Multidisciplinary weight management in locoregional breast cancer: results of a phase II study

Sixty-one women with newly diagnosed locoregional breast cancer (T 1–3, N0-1, M0) having an initial Body Mass Index (BMI) between 20 and 35 kg/m² who were receiving standard adjuvant treatment (chemotherapy, tamoxifen, and/or radiation) were asked to avoid weight gain (if initial BMI 25 kg/m²) or to lose up to 10 kg (if initial BMI 25–35 kg/m²) over one year. Women participated in twenty group sessions (10 weekly, 10 monthly) which involved a psychological supportive-expressive group intervention supplemented by individual weight goals, and nutrition and exercise programs. Fifty-five non-censored women (5 developed recurrence, 1 died of a subarachnoid hemorrhage) lost a mean of 0.53 ± 3.72 kg. Weight loss was greatest in initially overweight women (BMI 25 kg/m²) who lost 1.63 ± 4.11 kg (p = 0.01 compared to normal weight women) and in those not receiving chemotherapy who lost 2.15 ± 2.83 kg (p=0.0004 compared to those receiving chemotherapy). 70.9% met predefined criteria for success. Aerobic exercise increased significantly during the intervention (p = 0.00005) and was the strongest predictor of success (OR 1.73 for each additional 30 minutes of exercise weekly, p=0.003). Changes in caloric intake were not significant, but fat intake decreased and carbohydrate and fibre intake increased significantly during the intervention. Eating behavior and psychological status improved significantly. Thus, this multidisciplinary weight management intervention successfully prevented weight gain in women with newly diagnosed locoregional breast cancer, and helped overweight women lose weight.     

Respiratory arrest following intrathecal injection of sufentanil and bupivacaine in a parturient

Purpose

To present a case of respiratory arrest following the use of intrathecal sufentanil and bupivacaine for combined spinal-epidural anaesthesia in a healthy labouring parturient.

Clinical Features

A 20-yr-old term parturient received 10 μg sufentanil and 2.5 mg bupivacaine intrathecally as part of a combined spinal-epidural technique for labour analgesia. She had received no previous analgesics. Twenty-three minutes after the intrathecal injection she became unresponsive and suffered a respiratory arrest. Resuscitation included manual bag/mask ventilation with oxygen and intravenous naloxone.

Conclusion

Respiratory arrest is a rare but potentially life-threatening complication associated with the use of intrathecal opioids for labour analgesia. Vigilance in post-procedure patient monitoring is imperative.     

Loss of cables protein expression in human non-small cell lung cancer: a tissue microarray study

Loss of heterozygosity (LOH) on chromosome 18q is common in lung cancer. The genes involved in LOH on 18q in lung cancer have not been well characterized. Cables, a cyclin-dependent kinase (cdk) interacting protein, has recently been identified and mapped to human chromosome 18q11-12. Cables inhibits cell growth and suppresses tumor formation in nude mice, making it a candidate gene for 18q LOH in lung cancer. Little is known regarding Cables protein expression in human non-small cell lung cancer (NSCLC). In this study we examined Cables expression in 163 NSCLC and nonneoplastic lung specimens using tissue microarrays. Strong nuclear staining was present in normal lung and bronchial tissue. We also evaluated the Cables protein expression pattern and its correlation with histopathologic features and with clinical course of NSCLC. The results of the present study demonstrate for the first time that numerous NSCLCs (45%) lose Cables expression. Furthermore, more adenocarcinomas show a loss of this novel protein than do squamous counterparts. The relationship between tumor histology type and Cables expression appears to be statistically significant (P = 0.028). Our results suggest that Cables may be involved in the pathogenesis of NSCLC.     

Array-based comparative genomic hybridization of ductal carcinoma in situ and synchronous invasive lobular cancer

It has been increasingly recognized that ductal carcinoma in situ (DCIS), lobular carcinoma in situ (LCIS) and invasive cancer of the breast are often closely associated with one another. However, the genomic relationship between these histologically distinct entities has not been well characterized. Refinements in high-resolution comparative genomic hybridization (CGH) techniques allow for a detailed comparison of genomic alterations in synchronously occurring tumors. The following case illustrates how array CGH may be used to better understand whether synchronous neoplasms share a common origin.     

Measurement of EBV-IgG anti-VCA avidity aids the early and reliable diagnosis of primary EBV infection

Current serological methods for the diagnosis of Epstein-Barr virus (EBV) infection still differentiate poorly between primary infection and reactivation. This is particularly true when IgG and IgM antibodies are present simultaneously and only a single serum sample is provided for analysis. The demonstration of the IgG avidity state has the potential to distinguish recent from past or reactivated infection. An analysis of the kinetics of avidity maturation of anti-VCA antibodies in primary EBV infection was undertaken with longitudinally collected sets of sera from 28 well-characterised EBV cases and in sera from 35 cases with previous EBV infection and recent primary infection due to HIV, CMV, or hepatitis A. Antibodies directed against the viral capsid antigen (VCA) and Epstein-Barr nuclear antigen (EBNA-1) were sought, using a commercial enzyme immunoassay (EIA). In parallel with standard IgG anti-VCA detection, serum was incubated with 8 M urea to disrupt low-avidity complexes to allow calculation of the percentage avidity. In cases with primary EBV infection, the mean avidity rose from 54% at 6 weeks to 82% by 28 weeks after the onset of symptoms, but remained lower than that of the control sera (96%). The addition of the avidity measurement improved the sensitivity of IgG and IgM anti-VCA testing in diagnosis of primary EBV infection from 93% to 100%. The specificity of IgM anti-VCA testing alone was poor, with 14 of 35 cases (49%) demonstrating false-positive results, but it improved to 97% by the demonstration of high-avidity IgG anti-VCA. The combination of negative IgG anti-EBNA and low-avidity IgG anti-VCA had a sensitivity and specificity of 100%. The routine addition of IgG anti-VCA avidity estimation to diagnostic EBV serology is recommended.     

LM-PCR permits highly representative whole genome amplification of DNA isolated from small number of cells and paraffin-embedded tumor tissue sections.

Analysis of genetic changes is often hampered by insufficient starting DNA from limited clinical tissue specimens. We employed ligation-mediated PCR (LM-PCR) for global amplification of the genome to overcome this limitation, generating up to 5 microg of representative amplicons of genomic DNA from as little as one cell. We demonstrate successful global genome amplification in high-quality starting DNA source like laser-captured cultured cells, as well as partially degraded starting DNA from old formalin-fixed paraffin-embedded tissue sections. This process generates adaptor-tailed templates that can be repeatedly amplified almost ad infinitum. We have further modified this technique such that, instead of a single endonuclease digest, we can achieve higher amplicon coverage by combining 3 endonuclease digests prior to LM-PCR. As tested by examining amplification of STS sequences scattered genome-wide, the coverage was improved from the published 70% to 96%. The faithful representation of global losses and gains in the amplified genomic DNA was confirmed by array-comparative genomic hybridization. Further, we exemplify the utility of this technique for finer p53 point mutation analysis by PCR-SSCP. This technique is thus a clinically useful tool for globally amplifying and archiving DNA from finite sources like paraffin tissue sections, providing a potentially unlimited resource for genetic analyses.     

Assay of antibody to group A streptococcal carbohydrate by enzyme-linked immunosorbent assay.

An indirect enzyme-linked immunosorbent assay system for determination of antibody levels to the group A streptococcal cell wall carbohydrate antigen is described. Optimal conditions for antigen preparation, purification, and conjugation to poly-L-lysine for adequate adsorption to the solid phase are presented. Antibody titers of unknown sera were determined by comparison to known reference standard pool sera. A highly significant correlation (p less than 0.0001) was found between enzyme-linked immunosorbent assay antibody titers and antigen-binding capacity in a previously described radioimmunoassay. Utilizing an isotype-specific anti-immunoglobulin reagent and immunoabsorbent-purified antibody to group A streptococcal cell wall carbohydrate antigen, we were able to detect nanogram quantities of antibody by the enzyme-linked immunosorbent assay technique. This system will provide for more generalized use of group A streptococcal cell wall carbohydrate antigen antibody determinations for the study of immune responses after streptococcal infections and their complications.     

Increasing return compliance in a tuberculosis detection drive

This study explored the role of subject commitment as a variable for increasing compliance rates in a university-sponsored tuberculosis (TB) detection drive. Return rates for reaction readings were compared between those subjects who had made an overt commitment to return (either a verbal or a verbal plus written agreement) and those subjects who were exposed to a standardized, no commitment procedure. Return rates under both commitment conditions significantly increased. Contrary to expectation, subjects with a known family history of TB were found to be a high-risk group for noncompliance. For this group, obtaining both verbal and written agreement from subjects appeared to be the most efficacious procedure to increase compliance.The authors wish to thank Mr. Joe Hunt, James Leeper, Ph.D., and members of AED (Premedicai Honorary Society) for their assistance in this experiment.Currently a student in the College of Community Health Sciences, University of Alabama, University, Alabama 35486.     

Growth hormone receptor and insulin-like growth factor-I immunoreactivity in osteoclast-like cells during tooth eruption in the toothless (osteopetrotic) rat following treatment with colony-stimulating factor-1

In the toothless (tl/tl) osteopetrotic rat, teeth form but fail to erupt. Treatment of tl/tl rats with colony-stimulating factor-1 (CSF-1) activates bone resorption by osteoclasts, permits tooth eruption, and up-regulates the immunoreactivity of bone marrow mononuclear cells to growth hormone receptor (GHr) and insulin-like growth factor (IGF)-I. This study examined the distribution of tartrate-resistant acid phosphatase (TRAP) and immunoreactivity for GHr and IGF-I in osteoclast-like cells located on the alveolar bone margin, adjacent to the lower first molar crown, in 14-day-old normal and tl/tl rats, following treatment with CSF-1. Osteoclast-like cells demonstrated a positive reaction for TRAP, GHr, and IGF-I in all groups. However, in tl/tl tissue, osteoclast-like cells were generally negative for GHr. There was no significant difference in the total number of TRAP-, GHr-, and IGF-I-positive osteoclast-like cells on the adjacent bone margin in normal, normal treated with CSF-1, and tl/tl rats. CSF-1 treatment of the tl/tl rat significantly increased the total number of osteoclast-like cells, which were positive for TRAP (p < 0.001), GHr (p < 0.05) and IGF-I (p < 0.01).