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Biomedical subjects

P Faber

Publications and source records attributed to P Faber.

At least 19 recordsLinked to original sources

Methylthioninium chloride: pharmacology and clinical applications with special emphasis on nitric oxide mediated vasodilatory shock during cardiopulmonary bypass.

Vasodilatory shock after cardiopulmonary bypass is a common complication requiring treatment with high doses of inotropes and prolonged stays in the intensive care unit. The vasodilatory shock is initiated by an inflammatory response to the extracorporeal circuit. The inflammatory response results in endothelial synthesis and release of nitric oxide resembling the clinical features observed in vasodilatory shock caused by septicaemia. During vasodilatory shock, the inhibition of nitric oxide synthase and the nitric oxide/cyclic guanylyl monophosphate pathway is an attractive adjunct to therapy with traditional inotropes. Methylthioninium chloride inhibits nitric oxide/cyclic guanylyl monophosphate mediated vasodilation and can successfully be used as a supplement in the treatment of vasodilatory shock associated with cardiopulmonary bypass. The application of methylthioninium chloride in septicaemia has not produced comparable positive clinical results.

Adult↗

Effect of an acute fast on energy compensation and feeding behaviour in lean men and women.

AIM: Humans appear to defend against energy deficit to a greater extent than energy surplus. Severe dietary energy restriction resulting in 5-30% weight loss often leads to hyperphagia and weight regain in lean subjects. However, the period of time over which fasting is often endured in Western society are far shorter, approximately 1-2 days. This study examined how a 36 h fast effected the subsequent day's energy and nutrient intake in a group of 24 healthy, lean men and women. METHOD: Subjects underwent two 2 day treatments, termed 'fast' and 'maintenance'. During the 'fast' treatment, subjects were fed a maintenance diet on the day prior to the fast (day -1) to prevent overeating. They then consumed non-energy drinks only, from 20:00 h on day -1 to 08:00 h on day 2 (ad libitum feeding day), thus fasting for 36 h. On the 'maintenance' protocol, subjects received a maintenance diet throughout day 1. Throughout day 2 they had ad libitum access to a range of familiar foods, which were the same for both treatments. Body weight, blood glucose and respiratory quotient were used as compliance checks. Hunger was monitored on day's -1, 1 and 2 for the fast treatment only. RESULTS: On day 2, average energy intake was 10.2 vs 12.2 MJ/day (s.e.d. 1.0) on the post-maintenance and post-fast periods, respectively (P=0.049). Subjects altered feeding behaviour, in response to the fast, only at breakfast time, selecting a higher-fat meal (P<0.005). Compared to day -1, motivation to eat was elevated during the fast (P<0.05). This continued until breakfast was consumed during the re-feeding period (day 2), when values then returned to baseline. CONCLUSION: These data suggest that a 36 h fast, which generated a negative energy balance of approximately 12 MJ, did not induce a powerful, unconditioned stimulus to compensate on the subsequent day.

Adult↗

[Effects of excessive isocaloric intake of either carbohydrate or fat on body composition, fat mass, de novo lipogenesis and energy expenditure in normal young men].

Ten pairs of normal young men were overfed by 5 MJ per day for 21 days with either a carbohydrate-rich or a fat-rich diet (C- and F-group). The two subjects of a pair were requested to follow each other throughout the day to ensure similar physical activity. The increase in body weight and fat mass were not significantly different between the C- and the F-group. Heat production during sleep did not change during overfeeding. The accumulated faecal loss of energy, dry matter, carbohydrate and protein was significantly higher in the C- than in the F-group. Hepatic de novo lipogenesis was 212 g per 21 days in the C-group and was too low to be determined in the F-group. Whole body de novo lipogenesis was positive in six of the ten subjects in the C-group (mean: 332 g per 21 days). It is concluded that the increase in body weight and fat mass during overfeeding of isocaloric amounts of diets rich in carbohydrate or in fat was not significantly different, and that surplus of carbohydrate seemed to be converted to fat both by hepatic and extrahepatic de novo lipogenesis.

Adipose Tissue↗

Effects of isoenergetic overfeeding of either carbohydrate or fat in young men.

Ten pairs of normal men were overfed by 5 MJ/d for 21 d with either a carbohydrate-rich or a fat-rich diet (C- and F-group). The two subjects in each pair were requested to follow each other throughout the day to ensure similar physical activity and were otherwise allowed to maintain normal daily life. The increase in body weight, fat free mass and fat mass showed great variation, the mean increases being 1.5 kg, 0.6 kg and 0.9 kg respectively. No significant differences between the C- and F-group were observed. Heat production during sleep did not change during overfeeding. The RQ during sleep was 0.86 and 0.78 in the C- and F-group respectively. The accumulated faecal loss of energy, DM, carbohydrate and protein was significantly higher in the C- compared with the F-group (30, 44, 69 and 51% higher respectively), whereas the fat loss was the same in the two groups. N balance was not different between the C- and F-group and was positive. Fractional contribution from hepatic de novo lipogenesis, as measured by mass isotopomer distribution analysis after administration of [1-(13)C]acetate, was 0.20 and 0.03 in the C-group and the F-group respectively. Absolute hepatic de novo lipogenesis in the C-group was on average 211 g per 21 d. Whole-body de novo lipogenesis, as obtained by the difference between fat mass increase and dietary fat available for storage, was positive in six of the ten subjects in the C-group (mean 332 (SEM 191)g per 21 d). The change in plasma leptin concentration was positively correlated with the change in fat mass. Thus, fat storage during overfeeding of isoenergetic amounts of diets rich in carbohydrate or in fat was not significantly different, and carbohydrates seemed to be converted to fat by both hepatic and extrahepatic lipogenesis.

Adipose Tissue↗

A fast responding combined direct and indirect calorimeter for human subjects.

The construction and performance of a 5.4 m3 combined direct and indirect calorimeter for human subjects is described. The calorimeter was constructed for studies on human subjects primarily undergoing fast alterations in heat production and heat losses, e.g. after a meal or during physical exercise. A heat sink and a heat substitution principle is used to measure sensible heat losses directly. Evaporative heat losses are determined by measuring water vapour input and output. Indirect calorimetry is performed by measuring output air flow and changes in gas composition of the air entering and leaving the calorimeter. The response times (90%) for sensible heat and evaporative heat were found to be 4 min and 34 min, respectively. Three alcohol combustion tests gave a recovery of CO2 and O2 in the range 92-97%. The recovery of water was found to be in the range 56-89%.

Biomedical Engineering↗

Fat content affects heat capacity: a study in mice.

The specific heat capacity of the human body is a widely used number in calculations related to studies in energy metabolism and temperature regulation. A value of 3.47 kJ kg-1 K-1 has been used during the last century, but there have been no direct studies on the dependence of this value on the body fat content. We present here results of measurements of the specific heat capacity of lean and obese mice. The mice were killed and heated to 40.6 degrees C, transferred to a calorimeter and the specific heat capacity was determined from body mass of the mice and temperature rise of water in the calorimeter. We measured the fat fraction of body mass (mf), fat free body mass and water content of the mice and found a marked dependency of the specific heat capacity (Cp) on body fat. In obese mice (fat content 52.76% body wt) the heat capacity was 2.65 kJ kg-1 K-1 and in lean mice (fat content 7.55% body wt) the heat capacity was 3.66 kJ kg-1 K-1.

Animals↗

Alteration of integrated optical density and intercellular structure after induction chemotherapy and survival in lung carcinoma patients treated surgically.

Histologic sections of formalin-fixed, paraffin-embedded tissue consisting of 53 surgical specimens, 48 biopsy specimens and 29 intrapulmonary lymph nodes of human non-small cell lung carcinoma were Feulgen stained. The biopsy specimens were obtained before and the surgical specimens after induction chemotherapy (down staging). The integrated optical density (IOD) of tumor cell nuclei was measured using an automated image analysis system, and the attributed minimum spanning trees (MSTs) were computed. The measured features included IOD (DNA content of the nuclei), IOD entropy, S-phase-related fraction (SRF), percentage of tumor cells with an IOD > 5C (P5C), standard deviation of IOD and structural parameters (minimum distance between neighboring tumor cell nuclei, minimum distance between tumor cell nuclei and neighboring lymphocytes, MST entropy, minimum distance between neighboring proliferating tumor cell nuclei, etc.). The measured IOD and MST features showed significant differences in the biopsy specimens as compared to those measured in the surgically excised carcinomas and those growing in the intrapulmonary lymph nodes (lymph node metastases). After down staging, the SRF was significantly diminished, and the percentage of cells with an IOD > 5C increased (P < .05). The survival of patients was remarkably improved if both the carcinomas before and after induction chemotherapy displayed a low SRF, a low number of stemlines and low MST entropy.

Adenocarcinoma↗

[Pregnancy and laryngeal cancer].

Although cancer during pregnancy is not a common clinical problem, its occurrence is associated with much anxiety distress for patient and physician alike. Such concern arises from the fact, that two lives are involved, and that decisions regarding evaluation of treatment of the mother may have direct consequences for the foetus. We discuss treatment and prognosis of laryngeal cancer during pregnancy of a 33 year old patient.

Adult↗

Randomized, double-blind, multicenter trial on treatment of frequency, urgency and incontinence related to detrusor hyperactivity: oxybutynin versus propantheline versus placebo.

Clinical efficacy and adverse effects of oxybutynin and propantheline in the treatment of symptoms related to detrusor hyperactivity were studied in a randomized, controlled, double-blind multicenter trial. Of 169 patients entered into the study 154 were evaluable for statistical analysis. Mean grade of improvement (visual analogue scale) was significantly higher with oxybutynin (58.2%) versus propantheline (44.7%) and placebo (43.4%). Mean bladder volume at first involuntary cystometric contraction was significantly increased with oxybutynin (+57.0 ml.) versus placebo (-9.7 ml.). Mean maximum cystometric bladder capacity was also significantly increased with oxybutynin (+80.1 ml.) versus placebo (+22.5 ml.). Rate of inquired possible adverse effects was significantly higher for oxybutynin (63%) versus propantheline (44%) and placebo (33%). However, only 5 patients dropped out of the study because of adverse effects (oxybutynin 2 and propantheline 3). No serious or lasting adverse effects were encountered with dryness of the mouth being the major complaint. Oxybutynin has statistically significant effects on subjective symptoms and objective urodynamic parameters in patients with detrusor hyperactivity compared to propantheline.

Adolescent↗

[Senna-containing laxatives: excretion in the breast milk?].

The excretion of rhein, a cathartic with active metabolite from sennosides, was investigated in breast milk samples of 15 post-partum women for at least 24 h after the intake of a therapeutic dose (15 mg sennosides/day) of a standardized, fiber containing senna laxative (Agiolax). Rhein was analyzed by a HPLC-method with a lower limit of detection at 1 ng/ml rhein, taking into account a possible binding as monoglucuronide and monosulfate. Maximal concentrations up to 27 ng/ml and in 89% values below 10 ng/ml were measured. Related to the daily milk volume, 73% of the women excreted less than 2 ng rhein/day. Based on median values, 0.017% of the sennoside intake (calculated as rhein) was excreted in breast milk. The amount of rhein transmitted to the infant is therefore 0.3% of the rhein intake of the mother. This is far below the oral rhein dose necessary for inducing a laxative effect. Accordingly, none of the breast-fed infants (n = 8) showed any difference in stool consistency in comparison with the non breast-fed infants.

Adult↗

Relevance of rhein excretion into breast milk.

The excretion of rhein, a laxatively active metabolite of sennosides, was investigated in 100 breast milk samples of 20 post-partum women after intake of a standardized senna laxative (Agiolax), which also contains seeds of Plantago ovata as bulk substances. After daily doses of 5 g of the senna laxative containing 15 mg sennosides for 3 days, the rhein concentration in milk samples from every lactation during 24 h post-dose varied between 0 and 27 ng/ml with values below 10 ng/ml in 94%. Based on median values, 0.007% of the sennoside intake (calculated as rhein) was excreted in breast milk. None of the breast-fed infants had an abnormal stool consistency. Assuming a (theoretical) complete metabolism of sennosides to rhein in the mother, the amount of rhein delivered to the infant (ng/kg b.w.) is by the factor 10(-3) below the rhein intake of the mother.

Anthraquinones↗

Aminoglutethimide without hydrocortisone in the treatment of postmenopausal patients with advanced breast cancer.

In a phase II study, 38 evaluable patients with advanced progressive breast cancer were treated with 4 X 250 mg of aminoglutethimide per day without hydrocortisone supplementation. Partial remissions were observed in five patients (13%), with a median duration of 9 months (range, 7-15), and stable disease was observed in 17 patients (45%), with a median duration of 4 months (range, 2-11). The recorded side effects (CNS, cutaneous, gastrointestinal) were tolerable and transient and required drug discontinuation in only four patients. Serial determinations of serum hormone levels during aminoglutethimide treatment revealed a significant decrease in estradiol and an increase in gonadotropins, testosterone, and progesterone. No patients had adrenal insufficiency. In contrast, despite prolonged aminoglutethimide treatment and persisting hypoestrogenemia, both cortisol levels and adrenal responses to ACTH remained unaltered. It is concluded that aminoglutethimide alone is effective in the treatment of postmenopausal patients with breast cancer. Moreover, based on the present findings, a prospective randomized study is warranted to show that hydrocortisone supplementation appears to not be mandatory, either for increase in efficacy or for decrease in side effects of the treatment.

Adult↗