Elective laparoscopic-assisted colectomy for sigmoid diverticulitis.

OBJECTIVES: The aim of this study was to evaluate the safety and effectiveness of laparoscopic-assisted sigmoid colectomy for diverticulitis and to assess its postoperative advantages. METHODS: From 1999 to 2001, 5 patients were selectively operated on with a laparoscopic-assisted procedure for uncomplicated sigmoid diverticulitis. In the preceding period (September 1997 through December 1998), 4 patients underwent open procedures for the same pathology. The surgical indication with the same criteria was restrictive: at least 2 acute episodes had occurred that were treated with hospital admission and that were separated by an adequate period (2 months) of medical therapy. RESULTS: No conversions of laparoscopy to an open procedure were necessary. Age, sex, weight, morbidity, and mortality were similar between the 2 groups. Operative time was 180 minutes for laparoscopy and 120 minutes for laparotomy. Postoperative resumption of peristalsis was 24 hours versus 4 days, resumption of alimentation was on the second postoperative day versus the fifth postoperative day, and hospital stay was 7 days versus 12 days for laparoscopy and laparotomy, respectively. CONCLUSION: This study shows the feasibility and the advantages of elective laparoscopic-assisted colonic resection for uncomplicated sigmoid diverticulitis. The advantages of the laparoscopic approach are the lower need for analgesics and the more precocious ambulation, canalization, resumption of alimentation, and the shorter hospital stay.     

Severe but temporary injury to rabbit orbicularis oculi muscle using dihematoporphyrin ether and laser photochemomyectomy.

The use of local dihematoporphyrin ether (DHE) injections, followed by laser light activation, was investigated as a potential permanent myectomy treatment for muscle spasms, in particular blepharospasm and hemifacial spasm. DHE was injected into the eyelids of rabbits, followed by laser activation, as used in photochemotherapy. Four days after treatment, histological examination indicated that doses of greater than or equal to 0.5 mg of DHE and laser treatment with an energy density of at least 100 J/cm2 resulted in an almost total destruction of the orbicularis oculi muscle in the treated eyelid. The amount of muscle injury was dependent on both dose of DHE and energy density levels. Histologically, the tarsal glands and conjunctiva were damaged. Glandular tissue was markedly reduced, and the conjunctival epithelium showed hyperplasia and a loss of mucous cells. Six months after DHE and laser treatment, the majority of the muscle tissue had regenerated, although there was evidence of previous injury. While DHE injections combined with laser light activation were lethal to muscle at the site of treatment, this treatment was not permanent. The orbicularis oculi muscle retained its ability to regenerate. However, photochemomyectomy may be studied further as an adjuvant treatment to temporarily injure and debulk large muscles when botulinum toxin is contraindicated due to the large doses involved or as a permanent treatment when used together with an antimitotic agent such as doxorubicin.     

Metabolic expression of intrinsic developmental programs for dentine and enamel biomineralization in serumless,chemically-defined,organotypic culture

Summary Biomineralization was investigated using embryonic mouse mandibular first molars (M₁) cultured in the presence or absence of fetal calf serum. Metabolic features including cell division and Ca²⁺ and phosphate incorporation into dentine and enamel extracellular matrices were analyzed. The relative timing and magnitude of DNA synthesis for serumless cultures was comparable toin vivo controls. Isotopic calcium and phosphate incorporation into the mineral phase of dentine and enamel matrices, in the absence of serum, fluctuated during development. Molar tooth morphogenesis, cytodifferentiation, and extracellular matrix formation approximated late crown-stage development in serumless cultures. Von Kossa histochemical staining indicated calcium phosphate salt formation in serumless cultures. Analysis of anhydrous fixation-prepared enamel and dentine representing serumless cultured explants indicated that crystal size and orientation were comparable toin vivo enamel and dentine. In contrast, serum-supplemented cultures showed atypical crystal size and orientation. Calcium/phosphorous (Ca/P) ratio values for serumless cultures after 21 days showed Ca/P enamel values of 2.03 (SD±0.04, p<0.025) and dentine values of 1.89 (SD±0.01, p<0.025). Electron diffraction patterns of enamel and dentine formed in serumless cultures were principally those of highly-ordered crystalline hydroxyapatite. Our results suggest that tissue-specific dentine and enamel biomineralization is regulated by endogenous factors intrinsic to the developmental program of embryonic tooth organs during serumless culture.     

Degradation of Paclitaxel and Related Compounds in Aqueous Solutions III: Degradation Under Acidic pH Conditions and Overall Kinetics

Paclitaxel and related taxanes are complex molecules with numerous hydrolysable ester groups, possible epimerization at the 7‐position, and possessing a strained oxetane ring, a possible site for acid‐catalyzed cleavage. Presented here is the stability of paclitaxel, 10‐deacetylbaccatin III, baccatin III, and N‐benzoyl‐3‐phenylisoserine ethyl ester in aqueous solution over a pH range of 1–5 at various temperatures. Analysis of various samples was by HPLC–UV and LC–MS. Baccatin III, 10‐deacetylbaccatin III, and N‐benzoyl‐3‐phenylisoserine ethyl ester were found to undergo acid catalysis since pH‐rate profiles all followed a first‐order dependency in hydrogen ion concentration. No evidence of any epimerization was noted at acidic pH values. Baccatin III and 10‐deacetylbaccatin III showed similar degradation rates with possible products being possible dehydration around the 13‐hydroxy group and cleavage of the oxetane ring. Cleavage of the 10‐acetyl group of baccatin III was a minor initial pathway. N‐Benzoyl‐3‐phenylisoserine ethyl ester degraded significantly slower than both 10‐deacetylbaccatin III and baccatin III. At pH 2, paclitaxel degraded at a rate between that of N‐benzoyl‐3‐phenylisoserine ethyl ester and 10‐deacetylbaccatin III. The pH of maximum stability for all compounds appeared to be around pH 4. © 2009 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1288–1298, 2010     

Region of interest issues: the relationship between structure and function in the brain

The comparison of data sets from individual subjects between imaging modalities is necessary in order to evaluate the normal physiologic responses of the brain or the pathophysiological changes that accompany disease states. Similarly, it is critical to compare data between individuals both within and across imaging modalities. In a collaborative project with a number of university groups, we have developed a system that allows for the within-subject alignment and registration of three-dimensional data sets obtained from different modalities for the same individuals. These data make use of proposed criteria for the optimal solution to positron emission tomography image acquisition and analysis originally established through a series of international workshops. The analysis takes into account errors induced by image acquisition, registration, and alignment with regard to scaling, translation, and rotation. Using the principles of morphometrics and homologous landmarks, the between-subject warping of individual brain anatomy to match that of other individuals, groups or an idealized model can be obtained. Resultant information can provide averaged between-subject data for populations of normal individuals or patients with specific neurologic disorders. Such a system, provides the means by which to compare objectively quantitative data between individuals in a highly automated fashion.     

Neural control of fast-regular saccades and antisaccades: an investigation using positron emission tomography

 Regional cerebral blood flow changes related to the performance of two oculomotor tasks and a central fixation task were compared in ten healthy human subjects. The tasks were: (a) performance of fast-regular saccades; (b) performance of voluntary antisaccades away from a peripheral cue; (c) passive maintenance of central visual fixation in the presence of irrelevant peripheral stimulation. The saccadic task was associated with a relative increase in activity in a number of occipitotemporal areas. Compared with both the fixation and the saccadic task, the performance of antisaccades activated a set of areas including: the superior and inferior parietal lobules, the precentral and prefrontal cortex, the cingulate cortex, and the supplementary motor area. The results of the present study suggest that: (a) compared with self-determined saccadic responses the performance of fast regular, reflexive saccades produces a limited activation of the frontal eye fields; (b) in the antisaccadic task the inferior parietal lobes subserve operations of sensory-motor integration dealing with attentional disengagement from the initial peripheral cue (appearing at an invalid spatial location) and with the recomputation of the antisaccadic vector on the basis of the wrong (e.g., spatially opposite) information provided by the same cue. Received: 20 May 1996 / Accepted: 28 January 1997     

Employing a systematic approach to biobanking and analyzing clinical and genetic data for advancing COVID-19 research

Within the GEN-COVID Multicenter Study, biospecimens from more than 1000 SARS-CoV-2 positive individuals have thus far been collected in the GEN-COVID Biobank (GCB). Sample types include whole blood, plasma, serum, leukocytes, and DNA. The GCB links samples to detailed clinical data available in the GEN-COVID Patient Registry (GCPR). It includes hospitalized patients (74.25%), broken down into intubated, treated by CPAP-biPAP, treated with O₂ supplementation, and without respiratory support (9.5%, 18.4%, 31.55% and 14.8, respectively); and non-hospitalized subjects (25.75%), either pauci- or asymptomatic. More than 150 clinical patient-level data fields have been collected and binarized for further statistics according to the organs/systems primarily affected by COVID-19: heart, liver, pancreas, kidney, chemosensors, innate or adaptive immunity, and clotting system. Hierarchical clustering analysis identified five main clinical categories: (1) severe multisystemic failure with either thromboembolic or pancreatic variant; (2) cytokine storm type, either severe with liver involvement or moderate; (3) moderate heart type, either with or without liver damage; (4) moderate multisystemic involvement, either with or without liver damage; (5) mild, either with or without hyposmia. GCB and GCPR are further linked to the GCGDR, which includes data from whole-exome sequencing and high-density SNP genotyping. The data are available for sharing through the Network for Italian Genomes, found within the COVID-19 dedicated section. The study objective is to systematize this comprehensive data collection and begin identifying multi-organ involvement in COVID-19, defining genetic parameters for infection susceptibility within the population, and mapping genetically COVID-19 severity and clinical complexity among patients.Subject terms: Genetics research, Viral infection     

Could mitochondrial haplogroups play a role in sporadic amyotrophic lateral sclerosis?

Mitochondrial impairment has been implicated in the pathogenesis of the amyotrophic lateral sclerosis (ALS). Furthermore, mitochondrial-specific polymorphisms were previously related to other neurodegenerative diseases, such as Parkinson, Friedreich and Alzheimer disease. To investigate if specific genetic polymorphisms within the mitochondrial genome (mtDNA) could act as susceptibility factors and contribute to the clinical expression of sporadic ALS (sALS), we have genotyped predefined European mtDNA haplogroups in 222 Italian patients with sALS and 151 matched controls. Individuals classified as haplogroup I demonstrated a significant decrease in risk of ALS versus individuals carrying the most common haplogroup, H (odds ratio 0.08, 95% confidence interval 0.04-0.4, p < 0.01). Further stratification of the dataset by sex, age and site of onset of disease and survival failed to reach significance for association. Our study provides evidence of the contribution of mitochondrial variation to the risk of ALS development in Caucasians. Further it may help elucidate the mechanism of the mitochondrial dysfunction detectable in ALS, and may be of relevance in development of strategies for the treatment of this disease.