High-fat diets and seizure control in myoclonic-astatic epilepsy: a single center's experience.

PURPOSE: To determine the efficacy of the Modified Atkins Diet (MAD) and Ketogenic Diet (KD) in seizure control within a population of myoclonic-astatic epilepsy (MAE) patients. METHODS: This was a retrospective, single center study evaluating the seizure control by high fat diets. Seizure diaries kept by the parents performed seizure counts. All patients met the clinical criteria for MAE. RESULTS: Nine patients met the clinical criteria. We found that both the MAD and KD were efficacious in complete seizure control and allowed other medications to be stopped in seven patients. Two patients had greater than 90% seizure control without medications, one on the KD and the other on the MAD. Seizure freedom has ranged from 13 to 36 months, and during this time four patients have been fully weaned off of diet management. One patient was found to have a mutation in SLC2A1. CONCLUSION: Our results suggest that strictly defined MAE patients respond to the MAD with prolonged seizure control. Some patients may require the KD for seizure freedom, suggesting a common pathway of increased requirement for fats. Once controlled, those fully responsive to the Diet(s) could be weaned off traditional seizure medications and in many, subsequently off the MAD or KD.

Detection of inducible clindamycin resistance in beta-hemolytic streptococci by using the CLSI broth microdilution test and erythromycin-clindamycin combinations.

This study assessed an erythromycin-clindamycin (ERY-CC) broth test for inducible CC resistance in beta-hemolytic streptococci. One hundred one isolates of groups A, B, C, F, and G were tested by the CLSI broth microdilution method. Combinations of 1 and 0.25 microg/ml or 0.5 and 0.25 microg/ml of ERY and CC, respectively, detected all inducible isolates.

A noninvasive renal fungus ball caused by Rhizopus--a previously unreported manifestation of zygomycosis.

We describe the first reported case of renal zygomycosis presenting as an isolated fungus ball (bezoar) without renal parenchymal invasion. Since all previous descriptions of renal involvement have discussed tissue invasion, our case is unique in that the infection was confined solely in the renal pelvis and extended to the distal ureter without signs of contiguous renal infection. Our patient later developed renal insufficiency while receiving amphotericin B Lipid Complex (ABLC). The therapy was changed to posaconazole with subsequent clinical, mycologic, and radiographic improvement and the patient has remained free of recurrence 5 years after diagnosis.

Clinical predictors and risk factors for relapsing Clostridium difficile infection.

BACKGROUND: Clostridium difficile infection (CDI) is a common cause of morbidity among hospitalized patients. Multiple factors have been associated with primary CDI, but risk factors for CDI relapses are less well described. METHODS: This was a retrospective cohort study of patients with CDI over a 15-month period. We compared patients with relapsing and nonrelapsing CDI, including risk factors associated with primary CDI and other variables hypothesized to be associated with relapsing CDI and 90-day mortality. Multivariable logistic regression models were created to examine risk factors for relapse and 90-day mortality. RESULTS: One hundred twenty-nine consecutive patients with CDI were included; 38 (29%) had relapsing CDI. Factors associated with relapsing CDI included fluoroquinolone use (71% versus 49%, P = 0.04) and incidence of stroke (29% versus 12%, P = 0.02). In a regression model, use of a fluoroquinolone was associated with relapsing CDI (OR = 2.52, 95% CI = 1.11-5.72). Factors associated with 90-day mortality included higher Charlson comorbidity index score (4.34 +/- 1.71 versus 3.42 +/- 2.08, P = 0.02), severe CDI (58% versus 32%, P = 0.01), and the use of piperacillin/tazobactam (45% versus 23%, P = 0.03) or meropenem (10% versus 1%, P = 0.04). In the regression analysis, 90-day mortality was associated with severe CDI (OR = 1.76; 95% CI = 1.19-2.59). CONCLUSION: Fluoroquinolone use and prior stroke are associated with an increased risk of relapsing CDI. Relapsing CDI and severe CDI are both associated with increased 90-day mortality.

Moraxella lacunata septic arthritis in a patient with lupus nephritis.

Moraxella lacunata is a rare, usually commensal gram-negative rod most commonly associated with eye infections. We report a unique case of noniatrogenic M. lacunata bacteremia and septic knee arthritis in a patient with class III-IV lupus nephritis and speculate on the association between invasive Moraxella infection and renal impairment.

Practical outcomes of applying ensemble machine learning classifiers to High-Throughput Screening (HTS) data analysis and screening.

Over the years numerous papers have presented the effectiveness of various machine learning methods in analyzing drug discovery biological screening data. The predictive performance of models developed using these methods has traditionally been evaluated by assessing performance of the developed models against a portion of the data randomly selected for holdout. It has been our experience that such assessments, while widely practiced, result in an optimistic assessment. This paper describes the development of a series of ensemble-based decision tree models, shares our experience at various stages in the model development process, and presents the impact of such models when they are applied to vendor offerings and the forecasted compounds are acquired and screened in the relevant assays. We have seen that well developed models can significantly increase the hit-rates observed in HTS campaigns.

Comparative study of machine-learning and chemometric tools for analysis of in-vivo high-throughput screening data.

High-throughput screening (HTS) has become a central tool of many pharmaceutical and crop-protection discovery operations. If HTS screening is carried out at the level of the intact organism, as is commonly done in crop protection, this strategy has the potential of uncovering a completely new mechanism of actions. The challenge in running a cost-effective HTS operation is to identify ways in which to improve the overall success rate in discovering new biologically active compounds. To this end, we describe our efforts directed at making full use of the data stream arising from HTS. This paper describes a comparative study in which several machine learning and chemometric methodologies were used to develop classifiers on the same data sets derived from in vivo HTS campaigns and their predictive performances compared in terms of false negative and false positive error profiles.

Recent advances in the treatment of infections due to resistant Staphylococcus aureus.

PURPOSE OF REVIEW: This paper reviews recent data on the treatment of infections caused by drug-resistant Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA). This review will focus on new findings reported in the English-language medical literature from June 2003 to September 2004. RECENT FINDINGS: Despite the emergence of resistant and multidrug-resistant S. aureus, we have three effective drugs in clinical use for which little resistance has been observed: quinupristin-dalfopristin, linezolid, and daptomycin. Linezolid looks particularly promising in the treatment of MRSA pneumonia. Daptomycin displays rapid bactericidal activity in vitro, but, so far, clinical trials have only been conducted for the treatment of skin and soft-tissue infections. There are three drugs with broad-spectrum activity against Gram-positive organisms at an advanced stage of testing: two new glycopeptides with potent bacteriocidal activity and long half-lives (oritavancin and dalbavancin), and tigecycline, a minocycline derivative. These drugs have also shown efficacy in the treatment of skin and soft-tissue infections. SUMMARY: The promising data that have emerged in the last year indicate that we may have six available drugs to treat resistant S. aureus infections within the next few years. The next goal is to determine the appropriate indications and cost-effectiveness of each of these drugs in our treatment strategy against S. aureus and other Gram-positive pathogens.

Cell proliferation and apoptosis are altered in mice deficient in the NF-kappaB p50 subunit after treatment with the peroxisome proliferator ciprofibrate.

We previously showed that the peroxisome proliferator ciprofibrate increases hepatic NF-kappaB DNA binding activity in rats, mice, and hepatoma cell lines. Here, we analyzed the response to ciprofibrate in mice that lack the NF-kappaB p50 gene (p50-/-). Wild-type and p50-/- mice were fed a diet with or without 0.01% ciprofibrate for 10 days. NF-kappaB DNA binding activity was present and increased after ciprofibrate treatment in wild-type mice, but was not detected in p50-/- mice. The untreated p50-/- mice had a higher level of hepatic cell proliferation, as measured by BrdU labeling, than did untreated wild-type mice. However, the increase in proliferation was greater in ciprofibrate-fed wild-type mice than in ciprofibrate-fed p50-/- mice. The apoptotic index was low in wild-type mice in the presence or absence of ciprofibrate. Apoptosis was increased in untreated p50-/- mice compared to wild-type mice; apoptosis was reduced in p50-/- mice after ciprofibrate feeding. The c-Jun and JunB mRNA levels were higher in untreated p50-/- mice than in untreated control mice; c-Jun mRNA levels increased, whereas JunB mRNA levels decreased in both groups after ciprofibrate treatment. The c-Jun and JunB protein levels were the same in untreated wild-type and p50-/- mice and increased in both groups after ciprofibrate treatment. Several apoptosis-related mRNAs were higher in untreated p50-/- mice compared to untreated control mice; expression of these genes increased in both groups after ciprofibrate treatment. These data indicate that NF-kappaB contributes to the proliferative and apoptotic changes that occur in the liver in response to ciprofibrate.