Salivary gland hyalinizing clear‐cell carcinoma with cutaneous metastasis: A rare and deceptive tumor

Clear‐cell carcinoma (CCC) is an uncommon malignant tumor of minor salivary glands. It characteristically has a low‐grade morphology and a favorable outcome by most reports. An EWSR1‐ATF1 fusion can be detected in the majority of cases. We present a rare case of CCC, which had an aggressive course with the development of cutaneous metastases. Practicing dermatopathologists should be aware of this tumor given its low‐grade appearance and histopathologic resemblance to other primary cutaneous adnexal and metastatic neoplasms.     

Epigenetic Regulation of Placenta-Specific 8 Contributes to Altered Function of Endothelial Colony-Forming Cells Exposed to Intrauterine Gestational Diabetes Mellitus

Intrauterine exposure to gestational diabetes mellitus (GDM) is linked to development of hypertension, obesity, and type 2 diabetes in children. Our previous studies determined that endothelial colony-forming cells (ECFCs) from neonates exposed to GDM exhibit impaired function. The current goals were to identify aberrantly expressed genes that contribute to impaired function of GDM-exposed ECFCs and to evaluate for evidence of altered epigenetic regulation of gene expression. Genome-wide mRNA expression analysis was conducted on ECFCs from control and GDM pregnancies. Candidate genes were validated by quantitative RT-PCR and Western blotting. Bisulfite sequencing evaluated DNA methylation of placenta-specific 8 (PLAC8). Proliferation and senescence assays of ECFCs transfected with siRNA to knockdown PLAC8 were performed to determine functional impact. Thirty-eight genes were differentially expressed between control and GDM-exposed ECFCs. PLAC8 was highly expressed in GDM-exposed ECFCs, and PLAC8 expression correlated with maternal hyperglycemia. Methylation status of 17 CpG sites in PLAC8 negatively correlated with mRNA expression. Knockdown of PLAC8 in GDM-exposed ECFCs improved proliferation and senescence defects. This study provides strong evidence in neonatal endothelial progenitor cells that GDM exposure in utero leads to altered gene expression and DNA methylation, suggesting the possibility of altered epigenetic regulation.     

Renal fungus ball in a patient with retroperitoneal fibrosis: Unique complication in a rare disease

Candida fungus ball is a rare presentation of urinary tract infections among adult patients and is associated with considerable morbidity. Because clinical signs are not specific, diagnosis is often delayed. Furthermore, treatment is occasionally difficult, and the approach to such cases varies widely among different centers. In this report, we describe a patient with retroperitoneal fibrosis who developed a renal fungus ball. Management of this challenging case is discussed, and review of the literature is presented.     

Discrimination of bilateral differences in the loci of tactile stimulation is impaired in subjects with Parkinson's disease

We have compared the abilities of patients with idiopathic Parkinson's disease (PD), while on levodopa (L-dopa), and control subjects to discriminate bilateral differences in the loci of tactile stimulation. On each trial, one of a subject's forearms served as the reference arm and the other as the test arm. The two forearms were supinated and placed side-by-side on a table-top in front of the subject. Seven cutaneous test loci, 3 mm apart, were arrayed proximo-distally on the flexor aspect of each forearm, with the fourth (central) serving as a reference point. On each trial, two punctate tactile stimuli (of intensity well above perceptual threshold) were applied simultaneously to 1) one of the seven test loci on the test forearm and 2) the reference (central) locus on the reference arm. Subjects, with eyes closed, stated which forearm (test or reference) was stimulated more distally. Estimates of the difference limen (DL, a measure of discriminatory threshold) and the point of subjective equality (PSE, the test locus perceived to correspond to the reference locus) were derived from psychophysical functions (ogives). For each subject, one arm was defined as 'better' and the other as 'worse.' Among PD patients, this definition was in terms of the relative severity of clinical motor signs (combined scores for bradykinesia, rigidity and tremor) of the two arms, whereas among controls it was according to relative DL magnitudes (sensory/perceptual performance). The mean DL of the patients significantly exceeded that of control subjects on both the 'better' and 'worse' arms as test side, but mean PSE values did not differ significantly between groups. Thus, our PD patients were impaired in discriminating bilateral differences in the locations of tactile stimulation, while perceiving normally the relative locations of the proximo-distal centers of the two stimulus arrays.     

Predicting outcome based on Swenerton score in patients with metastatic breast cancer undergoing high-dose chemotherapy and autologous hematopoietic stem cell transplantation: implications for patient selection.

The aim of this study was to study the effectiveness of the Swenerton score in assessing extent of disease as an independent prognostic and predictive factor in patients with metastatic breast cancer (MBC) who receive high-dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplant (AHSCT). Two-hundred thirty-two patients with MBC underwent HDCT. Extent of disease was assessed quantitatively using the Swenerton score. A retrospective analysis was performed using Cox proportional hazards regression and logistic regression models. One hundred three (44%) patients had a complete response (CR) after HDCT. Bone marrow as source of hematopoietic stem cells, hormone-receptor-negative status, and visceral involvement correlated with both worse overall survival (OS) and progression-free survival (PFS). Short disease-free interval, multiple sites of metastatic disease, and less than 50% reduction in the Swenerton Score during induction chemotherapy correlated with worse OS. Patients in CR at the time of HDCT had better PFS than patients in partial response, stable disease, or progressive disease. Fifty-six patients who underwent conversion to CR after HDCT had a similar median OS (not reached v 74 months; P =.51) and PFS duration (22 v 44 months; P =.15) as patients who received HDCT after a CR to standard-dose chemotherapy (SDCT). Conversion to CR was predicted by a >/=50% reduction in the Swenerton score during SDCT (odds ratio [OR] 3.32, P <.01) and soft-tissue disease (OR 4.08, P <.01). The presence of multiple metastatic sites predicted decreased probability of conversion to CR (OR 0.34, P <.01). The Swenerton score provides a thorough estimate of disease extent, and reduction of Swenerton score by SDCT is potentially useful for selecting the optimal candidates for HDCT trials who may achieve long-term disease control.     

Relapses vs. reactions in multibacillary leprosy: proposal of new relapse criteria

Objectives To compare a new scoring system for multibacillary (MB) leprosy relapses, which combines time factor, risk factors and clinical presentation at relapse, to WHO criteria. Methods Data were collected on all relapses diagnosed between 1998 and 2004 at the Marie‐Adelaide‐Centre in Karachi, Pakistan, including case histories, clinical manifestations, follow‐up, bacterial indices, treatment and contacts. For the diagnosis of MB relapses a simple scoring system was developed and validated on a data‐set of mouse foot pads (MFP)‐confirmed relapses (Leprosy Reviews, 76 , 2005, 241). Its sensitivity was further evaluated in the Karachi relapse cohort. The P‐value was calculated with McNemar’s test with continuity correction. Results The new scoring system that combines time factor, risk factors and clinical presentation at relapse had a higher sensitivity in MFP‐confirmed relapses than the WHO‐criteria (95%vs. 65%, P < 0.01). The sensitivity of the scoring system was also significantly higher than the WHO criteria in the 57 cases of MB‐relapses diagnosed in Karachi (72%vs. 54%, P < 0.05). Conclusions This new simple scoring system for diagnosing MB‐relapses in leprosy should be further validated in a prospective study to confirm its superior sensitivity and to evaluate the specificity of these criteria by using MFP‐confirmation for patients presenting with signs of activity after treatment.     

Validity of self‐reported family history of cancer: A systematic literature review on selected cancers

Evidence regarding validity of self‐reported family history of cancer (FHC) has been reviewed only for breast, colorectal, prostate, ovarian, endometrial and uterine cancer. We aimed to systematically review studies assessing validity of self‐reported family history for the remaining cancer sites. We searched the Medline database for relevant studies published by January 2016. We extracted information on the study design and the positive predictive value (PPV) of self‐reported FHC, defined as the proportion of reported cancer diagnoses among relatives that was confirmed by a reference standard (as a measure of over‐reporting). We also extracted information on sensitivity of self‐reported FHC (as a measure of underreporting). Overall, 21 studies were included that provided information on the PPV of self‐reported FHC for relevant cancers and four studies also provided information on sensitivity. The PPV was highest (mostly >70%) for pancreatic, lung, thyroid and urinary system cancers and for leukemia and lymphoma, while it was lowest for stomach and liver cancer. Sensitivity was highest (>70%) for pancreatic cancer, lung cancer, brain cancer, melanoma, leukemia and lymphoma. For several cancers, sample sizes were low and the number of studies limited, particularly regarding sensitivity of self‐reported FHC. In conclusion, for some cancers (e.g., pancreatic cancer, lung cancer, leukemia, lymphoma) self‐reported FHC can be considered sufficiently valid to be useful, for example, in preventive counseling. For several cancers, it is not sufficiently studied or the pattern is inconsistent. This needs to be taken into account when using self‐reported information about FHC in clinical practice or epidemiological research.     

Novel biphasic role for lymphocytes revealed during resolving inflammation

Acute inflammation is traditionally described as the influx of polymorphonuclear leukocytes (PMNs) followed by monocyte-derived macrophages, leading to resolution. This is a classic view, and despite subpopulations of lymphocytes possessing innate immune-regulatory properties, seldom is their role in acute inflammation and its resolution discussed. To redress this we show, using lymphocyte-deficient RAG1(-/-) mice, that peritoneal T/B lymphocytes control PMN trafficking by regulating cytokine synthesis. Once inflammation ensues in normal mice, lymphocytes disappear in response to DP1 receptor activation by prostaglandin D(2). However, upon resolution, lymphocytes repopulate the cavity comprising B1, natural killer (NK), gamma/delta T, CD4(+)/CD25(+), and B2 cells. Repopulating lymphocytes are dispensable for resolution, as inflammation in RAG1(-/-) and wild-type mice resolve uniformly. However, repopulating lymphocytes are critical for modulating responses to superinfection. Thus, in chronic granulomatous disease using gp91phox(-/-) mice, not only is resolution delayed compared with wild-type, but there is a failure of lymphocyte re-appearance predisposing to exaggerated immune responses upon secondary challenge that is rescued by resolution-phase lymphocytes. In conclusion, as lymphocyte repopulation is also evident in human peritonitis, we hereby describe a transition in T/B cells from acute inflammation to resolution, with a central role in modulating the severity of early onset and orchestrating responses to secondary infection.     

Measuring the gap: from Home Office to the National Health Service in the provision of a one-stop shop sexual health service in a female prison in the UK

The Genitourinary (GU) Medicine Service was transferred from the Home Office to the NHS from April 2006 at this female prison to give prisoners access to the same quality of health care as the general public. Medline search showed no published data on the prevalence of sexually transmitted infections (STIs) among female prisoners in the UK. The main aim was to develop a one stop sexual health shop and to determine the prevalence and risk factors for STIs, to determine the uptake rate for HIV testing, hepatitis B vaccination and cervical cytology along with requests for usage of contraceptive services. Challenges were met when introducing change to bring the services in line with the local GU medicine clinic. Review of the service at one year along with retrospective case note review from May 2006 to August 2007 was done. Of the 545 new patients seen, history of substance abuse, IVDU, sexual abuse, sex worker and past history of hepatitis C virus and chlamydia were 86%, 41%,12%, 6%, 17% and 24% respectively.The uptake rate for both STI screen and blood-borne viruses (BBVs) testing was high at 87% and 69.3% respectively. STI was diagnosed in 19.6%. Prevalence rates were: Trichomonas vaginalis (TV) 8.2%, chlamydia 5.3%, gonorrhoea 0.2%, genital warts 5.3%, HIV 0.8%, hepatitis C virus 12% and hepatitis B virus 11%. The uptake rate for 1(st) dose hepatitis B vaccination and cervical cytology were 70% and 92% respectively, 36 accessed contraceptive services. Provision of one stop shop in a female prison is feasible and practical. STIs, particularly TV, and BBVs prevalence is high among the female inmates. Prevention methods targeting this population needs to be intensified.