Application of Pharmacodynamic Modeling for Designing Time-Variant Dosing Regimens to Overcome Nitroglycerin Tolerance in Experimental Heart Failure

Purpose. Prolonged continuous administration of nitroglycerin (NTG) leads to hemodynamic tolerance. We used a previously developed pharmacokinetic-pharmacodynamic (PK/PD) model of NTG tolerance in experimental heart failure to test whether dosage regimens, designed from this model, may allow avoidance of tolerance development upon continuous NTG inftision. Methods. Simulation experiments (using ADAPT II) were performed to evolve a time-variant infusion regimen that would theoretically provide sustained hemodynamic effect (30% reduction in left ventricular end-diastolic pressure, LVEDP) throughout 10 hours of drug dosing. A computer controlled infusion pump was utilized to deliver this time-variant input. Infusion experiments were then conducted in CHF rats to challenge the predictability of the applied PK/PD model. Results. Simulations showed that exponentially increasing input functions provided more sustained LVEDP effects when compared to linear or hyperbolic input functions delivering the same total NTG dose. A computer-selected infusion regimen of 6.56e^{0.00156×minutes} g/min was anticipated to provide the desired hemodynamic profile in our animal model. Experiments conducted in rats with congestive heart failure (n = 4) confirmed the prediction of sustained hemodynamic effect without tolerance (28 ± 4% reduction in LVEDP at 10 hrs). Conclusions. These findings support the utility of our PK/PD model of NTG tolerance in predicting NTG action, and serve as an example of therapeutic optimization through PK/PD considerations.     

Mini-swim-up: A new technique of sperm preparation for intracytoplasmic sperm injection

Purpose The male factor is nowadays one of the major problems in the treatment of infertility. New methods of assisted fertilization such as the intracytoplasmic sperm injection (ICSI) show better fertilization and pregnancy rates than classical IVF.Method In this study, we present a new technique of sperm preparation: the mini-swim-up.Conclusion This technique, used in conjunction with the ICSI procedure, improves pregnancy and fertility rates in cases of severe oligoasthenoteratozoospermia.     

Influence of a pre-operative enteral supplement on functional activities of peripheral leukocytes from patients with major surgery

Following severe trauma or major surgery patients develop functional alterations of host defense mechanisms which contribute an enhanced susceptibility towards microbial infections. Several studies have demonstrated that a specialized nutritional regimen may improve immune functions. We analyzed leukocyte functions from 40 patients undergoing major upper gastrointestinal surgery in a randomized placebo-controlled double-blind study. Patients were divided into two groups, one received 5 days pre-operatively an orally given experimental supplement enriched with omega-3-fatty acids, arginine, and ribonucleic acid (RNA), the other an isocaloric, control supplement. The experimental group generated significantly more leukotriene B(5) (LTB(5)) as compared to the control group. In contrast, the capacity to generate leukotriene B(4) (LTB(4)) as well as the synthesis of interleukin-8 (IL-8) was not significantly different in both groups. Additionally, lymphocyte/monocyte proliferation was analyzed and donor specific heterogeneities were observed; but no significant differences were found between the two nutritional regimens.     

The Use of Humor in Addressing the Sexuality of Elderly Nursing Home Residents

This paper is drawn from a large phenomenologically based study which investigated the nursing home carers' experiences of elderly residents' sexuality. Joking and teasing with the residents was an acknowledged way for staff to deal with sexuality in the nursing home. Whilst humor can be used in a therapeutic way to establish and maintain rapport, as well as to deal with incidents which are uncomfortable, joking is also known to be an effective way to manipulate and control people. Teasing can be used as an effective strategy to discourage certain types of behavior.     

Papillary clear cell adenocarcinoma of the groin arising from endometriosis

A 67-year-old woman presented with rapidly enlarging right anterior thigh mass. Clinical impression was of a primary sarcoma, but the histologic analysis of an incisional biopsy specimen showed adenocarcinoma with clear cell differentiation. Initially thought to be a metastasis, the malignant tumor appears to have arisen from extraabdominal endometriosis of the right groin. This case shows clinical, radiographic, and histologic findings that may help the orthopaedic surgeon recognize an unusual complication of extrapelvic endometriosis.     

Pulmonary embolism and myocardial hypoxia during extracorporeal membrane oxygenation

The treatment of a newborn with severe meconium aspiration by venoarterial extracorporeal membrane oxygenation (ECMO) was complicated by myocardial hypoxia with a marked decrease of myocardial contractility. The onset of the cardiac hypoxia was related to a pulmonary artery embolus. The origin of the embolus was a deep femoral vein thrombosis, caused by a central vein catheter, which was inserted 1 day before ECMO by venous cutdown. The possible pathophysiology of myocardial hypoxia in this patient is discussed, especially with regard to myocardial perfusion, supporting the hypothesis of coronary perfusion occuring with blood from the left ventricle and not from the arterial cannula in the aorta.     

Behandlungsstrategien bei prophylaxeresistenten bipolaren Störungen

Lithium is still regarded as the first choice substance in the prophylactic treatment of bipolar disorder. However, approximately one third of patients with a "classic" course of bipolar affective disorder do not adequately respond to lithium prophylaxis. The introduction of carbamazepine and valproic acid allowed a more differential syndrome- and course-orientated approach to the prophylactic treatment of bipolar disorder for the first time. However, about 10 to 20 percent of patients still remain refractory to standard regimes. Therefore, criteria for resistance to prophylactic treatment have to be further established. It has been suggested that at least two adequate trials of more than 12 months duration with sufficient drug blood levels have to be performed before refractoriness should be assumed. A severe subtype of affective disorder with poor response to lithium and other treatment approaches is a rapid cycling course which is characterised by at least four affective episodes per year. Here we present an overview of the currently available alternatives for prophylactic treatment, i.e. anticonvulsants, combination treatment, adjunctive thyroxine, calcium channel blockers, and more experimental approaches for treating refractory bipolar disorder patients. Suggestions for optimizing the prophylactic treatment of bipolar disorder are summarized in an algorithm.