Recent animal and human studies have suggested that leptin secretion is
closely linked to the functions of the
hypothalamic-pituitary-adrenal (HPA) axis and the immune system,
both of which are ...crucial in influencing the course and outcome of
critical illness. Therefore, we measured basal plasma leptin levels and
examined the circadian secretion of leptin, in parallel with the
hormones of the HPA axis and a key cytokine, interleukin-6, in
critically ill patients with acute sepsis. Sixteen critically ill
patients from the University of Leipzig Intensive Care Unit were
recruited for this study. All of these patients fulfilled the standard
diagnostic criteria for sepsis. Plasma leptin levels were measured in
all patients and controls at 0900 h. In addition, in a subgroup of
eight critically ill patients and all of the nine controls, plasma
leptin, cortisol, ACTH and interleukin-6 concentrations were measured
every 4 hours for 24 hours. Mean plasma leptin levels were three-fold
higher (18.9 ± 4.5 ng/mL) in critically ill patients than
controls (3.8 ± 1.0 ng/mL, P < 0.05). Similarly,
ACTH levels were lower (7.8 ± 3.4 pmol/L) in patients than in
controls (17.1 ± 1.5 pmol/L, P < .001), while
plasma cortisol levels were increased (947.6 ± 144 nmol/L) in
patients compared to controls (361.1 ± 29, P <
0.001). Morning plasma interleukin-6 levels were markedly elevated in
all patients with sepsis (1238.0 ± 543.1 pg/mL) versus
controls (6.4 ± 1.7, P < 0.001). The controls
exhibited a nyctohemeral fluctuation in plasma leptin levels with
peak levels at 23:00; in contrast, septic patients, had no nocturnal
rise of leptin. In healthy controls, plasma leptin and cortisol had
reciprocal circadian rhythms with high nocturnal leptin levels and low
nocturnal cortisol concentrations; in critically ill patients, this
relation was abolished. Mean leptin levels were three-fold higher in
patients who survived the septic episode (25.5 ± 6.2, n =
10) than in non-survivors (8.0 ± 3.7, n = 6,
P < 0.01). We conclude that in addition to its
function as an anti-obesity factor, leptin may play a role in a severe
stress state such as acute sepsis.
Leptin, produced by adipocytes, has homeostatic effects on body fat mass through inhibition of appetite and stimulation of the sympathetic nervous system. Several studies have reported that high‐dose ...exogenous glucocorticoids increase circulating leptin concentrations in humans. Conversely, leptin has inhibitory effects on the hypothalamic‐pituitary‐adrenal (HPA) axis, both at the hypothalamic and adrenal levels. We hypothesized that acute hypercortisolism, in the physiological range, may not alter leptin secretion. Four stimuli of the HPA axis were administered to eight healthy male volunteers in a placebo‐controlled study. On separate afternoons, in a randomised order, fasting subjects received i.v. injections of saline, naloxone (125 μg/kg); vasopressin (0.0143 IU/kg); naloxone and vasopressin in combination; or insulin (0.15 U/kg; a dose sufficient to induce hypoglycaemia). Plasma concentrations of adrenocorticotrophic hormone (ACTH), cortisol and leptin were measured before and for 120 min after the injection. The cortisol secretory response was greatest after insulin‐hypoglycaemia, this response was significantly greater than that following naloxone, naloxone/vasopressin, or vasopressin alone. Despite the cortisol release, leptin concentrations were not increased after any stimulus. Insulin‐hypoglycaemia was associated with a decrease in leptin concentration at 60 and 90 min, while naloxone did not alter leptin concentrations. However, basal leptin concentrations were positively correlated with integrated ACTH and cortisol responses to naloxone, but did not correlate with ACTH or cortisol responses to the other stimuli. Thus acute elevations of plasma cortisol, in the physiological range, do not appear to influence plasma leptin concentrations. The fall in plasma leptin concentration after insulin‐induced hypoglycaemia may reflect catecholamine secretion after this stimulus.
Abstract Antimicrobial drug resistance in Neisseria gonorrhoeae has become an increasing public health problem. Hence, surveillance of resistance development is of crucial importance to implement ...adequate treatment guidelines. Data on the spread of antibiotic resistance among gonococcal isolates in Germany, however, is scarce. In a resistance surveillance study conducted by the Paul Ehrlich Society for Chemotherapy between October 2010 and December 2011, 23 laboratories all over Germany were requested to send N. gonorrhoeae isolates to the study laboratory in Frankfurt am Main. Species verification was performed biochemically using ApiNH and with Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS). Antimicrobial susceptibility testing was performed using the Etest method. For molecular epidemiological analysis, N. gonorrhoeae strains were genotyped by means of N. gonorrhoeae multi-antigen sequence typing. A total of 213 consecutive gonococcal isolates were analyzed in this nationwide study. Applying EUCAST breakpoints, high resistance rates were found for ciprofloxacin (74%) and tetracycline (41%). Penicillin non-susceptibility was detected in 80% of isolates. The rate of azithromycin resistance was 6%, while all strains were susceptible to spectinomycin, cefixime, and ceftriaxone. Molecular typing of gonococcal isolates revealed a great heterogeneity of 99 different sequence types (ST), but ST1407 predominated ( n = 39). This is the first comprehensive German multi-centre surveillance study on antibiotic susceptibility and molecular epidemiology of N. gonorrhoeae with implications for antibiotic choice for treatment of gonorrhoea. The World Health Organization supports the concept that an efficacious treatment of gonorrhoea results in at least 95% of infections being cured. Accordingly, as spectinomycin is not available on the German market, only the third generation cephalosporins cefixime and ceftriaxone are regarded as valuable drugs for empirical treatment of gonorrhoea in Germany.
Primary aldosteronism is associated with hypertension secondary to salt and water retention, hypokalemia and impaired insulin secretion with glucose intolerance in some patients. The secretion of ...leptin, a hormone produced by adipocytes, may be altered by reduced insulin secretion in primary aldosteronism. We measured plasma leptin approximately 3 months before and 3 months after curing of primary aldosteronism in 18 patients (12 male, 6 female, body mass index 29.1+/-4.4, mean +/- SD). Patients were treated by unilateral laparoscopic adrenalectomy to remove an aldosterone-producing adenoma. There was a 46% postoperative increase in plasma leptin concentrations from 6.65+/-0.81 to 9.68+/-1.50 ng/ml (P=0.004), despite a non-significant fall in body mass index. Plasma leptin was noted to increase after adrenalectomy in 16 of the 18 patients. The patients also had improved blood pressure and a significant increase in plasma potassium post-operatively. It is proposed that increased insulin secretory capacity associated with correction of negative potassium balance may account for the increase in plasma leptin after curing primary aldosteronism. Further studies are indicated to identify the mechanism of plasma leptin suppression in primary aldosteronism.
To measure the effect of experimental endotoxemia and anti-inflammatory therapy on plasma dehydroepiandrosterone (DHEA) levels in humans.
Controlled, randomized, single-blind, prospective clinical ...study.
Monitored unit in research hospital.
Twelve healthy volunteers served as their own controls and were randomized to receive intravenous endotoxin (Escherichia coli) or saline separated by 1 wk. Six were randomized to receive ibuprofen, a cyclooxygenase inhibitor, and six were given placebo.
Measurement of vital signs and hormones during a 24-hr period.
All subjects given endotoxin had a significant increase in plasma DHEA, cortisol, and adrenocorticotropic hormone (ACTH) levels (all p = .02). DHEA levels were maximum at 2 hrs and returned to baseline values by 6 hrs. Ibuprofen administration significantly blunted the endotoxin-induced increase in DHEA secretion (p = .001), whereas the increase in cortisol and ACTH was not affected.
Acute endotoxemia leads to a rise in plasma DHEA levels in humans. Maximum levels of DHEA but not cortisol or ACTH were blunted by ibuprofen, suggesting a different regulation of these synthetic pathways in the adrenal cortex inner zone during acute inflammation.
Neutropenias, especially extended an long-lasting stages, lead to life-threatening endogenous infection. Therefore, after taking off materials for bacteriological investigations an empirical schedule ...of a combined high dose, treatment with broad-band antibiotics and/or antimycotics has immediately to be introduced and to continue until the body temperature and the peripheral blood granulocytes are normalized. In case of treatment failure one should complete the therapy by other additional antibiotics or correct the combination of its in respect to the results of the microbiological investigations. Supplements of this antimicrobial treatments are immunoglobulins and growth factors (G-CSF, GM-CSF). In case of an expected neutropenica the use of the selective gut decontamination or the reverse isolation of the patient can be of essential advantage.
Canaliculitis is a relatively rare dacryocanal infection which occurs most unilateral. It can easily be misinterpreted and not sufficiently treated. Typical agents of the canaliculitis are ...actinomyces, that can cause infections of the hollow spaces with formation of concrements. The clinical courses of two patients are shown. One of them was treated for a dacryocystitis for 3 years and the other one had been referred to the eye hospital for chalazion removal. Only a microbiologic examination including cultivation of the surgically obtained dacryolithes and secretion enabled us to a reliable proof of the actinomyces and to an appropriate therapy for canaliculitis.
We compared the efficacy and safety of once-daily fleroxacin and twice-daily ciprofloxacin in patients with complicated urinary tract infections.
Using a prospective, open, randomized, multicenter ...study design, 133 patients (67 fleroxacin, 66 ciprofloxacin) were treated with doses of either 200 mg. of fleroxacin once daily or 250 mg. of ciprofloxacin twice daily in phase 1. In phase 2, 211 patients (103 fleroxacin, 108 ciprofloxacin) received 400 mg. of fleroxacin once daily or 500 mg. of ciprofloxacin twice a day.
In phase 1, bacteriological efficacy was excellent only against sensitive pathogens, such as Escherichia coli (84% with fleroxacin, 88% with ciprofloxacin), but high failure rates were observed in infections caused by Pseudomonas species (56% with fleroxacin, 67% with ciprofloxacin) and gram-positive organisms (52% with fleroxacin, 67% with ciprofloxacin). In phase 2, bacteriological overall success rate was 88% in the fleroxacin group and 84% in the ciprofloxacin group. Clinical overall success was observed in more than 90% of patients in both groups (94% with fleroxacin, 93% with ciprofloxacin). No statistically significant differences between the drugs were observed in efficacy during phase 2, including a 4 to-6-week followup. Tolerance was also similar for fleroxacin and ciprofloxacin, with about 20% of patients reporting adverse events.
The results suggest that both fleroxacin and ciprofloxacin are safe and effective for the treatment of complicated urinary tract infections at the higher doses used in phase 2, with fleroxacin offering the advantage of a once-daily dosing regimen. Lower doses of fleroxacin (200 mg. once daily) should only be used to treat urinary tract infections caused by gram-negative organisms with minimum inhibiting concentrations of less than 0.5 mg./l.
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