Blastocyst Injection of Embryonic Stem Cells: A Simple Approach to Unveil Mechanisms of Corrections in Mouse Models of Human Disease

Embryonic stem cell (ESC) research is a promising area of investigation with enormous therapeutic potential. We have injected murine wild type (WT) ESCs into a variety of mutant murine blastocysts, which are predisposed to develop a human-like disease, such as muscular dystrophy or the embryonic lethal “thin myocardial syndrome”. In this review, we summarize data indicating that partial incorporation of ESCs is sufficient to prevent disease from occurring. We also present data indicating that blastocyst incorporation of ESCs may aid in the prevention of heart failure in stressed WT mice. In some cases, the rescue observed is predominantly non-cell autonomous and relies on the production of secreted factors from the ES-derived cells, but in others, cell replacement is required. Thus, congenital or acquired disease can be pre-emptively averted in mice by developmental injection of ESCs.     

Ogilvie syndrome after cesarean section. A clinical contribution

Following the observation of a case of acute pseudo-obstruction of the colon (Ogilvie's syndrome) after cesarean section, the Authors describe their clinical experience in relation to recently published reports. While discussing other features of the syndrome, the importance of radiological monitoring of the colonic stasis and the validity of perendoscopic decompression of the colon as an efficacious therapy are underlined.     

Randomized comparison of two chemotherapy, radiotherapy schemes for stage III and IV unresectable squamous cell carcinoma of the head and neck.

Between August 1983 and December 1986, 116 previously untreated patients with squamous cell carcinoma of the head and neck were randomized to receive induction chemotherapy followed by radiotherapy given in conventional fractions (55 patients, arm A) or an alternating chemotherapy and radiotherapy (3 courses of 20 Gy, 10 daily fractions each; 61 patients, arm B). The same chemotherapy was used in both arms: 6 mg/m2 vinblastine sulfate, hour 0; 30 mg bleomycin, hour 6; 200 mg methotrexate, hours 24 to 26; 45 mg leucovorin, hour 48. Forty-five patients had stage III disease and 71 had stage IV disease. All patients were evaluated for survival, 112 for toxicity, and 105 for analyses of response and time from the start of treatment until progression of disease. At the end of the combined treatment, we observed an overall response rate of 52% in arm A and an overall response rate of 64.9% in arm B. The incidence of mucositis was more relevant in arm B compared to arm A (P less than .00004). The difference in complete response, progression-free survival, and survival was statistically significant, with an advantage for arm B (P less than .03, P less than .02, and P less than .03, respectively). The analysis at a median follow-up of 36 months (range = 19 to 59) demonstrates a higher effectiveness for the alternating program.     

The refractive status and vision profile: a questionnaire to measure vision-related quality of life in persons with refractive error

OBJECTIVE/BACKGROUND: To describe the Refractive Status and Vision Profile (RSVP), a questionnaire that measures self-reported vision-related health status (symptoms, functioning, expectations, concern) in persons with refractive error. DESIGN: Cross-sectional study by survey. PARTICIPANTS: The RSVP was self-administered by 550 participants with refractive error (or history of refractive surgery) recruited from five refractive surgery practices and one optometric practice. Information on refraction, uncorrected and best-corrected visual acuity, and history of refractive surgery was obtained from physicians' records. METHODS: Internal consistency, test-retest reliability, agreement with global measures of vision (criterion validity), discriminant validity, content validity, and construct validity (associations of scale scores with patient status variables) were assessed using Cronbach's alpha, Spearman rank correlations, factor analysis, and multitrait analysis. OUTCOME MEASURES: Scores on the overall RSVP scale (S) and on eight RSVP subscales (functioning, driving, concern, expectations, symptoms, glare, optical problems, problems with corrective lenses) were calculated based on 42 items. RESULTS: Cronbach's alpha was 0.92 for S and ranged from 0.70 to 0.93 for RSVP subscales, indicating good internal consistency. Satisfaction with vision was more strongly associated with S than with refractive error or with visual acuity. Individuals with more refractive error had significantly lower (worse) scores for S and for subscales concern, functioning, driving, optical problems, and glare. Scores for S and for subscales concern, functioning, optical problems, and driving remained significantly associated with satisfaction with vision after adjustment for age, gender, corrective lens type, and refractive error. CONCLUSIONS: The RSVP measures a range of visual, functional, and psychologic impacts of refractive error that are likely to be important to patients. The RSVP would be a useful tool for evaluating interventions for correction of refractive error and may be useful for assessing refractive surgery candidates in clinical practice.     

Screening performance of functional and structural measurements of neural damage in open-angle glaucoma: a case-control study from the Baltimore Eye Survey

PURPOSE: To compare the sensitivity and specificity of four approaches to glaucoma screening. METHODS: Case patients were persons with possible, probable, or definite glaucomatous optic nerve damage, as judged by a glaucoma specialist using Humphrey 24-2 threshold findings and clinical assessment of disc and nerve fiber layer, identified in the population-based Baltimore Eye Survey Follow-up Study. Control patients were participants in the same study, frequency-matched for age, without evidence of glaucomatous optic nerve damage. Participants underwent optic disc photography (Topcon ImageNet), disc imaging (GlaucomaScope), scanning laser polarimetry (Nerve Fiber Analyzer), and suprathreshold field testing (Dicon). RESULTS: A total of 100 case patients with open-angle glaucoma and 149 control patients were included. Objective imaging had the best screening performance. For the GlaucomaScope, a criterion of cup-to-disc ratio of -0.68 had a sensitivity of 72% and specificity of 82% for detecting eyes with definite or probable glaucomatous optic nerve damage. For the nerve fiber layer, a criterion of The Number as > or = 20 had a sensitivity of 69% and specificity of 77% for detecting eyes with definite or probable glaucomatous optic nerve damage. Usable data could be obtained in 93% of participants with the Dicon and the Nerve Fiber Analyzer and in 82% and 87% of participants with the GlaucomaScope and Topcon instruments, respectively. CONCLUSIONS: Vertical cup-to-disc ratio, as measured by the GlaucomaScope or Topcon instruments, and the Nerve Fiber Layer neural network Number had the best combination of sensitivity and specificity among the instruments tested. The Nerve Fiber Analyzer had the highest percentage of participants with usable data.     

Quality of evaluation and management of children requiring timely orthopaedic surgery before admission to a tertiary pediatric facility

The purpose of this study was to investigate the quality of evaluation and management of children requiring timely orthopaedic surgery before admission to a tertiary pediatric facility. A retrospective chart review was performed on 372 consecutive children who underwent orthopaedic surgery for a diagnosis of fracture, infection, slipped capital femoral epiphysis (SCFE), or compartment syndrome during a 22-month period at the authors' facility. Of the 372 children, 142 children (38%) first received medical care elsewhere; these are the subjects of this study. Before being seen at the authors' institution, 27 children (19%) had a problem in treatment or diagnosis and 18 (13%) had a delay in diagnosis or treatment of greater than 48 hours. Problems in diagnosis included five children with unrecognized open fractures, four of whom did not receive antibiotics; six children with missed SCFE, five of whom were not made non-weight-bearing; and six missed closed fractures. Delay in treatment occurred for 15 fractures, with a mean delay of >7 days until surgical treatment. Insurance status and primary language of the family were not associated with problems or delays in treatment. Overall, 32% of children undergoing time-sensitive orthopaedic surgery at a tertiary pediatric center had problems or delays in the medical care they received before transfer.     

Intraoperative color Doppler ultrasound assessment of LIMA-to-LAD anastomoses in off-pump coronary artery bypass grafting

BACKGROUND: Although techniques for off-pump coronary artery bypass grafting (CABG) are continually being refined, angiographic follow-up studies have indicated a higher rate of anastomoses-related stenoses than expected after traditional on-pump CABG. This study was performed to evaluate the use of intraoperative epicardial color Doppler ultrasound to quality-assess left internal mammary artery (LIMA) to left anterior descending coronary artery (LAD) anastomoses performed on the beating heart. METHODS: Twenty-four LIMA-to-LAD anastomoses were evaluated with real-time epicardial ultrasound imaging using an ultrasound transducer positioned between the paddles of the stabilizer during off-pump procedures. The length of the anastomosis (D(A)), diameters of LIMA (D(M)), LAD at the toe of the anastomosis (D1), and 5 mm distally to the anastomosis (D2) were measured, and the ratios between these variables were calculated. The flow velocity through the anastomoses was visualized by color Doppler coding, and flow was assessed with transit-time flowmetry. RESULTS: The epicardial color Doppler ultrasound allowed accurate assessment of the anastomoses. Twenty-three (96%) of the primary anastomoses were confirmed as patent. Mean ratios of D1/D2, D(A)/D2, and D(M)/D2 were 0.89 +/- 0.13, 3.01 +/- 1.04 and 1.32 +/- 0.32, respectively. One anastomosis had a stenosis more than 50% detected by color Doppler ultrasound. After surgical revision, transit-time flow increased from 22 to 40 ml/min. CONCLUSIONS: Intraoperative color Doppler ultrasound allowed adequate imaging for quality assessment of LIMA-to-LAD anastomoses performed on the beating heart. One anastomosis was revised due to a technical error detected by epicardial color Doppler imaging. Epicardial ultrasound scanning is a valuable tool for intraoperative assessment of LIMA-to-LAD anastomoses during off-pump coronary surgery.     

Association between a GABRB3 polymorphism and autism

Autistic disorder (OMIM 209850) is a disease with a significant genetic component of a complex nature.(1) Cytogenetic abnormalities in the Prader-Willi/Angelman syndrome critical region (15q11-13) have been described in several individuals with autism.(1) For this reason, markers across this region have been screened for evidence of linkage and association, and a marker (155CA-2) in the gamma-aminobutyric acid type-A receptor beta3 subunit gene (GABRB3) has been associated in one study(2) but not others.(3-5) We completed an association analysis with 155CA-2 using the transmission disequilibrium test (TDT) in a set of 80 autism families (59 multiplex and 21 trios). We also used four additional markers (69CA, 155CA-1, 85CA, and A55CA-1) localized within 150 kb of 155CA-2. The use of multi-allelic TDT (MTDT) (P < 0.002), as well as the TDT (P < 0.004), demonstrated an association between autistic disorder and 155CA-2 in these families. Meiotic segregation distortion could be excluded as a possible cause for these results since no disequilibrium was observed in unaffected siblings. These findings support a role for genetic variants within the GABA receptor gene complex in 15q11-13 in autistic disorder.     

Correlation between peri-operative serum lactate levels and outcome in pancreatic resection for pancreatic cancer,preliminary report

This study was undertaken in order to verify if peri-operative serum lactate level changes, resulting from manipulation of the splanchnic circulation during pancreatectomy, reflected clinical outcome in twenty patients (9 males-11 females age 33 to 76) operated for pancreatic cancer. Lactate levels were evaluated at the beginning of the procedure (T0), after surgical manipulation before pancreatic resection (T1), after resection (T2), and 24 hours post-op. (T3). Furthermore, to highlight possible hemodynamic instability that could contribute to altered lactate clearance, mean arterial pressure (MAP) and central venous pressure (CVP) were continuously monitored during the study period. Peri-operative mortality within 60 days after surgery, Intensive Care Unit (ICU) length of stay, and peri-operative complications were the main indicators investigated in order to evaluate the impact of serial lactate levels in this patient population. Hyperlactatemia observed peri-operatively during pancreatic resection for cancer is significantly correlated with peri-operative mortality and also with longer ICU length of stay. Though, due to the relatively small number of the patients, more extensive investigation is needed in order to confirm such interesting preliminary data.