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Biomedical subjects

Hendrik Lehnert

Publications and source records attributed to Hendrik Lehnert.

At least 19 recordsLinked to original sources
PubMed2006

Accuracy of anthropometric indicators of obesity to predict cardiovascular risk.

CONTEXT: Obesity is associated with various cardiovascular risk factors. The body mass index (BMI) is the standard measure of overweight and obesity. However, more recently, waist to hip ratio (WHR) or waist circumference (WC) as more sensitive measures for visceral obesity have been proposed to be more indicative of cardiovascular risk. OBJECTIVE: This study was performed to test the predictive value of anthropometric parameters for the presence of several cardiovascular risk conditions. DESIGN: The DETECT (Diabetes Cardiovascular Risk-Evaluation: Targets and Essential Data for Commitment of Treatment) study is a cross-sectional, clinical-epidemiological study. PARTICIPANTS: We studied 5377 unselected subjects (2016 men, 3361 women) without arteriosclerotic disease, aged 20-79 yr, from the DETECT laboratory sample. SETTING: This study was conducted by primary care physicians. INTERVENTION: We measured anthropometric parameters and assessed cardiovascular risk by clinical examination, patient history, and a standardized laboratory program. MAIN OUTCOME MEASURES: We assessed the associations of BMI, WC, hip circumference, WHR, and waist to height ratio (WHtR) to cardiovascular risk by calculating the area under the receiver-operating characteristic curve and adjusted odds ratios for metabolic syndrome, dyslipidemia, and type 2 diabetes. RESULTS: The area under the receiver-operating characteristic curve for WHtR was significantly higher than for all other anthropometric parameters with respect to all risk conditions in women and to dyslipidemia and type 2 diabetes in men. The odds ratios for the presence of risk conditions with 1 sd increase of each anthropometric parameter were highest for WHtR or WC. CONCLUSIONS: There are some indications that WHtR or WC may predict prevalent cardiovascular risk better than BMI or WHR, even though the differences are small.

Adolescent↗
PubMed2006

[Prevalence, drug treatment and metabolic control of diabetes mellitus in primary care].

BACKGROUND AND PURPOSE: The primary care sector is of key importance for the management of patients with diabetes mellitus. The authors investigated (a) the prevalence of diabetes mellitus type 1 and type 2, (b) the type and frequency of non-drug and drug treatment and its association with the presence of diabetic complications, and (c) the quality of metabolic control by HbA1c. METHODS: Using a nationwide probability sample of 3,188 general practices (response rate [RR] 50.6%), a total of 55,518 (RR 93.5%) patients were assessed in a prospective cross-sectional study by their physicians in September 2003 in a standardized manner using questionnaires, physician interview, and laboratory assessments. In addition to diabetes mellitus, 28 diseases were explicitly screened for, among them typical macrovascular (coronary heart disease, cerebrovascular disease, peripheral arterial disease) and microvascular disease (neuropathy, nephropathy, retinopathy, diabetic foot) complications. RESULTS: The prevalence of diabetes mellitus was 0.5% (type 1) and 14.7% (type 2), respectively. 49.5% (type 1) and 50.2% (type 2) of patients had micro- or macrovascular complications. 6.8% did not receive any treatment, 13.5% received non-drug treatment, and 75.3% received oral antidiabetic drugs and/or insulin (26.6% a combination of two or more). Compared to diabetics without any complications, treatment intensity was significantly higher in patients with microvascular complications (odds ratio [OR] 3.02), but not in those with macrovascular complications only (OR 0.98). An HbA1c value>or=7.0% was recorded in 39.6% of patients. CONCLUSION: Compared to previous studies in this setting, the proportion of diabetics with drug treatment has increased. More patients receive antidiabetic drug combinations. Quality of blood sugar control appears to have improved as well.

Adolescent↗
PubMed2006

Brain uptake of intranasally applied radioiodinated leptin in Wistar rats.

Leptin is mainly synthesized and secreted by fat cells in proportion to adipose tissue mass. Under physiological conditions, this hormone reduces food intake and increases thermogenesis through interactions with neurons in the central nervous system. However, transport of leptin into the central nervous system via the blood-brain barrier is saturable, and in obesity the feedback signal to the brain is markedly insufficient. In recent experiments we have shown, that intranasal (i.n.) delivery of leptin reduces food intake in rats. The aim of the present study was to explore the distribution of i.n. delivered leptin within brain, blood, and peripheral tissues. Application of [(125)I]leptin (0.03, 0.1, and 0.2 mg/kg) into male Wistar rats' nares (n = 8 per group) leads to supraphysiological brain leptin concentrations 30 min after application, with contents in the hypothalamus (7.3 +/- 2.6, 5.9 +/- 1.6, and 13.8 +/- 5.7 ng/g; P = 0.023; F = 6.157) being significantly higher than the brain average (1.2 +/- 0.2, 3.9 +/- 1.0, and 6.0 +/- 1.9 ng/g). In contrast, contents in the occipital/entorhinal cortex were lower than the brain average, indicating a minor participation of the transport via cerebrospinal fluid, which would have favored cerebrospinal fluid-exposed surfaces. In experiments employing the application of unlabeled leptin administered iv, we were able to show that excess blood leptin does not diminish brain uptake of i.n. leptin (as indicated by [(125)I]leptin), supporting a direct transport from nose to brain by circumvention of the blood-brain barrier. This study thus clearly demonstrates a rapid and highly effective transport of leptin from nose to brain.

Adipose Tissue↗
PubMed2006

Hepatocellular neoplasms after intrahepatic transplantation of ovarian fragments into ovariectomized rats.

Intrahepatic transplantation of ovarian fragments in ovariectomized rats results in morphological abnormalities. The liver acini draining blood from ovarian grafts show alterations resembling chemically induced amphophilic hepatocellular preneoplasias. We investigated the long-term development of these estrogen-induced foci of altered hepatocytes (FAH). We divided 451 Lewis rats into one main group (MG) and 11 (7 female, 4 male) control groups and observed them for up to 30 months. MG animals were ovariectomized and received ovarian transplants into the right liver part. Different combinations of castration, transplantation of ovarian or testicular fragments, and administration of antiestrogenic toremifene were used in controls. In the MG, transplants showed signs of gonadotropic stimulation, and estrogen levels were strongly increased in the downstream liver acini. After 6 and 12 months, FAH developed in hepatocytes downstream of the transplants. After 18 months, 27% of the MG animals showed transformation of FAH into hepatocellular adenomas; this figure increased to 42% after 24 months (8/19), significantly outnumbering four spontaneous adenomas that developed between 18 and 30 months in 258 control animals. Hepatocellular carcinoma (HCC) appeared only in the MG. At 24 and 30 months, 18 HCCs developed; thus, 78% of MG animals showed at least one carcinoma. Administration of toremifene in ovariectomized and transplanted animals completely prevented hepatocarcinogenesis. Testicular grafts showed no influence on liver tissue. In conclusion, initially adaptive but preneoplastic alterations in hepatocytes downstream of intrahepatically transplanted ovarian fragments may transform into HCC, indicating a strong hepatocarcinogenic potential of high local levels of endogenous estrogens in the rat liver.

Adenoma, Liver Cell↗
PubMed2006

Phaeochromocytoma, new genes and screening strategies.

Following recent advances in the genetics of phaeochromocytomas and paragangliomas, the members of the European Network for the Study of Adrenal Tumours (ENS@T) Phaeochromocytoma Working Group have decided to share their genotyping data and to propose European recommendations for phaeochromocytoma/functional paraganglioma (PH/FPGL) genetic testing. Germline DNA from 642 patients was analysed by ENS@T teams. In 166 patients (25.9%) the disease was familial and caused by germline mutations in VHL (56), SDHB (34), SDHD (31), RET (31) or NF1 (14), causing von Hippel-Lindau disease, SDHB- or SDHD-PH/FPGL syndromes, multiple endocrine neoplasia type 2 (MEN 2) and type 1 neurofibromatosis (NF1), respectively. In almost 60% of inherited cases it was possible to formulate a probable genetic diagnosis based on family history and/or typical syndromic presentation. Genetic testing revealed mutations in 12.7% of cases with an apparently sporadic presentation. Several clinical characteristics, such as young age at onset, the presence of bilateral, extra-adrenal or multiple tumours or a malignant tumour, should be seen as indications for genetic testing. The ENS@T Phaeochromocytoma Working Group recommends the genetic testing of all patients with PH and FPGL and suggests a practice algorithm for the management of their exploration.

Adrenal Gland Neoplasms↗
PubMed2005

Codon-specific development of pheochromocytoma in multiple endocrine neoplasia type 2.

CONTEXT: Recent data suggest a codon-specific, age-related development of multiple endocrine neoplasia type 2. OBJECTIVE: The objective of this study was to delineate the codon-specific, age-related development of multiple endocrine neoplasia type 2-associated pheochromocytoma. DESIGN: We describe a cohort study with a mean observation period of 26.9 yr. SETTING: The study took place in a tertiary referral center at a university hospital. PATIENTS: Included in this study were 206 consecutive carriers (74 index, 132 nonindex) operated on at this institution who harbored point mutations in the RET (rearranged during transfection) protooncogene. INTERVENTION: The intervention was adrenalectomy for clinically confirmed pheochromocytoma. MAIN OUTCOME MEASURE: The main outcome measure was time to histopathological diagnosis of pheochromocytoma. RESULTS: Pheochromocytomas developed in 28% (five of 18) of carriers with mutations in codon 918, 29% (20 of 68) of carriers with mutations in codon 634, 14% (three of 21) of carriers with mutations in codon 618, 13% (two of 16) of carriers with mutations in codon 620, and 13% (two of 16) of carriers with mutations in codon 791. Earliest age of manifestation for each genotype was 22, 18, 29, 22, and 39 yr. Contralateral pheochromocytomas developed after 4 yr (one carrier each had a mutation in codon 618 or 620) and 5.2 yr (six carriers had mutations in codon 634). No pheochromocytomas were identified in carriers of mutations in codons 609 (n = 2), 611 (n = 8), 630 (n = 2), 768 (n = 8), 790 (n = 22), 804 (n = 18), and 891 (n = 7). CONCLUSIONS: Based on these and published preliminary data, annual screening for pheochromocytoma may be warranted from age 10 yr in carriers of RET mutations in codons 918, 634, and 630, and from age 20 yr in the remainder.

Adrenal Gland Neoplasms↗
PubMed2005

Insulin affects the neuronal response in the medial temporal lobe in humans.

In recent years, clear evidence has accumulated that insulin affects central nervous functions. Besides controlling metabolic processes such as energy homeostasis by the regulation of food intake through hypothalamic receptors, the peptide hormone also appears to be capable of modulating cognitive functions. Experimental and clinical evidence for insulin supports effects on learning and memory. This study explores the impact of insulin on neuronal activity using a picture encoding task in a functional magnetic resonance imaging approach. Ten subjects performed two independent scanning sessions, each session divided into one part of four baseline runs and a second part of four runs during either insulin or saline was infused. A hyperinsulinemic- euglycemic clamp technique was applied to keep the blood glucose concentrations normal during insulin infusion. Contrast images between the two parts revealed identical activation patterns during baseline and saline conditions while during the insulin condition a higher level of activation was detected within the fusiform gyrus in both hemispheres. Shorter reaction times during the insulin condition underlined the cognitive benefit. For the first time, we were able to demonstrate that insulin enhances neuronal activity within the medio-temporal lobe and increased performance in humans under in-vivo conditions.

Adult↗
PubMed2004

Central nervous and metabolic effects of intranasally applied leptin.

In obesity, due to the resistance of leptin receptors at the blood brain barrier, increased peripheral leptin levels cannot act appropriately at brain sites relevant for appetite regulation. In this study, we focused on the intranasal application of leptin. This mode of administration provides a promising tool for a direct access of peptides to the brain by circumventing the blood brain barrier. Male Wistar rats were treated daily with 0.1 or 0.2 mg/kg leptin intranasally for 4 wk. Compared with controls, leptin-treated animals gained significantly less weight and exhibited significantly reduced food and water intake. Corticotropin-releasing factor mRNA expression in the paraventricular nucleus showed a tendency for up-regulation by leptin; neuropeptide Y mRNA expression in the arcuate nucleus was decreased. In the central nucleus of the amygdala, corticotropin-releasing factor mRNA was significantly elevated in leptin-treated animals, suggesting a role in affective and/or emotional aspects of food intake. Serum leptin levels were unchanged, indicating a direct action of leptin in the central nervous system without prior access to the periphery. The intranasal application thus represents a useful tool to administer leptin in a noninvasive way with rapid permeation into the central nervous system.

Administration, Intranasal↗
PubMed2004

Hypertension in overweight and obese primary care patients is highly prevalent and poorly controlled.

BACKGROUND: Although the relationship between body weight and blood pressure (BP) is well established, there is a lack of data regarding the impact of obesity on the prevalence of hypertension in primary care practice. The objective of this study was to assess the prevalence of hypertension and the diagnosis, treatment status, and control rates of hypertension in obese patients as compared to patients with normal weight. METHODS: A cross-sectional point prevalence study of 45,125 unselected consecutive primary care attendees was conducted in a representative nationwide sample of 1912 primary care physicians in Germany (HYDRA). RESULTS: Blood pressure levels were consistently higher in obese patients. Overall prevalence of hypertension (blood pressure >/=140/90 mm Hg or on antihypertensive medication) in normal weight patients was 34.3%, in overweight participants 60.6%, in grade 1 obesity 72.9%, in grade 2 obesity 77.1%, and in grade 3 obesity 74.1%. The odds ratio (OR) for good BP control (<140/90 mm Hg) in diagnosed and treated patients was 0.8 (95% confidence interval [CI] 0.7-0.9) in overweight patients, 0.6 (95% CI 0.6-0.7) in grade 1, 0.5 (95% CI 0.4-0.6) in grade 2, and 0.7 (95% CI 0.5-0.9) in grade 3 obese patients. CONCLUSIONS: The increasing prevalence of hypertension in obese patients and the low control rates in overweight and obese patients document the challenge that hypertension control in obese patients imposes on the primary care physician. These results highlight the need for specific evidence-based guidelines for the pharmacologic management of obesity-related hypertension in primary practice.

Adolescent↗
PubMed2004

HYDRA: possible determinants of unsatisfactory hypertension control in German primary care patients.

The Hypertension and Diabetes Screening and Awareness (HYDRA) study is a cross-sectional point-prevalence study performed in September 2001; 45,125 primary care attendees were recruited from a representative nationwide sample of 1912 primary care practices in Germany. Around 42% of all patients presenting in these practices had hypertension (WHO definition). In approximately 70% of these patients, hypertension was diagnosed by doctors and 84% of diagnosed patients were on antihypertensive medication, but in less than 30% of treated patients was blood pressure controlled (< 140/90 mmHg). The control rate in all patients presenting with hypertension (including those patients unrecognized) was as low as 19%. The present analysis aimed to find explanations for this unsatisfactory outcome of hypertension control. The main finding was that the rate of diagnosis of hypertension is alarmingly low in young people, probably due to insufficient blood pressure screenings. The data further indicated that doctors still set their target of treatment according to outdated guidelines and that doctors still orientate their treatment primarily with regard to the diastolic pressure. These insights into the causes of unsatisfactory hypertension control may help to direct future educational programmes designed to improve hypertension management specifically to these deficits and thereby to improve control rates.

Adolescent↗
PubMed2004

High prevalence and poor control of hypertension in primary care: cross-sectional study.

OBJECTIVE: To report: (1) on the background, design and methods of the Hypertension and Diabetes Risk Screening and Awareness (HYDRA) study, (2) on the point prevalence of hypertension in primary care and (3) on the proportion of treated, controlled, and uncontrolled hypertension. DESIGN: Cross-sectional point prevalence study. SETTING: Representative nationwide sample of 1912 primary care practices in Germany. PARTICIPANTS: A total of 45,125 unselected primary care attendees. MAIN OUTCOME MEASURES: Prevalence of hypertension based on doctor's diagnosis, self-reported diagnosis, and blood pressure (BP) measurements. RESULTS: A total of 39% of all patients and 67% of patients aged 60 years or older, respectively, were diagnosed by their doctors as having hypertension. Eighty-four percent of diagnosed patients were on antihypertensive medication, 57% of which were rated by the physician as well controlled. When hypertension was defined as either current BP levels > or = 140/90 mmHg and/or current antihypertensive medication, the total point prevalence increased to 50%, while treatment and control rates (BP < 140/90 mmHg) dropped to 64 and 19%, respectively. CONCLUSIONS: Extrapolation of these findings to the entire primary care patient population seen in the over 20 000 primary care practices in Germany suggests that on an average day, over 700,000 patients with elevated BP are seen by primary care physicians, but that only around 132,000 of these patients are well controlled. Thus, this study not only documents the enormous burden of hypertensive patients in the primary health system, but also highlights the alarming lack of BP control in the vast majority of hypertensive patients.

Adolescent↗
PubMed2004

Lipid metabolism and insulin resistance in depressed patients: significance of weight, hypercortisolism, and antidepressant treatment.

Major depression increases cardiovascular risk despite lower cholesterol levels. Little is known about effects of antidepressants on metabolic risk factors. We studied lipoprotein composition, insulin sensitivity (quantitative insulin sensitivity check index), and saliva cortisol in 78 depressed patients before and after 35 days of amitriptyline or paroxetin treatment. Data were analyzed by principal component factor analyses and analysis of variance (ANOVA). At baseline, quantitative insulin sensitivity check index was inversely correlated with cortisol (r = -0.46; P = 0.005) in normal weight patients, with body mass index in overweight patients (r = -0.50; P < 0.001). In overweight patients, hypercortisolemia correlated inversely with total and low density lipoprotein cholesterol (eg, cortisol at 4:00 PM and low density lipoprotein cholesterol: r = -0.49, P = 0.002). After treatment, quantitative insulin sensitivity check index was unchanged. Triglycerides increased in responders to amitriptyline only (P < 0.05). Parameters of cholesterol metabolism improved slightly without differences between treatment groups (eg, high density lipoprotein: pre 43.5 +/- 12.0; post 47.6 +/- 13.0 mg/dL; P = 0.01; low density lipoprotein triglycerides, a measure of low density lipoprotein atherogenicity: pre 458 +/- 120; post 415 +/- 130 mg/g; P < 0,01). The inverse correlation of cortisol and cholesterol, at least in the obese subgroup, proposes a mechanism for the known association of depression with low cholesterol. As determinants of plasma lipids in major depression, we identified body mass index, insulin sensitivity, and cortisol. Although uncontrolled, our data suggest that treatment of depression exerts a mainly beneficial effect on lipid regulation.

Adult↗
PubMed2004

Malignant pheochromocytoma: current status and initiatives for future progress.

Pheochromocytomas are rare catecholamine-producing neuroendocrine tumors that are usually benign, but which may also present as or develop into a malignancy. Predicting such behavior is notoriously difficult and there are currently no curative treatments for malignant tumors. This report follows from a workshop at the Banbury Conference Center, Cold Spring Harbor, New York, on the 16th-18th November 2003, held to review the state of science and to facilitate future progress in the diagnosis and treatment of malignant pheochromocytoma. The rarity of the tumor and the resulting fragmented nature of studies, typically involving small numbers of patients, represent limiting factors to the development of effective treatments and diagnostic or prognostic markers for malignant disease. Such development is being facilitated by the availability of new genomics-based tools, but for such approaches to succeed ultimately requires comprehensive clinical studies involving large numbers of patients, stringently collected clinical data and tumor samples, and interdisciplinary collaborations among multiple specialist centers. Nevertheless, the well-characterized hereditary basis and the unique functional nature of these neuroendocrine tumors provide a useful framework that offers advantages for establishing the pathways of tumorigenesis and malignancy. Such findings may have relevance for understanding the basis of other more common malignancies where similar frameworks are not available. As the relevant pathways leading to pheochromocytoma are established it should be possible to take advantage of the new generation of drugs being developed to target specific pathways in other malignancies. Again the success of this will require well-designed and coordinated multi-center studies.

Adrenal Gland Neoplasms↗
PubMed2003

[Microbiological aspects and antibiotic therapy of diabetic foot infections].

IMMUNOLOGICAL AND MICROBIOLOGICAL ASPECTS OF DIABETIC FOOT INFECTIONS: Diabetic patients are at increased risk of severe skin and bone infections. Immunological disturbances are reasonable and due to altered specific and unspecific cellular immune responses. Analysis of epidemiology and microbial pathogenicity shows that staphylococci seem to be predestined to induce such infections. Staphylococcus aureus and coagulase-negative staphylococci are able to adhere to the wound ground by a sequela of mechanisms. Initial bacterial adherence is due to hydrophobicity, ion exchanges, and specific binding of bacterial adhesion molecules to cellular receptors. Moreover, staphylococci secrete polysaccharides which form a biofilm together with multilayer cell clusters. The highly structured communities within a biofilm are resistant to distinct immunoeffectors and have a decreased susceptibility to antibiotics in vivo. ASPECTS OF ANTIBIOTIC THERAPY: Assessing the severity of an infection is essential to selecting an antibiotic regimen, the mode of drug administration, and the duration of therapy. Regimens for severe and chronic infections are broader spectrum and often intravenously to obtain high drug concentrations immediately. Infections of the bone often require an antibiotic therapy for > 4 weeks, while a 1- to 2-week therapy for mild to moderate infections has been found to be effective. CONCLUSIONS: Because of the tremendous progress in diagnostics and therapy of diabetic foot infections, infectious complications can be successfully treated by appropriate wound care, metabolic control, and early surgical and antibiotic intervention. Bacterial biofilms involved into chronic infections are new aspects currently not visualized by clinical therapy. Besides the classic antimicrobial therapy, new concepts of an enzymatic therapy or the inhibition of bacterial "communication" (quorum sensing) are in progress and the hope for the future.

Anti-Bacterial Agents↗