Microdistributions of prospective BNCT-compound CuTCPH in tissue sections with a heavy ion microbeam.

Microdistributions of the prospective BNCT-compound CuTCPH, a carborane-containing tetraphenylporphyrin with one Cu atom in its molecular structure, have been obtained in tissue sections of different organs of tumor-bearing and normal Syrian hamsters injected with the boron compound by employing a heavy ion microbeam. High resolution X-ray spectroscopy following micro-PIXE (Particle Induced X-ray Emission with micrometer-sized beams) with a focused (16)O ion beam was used. Focusing was performed with a heavy-ion scanning high-precision magnetic quadrupole triplet microprobe. Squamous Cell Carcinomas were induced on the right Cheek Pouch of Syrian Hamsters (HCP), sampled, cryo-sectioned and freeze-dried. Two-dimensional maps of elemental concentration were obtained by scanning the beam over the samples. Very non-uniform Cu concentrations were found in all sections.     

A Pharmacodynamic Study of Morphine and Its Glucuronide Metabolites After Single Morphine Dosing in Cancer Patients with Pain

Eleven morphine naive patients with cancer-related pain were given a single dose of either intravenous morphine (n = 5) or oral morphine (n = 6). Blood sampling was performed over a 24-hr period and serial pain assessments were made using a categorical scale. Plasma samples were analyzed for morphine, morphine-6-glucuronide (M-6-G), morphine-3-glucuronide (M-3-G), and normorphine using high-performance liquid chromatography. In neither the intravenous nor oral group was there a correlation between analgesia duration and the half-lives of morphine and M-6-G. There was no correlation between the time to peak analgesia and time to peak concentration for morphine or M-6-G. There was no significant difference in absolute concentrations of M-6-G or M-3-6 nor in the ratio ofM-3-G to M-6-G at peak analgesia versus relapse.     

The B vitamin content of hospital meals and potential low intake by elderly inpatients

The content of thiamin, riboflavin, vitamin B6 (pyridoxamine, pyridoxal, pyridoxine), niacin and total folate were determined in the meal choices comprising a typical day's menu in a teaching hospital. Thiamine, riboflavine, and B6 were measured by HPLC analysis, folate by microbiological assay, and niacin content was calculated from food tables.
The results were compared with UK Recommended Daily Amounts (RDA) whenever possible (thiamine, riboflavine and niacin). Vitamin B6 and folate results were compared with the US Recommended Daily Dietary Amount (RDDA) as no British recommendation was available.
Elderly inpatients selected meals which, even if completely consumed, provided half the current recommendation for vitamin B6 and one-third of the recommendation for folate. More than half the meal selections provided less than recommended amounts of riboflavine, and in a quarter of cases less than the recommended amount of thiamine.     

Mixed Effects versus Fixed Effects Modelling of Binary Data with Inter-subject Variability

The question of whether or not a mixed effects model is required when modelling binary data with inter-subject variability and within subject correlation was reported in this journal by Yano et al. (J. Pharmacokin. Pharmacodyn. 28:389–412 [2001]). That report used simulation experiments to demonstrate that, under certain circumstances, the use of a fixed effects model produced more accurate estimates of the fixed effect parameters than those produced by a mixed effects model. The Laplace approximation to the likelihood was used when fitting the mixed effects model. This paper repeats one of those simulation experiments, with two binary observations recorded for every subject, and uses both the Laplace and the adaptive Gaussian quadrature approximations to the likelihood when fitting the mixed effects model. The results show that the estimates produced using the Laplace approximation include a small number of extreme outliers. This was not the case when using the adaptive Gaussian quadrature approximation. Further examination of these outliers shows that they arise in situations in which the Laplace approximation seriously overestimates the likelihood in an extreme region of the parameter space. It is also demonstrated that when the number of observations per subject is increased from two to three, the estimates based on the Laplace approximation no longer include any extreme outliers. The root mean squared error is a combination of the bias and the variability of the estimates. Increasing the sample size is known to reduce the variability of an estimator with a consequent reduction in its root mean squared error. The estimates based on the fixed effects model are inherently biased and this bias acts as a lower bound for the root mean squared error of these estimates. Consequently, it might be expected that for data sets with a greater number of subjects the estimates based on the mixed effects model would be more accurate than those based on the fixed effects model. This is borne out by the results of a further simulation experiment with an increased number of subjects in each set of data. The difference in the interpretation of the parameters of the fixed and mixed effects models is discussed. It is demonstrated that the mixed effects model and parameter estimates can be used to estimate the parameters of the fixed effects model but not vice versa.     

A new method for the prevention of skin sloughs and necrosis secondary to intravenous infiltration

Skin sloughs and necrosis from hypertonic solutions may occur in premature infants receiving peripheral intravenous fluid therapy. A simple multiple puncture method is proposed to remove the infiltrate and prevent skin sloughs.     

Effect of N-nitrosamines carcinogenic for oesophagus on O6-alkyl-guanine-DNA-methyl transferase in rat oesophagus and liver

Several O6-alkylGua adducts have been shown to be removed from DNA during its repair by transfer of the alkyl group to a cysteine residue in a specific AAP, with the formation of S-alkylcysteine. As the reaction is stoichiometric and irreversible, the AAP content of the cell can be reduced or depleted. In vivo depletion by a high dose of nitrosamine can be used to test for the formation of a repairable alkylation adduct at the O6-position of guanine. In addition, if the carcinogenic potency of a nitroso compound for a particular organ is related to the persistence of the adduct in DNA, potency would depend not on the level of alkylation attained after treatment, but on whether this was sufficient to deplete the AAP content of the organ concerned and so to slow down repair, i.e. depletion of AAP is a more relevant estimate of potency than is the initial extent of DNA alkylation. Dose-response studies on target and non-target organs showed that depletion of AAP correlated with organotropy for those nitrosamines known to methylate DNA, i.e. with NDMA for liver, and with NMBzA for oesophagus. With NDEA, the results supported the suggestion that other adducts in addition to O6-alkylGua may be involved. NMPhA, an oesophageal specific carcinogen, did not deplete AAP in oesophagus, and induced AAP in liver. This result adds to the evidence that NMPhA does not alkylate DNA.     

Plaque-type syringoma: two cases misdiagnosed as microcystic adnexal carcinoma

Background:  Plaque-type syringoma is a rare variant of syringoma. This benign neoplasm may be easily misdiagnosed as microcystic adnexal carcinoma (MAC), potentially resulting in unnecessary surgery with disfiguring consequences.
Methods:  We report two cases of plaque-type syringoma that were initially diagnosed as MAC. Microscopically, these lesions were composed of nests of cuboidal cells arrayed within sclerotic collagen in the upper dermis. The deep reticular dermis was spared. No perineural involvement was observed.
Results and Conclusions:  Our cases are discussed in the context of histopathologic diagnosis. Detailed histopathologic findings of syringoma, as well as other considerations in the differential diagnosis, are reviewed. We also include a review of all cases of plaque-type syringoma published to date.