Gravity Probe B: final results of a space experiment to test general relativity.

Gravity Probe B, launched 20 April 2004, is a space experiment testing two fundamental predictions of Einstein's theory of general relativity (GR), the geodetic and frame-dragging effects, by means of cryogenic gyroscopes in Earth orbit. Data collection started 28 August 2004 and ended 14 August 2005. Analysis of the data from all four gyroscopes results in a geodetic drift rate of -6601.8±18.3 mas/yr and a frame-dragging drift rate of -37.2±7.2 mas/yr, to be compared with the GR predictions of -6606.1 mas/yr and -39.2 mas/yr, respectively ("mas" is milliarcsecond; 1 mas=4.848×10(-9) rad).

Nanohertz frequency determination for the gravity probe B high frequency superconducting quantum interference device signal.

In this paper, we present a method to measure the frequency and the frequency change rate of a digital signal. This method consists of three consecutive algorithms: frequency interpolation, phase differencing, and a third algorithm specifically designed and tested by the authors. The succession of these three algorithms allowed a 5 parts in 10(10) resolution in frequency determination. The algorithm developed by the authors can be applied to a sampled scalar signal such that a model linking the harmonics of its main frequency to the underlying physical phenomenon is available. This method was developed in the framework of the gravity probe B (GP-B) mission. It was applied to the high frequency (HF) component of GP-B's superconducting quantum interference device signal, whose main frequency f(z) is close to the spin frequency of the gyroscopes used in the experiment. A 30 nHz resolution in signal frequency and a 0.1 pHz/s resolution in its decay rate were achieved out of a succession of 1.86 s-long stretches of signal sampled at 2200 Hz. This paper describes the underlying theory of the frequency measurement method as well as its application to GP-B's HF science signal.

Multifocal laser surgery: cutting enhancement by hydrodynamic interactions between cavitation bubbles.

Transparent biological tissues can be precisely dissected with ultrafast lasers using optical breakdown in the tight focal zone. Typically, tissues are cut by sequential application of pulses, each of which produces a single cavitation bubble. We investigate the hydrodynamic interactions between simultaneous cavitation bubbles originating from multiple laser foci. Simultaneous expansion and collapse of cavitation bubbles can enhance the cutting efficiency, by increasing the resulting deformations in tissue, and the associated rupture zone. An analytical model of the flow induced by the bubbles is presented and experimentally verified. The threshold strain of the material rupture is measured in a model tissue. Using the computational model and the experimental value of the threshold strain one can compute the shape of the rupture zone in tissue resulting from application of multiple bubbles. With the threshold strain of 0.7 two simultaneous bubbles produce a continuous cut when applied at the distance 1.35 times greater than that required in sequential approach. Simultaneous focusing of the laser in multiple spots along the line of intended cut can extend this ratio to 1.7. Counterpropagating jets forming during collapse of two bubbles in materials with low viscosity can further extend the cutting zone-up to approximately a factor of 1.5.

Multi-locus interactions predict risk for post-PTCA restenosis: an approach to the genetic analysis of common complex disease.

The complexity of recognizing the potential contribution of a number of possible predictors of complex disorders is increasingly challenging with the application of large-scale single nucleotide polymorphism (SNP) typing. In the search for putative genetic factors predisposing to coronary artery restenosis following balloon angioplasty, we determined genotypes for 94 SNPs representing 62 candidate genes, in a prospectively assembled cohort of 342 cases and 437 controls. Using a customized coupled-logistic regression procedure accounting for both additive and interactive effects, we identified seven SNPs in seven genes that, together, showed a statistically significant association with restenosis incidence (P <0.0001), accounting for 11.6% of overall variance observed. Among them are candidate genes for cardiovascular pathophysiology (apolipoprotein-species and NOS), inflammatory response (TNF receptor and CD14), and cell-cycle control (p53 and p53-associated protein). Our results emphasize the need to account for complex multi-gene influences and interactions when assessing the molecular pathology of multifactorial medical entities.

A novel multilocus genotyping assay to identify genetic predictors of stroke in sickle cell anaemia.

We describe a novel multilocus genotyping assay permitting simultaneous identification of 60 candidate markers for stroke in sickle cell anaemia (SCA). Based on cerebral magnetic resonance imaging (MRI), 69 patients were divided into stroke and control groups. The variant allele, CBS 278thr, showed protection from stroke, whereas the apoE3 allele showed a trend towards association with increased stroke risk. Several other variant alleles [TNFalpha (-308)A, CETP (-628)A, apoCIII (-641)A] showed a trend towards significant associations with stroke risk. These preliminary results on a small group of patients suggest that a multilocus genotyping assay may be valuable in identifying genes that increase the risk of stroke in SCA.

Blood loss in major liposuction procedures: a comparison study using suction-assisted versus ultrasonically assisted lipoplasty.

The blood loss that accompanies liposuction procedures has always been a concern. Tumescent injection of the targeted area of liposuction with dilute lidocaine and epinephrine solution has minimized intraoperative blood loss. Proponents of a newer ultrasonically assisted lipoplasty technique have claimed many benefits over traditional suction-assisted lipoplasty. However, few quantitative data are available on the intraoperative blood loss and the significance of postoperative anemia using the ultrasonic method. A prospective clinical observational design was used to investigate 38 patients undergoing suction-assisted lipoplasty and 37 patients undergoing ultrasound-assisted lipoplasty in whom the liposuction aspirate was expected to be more than 1000 ml. These patients were investigated with preoperative measurement of hemoglobin, platelet count, prothrombin time, partial thromboplastin time, and postoperative measurement of hemoglobin on the seventh postoperative day. In addition, hemoglobin concentration and whole blood volume were calculated from the infranatant portion of the liposuction aspirate. The mean +/- SD volume of the liposuction aspirate was 2901 +/- 1471 ml for suction-assisted compared with 2741 +/- 1086 ml for ultrasound-assisted lipoplasty. The mean +/- SD of whole blood volume in liposuction aspirate per case was 36 +/- 50.82 ml for suction-assisted lipoplasty and 36 +/- 28.62 ml for ultrasound-assisted lipoplasty. The mean +/- SD of the preoperative hemoglobin concentration was 13.93 +/- 0.99 g/dl for suction-assisted lipoplasty and 14.05 +/- 1.16 g/dl for ultrasound-assisted lipoplasty, whereas the mean +/- SD of the postoperative hemoglobin concentration was 13 +/- 1.42 g/dl for suction-assisted lipoplasty and 13.05 +/- 1.32 g/dl for ultrasound-assisted lipoplasty. The mean decrease in hemoglobin on the seventh postoperative day was 0.93 +/- 0.92 g/dl for suction-assisted lipoplasty and 1 +/- 0.64 g/dl for ultrasound-assisted lipoplasty. The volume of whole blood loss was estimated to be 12.4 ml in each 1000 ml of liposuction aspirate when using suction-assisted lipoplasty versus 13.1 ml when using ultrasound-assisted lipoplasty. All procedures were done under general anesthesia, and patients were discharged home on the same day. No blood transfusion was required. This study shows that blood loss using the ultrasonic technique is slightly higher, though insignificant, than when using suction. However, this study did not demonstrate a difference in the postoperative hemoglobin decrease between the two techniques.

Benign pneumoperitoneum associated with pneumomediastinum and pneumoretroperitoneum in ambulatory outpatients.

Perforation of a hollow viscus and other dangerous etiologies must always be considered in the evaluation of free peritoneal air. Pneumoperitoneum in the presence of pneumoretroperitoneum and pneumomediastinum, however, often results from air tracking from a pathologic source outside of the abdomen along the mesentery into the peritoneum. This syndrome is relatively benign, and should be considered when there are multiple sites of extraluminal air in order to minimize the risk of unnecessary exploratory laparotomy. Two cases of benign pneumoperitoneum associated with pneumomediastinum and pneumoretroperitoneum are presented.

Vocal cord and pharyngeal weakness with autosomal dominant distal myopathy: clinical description and gene localization to 5q31.

Distal myopathy refers to a heterogeneous group of disorders in which the initial manifestations are weakness and atrophy of the hands and feet. We report a family segregating an autosomal dominant distal myopathy, with multiple affected individuals in whom vocal cord and pharyngeal weakness may accompany the distal myopathy, without involvement of the ocular muscles. To our knowledge, this pedigree displays a distinct distal myopathy with the added features of pharyngeal and vocal cord dysfunction (VCPDM) that has not been previously reported. We mapped the MPD2 gene for VCPDM to chromosome 5q within a 12-cM linkage interval between markers D5S458 and D5S1972 in a large pedigree (a maximum LOD score of 12.94 at a recombination fraction of 0 for D5S393) and combined genome screening and DNA pooling successfully adapted to fluorescent markers. This technique provides for the possibility of fully automated genome scans.

Impact of laparoscopic cholecystectomy on indications for surgical treatment of gallstones.

BACKGROUND: The objective of this study was to compare the histology of gallbladders removed prior to the introduction of laparoscopic cholecystectomy with that found after the introduction of the laparoscopic technique to determine if there has been a change in the indications for surgical treatment of gallbladder disease. METHODS: A retrospective review of all patients undergoing cholecystectomy during 1989, 1992, and 1993 was completed at two large community teaching hospitals in two different geographic regions of the United States. Patients who underwent cholecystectomy as the primary procedure were studied. A total of 1,815 cases met the criteria for analysis. Histological diagnoses were categorized as acute cholecystitis with or without cholelithiasis, or chronic cholecystitis with cholelithiasis. RESULTS: The number of cholecystectomies performed increased by 58% from 1989 to 1993 (p < 0.05). The number of cholecystectomies for acute cholecystitis did not change. CONCLUSIONS: With the advent of laparoscopic cholecystectomy, the number of cholecystectomies significantly increased and the proportion of cholecystectomies performed for chronic disease also increased. There has been a significant change in the surgical management of gallbladder disease with increased willingness to recommend elective cholecystectomy. Further study is needed to determine if there is real benefit from earlier elective cholecystectomy.

Acoustic analysis of voice in individuals with amyotrophic lateral sclerosis and perceptually normal vocal quality.

Currently, early phonatory changes in amyotrophic lateral sclerosis (ALS) are not well understood. The aim of this study was to compare acoustic parameters of voice in ALS subjects who demonstrated perceptually normal vocal quality on sustained phonation with a control group. We hypothesized that objective analysis of voice would reveal significant differences on specific acoustic parameters of voice compared to the control group. Results revealed statistically significant differences between the two groups on measures related to frequency range and phonatory stability. The findings suggest that early bulbar signs affecting the laryngeal system may be present in patients with ALS before the occurrence of perceptually aberrant vocal characteristics.

Reduced X-ray resistance and homologous recombination frequencies in a RAD54-/- mutant of the chicken DT40 cell line.

rad54 mutants of the yeast Saccharomyces cerevisiae are extremely X-ray sensitive and have decreased mitotic recombination frequencies because of a defect in double-strand break repair. A RAD54 homolog was disrupted in the chicken B cell line DT40, which undergoes immunoglobulin gene conversion and exhibits unusually high ratios of targeted to random integration after DNA transfection. Homozygous RAD54-/- mutant clones were highly X-ray sensitive compared to wildtype cells. The rate of immunoglobulin gene conversion was 6- to 8-fold reduced, and the frequency of targeted integration was at least two orders of magnitude decreased in the mutant clones. Reexpression of the RAD54 cDNA restored radiation resistance and targeted integration activity. The reported phenotype provides the first genetic evidence of a link between double-strand break repair and homologous recombination in vertebrate cells.

Flow cytometry in colon cancer: does flow cytometric cell cycle analysis help predict for short-term recurrence in patients with colorectal carcinoma?

The purpose of this prospective study was to determine whether tumor ploidy or S-phase fraction measurements were of prognostic value in predicting short-term recurrence for colorectal carcinoma. A total of 52 patients underwent curative resection of colorectal carcinoma. Fresh suspensions of tumor cells were used for flow cytometric analysis. Patients underwent follow-up for possible recurrence, which then was related to ploidy status, S-phase fraction measurement, adjuvant therapy received, and Dukes stage. Disease-free probability was determined using Kaplan-Meier actuarial curves for various subgroups of the study populations. Results revealed that elevated S-phase fraction (>16%) did predict for a higher probability of recurrence in those patients receiving no postoperative adjuvant treatment. Among patients receiving postoperative adjuvant therapy, however, a higher S-phase fraction predicted for a lower probability of recurrence. These data suggest that the S-phase fraction does predict for disease-free probability and also predict response to adjuvant therapy in patients with colorectal carcinoma.

A new minimally invasive technique for cholecystectomy. Subxiphoid "minimal stress triangle": microceliotomy.

OBJECTIVE: The authors devised a minimally invasive technique for cholecystectomy via microceliotomy that provides safety attainable with the open conventional approach and postoperative results comparable to laparoscopic cholecystectomy. SUMMARY BACKGROUND DATA: Laparoscopic cholecystectomy has evolved as a minimally invasive outpatient procedure. Patients can return rapidly to preoperative status with minimal postoperative morbidity and pain, and the small scar size is cosmetically desirable. Unfortunately, there are reports of serious intraoperative complications, including injury to blood vessels, bowel, and the bile ducts, caused by failure to identify structures properly. The conventional cholecystectomy technique currently is relegated to patients on whom the laparoscopic procedure cannot be performed. METHODS: Cholecystectomy was performed through a 3-cm transverse high subxiphoid incision in the "minimal stress triangle." The location, anterior to Calot's triangle, was critical in providing a direct vertical view of the biliary ducts during dissection. Direct view cholecystectomy was performed using endoscopic instruments without pneumoperitoneum. Postoperative data were compared with both laparoscopic and open cholecystectomy results. RESULTS: Using the microceliotomy technique in the ambulatory setting, cholecystectomy was performed successfully in 99.3% (N = 143) of cases. Biliary leakage beyond the third postoperative day was caused by failure of clips or obstruction to bile flow. The postoperative morbidity, acceptability of scar, and analgesic requirements compare favorably with other techniques. Microceliotomy is cost effective. Portal hypertension is a contraindication for this procedure. CONCLUSIONS: The microceliotomy approach offers a viable, safe, and cost-effective alternative to the laparoscopic technique for cholecystectomy, especially when facilities for laparoscopy are not available or when the laparoscopic procedure cannot be performed.

Evaluation, treatment, and follow-up results of post polio patients with dysphagia.

Twenty consecutive patients were evaluated for reports of dysphagia from post-polio clinics. Only half the patients reported a history of swallowing problems at the time of their acute poliomyelitis. Each patient received a videofluorographic evaluation of the oral and pharyngeal phases of swallowing, and then was provided with recommendations to improve swallowing skills. A follow-up questionnaire was sent to all patients. The respondents had an average interval of 12 months since the initial evaluation. Of the 18 patients responding to the questionnaire, 14 (77%) reported regular use of the swallowing suggestions. Comparison of pre-evaluation results to followup of the 18 respondents yielded a statistically significant decline in the frequency of choking (p = 0.0156) and food sticking in the throat (p = 0.0195). We conclude that a dysphagia program can result in significant improvement of the swallowing symptoms reported with the post-polio population.