D-dimer levels decline after immunosuppressive treatment rather than anticoagulant treatment in severe autoimmune chronic spontaneous urticaria.

Summary: Chronic spontaneous urticaria (CSU) is a common dermatological condition presenting with wheals and/or angioedema for more than 6 weeks. The role of autoimmunity and inflammation in the pathogenesis of CSU have been studied, but the precise mechanism remains unknown. Association with coagulation cascade has been suggested based on the observations of increased coagulation indicators such as serum D-dimer levels. We report an omalizumab refractory case of severe CSU with high D-Dimer levels that declined only after disease remission with cyclosporine treatment but not with anticoagulation. Activation of coagulation cascade occurs secondary to the pro-inflammatory state in CSU patients and the correlation between D-dimer levels and disease activity may indicate the need for more studies to better understand the relationship of D-dimer levels and Omalizumab resistance. Clinicians should consider this relationship in CSU patients with significant D-dimer levels before considering treatment with anticoagulants.

Prognostic factors in 161 patients with mucosal melanoma: a study of German Central Malignant Melanoma Registry.

BACKGROUND: Mucosal melanoma is a rare malignancy which represents approximately 1% of all melanomas. It is shown that mucosal melanomas have a different biology and less favourable prognosis than its cutaneous counterpart. OBJECTIVES: Predictive and prognostic factors of survival for mucosal melanoma have not yet been elucidated. The aim of this study was to investigate risk factors affecting the course of mucosal melanoma patients followed in our clinic. METHODS: One hundred and sixty-one patients with mucosal melanoma prospectively documented in the German Central Malignant Melanoma Registry (CMMR) were included in this study. Gender, age, localization, stage at first medical examination, tumour thickness and mutational status were documented. The American Joint Committee on Cancer (AJCC), 7th edition was used to define tumour stage. Kaplan-Meier survival curves were evaluated compared with the log-rank test. Multivariate Cox proportional hazard models were used to identify significant independent prognostic factors. RESULTS: According to the localization, patients were categorized in 44.7% oral-nasal, 28.6% genital, 20.5% anorectal and 6.2% visceral. Genital mucosal melanomas had the most favourable 5-year OS rate (58.6%) followed by visceral (58.3%) and oral-nasal (39.3%). Anorectal melanomas had the worst OS time (median: 21 ± 4.8 months) and 5-year survival rate (22.7%). Patients <60 years had a better survival than the older group (P = 0.013). Tumour stage at the time of the first medical examination was also a significant factor for survival (P = 0.001). Gender and mutational status were found to have no effect on survival. Age (<60 years vs. ≥60 years; HR = 2.1) and stage at first medical examination (Stage I vs. Stage IV; HR = 8.2) are shown to be significant independent prognostic factors on multivariate Cox regression analysis, but not localization. CONCLUSION: In this study, we observed that older age and advanced stage have significant negative effects on the survival of mucosal melanoma. Thus, the AJCC staging system is applicable for mucosal melanoma.

Late recurrence of melanoma after 10 years - Is the course of the disease different from early recurrences?

BACKGROUND: It is known that melanoma can metastasize and recur many years after the first diagnosis. Although predictive and prognostic factors for melanoma are well defined, there is still insufficient information about the factors affecting the recurrence period and the effect of the recurrence time to survival. OBJECTIVES: This study investigates the course of melanoma to show prognostic factors comparing early and late recurrence patients. The main objective is to uncover the effect of the recurrence time on the progression of the disease. METHODS: In this retrospective study, late recurrence (LR) was defined as melanoma recurrence 10 years after the first diagnosis and early recurrence (ER) was defined as recurrence within 10 years. Gender, age, localization of primary tumour, time to first metastasis, survival rates, histological subtype, stage, tumour thickness, invasion level, ulceration and regression of the primary melanoma were documented. Survival curves were evaluated using the Kaplan-Meier and compared with the log-rank test. Multivariate Cox proportional hazard models were used to identify significant independent prognostic factors for melanoma-specific survival (MSS). RESULTS: A total of 1537 melanoma patients were analysed. Early metastasis was developed in 1438 patients (93.6%), and 99 patients (6.4%) developed late metastasis. Late recurrence patients were younger (P < 0.001) and had fewer ulcerated (P = 0.005), fewer head/neck localized (P = 0.009) and thinner (P < 0.001) melanomas than ER patients. The MSS time (mean ± SD) was nearly identical for LR (31 ± 4.4 months 95% CI [22.3-39.7]) and ER (32 ± 1.9 months [28.3-35.7]). Multivariate regression analysis revealed male gender (hazard ratio [HR = 1.4, P < 0.001), truncal tumour localization (HR = 1.7, P < 0.001), tumour thickness (HR = 1.4, P < 0.045) and ulceration (HR = 1.3, P < 0.008) as significant independent prognostic factors for MSS. CONCLUSION: Although ER and LR patients are found to have different clinicopathologic features, the time of the first recurrence after diagnosis do not seem to have an effect on the survival.

Alexithymia in diabetes mellitus.

BACKGROUND: Diabetes mellitus is a chronic, progressive disease with complex therapy protocols requiring major coping efforts from patients to achieve and maintain glycaemic control in order to reduce risk of diabetic complications. Disease coping strategies including good knowledge of diabetes and high ability of self-care have been reported to be impaired by alexithymic features. Alexithymia is a psychological construct characterised by inability to express emotions verbally, poor imagination and operational thinking, leading to failure in psychological self-regulation. OBJECTIVE: To compare prevalence of alexithymia and mean Toronto Alexithymia Scale-26 (TAS-26) scores in diabetic patients with non-diabetic controls; to investigate the association of alexithymia with glycemic control in diabetes. METHOD: In this cross- sectional study, TAS-26 scores of 193 diabetic patients and 49 non-diabetic controls were compared. Disease related factors were obtained from patient records. Alexithymia was used as a continuous (mean TAS-26 scores) and semi-quantitative (dichotomised into non-alexithymic 11>TAS-26 scores>11 and alexithymic individuals) variable. Descriptive data are presented as mean +/- SD, median (range) or %. Differences in means were compared via Independent-Samples T Test and One-Way ANOVA. Proportions were analysed with chi-square test and odds ratios (OR) were calculated via cross tabulation with a confidence interval (CI) of 95%. P<0.05 was considered statistically significant. RESULTS: The control group was similar with respect to age, gender and education with the diabetic group. In the diabetic study population (n=193, male/female: 42/58%, age 54.2 +/- 14.0 years, median diabetes duration 7 years (1-32 years), postprandial blood glucose (PBG) 243 +/- 110 mg/dl HbA1 c 7.3 +/- 3.6%) prevalence of alexithymia was significantly higher than in the control group (65 % in diabetics vs. 45 % in controls, p=0.011; mean TAS-26 score 12.3 +/- 3.7 vs. 10.6 +/- 3.6, p=0.004, respectively). Poor postprandial glycaemic control (p=0.002), female gender (p=0.026), combination therapy (p=0.037) and poor educational level (p=0.005) were positively associated with TAS-26 scores in diabetic individuals. Alexithymic diabetic patients were less educated (OR=1.2, p=0.046) and under worse glycaemic control (OR=2.4, p=0.005) compared to their non-alexithymic counterparts.

Clinicopathological implication of cripto expression in early stage invasive cervical carcinomas.

This study evaluates the expression of cripto (CR-1) protein in matched sets of non-neoplastic cervical epithelium, primary cervical carcinoma and metastatic tumours in the lymph nodes to investigate its role in uterine cervical cancer development and progression. Ninety-four primary cervical carcinomas in an early clinical stage and having the same surgical treatment modality were analysed. Immunoreactivity in the primary tumour was compared with that of non-neoplastic cervical epithelium and metastatic lymph nodes. The conventional clinicopathological prognostic variables for cervical carcinomas such as grade, tumour size, depth of invasion, parametrial and endometrial extension, lymphovascular space involvement and lymph node metastasis status were also compared with CR-1 expression of the primary tumour. Strong CR-1 immunopositivity was significantly correlated with tumour size and lymphovascular space involvement (P < 0.05). Furthermore, a significant relationship was found between CR-1 immunoreactivity and endometrial extension as well as parametrial involvement (P < 0.05). Interestingly, the CR-1 expression level was increased in metastatic lymph nodes compared with their primary tumours. These results suggest that CR-1 may contribute to disease progression in cervical carcinomas.

Lumbosacral plexopathy after dual kidney transplantation.

A 58-year-old man underwent dual kidney transplantation. He was unable to move his right leg after surgery. This was caused by extensive lumbosacral plexopathy on the side of surgery. Lumbosacral plexopathy after kidney transplantation is uncommon, because the plexus has rich anastomotic blood supply, and ischemic injury is unlikely. However, isolated femoral neuropathy after renal transplantation has been reported, as the distal portion of this nerve is supplied by branches of internal iliac artery only and is more prone to ischemic injury during surgery. Dual-kidney transplantation involves a larger dissection, and the procedure takes 60 to 90 minutes longer than single-kidney transplantation. It involves more vascular reconstruction. This may predispose the lumbosacral plexus to ischemic injury. To the best of our knowledge, this is the first reported case of lumbosacral plexopathy after a dual kidney transplantation, and this may be seen more frequently because this procedure is becoming more common.

Pregnancy in infertile PCOD patients. Complications and outcome.

OBJECTIVE: To evaluate the complications and outcome of pregnancy in women with polycystic ovary disease (PCOD). STUDY DESIGN: The course and outcome of 47 singleton pregnancies in women with well-documented PCOD were compared with those in 100 healthy controls. RESULTS: Women with PCOD had a significantly higher body mass index as compared to the control group (P < .05); however, the proportion of lean versus obese subjects in the two groups was similar. The incidence of an abnormal glucose challenge test, gestational diabetes mellitus and pregnancy-induced hypertension was significantly increased in pregnant women with PCOD (P < .05). When lean PCOD subjects were compared with lean control subjects, the difference in the incidence of the above complications was still significant (P < .05). The incidence of pregnancy complications was similar when obese PCOD subjects were compared with obese controls. CONCLUSION: Women with PCOD were at increased risk of gestational diabetes and pregnancy-induced hypertension, and this risk appeared to be independent of body mass index.

nm23 expression in carcinoma of the uterine cervix.

To evaluate the significance of nm23 protein expression in cervical carcinoma, 83 patients with stage IB disease, treated primarily with surgery were studied immunohistochemically. Of the cases 57 were squamous carcinoma, 9 were adenocarcinoma, 14 were adenosquamous carcinoma and 3 were small-cell carcinoma. nm23 expression was positive in 63% of the cases. Although positive expression was more common in squamous and adenosquamous type tumors, negative expression was dominant in adenocarcinoma (P<0.05). When nm23 expression was compared with the clinicopathologic risk factors, there was no correlation of expression with the grade, deep invasion of the stroma, parametrial involvement and lymph node metastasis. But expression was inversely correlated with the number of metastatic lymph nodes (P<0.05). Although 3 or more lymph node metastases is a very poor prognostic sign, nm23 expression was not correlated either with recurrence or survival. Expression was negative in 77% of metastatic lymph nodes and in all of the recurrences. The predominance of negative expression in metastatic lymph nodes (P<0.05) and recurrences seems to be related to the aggressive behavior of the negative clone in the heterogeneous primary tumor.

Response to high-dose interferon-alpha after failure of standard therapy in MPGN associated with hepatitis C virus infection.

A 42-year-old man developed mixed cryoglobulinemia secondary to hepatitis C virus (HCV) infection with hypocomplementemia and nephrotic syndrome. His renal biopsy showed membranoproliferative glomerulonephritis type I (MPGN). Despite treatment with interferon-alpha, three million units three times a week for a total of 6 months, the patient continued to have hypocomplementemia, cryoglobulinemia, and nephrosis. After a course of high-dose interferon-alpha treatment consisting of ten million units daily for 2 weeks followed by 10 million units three times per week for an additional 6 weeks, HCV RNA and cryoglobulin testing became negative, complement levels increased to normal levels, and nephrotic syndrome remitted. This case confirms an association between HCV infection and MPGN and suggests a role for high-dose interferon-alpha treatment when conventional interferon therapy fails.

Pyelocaliectasis and intrarenal artery doppler indices in uncomplicated pregnancies.

The effect of pyelocaliectasis on intrarenal arterial Doppler indices was evaluated in healthy pregnant women with respect to nonpregnant controls. There was no significant difference between the pregnant and nonpregnant subjects regarding the systolodiastolic ratio, resistivity index and pulsatility index throughout the second and third trimesters (p for all > 0.05). There were 134 kidneys with grade 0, 38 kidneys with grade I and 24 cases with grade II pyelocaliectasis in the pregnant population. Grade II caliectasis was found only in the right kidneys. The nonpregnant women all had grade 0 caliectasis. Doppler indices were not significantly different in various grades of caliectasis, and right and left kidneys had similar Doppler indices. The results of this study suggest that pyelocaliectasis increases with advancing gestational age and is more frequent and prominent on the right side but has no effect on intrarenal Doppler indices in healthy pregnant women. In cases of prominent alterations in Doppler indices, renal pathological conditions should be sought.

Prostate androgen receptor: immunohistological localization and mRNA characterization.

Four androgen receptor (AR) specific monoclonal antibodies were used for the immunohistochemical localization of AR in the human prostate tissue. The prostate tissue consisted of alveoli embedded in fibromuscular stroma and lined with a single layer of columnar secretory epithelial cells. The immunoreactive ARs were found predominantly in the nuclei of epithelial cell, suggesting ARs, like estrogen receptors and progesterone receptors, are mainly nuclear proteins. Northern blot hybridization showed that AR mRNA is about 9 kilobases (kb) and relative abundant in the androgen-sensitive organs, such as ventral prostate, dorsolateral prostate and seminal vesicle.

Chronic regulation of transepithelial Na+ transport by the rate of apical Na+ entry.

In several settings in vivo, prolonged inhibition of apical Na+ entry reduces and prolonged stimulation of apical entry enhances the ability of renal epithelial cells to reabsorb Na+, an important feature of the load-dependent regulation of renal tubular Na+ transport. To model this load dependency, apical Na+ entry was inhibited or stimulated for 18 h in A6 cells and vectorial transport was measured as short-circuit current (Isc) across monolayers on filter-bottom structures. Basal amiloride-sensitive Isc represents the activity of apical Na+ channels, whereas Isc after permeabilization of the apical membrane to cations with nystatin represents maximal activity of the basolateral Na(+)-K(+)-ATPase. Chronic inhibition of apical Na+ entry by 18-h apical exposure to amiloride or replacement of apical Na+ with tetramethylammonium (TMA+), followed by washing and restoration of normal apical medium, revealed a persistent decrease in Isc that remained despite exposure to nystatin. Both basal and nystatin-stimulated Isc recovered progressively after restoration of normal apical medium. In contrast, chronic stimulation of apical Na+ entry by short circuiting the epithelium increased Isc in the absence and presence of nystatin, indicating upregulation of both apical Na+ channels and basolateral Na(+)-K(+)-ATPase. Basolateral equilibrium [3H]ouabain binding was reduced to 67 +/- 5% in TMA+ vs. control cells, whereas values in 18-h short-circuited cells increased by 42 +/- 19%. The results demonstrate that load dependency of tubular Na+ transport can be modeled in vitro and indicate that the regulation of Na(+)-K(+)-ATPase observed in these studies occurs in part by changes in the density of functional transporter proteins within the basolateral membrane.