Patient and Physician Perceptions of Changes in Surgical Care in Mongolia 9 Years After Roll-out of a National Training Program for Laparoscopy.

INTRODUCTION: In 2005, the general population of Mongolia was not aware of laparoscopic surgery and was skeptical about the safety of surgical care. A 9-year initiative to expand laparoscopic surgery was initiated by Mongolian surgeons. This study examines the current barriers to and perceptions of surgical care following laparoscopic surgical expansion countrywide. MATERIALS AND METHODS: In September 2013, interviews were conducted with 71 patients, and 39 physicians in Mongolia. Patients and physicians were interviewed using separate sets of interview questions. Questions were designed to gauge perceptions of surgical care in Mongolia evaluating for access, affordability, sustainability, barriers to care, quality, and knowledge of laparoscopy. Responses were fine coded for statistical analysis. RESULTS: 79 % of patients felt surgical care was improving in Mongolia, and 76 % would choose laparoscopy if available. Physicians (100 %) felt laparoscopic surgery had improved surgical care in Mongolia. Barriers to care for patients were time to work up and diagnosis (37 %), and funding an operation (39 %). None of the 36 % of patients who stated funding an operation would be difficult identified government sources of funding (p < 0.001). Physicians identified insufficient equipment supply (69 %), insufficient training (41 %), and cost (38 %) as barriers for laparoscopy. 74 % of physicians felt that Mongolian physicians return or stay in Mongolia after training, defying the trend of migration in low-resource settings. DISCUSSION: Improved local patient and physician perception of laparoscopy is propelling the expansion of laparoscopy in Mongolia.

Impact of anti-HER2 therapy on overall survival in HER2-overexpressing breast cancer patients with brain metastases.

BACKGROUND: Trastuzumab-based therapy after diagnosis of brain metastases (BM) may improve survival due to prolonged systemic disease control. We investigated whether lapatinib may yield additional survival benefit. METHODS: Eighty patients with BM from HER2-positive breast cancer were identified. Karnofsky Performance Score (KPS) of at least 70 was required. We included a control group of 37 patients treated before 2003, when continuation of trastuzumab after diagnosis of BM was not yet recommended. Remainders received either trastuzumab or lapatinib and trastuzumab (either concomitantly or sequentially) with or without chemotherapy. RESULTS: Median overall survival (OS) in patients receiving trastuzumab after diagnosis of BM was 13 months; corresponding numbers were 9 months in patients treated with chemotherapy, and 3 months with radiotherapy alone. Median OS was not reached in the lapatinib group. Addition of lapatinib prolonged OS over trastuzumab alone (P=0.002). After correction for potential confounders, lapatinib therapy remained an independent positive predictor for survival (HR 0.279; P=0.012). INTERPRETATION: This retrospective single-centre study suggests that the introduction of lapatinib improved survival in patients with BM from HER2-positive breast cancer. Patients with KPS ≥70 may benefit when treated with lapatinib in addition to trastuzumab after completion of local therapy.

Nerve injury-induced mechanical but not thermal hyperalgesia is attenuated in neurokinin-1 receptor knockout mice.

Mice lacking the gene encoding for substance P and neurokinin A, or the NK-1 receptor, exhibit alterations in behavior to various acute nociceptive stimuli. However, behavioral responses of NK-1 mutant animals have not been well characterized in models of chronic pain. We studied the behavioral responses of NK-1 knockout and wild-type control mice to thermal and mechanical stimuli before and after inducing chronic neuropathic pain by unilateral ligation of the L5 spinal nerve. Mechanical hyperalgesia was evaluated by determining the frequency of withdrawal to von Frey monofilaments applied to the hind paws. Nerve injury-induced hyperalgesia to thermal stimuli was examined by determining responses to radiant heat and cooling stimuli. The contribution of the sympathetic nervous system to mechanical hyperalgesia was evaluated by administering 3 mg/kg phentolamine, an alpha-adrenergic antagonist, subcutaneously. Following spinal nerve injury, withdrawal frequencies to mechanical stimulation increased in wild-type mice within 1 day and persisted during the 9-week observation period, whereas in the knockout mice, withdrawal frequencies did not increase significantly. In contrast, withdrawal latencies to radiant heat decreased up to 2 weeks after nerve injury in both the NK-1 and the wild-type mice. Similarly, the increase in withdrawal frequency to the cooling stimuli following the nerve injury was not different in the NK-1 knockout and wild-type mice. Mechanical hyperalgesia in the wild-type mice was not reversed by systemic administration of phentolamine, suggesting that the pain is not sympathetically maintained. The results indicate that NK-1 receptors contribute to the development of mechanical, but not thermal, hyperalgesia in neuropathic pain.

Life experiences among urban adolescents: examining the role of context.

Interest in the influence of context on the psychosocial development of adolescents led to the examination of neighborhood effects on the experience of adolescent life stress. Because of concerns regarding the population and ecological validity of existing measures of adolescent life events, the research group developed a scale for the measurement of life events among urban adolescents based on data from focus group interviews in the community of interest. Investigators utilized three strategies to examine the impact of neighborhood on adolescents' perceptions of life stress in a sample of 114 adolescents (mean age = 15). Results indicated that life stress in the peer domain varied by the adolescent's neighborhood of residence. In addition, family/community stress was linearly related to neighborhood indices of economic resources.

Preparation and antimicrobial assessment of 2-thioether-linked quinolonyl-carbapenems.

This reports the synthesis and in vitro antimicrobial properties of a series of 2-thioether-linked quinolonyl-carbapenems. Although the title compounds exhibited broad spectrum activity, the MICs were generally higher than those observed for selected benchmark carbapenems, quinolonyl-penems, and quinolones. Enzyme assays suggested that the title compounds are potent inhibitors of penicillin binding proteins and inefficient inhibitors of bacterial DNA-gyrase. Uptake studies indicated that the new compounds are not substrates for the norA encoded quinolone efflux pump.

HCO+ imaging of comet Hale-Bopp (C/1995 O1).

The HCO+ J = 1-0 rotational transition at 89.189 GHz has been mapped in comet Hale-Bopp (C/1995 O1) over a total of 38 individual days spanning the period 1997 March 10-June 20 with the Five College Radio Astronomy Observatory 14 m antenna. HCO+ is detectable over an extended region of the comet, with the peak emission commonly located 50,000-100,000 km in the antisolar direction. Maps made throughout the apparition show significant variability in the structure of the HCO+ coma, sometimes on timescales of several hours. The HCO+ brightness is usually depressed at the nucleus position, and on some occasions, the emission is spread into a ring around the position of the nucleus. Individual spectra within the maps display broad (approximately 4 km s-1) lines redshifted by 1-2 km s-1 or more from the nominal velocity of the nucleus, with the redshift typically increasing in the antisolar direction. The spectra and maps may be generally explained by models in which the ions are accelerated tailward at a rate on the order of 10 cm s-2, provided that HCO+ is destroyed within 50,000-100,000 km of the nucleus.

An unusual case of urinary incontinence, ataxia-telangiectasia, and metastatic dysgerminoma: case report and review of the literature.

Ataxia-telangiectasia (A-T) is a rare autosomal recessive disease notable for neurodegeneration, chromosomal instability, and a predisposition to cancer. It presents in childhood with a variable phenotype. We report the first case of an A-T related tumor presenting as urinary incontinence, and the first case of 2-year survival in an A-T patient with metastatic dysgerminoma.

Hydrogenation of interstellar molecules: a survey for methylenimine (CH2NH).

Methylenimine (CH2NH) has been convincingly detected for the first time outside the Galactic center as part of a study of the hydrogenation of interstellar molecules. We have observed transitions from energy levels up to about 100 K above the ground state in the giant molecular clouds W51, Orion KL and G34.3 + 0.15. In addition, CH2NH was found at the " radical-ion peak" on the quiescent ridge of material in the Orion molecular cloud. The abundance ratio CH2NH/HCN at the radical-ion peak agrees with the predictions of recent gas-phase chemical models. This ratio is an order of magnitude higher in the warmer cloud cores, suggesting additional production pathways for CH2NH, probably on interstellar grains.

Collisional quenching of OH radio emission from comet Hale-Bopp.

Observations of comets in the 18-cm OH transitions offer a means to probe gas production, kinematics, and OH excitation in comets. We present initial results of OH observations of comet Hale-Bopp obtained with the NRAO 43 m antenna located in Greenbank, WV. Maps of the emission provide strong constraints on the amount of quenching of the inversion of the OH ground state A-doublet in the coma. Analysis of the total radio OH flux and maps of its radial brightness distribution indicate a quenched region on the order of approximately 500,000 km during March and April 1997. This large value is generally consistent with previous observations of radio OH quenching in lower production rate comets when the high production rate of comet Hale-Bopp is considered.

HCO+ in the coma of comet Hale-Bopp.

Maps of comet C/1995 O1 (Hale-Bopp) in the millimeter-wave emission of the ion HCO+ revealed a local minimum near the nucleus position, with a maximum about 100,000 km in the antisolar direction. These observed features of the HCO+ emission require a low abundance of HCO+ due to enhanced destruction in the inner coma of the comet, within a region of low electron temperature (Te). To set constraints on the formation of HCO+ in the coma, as well as the location and magnitude of the transition to higher Te, the data are compared with the results of ion-molecule chemistry models.

Reduction of paraphimosis with hyaluronidase.

The use of hyaluronidase facilitates reduction of paraphimosis. It acts by dispersing extracellular edema, permitting easy reduction of the foreskin. Its use is applicable both in the hospital and outpatient setting. Hyaluronidase is widely available and keeps well if refrigerated. It is effective for children and adults.

Genetic linkage in Pseudomonas aeruginosa of algT and nadB: mutation in nadB does not affect NAD biosynthesis or alginate production.

The 68-min region of the chromosome of Pseudomonas aeruginosa (Pa) contains the gene algT, encoding a putative alternate sigma factor similar to sigma E in Escherichia coli, that is required for the expression of several genes in the alginate biosynthetic regulon. Sequences immediately upstream from algT were found to contain a divergently expressed open reading frame encoding a 60-kDa protein with 64 and 36% identity to the nadB gene products of E. coli and Bacillus subtilis, respectively. The nadB gene encodes L-aspartate oxidase and has been shown in several bacteria to be essential for de novo nicotinamide-adenine dinucleotide (NAD) biosynthesis. Pa nadB complemented the growth requirement for nicotinic acid in a nadB mutant strain of E. coli, suggesting that this gene encodes a functional homologue of L-aspartate oxidase. A nadB::Tn501 mutant was constructed by gene replacement in the alginate-producing strain, Pa FRD. This NadB- mutant still produced alginate and appeared normal with respect to the regulation of alginate synthesis. Interestingly, the NadB- mutant did not have an auxotrophic phenotype for nicotinic acid, indicating that this nadB was not essential for NAD biosynthesis in Pa. These results suggest the possibility that Pa has an alternate mechanism for de novo NAD biosynthesis.

Use of a standardized personal medical record by patients with hypertension: a randomized controlled prospective trial.

It is widely believed that patients' compliance can be increased by persuading them to participate in their own care. We tested whether patients with hypertension could manage their own clinical records and whether their doing so would affect the quality of their care. Two hundred patients were randomly assigned to an intervention or a control group. Those in the intervention group were asked to complete a 10-page booklet containing a personal standardized medical record. All patients were scheduled for a follow-up appointment at the end of one year and were referred to their general practitioners for interim care. At the end of the follow-up period, the proportion of patients seen was comparable in the two groups. More of the patients in the intervention group than in the control group filled out a questionnaire as requested, and more added comments. Within the intervention group, the proportion of patients seen and the fall in systolic blood pressure were significantly higher among the 44 patients who had completed the personal record as requested than among the 57 who had not. Patients who completed the personal record also had fewer compliance problems.

Mucoid-to-nonmucoid conversion in alginate-producing Pseudomonas aeruginosa often results from spontaneous mutations in algT, encoding a putative alternate sigma factor, and shows evidence for autoregulation.

The mucoid phenotype is common among strains of Pseudomonas aeruginosa that cause chronic pulmonary infections in patients with cystic fibrosis and is due to overproduction of an exopolysaccharide called alginate. However, the mucoid phenotype is unstable in vitro, especially when the cells are incubated under low oxygen tension. Spontaneous conversion to the nonmucoid form is typically due to mutations (previously called algS) that are closely linked to the alginate regulatory gene algT, located at 68 min on the chromosome. Our sequence analysis of algT showed that its 22-kDa gene product shares homology with several alternate sigma factors in bacteria, suggesting that AlgT (also known as AlgU) interacts directly with RNA polymerase core to activate the promoters of alginate genes. AlgT showed striking sequence similarity (79%) to sigma E of Escherichia coli, an alternate sigma factor involved in high-temperature gene expression. Our analysis of the molecular basis for spontaneous conversion from mucoid to nonmucoid, in the cystic fibrosis isolate FRD, revealed that nonmucoid conversion was often due to one of two distinct missense mutations in algT that occurred at codons 18 and 29. RNase protection assays showed that spontaneous nonmucoid strains with the algT18 and algT29 alleles have a four- to fivefold reduction in the accumulation of algT transcripts compared with the wild-type mucoid strain. Likewise, a plasmid-borne algT-cat transcriptional fusion was about 3-fold less active in the algT18 and algT29 backgrounds compared with the mucoid wild-type strain, and it was 20-fold less active in an algT::Tn501 background. These data indicate that algT is autoregulated. The spontaneous algT missense alleles also caused about fivefold-reduced expression of the adjacent negative regulator, algN (also known as mucB). Transcripts of algN were essentially absent in the algT::Tn501 strain. Thus, algT regulates the algTN cluster, and the two genes may be cotranscribed. A primer extension analysis showed that algT transcription starts 54 bp upstream of the start of translation. Although the algT promoter showed little similarity to promoters recognized by the vegetative sigma factor, it was similar to the algR promoter. This finding suggests that AlgT may function as a sigma factor to activate its own promoter and those of other alginate genes. The primer extension analysis also showed that algT transcripts were readily detectable in the typical nonmucoid strain PAO1, which was in contrast to a weak signal seen in the algT18 mutant of FRD. A plasmid-borne algT gene in PAO1 resulted in both the mucoid phenotype and high levels of algT transcripts, further supporting the hypothesis that AlgT controls its own gene expression and expression of genes of the alginate regulon.