Peritoneal Cytokine Levels Can Predict Anastomotic Leak on the First Postoperative Day.

BACKGROUND: Accumulating evidence suggests that peritoneal cytokine concentrations may predict anastomotic leak after colorectal surgery, but previous studies have been underpowered. OBJECTIVE: We aimed to test this hypothesis by using a larger prospectively collected data set. DESIGN: This study is an analysis of prospectively collected data. SETTINGS: This study was conducted at 3 public hospitals in Auckland, New Zealand. PATIENTS: Patients undergoing colorectal surgery recruited as part of 3 previous randomized controlled trials were included. MAIN OUTCOME MEASURES: Data on peritoneal and plasma levels of interleukin-6, interleukin-8, interleukin-10, and tumor necrosis factor-α on day 1 after colorectal surgery were reanalyzed to evaluate their predictive value for clinically important anastomotic leak. Area under receiver operating characteristic curve analysis was performed. RESULTS: A total of 206 patients with complete cytokine data were included. The overall anastomotic leak rate was 8.3%. Concentration levels of peritoneal interleukin-6 and interleukin-10 on day 1 after colorectal surgery were predictive of anastomotic leak (area under receiver operating characteristic curve, 0.72 and 0.74; p = 0.006 and 0.004). Plasma cytokine levels of interleukin-6 were higher on day 1 after colorectal surgery in patients who had an anastomotic leak, but this was a poor predictor of anastomotic leak. Levels of other peritoneal and plasma cytokines were not predictive. LIMITATIONS: The study was not powered a priori for anastomotic leak prediction. Although the current data do suggest that peritoneal levels of interleukin-6 and interleukin-10 are predictive of leak, the discriminative value in clinical practice remains unclear. CONCLUSIONS: Peritoneal levels of interleukin-6 and interleukin-10 on day 1 after colorectal surgery can predict clinically important anastomotic leak.

A trithorax-like gene is interrupted by chromosome 11q23 translocations in acute leukaemias.

Some acute lymphocytic leukaemias, particularly those in young children, are associated with a t(4;11)(q21;q23) reciprocal translocation. We have cloned the translocation breakpoint on chromosome 11q23 and isolated corresponding RNA transcripts from this region. The translocation occurs within a cluster of Alu repetitive elements located within an intron of a gene that gives rise to 11.5 (kb) transcript spanning the translocation breakpoint. The 11.5 kb transcript encodes a protein that is highly homologous to the Drosophila trithorax gene, a developmental regulator. An analysis of a series of leukaemic patients carrying t(4;11) and t(9;11) translocations indicate that the majority of breakpoints in infant leukaemias lie within a 5 kb region.

Human trithorax gene rearrangements in therapy-related acute leukaemia after etoposide treatment.

Molecular analysis of leukaemic blasts from 9 patients with secondary myeloid leukaemia reveals rearrangements of the human trithorax gene (Htrx-1) in three patients, including one in whom abnormalities of chromosome 11 band q23 were not detected by conventional cytogenetics. All three patients had been treated with epipodophyllotoxins, whilst none of the six without rearrangements had received these agents. The patients with rearrangements also presented with different clinical features. These findings support the separation of secondary leukaemia into two classes, and correlate rearrangements of the Htrx-1 gene with a group of secondary leukaemias that follow specific cancer treatment regimens.

Vitamin D receptor alleles and rates of bone loss: influences of years since menopause and calcium intake.

A genetic marker for the 1,25-dihydroxyvitamin D receptor (VDR) is reported to account for much of the heritable component of bone density. It is not known whether VDR genotype influences bone accretion or loss, or how it is related to calcium metabolism. The VDR genotype was determined in 229 healthy postmenopausal women who previously participated in a calcium trial. VDR alleles were designated according to presence (b) or absence (B) of the BsmI restriction enzyme cutting site. There were 83 bb, 102 Bb, and 44 BB individuals. Two-thirds of the women took 500 mg of calcium supplement (mean calcium intake = 892 mg/day) and one-third a placebo (mean = 376 mg/day). Bone mineral density (BMD) at the femoral neck, spine, and radius were measured by dual- and single-photon absorptiometry at baseline and after 1 and 2 years. Among women more than 10 years postmenopausal, those with the BB genotype had the lowest femoral neck BMD. Rates of bone loss over 2 years were greater in the BB group at all sites (e.g., at the femoral neck, bb, 0.45 +/- 0.43; Bb, -0.01 +/- 0.40; BB, -0.99 +/- 0.50%/year; BB vs. bb, p = 0.01), and this trend was found both in women < 10 years since menopause (e.g., at the radius, bb, 0.43 +/- 0.47; Bb, -0.37 +/- 0.42; BB, -1.20 +/- 0.59% per year; BB vs. bb, p = 0.02) and those > or = 10 years (radius, bb, -0.71 +/- 0.41; Bb, 0.08 +/- 0.39; BB, -1.41 +/- 0.49% per year; BB vs. Bb, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Genome screen for QTLs contributing to normal variation in bone mineral density and osteoporosis.

A major determinant of the risk for osteoporosis is peak bone mineral density (BMD), which is largely determined by genetic factors. We recently reported linkage of peak BMD in a large sample of healthy sister pairs to chromosome 11q12-13. To identify additional loci underlying normal variations in peak BMD, we conducted an autosomal genome screen in 429 Caucasian sister pairs. Multipoint LOD scores were computed for BMD at four skeletal sites. Chromosomal regions with LOD scores above 1.85 were further pursued in an expanded sample of 595 sister pairs (464 Caucasians and 131 African-Americans). The highest LOD score attained in the expanded sample was 3.86 at chromosome 1q21-23 with lumbar spine BMD. Chromosome 5q33-35 gave a LOD score of 2.23 with femoral neck BMD. At chromosome 6p11-12, the 464 Caucasian pairs achieved a LOD score of 2.13 with lumbar spine BMD. Markers within the 11q12-13 region continued to support linkage to femoral neck BMD, although the peak LOD score was decreased to 2.16 in the sample of 595 sibling pairs. Our study is the largest genome screen to date for genes underlying variations in peak BMD and represents an important step toward identifying genes contributing to osteoporosis in the general population.

A bacteriological examination of breast pumps.

In an investigation of the source of an outbreak of Serratia marcescens infection in a special care baby unit, several breast pumps used in the hospital and community were examined. The epidemic strain was isolated from two pumps and other Gram-negative organisms, Staphylococcus aureus and Streptococcus faecalis were isolated from seven. The findings indicate that breast pumps may be a potential source of contamination of the user, her breast milk, infant and environment. Our recommendations regarding the use of breast pumps are presented.

Effects of reward and nonreward on frustration and attention in attention deficit disorder.

The effects of reward schedule (100%, 50%, and 30%) and termination of rewards (extinction) on 30 attention deficit disorder with hyperactivity (ADD-H) and 30 normal children were studied using measures of frustration (speed/strength of lever pulling) and attention (reaction time to a light signal). ADD-Hs pulled harder on the lever than controls during extinction and on the lowest (30%) partial schedule, providing empirical evidence that they respond with greater frustration than normals when expected rewards fail to appear. The groups did not differ on the attentional measure on 100% reward. However, the partial schedules appeared to have an alerting or motivating effect on the controls, so that they responded more quickly and consistently than ADD-Hs on the partial schedules. Findings are discussed with reference to opposing theories regarding the nature of the abnormal response of ADD-Hs to reward.

Effects of reward on delayed reaction time task performance of hyperactive children.

This experiment was designed to investigate the effects of continuous, partial, and noncontingent schedules of reward, as well as the withdrawal of rewards, on the performance of hyperactive and normal control children on a delayed reaction time task. Although noncontingent reward resulted in faster reaction times for control subjects, performance of hyperactives deteriorated under noncontingent reward and improved when it was withdrawn. Also, reaction times of controls during extinction remained superior to baseline, whereas performance of hyperactives returned to baseline level. It was suggested that these and other findings reviewed point to an unusual sensitivity to rewards in hyperactive children.

Effects of reinforcement on concept identification in hyperactive children.

The effects of continuous and partial reward on the performance of hyperactive and normal children on a concept identification task were compared. Because reduction in information feedback is usually associated with partial reward schedules, the study was designed to yield information regarding the contribution of reduced feedback to performance in the partial reward condition. Previous findings of a performance deficit in hyperactives under partial reward were replicated. The findings help rule out an information feedback explanation for this deficit. The authors suggest that a motivational factor involving the elicitation of frustration when expected rewards fail to appear may be responsible for the poor performance of hyperactives on the partial schedule.

Assessment of a cognitive training program for hyperactive children.

Modeling, self-verbalization, and self-reinforcement techniques were used to train hyperactive children in more effective and less impulsive strategies for approaching cognitive tasks, academic problems, and social situations. Eighteen hyperactive children took part in the training program. The control group, which received no training, consisted of 11 children, matched with the experimental group on age, IQ, and measures of hyperactivity and impulsivity. Several tests and measures, some of which have been shown to differentiate between hyperactive and normal children, were administered prior to training at the end of the 3-month training period, and after a further 3-month period in which no training took place. The trained group showed significantly greater improvement on several of the measures, both at the time of posttesting and on the follow-up evaluation.

Lateralization in attainment and maintenance of neonatal head posture: further external validation.

Consistencies in lateral head turning of 50 healthy, term neonates were examined to determine relations between attainment and maintenance of lateral head position. The majority showed lateral consistencies, typically rightward, in initial head turn from midline per trial, in direction of the majority of all head turns from midline per trial and in direction turned for the majority of time per trial. Head position prior to testing was related to the three indices. The results of work to date, including the current study, have proven very consistent in nature, yielding the most reliable measure of an element of lateralized behavior in the neonate.

Cloning and characterization of the t(X;11) breakpoint from a leukemic cell line identify a new member of the forkhead gene family.

Chromosome translocations involving 11q23 are associated with a number of different types of leukemia. These translocations fuse a gene encoding a putative transcription factor, HTRXI, to genes on other chromosomes. We report cloning and sequencing the t(X;11) breakpoint region from a cell line established from an infant with acute lymphocytic leukemia. The gene AFXI, on the X chromosome, is expressed in a variety of cell types. Sequence analysis indicates a high degree of homology between AFXI and the forkhead family of transcription factors. The high degree of identity within the forkhead region and the lack of homology outside that region suggest that AFXI represents a novel forkhead family member. It is predicted that a chimeric fusion protein with altered DNA binding activity will be the result of the translocation.

A clinical assessment of Modifast in U.K. general practice.

Between April and October 1983, 443 subjects were offered a month's course of Modifast by their general practitioners. Modifast is a very low calorie formula diet containing 1.7MJ (410 kcal) and 70g protein per day. Results available on 335 of these individuals indicate that 217 completed a four week course and achieved an average weight loss of 6.6 kg, whilst those that did not complete the course achieved a 2.6 kg weight loss. Concurrent disease was present in 44.5% of subjects. The product was rated on average, tolerable, but side effects, albeit generally minor and transient, were reported by one third. Nearly two-thirds of the initially hypertensive patients became normotensive. Modified fasting is an acceptable and effective initial approach to weight loss in general practice.

Detection of single-base mutations in a mixed population of cells: a comparison of SSCP and direct sequencing.

Single-base-pair changes in several genes have been shown to be important in carcinogenesis. We have compared the sensitivity of two commonly used techniques for detection of single-base-pair changes. Defined populations of cells were prepared by mixing wild-type Chinese hamster ovary cells with cells carrying a known mutation in the CTP synthetase gene. RNA was extracted and analyzed for the mutation by single-strand conformational polymorphism and direct sequence analysis of polymerase chain reaction products. We found that both techniques were able to detect the mutation when it was present in 25% of the cells, but that direct sequencing was slightly more sensitive and able to detect the mutation when it was present in only 20% of the population.

Ayurvedic agents produce differential effects on murine and human melanoma cells in vitro.

This study was performed to evaluate the relative efficacy of Maharishi Amrit Kalash ambrosia (MAK-5) and Maharishi Amrit Kalash nectar (MAK-4) on murine (B-16) and human (SK-Mel) melanoma cells in culture. Ethanol extract (EE) of MAK-5 (EE-MAK-5) induced morphological differentiation (enlargement of soma and nuclei and formation of long dendritic processes) and growth inhibition in mouse melanoma cells, whereas EE-MAK-5 inhibited only growth in human melanoma cells. Murine melanoma cells were more sensitive (about 3 times) than human melanoma cells in culture to EE-MAK-5; the aqueous extract (AE) of MAK-5 (AE-MAK-5) was ineffective in both cells. Boiling EE-MAK-5 for 10 minutes or exposing it to light at room temperature for 72 hours did not alter growth-inhibiting potency. Ethanol extract of another herbal agent, MAK-4 (EE-MAK-4), inhibited growth in human melanoma cells but not in mouse melanoma cells. AE-MAK-4 was ineffective for both cells. These results suggest that murine and human melanoma cells respond differently to MAK-5 and MAK-4 and that human melanoma growth-inhibiting agents are present in both EE-MAK-5 and EE-MAK-4.

Batched analysis of genotypes.

Polymorphic microsatellite markers are widely used in molecular analyses. The range of allele sizes and the allele frequencies within a population are important characteristics of the marker. Their determination previously has involved genotyping a large number of individuals. We have developed a technique for defining these characteristics by coamplification of many samples in a DNA pool. Groups of 32 and 42 DNA samples were genotyped and results were compared with those from individual genotype determinations. To improve the accuracy in the estimation of allele frequencies, arithmetic removal of stutter bands was carried out and the consistency of each marker was characterized. This approach was also applied to a group of 94 individuals. All of the work has been done using nonradioactive methods. Potential applications of this technique are in population genetics, high throughput genotyping, and loss of heterozygosity studies.

A comparison of the effects of zolpidem and placebo on respiration and oxygen saturation during sleep in the healthy elderly.

1. In a double-blind placebo controlled trial, zolpidem 10 mg, a new imidazopyridine hypnotic drug, was administered to 10 elderly female patients and placebo to 11, all recovering from hip and knee replacement surgery. Respiratory monitoring with an inductance plethysmograph and pulse oximeter showed that treatment over a 4 night period did not increase significantly the severity, frequency or duration of hypoxaemic episodes leading to SaO2 less than 90% or less than 85% when compared with placebo. Confidence intervals (corrected for baseline differences) for the median differences between the two groups on night 7, the fourth night of treatment, were from -1.85 to 0.480 and from -1.07 to 0 respectively for the frequency, and from -0.76 to 0.15 and -0.5 to 0 for the duration of the hypoxaemic episodes. The incidence of sleep related respiratory disturbances was not significantly increased compared with placebo on any night. 2. Respiratory monitoring using a simple inductance plethysmograph and pulse oximeter is acceptable to patients and staff. 3. The evaluation of all hypnotic and sedative drugs should include their effects on respiration during sleep.