Guidelines for the diagnosis and outpatient management of diabetic peripheral neuropathy

AIMS: This series analyses the results of conservative surgery for large lower pole breast cancers by lumpectomy associated with a bilateral remodelling mammoplasty, in order to avoid residual deformities. METHODS: This retrospective study concerns 50 patients with a lower pole breast cancer treated between 1986 and 1996 by lumpectomy, mammoplasty and irradiation. The contralateral breast was immediately made symmetrical in all cases. The mean tumour size was 32.5 mm. RESULTS: The mean weight of the lumpectomy specimen was 270 g. Resection margins were tumour-free in 90% of cases. The main complication observed was delayed healing, thus postponing post-operative treatment in 6.5% of cases. The median follow-up was 48 months. The 5-year actuarial ipsilateral local recurrence rate was 7% and 5-year actuarial metastasis-free and overall survival rates were 81 and 97%, respectively. Cosmesis was satisfactory in 85% of patients. We observed better results when radiotherapy was performed after rather than prior to surgery (92 vs. 67%: NS). CONCLUSIONS: Performing a bilateral mammoplasty at the time of initial surgery for large breast cancers situated in the lower quadrants of the breast facilitates larger lumpectomies with good cosmetic results.     

Chronic fluoride exposure does not cause detrimental, extraskeletal effects in nutritionally deficient rats

On the basis of observations that endemic fluorosis occurs more often in malnourished populations, a series of studies tested the hypothesis that deficient dietary intake of calcium, protein or energy affects fluoride metabolism so that the margin of safe fluoride exposure may be reduced. The objective of the investigation was to determine whether changes in fluoride metabolism in nutritionally deficient rats resulted in manifestation of any extraskeletal toxic fluoride effects not observed in healthy animals. This investigation included two studies, one that monitored the effect of calcium deficiency on the effects of chronic fluoride exposure, and a second study that observed fluoride effects in rats that were deficient either in protein or in energy and total nutrient intake. Control and experimental rats received drinking water containing 0, 0.26 (5), 0.79 (15) or 2.63 (50) mmol fluoride/L (mg/L) for 16 or 48 wk. Control rats were fed optimal diets and experimental rats were fed diets deficient in calcium (Study 1) or protein (Study 2). An additional group of experimental rats (Study 2) was provided with a restricted amount of diet; thus these rats were deficient in energy and total nutrient intake. The intake, excretion and retention of fluoride were monitored; after the rats were killed, tissue fluoride levels and biochemical markers of tissue function were analyzed. Bone marrow cells were harvested from some of the rats, after 48 wk of treatment, for determining the frequency of sister chromatid exchange, a marker of genetic damage. Although there were significant differences among fluoride treatment groups in fluoride excretion and retention that resulted in significantly greater fluoride levels in tissues of the experimental rats, we were unable to detect any harmful, extraskeletal biochemical, physiologic or genetic effects of fluoride in the nutritionally deficient rats.     

The use of cantilever bridges

Replacement of missing teeth with fixed bridgework often involves producing full crown retainers on teeth on both sides of an edentulous space. Unfortunately, this approach can result in the destruction of much healthy tooth tissue, and the clinician must balance the benefits of replacing missing teeth with the amount of tooth preparation required. Current thinking in restorative dentistry places the preservation of tooth tissue at a premium, and most practitioners are happy to use techniques that embrace this philosophy. Because of this, cantilever bridges have an increasing role in dental practice, where the replacement for a missing tooth or teeth has one or more abutments on only one side of the edentulous space, being unsupported at the other. Cantilever bridges fall into several types, depending on the number of abutments and types of retainers. This article describes the various cantilever bridge designs, considers the biomechanics of these restorations, and provides guidelines for their clinical use.     

Sequence capture-PCR improves detection of mycobacterial DNA in clinical specimens

The rapid identification of mycobacterial DNA in clinical samples by PCR can be useful in the diagnosis of tuberculous infections, but several large studies have found that the sensitivity of this approach is not better than that of culture. In order to improve the sensitivity of detection of mycobacterial DNA in clinical specimens from patients with paucibacillary forms of tuberculosis, we have developed a procedure permitting the specific capture of mycobacterial DNA in crude samples prior to amplification, thereby concentrating the target sequences and removing irrelevant DNA and other potential inhibitors of the amplification reaction (sequence capture-PCR). By using this approach to capture and amplify two different sequences specific for organisms of the Mycobacterium tuberculosis complex (IS6110 and the direct repeat region), it was possible to detect as little as one genome of mycobacterial DNA in samples containing up to 750 micrograms of total DNA, representing a 10- to 100-fold increase in sensitivity compared with that obtained by purifying total DNA prior to amplification. Detection of the IS6110 sequence in pleural fluid samples from patients with tuberculous pleurisy by sequence capture-PCR gave positive results in 13 of 17 cases, including 3 of 3 culture-positive samples and 10 of 14 culture-negative samples. In contrast, when total DNA was purified from these samples by adsorption to a silica matrix prior to amplification, only the three culture-positive samples were positive by PCR. The sensitivity of detection of the direct repeat sequence in these samples by sequence capture-PCR was similar to that of IS6110 and, in addition, permitted immediate typing of the strains from some patients. We conclude that sequence capture-PCR improves the sensitivity of detection of mycobacterial DNA in paucibacillary samples. This approach should be useful in detecting rare target sequences from organisms implicated in other pathologic processes.     

Lorazepam-valproate interaction: studies in normal subjects and isolated perfused rat liver

Valproate (VPA) has been shown to interact with all the major antiepileptic drugs (AEDs) through two mechanisms of action: displacement from albumin binding sites and inhibition of drug metabolism. More recently, evidence showed that VPA inhibits the elimination of drugs metabolized by glucuronide conjugation. Lorazepam (LZP), which is primarily eliminated by conjugation with glucuronic acid, is administered concurrently with VPA both in treatment of epilepsy and in patients treated with VPA for psychiatric disorders. Therefore, a significant drug interaction is likely. We investigated such interaction both in in vitro isolated perfused rat liver (IPRL) and in normal subjects. LZP [2 mg, intravenous (i.v.) bolus] was administered to 8 normal volunteers before and after chronic dosing with VPA. In 6 of 8 subjects, VPA significantly decreased LZP plasma clearance by an average of 40% (p < 0.05) and increased LZP concentrations by decreasing formation clearance of the LZP glucuronide. In the IPRL studies, VPA also significantly decreased formation of LZP glucuronide (from 0.72 +/- 0.14 to 0.22 +/- 0.15 ml/h/kg, p < 0.05), indicating that IPRL is a useful tool for evaluation of the effect of VPA on drugs eliminated by glucuronide conjugation.     

Edge-to-edge interfaces in Ti?Al modeled with the embedded atom method

The atomistic structure and energies of high-index interphase boundaries are explored using a combination of molecular statics and dynamics simulations with embedded atom potentials. We investigate planar boundaries between the α₂ and γ phases in the Ti−Al system. The class of boundaries considered has a high-index boundary orientation; the orientation relationship between the α₂ and γ phases also is high index, and a set of planes from each phase meet edge to edge at the boundary plane. For the particular case of a boundary that is commensurate in one direction and coincides with a moiré plane given by the so-called “Δg” diffraction condition, the boundary is not structurally singular, but it is energetically stable and does not appear to dissociate into other low-energy configurations. Misfit compensating defects are not observed; misfit in directions other than the commensurate one appears to be distributed uniformly. The boundary energy is evaluated as a function of the orientation of the boundary plane, and the edge-to-edge (moiré) boundary is found to lie in an energy cusp. This article is based on a presentation made in the “Hume-Rothery Symposium on Structure and Diffusional Growth Mechanisms of Irrational Interphase Boundaries,” which occurred during the TMS Winter meeting, March 15–17, 2004, in Charlotte, NC, under the auspices of the TMS Alloy Phases Committee and the co-sponsorship of the TMS-ASM Phase Transformations Committee.     

Metric-based reasoning about pseudocode design in the partial metrics system

The goal of the PMS project is to produce an environment in which the intelligent online assessment of the design for large-scale ADA programming projects is provided. The focus is on the representation of knowledge about the design process for an individual module. Changes in pseudocode complexity are measured in terms of partial metrics. These metrics can take the designers inferences about the pseudocode program structure into account when assessing module complexity. Next, a model of the stepwise refinement process is given which demonstrates how pseudocode elaboration decisions can be modelled in partial metric terms. Finally, the decisions associated with each refinement step for 17 example refinements taken from the computer science literature are described using partial metrics.     

Contraindications to metformin therapy in patients with NIDDM

OBJECTIVE: Treatment with metformin is occasionally associated with the development of severe lactic acidosis. However, this is usually observed in patients with major contraindications to the drug. In this study, we aimed to determine the prevalence of conditions currently regarded as either contraindications or cautions to the use of metformin in patients with NIDDM. RESEARCH DESIGN AND METHODS: The case notes of metformin-treated NIDDM patients (mean age 62 years) attending a United Kingdom university hospital diabetes clinic over a 3-month period were reviewed according to criteria reflecting a pragmatic view of current prescribing recommendations. RESULTS: Of 89 consecutive patients whose notes could be evaluated in detail, only 41 (46%) had no contraindications or cautions to metformin whatsoever. Concomitant chronic disorders associated with a potentially increased risk of hyperlactatemia were renal impairment (n = 2; plasma creatinine concentrations 1.7 and 2.3 mg/dl, respectively), cardiac failure (n = 2), and chronic liver disease (n = 2). Other potentially relevant disorders included ischemic heart disease (n = 20), clinical proteinuria (n = 14), peripheral vascular disease (n = 22), and pulmonary disease (n = 7). Multiple conditions (i.e., two, three, or four) were present in eight, five, and one patient(s), respectively. CONCLUSIONS: More than half the patients in our series had concomitant conditions or complications conventionally regarded as cautions or contraindications to metformin; approximately 10% had a multiplicity of such conditions. Regular surveillance is necessary to detect the development of complications such as renal impairment. Vigilance is also required in view of the increased risk of major intercurrent illnesses, which may independently disturb lactate metabolism in patients with NIDDM. Metformin should be withdrawn promptly under such circumstances.