When ignorance is bliss: weight perception, body mass index and quality of life in adolescents.

BACKGROUND/OBJECTIVES: Body weight is negatively associated with adolescent Health-Related Quality of Life (HRQoL). Despite this well-established relationship, some adolescents with obesity do not display the expected HRQoL decreases. This study hypothesised weight perception as a moderator of the association between weight status and adolescent HRQoL. SUBJECTS/METHODS: Subjects were secondary school students from an obesity prevention project in the Barwon South-West region of Victoria, Australia, entitled It's Your Move (N=3040). Measures included standardised body mass index (BMI-z; World Health Organization growth standards), weight perception and HRQoL, measured by the Paediatric Quality of Life Inventory. Linear regression and average marginal effect analyses were conducted on cross-sectional baseline data to determine the significance of any interaction between weight perception and measured weight status in shaping adolescent HRQoL. RESULTS: The BMI-z/perceived weight status interaction was significantly associated with adolescent HRQoL outcomes. Adolescents with BMI z-scores in the overweight/obesity range who perceived themselves as overweight had lower HRQoL than those who perceived themselves as 'about right.' Conversely, adolescents with BMI scores in the lower end of the normal range or in the thinness range who perceived themselves as underweight had lower HRQoL than those with 'about right' perceptions. CONCLUSIONS: This was the first study to report third-variable impacts of a body-perception variable on the relationship between adolescent weight status and HRQoL. Adolescents' weight perceptions significantly moderated the relationship between overweight/obesity and reduced HRQoL. Adolescents who were outside the normal weight range and misperceived their objectively measured weight status enjoyed a higher HRQoL than adolescents whose weight perception was concordant with their actual weight status. These findings suggest that practitioners may need to exercise caution when educating adolescents about their weight status, as such 'reality checks' may negatively impact on adolescent HRQoL. It is suggested that more research be conducted to examine this potential effect.

Priority recommendations for the implementation of patient-reported outcomes in clinical cancer care: a Delphi study.

PURPOSE: The aim of this study was to develop priority recommendations for the service level implementation of patient-reported outcomes (PROs) into clinical cancer care. METHODS: Development of draft guidance statements was informed by a literature review, the Knowledge to Action (KTA) implementation framework, and discussion with PRO experts and cancer survivors. A two-round modified Delphi survey with key stakeholders including cancer survivors, clinical and research experts, and Information Technology specialists was undertaken. Round 1 rated the importance of the statements and round 2 ranked statements in order of priority. RESULTS: Round 1 was completed by 70 participants with round 2 completed by 45 participants. Forty-seven statements were rated in round 2. In round 1, the highest agreement items (>90% agreement) included those that focused on the formation of strong stakeholder partnerships, ensuring ongoing communication within these partnerships, and the use of PROs for improvement and guidance in clinical care. Items ranked as the highest priorities in round 2 included assessment of current staff capabilities and service requirements, mapping of workflows and processes to enable collection, and using collected PROs to guide improved health outcomes. CONCLUSIONS: This stakeholder consultation process has identified key priorities in PRO implementation into clinical cancer care that include clinical relevance, stakeholder engagement, communication, and integration within the existing processes and capabilities. IMPLICATION FOR CANCER SURVIVORS: Routine adoption of PRO collection by clinical cancer services requires multiple implementation steps; of highest priority is strong engagement and communication with key stakeholders including cancer survivors.

The effect of sporting events on emergency department attendance rates in a district general hospital in Northern Ireland.

BACKGROUND: Previous studies have reported a conflicting relationship between the effect of live and televised sporting events on attendance rates to emergency departments (ED). The objectives of this study were to investigate the relationship of major sporting events on emergency department attendance rates and to determine the potential effects of such events on service provision. METHODS: A retrospective analysis of ED attendances to a district general hospital (DGH) and subsequent admissions over a 24-h period following live and televised sporting activities was performed over a 5-year period. Data were compiled from the hospital's emergency record books including the number of attendances, patient demographics, clinical complaint and outcome. Review patients were excluded. Analysis of sporting events was compiled for live local, regional and national events as well as world-wide televised sporting broadcasts. RESULTS: A total of 137,668 (80,445 men) patients attended from April 2002 to July 2007. Mean attendance rate per day was 80 patients (men = 47). Mean admission rate was 13.6 patients per day. Major sporting events during the study period included; Soccer: 4 FA Cup and 1 World Cup (WC) finals; Rugby: 47 Six Nations, 25 Six nations games involving Ireland, 1 WC final, 2 WC semi-finals, 2 WC quarter-finals and 4 WC games involving Ireland; and Gaelic Football [Gaelic Athletic Association (GAA)]: 5 All-Ireland finals, 11 semi-finals, 11 quarter-finals and 5 provincial finals. There was a significantly higher patient admission rate during the soccer FA Cup final, Rugby Six Nations and games involving Ireland and for GAA semi- and quarter-final games (p = 0.001-0.01). There was no difference identified in total attendance or non-admission rates for sporting events throughout the study period. Although there was no correlation identified between any of these sporting events and total emergency department attendances (r < 0.15, p > 0.07), multinomial logistic regression demonstrated that FA Cup final (p = 0.001), Rugby Six Nations (p = 0.019), Rugby WC games involving Ireland (p = 0.003), GAA All-Ireland semi- and quarter-finals (p = 0.016; p = 0.016) were predictors of patient admission rates. CONCLUSION: This study suggests that live or televised sporting events do not significantly affect ED attendances to a DGH. However, some events appeared to be predictors of patient admission rates. Although it may be beneficial to consider the effect of sporting events on service stratification during these periods, the overall effect is probably minimal and should not create a major concern for future service provision despite the implementation of the European Working Time Directive.

Acetyl-l-carnitine and nucleoside reverse transcriptase inhibitor-associated neuropathy in HIV infection.

OBJECTIVES: Antiretroviral toxic neuropathy (ATN) is associated with dideoxynucleoside reverse transcriptase inhibitor use in patients infected with HIV, possibly as a result of mitochondrial toxicity. Acetyl-l-carnitine (ALC) has been linked to symptomatic improvement in ATN. We present an open-label single-arm pilot study to evaluate changes in intra-epidermal nerve fibre (IENF) density and mitochondrial DNA (mtDNA) copies/cell among subjects treated with 3000 mg ALC daily. METHODS: Punch skin biopsies were examined at baseline and after 24 weeks of therapy. Participants reported neuropathic symptoms using the Gracely Pain Intensity Score. Neurological examinations were completed. RESULTS: Twenty-one subjects completed the study. ALC was generally well tolerated. The IENF density did not change in cases completing 24 weeks of ALC therapy, with median (90% confidence interval) IENF changes of -1.70 (-3.50, infinity) (P=0.98) and 2.15 (-0.10, infinity) (P=0.11) for the distal leg and proximal thigh, respectively. Fat mtDNA copies/cell did not change with therapy. Improvements in neuropathic pain (P<0.01), paresthesias (P=0.01), and symptoms of numbness (P<0.01) were noted. Similarly, improvement was noted on the Gracely Pain Intensity Score. CONCLUSIONS: ALC therapy coincided with improvements in subjective measures of pain in this open-label single-arm study. However, changes were not observed in objective measures of IENF density or mtDNA levels, providing little objective support for use of ALC in this setting.

Sustaining obesity prevention in communities: a systematic narrative synthesis review.

Obesity is a global problem for which sustainable solutions are yet to be realized. Community-based interventions have improved obesity-related behaviours and obesity in the short term. Few papers have explored how to make the interventions and their intended outcomes sustainable. The aim of this paper is to identify factors that contribute to the sustainability of community-based obesity prevention interventions and their intended outcomes. A systematic narrative synthesis review was conducted of published community-based obesity prevention interventions to identify factors contributing to intervention sustainability. Data extracted were included study authors' perspectives of intervention success and sustainability. Eighty-one papers met the inclusion criteria, and from these we identified ten factors that contribute to sustainability: resourcing, leadership, workforce development, community engagement, partnerships, policy, communications, adaptability, evaluation and governance. This review of community-based obesity prevention interventions gives rise to optimism that sustainable change is possible. We propose a framework to help practitioners build sustainability into their interventions and report on them so that others can also benefit.

Comparing complex perspectives on obesity drivers: action-driven communities and evidence-oriented experts.

INTRODUCTION: The Foresight obesity map represents an expert-developed systems map describing the complex drivers of obesity. Recently, community-led causal loop diagrams have been developed to support community-based obesity prevention interventions. This paper presents a quantitative comparison between the Foresight obesity systems map and a community-developed map of the drivers of obesity. METHODS: Variables from a community-developed map were coded against the thematic clusters defined in the Foresight map to allow comparison of their sizes and strength of adjoining causal relationships. Central variables were identified using techniques from network analysis. These properties were compared to understand the similarities and differences between the systems as defined by the two groups. RESULTS: The community map focused on environmental influences, such as built physical activity environment (18% of variables) and social psychology (38%). The Foresight map's largest cluster was physiology (23%), a minimal focus in the community map (2%). Network analysis highlighted media and available time within both maps, but variables related to school and sporting club environments were unique to the community map. CONCLUSION: Community stakeholders focus on modifiable social and environmental drivers of obesity. Capturing local perspectives is critical when using systems maps to guide community-based obesity prevention.

Fetal membrane healing after spontaneous and iatrogenic membrane rupture: a review of current evidence.

In view of the important protective role of the fetal membranes, wound sealing, tissue regeneration, or wound healing could be life saving in cases of preterm premature rupture of the membranes. Although many investigators are studying the causes of preterm premature rupture of membranes, the emphasis has not been on the wound healing capacity of the fetal membranes. In this review, the relevant literature on the pathophysiologic condition that leads to preterm premature rupture of membranes will be summarized to emphasize a continuum of events between rupture and repair. We will present the current knowledge on fetal membrane wound healing and discuss the clinical implications of these findings. We will critically discuss recent experimental interventions in women to seal or heal the fetal membranes after preterm premature rupture of membranes.

Expression of pro form of prostate-specific antigen by mammalian cells and its conversion to mature, active form by human kallikrein 2.

To study the expression, biosynthesis, and processing of prostate-specific antigen (PSA) in mammalian cells, recombinant PSA was expressed in Syrian hamster tumor cell line AV12-664 (AV12-PSA). Expression of PSA was monitored by the Tandem-MP PSA assay. PSA was secreted into the medium during the logarithmic phase of cell growth at >9 microg/ml and was stable. The PSA purified from spent medium of AV12-PSA cells did not exhibit any enzymatic activity and did not complex with the protease inhibitor, alpha-1-antichymotrypsin. These findings indicated that an inactive form of PSA was expressed by AV12-PSA cells. NH2-terminal sequencing confirmed the identity of the PSA purified from the spent medium of AV12-PSA cells to be pro-PSA. This demonstrates that PSA is expressed as pro-PSA by mammalian cells and suggests that pro-PSA may be present in biological fluids. Human kallikrein 2 (hK2), another member of the hK family, is also expressed predominantly in prostate epithelium. Although hK2 has been shown to exhibit trypsin-like activity, little is known about its natural substrates. Using purified proteins, we show that hK2 can convert pro-PSA to mature, enzymatically active PSA, thus establishing a physiological connection between hK2 and PSA. These findings imply that hK2 may be regulating PSA activity in vivo.

Identification of a novel complex between human kallikrein 2 and protease inhibitor-6 in prostate cancer tissue.

Human kallikrein (hK) 2 is an arginine-selective serine protease expressed predominantly in the prostate that has an 80% sequence identity with prostate-specific antigen. Expression of hK2 is elevated in the tumor epithelium compared to benign prostate tissue. We have purified, sequenced, and identified a novel hK2 complex in prostate tissue consisting of hK2 and a serine protease inhibitor known as protease inhibitor-6 (PI-6). This 64-kDa SDS-PAGE stable complex is elevated in the tumor and is approximately 10% of total hK2. No comparable complex of prostate-specific antigen was detected. PI-6, also known as cytoplasmic antiprotease, has been characterized as an intracellular inhibitor of trypsin and chymotrypsin-like proteases, which has high homology to plasminogen activator inhibitor 1 and 2. The physiological role of PI-6 in the prostate and its relationship to hK2 and prostate cancer are under investigation.

Expression of human glandular kallikrein, hK2, in mammalian cells.

The human kallikrein family consists of three members, hK1, hK2, and hK3 [prostate-specific antigen (PSA)]. PSA is a widely accepted marker for prostate cancer. The mRNAs for both hK2 and PSA are localized predominantly to prostate epithelium and are regulated by androgens. In addition, hK2 has 78% amino acid homology to PSA. Although similarities to PSA make hK2 a potential prostate cancer marker, they also impede biochemical characterization of hK2 in those human tissues and body fluids where PSA is abundant. To study the expression, biosynthesis, and processing of hK2, recombinant hK2 was expressed in the adenovirus-induced Syrian hamster tumor cell line AV12-664 (AV12-hK2). Expression of hK2 was analyzed by Western blots and ELISA using monoclonal antibodies HK1G 464.3 [specific for prohK2 (phK2)] and HK1D 106.4 [specific for phK2 and mature hK2 (hK2)1. Western blot and ELISA analyses showed that phK2 was secreted into the media by AV12-hK2 cells on day 1 and was gradually converted to the mature form of hK2 by day 7. N-terminal amino acid sequencing verified the Western blot and ELISA data. This demonstrates for the first time that hK2 is secreted as phK2 and converted to hK2 extracellularly. In addition, hK2 detected in day 4-7 AV12-hK2-spent media was enzymatically active. Recombinant hK2 was also expressed in human prostate carcinoma cell lines, PC3 (PC3-hK2) and DU145 (DU145-hK2), that do not express endogenous hK2 or PSA. Similar to AV12-hK2 cells, both cell lines secreted phK2 that was converted to hK2 extracellularly. phK2 was the major form detected in the spent media of PC3-hK2 cells, even after 7 days, indicating a slow conversion of phK2 to hK2. hK2 was the predominant form detected in the spent media of DU145-hK2 starting on day 1, indicating the rapid conversion of phK2 to hK2. In this study, we demonstrate that hK2 exists in different forms and is secreted as phK2. phK2 is then converted to enzymatically active hK2 extracellularly.

A precursor form of prostate-specific antigen is more highly elevated in prostate cancer compared with benign transition zone prostate tissue.

Prostate-specific antigen (PSA) is a widely used serum marker for prostate cancer (PCa), but in the critical diagnostic range of 4-10 ng/ml it has limited specificity for distinguishing early PCa from benign prostatic hyperplasia (BPH). PSA in serum is comprised of a variety of both "free" and "complexed" forms that have been used to improve the specificity of PSA for prostate cancer detection. We previously reported that pro PSA (pPSA), the zymogen or precursor form of PSA, is a component of free PSA in the serum of PCa patients. In the current study, we examined prostate tissues to understand the origin and specificity of pPSA. PSA was immuno-affinity purified from matched sets of prostate tissues including peripheral zone cancer (PZ-C); peripheral zone noncancer; and benign tissue from the transition zone (TZ), the primary site of BPH within the prostate. We found that pPSA is differentially elevated in PZ-C, but is largely undetectable in TZ. N-terminal sequencing revealed that the pPSA was comprised primarily of [-2]pPSA and minor levels of [-4]pPSA, containing pro leader peptides of 2 and 4 amino acids, respectively. The median value of pPSA was 3% in PZ-C and 0% (undetectable) in TZ (P < 0.0026). No pPSA was detected in 13 of 18 transition zone specimens (72%), but only 2 of the 18 matched cancer specimens (11%) contained no measurable pPSA. These results demonstrate that pPSA is more highly correlated with prostate cancer than with BPH. The pPSA in serum may represent a more cancer-specific form of PSA that could help distinguish prostate cancer from BPH.

A truncated precursor form of prostate-specific antigen is a more specific serum marker of prostate cancer.

Prostate-specific antigen (PSA) is a widely used serum marker for prostate cancer (PCa) but has limited specificity for distinguishing early PCa from benign prostatic hyperplasia, because both PCa and benign prostatic hyperplasia release PSA into the serum. We have identified previously a truncated form of precursor PSA (pPSA) in prostate tumor extracts consisting of PSA with a serine-arginine pro leader peptide ([-2]pPSA) instead of the normally expressed 7 amino acid pro leader peptide. In the current study we developed monoclonal antibodies to detect [-2]pPSA and other isoforms of pPSA for Western blot analysis. PSA was immunoaffinity purified from 100 to 200 ml of serum from each of five men with biopsy-proven cancer and three biopsy-negative men, all with total PSA levels in the diagnostically relevant range near 10 ng/ml. The truncated [-2]pPSA was estimated to range from 25 to 95% of the free PSA in the five PCa samples but only 6-19% of the free PSA in the biopsy-negative men. Immunohistochemical studies showed positive staining for [-2]pPSA in PCa epithelium and that [-2]pPSA was enriched in cancer cell secretions. In vitro activation studies showed that human kallikrein 2 and trypsin readily activated full-length pPSA but were unable to activate [-2]pPSA to mature PSA. Thus, [-2]pPSA, once formed, is a stable but inactive isoform of PSA. Truncated [-2]pPSA may represent an important new diagnostic marker for the early detection of PCa.

Expectant treatment or cholecystectomy after endoscopic retrograde cholangiopancreatography for choledocholithiasis in patients over 80 years old?

BACKGROUND: It is recommended that most patients between 18-80 years old, who have had an endoscopic retrograde cholangiopancreatography (ERCP) for choledocholithiasis, should be offered cholecystecytomy. However, we were uncertain whether this was the correct advice for patients over 80. METHOD: A retrospective case note analysis was performed on 81 patients over 80, who had had an ERCP for choledocholithiasis. The primary end points were further biliary symptoms, cholecystectomy, death from biliary independent causes, and those still alive without further biliary symptoms. RESULTS: The records of 81 patients (median age 87; range, 80-96 years) were analyzed. Of the patients, 11% experienced further biliary symptoms at a median time of 4.5 months [interquartile range (IQR), 2.25-8.5 months] from the ERCP; 6% received cholecystectomy; 61% were still alive with no further biliary symptoms at a median time of 17 months (IQR, 12.25-23.75 months) after ERCP; and 22% had died from biliary independent causes at a median time of 9 months after ERCP (IQR, 3-12 months). CONCLUSION: Expectant treatment can be recommended in this group of patients. Those who do present with further biliary symptoms do so soon after ERCP. Therefore, we recommend follow-up for 12 months after ERCP, prior to discharge.

Long-term treatment with recombinant nerve growth factor for HIV-associated sensory neuropathy.

HIV-associated distal sensory polyneuropathy (DSP) is a common complication of AIDS. No effective treatment is available. The authors investigated the long-term effect (48 weeks) of the neurotrophin nerve growth factor (NGF) in an open-label study of 200 subjects with HIV-associated DSP. Similar to their previously reported double-blind study, the authors showed that NGF was safe and well tolerated and significantly improved pain symptoms. However, there was no improvement of neuropathy severity as assessed by neurologic examination, quantitative sensory testing, and epidermal nerve fiber density.

A phase II trial of nerve growth factor for sensory neuropathy associated with HIV infection. AIDS Clinical Trials Group Team 291.

OBJECTIVE: To evaluate the safety and efficacy of recombinant human nerve growth factor (rhNGF) in HIV-associated sensory neuropathy (SN) within a multicenter, placebo-controlled, randomized trial (ACTG 291). BACKGROUND: SN affects 30% of individuals with AIDS, is worsened by neurotoxic antiretrovirals, and its treatment is often ineffective. NGF is trophic for small sensory neurons and stimulates the regeneration of damaged nerve fibers. METHODS: A total of 270 patients with HIV-associated SN were randomized to receive placebo, 0.1 microg/kg rhNGF, or 0.3 microg/kg rhNGF by double-blinded subcutaneous injection twice weekly for 18 weeks. The primary outcome was change in self-reported neuropathic pain intensity (Gracely Pain Scale). Secondary outcomes included an assessment of global improvement in neuropathy by patients and investigators, neurologic examination, use of prescription analgesics, and quantitative sensory testing. In a subset, epidermal nerve fiber densities were determined in punch skin biopsies. RESULTS: Both doses of NGF produced significant improvements in average and maximum daily pain compared with placebo. Positive treatment effects were also observed for global pain assessments (p = 0.001) and for pin sensitivity (p = 0.019). No treatment differences were found with respect to mood, analgesic use, or epidermal nerve fiber densities. Injection site pain was the most frequent adverse event, and resulted in unblinding in 39% of subjects. Severe transient myalgic pain occurred in eight patients, usually from accidental overdosing. There were no changes in HIV RNA levels or other laboratory indices. CONCLUSIONS: We found a positive effect of recombinant human nerve growth factor on neuropathic pain and pin sensitivity in HIV-associated sensory neuropathy. rhNGF was safe and well tolerated, but injection site pain was frequent.

Stimulus access to the accessory olfactory system in the prenatal and perinatal rat.

The fetal rat can detect odors in its amniotic fluid. Indirect evidence suggests that the accessory olfactory system may be mediating chemoreception prenatally. The primary goal of this study was to determine if stimuli in the amniotic fluid gain access to the receptor neurons of the accessory olfactory system that are sequestered inside the vomeronasal organ. Other goals of the study were to compare the access of stimuli to the vomeronasal organ in the prenatal and young postnatal rat and to examine the role of the autonomic nervous system in this process. On the day before birth fluorescent beads (0.95 microns diameter) were injected into the amniotic sacs of rat fetuses from seven dams. After 4-6 h one group of mothers received an i.p. injection of epinephrine (either 60 or 75 micrograms) and another group received no injection. One hour later pups were collected and processed for histological examination using fluorescence microscopy. A portion of the fetuses from both treatment groups had significant numbers (< 50) of beads in their nasal passages. Some of these subjects also had beads in the vomeronasal organ. There was no significant difference in the proportion of subjects with beads in the nasal cavities or vomeronasal organ across the two treatments. In a second experiment, five- to seven-day-old rat pups had beads infused into one naris. After 3-4 h one group was injected i.p. with epinephrine (2-4 micrograms), while a second group received no injection. As expected, virtually all the subjects had large numbers of beads in their nasal cavities upon post mortem examination.(ABSTRACT TRUNCATED AT 250 WORDS)

Investigations of cytoskeletal elements in cultured bovine meshwork cells.

An ultrastructural, immunohistochemical, and functional study was conducted on cultured bovine meshwork cells. Particular emphasis was placed on the organization of the cytoskeleton, and the cells were viewed either as whole cells or following detergent extraction. For ultrastructural examination, several modes of viewing were adopted, including a detector situated above the specimens collecting secondary electrons (SE), a detector situated beneath the specimen collecting transmitted electrons (STEM), and conventional transmission electron microscopy at 100 KV (TEM). In whole cell mounts, information was obtained about the organization of the cytoskeleton and its relationship to other cytoplasmic organelles. Extraction procedures removed much of the plasma membrane and most organelles. The nucleus and cytoskeleton remained and stress fibers were prominent. Immunohistochemistry showed that the actin content of the cytoskeleton could be preserved after detergent extraction. Detergent-extracted cells decreased their surface area when exposed to MgATP in a dose-dependent manner. The decrease in surface area was associated with disassembly of cytoskeletal stress fibers and was optimal with 1 mM MgATP. Whether or not the change in surface area could be considered a "contractile event" was discussed.

Identification of both NK1 and NK2 receptors in guinea-pig airways.

1. NK1 and NK2 receptors have been characterized in guinea-pig lung membrane preparations by use of [125I-Tyr8]-substance P and [125I]-neurokinin A binding assays in conjunction with tachykinin-receptor selective agonists ([Sar9Met(O2)11]substance P for NK1 and [beta Ala8]neurokinin A (4-10) for NK2) and antagonists (CP-99,994 for NK1 and SR48968 for NK2). 2. The presence of high affinity, G-protein-coupled NK1 receptors in guinea-pig lung parenchymal membranes has been confirmed. The rank order of affinity for competing tachykinins was as predicted for an NK1 receptor: substance P = [Sar9Met(O2)11]substance P > substance P-methyl ester = physalaemin > neurokinin A = neurokinin B >> [beta Ala8]neurokinin A (4-10). The novel NK1 antagonist CP-99,994 has a Ki of 0.4 nM at this NK1 site. 3. In order to characterize [125I]-neurokinin A binding to guinea-pig lung, the number of [125I]-neurokinin A specific binding sites was increased 3-4 fold by purification of the parenchymal membranes over discontinuous sucrose gradients. The rank order of affinity determined for NK1- and NK2-receptor agonists and antagonists in competition for these sites showed that the majority (80%) of [125I]-neurokinin A specific binding was also to the NK1 receptor. 4. Under conditions where the guinea-pig lung parenchymal NK1 receptor was fully occupied by a saturating concentration of either [Sar9Met(O2)11]substance P (1 microM) or CP-99,994 (2.7 microM), residual [125I]-neurokinin A specific binding was inhibited in a concentration-dependent manner by both [beta Ala8]neurokinin A and SR48968. This result shows that the NK2 receptor is also present in these preparations. 5. Similar studies using guinea-pig tracheal membranes demonstrated that [125I]-neurokinin A specific binding was composed of a NK1-receptor component (60%), inhibited by both [Sar9Met(02)11]substance P and CP-99,994, and a significant NK2-receptor component, inhibited by both [beta Ala 8]neurokinin A andSR48968.6. In summary, these data demonstrate that guinea-pig lung parenchyma and guinea-pig trachea express both NK1 and NK2 receptors.

The management of acid-related dyspepsia in general practice: a comparison of an omeprazole versus an antacid-alginate/ranitidine management strategy. Compete Research Group [corrected].

BACKGROUND: There is need for an evidence-based comparison of clinical management strategies to provide the rationale for selection of a particular therapeutic approach to treatment. Ideal dyspepsia treatment should quickly and conveniently alleviate patient symptoms whilst also minimizing the use of healthcare resources. AIM: To examine dyspepsia symptom relief over 16 weeks and compare an omeprazole clinical management strategy with a commonly used combination of antacid-alginate followed by H2-antagonist. METHODS: Seven hundred and twenty-five patients participated in this randomized, open, parallel group comparison over 16 weeks. Patients were randomized to receive either an omeprazole treatment strategy (363) consisting of omeprazole 10 mg stepping up to 20 mg and 40 mg as required, or an antacid-alginate/ranitidine treatment strategy (362) consisting of antacid-alginate 10 mL q.d.s. stepping up to ranitidine 150 mg b.d. and 150 mg q.d.s. as required. RESULTS: A greater proportion of patients receiving the omeprazole clinical management strategy had achieved the stringent health target of complete symptom relief (61 vs. 40%, P < 0.0001) at 16 weeks. Forty-six per cent of omeprazole-treated patients were symptom free after the first 10 mg step compared to only 17% in the antacid-alginate treated group (P = 0.0001). Total relief of heartburn, the most common symptom at entry, was achieved by more patients in the omeprazole treatment group than the antacid-alginate/ranitidine treatment group, 62 vs. 36%, respectively, at 4 weeks, and 81 vs. 60% at 16 weeks (P = 0.0001). CONCLUSION: Treatment with the omeprazole clinical management strategy was superior to the antacid-alginate/ranitidine management strategy in providing relief of acid-related dyspepsia symptoms after 16 weeks. In addition, the omeprazole treatment strategy involved fewer GP consultations and thus minimized the use of other healthcare resources.

A randomized trial of three antibiotic regimens for the treatment of pyelonephritis in pregnancy.

OBJECTIVE: To compare the effectiveness of three antibiotic regimens for the treatment of acute pyelonephritis in pregnancy. METHODS: One hundred seventy-nine pregnant women earlier than 24 weeks' gestation who had acute pyelonephritis were randomized to 1) intravenous (i.v.) ampicillin and gentamicin, 2) i.v. cefazolin, or 3) intramuscular ceftriaxone. All participants then completed 10-day courses of oral cephalexin after primary treatment. A urine culture was performed on admission and 5-14 days after completion of therapy. Surveillance for persistent or recurrent infection and obstetric complications continued until delivery. On the basis of a two-sided hypothesis test and with alpha = .025, 60 subjects were needed in each group for statistical power greater than 80% to detect a difference between ceftriaxone and other antibiotics if hospital length of stay differed by 1 or more days. RESULTS: The treatment groups were similar in age, parity, temperature, gestational age, and initial white blood cell count. There were no statistically significant differences in length of hospitalization, hours until becoming afebrile, days until resolution of costovertebral angle tenderness, or infecting organism. There were no statistically significant differences in birth outcomes between the three groups. The average (standard deviation) age at delivery was 38.8 +/- 3.6 weeks. The average birth weight was 3274 +/- 523 g. Eleven (6.9%) of 159 subjects delivered prematurely. Escherichia coli was the most common uropathogen isolated (137 of 179, 76.5%). Blood cultures were positive for organisms in 15 cases (8.4%). At follow-up examination within 2 weeks of initial therapy, eight (5.0%) of 159 subjects had urine cultures positive for organisms. Ten women (6.3%) had cultures positive for organisms later in their antepartum course, and 10 other participants (6.3%) developed recurrent pyelonephritis. CONCLUSION: There are no significant differences in clinical response to antimicrobial therapy or birth outcomes among subjects treated with ampicillin and gentamicin, cefazolin, or ceftriaxone for acute pyelonephritis in pregnancy before 24 weeks' gestation.