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Biomedical subjects

E Haus

Publications and source records attributed to E Haus.

At least 19 recordsLinked to original sources

Why continued surveillance? Intermittent blood pressure and heart rate abnormality under treatment.

Several opinion leaders have monitored their blood pressure systematically a sufficient number of times a day for chronomic (time structural) analyses, from the time of encountering chronobiology until their death; they set an example for others who also may not wish to base treatment on single spotchecks in a health care office. Such self-measurements, while extremely helpful, were not readily feasible without a noteworthy interruption of activities during waking as well as of sleep. New, relatively unobtrusive instrumentation now makes monitoring possible and cost-effective and will save lives. Illustrative results and problems encountered in an as-one-goes self-survey by GSK, a physician-scientist, are presented herein. Both MESOR-hypertension and CHAT (circadian hyper-amplitude-tension) can be intermittent conditions even under treatment, and treatment is best adjusted based on monitoring, rather than "flying blind".

Adult↗

Circadian rhythms and clinical medicine with applications to hypertension.

Circadian (24-h) rhythms are important to the practice of medicine. The phasing and amplitude of key physiologic and biochemical circadian rhythms contribute to predictable-in-time patterns in the manifestation and exacerbation of most medical conditions. Moreover, body rhythms can significantly affect responses of patients to diagnostic tests and medications. Rhythmicity in the pathophysiology of medical conditions is the rationale for chronotherapeutics--that is purposeful variance of the concentration of medicines in synchrony with biologic rhythm determinants of disease activity--to optimize treatment outcomes. This article discusses the concept of biologic time structure and its relevance to the practice of medicine, with a focus on hypertension and cardiovascular issues.

Antihypertensive Agents↗

Circadian rhythms of basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), cortisol, and melatonin in women with breast cancer.

BACKGROUND: Circadian rhythms in plasma concentrations of many hormones and cytokines determine their effects on target cells. METHODS: Circadian variations were studied in cortisol, melatonin, cytokines (basic fibroblast growth factor IbFGF], EGF, insulin-like growth factor-1 [IGF-1]), and a cytokine receptor (insulin-like growth factor binding protein-3 [IGFBP-3]) in the plasma of 28 patients with metastatic breast cancer. All patients followed a diurnal activity pattern. Blood was drawn at 3h intervals during waking hours and once during the night, at 03:00. The plasma levels obtained by enzyme-linked immunoassay (ELISA) or radioimmunoassay (RIA) were evaluated by population mean cosinor (using local midnight as the phase reference) and by one-way analysis of variance (ANOVA). RESULTS: Cortisol and melatonin showed a high-amplitude circadian rhythm and a superimposed 12h frequency. bFGF showed a circadian rhythm with an acrophase around 13:00 with a peak-to-trough interval (double amplitude) of 18.2% and a superimposed 12h frequency. EGF showed a circadian rhythm with an acrophase around 14:20, a peak-to-trough interval of 25.8%, and a superimposed 12h frequency. IGF-1 showed a high value in the morning, which is statistically different (t test) from the low value at 10:00, but a regular circadian or ultradian rhythm was not recognizable as a group phenomenon. IGFBP-3 showed a low-amplitude (peak-to-trough difference 8.4%) circadian rhythm with the acrophase around 11:00 and low values during the night. CONCLUSIONS: (1) Circadian periodicity is maintained in hospitalized patients with metastatic breast cancer. (2) Ultradian (12h) variations were superimposed on the circadian rhythms of the hormones and several of the cytokines measured. (3) Studies of hormones and cytokines in cancer patients have to take their biologic rhythms into consideration. (4) The circadian periodicity of tumor growth stimulating or restraining factors raises questions about circadian and/or ultradian variations in the pathophysiology of breast cancer.

Analysis of Variance↗

Clinical chronobiology and chronotherapeutics with applications to asthma.

The concept of homeostasis (i.e., constancy of the milieu interne) has long dominated the teaching and practice of medicine. Concepts and findings from chronobiology, the scientific study of biological rhythms, challenge this construct. Biological processes and functions are not at all constant; rather, they are organized in time as rhythms with period lengths that range in duration from as short as a second or less to as long as a year. It is the body's circadian (24 h) rhythms that have been researched most intensely. The peak and trough of these rhythms are ordered rather precisely in time to support the biological requirements of activity during the day and sleep at night. The timing of the peak and trough plus the magnitude of variation (amplitude) of physiological and biochemical functions during the 24 h give rise to predictable-in-time, day-night patterns in the manifestation and exacerbation of many common medical conditions. Circadian rhythms also can influence the response of patients to diagnostic tests and therapeutic interventions according to their timing with reference to body rhythms. Rhythms in the pathophysiology of medical conditions and patient tolerance to medications constitute the basis for chronotherapeutics, the timing of treatment in relation to biological rhythm determinants as a means of optimizing beneficial effects and safety. The article discusses recent advances in medical chronobiology and chronotherapeutics and their relevance to clinical medicine in general and the management of asthma in particular. Indeed, since asthma is a disease that exhibits rather profound circadian rhythmicity, investigation of its pathophysiology and therapy necessitates a chronobiologic approach.

Anti-Asthmatic Agents↗

Biologic rhythms in the immune system.

In all of its components, the immune system shows regularly recurring, rhythmic variations in numerous frequencies; the circadian (about 24 h) rhythms are the best explored. The circadian variations in immunocompetent cells circulating in the peripheral blood are of a magnitude to require attention in medical diagnostics. Both the humoral arm and the delayed (cellular) arm of the immune system function in a rhythmic manner. The response of the immune system to introduction of an antigen and to challenge of the sensitized organism varies in extent in the circadian frequency range and also in lower frequencies, for example, of about a week (circaseptan) or seasonally (circannual). The medical application of the biologic rhythms of the immune system extends to diagnostic measures, as well as treatment.

Animals↗

Melatonin levels in women with fibromyalgia and chronic fatigue syndrome.

OBJECTIVE: Fibromyalgia (FM) and chronic fatigue syndrome (CFS) are stress associated disorders mainly affecting women. FM is characterized primarily by widespread musculoskeletal pain, and CFS by profound debilitating fatigue, but there is considerable overlap of clinical symptoms between these 2 syndromes. Neuroendocrine abnormalities have been noted in both FM and CFS and desynchronization of circadian systems has been postulated in their etiology. The pineal hormone melatonin is involved in synchronizing circadian systems and the use of exogenous melatonin has become widespread in patients with FM and CFS. METHODS: We examined the characteristics and relationship of melatonin and cortisol levels in premenopausal women with FM (n = 9) or CFS (n = 8), compared to age and menstrual cycle phase matched controls. Blood was collected from an indwelling intravenous catheter every 10 min over 24 h, and plasma melatonin and cortisol were determined by radioimmunoassay at 60 and 10 min intervals, respectively. RESULTS: Night time (23:00-06:50) plasma melatonin levels were significantly higher in FM patients compared to controls (p<0.05), but there was no significant difference in melatonin levels between CFS patients and controls. No differences in the timing of cortisol and melatonin secretory patterns and no internal desynchronization of the 2 rhythms were found in either patient group, compared to controls. CONCLUSION: Raised plasma melatonin concentrations have been documented in several other conditions that are associated with dysregulation of neuroendocrine axes. Increased melatonin levels may represent a marker of increased susceptibility to stress induced hypothalamic disruptions. These data indicate that there is no rationale for melatonin replacement therapy in patients with FM and CFS.

Adolescent↗

Time-dependent variations of the skin barrier function in humans: transepidermal water loss, stratum corneum hydration, skin surface pH, and skin temperature.

Although circadian rhythms have been described for many human functions, there are minimal data on circadian rhythms related to skin physiology. This study investigated the circadian rhythmicity of skin variables related to skin barrier function in humans. We measured transepidermal water loss, stratum corneum moisture, skin surface pH, and skin temperature in 16 healthy volunteers (nine men and seven women, aged 23-53 y). Subjects were sampled every 2 h in two sessions over a 24 h span. Twelve samples were obtained for each variable in the following sites: forehead, forearm, upper back, and shin. We used cosinor analysis and ANOVA to validate observed differences. Time-dependent rhythms were detected in most skin variables except in stratum corneum hydration. We found a statistically significant circadian rhythmicity characterized by cosinor analysis in transepidermal water loss, skin surface pH, and skin temperature on the forearm, forehead, and shin. Peak-trough differences occurred in all locations. The values of the same variables measured at different sites correlated positively, whereas the values of the different variables did not. These results suggest that skin permeability is higher in the evening and night than in the morning. These data may be clinically relevant in several aspects applied to skin physiology and topical drug application.

Adult↗

Urinary tract infections in the homebound elderly.

The incidence of bacteriuria is widespread in the elderly. Because home care nurses serve elderly clients with multiple problems, bacteriuria is often encountered in the home care setting. The elderly may present with typical signs and symptoms of infection. However, the indications are often vague and nonspecific. Bacteria in the urine often presents with no symptoms and is best left untreated. The responsibilities of the nurse include evaluating signs and symptoms presented by their clients and overseeing therapeutic plans, specimen collection, infection control practices, catheter care, education, and prevention. It is important that prevention always receive top priority.

Age Distribution↗

Circannual variation of cell proliferation in lymphoid organs and bone marrow of BDF1 male mice on three lighting regimens.

BDF1 male mice, which had been raised for several generations on a lighting regimen of LD 12:12, were studied. Experiments were conducted over 24 h spans during winter, spring, summer, and fall. For 3-4 weeks prior to each study, one-third of the animals were kept on a lighting regimen of 8 h of light alternating with 16 h of darkness (LD 8:16), one-third was kept on a regimen of LD 12:12, and one-third was kept on a regimen of LD 16:8. Subgroups of mice on all three lighting regimens were killed at 4 h intervals over a 24 h span. At 20 minutes prior to sacrifice, the animals received 5 microCi of 3H-thymidine/0.2 ml/20 gm body weight intraperitoneally. The thymidine uptake in DNA (DPM[3H]/microgram DNA) was studied as an index of cell proliferation in the thymus, inguinal lymph node, spleen, femur, and a segment of the lumbar vertebral column. A circannual variation of 3H-thymidine uptake in DNA was found in all organs irrespective of the lighting regimen under which the animals were kept. The timing of the circannual variation, however, varied among the organs. In the thymus, the lowest thymidine uptake occurred during summer, with higher thymidine uptake during the other three seasons. In the inguinal lymph node, the peak in thymidine uptake was in the spring, with lower values during the other three seasons, the lowest during summer. In the spleen, the highest thymidine uptake occurred in the mice on all three lighting regimens during fall, with lower uptake during winter, spring, and summer. In the bone marrow of both the femur and the vertebral column, the thymidine uptake was high in winter and fall and low in spring and summer. Serum corticosterone measurements were available in winter, spring, and fall, and they showed statistically significant lower values in winter and fall than in spring. The conclusion was drawn that circannual rhythms of 3H-thymidine uptake in the DNA of the thymus, spleen, lymph nodes, and bone marrow are found in mice reared for generations under a LD 12:12 lighting regimen and persist if the animals are kept under a regimen of LD 8:16 or LD 16:8 for 3-4 weeks prior to sacrifice.

Animals↗

The pattern of hormonal circadian time structure (acrophase) as an assessor of breast-cancer risk.

Through many hormones are secreted in a pulsatile manner, their secretion pattern can be superimposed by a 24-hour sinusoidal curve. The sinusoidal curve is then characterized by the estimated peak clock time location (acrophase), the adjusted mean (mesor) and the amplitude. When the distribution of the acrophases of 12 hormones was compared among women with regard to their age and to the level of risk of developing breast cancer, statistically significant differences were revealed between distribution patterns of acrophases of women with high (n = 12 and 45 circadian profiles) or low (n = 12 and 41 circadian profiles) risk of developing breast cancer. However, when the amplitude/mesor ratios of the corresponding hormonal rhythms were analyzed, significant differences occurred between age groups rather than between risk levels. These observations suggest that the endocrine time structure between individual women can be used as an assessor of breast-cancer risk.

Adult↗

Clinical relevance of about-yearly changes in blood pressure and the environment.

Changes identified by inferential statistics from summer to winter of high to low arterial blood pressures (BP) have been quantified as a large predictable about-yearly BP swing. This condition of a large annual BP amplitude (LABPA) raises concern about hypotension as well as hypertension and raises new questions regarding appropriate guidelines for diagnosis and treatment. Recommendations made in the fall on the basis of data collected in the summer may be totally inadequate in dealing with the patient's condition in the winter. In order to avoid such mistakes, it is imperative to implement a systematic surveillance of BP in the light of current chronobiological limits. Patients with a large circannual BP amplitude are particularly suited for a study of the underlying hormonal mechanisms. The longitudinal monitoring of their BP is also amenable to the study of environmental influences from near and far.

Aldosterone↗

Changes in human blood pressure with season, age and solar cycles: a 26 year record.

The record was studied of a 71-year-old, diurnally active (0700-2200 hours) male psychiatrist (G.N.) who self-measured systolic and diastolic blood pressure (BPS and BPD) mostly but not exclusively on Sunday mornings, from 1969 to 1994. A large about-yearly change was revealed which increased with age and was accompanied by a decreasing trend in the yearly rhythm-adjusted mean (MESOR; P < 0.01). According to conventional criteria that specify only upper limits of acceptability, G.N. was hypertensive in summer and normotensive in other seasons. Since changes in both MESOR and circannual amplitude occurred, a systematic surveillance of BP is the chronobiological recommendation.

Age Factors↗

Stimulation of the secretion of dehydroepiandrosterone by melatonin in mouse adrenals in vitro.

Adrenals of young adult male mice kept on a LD 12:12 lighting regimen for three weeks prior to study and harvested at four different circadian stages were incubated for 2 hours with 0.4 IU synthetic ACTH in 2 ml Krebs-Ringer buffer (KR), or with 50, 150, and 450 microM of melatonin in KR containing 0.4 IU ACTH. The addition of melatonin to ACTH leads to a dose dependent stimulation of production and/or secretion of DHEA into the incubation medium irrespective of the circadian stage of harvesting of the adrenals. This relationship is of interest in view of the simultaneous decrease of dehydroepiandrosterone and melatonin in the course of aging, and the effects of these compounds upon aging related changes.

Adrenal Glands↗

Resonance of about-weekly human heart rate rhythm with solar activity change.

In several human adults, certain solar activity rhythms may influence an about 7-day rhythm in heart rate. When no about-weekly feature was found in the rate of change in sunspot area, a measure of solar activity, the double amplitude of a circadian heart rate rhythm, approximated by the fit of a 7-day cosine curve, was lower, as was heart rate corresponds to about-weekly features in solar activity and/or relates to a sunspot cycle.

Adult↗

[Chronobiological approach of aging].

Ageing is a complex, multifactorial phenomenon. The existence of biologic rhythms as well as the study of their modifications or their alteration in the aged are useful and pertinent to understand the biologic age. These modifications, if any, may be interpreted as a change in the adaptability of aged subjects to environmental factors. The loss or decrease of adaptation capacity with ageing is worth quantifying. This paper rounds up the question.

Aged↗

Biologic rhythms in hematology.

The number of circulating blood cells and their function, as expressed by phagocytosis, the response to mitogens or by the natural killer cell activity, and the formation of blood cells in the bone marrow, and their response to toxic (e.g. chemotherapeutic) agents show biologic rhythms in several frequencies of which the circadian rhythms are most extensively explored. Some of these rhythms show large enough amplitudes to be clinically important, especially if consecutive samples of the same patients are to be evaluated. Rhythm disturbances characterize hematologic and immune related disease states like, e.g., infection with HIV. Circadian rhythms in the aggregability and adhesiveness of blood platelets contribute to the transient state of hypercoagulability during the morning hours which is thought to lead to the peak incidence at this time of myocardial infarction, cerebral infarct, and sudden cardiac death. The rhythmic, and thus in their timing to a certain degree, predictable changes in responsiveness of the hematopoietic and immune system provide an opportunity to improve the effects of growth factors and cytokines, and decrease their undesirable side effects. Timing of cancer chemotherapy at the time of maximal resistance of the hematopoietic system to a certain drug may improve the often dose limiting toxicity of the agent. Some preliminary results suggest that not only treatment toxicity may be diminished, but also efficacy may be improved. This approach is made difficult by the large individual differences in the timing of the rhythms, and by the interaction of circadian, circaseptan, and circannual rhythms which have, thus far, been only incompletely explored.

Adult↗