Atrazine induces complete feminization and chemical castration in male African clawed frogs (Xenopus laevis)

The herbicide atrazine is one of the most commonly applied pesticides in the world. As a result, atrazine is the most commonly detected pesticide contaminant of ground, surface, and drinking water. Atrazine is also a potent endocrine disruptor that is active at low, ecologically relevant concentrations. Previous studies showed that atrazine adversely affects amphibian larval development. The present study demonstrates the reproductive consequences of atrazine exposure in adult amphibians. Atrazine-exposed males were both demasculinized (chemically castrated) and completely feminized as adults. Ten percent of the exposed genetic males developed into functional females that copulated with unexposed males and produced viable eggs. Atrazine-exposed males suffered from depressed testosterone, decreased breeding gland size, demasculinized/feminized laryngeal development, suppressed mating behavior, reduced spermatogenesis, and decreased fertility. These data are consistent with effects of atrazine observed in other vertebrate classes. The present findings exemplify the role that atrazine and other endocrine-disrupting pesticides likely play in global amphibian declines.     

Nucleotide excision repair deficiency is intrinsic in sporadic stage I breast cancer

The molecular etiology of breast cancer has proven to be remarkably complex. Most individual oncogenes are disregulated in only approximately 30% of breast tumors, indicating that either very few molecular alterations are common to the majority of breast cancers, or that they have not yet been identified. In striking contrast, we now show that 19 of 19 stage I breast tumors tested with the functional unscheduled DNA synthesis assay exhibited a significant deficiency of DNA nucleotide excision repair (NER) capacity relative to normal epithelial tissue from disease-free controls (n = 23). Loss of DNA repair capacity, including the complex, damage-comprehensive NER pathway, results in genomic instability, a hallmark of carcinogenesis. By microarray analysis, mRNA expression levels for 20 canonical NER genes were reduced in representative tumor samples versus normal. Significant reductions were observed in 19 of these genes analyzed by the more sensitive method of RNase protection. These results were confirmed at the protein level for five NER gene products. Taken together, these data suggest that NER deficiency may play an important role in the etiology of sporadic breast cancer, and that early-stage breast cancer may be intrinsically susceptible to genotoxic chemotherapeutic agents, such as cis-platinum, whose damage is remediated by NER. In addition, reduced NER capacity, or reduced expression of NER genes, could provide a basis for the development of biomarkers for the identification of tumorigenic breast epithelium.     

Prognostic significance of leukopenia at the time of diagnosis in acute myeloid leukemia

We investigated the clinical significance of leukopenia at the time of diagnosis in a cohort of 225 patients with newly diagnosed acute myeloid leukemia (AML) at a single institution. Leukocyte count was treated as a continuous variable and, using a receiver operating characteristic curve (ROC), a cutoff of 3,600/μL had the best sensitivity and specificity for remission (complete remission [CR]), relapse-free survival [RFS], and overall survival [OS]). In a multivariable model, leukopenia at diagnosis had no effects on CR (hazard ratio [HR] = 2.02; confidence interval [CI], 0.9-4.3; P = .07), RFS (HR = 0.93; CI, 0.5-1.5; P = .8), or OS (HR = 1.05; CI, 0.7-1.5; P = .7). No differential expression of cell surface molecules (CD34, c-Kit, CXCR4, PECAM, VLA2, VLA-, VLA4, VLA5, and FLT3) was observed on simultaneously obtained marrow and blood blasts in the high- vs. low-leukocyte groups. We conclude that leukopenia at diagnosis carries no prognostic significance in AML.     

Unsuccessful treatment of a collapsed thoracic stent graft by Palmaz stent

A Gore TAG Excluder stent graft was deployed in a 35-year-old woman for an isthmic saccular aneurysm. At 12-hour follow-up, we diagnosed a proximal collapse. A Palmaz stent was used to reopen the proximal segment. Two months later, she presented with a transient ischemic attack (embolic process) related to a suboptimal apposition of the Palmaz stent in the distal aortic arch. This led to open surgical replacement of the ascending aorta and aortic arch with reimplantation of the supraaortic branches. Reopening of a stent graft collapse with a Palmaz stent might be a short-term solution; however, its presence can lead to embolic complications.     

Is the laparoscopic approach to colectomy safe for the morbidly obese?

Background

The feasibility and safety of laparoscopic colectomy (LC) for morbidly obese patients has not been reported previously. This study aimed to assess the clinical outcomes of patients with a body mass index (BMI) of 40 kg/m³ or more who undergo laparoscopic colorectal surgery.

Methods

Prospectively accrued data for patients with a BMI of 40 kg/m³ or more (group A) who undergo LC were compared with those for patients with BMI lower than 30 kg/m³ (group B) matched for year of surgery, indication, operating surgeon, and type of procedure.

Results

Each group had 36 patients. The group A patients were significantly younger (54 vs. 61 years; P = 0.04), had higher American Society of Anesthesiology (ASA) scores (P = 0.001), and had diabetes mellitus (P = 0.04). The indications for surgery and the operations performed were similar. The two groups had similar operating times (177.9 vs. 136.4 min; P = 0.12), estimated blood losses (222.3 vs. 157 ml; P = 0.1), median lengths of hospital stay (LOS) (4.5 vs. 4 days; P = 0.2), and returns of bowel function (4.2 vs. 3.9 days; P = 0.45). Group A had significantly longer incisions (6.9 vs. 5 cm; P = 0.02). Conversions (5 vs. 3 patients; P = 0.7), readmissions (12 vs. 6 patients; P = 0.46), reoperations (5 vs. 3 patients; P = 0.17), wound infections (7 vs. 2 patients; P = 0.14), anastomotic leaks (3 vs. 2 patients; P = 0.7), and abdominal abscesses (3 vs. 2 patients; P = 0.7) were more predominant in group A, although the differences did not reach statistical significance.

Conclusions

Laparoscopic colectomy is feasible for morbidly obese patients and results in recovery of intestinal function and LOS equivalent to that for nonobese patients. As expected, morbidity and conversion rates are higher for morbidly obese patients undergoing LC than for nonobese patients.     

Intravenous immunoglobulin therapy in intractable childhood epilepsy: Open-label study and review of the literature

Our aim was to investigate the long term effectiveness of intravenous immunoglobulin (IVIG) against intractable childhood epilepsy in the era of new antiepileptics and to determine the predictors of a favorable response in a prospective open-label add-on study. Of thirty-seven 9.9 ± 0.9-year-old patients (11 with partial seizures, 26 with generalized seizures of whom 9 had West syndrome and 17 Lennox–Gastaut syndrome) followed for 15 ± 3 months, 43% had a >50% decrease in seizures (including 15% seizure free, 229 ± 58 compared with 104 ± 3 seizures/month, P = 0.035: generalized 246 ± 318 to 117 ± 200, P = 0.025, partial 191 ± 437 to 72 ± 179, P > 0.05; power = 0.2). Males were more likely to respond than females (P = 0.011, odds ratio = 9.3). Review of the literature revealed nine other articles reporting efficacy of IVIG against epileptic seizures. Only one other used statistical methods and, unlike ours, showed only a trend toward seizure frequency reduction without achieving statistical significance, presumably because it was underpowered. These results indicate large-scale controlled studies of IVIG in epilepsy are still needed.     

Improving on-time surgical starts in an operating room

Background

Operating rooms are expensive to run, and hospitals strive to be efficient. The purpose of this study was to evaluate an initiative to improve starting on time in the operating room in an academic pediatric hospital.

Methods

We used an 8-step approach to transforming an organization. A multidisciplinary team defined on-time starts, identified reasons for delays and instituted changes, including improving the same-day admission process, instituting a huddle of operating room staff each morning and providing feedback about on-time starts to staff.

Results

The most common reasons for delay were surgeon and anesthesiologist unavailability and lack of preparedness of patients. The percentage of operations that began on time, defined as the patient being in the room, increased from about 6% to 60% over a 9-month period.

Conclusion

A targeted, multifaceted and multidisciplinary approach can increase the percentage of operations that begin on time in a pediatric hospital.