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PubMed2004

Physiological, pharmacokinetic, and pharmacodynamic changes in space.

Medications have been taken since the first Mercury flight in 1967 and, since then, have been used for several indications such as space motion sickness, sleeplessness, headache, nausea, vomiting, back pain, and congestion. As the duration of space missions get longer, it is even more likely that astronauts will encounter some of the acute illnesses that are frequently seen on Earth. Microgravity environment induces several physiological changes in the human body. These changes include cardiovascular degeneration, bone decalcification, decreased plasma volume, blood flow, lymphocyte and eosinophil levels, altered hormonal and electrolyte levels, muscle atrophy, decreased blood cell mass, increased immunoglobulin A and M levels, and a decrease in the amount of microsomal P-450 and the activity of some of its dependent enzymes. These changes may be expected to have severe implications on the pharmacokinetic and pharmacodynamic properties of drug substances.

Aerospace Medicine↗
PubMed2003

The importance of exercising in space.

As a direct consequence of exposure to microgravity, astronauts experience a set of physiological changes which can have serious medical implications when they return to earth. Most immediate and significant are the headward shift of body fluids and the removal of gravitational loading from bone and muscles, which lead to progressive changes in the cardiovascular and musculoskeletal systems. Cardiovascular adaptations result in an increased incidence of orthostatic intolerance (fainting) following flight, decreased cardiac output, and reduced capacity for exercise. Changes in the musculoskeletal system contribute significantly to impaired function experienced in the post-flight period. The underlying factor producing these changes is the absence of gravity, and countermeasures are therefore designed primarily to simulate earthlike movements, stresses, and system interactions. Exercise is one approach that has had wide operational use and acceptance in both the US and Russian space programmes, and it has enabled humans to stay relatively healthy in space for well over a year. Although it remains the most effective countermeasure currently available, significant physiological degradation still occurs. The development of other countermeasures will be necessary for missions of longer duration, for example for human exploration of Mars.

Acceleration↗
PubMed2006

Bone demineralization and vertebral fractures in endogenous cortisol excess: role of disease etiology and gonadal status.

INTRODUCTION: The effects of endogenous cortisol (F) excess on bone mass and vertebral fractures have still not been thoroughly investigated. The aim of this cross-sectional case-control study was to investigate factors influencing bone demineralization and vertebral fractures in different conditions of F excess, i.e. Cushing's disease and adrenal and ectopic Cushing's syndrome. MATERIALS AND METHODS: Eighty consecutive patients and 80 controls were prospectively enrolled: 37 patients (21 females) with pituitary ACTH-secreting adenoma, 18 (14 females) with adrenocortical adenoma, 15 (11 females) with adrenal carcinoma of mixed secretion, and 10 (three females) with ectopic ACTH secretion. The groups had similar age. At diagnosis, bone mineral density (BMD) was determined by the dual-energy x-ray absorptiometry technique at the lumbar spine (L1-L4) and femoral neck; vertebral fractures were investigated by standard spinal radiographs. RESULTS: When comparing the groups with different etiology of F excess, the patients with ectopic ACTH secretion had higher F and lower BMD values than the other subgroups. Morning F (P = 0.03) and testosterone levels (P = 0.04) correlated with lumbar BMD. Vertebral fractures were found in 61 (76%) of the patients, were multiple in 52 (85%) of the cases, and clinically evident in 32 (52%). Only multiple fractures were more frequent in patients with ectopic ACTH hypersecretion (P < 0.05). Lumbar spine BMD was the best predictor of vertebral fractures (P < 0.01). Surprisingly, amenorrheic and eumenorrheic women had similar BMD values and fracture prevalence. CONCLUSION: A high prevalence (76%) of vertebral fracture was revealed, regardless of the etiology of the patients' hypercortisolism. The harmful effects of F excess at the spine were partly counterbalanced by the increased androgen production but were not affected by gonadal status in women.

Adenoma↗
PubMed1999

[Bone demineralization in Crohn's disease, its diagnosis, therapy and prevention].

In 20-60% of patients with Crohn's disease bone demineralization is found, usually osteoporosis, but also osteoporosis with malatic features. The cause is the reduced calcium intake (loss of appetite, lactose intolerance and malabsorption), reduced vitamin D intake and corticoid therapy. Nowadays the diagnosis is facilitated by the use of densitometers (ultrasonic and DEXA) and markers of osteoresorption and new bone formation. In treatment in addition to calcium and vitamin D used for a long time, fluorides are administered (only as monofluorophosphate), nasal thyrocalcitonin and bisphosphonates of the third series (alendronate). In postmenopausal women also hormonal treatment can be used unless contraindicated. However, burdening of the bones with regular exercise is a necessity. For prevention adequate calcium and vitamin D intake is important, non-smoking, and exercise.

Bone Demineralization, Pathologic↗
PubMed1999

Acromioclavicular joint subluxation is rare in rheumatoid arthritis. A radiographic 15-year study.

AIM: To conduct a radiographic assessment of the occurrence of the acromioclavicular joint subluxation in patients with long-standing rheumatoid arthritis. METHODS: A cohort of 74 patients with seropositive rheumatoid arthritis was followed prospectively for 15 years. At the 15-year visit, plain radiographs of both shoulders (n = 148) were obtained using a standard method. Acromioclavicular joint destruction was evaluated using Larsen's method, and radiographic subluxation was measured on the radiographs using two different methods. In one of these methods (method A), the distance between the upper edge of the coracoid process and the upper surface of the clavicle was measured. The other method (method B) involved measurement of the alignment of the upper joint margins of the acromion and clavicle. RESULTS AND CONCLUSION: Two of the 148 acromioclavicular joints fulfilled criteria for subluxation with method B. Neither measurement A nor measurement B differed significantly between unaffected joints (Larsen's grade 0 or 1) and affected joints (Larsen's grade > or = 2). In addition, neither measurement was correlated with the stage of acromioclavicular joint destruction (r < 0.10 for both measurements). Measurements A and B were significantly correlated to each other (r = 0.23; 95% CI, 0.07 to 0.38). The two subluxations (one upward and one downward) occurred among the nine joints with the most severe destructive lesions (Larsen's grade 5). In conclusion, acromioclavicular joint subluxation is rare in rheumatoid arthritis, occurring only when destruction of the joint is severe. The method B used in this study may prove useful for both population studies and routine clinical work.

Acromioclavicular Joint↗
PubMed1999

Effect of multiple intravenous pamidronate courses in Paget's disease of bone.

BACKGROUND: Pamidronate is a bisphosphonate whose short-term biological efficacy in Paget's disease of bone was convincingly established many years ago. A less well studied area is the efficacy of pamidronate in slowing disease progression and in preventing and treating complications. MATERIAL AND METHODS: We conducted an uncontrolled retrospective study of 79 Paget's disease patients given multiple intravenous pamidronate courses over a mean period of 45 +/- 19 months. The pamidronate dose per course was 180 mg, usually given over three days. The disease was severe and in some cases had proved refractory to other medications. Reasons for pamidronate therapy were pain or other subjective symptoms; established bone, joint, or nervous system complications; or prevention or these complications in patients with involvement of high-risk sites. RESULTS: Bone and joint pain improved under therapy, and in 78% of cases the outcome in terms of complication treatment and/or prevention was favorable. An important finding was waning of the clinical and biological effects of pamidronate as the number of courses increased. Fourteen percent of patients developed resistance to pamidronate, which seemed more closely related to disease extension than to focal lesion activity. CONCLUSION: These data suggest that a prompt return to normal of laboratory markers, most notably total alkaline phosphatase, should be sought, if needed by using higher doses than in our study.

Adult↗
PubMedDate not supplied

Space medicine.

How does the human body adapt to conditions of weightlessness, and are the changes reversible?

Adaptation, Physiological↗
PubMed2001

[Bone complication in diabetic subjects with good metabolic control and without any late complications: selected problems. Part I: calcium, phosphorus and magnesium metabolism].

The aim of the study was to evaluate whether in diabetics with good metabolic control and without any diabetic complications, disturbances of calcium, phosphorus and magnesium metabolism or hormonal regulation (parathormone/calcitonin) were present, and if they depended on type of diabetes, duration time of diabetes, kind of hypoglycaemic treatment, sex or age of patients. 83 subjects were examined, including: 14 with type 1 diabetes mellitus, 49 with type 2 diabetes mellitus and 20 healthy persons. All tests were performed in standarized low-calcium diet conditions. In basal conditions both serum concentrations and daily urine excretion of calcium, phosphorus, magnesium were estimated. Oral and intravenous calcium load tests with simultaneous parathormone, calcitonin, calcium, magnesium and phosphorus concentrations estimation were done. The final conclusions were as follow: Both in type 1 diabetes mellitus and type 2 diabetes mellitus subjects with good metabolic compensation and without advanced diabetic complications a tendency to early disturbances of calcium-phosphorus metabolism is observed. Physiological hormonal control (parathormone/calcitonin) is preserved. Correlations between mineral metabolism and type of diabetes, duration time of diabetes, daily insulin dose, body mass index and sex are observed. Kind of hypoglycaemic treatment has only slight influence on the mineral metabolism.

Adult↗
PubMed2001

[The assessment of the value of ultrasound and magnetic resonance imaging in diagnosing hand joint arthritis].

The main imaging investigation used in diagnosing rheumatoid arthritis is radiography of the hands and feet. It allows visualisation of bone erosions--typical of the disease. However, bone erosions occur during the later stages of the rheumatoid arthritis and are preceded by synovitis. The aims of the study were to use ultrasound (US) and magnetic resonance imaging (MRI) in examining joints in patients suffering from chronic arthritis, and also to assess the value of these methods in diagnostics. In 61 patients with chronic arthritis (39 with rheumatoid arthritis--RA, and 22 with another etiology arthritis), plain radiography, US and MRI of the hands was performed. MRI and US were more sensitivity in visualisation of bone erosions than plain radiography. Both methods showed synovitis in all patients with RA. In detecting bone erosions in the hand joints MRI and US are more sensitive methods than plain radiography. Both methods detect synovitis and tenosynovitis. Inflammatory changes shown using the MRI and US are more intensive in RA than in patients suffering from another etiology arthritis.

Adolescent↗
PubMed2001

[Bone complications in diabetic subjects with good metabolic control and without any long-term complications--certain problems. Part III: The influence of hypertension and type 2 diabetes mellitus co-incidence of calcium, phosphorus and magnesium metabolism].

Both high morbidity and potentiation of systemic complications emphasise significance of diabetes mellitus and hypertension co-incidence. The aim of the study was to analyse the influence of hypertension accompanied with type 2 diabetes mellitus on calcium phosphorus and magnesium metabolism. The study was performed in standard low-calcium diet conditions on the group of 49 patients with type 2 diabetes mellitus (among them 27 had hypertension), 14 patients with essential hypertension and 20 healthy persons. Both serum and urine concentration of creatinine, calcium, phosphorus, hydroxyproline, hydroxylysine and uric acid were analysed. Oral calcium load test was done. Serum alkaline phosphatase activity and oxalic acid urine excretion were also estimated. There were no significant differences between diabetic patients with and without hypertension as far as calcium, phosphorus or magnesium metabolism were concerned.

Adult↗
PubMed1976

Biomedical results of the Skylab Program.

Skylab, the fourth in a logical sequence of USA manned space flight projects following Mercury, Gemini and Apollo, presented life scientists with their first opportunity for an in-depth study of man's response to the space environment. Extensive medical investigations were undertaken to increase our understanding of man's adaptation to the space environment and his readaptation to gravity upon return to earth. The flight durations of the three Skylab missions were progressively increased from 28 days to 59 days and, finally, 84 days. The results of these investigations of the various body systems clearly demonstrated that man can adapt to zero gravity and perform useful work during long-duration space flight. However, definite changes (some unexpected) in the vestibular, cardiovascular, musculo-skeletal, renal and electrolyte areas were documented. The most significant were: the occurrence of space motion sickness early in the missions; diminished orthostatic tolerance, both in-flight and post-flight; moderate losses of calcium, phosphorus and nitrogen; and decreased tolerance for exercise post-flight. The mechanisms responsible for these physiological responses must be understood and, if necessary, effective countermeasures developed before man can endure unlimited exposure to space flight.

Adaptation, Physiological↗
PubMed1968

The medical legacy of Gemini.

The Mercury and Gemini space flights have provided approximately 2,000 manhours of weightless exposure which can be used in comparing flight results with the predicted effects of manned space flight. In general the environmental hazards and the effects upon man appear to be of less magnitude than originally anticipated. The effects noted on the various body systems are summarized. The principal physiologic changes noted were orthostatism for some 50 hours post-flight, reduced red cell mass, and reduced X-ray density in the os calcis and the small finger. Much was learned about man's ability to work in a pressurized suit in the extravehicular condition. Early biochemical findings have pointed the way to future investigations. All of these findings are of importance in relation to the planning for future long duration missions. Although much remains to be learned, it does appear from an overview of this medical legacy that if man is properly supported and evaluated his limitations will not be a barrier to the exploration of the universe.

Adaptation, Physiological↗