Truncated NF2 proteins are not detected in meningiomas and schwannomas

Neurofibromatosis type 2 is caused by mutations in the NF2 tumor suppressor gene. The NF2 gene encodes a 595‐aminoacid protein, presumably functioning as a membrane‐organizing element. Theoretically, the majority of mutations found in the NF2 gene should lead to a truncated protein product. Using immunoprecipitation with an antibody raised to N‐terminal sequences of the NF2 protein, the authors sought to demonstrate the presence of truncated NF2 proteins in tumors. From 17 of 19 tumors (14 meningiomas and five schwannomas), 12 of which have previously been shown to harbor truncating NF2 mutations, wild‐type NF2 protein was immunopreci‐pitated. From two tumors no protein was precipitated. Truncated NF2 proteins were not observed. The authors conclude that mutant NF2 proteins are unstable and undergo accelerated degradation.     

Intriguing issues of EGFR targeting in head and neck cancer

We have read the recent comprehensive review by Cruz et al.[1] regarding the targeting of receptor tyrosine kinases andtheir therapeutic perspectives in head and neck squamous cellcarcinomas (HNSCC). The major focus of this report was epidermalgrowth factor receptor (EGFR) biology and targeting. However,we feel     

Photomechanical delivery of 100-nm microspheres through the stratum corneum: implications for transdermal drug delivery

BACKGROUND AND OBJECTIVES: Photomechanical waves (PWs) render the stratum corneum permeable and allow molecules to diffuse into the epidermis. The aim of this study was to investigate the probe size that could be delivered through the stratum corneum and into the epidermis. STUDY DESIGN/MATERIALS AND METHODS: A single PW was applied onto the rat skin in vivo. Aqueous suspensions of fluorescent microspheres, 100 nm in diameter, were used as probes for transdermal delivery. The presence of the microspheres in the epidermis was measured by a fiber-based spectrofluorimeter after the stratum corneum was removed by tape-stripping (TS). RESULTS: Exposure of the rat skin to a PW permeabilized the stratum corneum and allowed the fluorescent microspheres to diffuse into the epidermis. CONCLUSIONS: The experiments show that PWs can facilitate the delivery of very large molecules and probes into the epidermis.     

Right heart pressure determination by Doppler in infants with tricuspid regurgitation

Doppler and direct measurements of right ventricle to right atrial pressure drop were made during cardiac catheterisation on 28 occasions in 26 infants with congenital heart disease. Age was 10 days to 12 months (median 4.5 months), and weight was 3.1 to 9.0 kg (median 4.7 kg). We measured peak velocity of tricuspid regurgitation by continuous wave Doppler, and the pressure drop was calculated using the modified Bernoulli equation (delta p = 4v2). There was a high correlation (r = 0.95) between direct and Doppler measurements. Doppler values tended to underestimate the right ventricle to right atrial pressure drop, but this was not of clinical significance (mean 2 mm Hg). The 95% confidence interval for the Doppler velocity was -0.41 to +0.26 m/sec, and was consistent across the range of pressures studied. Variability between observers was tested, by two observers performing sequential paired examinations on 16 newborn babies with tricuspid regurgitation. The coefficient of repeatability was 6.3 mm Hg (95% confidence interval 4.7 to 9.5 mm Hg) or 0.26 m/sec (0.18 to 0.50 m/sec). This method of right ventricular pressure estimation, validated previously only in older children and adults, is a reproducible and accurate technique in infants with tricuspid regurgitation.     

Diagnostic and clinical implications of lineage fidelity in acute leukemia patients undergoing allogeneic stem cell transplantation

We report on a series of five acute leukemia patients who have undergone allogeneic bone marrow transplantation. Initially, these patients were classified as having biphenotypic leukemia; however, subsequent developments in the perception of what constitutes lineage fidelity has resulted in controversy regarding the diagnosis. Flow cytometry and non-random cytogenetic results have had a major impact on redefining the concept of biphenotypic disease. In this report we review the diagnostic dilemma associated with defining acute leukemia lineage fidelity as diagnostic techniques evolve. While our unique focus on the treatment of biphenotypic leukemia patients represents a small population, we verify the single most promising therapy where otherwise the diagnosis is dismal.     

Failure of ablation of a mediastinal parathyroid adenoma by repeated contrast staining

In a patient with primary hyperparathyroidism an attempt was made to ablate a middle mediastinal parathyroid gland by forceful staining with radiographic contrast material. The gland was stained on two separate occasions, two weeks apart. Both times the serum calcium level temporarily fell to the normal range but reverted to abnormal levels. The patient ultimately required surgery for correction of hypercalcemia. The mechanism of staining and possible reasons for failure as well as potential complications are discussed.     

Phototargeting oral black-pigmented bacteria

We have found that broadband light (380 to 520 nm) rapidly and selectively kills oral black-pigmented bacteria (BPB) in pure cultures and in dental plaque samples obtained from human subjects with chronic periodontitis. We hypothesize that this killing effect is a result of light excitation of their endogenous porphyrins. Cultures of Prevotella intermedia and P. nigrescens were killed by 4.2 J/cm2, whereas P. melaninogenica required 21 J/cm2. Exposure to light with a fluence of 42 J/cm2 produced 99% killing of P. gingivalis. High-performance liquid chromatography demonstrated the presence of various amounts of different porphyrin molecules in BPB. The amounts of endogenous porphyrin in BPB were 267 (P. intermedia), 47 (P. nigrescens), 41 (P. melaninogenica), and 2.2 (P. gingivalis) ng/mg. Analysis of bacteria in dental plaque samples by DNA-DNA hybridization for 40 taxa before and after phototherapy showed that the growth of the four BPB was decreased by 2 and 3 times after irradiation at energy fluences of 4.2 and 21 J/cm2, respectively, whereas the growth of the remaining 36 microorganisms was decreased by 1.5 times at both energy fluences. The present study suggests that intraoral light exposure may be used to control BPB growth and possibly benefit patients with periodontal disease.