4.5-gram monofilament sensation beneath both first metatarsal heads indicates protective foot sensation in diabetic patients

BACKGROUND: Loss of protective plantar foot sensation is the major cause of diabetic foot ulcerations and ultimate limb loss. Identification of patients without protective sensation can reduce the risk of unrecognized foot injury. The current recommended screening protocol requires 10-g monofilament testing of ten foot sites with use of a forced-choice paradigm. The objective of the present study was to determine whether testing of fewer than ten sites could provide accuracy comparable with that obtained by testing all ten sites. METHODS: A cross-sectional comparative study of plantar sensory levels in diabetic subjects with and without plantar ulceration was conducted in a tertiary-care teaching hospital setting. We examined forty-seven diabetic subjects with a history of foot ulceration and forty-five diabetic subjects with no history of foot ulceration. Plantar sensory threshold values at five sites on the sole of each foot were measured with a quasi-continuous range of applied forces, and receiver operating characteristic analysis techniques were applied. RESULTS: Screening on the basis of only the maximum force threshold for the left and right first metatarsal head sites provided comparable or better performance at high levels of sensitivity than did either the mean or the maximum force threshold across all ten sites. A sensory threshold of 4.5 g for both the left and right first metatarsal head sites predicted the risk of ulceration with a sensitivity of 100% and a specificity of 67%. CONCLUSIONS: Testing of diabetic patients for protective sensation may be simplified to testing under both first metatarsal heads with a 4.5-g monofilament. If a patient cannot sense the application of a 4.5-g monofilament under either first metatarsal head, he or she probably has lost protective sensation and should be considered to be at risk for undetected injury.     

An evaluation of continuous positive airway pressure (CPAP) therapy in the treatment of hypernasality following traumatic brain injury: a report of 3 cases

OBJECTIVE: To evaluate the effectiveness of continuous positive airway pressure (CPAP) therapy in the treatment of hypernasality following traumatic brain injury (TBI). DESIGN: An A-B-A experimental research design. Assessments were conducted prior to commencement of the program, midway, immediately posttreatment, and 1 month after completion of the CPAP therapy program. PARTICIPANTS: Three adults with dysarthria and moderate to severe hypernasality subsequent to TBI. OUTCOME MEASURES: Perceptual evaluation using the Frenchay Dysarthria Assessment, the Assessment of Intelligibility of Dysarthric Speech, and a speech sample analysis, and instrumental evaluation using the Nasometer. RESULTS: Between assessment periods, varying degrees of improvement in hypernasality and sentence intelligibility were noted. At the 1-month post-CPAP assessment, all 3 participants demonstrated reduced nasalance values, and 2 exhibited increased sentence intelligibility. CONCLUSIONS: CPAP may be a valuable treatment of impaired velopharyngeal function in the TBI population.     

Indoor gardening older adults: effects on socialization, activities of daily living, and loneliness

This study examined the effects of indoor gardening on socialization, activities of daily living (ADLs), and perceptions of loneliness in elderly nursing home residents. A total of 66 residents from two nursing homes participated in this two-phase study. In phase one, experimental group 1 participated once a week for 5 weeks in gardening activities while a control group received a 20-minute visit. While no significant differences were found between groups in socialization or perceptions of loneliness, there were significant pretest-posttest differences within groups on loneliness and guidance, reassurance of worth, social integration, and reliable alliance. The results also demonstrated gardening interventions had a significant effect on three ADLs (transfer, eating, and toileting). Phase two examined differences in the effects of a 5-week versus a 2-week intervention program. Although no significant within-group differences were noted in socialization, loneliness, or ADLs, the 5-week program was more effective in increasing socialization and physical functioning.     

Cohort mortality study of capacitor manufacturing workers, 1944-2000

A mortality study of workers employed between 1944 and 1977 at an electrical capacitor manufacturing plant where polychlorinated biphenyls (PCBs), chlorinated naphthalenes, and other chemicals were used was undertaken. Age, gender, and calendar year-adjusted standardized mortality ratios (SMRs) were calculated for 2885 white workers. Total mortality and all-cancer mortality were similar to expected in both males and females. Females employed 10 or more years had a significantly elevated SMR of 6.2 for liver/biliary cancer. Intestinal cancer was significantly elevated in females employed 5 or more years after PCBs were introduced (SMR = 2.2). In males, stomach cancer (SMR = 2.2) and thyroid cancer (SMR = 15.2) were significantly elevated. Although individual exposure assessment was limited, PCBs alone or in combination with other chemicals could be associated with increased risks for liver/biliary, stomach, intestinal, and thyroid cancer.     

11beta-alkyl-Delta9-19-nortestosterone derivatives: high-affinity ligands and potent partial agonists of the androgen receptor

We report the synthesis of novel steroidal androgen receptor ligands comprising 11beta-alkyl-Delta(9)-derivatives of 19-nortestosterone. These compounds are structurally related to the antiprogestin, antiglucocorticoid, and antiandrogen drug mifepristone (RU486). Nortestosterone analogues bearing 11beta-octyl and 11beta-decyl side-chains bind tightly to recombinant AR protein (IC(50) = 6.6 nM and IC(50) = 0.8 nM), block AR dimerization, exhibit activity against LNCaP prostate cancer cells, and comprise partial AR agonists with low antiglucocorticoid activity.     

The effect of DB-67, a lipophilic camptothecin derivative,on topoisomerase I levels in non-small-cell lung cancer cells

Purpose To determine the in vitro drug sensitivity of two non-small-cell lung cancer cell lines after treatment with the novel lipophilic camptothecin derivative, 7-tert-butyldimethylsilyl-10-hydroxycamptothecin (DB-67), to determine if topoisomerase I protein levels decrease after treatment with DB-67, and to assess the duration and extent of topoisomerase I modulation after DB-67 exposure, in order to provide information about drug resistance that may be useful in determining an appropriate dosing schedule for DB-67.Methods The growth inhibition of the non-small-cell lung cancer cell lines A549 and H460 after exposure to DB-67 was evaluated with the MTS assay. A549 and H460 cells were treated for various times with DB-67 and topoisomerase I levels were determined by western blot analysis. In addition, A549 and H460 cells were treated with DB-67 for 24 h and topoisomerase I levels were determined by western blot analysis daily for 1 week after drug removal.Results DB-67 inhibited the growth of both A549 and H460 cells grown in culture; the A549 cells were more resistant to the cytotoxic effects of DB-67 than H460 cells. Notably, A549 cells had approximately one-half the baseline topoisomerase I than H460 cells. Topoisomerase I protein levels significantly decreased after 8–18 h of exposure to DB-67. Both A549 and H460 cells treated with DB-67 for 24 h had only negligible amounts of topoisomerase I at the end of treatment. However, within 24 h of drug removal topoisomerase I levels returned to near baseline levels in both cell lines.Conclusions The decrease in topoisomerase I levels caused by DB-67 may represent a mechanism of resistance to this novel camptothecin derivative. Dosing DB-67 once every 48–72 h may maximize the interaction of the drug with topoisomerase I and should be considered as a potential dosing schedule in the preclinical and clinical development of this compound.     

Low-field magnetic stimulation in bipolar depression using an MRI-based stimulator

OBJECTIVE: Anecdotal reports have suggested mood improvement in patients with bipolar disorder immediately after they underwent an echo-planar magnetic resonance spectroscopic imaging (EP-MRSI) procedure that can be performed within clinical MR system limits. This study evaluated possible mood improvement associated with this procedure. METHOD: The mood states of subjects in an ongoing EP-MRSI study of bipolar disorder were assessed by using the Brief Affect Scale, a structured mood rating scale, immediately before and after an EP-MRSI session. Sham EP-MRSI was administered to a comparison group of subjects with bipolar disorder, and actual EP-MRSI was administered to a comparison group of healthy subjects. The characteristics of the electric fields generated by the EP-MRSI scan were analyzed. RESULTS: Mood improvement was reported by 23 of 30 bipolar disorder subjects who received the actual EP-MRSI examination, by three of 10 bipolar disorder subjects who received sham EP-MRSI, and by four of 14 healthy comparison subjects who received actual EP-MRSI. Significant differences in mood improvement were found between the bipolar disorder subjects who received actual EP-MRSI and those who received sham EP-MRSI, and, among subjects who received actual EP-MRSI, between the healthy subjects and the bipolar disorder subjects and to a lesser extent between the unmedicated bipolar disorder subjects and the bipolar disorder subjects who were taking medication. The electric fields generated by the EP-MRSI scan were smaller (0.7 V/m) than fields used in repetitive transcranial magnetic stimulation (rTMS) treatment of depression (1-500 V/m) and also extended uniformly throughout the head, unlike the highly nonuniform fields used in rTMS. The EP-MRSI waveform, a 1-kHz train of monophasic trapezoidal gradient pulses, differed from that used in rTMS. CONCLUSIONS: These preliminary data suggest that the EP-MRSI scan induces electric fields that are associated with reported mood improvement in subjects with bipolar disorder. The findings are similar to those for rTMS depression treatments, although the waveform used in EP-MRSI differs from that used in rTMS. Further investigation of the mechanism of EP-MRSI is warranted.     

Measuring factors underlying intendedness of women's first and later pregnancies

CONTEXT: Unintended pregnancy is associated with poor health outcomes for mothers and infants, and is indicative of gaps in family planning services. Conventional measures of pregnancy intendedness do not reflect the multiple factors affecting a woman's pregnancy-related intentions and attitudes. METHODS: Data collected between March 2002 and February 2003 from 701 women in a public family planning clinic and 671 women in a public prenatal clinic in New Orleans were analyzed to examine factors underlying intendedness (including attitudes toward pregnancy and motivations to achieve or avoid pregnancy). RESULTS: In factor analyses, variables measuring pregnancy intendedness were represented by a single latent factor, pregnancy desirability. For first pregnancy, variables that best captured desirability were those measuring happiness, effort in achieving the pregnancy, extent of looking forward to telling friends, whether the pregnancy was intended (i.e., came at the right time or later), and whether the woman wanted to have a baby with her partner. For last or current pregnancies that were second or higher order ones, they were happiness, pregnancy wantedness, effort in achieving the pregnancy, whether the pregnancy was planned and whether the woman wanted to have a baby with her partner. Among women younger than 18 at first pregnancy, happiness and whether a woman wanted a baby with her partner were the only items that captured pregnancy desirability. CONCLUSIONS: Future surveys on pregnancy intendedness could reduce the number of questions used to capture pregnancy desirability. This should help standardize surveillance systems and permit better assessment of trends in pregnancy desirability over time.     

Helplessness and escape performance: glutamate-adenosine interactions in the frontal cortex

Adenosine has been implicated as a proximate mediator of escape deficits in the learned helplessness paradigm, suggesting that neuronal overactivation-a typical precursor to adenosine release-precedes the inescapable shock-induced impairment (T. R. Minor, W. C. Chang, & J. L. Winslow, 1994). In the present experiments, glutamate (100 microg) injection into the rat frontal cortex produced a deficit in escape performance. Pretest treatment with the adenosine receptor antagonist caffeine (7 mg/kg ip) reversed the effect of glutamate when infused 1 hr. but not 72 hr, after glutamate injection. Finally, microinjection of 2-amino-5-phosphonovaleric acid (5 ng) into the frontal cortex prior to inescapable shock prevented the escape deficit. These findings are consistent with the involvement of N-methyl-D-aspartate receptor activation in the frontal cortex in the helplessness effect.