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Biomedical subjects

M Heer

Publications and source records attributed to M Heer.

At least 19 recordsLinked to original sources
PubMed2007

Whole-body vibration can reduce calciuria induced by high protein intakes and may counteract bone resorption: A preliminary study.

Excess protein intake can adversely affect the bone via an increase in calcium excretion, while suitable mechanical loading promotes osteogenesis. We therefore investigated whether vibration exposure could alleviate the bone mineral losses associated with a metabolic acidosis. Ten healthy individuals aged 22 - 29 years (median = 25) underwent three 5-day study periods while monitoring their dietary intake. The study consisted of recording the participants' usual dietary intake for 5 consecutive days. Participants were then randomly divided into two groups, one of which received a protein supplement (2 g x kg(-1) body mass x day(-1); n = 5) and the other whole-body low-magnitude (3.5 g), low-frequency (30 Hz) mechanical vibration (WBV) delivered through a specially designed vibrating plate for 10 min each day (n = 5). Finally, for the third treatment period, all participants consumed the protein supplement added to their normal diet and were exposed to WBV exercise for 10 min per day. Daily urine samples were collected throughout the experimental periods to determine the excretion of calcium, phosphate, titratable acid, urea, and C-telopeptide. As expected, when the participants underwent the high protein intake, there was an increase in urinary excretion rates of calcium (P < 0.001), phosphate (P < 0.003), urea (P < 0.001), titratable acid (P < 0.001), and C-telopeptide (P < 0.05) compared with baseline values. However, high protein intake coupled with vibration stimulation resulted in a significant reduction in urinary calcium (P = 0.006), phosphate excretion (P = 0.021), and C-telopeptide (P < 0.05) compared with protein intake alone, but did not affect titratable acid and urea output. The participants showed no effect of WBV exercise alone on urinary excretion of calcium, phosphate, urea, titratable acid, or C-telopeptide. The results indicate that vibration stimulation can moderate the increase in bone resorption and reduction in bone formation caused by a metabolic acidosis.

Acidosis↗
PubMed2006

Tyramine in the assessment of regional adrenergic function.

Regional adrenergic function is difficult to assess in humans. Tyramine given through a microdialysis probe may be a useful tool in this regard. However, tyramine data is hard to interpret given the drug's complex mode of action. We characterized the response to tyramine, isoproterenol, and dopamine in adipose tissue with microdialysis probes in normal subjects. We measured glycerol concentrations to follow changes in lipolysis and monitored tissue perfusion with ethanol dilution. During perfusion with tyramine, dialysate glycerol concentration increased dose-dependently from 83+/-8 microM at baseline to 181+/-18 microM at 3.5 mM tyramine (p<0.001) followed by a fall down to 121+/-9 microM at 35 mM tyramine (p<0.001). Propranolol almost completely blocked this response. A similar lipolytic response was not observed in isolated human adipocytes. Dopamine <35 microM did not replicate the tyramine-induced lipolysis; however, dopamine >35 microM potently inhibited lipolysis. We conclude that tyramine-induced lipolysis is explained by a pre-synaptic mechanism. Tyramine applied through a microdialysis probe in concentrations up to 3.5 mM can be used to assess pre- and post-synaptic mechanisms regulating lipid mobilization.

Adipocytes↗
PubMed2006

Comparison of generic cyclosporine microemulsion versus neoral in de novo renal transplant recipients managed by 2-hour postdose monitoring.

INTRODUCTION: The bioequivalence of generic formulations is established by measuring pharmacokinetic parameters in healthy volunteers. Cyclosporine (CsA) absorption and exposure is known to differ between healthy volunteers and transplant recipients. Therefore bioequivalence testing may be inadequate to ensure therapeutic equivalence. We sought to compare the efficacy of generic cyclosporine (ArpimuneME, RPG Life Sciences) versus Sandimmune Neoral in de novo renal transplant recipients. METHODS: A prospective single-center, open-label study enrolled 20 de novo renal transplant patients (group 1: mean age 30.55 +/- 9.81 years, M:F 19:1, mean donor age 43.4 +/- 10.8). All patients received ArpimuneME along with azathioprine and prednisolone. The results were compared with 17 matched controls (group 2: mean age 28.1 +/- 9.5 years, M:F 13:4, mean donor age 47.8 +/- 6.8) who received Neoral and were transplanted during the same period. C(2) levels were monitored by the cloned enzyme donor immunoassay (CEDIA). RESULTS: Patient and graft survivals were 100% and 100% and 100% and 92.8% in groups 1 and 2, respectively (P = NS). Six patients (30%) experienced rejection in group 1 as compared eight patients (47.1%) in group 2. Mean CsA levels (ng/mL) during the first month were 1419.1 +/- 213.6 and 1460.5 +/- 290.7 and at 3 months, 1296.3 +/- 227.8 and 1342.4 +/- 303.4 in the two groups, respectively (P = NS). The mean serum creatinine levels (mg%) in group 1 and group 2 were 1.6 +/- 0.8 and 2.0 +/- 1.4 at discharge and 1.5 +/- 0.4 and 1.5 +/- 0.8 at 6 months, respectively (P = NS). CONCLUSION: Use of a generic microemulsion form of CsA provided safe and effective immunosuppression compared with Sandimmune Neoral when drug monitoring was performed by C(2) levels.

Adult↗
PubMed2006

Oxidative status in stable renal transplantation.

Increased oxidative stress and hyperhomocysteinemia are frequently observed in patients with end-stage renal disease. The effects of kidney transplantation on oxidative state are incompletely understood. With an aim to evaluate the prevalence and severity of oxidative stress in living donor renal transplant recipients, we conducted a cross-sectional study. Thirty-five renal transplant recipients (mean age 34 years; body mass index 21.93 +/- 1.92) with normal renal function (mean serum creatinine 1.41 +/- 0.33 mg%) were enrolled in the study. All patients were on cyclosporine-based immunosuppression. We assessed serum nitric oxide (NO) levels, plasma total homocysteine levels (tHCy), and malonaldehyde (MDA) levels. We evaluated the antioxidant power ferric reducing ability of plasma (FRAP) assay. The mean duration to the first sampling was 9.23 months after transplantation. Fourteen age- and sex-matched normotensive people were used as controls. The mean tHCy was significantly higher among patients (15.29 +/- 0.66 mmol/L compared with controls (9.58 +/- 2.90 mmol/L; P < .05). The MDA levels in patients (6.405 +/- 2.05 nmol/mL) were comparable to controls (6.093 +/- 1.93 nmol/mL; P = .099). The status of antioxidative power as measured by FRAP showed a trend to higher antioxidative status (697.57 +/- 103.07 mmol/L) in patients compared with controls (518 +/- 120.99 mmol/L; P = NS). The mean NO levels in patients (545.01 +/- 281.49 mmol/mL) were significantly higher than controls (183.49 +/- 64.53 nmol/mL; P < .05). Stable renal transplant recipients display a pattern of increased oxidant stress that may be counterbalanced by an enhanced antioxidant mechanisms.

Adult↗
PubMed2006

Comparison of enteric-coated mycophenolate sodium with mycophenolate mofetil in living renal allograft transplantation.

OBJECTIVE: Enteric-coated mycophenolate sodium (MPS) has been developed to decrease the GI side effects of mycophenolate mofetil (MMF). We did a retrospective analysis of 112 patients to compare the safety and efficacy of enteric coated MPS vs MMF in living renal transplantation. METHODS: Patients were divided into two groups. Group A who received MPS [Novartis, Basel, Switzerland] [1.08-1.44 g/d] included 53 patients of mean age 33.5 +/- 11.9 yrs, and M:F gender ratio 37:15 with a mean donor age of 43.2 +/- 9.9 years. Group B who received MMF [1.5-2.0 g/d] included 59 subjects of mean age 33.2 +/- 9.9 yrs and M:F gender ratio 57:6, with a mean donor age of 41.4 +/- 10.9 years. All patients received cyclosporine and prednisolone in addition to mycophenolate. Mean follow-up in the two groups was 11.6 +/- 7.0 and 12.6 +/- 8.5 months, respectively. RESULTS: There were 11 (20.7%) rejection episodes in Group A and 12 (20.3%) rejection episodes in Group B (P = NS). Incidence of CMV disease was 9.61% and 10.1%, and of other infections, 88.7% and 74.7% in Groups A and Group B, respectively [P = NS]. The incidence of GI (18.9% & 20.3%) and hematologic toxicities (9.4% & 5.1%) were similar in the groups. Patient and graft survivals in Group A were 91.9% & 86.6%, and in Group B was 91.3% & 91.3%, respectively [P = NS]. CONCLUSION: Mycophenolate sodium is an alternative immunosuppressant to mycophenolate mofetil in kidney transplant recipients with a similar efficacy and safety profile.

Adult↗
PubMed2005

Regulation of body fluid and salt homeostasis--from observations in space to new concepts on Earth.

The present manuscript summarizes recent discoveries that were made by studying salt and fluid homeostasis in weightlessness. These data indicate that 1. atrial natriuretic peptide appears not to play an important role in natriuresis in physiology, 2. the distribution of body fluids appears to be tightly coupled with hunger and thirst regulation, 3. intrathoracic pressure may be an important co-regulator of body fluid homeostasis, 4. a so far unknown low-affinity, high capacity osmotically inactive sodium storage mechanism appears to be present in humans that is acting through sodium/hydrogen exchange on glycosaminoglycans and might explain the pathophysiology, e.g., of salt sensitive hypertension. The surprising and unexpected data underline that weightlessness is an excellent tool to investigate the physiology of our human body: If we knew it, we should be able to predict changes that occur when gravity is absent. But, as data from space demonstrate, we do not.

Body Fluids↗
PubMed2005

Successful live related renal transplant in a case of tuberous sclerosis.

Tuberous sclerosis (TS) is an autosomal dominant multisystemic disease involving primarily the skin, the brain and the kidneys. Inspite of the kidney being involved in 40-80% of patients with this disease, the incidence of end stage renal disease is only about 1%. There are only 34 reported cases of successful renal transplantation in tuberous sclerosis patients with end stage renal disease. We report a case of successful renal transplantation in a patient of tuberous sclerosis with bilateral polycystic kidneys presenting with renal failure who also underwent bilateral native nephrectomies on follow up.

Adult↗
PubMed2004

Therapeutic implication of quantitative pp65 antigen assay in living renal transplant in a high seroendemic population.

Various methods have been used to diagnose cytomegalovirus (CMV) infection/disease; however, pp65 antigenemia assay has emerged as a good marker for CMV disease in a high seroendemic population. We studied the role of quantitative pp65 antigen assay in live related renal transplant recipients in a high seroendemic population. Between November 1998 and May 2003, a total of 350 blood samples from 250 symptomatic patients were tested by quantitative pp65 antigen assay; 14% of the patients tested positive. There were 5 (14%) low-positive and 30 (86%) high-positive patients. All high-positive patients had CMV disease. The response to antiviral therapy monitored by the assay was dramatic, and one low-positive patient responded to reduction in immunosuppression. In conclusion, pp65 antigen assay is a good test for diagnosing CMV disease and monitoring response to antiviral therapy in a high seroendemic population.

Cytomegalovirus Infections↗
PubMed2004

Intestinal cryptosporidiasis in living related renal transplant recipients.

Cryptosporidium infestations are common in immunocompromised AIDS patients. However, the literature in renal transplant recipients is scarce. We conducted a study to know the prevalence, disease manifestations, and management of cryptosporidial infestations in live related renal transplant recipients. Cryptosporidial infestations were observed in 20% of patients, including 16.6% who had symptomatic diarrhea. We conclude that the prevalence is high in the transplant population, but only a few patients are symptomatic. Clinicians should routinely request special stains to demonstrate cryptosporidium in stool specimens.

Adult↗
PubMed2004

Role of postdose cyclosporine monitoring in living renal transplant recipients.

Achieving optimal cyclosporine (Neoral) absorption is critical for successful graft outcome. Recently there have been studies on postdose monitoring of cyclosporine. Two- and 3-hour postdose cyclosporine levels measured by radioimmunoassay were correlated with occurrence of rejection and cyclosporine nephrotoxicity in 30 patients; C(2) and C(3) levels were significantly lower than the desired therapeutic levels in patients with acute rejection. Based on our study and those of others we suggest C(3) levels should be adopted in clinical practice.

Acute Disease↗
PubMed2004

High serum leptin levels subsequent to weight gain predict renewed weight loss in patients with anorexia nervosa.

It has repeatedly been shown that high serum leptin levels at target weight ensue from therapeutically induced weight gain in patients with anorexia nervosa (AN). It was hypothesized that elevated leptin levels may be an important factor underlying the difficulties of maintaining the target-weight in AN patients after re-feeding. The aim of this study was to examine if serum leptin levels at discharge from inpatient treatment predict renewed weight loss within 2 months after discharge and upon a 1 yr follow-up. Univariate variance analysis (ANOVA) revealed that 60% (cor. R2=0.60, P=0.002) of the variance in the BMI standard deviation score (BMI-SDS) 2 months after discharge was explained by the model consisting of the independent variables lg10 leptin levels at discharge (P=0.019) and at admission (P=0.069) and BMI-SDS at admission (P=0.002) and delta BMI between admission and discharge (P=0.047). Similarly, 60% (cor. R2=0.60, P=0.005) of the variance in BMI-SDS 1 yr after discharge was explained by lg10 leptin levels at discharge (P=0.046) and at admission (P=0.052) and BMI-SDS at admission (P=0.008) and 2 months after discharge (P=0.007) and delta BMI between admission and discharge (P=0.933). Patients with a poor outcome after 1 yr (n=9, ANCOVA, group: descriptive P=0.041), but not recovered patients (n=9, P=0.649), had lg10 leptin levels at discharge higher than those of controls when adjusted for BMI and % body fat at discharge. In conclusion, high serum leptin levels at discharge from inpatient treatment may indicate a risk for renewed weight loss and an unfavorable 1 yr outcome in AN.

Adolescent↗
PubMed2003

Reproductive function during weight gain in anorexia nervosa. Leptin represents a metabolic gate to gonadotropin secretion.

The adipocyte hormone leptin plays an important part in the reproductive function and in energy homeostasis. Only single studies have addressed the relationship between leptin and the hypothalamus-pituitary-gonadal axis (HPG) in anorexia nervosa (AN). In the present study 18 female adolescents with AN were investigated during weight gain. Leptin, LH, FSH, fT3, BMI and body composition were measured in the 1(st), 3(rd), 7(th) and 11(th) week of inpatient treatment. 18 eumenorrheic age- and gender-matched controls were examined once during the early follicular phase of their menstrual cycle. Our results demonstrate a critical leptin level of 1.2 ng/ml for an increase of FSH and confirmed a leptin threshold level of 1.85 ng/ml for LH. It may be concluded that leptin represents a metabolic gate to gonadotropin secretion. Once this is exceeded other biological mechanisms seem to be important for the complete recovery of the reproductive function and the resumption of menses.

Adolescent↗
PubMed2002

Dietary treatment enhances bone formation in malnourished patients.

Patients with anorexia nervosa often suffer from osteopenia or osteoporosis. We therefore examined if a dietary treatment including an individually determined high caloric intake, Calcium and Vitamin D supplementation would improve bone metabolism in these patients. We studied 19 female patients aged 14.1 years, BMI 14.2 kg/m 2 and a healthy control group aged 15.1 years, BMI 20.8 kg/m 2 . The subjects were studied at baseline and at several fixed points of time during one year of treatment for bone formation and resorption markers. During the treatment there were no changes in the resorption marker CTX. After 15 weeks we found a significant increase of the bone formation marker PICP. Thus dietary treatment seems to be a promising tool to counteract bone loss in these patients.

Journal Article↗
PubMed2001

Validity of microgravity simulation models on earth.

Many studies have used water immersion and head-down bed rest as experimental models to simulate responses to microgravity. However, some data collected during space missions are at variance or in contrast with observations collected from experimental models. These discrepancies could reflect incomplete knowledge of the characteristics inherent to each model. During water immersion, the hydrostatic pressure lowers the peripheral vascular capacity and causes increased thoracic blood volume and high vascular perfusion. In turn, these changes lead to high urinary flow, low vasomotor tone, and a high rate of water exchange between interstitium and plasma. In contrast, the increase in thoracic blood volume during a space mission is combined with stimulated orthosympathetic tone and lowered urine flow. During bed rest, body tissues are compressed by pressure from gravity, whereas microgravity causes a negative pressure around the body. The differences in renal function between space and experimental models appear to be explained by the physical forces affecting tissues and hemodynamics as well as by the changes secondary to these forces. These differences may help in selecting experimental models to study possible effects of microgravity.

Baroreflex↗
PubMed2001

Renal hemodynamics in space.

Renal excretory function and hemodynamics are determined by the effective circulating plasma volume as well as by the interplay of systemic and local vasoconstrictors and vasodilators. Microgravity results in a headward shift of body fluid. Because the control conditions of astronauts were poorly defined in many studies, controversial results have been obtained regarding diuresis and natriuresis as well as renal hemodynamic changes in response to increased central blood volume, especially during the initial phase of space flight. Renal excretory function and renal hemodynamics in microgravity are affected in a complex fashion, because during the initial phase of space flight, variable mechanisms become operative to modulate the effects of increased central blood volume. They include interactions between vasodilators (dopamine, atrial natriuretic peptide, and prostaglandins) and vasoconstrictors (sympathetic nervous system and the renin-angiotensin system). The available data suggest a moderate rise in glomerular filtration rate during the first 2 days after launch without a significant increase in effective renal plasma flow. In contrast, too few data regarding the effects of space flight on renal function during the first 12 hours after launch are available and are, in addition, partly contradictory. Thus, detailed and well-controlled studies are required to shed more light on the role of the various factors besides microgravity that determine systemic and renal hemodynamics and renal excretory function during the different stages of space flight.

Diuresis↗
PubMed2001

Water and sodium balance in space.

We have previously shown that fluid balances and body fluid regulation in microgravity (microG) differ from those on Earth (Drummer et al, Eur J Physiol 441:R66-R72, 2000). Arriving in microG leads to a redistribution of body fluid-composed of a shift of fluid to the upper part of the body and an exaggerated extravasation very early in-flight. The mechanisms for the increased vascular permeability are not known. Evaporation, oral hydration, and urinary fluid excretion, the major components of water balance, are generally diminished during space flight compared with conditions on Earth. Nevertheless, cumulative water balance and total body water content are stable during flight if hydration, nutritional energy supply, and protection of muscle mass are at an acceptable level. Recent water balance data disclose that the phenomenon of an absolute water loss during space flight, which has often been reported in the past, is not a consequence of the variable microG. The handling of sodium, however, is considerably affected by microG. Sodium-retaining endocrine systems, such as renin-aldosterone and catecholamines, are much more activated during microG than on Earth. Despite a comparable oral sodium supply, urinary sodium excretion is diminished and a considerable amount of sodium is retained-without accumulating in the intravascular space. An enormous storage capacity for sodium in the extravascular space and a mechanism that allows the dissociation between water and sodium handling likely contribute to the fluid balance adaptation in weightlessness.

Aldosterone↗
PubMed2001

Body mass changes, energy, and protein metabolism in space.

Most astronauts lose body mass during their stay in microgravity. The early hypothesis, which attributed this phenomenon to an increase in diuresis and natriuresis after entering microgravity, is now untenable. Although a fluid shift from the lower to the upper body occurs, it does not lead to a marked fluid loss in the first 2 days of space flight. The continuous day-by-day body mass measurement during the Euromir 94 mission showed that there was a gradual reduction over the entire mission instead of a rapid loss of 2 to 3 kg at the beginning of a mission. The daily energy intake during this mission and the negative energy balances found in the Skylab and LMS-Mission show that lowered body mass is very likely caused by an insufficient energy consumption and its accompanying effects. These include the metabolization of endogenous energy stores, ie, glycogen, protein, and fat. Mobilization of glycogen and protein buffers will also cause the water that is bound to both to be lost. Thus, a gradual decrease in body mass and a concomitant reduction in total body fluid occurs without a significant increase in urine flow or natriuresis. In conclusion, the body mass loss in microgravity is likely a result of undernutrition instead of diuresis and natriuresis caused by the fluid shift.

Animals↗