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Biomedical subjects

M Heer

Publications and source records attributed to M Heer.

At least 37 records · Page 2Linked to original sources

Calcium metabolism in microgravity.

Unloading of weight bearing bones as induced by microgravity or immobilization has significant impacts on the calcium and bone metabolism and is the most likely cause for space osteoporosis. During a 4.5 to 6 month stay in space most of the astronauts develop a reduction in bone mineral density in spine, femoral neck, trochanter, and pelvis of 1%-1.6% measured by Dual Energy X-ray Absorption (DEXA). Dependent on the mission length and the individual turnover rates of the astronauts it can even reach individual losses of up to 14% in the femoral neck. Osteoporosis itself is defined as the deterioration of bone tissue leading to enhanced bone fragility and to a consequent increase in fracture risk. Thinking of long-term missions to Mars or interplanetary missions for years, space osteoporosis is one of the major concerns for manned spaceflight. However, decrease in bone density can be initiated differently. It either can be caused by increases in bone formation and bone resorption resulting in a net bone loss, as obtained in fast looser postmenopausal osteoporosis. On the other hand decrease in bone formation and increase in bone resorption also leads to bone losses as obtained in slow looser postmenopausal osteoporosis or in Anorexia Nervosa patients. Biomarkers of bone turnover measured during several missions indicated that the pattern of space osteoporosis is very similar to the pattern of Anorexia Nervosa patients or slow looser postmenopausal osteoporosis. However, beside unloading, other risk factors for space osteoporosis exist such as stress, nutrition, fluid shifts, dehydration and bone perfusion. Especially nutritional factors may contribute considerably to the development of osteoporosis. From earthbound studies it is known that calcium supplementation in women and men can prevent bone loss of 1% bone per year. Based on these results we studied the calcium intake during several European missions and performed an experiment during the German MIR 97 mission where we investigated the effects of high calcium intake (>1000 mg/d) and vitamin D supplementation (650 IU/d) on the calcium and bone metabolism during 21 days in microgravity. In the MIR 97 mission high calcium intake and vitamin D supplementation led to high ionized calcium levels and a marked decrease in calcitriol levels together with decreased bone formation and increased bone resorption markers. Our conclusion from the MIR 97 mission is that an adequate calcium intake and vitamin D supplementation during space missions is mandatory but, in contrast to terrestrial conditions, does not efficiently counteract the development of space osteoporosis.

Bone and Bones↗

Biological dosimetry to determine the UV radiation climate inside the MIR station and its role in vitamin D biosynthesis.

The vitamin D synthesis in the human skin, is absolutely dependent on UVB radiation. Natural UVB from sunlight is normally absent in the closed environment of a space station like MIR. Therefore it was necessary to investigate the UV radiation climate inside the station resulting from different lamps as well as from occasional solar irradiation behind a UV-transparent quartz window. Biofilms, biologically weighting and integrating UV dosimeters successfully applied on Earth (e.g. in Antarctica) and in space (D-2, Biopan I) were used to determine the biological effectiveness of the UV radiation climate at different locations in the space station. Biofilms were also used to determine the personal UV dose of an individual cosmonaut. These UV data were correlated with the concentration of vitamin D in the cosmonaut's blood and the dietary vitamin D intake. The results showed that the UV radiation climate inside the Mir station is not sufficient for an adequate supply of vitamin D, which should therefore be secured either by vitamin D supplemental and/or by the regular exposure to special UV lamps like those in sun-beds. The use of natural solar UV radiation through the quartz window for 'sunbathing' is dangerous and should be avoided even for short exposure periods.

25-Hydroxyvitamin D 2↗

Effects of elevated carbon dioxide environment on calcium metabolism in humans.

BACKGROUND: Chronic respiratory acidosis induced by an elevated carbon dioxide (CO2) environment should provoke hypercalciuria with related total body and subsequent bone calcium losses. We examined this hypothesis in four healthy male volunteers, who were exposed during a 25-d period to an 0.7% CO2 environment within a deep diving isolation chamber. Three months later the same subjects were reexamined during a second campaign being exposed to a 1.2% CO2 atmosphere. METHODS: The subjects received a constant calcium intake (1.4 g.d-1) and vitamin D supplement (1000 IU.d-1) during both campaigns. Calcium balance (oral calcium intake minus urinary and fecal calcium output) was evaluated. Serum calcium concentrations and biomarkers of bone metabolism were measured, in order to evaluate bone turnover. Additionally, the response to an acute oral calcium load was examined as a sensitive measure of changes in calcium metabolism. RESULTS: Both, urinary calcium excretion (from 245 +/- 38 to 199 +/- 31 mg.d-1; mean +/- SE, 0.7% and 1.2%, respectively) and fecal calcium losses (from 1229 +/- 128 to 996 +/- 62 mg.d-1) were significantly reduced in the higher (1.2%) CO2 atmosphere. Although more calcium was retained in the body during the 1.2% than during the 0.7% CO2 campaign, serum calcium concentrations and biomarkers of bone formation were significantly lower in the higher CO2 campaign. Furthermore, bone resorption was slightly increased in the 1.2% experiment. CONCLUSION: Elevated CO2 atmosphere may dose-dependently preserve body calcium without a parallel improvement of bone substance.

Acidosis, Respiratory↗

Increased renal natriuretic peptide (urodilatin) excretion in heart failure patients.

Accumulating evidence suggests that urodilatin, a kidney-derived member of the natriuretic peptide family, contributes as a major mediator of sodium excretion to body fluid regulation in healthy men. In contrast to other members of the natriuretic peptide family, pathophysiological data for the renal natriuretic peptide have still been missing. The present study compares renal synthesis of urodilatin in patients with congestive heart failure (CHF) and healthy volunteers. Because urodilatin excretion, considerably increases with increasing nutritive sodium intake (p<0.004), the CHF patients (15 NYHA I/II, 8 NYHA III/IV) were kept on a 165 mmol/day sodium diet and 6 healthy volunteers on a identical nutritive sodium intake level were selected as proper controls. Although urodilatin excretion significantly increased (p<0.027) with increasing severity of CHF and was therefore significantly higher in mild CHF (40.7 +/- 2.5 fmol/min) and severe CHF (54.7 +/- 6.6 fmol/min) than in healthy controls (3.2 +/- 4.2 fmol/min), both groups of CHF patients retained sodium and had significantly lower sodium excretion rates (NYHA I/II 79.0 +/- 6.9 micromol/min, NYHA III/IV 97.9 +/- 12.7 micromol/min) than the healthy controls (139 +/- 3.4 micromol/min). Our data suggest that renal urodilatin synthesis, may not be involved in the etiology of sodium retention in CHF, but may rather be stimulated to counteract antinatriuresis during CHF.

Adolescent↗

Local ischemia causes carcinoma-like changes of the rectum.

PURPOSE: Bioptic specimens of typical cancerous changes in the rectum usually reveal signs of malignancy. Our goal was to describe the clinical feature, histologic findings, and long-term outcome of patients in whom typical findings of carcinoma of the rectum were discovered by endoscopy, but whose histologic data did not confirm the diagnosis of a malignant disease. METHODS: We conducted a retrospective review of eight patients seen in our hospital with a clinical diagnosis of colorectal cancer. RESULTS: All patients had typical macroscopic findings of colorectal cancer. Endoscopic examination was performed because of chronic gastrointestinal symptoms (tenesmus, diarrhea, hematochezia, recurrent rectal prolapses; n = 5), incidental masses detected by rectal palpation (n = 2), or acute rectal bleeding (n = 1). Instead of confirming malignancy, all histologic specimens showed typical signs of intestinal ischemia. In three patients, tumors were removed by endoscopy; the other patients received symptomatic therapy. All patients were followed for an average period of 46 months. In five patients, symptoms disappeared completely. Three patients continued to suffer from intestinal discomfort. In one case, progression of ischemic damage led to subtotal stenosis, which necessitated proctectomy. CONCLUSIONS: Our results indicate that, despite its rarity, "ischemic pseudocarcinoma" is an important differential diagnosis to cancer of the rectum. Prognosis is generally good. Only patients suffering from chronic symptoms may require surgical treatment.

Adult↗

Body fluid metabolism at actual and simulated microgravity.

Recent observations from space missions indicate that weightlessness does not induce an increase in diuresis and natriuresis in astronauts. Rather, both oral fluid and sodium intake as well as renal fluid and sodium output appear reduced compared with the preflight condition. In addition, influences of reduced energy intake may be more important for total body fluid content inflight than generally assumed. Decreases in plasma volume and observations of upper body edema formation inflight indicate, in addition, an increased extravasation as a result of the headward fluid shift in weightlessness. Current simulations models of microgravity for body fluid metabolism are valid for simulations of the central fluid shift occurring in microgravity. Since weightlessness appears to decrease central venous pressure and does not induce an increased renal fluid and sodium excretion, while simulations models have opposite effects, additional models to simulate adaptation of body fluid metabolism to weightlessness might be necessary.

Adaptation, Physiological↗

Postprandial natriuresis in humans: further evidence that urodilatin, not ANP, modulates sodium excretion.

We examined the effects of a high-salt (100 mmol NaCl) and a low-salt (5 mmol NaCl) meal on the renal excretion of sodium and chloride in 12 healthy male upright subjects. We also measured the urinary excretion of urodilatin [ANP-(95-126)], and the plasma or serum concentrations of atrial natriuretic peptide [ANP-(99-126)], aldosterone, and renin. The high-salt meal produced a postprandial natriuresis (urinary sodium excretion from 59.0 to a peak rate of 204.6 mumol/min in 3rd h after ingestion of meal) and chloride excretion. In parallel, the urinary excretion of urodilatin increased from 35.7 to a peak rate of 105 fmol/min. The effect of high-salt intake on urinary sodium, chloride, and urodilatin excretion was significant (analysis of variance, P < 0.01), and close significant correlations were observed between urodilatin and sodium excretion (mean R = 0.702) as well as between urodilatin and chloride excretion (mean R = 0.776). In contrast, plasma ANP, which was acutely elevated 15 min after high-salt intake, was already back to low-salt values 1 h later. It did not parallel the postprandial natriuretic profile, and no positive correlation between plasma ANP and sodium excretion was observed. These results provide further evidence that urodilatin, not ANP, is the member of this peptide family primarily involved in the regulation of the excretion of sodium and chloride.

Aldosterone↗

Renal and endocrine responses in humans to isotonic saline infusion during microgravity.

It was the purpose of this study to investigate how the endocrine and renal mechanisms of fluid volume control in humans (n = 4) adapt to microgravity by applying an intravenous isotonic saline infusion. The acute ground-based supine (Sup) and seated (Seat) positions were chosen as references. During microgravity, renal sodium excretion (UNaV) was doubled during the second and third hours after infusion compared with during Seat (P < 0.05) but blunted during the first hour after infusion compared with during Sup, leading to a reduction in cumulative UNaV (59 +/- 15 vs. 108 +/- 12 mmol/5 h; P < 0.05). Plasma norepinephrine (NE) attained the highest value 3 h after infusion during microgravity (31 +/- 5 x 10(-2) ng/ml vs. 19 +/- 1 and 13 +/- 3 x 10(-2) ng/ml for Seat and Sup, respectively; P < 0.05). Inflight levels of plasma renin and aldosterone were very similar to levels during Seat. In conclusion, 1) the microgravity-adapted renal responses to infusion reflected a condition in between that of ground-based Seat and Sup, respectively, and 2) the plasma levels of NE, renin, and aldosterone were elevated inflight and not related to the changes in UNaV and urinary flow rate. These observations are in contrast to results of ground-based simulation experiments and might partly have been caused by a prior inflight reduction in extracellular fluid volume. The high levels of NE during microgravity warrant further investigation.

Adult↗

Water immersion: analysis of diurnal rhythms of water and electrolyte excretion.

The biorhythmological structure of water-electrolyte metabolism was studied in humans during 7-day "dry" immersion. Results were processed with a set of mathematical methods in order to identify a parameter which would allow to obtain scientifically valid, reliable data without violation of any ethic constraints inherent to investigations with healthy test-subjects. Even this period of immersion gravely impacted functioning of kidney as an executive organ in the system of water-electrolyte homeostasis. Data of this study point to applicability of Cosinor analysis for quantitative assessment of fluctuation patterns in parameters of close to harmonical circadian rhythms, and variation analysis and normalized mean for rhythms of arbitrary forms.

Adult↗

Antinatriuretic kidney response to weightlessness.

We have tested the effects of weightlessness on renal function in one subject who flew the recent week-long Russian-German MIR'92 space mission. Urine flow, renal sodium excretion, and the excretion of urodilatin were measured during the first and last days of the flight. Our results demonstrated, in contrast to expectations, that urine flow and sodium excretion during weightlessness were actually lower than the values obtained during preflight measurements. These results therefore are inconsistent with the commonly held hypothesis that weightlessness induces a diuresis and natriuresis in human subjects. It would seem that further studies are necessary to resolve this issue and to determine whether currently used ground-based models of weightlessness correctly predict physiological adaptations that occur during space flight.

Atrial Natriuretic Factor↗

Malignant biliary obstruction: clinical and histopathologic correlation after treatment with self-expanding metal prostheses.

PURPOSE: To analyze clinical and autopsy findings in patients with malignant biliary obstruction treated with biliary endoprostheses. MATERIALS AND METHODS: Stents were inserted endoscopically in nine patients and transhepatically in 50. In 24 patients, autopsy was performed; in 22 cases, histologic analysis of the area in which the stent was placed was available. RESULTS: The technical success rate was 100%, and the clinical success rate was 92%. Complications occurred in 16 patients, with one procedure-related death. The rate of severe complications was 19%, primarily due to acute cholangitis (n = 9). Mean survival time was 175 days. Stent obstruction was found in 12 patients and occurred on average 196 days after stent placement. Secondary treatment was successful in all 12 patients. Only one of 24 autopsy specimens demonstrated macroscopic nonobstructive tumor ingrowth. Histologic analysis showed that the main reaction to the stent was connective tissue formation, which never occurred before 3 months. Invasion by tumor cells was noted in only five cases. CONCLUSION: Tumor ingrowth is not a major cause of stent obstruction.

Adult↗

[Ischemic ulcer of stomach and duodenum: an unusual cause of a common disease].

Ischemia is a rare cause of gastric and duodenal ulcers. For the present study clinical and anatomo-pathologic data from cases published so far and from twelve own patients with ischemic ulcers have been investigated. Histopathology leads to the diagnosis of an ischemic cause with great accuracy. Our results show that ischemic ulcers occur often at gastric sites unusual for a peptic ulcer, and in some cases they look macroscopically different from peptic ulcers. The most common symptom was severe gastrointestinal bleeding. Pain, typical for peptic ulcers, has only rarely been noted by patients. Lethal courses were usually due to gastrointestinal bleeding resistant to therapy. Resection of the involved gastric or duodenal segment or surgical or angiologic reconstruction of the vessels respectively are promising therapeutic means. Without therapeutic intervention very different courses have been observed, ranging from spontaneous healing to fatal gastrointestinal bleeding. The benefit of inhibitors of acid secretion is so far unclear.

Aged↗

Reduced natriuresis during weightlessness.

The kidney response to weightlessness was measured in one volunteer during a 1-week space mission. Shortly after entering microgravity and later during the mission, consecutive urine sampling periods were monitored, covering in total about 50% of the inflight time. Preflight references were a sequence of ground-based experiments, which evaluated body fluid metabolism with different degrees of standardization. Additional variables, such as circadian rhythms and cortisol-associated stress, were also monitored. In contrast to current hypotheses, the volunteer showed a pronounced reduction in natriuresis and diuresis during the entire space flight, despite a considerable weight loss. For the first time, the urinary excretion of the renal natriuretic peptide urodilatin was also measured. Both, during the preflight experiments and during weightlessness, close correlations between urodilatin excretion and sodium excretion were observed. However, the correlation between natriuresis and urodilatin excretion was considerably altered during weightlessness. We conclude that the loss of body weight during space flight is not related to an increased renal fluid loss and that urodilatin might counteract the decrease in renal excretion observed in weightlessness.

Atrial Natriuretic Factor↗

Long-term elevations of dietary sodium produce parallel increases in the renal excretion of urodilatin and sodium.

The effects of dietary sodium intake on the renal excretion of urodilatin and of sodium were examined in six healthy male subjects. The 24-day study period was divided into three phases of 8 days each. Subjects ingested 2.8 mequiv sodium (kg body weight)-1 day-1 during the first phase, 5.6 mequiv (kg body weight)-1 day-1 during the second phase, and 8.4 mequiv (kg body weight)-1 day-1 during the third phase. The excretion of both sodium (P < 0.002) and urodilatin (P < 0.006) increased in response to the increasing dietary sodium, while urine flow did not change. Urinary urodilatin excretion correlated closely with renal sodium excretion (P < 0.001). Serum aldosterone levels (P < 0.01) as well as serum renin levels (P < 0.05) significantly decreased with increasing sodium intake. Plasma [Arg]vasopressin levels increased significantly (P < 0.05). Plasma atrial natriuretic factor and cGMP levels as well as urinary cGMP excretion rates were unaltered by the changes in sodium intake. We conclude from these results that the renal natriuretic peptide, urodilatin, but not the main cardiac member of the natriuretic peptide family may be involved in the regulation of day-to-day sodium balance.

Adult↗

Biliary obstruction: treatment with self-expanding metal prostheses.

The authors percutaneously and endoscopically inserted 58 Wallstent endoprostheses in 42 consecutive patients with benign and malignant obstructive biliary stenoses. The three patients with benign obstructive jaundice were followed up for 48 months. Two of the stents occluded due to sludge formation, prompting percutaneous reentry. The 39 patients with malignant disease were followed up for 18 months. Twenty-six of these patients died 3 days to 1.5 years (mean, 133 days) after the procedure. Thirteen are alive after 2-12 months (mean, 242 days). Recurrent jaundice occurred in 11 patients (28%): in four patients due to tumor growth over the proximal end of the stent, in one patient due to excessive gallbladder hydrops, and in six patients due to liver failure. Although autopsy investigations revealed the possibility of tumor growth onto the inner surface of the stent through the stainless steel mesh of the endoprosthesis, stent occlusion by tumor ingrowth into the lumen was not encountered.

Adult↗

Effects of an acute saline infusion on fluid and electrolyte metabolism in humans.

Several hormonal systems participating in body fluid and electrolyte homeostasis were investigated in six healthy volunteers in a supine body position during a period of 9 days and nights. Under strictly controlled conditions, striking circadian rhythms were observed for plasma levels of vasopressin, renin, aldosterone, guanosine 3',5'-cyclic monophosphate, cortisol, and epinephrine. Nocturnal decreases and diurnal increases in urine flow rate and urinary excretion of electrolytes were observed and closely paralleled the urinary excretion of urodilatin. During 48 h after an acute isotonic saline infusion (2 liters within 25 min) and after a 48-h control experiment the urinary excretion of H2O and electrolytes, and simultaneously the alterations in endocrine systems participating in body fluid homeostasis, were determined. Urine flow and urinary electrolyte excretion rates were significantly increased during 2 days after the saline infusion. The largest increase in urinary fluid and electrolyte excretion was observed between 3 and 22 h postinfusion. These long-term changes were paralleled by altered H2O and Na balances and also by elevated body weights that returned to baseline values with an approximate half-life of 7 h. These data suggest that vasopressin, atrial natriuretic peptide, and catecholamines are unlikely to be of major importance for the renal response to this hypervolemic stimulus. The renin-aldosterone system was suppressed during 2 days postinfusion. This suppression correlated with the effects of saline load on Na excretion. However, the closest relation with Na excretion was observed for the kidney-derived member of the atrial natriuretic peptide family, urodilatin, which was considerably increased during the long-term period up to 22 h postinfusion. Thus these data show that the human body in supine position requires approximately 2 days to regulate the amount of Na and H2O provided by an acute saline infusion. The data also suggest that urodilatin and the renin-aldosterone system might participate in the long-term renal response to an acute saline infusion and also in the mediation of circadian urinary excretion rhythms.

Adult↗

Diuresis and natriuresis following isotonic saline infusion in healthy young volunteers before, during, and after HDT.

In the present study the response to acute saline loading was investigated. During a 24-day study period six male subjects followed a standardized diet including a daily intake of 40 ml water and 125 mg NaCl per kg body weight. Before, during, and after a ten-day period of 6 degrees head down tilt (HDT) each volunteer received an intravenous 0.9% saline infusion of 22 ml/kg body weight over 20 minutes. HDT produced significant losses in body weight and in blood volume, but the responses to saline loading were similar during all phases of the study. Plasma levels of atrial natriuretic peptide (ANP) did not increase, while plasma levels of cyclic GMP increased by about 40% 90 minutes after each infusion. Urine flow nearly doubled during second hour post-infusion. Sodium excretion showed a 3-fold increase and remained elevated during the third hour, while potassium excretion was significantly reduced. Urinary excretion of cyclic GMP reached a peak during the second hour post-infusion. At the end of these short-term periods the cumulative water- and sodium-balance data disclosed that only about 20% of the infused water and less than 15% of the infused sodium was excreted during each experiment. In addition to the short-term renal response, urine flow and sodium excretion remained significantly elevated for more than 48 hours after each saline load. The long-term renal response was paralleled by an increased excretion of urinary cyclic GMP. HDT produced significant changes in body fluid distribution, but only minor changes in the regulatory responses to an acute saline load. We conclude from these data that the excretion of an acute isotonic saline load requires several days and that the renal response appears to be independent of the secretion of ANP from the heart.

Adult↗