The efficacy of the ketogenic diet-1998: a prospective evaluation of intervention in 150 children

OBJECTIVE: The ketogenic diet is a high-fat, low-protein, low-carbohydrate diet developed in the 1920s for the treatment of children with difficult to control seizures. Despite advances in both the pharmacotherapy and the surgery of epilepsy, many children continue to have difficult-to-control seizures. This prospective study sought to determine the ketogenic diet's effectiveness and tolerability in children refractory to today's medications. METHODS: One hundred fifty consecutive children, ages 1 to 16 years, virtually all of whom continued to have more than two seizures per week despite adequate therapy with at least two anticonvulsant medications, were prospectively enrolled in this study, treated with the ketogenic diet, and followed for a minimum of 1 year. Seizure frequency was tabulated from patients' daily seizure calendars and seizure reduction calculated as percentage of baseline frequency. Adverse events and reasons for diet discontinuation were recorded. RESULTS: The children (mean age, 5.3 years), averaged 410 seizures per month before the diet, despite an exposure to a mean of 6.2 antiepileptic medications. Three months after diet initiation, 83% of those starting remained on the diet and 34% had >90% decrease in seizures. At 6 months, 71% still remained on the diet and 32% had a >90% decrease in seizures. At 1 year, 55% remained on the diet and 27% had a >90% decrease in seizure frequency. Most of those discontinuing the diet did so because it was either insufficiently effective or too restrictive. Seven percent stopped because of intercurrent illness. CONCLUSIONS: The ketogenic diet should be considered as alternative therapy for children with difficult-to-control seizures. It is more effective than many of the new anticonvulsant medications and is well tolerated by children and families when it is effective.     

CT-Based Needle Marking of Superficial Intracranial Lesions for Minimal Invasive Neurosurgery

A CT-based method of marking superficial intracranial lesions with a needle is presented. This form of neuronavigation can be applied in every neurosurgical centre. Owing to its rapid application it is also suitable for cases of emergency. The neurosurgical approach can be centred precisely over the lesion providing for a minimally invasive operation. The method has proved its efficacy in numerous cases of haematomas and cystic lesions.     

Immunotherapy of metastatic renal cell carcinoma with tumor lysate-pulsed autologous dendritic cells.

PURPOSE: We wanted to evaluate feasibility and safety of dendritic cell-based immunotherapy in patients with metastatic renal cell carcinoma (RCC). EXPERIMENTAL DESIGN: Patients with metastatic RCC (n = 35) received vaccinations (i.v. or i.d.) of CD83+ autologous monocyte-derived dendritic cells (moDCs). MoDCs were loaded with lysate of cultured autologous or allogeneic permanent tumor cells (A-498) as well as keyhole limpet hemocyanin as control and helper antigen. Maturation of moDCs was induced by a combination of tumor necrosis factor alpha, interleukin 1 beta, interleukin 6, and prostaglandin E2. RESULTS: Treatment was associated with transient flu-like symptoms. In 2 of 27 evaluable patients, any evidence of disease disappeared (complete response). In both cases, metastatic tissue had been the source of tumor antigen. One patient had an objective partial response. Seven patients had stable disease, the remaining 17 patients had progressive disease. In 11 of 11 patients evaluated, moDCs induced strong immune responses against keyhole limpet hemocyanin. In 5 of 6 patients tested, enhanced immune responses against oncofetal antigen (immature laminin receptor; OFA/LRP) could also be detected. The strongest responses against OFA/LRP were detectable in 2 patients with complete response and partial response, respectively. At the time of submission, mean follow up is 32 months and 8 patients are currently alive. CONCLUSIONS: Our data indicate that moDC-based vaccination is well tolerated and has immunological as well as clinical effects in patients with metastatic RCC. OFA/LRP might be an attractive candidate antigen for DC-based immunotherapy of RCC.     

TP53 mutation and survival in aggressive B cell lymphoma

TP53 is mutated in 20–25% of aggressive B‐cell lymphoma (B‐NHL). To date, no studies have addressed the impact of TP53 mutations in prospective clinical trial cohorts. To evaluate the impact of TP53 mutation to current risk models in aggressive B‐NHL, we investigated TP53 gene mutations within the RICOVER‐60 trial. Of 1,222 elderly patients (aged 61–80 years) enrolled in the study and randomized to six or eight cycles of CHOP‐14 with or without Rituximab (NCT00052936), 265 patients were analyzed for TP53 mutations. TP53 mutations were demonstrated in 63 of 265 patients (23.8%). TP53 mutation was associated with higher LDH (65% vs. 37%; p < 0.001), higher international prognostic index‐Scores (IPI 4/5 27% vs. 12%; p = 0.025) and B‐symptoms (41% vs. 24%; p = 0.011). Patients with TP53 mutation were less likely to obtain a complete remission CR/CRu (CR unconfirmed) 61.9% (mut) vs. 79.7% (wt) (p = 0.007). TP53 mutations were associated with decreased event‐free (EFS), progression‐free (PFS) and overall survival (OS) (median observation time of 40.2 months): the 3 year EFS, PFS and OS were 42% (vs. 60%; p = 0.012), 42% (vs. 67.5%; p < 0.001) and 50% (vs. 76%; p < 0.001) for the TP53 mutation group. In a Cox proportional hazard analysis adjusting for IPI‐factors and treatment arms, TP53 mutation was shown to be an independent predictor of EFS (HR 1.5), PFS (HR 2.0) and OS (HR 2.3; p < 0.001). TP53 mutations are independent predictors of survival in untreated patients with aggressive CD20+ lymphoma. TP53 mutations should be considered for risk models in DLBCL and strategies to improve outcome for patients with mutant TP53 must be developed.     

Copper Iodide on Spacer Fabrics as Textile Thermoelectric Device for Energy Generation

The integration of electronic functionalities into textiles for use as wearable sensors, energy harvesters, or coolers has become increasingly important in recent years. A special focus is on efficient thermoelectric materials. Copper iodide as a p-type thermoelectrically active, nontoxic material is attractive for energy harvesting and energy generation because of its transparency and possible high-power factor. The deposition of CuI on polyester spacer fabrics by wet chemical processes represents a great potential for use in textile industry for example as flexible thermoelectric energy generators in the leisure or industrial sector as well as in medical technologies. The deposited material on polyester yarn is investigated by electron microscopy, x-ray diffraction and by thermoelectric measurements. The Seebeck coefficient was observed between 112 and 153 µV/K in a temperature range between 30 °C and 90 °C. It is demonstrated that the maximum output power reached 99 nW at temperature difference of 65.5 K with respect to room temperature for a single textile element. However, several elements can be connected in series and the output power can be linear upscaled. Thus, CuI coated on 3D spacer fabrics can be attractive to fabricate thermoelectric devices especially in the lower temperature range for textile medical or leisure applications.     

Altered Regulation of mRNA and miRNA Expression in Epithelial and Stromal Tissue of Keratoconus Corneas

PurposeEvaluation of mRNA and microRNA (miRNA) expression in epithelium and stroma of patients with keratoconus.MethodsThe epithelium and stroma of eight corneas of eight patients with keratoconus and eight corneas of eight non-keratoconus healthy controls were studied separately. RNA was extracted, and mRNA and miRNA analyses were performed using microarrays. Differentially expressed mRNAs and miRNAs in epithelial and stromal keratoconus samples compared to healthy controls were identified. Selected genes and miRNAs were further validated using RT-qPCR.ResultsWe discovered 170 epithelial and 1498 stromal deregulated protein-coding mRNAs in KC samples. In addition, in epithelial samples 180 miRNAs and in stromal samples 379 miRNAs were significantly deregulated more than twofold compared to controls. Pathway analysis revealed enrichment of metabolic and axon guidance pathways for epithelial cells and enrichment of metabolic, mitogen-activated protein kinase (MAPK), and focal adhesion pathways for stromal cells.ConclusionsThis study demonstrates significant differences in the expression and regulation of mRNAs and miRNAs in the epithelium and stroma of Patients with KC. Also, in addition to the well-known target candidates, we were able to identify further genes and miRNAs that may be associated with keratoconus. Signaling pathways influencing metabolic changes and cell contacts are affected in epithelial and stromal cells of patients with keratoconus.     

Stent implantation and balloon angioplasty for treatment of branch pulmonary artery stenosis in children

OBJECTIVES: Comparison of the results of branch pulmonary artery stenosis treated with balloon angioplasty (BA) or stent implantation (SI) in children. BACKGROUND: Branch pulmonary artery stenosis may be treated with BA or SI. METHODS: We compared the results of 147 interventions of branch pulmonary artery stenosis in 87 children (median age 3.6 years). Patients were treated during 1989-2000 with BA and during 2001-2004 with SI. Primary endpoints were acute complications and reintervention during follow up. Secondary variables were age, vessel diameter increase, acute success rate, balloon/vessel diameter ratio, pulmonary artery hypoplasia indices, and procedure related factors. RESULTS: The acute vessel diameter increase with BA (4.31 +/- 1.98 vs. 7.15 +/- 2.31 mm) and SI (3.71 +/- 1.58 vs. 6.97 +/- 2.68 mm) was significant within both groups (P < 0.001), but not between both groups. The reintervention rate was comparable between both groups, but median time to reintervention was shorter after SI in infants compared to BA. The balloon/vessel diameter ratio was on average higher in BA than the stent/vessel diameter ratio in SI (3.49 +/- 2.16 vs. 2.42 +/- 0.56; P < 0.05) and was a significant risk factor (P < 0.01) for the higher complication rate after BA (BA: 14.1% vs. SI: 4.8%). No mortality occurred in both groups. CONCLUSION: BA and SI are safe interventional catheter therapies of branch pulmonary artery stenosis. The immediate results of BA and SI are comparable. The higher complication rate after BA, especially in infants, was associated with a higher balloon/vessel diameter ratio. SI seems to be a safe permanent alternative with foreign material, but requires more reinterventions in infants due to its therapeutic strategy.     

INFLUENCE OF pH AND OF CERTAIN OTHER CONDITIONS ON THE STABILITY OF THE INFECTIVITY AND RED CELL AGGLUTINATING ACTIVITY OF INFLUENZA VIRUS

A study has been made of the pH stability of centrifugally purified strains of influenza virus with respect to the biological properties of mouse infectivity and chicken red blood cell agglutinating activity. Observations also were made on the importance of composition of buffer, temperature of storage, and concentration of virus protein to the stability of the virus. When tested for stability at a protein concentration of 0.1 mg. per cc. in phosphate buffer, the infectivity of PR8 virus was found to be most stable at pH 6.5–7; the swine virus, at pH 7–7.9; and the Lee strain, at a pH of 7.9 or higher. The CCA activity of the PR8 virus in phosphate buffer was most stable at pH 7, that of the swine virus at pH 7–8, and that of the Lee virus at a pH greater than 9. Furthermore, the Lee virus was much less stable in dilute solution in phosphate buffer, even under optimum conditions of pH, than either the PR8 or swine strains. The different strains of influenza virus were found to possess certain characteristics in common. They lost infectivity and CCA activity on the acid side of optimum pH conditions much more rapidly than on the alkaline side. Under suitable conditions of buffer and pH, the infectivity decreased while the CCA activity remained unchanged. In general, the rate of loss in infectivity was greater than the rate of loss in CCA activity. When tests of stability were carried out at a protein concentration of 0.1 mg. per cc. in a composite phosphate-glycine-NaCl buffer, the virus strains showed less marked differences and possessed much higher stabilities of CCA activity and infectivity than when stored at the same concentration in phosphate buffer alone. Under the modified conditions, all three viruses possessed maximum stabilities of CCA activity and infectivity at pH 7–8 with the exception of the PR8 virus whose infectivity appeared more stable at pH 7 than at pH 8. In detailed experiments with the Lee virus, it was found that the infectivity and CCA activity of this strain at pH 7 and at a protein concentration of 0.1 mg. per cc. were maintained best in the composite phosphate-glycine-NaCl buffer, less well in a buffer containing glycine and NaCl, and least well in phosphate buffer alone. In tests with PR8 virus, the activity was found to be much more stable at 4° C. than at 23° C. When stored at a concentration of 2 mg. per cc. at 4° C. in phosphate buffer at pH 7, the PR8 and Lee strains were found to be much more stable than when stored at the concentration of 0.1 mg. per cc. At the higher concentration, no significant losses in either infectivity or CCA activity were observed over a period of 2 months.