Complications of Psychotropic and Pain Medications in an Ultrarapid Metabolizer Patient at the Upper 1% of Cytochrome P450 (CYP450) Function Quantified by Combinatorial CYP450 Genotyping

A 44-year-old Caucasian woman presented with a history of empirical treatment with 20 pain and psychotropic medications, as well as dual comorbidity of intractable pain and depression. A multiple gain-of-function profile in the CYP450 family of cytochrome P450 (CYP450) drug metabolism isoenzymes was discovered. The patient was a homozygote of suprafunctional alleles for both CYP2D6 (^*35/^*35) and CYP2C19 (^*17/^*17) genes and functional alleles for CYP2C9 (^*1/^*1), which account for aggregate drug metabolism function at the upper 1% of the population. The patient improved clinically with discontinuation of psychotropics and pain medications that were substrates of CYP2D6 and/or CYP2C19, suggesting that much of her symptomatology was drug induced. Combinatorial genotyping of CYP450 genes is diagnostically useful in individuals with histories of multiple side effects or drug resistance, which could be avoided by genetically informed therapeutics in behavioral health.     

The dynamics of cardiac defense: From attention to action

The attentional and motivational significance of cardiac defense is examined in two studies. In Study 1, cardiac defense was evoked by an intense acoustic stimulus in the context of either a visual search or a memory search task using letters as stimuli. Results showed a potentiation of the long latency acceleration of cardiac defense in the visual search task. In Study 2, participants performed the same visual search task using pleasant, neutral, and unpleasant pictures as stimuli. Results showed a further potentiation of the long latency acceleration of cardiac defense when the visual search task was performed with unpleasant, compared to pleasant or neutral pictures. These results indicate that cardiac defense has both attentional and motivational contributions, where the attentional significance is related to increased sensory processing, whereas the motivational significance is associated with preparation for active defense.     

Prognostic Value of Subdivisions of Nighttime Blood Pressure Fall in Hypertensives Followed Up for 8.2 Years. Does Nondipping Classification Need to Be Redefined?

J Clin Hypertens(Greenwich). 2010;12:508–515. © 2010 Wiley Periodicals, Inc. To evaluate the long-term prognostic significance of different ranges of the percentage fall in nighttime blood pressure (BP) of the nondipping pattern, 1200 hypertensive patients (645 women, age 51±12 years) underwent ambulatory BP monitoring under stabilized therapy. The occurrence of cardiovascular (CV) events was followed for 9833 patient-years and analyzed by the Cox hazard model. There were 152 CV fatal/nonfatal events (79 strokes, 51 coronary events, 22 others) during the 15.2 years of follow-up. According to nighttime BP fall (%) the authors noted: <0% (reverse-dippers [RD], n=83); 0%–4.9% (nondippers 1 [ND1], n=207); 5%–9.9% (nondippers 2 [ND2], n=311), 10%–19.9% (dippers [D], n=523); and ≥20% (extreme dippers [ED], n=76). After adjustment for confounding variables, hazard ratios (95% confidence interval) of CV event and stroke in RD vs D were 2.29 (1.31–3.99) and 2.46 (1.11–5.49); of ND1 vs D were 1.42 (1.12–1.79) and 1.62 (1.17–2.23); and of ND1 vs ND2 were 2.24 (1.33–3.75) and 2.30 (1.15–4.58). No differences were found in RD vs ND1 and ND2 vs D. Nondippers have a higher CV risk than dippers but only for a nighttime BP fall <5% suggesting that the limits for nondipping should be redefined for a stratification of CV risk.     

Is distortion of the bioprosthesis ring a risk factor for early calcification ?

We report a case of a male patient who received an implantation of a Starr-Edwards-caged-ball-valve-prosthesis in 1967. The surgery and postoperative course were without complications and the patient recovered well after the operation. For the next four decades, the patient remained asymptomatic - no restrictions on his lifestyle and without any complications. In 2006, 39 years after the initial operation, we performed a Bentall-Procedure to treat an aortic ascendens aneurysm with diameters of 6.0 × 6.5 cm: we explanted the old Starr-Edwards-aortic-caged-ball-valve-prosthesis and replaced the ascending aorta with a 29 mm St.Jude Medical aortic-valve-composite-graft and re-implanted the coronary arteries. This case represents the longest time period between Starr-Edwards-caged-ball-valve-prothesis-implantation and Bentall-reoperation, thereby confirming the excellent durability of this valve.     

Ward mortality after ICU discharge: a multicenter validation of the Sabadell score

Background  

Tools for predicting post-ICU patients’ outcomes are scarce. A single-center study showed that the Sabadell score classified patients into four groups with clear-cut differences in ward mortality.     

Adjuvant radio-chemotherapy after extended or simple cholecystectomy in gallbladder cancer

Purpose  

To analyse results of combined treatment of adjuvant radio-chemotherapy (RT-CT) in patients diagnosed with gallbladder cancer (GBC) after complete resection. Methods and material From June 1993 until July 2006, 67 patients with a diagnosis of GBC who underwent R0 surgical resection and were staged as T1b-2-3N0-1M0 received adjuvant RT-CT. Radiotherapy consisted of whole abdominal irradiation (20 Gy at 100 cGy daily) plus a boost to the tumour bed for a total of 45–59.4 Gy. Concomitant chemotherapy (fluoropyrimidines) was given. Overall survival (OS) and median survival were analysed in relation to different prognostic factors.