Vaginal metastasis presenting as postmenopausal bleeding

Vaginal cancer is rare worldwide and represents 2% of all gynaecological cancers in Singapore. Primary vaginal malignancies are rare and vaginal metastases constitute the majority of vaginal malignancies. Most of these metastases arise from the cervix, endometrium or ovary, although they can also metastasise from distant sites such as the colon, breast and pancreas. We report a rare case of vaginal metastasis in a patient with previous gastric and rectal adenocarcinomas. An 89-year-old woman with a history of gastric and rectal malignancy presented with postmenopausal bleeding. A 2-cm vaginal tumour at the introitus was discovered upon examination. This case demonstrates the importance of performing a gynaecological examination during follow-up for patients with a history of malignancy. The prognosis for vaginal metastasis is poor, as it is often associated with disseminated disease. Depending on the extent of the lesions, radiotherapy or surgery can be considered.     

Changing Blue Fluorescent Protein to Green Fluorescent Protein Using Chemical RNA Editing as a Novel Strategy in Genetic Restoration

Using the transition from cytosine of BFP (blue fluorescent protein) gene to uridine of GFP (green fluorescent protein) gene at position 199 as a model, we successfully controlled photochemical RNA editing to effect site‐directed deamination of cytidine (C) to uridine (U). Oligodeoxynucleotides (ODNs) containing 5′‐carboxyvinyl‐2′‐deoxyuridine (^CVU) were used for reversible photoligation, and single‐stranded 100‐nt BFP DNA and in vitro‐transcribed full‐length BFP mRNA were the targets. Photo‐cross‐linking with the responsive ODNs was performed using UV (366 nm) irradiation, which was followed by heat treatment, and the cross‐linked nucleotide was cleaved through photosplitting (UV, 312 nm). The products were analyzed using restriction fragment length polymorphism (RFLP) and fluorescence measurements. Western blotting and fluorescence‐analysis results revealed that in vitro‐translated proteins were synthesized from mRNAs after site‐directed RNA editing. We detected substantial amounts of the target‐base‐substituted fragment using RFLP and observed highly reproducible spectra of the transition‐GFP signal using fluorescence spectroscopy, which indicated protein stability. ODNc restored approximately 10% of the C‐to‐U transition. Thus, we successfully used non‐enzymatic site‐directed deamination for genetic restoration in vitro. In the near future, in vivo studies that include cultured cells and model animals will be conducted to treat genetic disorders.     

Sampling Males Who Inject Drugs in Haiphong,Vietnam: Comparison of Time-Location and Respondent-Driven Sampling Methods

Accurate measurements of HIV prevalence and associated risk factors among hidden and high-risk groups are vital for program planning and implementation. However, only two sampling methods are purported to provide representative estimates for populations without sampling frames: time-location sampling (TLS) and respondent-driven sampling (RDS). Each method is subject to potential biases and questionable reliability. In this paper, we evaluate surveys designed to estimate HIV prevalence and associated risk factors among people who inject drugs (PWID) sampled through TLS versus RDS. In 2012, males aged ≥16 years who reported injecting drugs in the previous month and living in Haiphong, Vietnam, were sampled using TLS or RDS. Data from each survey were analyzed to compare HIV prevalence, related risk factors, socio-demographic characteristics, refusal estimates, and time and expenditures for field implementation. TLS (n = 432) and RDS (n = 415) produced similarly high estimates for HIV prevalence. Significantly lower proportions of PWID sampled through RDS received methadone treatment or met an outreach worker. Refusal estimates were lower for TLS than for RDS. Total expenditures per sample collected and number of person-days of staff effort were higher for TLS than for RDS. Both survey methods were successful in recruiting a diverse sample of PWID in Haiphong. In Vietnam, surveys of PWID are conducted throughout the country; although the refusal estimate was calculated to be much higher for RDS than TLS, RDS in Haiphong appeared to sample PWID with less exposure to services and required fewer financial and staff resources compared with TLS.     

Extensive Bone Marrow Necrosis in a Case of Acute Myeloid Leukemia Transformed from a Myeloproliferative Neoplasm

Extensive necrosis affecting more than 50%percnt; of the bone marrow is an extremely rare histopathological finding. Relatively little is known about its clinical significance because it is most commonly identified at autopsy – whether it is an independent prognostic marker or whether it is a surrogate marker of underlying disease burden remains unclear. We describe herein a case of a 66-year-old patient with acute myeloid leukemia who presented with acute bone marrow failure and was found to have extensive necrosis. We include presenting clinical features, pathology attained at biopsy, and the challenge of treatment. Bone marrow necrosis is a rare but important clinicopathological entity whose recognition may herald the way for more effective prognostication of underlying disease.Key Words: Bone marrow necrosis, Acute myeloid leukemia, Myeloproliferative neoplasm     

Does limited placement of bioresorbable membrane of modified sodium hyaluronate and carboxymethylcellulose (Seprafilm®) have possible short-term beneficial impact?

PURPOSE: The aim of the study was to assess the impact of sodium hyaluronate and carboxymethylcellulose membrane (Seprafilm®) on postoperative intestinal obstruction as judged by the rates of bowel obstruction and laparotomy for bowel obstruction. A secondary aim was to assess early postoperative morbidity. METHODS: All patients who had Seprafilm® placed during colorectal surgery between June 1993 and October 1998 were included in the study group and compared with a matched group of patients without Seprafilm®. All patients were assessed for intestinal obstruction and complications by telephone interview and chart review. Statistical tests for independence were used where appropriate; alpha was 0.05 for all tests, and the two groups were tested for case matching. Fisher's exact test was used to compare gender distribution, nature of diagnosis (inflammatoryvs. noninflammatory), and urgency of surgery (electivevs. emergency). The age distribution, number of prior abdominal surgeries, and operative time were compared by Student'st-test. Approximation of Katz test was used for independent proportions to compare the two groups for early postoperative morbidity and overall incidence of intestinal obstruction and surgical enterolysis. The incidence of intestinal obstruction between the two groups was also compared with Kaplan-Meier product limit method and log-rank test. RESULTS: Two hundred fifty-nine patients in whom Seprafilm® was placed were compared with a well-matched control cohort of 179 patients. The two groups did not differ in gender or age. One-half of each group had inflammatory conditions, and approximately 90 percent of each group underwent elective operations. The operative times were similar. Both groups had a similar number of abdominal operations before inclusion (mean = 1.2, both groups). Early morbidity rates were 17.8 percent for the Seprafilm® group and 15.6 percent for the controls, with mortality rates of 0.8 percent and 0.0 percent, respectively. There were 12 intestinal obstructions in 12 patients in the Seprafilm® group and 12 intestinal obstructions in 11 patients in the control group at a follow-up period of 65 months in the Seprafilm® group and 81 months in the control group. Eight of the 12 intestinal obstructions in the Seprafilm® group resolved with conservative management while only 5 of 12 in the control group responded without surgery. Thus the enterolysis rate was 1.5 percent in the Seprafilm® group and 3.9 percent in the control group, demonstrating a trend in favor of Seprafilm®. There were no statistically significant differences in the incidence of either overall or abdominopelvic septic complications between the Seprafilm® (3.4 percent) and control (1.1 percent) groups. CONCLUSION: During short-term follow-up in this nonprospective, nonrandomized study, limited placement of Seprafilm® did not significantly reduce the need for surgical enterolysis for intestinal obstruction or significantly adversely affect the morbidity rate. However, a long-term, prospective, randomized trial is underway to elucidate these issues.Supported by an educational grant from Genzyme Surgical Products, Inc.Presented at the Association of Coloproctology of Great Britain and Ireland, Southport, UK, July 10 to 12, 1999.     

Irinotecan treatment and senescence failure promote the emergence of more transformed and invasive cells that depend on anti-apoptotic Mcl-1

Induction of senescence by chemotherapy was initially characterized as a suppressive response that prevents tumor cell proliferation. However, in response to treatment, it is not really known how cells can survive senescence and how irreversible this pathway is. In this study, we analyzed cell escape in response to irinotecan, a first line treatment used in colorectal cancer that induced senescence. We detected subpopulations of cells that adapted to chemotherapy and resumed proliferation. Survival led to the emergence of more transformed cells that induced tumor formation in mice and grew in low adhesion conditions. A significant amount of viable polyploid cells was also generated following irinotecan failure. Markers such as lgr5, CD44, CD133 and ALDH were downregulated in persistent clones, indicating that survival was not associated with an increase in cancer initiating cells. Importantly, malignant cells which resisted senescence relied on survival pathways induced by Mcl-1 signaling and to a lesser extent by Bcl-xL. Depletion of Mcl-1 increased irinotecan efficiency, induced the death of polyploid cells, prevented cell emergence and inhibited growth in low-adhesion conditions. We therefore propose that Mcl-1 targeting should be considered in the future to reduce senescence escape and to improve the treatment of irinotecan-refractory colorectal cancers.     

Therapeutic efficacy of three silver dressings in an infected animal model

The organic salt AgNO3 has been available as a topical armamentarium to the medical arena for centuries and for burns for the past 60 years. Thirty-five (1968) years later, Charles Fox introduced and popularized a new topical agent known as silver sulfadiazine. More recently, several new slow-release silver dressings came to the forefront. Acticoat (Smith & Nephew, Largo, FL) Silverlon (Argentum, Lakemont, GA) & Silvasorb (Medline Industries, Inc, Mundelein, IL). Because the standard of care is to change dressings daily, our study focused in on weekly dressing changes as a cost-containment issue. Sprague-Dawley rats received a standard contact burn (20% TBSA). On day 3, the wound was excised and infected with Pseudomonas aeruginosa and Staphylococcus aureus at 5.0 x 10 cfu/ml. The animals were divided into four groups (n = 5 each group): untreated control, Acticoat group, Silvasorb group, and Silverlon group. The dressings remained on the wounds for 10 days when the wounds were quantitatively assessed. Mean wound counts of the control ranged from 1.2 x 10(5) to 6.5 x 10(5) for P. aeruginosa and S. aureus, respectively. Acticoat dressing counts for both organisms were 0 and 1.8 x 10(3) (median alpha); Silvasorb was 0 and 6.3 x 10(3) and Silverlon was 1.5 x 10(4) x 7.4 x 10(4) (median), Acticoat and Silvasorb were both significantly lower (P < .05) than the control for P. aeruginosa, and Acticoat was significantly lower (P < .05) than the control for S. aureus. Although counts for Silvasorb (M) appear significantly lower than the controls for S. aureus, the numbers were not sufficient to be significant. However, Silverlon did achieve a slight significance. These preliminary data suggest that weekly dressing changes with these new silver dressings are feasible and economically and medically congruous.     

Re-examining the cognitive phenotype in autism: A study with young Chinese children

Deficits consistently found in autism include an impaired “theory of mind”, weak central coherence, and deficits in executive function. The current study examined whether this traditional cluster of symptoms existed in a group of Chinese-speaking children with autism. Sixteen high-functioning, non-retarded children with autism were matched to 16 typically developing (TD) children on gender, non-verbal IQ and age. Non-verbal IQ's of all participants were measured using the Raven Progressive Matrices. Each participant was tested individually on measures of “theory of mind”, central coherence and executive function. Results indicated that most, but not all, participants with autism performed significantly poorer on two standard measures of first-order “theory of mind,” although there was no significant difference on two other measures of that domain. As expected, they performed significantly worse on executive function tasks. However, the hypothesis of weak central coherence in autism was not substantiated. There was no evidence that these three cognitive impairments co-existed in individuals with autism. More likely, each of these deficits appears singly or in pair instead of forming a cluster.