The learning curve for interpretation of oesophageal high-resolution manometry: a prospective interventional cohort study.

BACKGROUND: High-resolution manometry has become the preferred choice of oesophagologists for oesophageal motor assessment, but the learning curve among trainees remains unclear. AIM: To determine the learning curve of high-resolution manometry interpretation. METHODS: A prospective interventional cohort study was performed on 18 gastroenterology trainees, naïve to high-resolution manometry (median age 32 ± 4.0 years, 44.4% female). An intake questionnaire and a 1-h standardised didactic session were performed at baseline. Multiple 1-h interpretation sessions were then conducted periodically over 15 months where 10 studies were discussed; 5 additional test studies were provided for interpretation, and results were compared to gold standard interpretation by the senior author. Hypothetical management decisions based on trainee interpretation were separately queried. Accuracy was compared across test interpretations and sessions to determine the learning curve, with a goal of 90% accuracy. RESULTS: Baseline accuracy was low for abnormal body motor patterns (53.3%), but higher for achalasia/outflow obstruction (65.9%). Recognition of achalasia reached 90% accuracy after six sessions (P = 0.01), while overall accurate management decisions reached this threshold by the 4th session (P < 0.001). Based on our data, the threshold of 90% accuracy for recognition of any abnormal from normal pattern was reached after 30 studies (3rd session) but fluctuated. Diagnosis of oesophageal body motor patterns remained suboptimal; accuracy of advisability of fundoplication improved, but did not reach 90%. CONCLUSIONS: High-resolution manometry has a steep learning curve among trainees. Achalasia recognition is achieved early, but diagnosis of other abnormal motor patterns and management decisions require further supervised training.

Liver transplantation for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is an increasing problem in the USA and worldwide. Current treatments for HCC include chemoembolization, radioembolization, liver resection, and liver transplantation in the setting of selected cirrhotic patients. Liver transplantation for HCC was controversial initially, but is now widely accepted as a curative approach. Cirrhotic patients who meet standards for transplantation and have a tumor burden within Milan criteria are eligible for transplantation and receive Model for End-Stage Liver Disease (MELD) exception points once listed. Given the decline in availability of donor organs, rewarding MELD exception points and performing liver transplants in these patients remain controversial. Despite this, various guidelines propose expanding eligibility criteria for cirrhotics with HCC, due to post-transplant outcomes comparable to patients transplanted without HCC. Following the transplant, issues include optimizing the type and amount of immunosuppression and screening for and treating recurrence of HCC.

Production of ansamycin polyketide precursors in Escherichia coli.

For the heterologous production of ansamycin polyketides such as rifamycin and geldanamycin in Escherichia coli, a number of unusual but important tools must be engineered into the bacterium. Here we demonstrate efficient production of the starter unit 3-amino-5-hydroxybenzoic acid (AHBA) and the methoxymalonyl extender unit in E. coli. Previous work has demonstrated the production of the ansamycin starter unit AHBA in E. coli in low yield. It was shown that the low yield is primarily due to acetylation of AHBA into N-acetyl-AHBA. Three methods for minimizing this side reaction were evaluated. First, a putative N-arylamine-acetyltransferase (NAT) was deleted from the E. coli chromosome, although this did not alter N-acetyl-AHBA production. Next, E. coli grown in media devoid of glucose yielded a nearly equal mixture of AHBA and N-acetyl-AHBA. Lastly, the NAT inhibitor glycyrrhizic acid was shown to further inhibit the acetylation reaction. The entire set of genes for synthesizing the methoxymalonyl extender unit was transferred from the geldanamycin producer Streptomyces hygroscopicus into E. coli. The pathway specific ACP isolated from the resulting recombinant strain was found to predominantly occur as methyoxymalonyl-ACP. Together, these findings set the stage for engineered biosynthesis of ansamycin polyketides in E. coli.

Selected neurologic complications in the patient with cancer. Brain metastases and spinal cord compression.

Nurses play a key role in care of patients with brain metastases and spinal cord compression. Care of this patient population is unique because the skills and knowledge of medical-surgical, neurologic, oncologic, and critical care nurses are required. With the wide variability among patients, a highly individualized care plan is necessary to meet the tremendous challenges of caring for patients with metastatic central nervous system disease.

The effect of sympatholytics on uncontrolled hemorrhage.

OBJECTIVE: To assess the possible benefits of sympatholytics on uncontrolled hemorrhage in unanesthetized rats. DESIGN: A randomized laboratory study using rats to test the effects of sympatholytics on uncontrolled hemorrhage. SETTING: Research laboratory. SUBJECTS: Forty female Sprague-Dawley rats, randomly assigned into four groups according to the treatment: untreated (Control); alpha-adrenergic blockade with phenoxybenzamine (Alpha); beta-adrenergic blockade with propranolol (Beta); and a combined alpha- and beta-adrenergic blockade by phenoxybenzamine and propranolol (Alpha/Beta). INTERVENTION: After cannulation under light ether, the rats were allowed to awaken. A baseline blood sample was withdrawn. The uncontrolled hemorrhage was initiated by tail resection and allowed to continue without intervention for the duration of the experiment. After 15 mins, 80 mL/kg isotonic saline fluid was infused at 4.4 mL/min. At 60 mins, another blood sample was drawn; changes in mean arterial pressure, hematocrit, blood loss, and mortality were observed for up to 180 mins. MAIN OUTCOME MEASURE: Survival, mortality, blood loss (amount, prevalence, and rate), and hemodynamic variables (mean arterial pressure, pulse rate, hematocrit). RESULTS: In the Alpha group, there was a reduction in spontaneous blood loss compared with the control group (2.9 vs. 10.6 mL/kg, respectively) and 100% survival. In contrast, the Beta group exhibited an increase in tail blood loss (21.1 mL) and a decreased survival (10%). Despite the enhanced hemorrhage in the Alpha/Beta group (17.0 mL/kg) compared with controls, the survival rate in both of these groups was 60%. In all groups, no significant increase in tail blood loss was observed after 60 mins. CONCLUSIONS: An alpha-adrenergic blockade increased survival in uncontrolled hemorrhage by significantly reducing spontaneous blood loss. Conversely, a beta-adrenergic blockade significantly decreased survival and increased blood loss, whereas a combined blockade significantly increased blood loss without affecting survival.

The effects of varying fluid volume and rate of resuscitation during uncontrolled hemorrhage.

BACKGROUND: The role of rate and volume of infusion in survival from experimental uncontrolled hemorrhage was evaluated. METHODS: Hemorrhage was initiated using tail resection in 43 female rats assigned to the following five groups: nonresuscitated; resuscitated with moderate volume, slower rate; resuscitated with moderate volume, faster rate; resuscitated with high volume, slower rate; and resuscitated with high volume, faster rate. RESULTS: A trend toward improved survival was noted with faster rate of infusion (60 vs. 33.3% survival rate with moderate volume and 28.6 vs. 12.5% with high volume, compared with 16.7% in the nonresuscitated animals). CONCLUSION: Rapid infusion of moderate volume of isotonic saline improved survival in uncontrolled hemorrhage. Extreme volumes, infused rapidly, also resulted in higher survival rates compared with those observed in nonresuscitated rats.

Developmental care teams in the neonatal intensive care unit: survey on current status.

Developmental Care Teams (DCT) have evolved in Neonatal Intensive Care Units (NICUs) in response to mounting evidence that developmental care is cost-effective and improves outcomes of critically ill newborns. Lack of national practice guidelines and standardized roles for DCT members prompted formulation and distribution of a questionnaire to obtain information regarding staff membership of DCTs, budgeting for DCTs, utilization of developmental care in practice, and education and developmental training of NICU staff. Questionnaires were sent to 50 NICUs in 30 states, with a return rate of 62% (31 of 50), representing 18 different states. Of those who responded, 64% had a DCT, and an additional 24% were in various phases of starting a team. Forty-three percent of the teams meeting on a regular basis did so monthly. Only 30% of those with a DCT had a dedicated budget to cover operating costs of their developmental program. Fifty-two percent of respondents had Neonatal Individualized Developmental Care and Assessment Program (NIDCAP)-certified staff at their institutions; however, nine other types of developmental specialists were also listed. Only four respondents indicated utilization of set criteria for initiation of a DCT consult, and 74% of those with DCTs initiated consults "when the need arises." NIDCAP assessments were used for parent teaching (54%), care plans (69%), care recommendations (46%), and at caregiver "discretion" (39%). The results of the survey validated an intense interest in developmental care. Approach to developmental care is variable between NICUs and implementation as outlined by NIDCAP is unusual. Practical guidelines for utilization and funding of DCTs are needed.

A comparison of temperature-taking methods in neonates.

PURPOSE: The purpose of this study was to compare temperature measurements from glass/mercury thermometers to Tempa.Dot Single-Use Clinical Thermometer, B-D Digital Fever Thermometer, Mon-a-Therm Model 1000 Skin Temperature Monitor, IVAC CORE.CHECK Tympanic Thermometer, and IncuTemp3 radiant warmer skin temperature sensor measurements. The effects of ten environmental, developmental, and pharmacological factors on thermometer readings were also assessed. DESIGN: The design was descriptive. SAMPLE: The convenience sample included 220 infants > or = 1,500 gm (average weight of 2,715 +/- 743 gm). Average age was 17 +/- 22 days of life. MAIN OUTCOME VARIABLE: The outcomes were comparisons between the "reference" axillary glass/mercury thermometer readings and axillary, skin, and tympanic measurements obtained from other thermometers. RESULTS: The B-D Digital Fever thermometer had the highest correlation with the glass/mercury thermometer for axillary temperature. Tempa.DOT measurements showed the next highest correlation with the glass/mercury thermometer measurements. Tympanic temperature measured by CORE.CHECK was moderately correlated with the glass/mercury thermometer measurement. Skin temperatures were influenced by nesting, clothing, swaddling, and probe site placement. Tympanic readings showed effects of bed type and environmental temperature.