A systematic approach for identifying and presenting mechanistic evidence in human health assessments

Clear documentation of literature search and presentation methodologies can improve transparency in chemical hazard assessments. We sought to improve clarity for the scientific support for cancer mechanisms of action using a systematic approach to literature retrieval, selection, and presentation of studies. The general question was “What are the mechanisms by which a chemical may cause carcinogenicity in the target tissue?”. Di(2-ethylhexyl)phthalate was used as a case study chemical with a complex database of >3000 publications. Relevant mechanistic events were identified from published reviews. The PubMed search strategy included relevant synonyms and wildcards for DEHP and its metabolites, mechanistic events, and species of interest. Tiered exclusion/inclusion criteria for study pertinence were defined, and applied to the retrieved literature. Manual curation was conducted for mechanistic events with large literature databases. Literature trees documented identification and selection of the literature evidence. The selected studies were summarized in evidence tables accompanied by succinct narratives. Primary publications were deposited into the Health and Environmental Research Online (http://hero.epa.gov/) database and identified by pertinence criteria and key terms to permit organized retrieval. This approach contributes to human health assessment by effectively managing a large volume of literature, improving transparency, and facilitating subsequent synthesis of information across studies.     

Suprapubic Cystotomy

Suprapubic cystotomy is a simple but practical means of bladder drainage in the postoperative gynecologic surgical patient. The two technics described here are open direct cystotomy in the abdominal procedure and blind transabdominal cystotomy in the vaginal procedure. These approaches reduce morbidity, use of sedation, need for antibiotics, postoperative nursing care, and hospitalization time.     

Lymph node non-Hodgkin's lymphoma incidentally discovered during a nephrectomy for renal cell carcinoma

We report the case of a left laparoscopic nephroureterectomy with the incidental discovery of a non-Hodgkin’s lymphoma in one of the lymph nodes of the renal hilum. A laparoscopic nephroureterectomy was decided on for a 64-year-old man. Renal cell carcinoma in the kidney and one lymph node of the renal hilum with non-Hodgkin’s lymphoma was found. Chemotherapy was not started for the lymphoma discovery. There are no signs of relapse after two years of follow up. Coexistence in the same patient is an extremely rare condition. We review the literature about this issue to clarify this association.     

Reduced stem cell mobilization in mice receiving antibiotic modulation of the intestinal flora: involvement of endotoxins as cofactors in mobilization

Since endotoxins are potent inducers of stem cell mobilization, we hypothesized that their presence in the gut may play a role in cytokine-induced mobilization. To address this possibility we added ciprofloxacin and polymyxin B to the drinking water of Balb/c mice mobilized with either interleukin-8 (IL-8), granulocyte colony-stimulating factor (G-CSF), or flt3 ligand (FL). The yield of colony-forming units (CFUs) was significantly reduced in all mice treated with these antibiotics when compared with controls (IL-8: 192 +/- 61 vs 290 +/- 64, P <.05; G-CSF: 1925 +/- 1216 vs 3371 +/- 1214, P <.05; FL: 562 +/- 213 vs 1068 +/- 528, P <.05). Treatment with ciprofloxacin eliminated only aerobic Gram-negative bacteria from the feces without effect on mobilization. Polymyxin B treatment did not result in decontamination but significantly reduced the number of mobilized hematopoietic progenitor cells (HPCs) most likely due to the endotoxin binding capacity of polymyxin B. More than 90% of the gastrointestinal flora consists of anaerobic bacteria. Elimination of the anaerobic flora by metronidazol led to a significantly reduced number of mobilized HPCs when compared with controls (IL-8: 55 +/- 66 vs 538 +/- 216, P <.05). Germ-free OF1 mice showed a significantly reduced mobilization compared with their wild-type controls (IL-8 controls: 378 +/- 182, IL-8 germ free: 157 +/- 53, P <.05). Finally, we performed reconstitution experiments adding Escherichia coli-derived endotoxins to the drinking water of decontaminated mice. This resulted in partial restoration of the IL-8-induced mobilization (67 +/- 28 vs 190 +/- 98.1, P <.01). Our results indicate that endotoxins serve as cofactors in cytokine-induced mobilization. Modification of the endotoxin content by antibiotic treatment may affect the yield of cytokine-induced mobilization.     

The influence of oxygen therapy on the hypercapnia in patients with chronic obstructive pulmonary disease

BACKGROUND/AIM: Oxygen therapy is a necessary therapeutic method in treatment of severe chronic respiratory failure (CRF), especially in phases of acute worsening. Risks which are to be taken into consideration during this therapy are: unpredictable increase of carbon dioxide in blood, carbonarcosis, respiratory acidosis and coma. The aim of this study was to show the influence of oxygen therapy on changes of arterial blood carbon dioxide partial pressure. METHODS: The study included 93 patients in 104 admittances to the hospital due to acute exacerbation of CFR. The majority of the patients (89.4%) had chronic obstructive pulmonary disease (COPD), while other causes of respiratory failure were less common. The effect of oxygenation was controlled through measurement of PaO2 and PaCO2 in arterial blood samples. To analyse the influence of oxygen therapy on levels of carbon dioxide, greatest values of change of PaO2 and PaCO2 values from these measurements, including corresponding PaO2 values from the same blood analysis were taken. RESULTS: The obtained results show that oxygen therapy led to the increase of PaO2 but also to the increase of PaCO2. The average increase of PaO2 for the whole group of patients was 2.42 kPa, and the average increase of PaCO2 was 1.69 kPa. There was no correlation between the initial values of PaO2 and PaCO2 and changes of PaCO2 during the oxygen therapy. Also, no correlation between the produced increase in PaO2 and change in PaCO2 during this therapy was found. CONCLUSION: Controlled oxygen therapy in patients with severe respiratory failure greately reduces the risk of unwanted increase of PaCO2, but does not exclude it completely. The initial values of PaO2 and PaCO2 are not reliable parameters which could predict the response to oxygen therapy.     

Imaging considerations in intraductal papillary mucinous neoplasms of the pancreas

With the widespread use of cross-sectional imaging, particularly computed tomography (CT) and magnetic resonance imaging (MRI), and the continuous improvement in the image quality of these techniques, the diagnosis of incidental pancreatic cysts has increased dramatically in the last decades. While the vast majority of these cysts are not clinically relevant, a small percentage of them will evolve into an invasive malignant tumor making their management challenging. Mucinous cystic neoplasms and intraductal papillary mucinous neoplasms (IPMN) are the most common pancreatic cystic lesions with malignant potential. Imaging findings on CT and MRI correlate tightly with the presence of malignant degeneration in these neoplasms. IPMN can be classified based on their distribution as main duct, branch duct or mixed type lesions. MRI is superior to CT in demonstrating the communication of a branch duct IPMN with the main pancreatic duct (MPD). Most branch duct lesions are benign whereas tumors involving the MPD are frequently associated with malignancy. The presence of solid nodules, thick enhancing walls and/or septae, a wide (> 1 cm) connection of a side-branch lesion with the MPD and the size of the tumor > 3 cm are indicative of malignancy in a branch and mixed type IPMN. A main pancreatic duct > 6 mm, a mural nodule > 3 mm and an abnormal attenuating area in the adjacent pancreatic parenchyma on CT correlates with malignant disease in main duct and mixed type IPMN. An accurate characterization of these neoplasms by imaging is thus crucial for selecting the best management options. In this article, we review the imaging findings of IPMN including imaging predictors of malignancy and surgical resectability. We also discuss follow-up strategies for patients with surgically resected IPMN and patients with incidental pancreatic cysts.     

Magnetic resonance spectroscopy of the thalamus in patients with typical absence epilepsy.

PURPOSE: To investigate possible neuronal dysfunction of the thalamus in patients suffering from typical absence epilepsy, using magnetic resonance spectroscopy (MRS). Special attention was paid to levels of N-acetylaspartate (NAA) and creatine (Cr), and to the NAA/Cr ratio. METHODS: MRS was performed over the right and left thalamus in nine patients suffering from typical absence epilepsy, and in nine sex- and age-matched healthy controls. All patients and controls were examined using a standard MRS-CSI (chemical shift imaging) technique. RESULTS: Statistical analysis of the obtained data demonstrated a significantly lower thalamic NAA/Cr ratio in patients with typical absence epilepsy when compared to the healthy controls. Our MRS data showed symmetrical distribution of NAA/Cr ratio in the right and left thalamus within both the patient group and the group of healthy controls. No significant correlation between the patients' thalamic NAA/Cr values and the duration of the epilepsy or seizure frequency was revealed. CONCLUSIONS: The present MRS data clearly indicate neuronal dysfunction in the thalami of patients with typical absence epilepsy. In agreement with other recent MRS findings in different idiopathic generalized epilepsy syndromes, our results confirm the role of the thalamus as an important structure in the pathogenesis of typical absence epilepsy.