Postoperative adaptation of the small intestine after total colectomy and J-pouch-anal anastomosis

Twelve patients who underwent total colectomy and J-pouch-anal anastomosis were followed up to 3 years after surgery to evaluate the functional and morphologic changes of the small-bowel reservoir. Intestinal absorption was impaired for lactose in 18 percent, for D-xylose in 27 percent, and for⁷⁵SeHCAT in 83 percent. Morphologic changes in ileal-pouch specimens consisted of a marked flattening of the villi and augmentation in crypt number and length. The number of Paneth's cells was increased compared with normal ileum. Parameters, indicating neorectal function such as stool frequency, pouch volume, and intestinal transit, improved in time during the postoperative course. Because of impaired small-bowel function, which is not restricted to the pouch reservoir, the ileum acquires progressive colonic capacities in accordance with its morphologic transformation to a colonic type mucosa. None of our patients developed clinical malabsorption requiring regular therapeutic substitution beyond a well-balanced diet due to these morphologic and functional changes and postoperative acceptance was good or excellent in all but one case. Read at the XIIth Biennial Congress of the International Society of University Colon and Rectal Surgeons, Glasgow, Scotland, July 10 to 14, 1988.     

Prospective randomized trial comparing short-term antibiotic therapy versus standard therapy for acute uncomplicated sigmoid diverticulitis

Purpose

To date, the standard therapy used for acute episodes of uncomplicated sigmoid diverticulitis has been a 7–10-day antibiotic treatment regimen. Thanks to the development of highly potent, broad-spectrum antibiotics such as ertapenem, the question arises as to whether the duration of treatment of acute uncomplicated sigmoid diverticulitis can be reduced by using highly effective antibiotics.

Methods

To compare the efficacy of short-term therapy (4 days) versus standard therapy (7 days) for uncomplicated sigmoid diverticulitis, a prospective randomized multicenter trial was conducted. Patients were randomized to treatment groups after 4 days. Both patient groups were monitored until discharge and were followed up after 4–6 weeks and 52 months. The results were standardized and statistically evaluated.

Results

Between 16 December 2004 and 15 November 2007, 123 patients from 11 hospitals were enrolled in the study. Seventeen patients dropped out. In the remaining 106 cases, no significant differences were discerned between the two groups in terms of the basic data, apart from the mean number of diverticulitis episodes (short term 1.28?±?0.64 versus standard 1.64?±?1.07, p?=?0.037). The mean hospital stay was 8.8 days, with significant differences seen between short-term and standard therapy (7.8?±?2.8 versus 9.7?±?3.2 days; p?=?0.002). After 4 days, treatment was classified as having proved successful in 98.0% of cases and after 7 days in 98.2% of cases. An overall success rate of 95.1% (94.0% versus 96.2%, n.s.) was recorded after 1 month.

Conclusion

The results obtained with short-term ertapenem therapy (4 days) showed that this was as effective as standard therapy (7 days) for treatment of uncomplicated sigmoid diverticulitis.     

Erratum to: Prospective randomized trial comparing short-term antibiotic therapy versus standard therapy for acute uncomplicated sigmoid diverticulitis

Purpose  

To date, the standard therapy used for acute episodes of uncomplicated sigmoid diverticulitis has been a 7–10-day antibiotic treatment regimen. Thanks to the development of highly potent, broad-spectrum antibiotics such as ertapenem, the question arises as to whether the duration of treatment of acute uncomplicated sigmoid diverticulitis can be reduced by using highly effective antibiotics.     

Hypertension in special populations: chronic kidney disease, organ transplant recipients, pregnancy, autonomic dysfunction, racial and ethnic populations

The benefits of appropriate blood pressure (BP) control include reductions in proteinuria and possibly a slowing of the progressive loss of kidney function. Overall, medication therapy to lower BP during pregnancy should be used mainly for maternal safety because of the lack of data to support an improvement in fetal outcome. The major goal of hypertension treatment in those with baroreceptor dysfunction is to avoid the precipitous, severe BP elevations that characteristically occur during emotional stimulation. The treatment of hypertension in African Americans optimally consists of comprehensive lifestyle modifications along with pharmacologic treatments, most often with combination, not single-drug, therapy.     

Recommendations for an update of 2003 European regulatory requirements for registration of drugs to be used in the treatment of RA

Since 2003, the European Medicines Agency (EMA) document, 'Points to consider on clinical investigation of medicinal products other than NSAIDs (nonsteroidal anti-inflammatory drugs) for the treatment of rheumatoid arthritis' has provided guidance for the clinical development of both biologic and non-biologic disease-modifying antirheumatic drugs (DMARDs). In the last few years, several new products have been developed or are in development for the treatment of RA, which offer significant efficacy with regard to disease control, including prevention of structural damage and disability. Concurrently, novel insights have been gained with respect to the assessment of disease activity, joint damage and disability. New treatment strategies have been established which relate to early therapy, tight control and rapid switching of medication. Accordingly, several new EULAR/ACR recommendations have been or are being developed. Several important additions and changes are needed in the 2003 guidance to incorporate the current scientific knowledge into clinical trial design for the development of future products. Under the auspices of the Group for the Respect of Ethics and Excellence in Science (GREES), a group of experts in the field of RA and clinical trial design met to provide a consensus recommendation for an update to the 2003 EMA guidance document.     

The Phage Therapy Paradigm: Prêt-à-Porter or Sur-mesure?

Pharmaceutical Research -     

In vivo requirement of TGF-β/GDNF cooperativity in mouse development: focus on the neurotrophic hypothesis

Neurotrophic factors are well-recognized extracellular signaling molecules that regulate neuron development including neurite growth, survival and maturation of neuronal phenotypes in the central and peripheral nervous system. Previous studies have suggested that TGF-β plays a key role in the regulation of neuron survival and death and potentiates the neurotrophic activity of several neurotrophic factors, most strikingly of GDNF. To test the physiological relevance of this finding, TGF-β2/GDNF double mutant (d-ko) mice were generated. Double mutant mice die at birth like single mutants due to kidney agenesis (GDNF−/−) and congential cyanosis (TGF-β2−/−), respectively. To test for the in vivo relevance of TGF-β2/GDNF cooperativity to regulate neuron survival, mesencephalic dopaminergic neurons, lumbar motoneurons, as well as neurons of the lumbar dorsal root ganglion and the superior cervical ganglion were investigated. No loss of mesencephalic dopaminergic neurons was observed in double mutant mice at E18.5. A partial reduction in neuron numbers was observed in lumbar motoneurons, sensory and sympathetic neurons in GDNF single mutants, which was further reduced in TGF-β2/GDNF double mutant mice at E18.5. However, TGF-β2 single mutant mice showed no loss of neurons. These data point towards a cooperative role of TGF-β2 and GDNF with regard to promotion of survival within the peripheral motor and sensory systems investigated.     

ATP13A2 variants in early‐onset Parkinson's disease patients and controls

Four genes responsible for recessively inherited forms of Parkinson's disease (PD) have been identified, including the recently discovered ATP13A2 (PARK9) gene. Our objective was to investigate the role of this gene in a large cohort of PD patients and controls. We extensively screened all 29 exons of the ATP13A2 coding region in 112 patients with early‐onset PD (EOPD; <40 years) of mostly European ethnic origin and of 55 controls. We identified four carriers (3.6%) of novel single heterozygous ATP13A2 missense changes that were absent in controls. Interestingly, the carrier of one of these variants also harbored two mutations in the Parkin gene. None of the carriers had atypical features previously described in patients with two mutated ATP13A2 alleles (Kufor–Rakeb syndrome). Our data suggest that two mutated ATP13A2 alleles are not a common cause of PD. Although heterozygous variants are present in a considerable number of patients, they are—based on this relatively small sample—not significantly more frequent in patients compared to controls. © 2009 Movement Disorder Society     

The role of perceived parenting in familial aggregation of anxiety disorders in children

This study was designed to explore the role of perceived parenting style in the familial aggregation of anxiety disorders. We examined the association between parental and child anxiety diagnoses, and tested whether this association was partly due to a perceived parenting style. The study was conducted in a clinical sample as well as in a control sample. Parental lifetime and current anxiety diagnoses were significantly associated with child anxiety diagnoses. When maternal and paternal lifetime and current anxiety diagnoses were entered as separate predictors, only maternal current anxiety diagnoses appeared to be significant. Perceived parenting style was assessed with the dimensions "overprotection," "emotional warmth," "rejection," and "anxious rearing." Results indicated that only maternal and paternal 'overprotection' was significantly but negatively associated with child anxiety. However, further analyses showed that 'overprotection' did not have a significant mediating role in the familial aggregation of anxiety disorders.