Long-term functional outcomes after total wrist arthrodesis.

Current literature surrounding functional outcomes after total wrist arthrodesis is limited by short follow-up or limited use of validated patient reported outcome measures (PROMs). The primary aim of this study was to describe long-term functional outcomes following wrist arthrodesis. Secondary aims were to describe the incidence of complications and patient satisfaction. This was a retrospective single-center study. Patients with a minimum of 10-year follow-up completed a questionnaire including the Patient-Rated Wrist Evaluation (PRWE), the Quick version of the Disabilities of the Arm, Shoulder and Hand (Quick-DASH) score, the EQ-5D-5L score, and a question assessing satisfaction. Presence of a complication was also assessed. During the study period 66 patients underwent total arthrodesis. At a median follow-up of 15 years, complete patient reported outcomes were available for 34 patients. Thirty-two patients were lost to follow-up. Mean age at surgery was 49 and 16 patients were female. Mean PRWE and Quick-DASH scores were 44.8 (SD 27.7; range 0-96) and 41.9 (SD 23.6; range 2.3-97.7) respectively. Twenty-eight patients were satisfied. Nine patients reported complications. There were six cases of hardware removal and two cases of prominent metalwork. One patient underwent revision surgery for non-union. Presence of a complication did not affect the Quick-DASH or PRWE scores. Median EQ-5D-5L score was 0.7. This long-term follow-up suggests high levels of patient satisfaction and health related quality of life, despite significant functional disability. The complication rates are not insignificant, although the presence of a complication did not affect functional outcomes.

Smoking habits of UK military personnel on deployment: Exercise SAIF SAREEA 3.

INTRODUCTION: Changes of environment brought about by deployments are often attributed to an increase in smoking of service personnel. Electronic cigarettes are recognised as being a viable aid to quitting smoking but are currently banned from sale in Oman and were therefore banned during exercise SAIF SAREEA 3 (SS3). This paper sought to establish whether smoking increased on this exercise and for what reasons. Also, if deployed smoking cessation services are likely to be used, if available. METHODS: Questionnaires were distributed to deployed troops at various locations in theatre for data collection. RESULTS: Smoking prevalence increased by 5.2% (29) in the deployed population by the end of the exercise. The largest increase was seen in those smoking 20 cigarettes a day or more, rising by 269.8% (73) with a mean increase of 9 cigarettes per day. During the exercise the number of personnel using electronic cigarettes decreased and individuals' rate of electronic cigarette use also decreased. Those who smoked less during the exercise did mainly through choice (56.8%). 50% (280) of all individuals who increased smoking habits during the exercise did so out of boredom. CONCLUSIONS: During exercise SS3 the number of individuals who smoked and the quantity they smoked increased. The ban on electronic cigarettes in Oman and while on exercise potentially had an effect on the increased smoking habits. There is an argument to include smoking cessation material in medical modules to prevent ex-smokers from restarting, continue to aid those quitting and potentially lessen severity of increasing smoking habits while deployed.

Conservative surgery for ovarian torsion in young women: perioperative complications and national trends.

OBJECTIVE: To analyse populational trends and perioperative complications following conservative surgery versus oophorectomy in women <50 years of age with ovarian torsion. DESIGN: Population-based retrospective observational study. SETTING: Nationwide Inpatient Sample in the USA (2001-2015). POPULATION: In all, 89 177 ovarian torsions including 20 597 (23.1%) conservative surgeries and 68 580 (76.9%) oophorectomies. METHODS: (1) Trend analysis to assess utilisation of conservative surgery over time, (2) multivariable binary logistic regression to identify independent factors associated with conservative surgery and (3) inverse probability of treatment weighting with a generalised estimating equation to analyze perioperative complications. MAIN OUTCOME MEASURES: Trends, characteristics and complications related to conservative surgery. RESULTS: Performance of conservative surgery increased from 18.9 to 25.1% between 2001 and 2015 (32.8% relative increase, P = 0.001) but decreased steadily after age 15, and sharply declined after age 35 (P < 0.001). On multivariable analysis, younger age exhibited the largest effect size for conservative surgery among the independent factors (adjusted odds ratios 3.39-7.96, P < 0.001). In the weighted model, conservative surgery was associated with an approximately 30% decreased risk of perioperative complications overall (10.0% versus 13.6%, odds ratio 0.73, 95% confidence interval 0.62-0.85, P < 0.001) and was not associated with venous thromboembolism (0.2 versus 0.3%, P = 0.457) or sepsis (0.4 versus 0.3%, P = 0.638). CONCLUSION: There has been an increasing utilisation of conservative surgery for ovarian torsion in the USA in recent years. Our study suggests that conservative surgery for ovarian torsion may not be associated with increased perioperative complications. TWEETABLE ABSTRACT: Conservative surgery for ovarian torsion may not be associated with increased perioperative complications.

Medication taking in a national sample of dependent older people.

BACKGROUND: Polypharmacy is associated with inappropriate medication use, and subsequently increasing older persons' risk of drug-related harm and health-related costs to individuals and society. OBJECTIVE: To examine and describe, using a national sample of patient-level medication data, the prevalence of older people's polypharmacy and medication use across dependency levels. To examine oral and general pain prevalence and associated analgesic usage. METHODS: Medication data from the 2012 New Zealand Older People's Oral Health Survey, a nationally-representative, cross-sectional study of dependent older people's oral health, were analysed descriptively, comparing classes and sub-classes of drugs and nutrient supplements taken across four categories of dependency: very low (own homes receiving in-home support), low, high and psychogeriatric (all receiving aged residential care). Self-reported current general pain and frequency of orofacial pain data were cross-tabulated by sub-classes of analgesics taken. RESULTS: All participants were taking at least one medication overall, 53.2% (95% CI: 50.4, 56.0) took between five and nine (polypharmacy), and 13.9% (95% CI: 17.4, 22.5) took 10 or more (hyperpolypharmacy). Antihypertensives, analgesics, antiulcer drugs, aspirin, laxatives, statins and antidepressants were the most common drug classes taken, the proportions differing between psychogeriatric level care and all other dependency groups. Overall, simple analgesics were taken (34.5%; 95%CI: 30.8, 38.4) more commonly than other analgesics; the use of nonsteroidal anti-inflammatory drugs was low (3.6%; 95% CI: 2.7, 4.7). Of those reporting experiencing extreme general bodily pain, 63.3% (95% CI: 56.6, 69.4) took an analgesic, more than those experiencing mouth pain occasionally or often. Fat-soluble vitamins were the most common vitamin supplement taken (32.0%; 95%CI: 27.0, 37.4). CONCLUSIONS: Polypharmacy and hyperpolypharmacy are common among older people, regardless of dependency level, and pain may be undertreated.

Just a routine operation: a critical discussion.

This article has summarised a critical discussion of the human factors that contributed to the death of a patient from a failure to respond appropriately to a 'can't intubate, can't ventilate' scenario. The contributory factors included the clinical team's inability to communicate, prioritise tasks and demonstrate effective leadership and assertive followership. The film Just a routine operation has now been in circulation for several years. When a system is designed and introduced with the intention of making a change to clinical practice, it can quickly become just another component of an organisation's architecture and complacency around its use can develop. This article has been written specifically for perioperative practitioners to renew the debate around the human factors that contribute to patient harm. By critically discussing Just a routine operation and attempting to review why the incident occurred, this article has attempted to emphasise that some of the conditions and behaviours that contributed to the death of Elaine Bromiley may be latent within our organisations and teams, and may continue to contribute to failures that affect patient safety.

Clostridium difficile associated risk of death score (CARDS): a novel severity score to predict mortality among hospitalised patients with C. difficile infection.

BACKGROUND: Clostridium difficile infection (CDI) is a public health threat and associated with significant mortality. However, there is a paucity of objectively derived CDI severity scoring systems to predict mortality. AIM: To develop a novel CDI risk score to predict mortality entitled: Clostridium difficile associated risk of death score (CARDS). METHODS: We obtained data from the United States 2011 Nationwide Inpatient Sample (NIS) database. All CDI-associated hospitalisations were identified using discharge codes (ICD-9-CM, 008.45). Multivariate logistic regression was utilised to identify independent predictors of mortality. Clostridium difficile associated risk of death score was calculated by assigning a numeric weight to each parameter based on their odds ratio in the final logistic model. Predictive properties of model discrimination were assessed using the c-statistic and validated in an independent sample using the 2010 NIS database. RESULTS: We identified 77 776 hospitalisations, yielding an estimate of 374 747 cases with an associated diagnosis of CDI in the US, 8% of whom died in the hospital. The eight severity score predictors were identified on multivariate analysis: age, cardiopulmonary disease, malignancy, diabetes, inflammatory bowel disease, acute renal failure, liver disease and ICU admission, with weights ranging from -1 (for diabetes) to 5 (for ICU admission). The overall risk score in the cohort ranged from 0 to 18. Mortality increased significantly as CARDS increased. CDI-associated mortality was 1.2% with a CARDS of 0 compared to 100% with CARDS of 18. The model performed equally well in our validation cohort. CONCLUSION: Clostridium difficile associated risk of death score is a promising simple severity score to predict mortality among those hospitalised with C. difficile infection.

Bubble-detector measurements of neutron radiation in the international space station: ISS-34 to ISS-37.

Bubble detectors have been used to characterise the neutron dose and energy spectrum in several modules of the International Space Station (ISS) as part of an ongoing radiation survey. A series of experiments was performed during the ISS-34, ISS-35, ISS-36 and ISS-37 missions between December 2012 and October 2013. The Radi-N2 experiment, a repeat of the 2009 Radi-N investigation, included measurements in four modules of the US orbital segment: Columbus, the Japanese experiment module, the US laboratory and Node 2. The Radi-N2 dose and spectral measurements are not significantly different from the Radi-N results collected in the same ISS locations, despite the large difference in solar activity between 2009 and 2013. Parallel experiments using a second set of detectors in the Russian segment of the ISS included the first characterisation of the neutron spectrum inside the tissue-equivalent Matroshka-R phantom. These data suggest that the dose inside the phantom is ∼70% of the dose at its surface, while the spectrum inside the phantom contains a larger fraction of high-energy neutrons than the spectrum outside the phantom. The phantom results are supported by Monte Carlo simulations that provide good agreement with the empirical data.

Pertuzumab for the treatment of patients with previously untreated HER2-positive metastatic breast cancer.

Pertuzumab is a humanized monoclonal antibody directed at the dimerization domain of the receptor tyrosine-protein kinase erbB-2 (HER2) receptor. It possesses a unique and complimentary mechanism of action compared to trastuzumab, which has historically been the cornerstone of therapy for HER2-amplified breast cancer. Clinical trials demonstrate improved outcomes, with minimal increases in toxicity with the addition of pertuzumab to trastuzumab in patients with HER2-positive metastatic breast cancer, indicating the advantage of dual HER2 receptor blockade. Pertuzumab is approved as first-line therapy in combination with trastuzumab and docetaxel for HER2-positive metastatic breast cancer, with future opportunities to investigate its efficacy in other stages of breast cancer, as well as in the treatment of other malignancies.

Regional activation in the rat brain during visceral stimulation detected by c-fos expression and fMRI.

AIM: The aim of the study was to determine and compare the areas of brain activated in response to colorectal distention (CRD) using functional magnetic resonance imaging (fMRI) and c-fos protein expression. METHODS: For fMRI study (3.0 T magnet), anaesthetized rats underwent phasic CRD, synchronized with fMRI acquisition. Stimulation consisted of eight cycles of balloon deflation (90 s) and inflation (30 s), at 40, 60 or 80 mmHg of pressure. For c-fos study two sets of experiments were performed on anaesthetized rats: comparing (A) brain activation in rats with the inserted colorectal balloon (n = 5), to the rats without the balloon (n = 5); and (B) rats with inserted balloon (n = 10), to the rats with inserted and distended balloon (n = 10). The pressure of 80 mmHg was applied for 2 h of 30 s inflation and 90 s deflation, alternating cycles. RESULTS: Functional MRI revealed significant activation in the amygdala, hypothalamus, thalamus, cerebellum and hippocampus. Significant increase in c-fos expression was observed in amygdala and thalamus in the first set of experiments, and hypothalamus and parabrachial nuclei in the second. CONCLUSION: The two methods are not interchangeable but appeared to be complementary: fMRI was more sensitive, whereas c-fos had much greater resolution.

Removal of local field gradient artefacts in BOLD contrast imaging of head and neck tumours.

Monitoring of oxygenation in tumours is an important issue in predicting the success of anti-cancer treatments such as radiotherapy. Gradient echo (GE) imaging sequences can be used for monitoring changes in tumour blood flow and oxygenation. However, the application of this method in head and neck tumours is hampered by significant artefacts and losses of the MR signal near air-tissue interfaces. We investigated the usefulness of a gradient-echo slice excitation profile (GESEPI) sequence that should keep the oxygen contrast while recovering the signal loss caused by susceptibility artefacts. A tumour model was implanted in the neck and in the leg of mice. MR imaging was performed at 4.7 T. GE and GESEPI sequences were used for monitoring the blood oxygen level dependent (BOLD) contrast after carbogen breathing. The pO2 was also monitored in tumours using an OxyLite probe (Oxford Optronics). Using the tumours implanted in the leg, we found that the variations of signal intensity after carbogen breathing were similarin both sequences. In the tumour implanted in the neck, it was possible, using GESEPI sequences, to recover the signal loss caused by susceptibility artefacts and to monitor the effect of carbogen-induced changes in the tumour.

Clinical and pathologic features of Mycobacterium fortuitum infections. An emerging pathogen in patients with AIDS.

The clinical and pathologic features of Mycobacterium fortuitum infection in 11 patients with AIDS were characterized. Nine patients had cervical lymphadenitis; 2 had disseminated infection. The infection occurred late in the course of AIDS, and the only laboratory abnormality seen in more than half of patients (7/11) was relative monocytosis. Absolute monocytosis also was seen in 4 of 11 patients. In both cytologic and histologic preparations, the inflammatory pattern was suppurative with necrosis or a mixed suppurative-granulomatous reaction. M fortuitum, a thin, branching bacillus, stained inconsistently in direct smear and histologic preparations. Staining was variable with Gram, auramine, Brown-Hopps, Gram-Weigert, Kinyoun, Ziehl-Neelsen, modified Kinyoun, and Fite stains. Organisms, when present, were always seen in areas of suppurative inflammation. Incorrect presumptive diagnosis, based on misinterpretation of clinical signs and symptoms or on erroneous identification of M fortuitum bacilli as Nocardia species, led to a delay in proper therapy for 7 of 11 patients. Definitive therapy after culture identification resulted in complete resolution of infection in all patients except 1.

Radio frequency magnetic field mapping of a 3 Tesla birdcage coil: experimental and theoretical dependence on sample properties.

The RF B(1) distribution was studied, theoretically and experimentally, in phantoms and in the head of volunteers using a 3 T MRI system equipped with a birdcage coil. Agreement between numerical simulation and experiment demonstrates that B(1) distortion at high field can be explained with 3D full-Maxwell calculations. It was found that the B(1) distribution in the transverse plane is strongly dependent on the dielectric properties of the sample. We show that this is a consequence of RF penetration effects combined with RF standing wave effects. In contrast, along the birdcage coil z-axis the B(1) distribution is determined mainly by the coil geometry. In the transverse plane, the region of B(1) uniformity (within 10% of the maximum) was 15 cm with oil, 6 cm with distilled water, 11 cm with saline, and 10 cm in the head. Along z the B(1) uniformity was 9 cm with phantoms and 7 cm in the head.

Treatment of severe thrombocytopenia in alloimmunized, transfusion-refractory patients.

A significant proportion of patients with hematologic malignancies who are exposed to multiple transfusions will develop alloantibodies to platelet human leukocyte antigens (HLA), resulting in poor responses to subsequent platelet transfusions. Transfusion of HLA-identical platelets is an effective method of platelet support in these patients, but perfectly HLA-matched platelets are often not available. In this paper, we review the recent literature on platelet transfusion support in alloimmunized individuals and illustrate alternative management strategies with cases from our own practice.

Monte Carlo calculations on HIV-1 reverse transcriptase complexed with the non-nucleoside inhibitor 8-Cl TIBO: contribution of the L100I and Y181C variants to protein stability and biological activity.

A computational model of the non-nucleoside inhibitor 8-Cl TIBO complexed with HIV-1 reverse transcriptase (RT) was constructed in order to determine the binding free energies. Using Monte Carlo simulations, both free energy perturbation and linear response calculations were carried out for the transformation of wild-type RT to two key mutants, Y181C and L100I. The newer linear response method estimates binding free energies based on changes in electrostatic and van der Waals energies and solvent-accessible surface areas. In addition, the change in stability of the protein between the folded and unfolded states was estimated for each of these mutations, which are known to emerge upon treatment with the inhibitor. Results from the calculations revealed that there is a large hydrophobic contribution to protein stability in the native, folded state. The calculated absolute free energies of binding from both the linear response, and also the more rigorous free energy perturbation method, gave excellent agreement with the experimental differences in activity. The success of the relatively rapid linear response method in predicting experimental activities holds promise for estimating the activity of the inhibitors not only against the wild-type RT, but also against key protein variants whose emergence undermines the efficacy of the drugs.

Human articular cartilage: influence of aging and early symptomatic degeneration on the spatial variation of T2--preliminary findings at 3 T.

PURPOSE: To determine if age and early symptomatic degeneration alter the spatial dependency of cartilage T2. MATERIALS AND METHODS: In 25 asymptomatic volunteers and six volunteers with symptoms of patellar chondromalacia, quantitative T2 maps of patellar cartilage were obtained with a multiecho, spin-echo magnetic resonance imaging sequence at 3.0 T. Spatial variation in T2 was evaluated as a function of participant age and symptoms. RESULTS: All asymptomatic volunteers demonstrated a continuous increase in T2 from the radial zone to the articular surface. In the population aged 46-60 years compared with younger volunteers, there was a statistically significant (P < .05) increase in T2 of the transitional zone. In symptomatic volunteers, the increase in T2 was larger in magnitude and focal in distribution. In five of the six symptomatic volunteers, the increase in T2 was greater than the 95% prediction interval determined from data in the corresponding age-matched asymptomatic population. CONCLUSION: Aging is associated with an asymptomatic increase in T2 of the transitional zone of articular cartilage. Preliminary results indicate this diffuse increase in T2 in senescent cartilage is different in appearance than the focally increased T2 observed in damaged articular cartilage.

Effects of the ovarian cycle on sympathetic neural outflow during static exercise.

We compared reflex responses to static handgrip at 30% maximal voluntary contraction (MVC) in 10 women (mean age 24.1 +/- 1.7 yr) during two phases of their ovarian cycle: the menstrual phase (days 1-4) and the follicular phase (days 10-12). Changes in muscle sympathetic nerve activity (MSNA; microneurography) in response to static exercise were greater during the menstrual compared with follicular phase (phase effect P = 0.01). Levels of estrogen were less during the menstrual phase (75 +/- 5.5 vs. 116 +/- 9.6 pg/ml, days 1-4 vs. days 10-12; P = 0.002). Generated tension did not explain differences in MSNA responses (MVC: 29.3 +/- 1.3 vs. 28.2 +/- 1.5 kg, days 1-4 vs. days 10-12; P = 0.13). In a group of experiments with the use of 31P-NMR spectroscopy, no phase effect was observed for H+ and H2PO-4 concentrations (n = 5). During an ischemic rhythmic handgrip paradigm (20% MVC), a phase effect was not observed for MSNA or H+ or H2PO-4 concentrations, suggesting that blood flow was necessary for the expression of the cycle-related effect. The present studies suggest that, during static handgrip exercise, MSNA is increased during the menstrual compared with the follicular phase of the ovarian cycle.

Disseminated Histoplasma capsulatum infection presenting as genital ulcerations.

BACKGROUND: Histoplasma capsulatum infection in adults is most often subclinical but can result in disseminated disease with weight loss, fever, hepatosplenomegaly, and oropharyngeal ulcerations. Genital ulceration as the presenting sign of the disease has been reported rarely. CASE: A 63-year-old woman presented with multiple vaginal ulcerations due to chronic disseminated H capsulatum infection. Initial diagnosis was made by Papanicolaou and Giemsa-stained vulvar smears. Ketoconazole therapy resulted in clearing of the lesions in 5 weeks. CONCLUSION: Chronic disseminated histoplasmosis is an insidious and potentially fatal disease that can present rarely as genital mucocutaneous ulcerations in women. Prompt presumptive diagnosis can be accomplished by examination of smears obtained by ulcer abrasion, permitting institution of appropriate therapy.

Second malignant neoplasms in children after treatment of soft tissue sarcoma.

Currently, approximately 67% of children diagnosed with cancer can be expected to survive more than 5 years. Among the most significant late effects of cancer therapy is the development of second malignant neoplasm (SMN). This study was performed to identify the factors associated with the development of second malignant neoplasms after treatment for soft tissue sarcomas in childhood. Retrospectively the charts of 20 children who developed second malignant neoplasms after treatment for primary childhood soft tissue sarcoma were reviewed. Presentation, age at diagnosis, tumor histology, extent of tumor, treatment, family histories (when available), and outcome were recorded. The mean age of the patients (10 boys, 10 girls) was 8.5 years of age (range, 1 to 20 years). Most primary tumors were rhabdomyosarcoma (14/20) and occurred in an extremity (10/20). Ninety percent of the patients (18/20) had a complete response to treatment of the primary cancer. Eleven out of 20 received combined chemotherapy and radiation therapy. The most common secondary malignancy was a bone sarcoma (6/20), followed by brain tumors (n = 3), leukemia (n = 2), and other sarcomas (n = 2). Four of the bone sarcomas developed in the field of radiation treatment. Median follow-up was 16 years (range, 1 to 26 years). The median time to development of a SMN was 11.4 years (range, 1.5 to 21 years). Survival after a second malignancy was only 30%. Two patients developed a third malignant neoplasm. The occurrence of a secondary malignancy represents a serious complication of childhood cancer. Certain tumors are related directly to treatment such as osteosarcoma within irradiated fields and secondary leukemias or lymphomas after certain chemotherapy regimens. Combined radiotherapy and chemotherapy may play an additive role in the development of second malignant neoplasms. Genetic factors may predispose affected patients to the development of both primary and secondary malignancies. Close surveillance of children previously treated for childhood cancers is warranted.

Crystal structures of 8-Cl and 9-Cl TIBO complexed with wild-type HIV-1 RT and 8-Cl TIBO complexed with the Tyr181Cys HIV-1 RT drug-resistant mutant.

Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) is an important target for chemotherapeutic agents used in the treatment of AIDS; the TIBO compounds are potent non-nucleoside inhibitors of HIV-1 RT (NNRTIs). Crystal structures of HIV-1 RT complexed with 8-Cl TIBO (R86183, IC50 = 4.6 nM) and 9-Cl TIBO (R82913, IC50 = 33 nM) have been determined at 3.0 A resolution. Mutant HIV-1 RT, containing Cys in place of Tyr at position 181 (Tyrl81Cys), is highly resistant to many NNRTIs and HIV-1 variants containing this mutation have been selected in both cell culture and clinical trials. We also report the crystal structure of Tyrl81Cys HIV-1 RT in complex with 8-Cl TIBO (IC50 = 130 nM) determined at 3.2 A resolution. Averaging of the electron density maps computed for different HIV-1 RT/NNRTI complexes and from diffraction datasets obtained using a synchrotron source from frozen (-165 degrees C) and cooled (-10 degrees C) crystals of the same complex was employed to improve the quality of electron density maps and to reduce model bias. The overall locations and conformations of the bound inhibitors in the complexes containing wild-type HIV-1 RT and the two TIBO inhibitors are very similar, as are the overall shapes and volumes of the non-nucleoside inhibitor-binding pocket (NNIBP). The major differences between the two wild-type HIV-1 RT/TIBO complexes occur in the vicinity of the TIBO chlorine substituents and involve the polypeptide segments around the beta5-beta6 connecting loop (residues 95 to 105) and the beta13-beta14 hairpin (residues 235 and 236). In all known structures of HIV-1 RT/NNRTI complexes, including these two, the position of the beta12-beta13 hairpin or the "primer grip" is significantly displaced relative to the position in the structure of HIV-1 RT complexed with a double-stranded DNA and in unliganded HIV-1 RT structures. Since the primer grip helps to position the template-primer, this displacement suggests that binding of NNRTIs would affect the relative positions of the primer terminus and the polymerase active site. This could explain biochemical data showing that NNRTI binding to HIV-1 RT reduces efficiency of the chemical step of DNA polymerization, but does not prevent binding of either dNTPs or DNA. When the structure of the Tyr181Cys mutant HIV-1 RT in complex with 8-Cl TIBO is compared with the corresponding structure containing wild-type HIV-1 RT, the overall conformations of Tyr181Cys and wild-type HIV-1 RT and of the 8-Cl TIBO inhibitors are very similar. Some positional changes in the polypeptide backbone of the beta6-beta10-beta9 sheet containing residue 181 are observed when the Tyr181Cys and wild-type complexes are compared, particularlty near residue Val179 of beta9. In the p51 subunit, the Cys181 side-chain is oriented in a similar direction to the Tyr181 side-chain in the wild-type complex. However, the electron density corresponding to the sulfur of the Cys181 side-chain in the p66 subunit is very weak, indicating that the thiol group is disordered, presumably because there is no significant interaction with either 8-Cl TIBO or nearby amino acid residues. In the mutant complex, there are slight rearrangements of the side-chains of other amino acid residues in the NNIBP and of the flexible dimethylallyl group of 8-Cl TIBO; these conformational changes could potentially compensate for the interactions that were lost when the relatively large tyrosine at position 181 was replaced by a less bulky cysteine residue. In the corresponding wild-type complex, Tyr181 iin the p66 subunit has significant interactions with the bound inhibitor and the position of the Tyr181 side-chain is well defined in both subunits. Apparently the Tyr181 --> Cys mutation eliminates favorable contacts of the aromatic ring of the tyrosine and the bou

Early impact of new health care legislation on the pediatric surgical experience of surgical residents.

On January 1, 1994, Tennessee implemented TennCare, an insurance program for the state's medically uninsured and those who were previously covered by Medicaid. To determine how this change has affected the pediatric surgical experience of residents in training, we reviewed our institution's operative case logs from the first quarter of 1994 and compared them with logs for the first quarter of the years 1990 through 1993. Cases were classified according to urgency and necessity of surgical procedures. No significant change was noted in the number of patients having operations for the most necessary or urgent conditions, such as solid tumors or appendicitis. In contrast, the number of elective operations, principally for hernias, decreased significantly during the same period. While Tennessee's legislative change apparently has not affected the volume of urgent surgical cases, it has significantly decreased surgical residents' elective pediatric surgical experience.