine triphosphatase), and calcium pump (Ca2+-adenosine triphosphatase) activity. Recent ex vivo studies with fresh lymphocytes and in vitro studies with cultured lymphoblasts suggest that there may be an enduring trait-related abnormality in Na+,K+-adenosine triphosphatase as well. We have previously found that the lymphocyte transmembrane potential (TMP) varies with mood state. To examine the question of trait-related changes in TMP, we studied TMP of immortalized lymphoblasts from 14 patients with bipolar illness, nine unaffected siblings, and eight normal subjects. TMP was the same in all three groups. These preliminary data suggest that TMP is a state-- rather than a trait-related marker.

Urban/rural elderly health status differences: the dichotomy reexamined.

Health policy research analyzes urban/rural differences as a simple dichotomy. Research characterizes the rural elderly as having a higher incidence of sickness, dysfunction, disability, restricted mobility, and acute and chronic conditions than their urban counterparts. However, population density as a dichotomy may obscure urban, rural, or urban/rural differences. Interviews measuring health status were conducted with a representative sample of 2,300 elderly people in six Northeastern Ohio counties constituting an urban/rural continuum. On medical condition, use of medical aids, and symptoms, health status improved significantly when moving from rural to urban, but correlations were small. Using dichotomies, urban elderly reported fewer medical conditions and symptoms than rural elderly, but four other health-status variables revealed no significant association and results differed depending on how dichotomies were defined. When individual communities were compared few urban/rural patterns emerged. Controlling for demographics did not change interpretations. Findings question blanket assertions about urban/rural health-status differences. Medical resources may be misallocated. Rather than assuming poor health status among the rural elderly, researchers must verify differences through community-based research.

Alcohol, drugs, and urban violence in a small city trauma center.

Substance abuse and urban trauma go hand in hand. But research focuses on large cities served by major academic medical centers. Do small cities face the same problems? Two hundred thirty-three urban trauma inpatients from a metro area of 250,000 were studied using patient interviews and medical records. As in large cities, one half used alcohol or drugs when attacked. Seventy percent were likely to be young, male, poor African-Americans. Only 3% were gang members, but demographic characteristics failed to explain substance abuse as they have for larger cities. A culture of violence pervades the small city, as it does in large urban ghettos. Two fifths were repeat urban trauma victims. Two fifths witnessed assaults in the past year. One third carried a knife or gun. Fifteen percent used a weapon on another person in the last year. Contextual variables, like being hurt in a bar, were related to drinking and drugs. The best predictor of present substance abuse and urban trauma was medical history of substance abuse. The need for (a) toxicology screens for all trauma victims, (b) referrals to substance abuse programs, (c) targeting at-risk populations for prevention, and (d) eliminating environments fostering violence and substance abuse is supported.

Repeat victims of violence in an urban trauma center.

Repeat victims of violence are overwhelming urban trauma centers, yet little is written about them in the medical literature. This study combined medical record and survey data to study urban trauma recidivism among patients presenting at the Emergency Department [ED] of St. Elizabeth Hospital in Youngstown, Ohio during a 4-year period. Two-fifths of urban trauma patients were repeat victims. Repeat victims were more likely to be poor African-American males, have substance abuse and mental health problems, and live in neighborhoods where violence is pervasive. Most have no health insurance. Demographic characteristics were less important in explaining recidivism than were the circumstances surrounding violent behaviors. ED physicians must be trained to take into account a wide variety of environmental, personal, and circumstantial factors in treating and managing urban trauma patients. This may require reforms in health care financing.

Agreement between telephone survey and medical record data for the elderly patient.

OBJECTIVE: This study compares agreement between telephone survey and ambulatory medical record data for an elderly patient population. METHODS: Medical records and telephone survey responses are used to compare health status (chronic medical condition, symptomatology, and functional status) of 142 elderly patients randomly selected from a family practice residency and a geriatric fellowship practice. Chart abstraction was performed by two resident and two faculty physicians after a training period designed to assure high inter-reviewer reliability. Telephone surveys were completed by two professional interviewers. Health status measures were taken from standard, published instruments. The kappa statistic was used to measure the agreement between medical record and survey data. RESULTS: Overall, there is little agreement between the medical record and the telephone survey results on chronic medical condition, symptomatology, and functional status. CONCLUSIONS: Medical records abstractions and telephone survey methodologies did not yield comparable health status data when applied to the same elderly patient population. Functional status assessment and symptomatology are particularly problematic, but even the presence or absence of chronic diseases is often inconsistent in the two data sources.

Health status among elderly Hungarians and Americans.

Selected health status data for elderly populations from similar industrial cities-Youngstown, Ohio, USA, and Debrecen, Hungary-were compared. Because of their impoverished health care system, unregulated heavily industrialized society, and unhealthful life-styles Hungarians were hypothesized to have poorer health status than Americans, even after taking into account demographic mediating factors. The study provides a health status baseline for elderly Hungarians shortly after communism's fall in 1989-1990 and shows how great a gap exists between Hungarian health status and that in the West. Hungarians were in much poorer health as measured by functional status, symptomatology, medical condition, depression, and subjective health status. Distinctions persisted when controlling for gender, age, and education. Poverty-level (and income) did not explain health status differences. The paper concludes that Hungary should pay more attention to health promotion, prevention, and primary care, as well as to reforming patient management in hospitals, nursing homes, and home care programs.

Access to medical care among the elderly in rural northeastern Ohio.

BACKGROUND: Conventional wisdom holds that the elderly living in rural areas suffer poor health and have limited access to health care compared with their urban peers. The relation between poor health and limited access, however, has yet to be adequately defined. METHODS: We conducted a telephone survey of 1000 elderly persons living in four rural northeastern Ohio counties using a proportional random-digit dialing method. RESULTS: Many rural elderly respondents appeared to suffer poor health and have limited access to medical care. However, a detailed analysis revealed that poor health and limited access were more perceptual than actual. CONCLUSIONS: Elderly persons living independently in rural northeast Ohio have much better health and access to care than suggested by the literature.

The effect on retirees of losing retirement and health insurance benefits.

BACKGROUND AND OBJECTIVES: The recent economic downturn has led to instability in the private health insurance industry. Although loss of medical benefits is assumed to have a negative effect on health, documentation is lacking. LTV Corporation (Ling-Temco-Vought) filed for bankruptcy and interrupted medical insurance for its retirees for six months. METHODS: Using a structured interview format, we surveyed community-living LTV retirees whose medical insurance had been interrupted. We sought to predict health status using a variety of measures. RESULTS: The vast majority of retirees were generally unaffected by the loss of medical benefits. Of the 191 LTV retirees from Youngstown, Ohio, who were interviewed shortly after health benefit loss, 13.8% reported longer-term health effects (continued decline in subjective health status), whereas 8.5% had short-term effects (decline followed by return to good or excellent health status). Although 10.5% of workers experienced serious health problems during the crisis, only one worker was unable to pay for health care as a result of the benefits loss. A discriminant analysis yielded excellent results in predicting longer-term deteriorating health status. CONCLUSIONS: Implications for community-oriented primary care service models are discussed, as well as the utility of demographic targeting for retirees losing health benefits.

Volunteers for community health. An Ohio hospital sponsors parish nursing programs for area churches and synagogues.

Since 1989, St. Elizabeth Hospital Medical Center, Youngstown, OH, has been conducting a hospital-based, multidenominational volunteer parish nurse program, which now extends to 11 Roman Catholic, Lutheran, Presbyterian, Methodist, Jewish, and Greek Orthodox congregations. Seventeen volunteer nurses are involved, responding to needs within their congregations by providing a variety of healthcare and educational services while revitalizing the Church's healing ministry. Volunteers selected are competent, experienced registered nurses who can relate to and communicate with people of all ages, accurately assess health-related problems, and make appropriate nursing decisions. Parish nurses focus on preventive care, health maintenance, and personal responsibility for maintaining a healthy life-style. Volunteer nurses determine their own schedule, contributing as much time as they can. Each volunteer nurse is responsible for developing a record-keeping system, documenting his or her parish activities, and submitting a quarterly report of volunteer hours and activities to the hospital. Hospital supports include the initial two-day orientation; monthly meetings at the hospital for information sharing, education, and mutual support; and nursing continuing education programs In addition, an advisory committee provides program support and education. St. Elizabeth Hospital Medical Center is exploring several methods of enhancing its health ministry outreach to congregations in dire need of such services.

Worried wellness: how meaningful is the concept in managing elderly patients?

The concept of "worried wellness" is poorly defined for research purposes, and little is known about the worried-well elderly. To study the incidence of worried wellness in the elderly and define the clinical utility of the term, researchers conducted a structured interview with 733 independently living community elderly and 250 elderly patients from a family practice residency-teaching practice. The interview combined standard subjective health questions with specific additional measures of worry to form a "worry" scale. The worry data were cross-tabulated with "wellness" parameters that included symptomatology, presence of chronic medical conditions, use of medical equipment, and activities of daily living. A wide range of prevalences for worry were found, depending on the measure used. Wellness data were more consistent: though the vast majority of elderly were fully functional, 9 out of 10 subjects had at least one medical condition. Cross-tabulation based on individual items from the worry and wellness measures yielded a prevalence of one-third or less, depending on the measure used. However, composite analyses for both liberal and conservative measures of worry disclosed very few cases of worried wellness in the patient or community samples. This finding points to a very low incidence of the phenomenon among the elderly and raises significant doubt about the clinical utility of the term "worried wellness."

Assessing the denominator problem in community-oriented primary care.

Determination of health care needs is an essential cornerstone of community-oriented primary care (COPC). Many physicians, lacking research resources, may generalize their own patient registry data to the community. But practice populations are likely to differ significantly from community populations. This study compared demographics, health status, and medical care utilization in a sample of 990 elderly living in the community and 250 elderly patients registered at the St. Elizabeth Hospital Family Health Center in Youngstown, Ohio. The community survey and patient registries were comparable on key demographic characteristics. But statistically significant differences were observed for functional status and a number of chronic medical conditions. Comparisons of symptomatology, use of health aides, subjective health status, depression, and stress produced no significant differences. Overall health care utilization patterns were similar. The elderly family health center patients were more representative of the non-institutionalized elderly in the community than expected. And although the clinical significance remains uncertain, these findings suggest that this practice sample may be used with caution for COPC planning. But considerably more research must be undertaken in a variety of practice settings before the use of practice populations for COPC planning is widely applied.