Failure of femoral head fixation: a cadaveric analysis of lag screw cut-out with the gamma locking nail and AO dynamic hip screw

The most commonly reported failure mode of sliding hip screws in published literature is cut-out of the lag screw. This study investigates the resistance to failure of the femoral head, with lag screws used in two types of sliding hip screws, the gamma locking nail (Howmedica) and the dynamic hip screw (DHS) (Synthes). The investigation consisted of biomechanical tests under static loading conditions on 12 pairs of cadaveric femoral heads, to establish the failure loads due to screw cut-out for the two implant lag screws. The gamma nail appeared to reduce the tendency to cut-out in the osteoporotic bone (soft) associated with elderly patients in whom these devices are commonly used (p < 0.05). In high density bone (hard) the gamma lag screw also appeared to be stronger, because the DHS showed a tendency to bend. The larger diameter of the gamma nail lag screw resists bending and appears to reduce the risk of cut-out compared with the DHS.     

Discovery of selective, small-molecule inhibitors of RNA complexes--I. The Tat protein/TAR RNA complexes required for HIV-1 transcription

We have developed a therapeutic program focusing on the inhibition of a human immunodeficiency virus-1 specific protein-RNA interaction. This program begins with a search for small organic molecules that would interfere with the binding of Tat protein to TAR RNA. The methodologies chosen to study the HIV-1 Tat-TAR interaction and inhibition include gel mobility shift assays, scintillation proximity assays, filtration assays, and mass spectrometry. These methods helped establish in vitro high-throughput screening assays which rapidly identified Tat-TAR inhibitors from our corporate compound library. Tat-activated reporter gene assays were then used to investigate the cellular activities of the Tat-TAR inhibitors. The cellular activity, selectivity, and toxicity data for select Tat-TAR inhibitors were determined. Evaluation of both the cellular data and the Tat-TAR inhibition results led to further testing in anti-HIV-1 infection assays.     

Dietary variety via sweetening and voluntary feed intake of lactating dairy cows

The effects of choice of diets on feed intake were studied using 12 lactating Holstein cows. A switchback design was used that had three periods and two sequential blocks. Diets were 1) a control total mixed ration (TMR), which consisted of alfalfa haylage, corn silage, and a concentrate mixture based on ground corn and soybean meal (25:25:50 on a dry matter basis) and 2) a sweetened TMR in which a brown sugar food product constituted 1.5% of the dietary dry matter. Treatments consisted of the control TMR fed on both sides of divided feed bunks, the sweetened TMR fed on both sides of divided feed bunks, or both TMR fed on alternating (daily) sides of divided feed bunks in tie stalls. Periods were 2 wk in duration, and cows averaged 67 and 53 d of lactation at the start of blocks 1 and 2, respectively. The dry matter intake, body weight, milk yield, and percentages of milk fat, protein, and solids not fat were similar when either TMR was fed alone. A choice of control TMR or sweetened TMR did not affect any of these variables. The dry matter intake, body weight, milk yield, and milk protein percentage were affected by block; however, these effects were probably caused by differences between the blocks in environment and stage of lactation. The results of this experiment might have been affected by the composition of the control TMR, its similarity to the sweetened TMR, availability of both diets simultaneously when a choice was offered, and use of a TMR instead of separate feeds or simpler mixtures.     

Relation between sexual abuse in childhood and adult depression: case-control study

OBJECTIVE: To examine the association between sexual abuse in childhood and adult depression in women. DESIGN: Two stage, case detection and case identification design, using the 30-item general health questionnaire and the Beck depression inventory for screening and the affective items relating to current functioning on the schizophrenia and affective disorders schedule to identify depressed cases. Details of sexual abuse in childhood were elicited retrospectively by semistructured interview, and social problems by the social problems questionnaire. SETTING: Three general practices, in middle class suburban, deprived inner city, and rural areas. SUBJECTS: 1189 women were screened and 237 subsequently interviewed; 132 were depressed. RESULTS: 49 (37%) of the depressed interviews and 24 (23%) of the non-depressed interviews reported experience of sexual abuse when they were aged under 16 years. A positive association existed between the more severe abuse and depression--all those who had experienced penetration were depressed as adults. A relation was also found between sexual abuse in childhood and sexual problems, housing problems, and problems with their children at school. CONCLUSION: A positive association between child sexual abuse and depression was confirmed, but this was confined to more severe abuse (penetration or attempted penetration).     

Quantitation of three-month intraindividual variability and influence of sex and menstrual cycle phase on CYP1A2, N-acetyltransferase-2, and xanthine oxidase activity determined with caffeine phenotyping

OBJECTIVE: To evaluate intraindividual variability and the effects of sex and menstrual cycle phase on the activity of cytochrome P450 1A2 (CYP1A2), N-acetyltransferase 2 (NAT2), and xanthine oxidase. METHODS: Ten white men were given 2 mg/kg caffeine orally every 14 days for 3 months. The same dosage of caffeine was given to 10 premenopausal white women during the midfollicular and midluteal phases of three complete menstrual cycles. Phenotype was determined with urinary caffeine metabolite ratios. RESULTS: For CYP1A2, mean metabolic ratio (+/- SD) was 5.97 +/- 2.78 during the midfollicular phase and 5.32 +/- 1.99 during the midluteal phase (p = 0.2). For extensive and poor metabolizer of NAT2. Mean midfollicular phase metabolite ratios were 0.71 +/- 0.060 and 0.37 +/- 0.030, and mean midluteal phase metabolite ratios were 0.69 +/- 0.076 and 0.39 +/- 0.053 (p = 0.9). For xanthine oxidase, mean midfollicular phase metabolite ratio was 0.63 +/- 0.06 and mean midluteal phase metabolite ratio was 0.63 +/- 0.05 (p = 0.3). Among the men, mean CYP1A2, NAT2 rapid and slow acetylator, and xanthine oxidase indices were 9.42 +/- 10.18, 0.66 +/- 0.021, 0.31 +/- 0.056, and 0.64 +/- 0.03. There were no differences in metabolite ratios between men and women for CYP1A2, NAT2 extensive metabolizers, or xanthine oxidase. A statistically significant sex difference was found for poor metabolizers of NAT2 (p < 0.05). Median coefficients of variation for CYP1A2, NAT2 extensive and poor metabolizers, and xanthine oxidase ratios were 16.8% (range, 4.5% to 49.3%), 2.9% (range, 2.2% to 4.7%), 13.4% (range, 7.5% to 27.2%), and 4.5% (range, 2.3% to 13.0%). CONCLUSION: Stratification by menstrual cycle phase or sex need not be performed for pharmacokinetic or clinical investigations of substrates for CYP1A2, NAT2, or xanthine oxidase in which the subject are adults.     

Nitrogen mustard up-regulates Bcl-2 and GSH and increases NTP and PCr in HT-29 colon cancer cells

We hypothesized that unexplained increases in nucleoside triphosphates (NTP) observed by 31P magnetic resonance spectroscopy (MRS) after treatment of tumours by DNA-damaging agents were related to chemotherapy-induced up-regulation of the bcl-2 gene and DNA damage prevention and repair processes. To test this hypothesis, we treated HT-29 cells with 10(-4) M nitrogen mustard (HN2) and performed sequential perchloric acid extractions in replicate over 0-18 h. By reference to an internal standard (methylene diphosphonic acid), absolute changes in 31P-detectable high-energy phosphates in these extracts were determined and correlated with changes in bcl-2 protein levels, cell viability, cell cycle, apoptosis and total cellular glutathione (GSH) (an important defence against DNA damage from alkylating agents). After HN2 administration, bcl-2 protein levels in the HT-29 cell line rose at 2 h. Cell viability declined to 25% within 18 h, but apoptosis measured using fluorescence techniques remained in the 1-4% range. Increased cell division was noted at 4 h. Two high-energy interconvertible phosphates, NTP (P < or = 0.006) and phosphocreatine (PCr) (P < or = 0.0002), increased at 2 h concurrently with increased levels of bcl-2 protein and glutathione. This study demonstrates that bcl-2 and glutathione are up-regulated by HN2 and links this to a previously unexplained 31P MRS phenomenon: increased NTP after chemotherapy.     

An examination of the distinction between nouns and verbs: associations with two different kinds of motion

Four experiments provide evidence that people are biased to associate particular types of motion with nouns and different types of motion with verbs. Novel nouns and verbs were related to two types of motion: (1) path, or the direction of motion of one character with respect to the other character, and (2) movement orientation, or the direction a character was facing as it moved. Subjects associated verbs more strongly with path than with movement orientation. In contrast, they associated nouns more strongly with movement orientation than with path. Movement orientation was associated with both object categories and verbs, inconsistent with a complete division of labor between these two types of categories. These results are consistent, however, with the notion that people are biased to associate verbs with relations between objects, whereas they are biased to associate object categories with motions defined with respect to the object carrying out those motions.