STAT3 cooperates with the non-canonical NF-κB signaling to regulate pro-labor genes in the human placenta.

INTRODUCTION: Our recent studies have shown that constitutively activated non-canonical RelB/NF-κB2 (p52) in the human placenta positively regulates the pro-labor genes CRH and COX-2. STAT3 regulates NF-κB2 (p100) processing to active p52, and in turn, nuclear activation of RelB/p52, by directly binding to p100/p52 in a variety of cancer cells. In the current study, we tested the hypothesis that STAT3 is involved in regulation of pro-labor genes by associating with RelB/p52 heterodimers in the human placenta. METHODS: We used a variety of techniques including immunohistochemical staining, gene silencing, ectopic expression, chromatin immunoprecipitation, Western blot, RT-qPCR, and immunofluorescence assays in primary culture of cytotrophoblast and placental tissues. RESULTS: We found that knockdown of STAT3 led to down-regulation of both CRH and COX-2 in a dose-dependent manner. By using chromatin immunoprecipitation, we further showed that interaction of RelB with the CRH or COX-2 gene promoters decreased when STAT3 was depleted. Immunofluorescence demonstrated co-localization of STAT3 with RelB or p100/p52 in both the cytoplasm and nucleus of term cytotrophoblasts. DISCUSSION: Collectively, these results suggest that STAT3 constitutes part of the RelB/p52-containing activator complex that positively regulates pro-labor genes in the human placenta.

Increased mortality rate and suicide in Swedish former elite male athletes in power sports.

Physical training has been shown to reduce mortality in normal subjects, and athletes have a healthier lifestyle after their active career as compared with normal subjects. Since the 1950s, the use of anabolic androgenic steroids (AAS) has been frequent, especially in power sports. The aim of the present study was to investigate mortality, including causes of death, in former Swedish male elite athletes, active 1960-1979, in wrestling, powerlifting, Olympic lifting, and the throwing events in track and field when the suspicion of former AAS use was high. Results indicate that, during the age period of 20-50 years, there was an excess mortality of around 45%. However, when analyzing the total study period, the mortality was not increased. Mortality from suicide was increased 2-4 times among the former athletes during the period of 30-50 years of age compared with the general population of men. Mortality rate from malignancy was lower among the athletes. As the use of AAS was marked between 1960 and 1979 and was not doping-listed until 1975, it seems probable that the effect of AAS use might play a part in the observed increased mortality and suicide rate. The otherwise healthy lifestyle among the athletes might explain the low malignancy rates.

Classical swine fever virus infection modulates serum levels of INF-α, IL-8 and TNF-α in 6-month-old pigs.

Several studies have highlighted the important role of cytokines in disease development of classical swine fever virus (CSFV) infection. In the present study, we examined the kinetics of 7 porcine cytokines in serum from pigs infected with 3 different CSFV strains. Based on the clinical picture in 6-month-old Danish pigs, the strains used for inoculation were classified as being of low (Bergen), low to moderate (Eystrup) and moderate to high (Lithuania) virulence. The cytokines interferon-alpha (INF-α), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α) showed increased levels after CSFV infection with more or less comparable course in the 3 groups. However, the cytokine level peaked with a 2-3 days delay in pigs infected with the low virulent strain compared to those infected with a moderately or highly virulent strain. These findings may indicate that INF-α, IL-8 and TNF-α are involved in the immune response during CSFV infection with strains of different virulence.

Use of neostigmine to relieve a suspected colonic pseudoobstruction in pregnancy.

Neostigmine is a treatment option for colonic pseudoobstruction. However, experience in using neostigmine for this indication in pregnant women is limited. We present a case of a woman with an estimated fetal gestational age of 34 weeks presented with what was believed to be a pseudoobstruction and when conservative management failed, neostigmine was administered with no adverse side effects. Ultimately, the patient was found to have a mechanical obstruction and we discuss the challenges in making this diagnosis in pregnancy. Neostigmine may be a viable alternative to colonoscopy in pregnant women for whom mechanical obstruction is properly excluded.

Malignant disease and cardiovascular morbidity in hypopituitary adults with or without growth hormone replacement therapy.

A retrospective comparison was performed between 1411 hypopituitary adults without GH replacement [mean age, 56.9 (sd 18.6) yr] and the normal population in terms of fatal and nonfatal morbidity. A similar prospective comparison was then made in 289 hypopituitary patients on long-term GH replacement [mean age, 47.6 (sd 14.8) yr; mean duration of GH treatment, 60 months]. In the 1411 hypopituitary patients without GH replacement, overall mortality (P < 0.001), and the rates of myocardial infarctions (P < 0.01), cerebrovascular events (P < 0.001), and malignancies (P < 0.001) were increased compared with the normal population. Colorectal cancer was the most common malignancy in this cohort (P < 0.001 vs. the background population). In the 289 hypopituitary patients on GH replacement, overall mortality and the rate of malignancies were similar to the normal population. In the hypopituitary adults on GH therapy, the rate of myocardial infarctions was lower than that in the background population (P < 0.05), and there was a tendency toward an increased rate of cerebrovascular events. In conclusion, overall mortality and the rate of myocardial infarctions were increased in hypopituitary patients without GH replacement. An increased rate of malignancies was observed in the hypopituitary adults without GH therapy, with a predominance of colorectal cancer. GH replacement appeared to provide protection from myocardial infarctions. The rate of cerebrovascular events tended to be increased also in hypopituitary adults on GH therapy.

[Transbrachial selective carotid DSA in outpatients: safety and efficacy]. / Diagnostische Sicherheit und Effizienz ambulanter transbrachialer selektiver Karotisangiographien.

PURPOSE: To describe safety and efficacy of transbrachial selective carotid digital subtraction angiography (DSA) in outpatients. MATERIALS AND METHODS: From July 1999 to November 2001, selective carotid angiography was performed in 141 outpatients preferably using a left brachial arterial approach. The average age of the patients was 68 years (range: 39 - 89 years). After flush aortography through a 4F-pigtail catheter, bilateral selective common carotid artery (CCA) catheterization was performed with 4F-Sidewinder-1 or Sidewinder-2 catheters. In 49 patients, Doppler-sonography was performed before or after arteriography. A total of 41 patients underwent carotid surgery. RESULTS: Selective catheterization of the CCA was successful in 96 % of the cases. The diagnostic quality of the opacified aorta and CCA images was good to excellent. The overall complication rate did not exceed 2.1 %, and severe complications were not observed. One patient showed transient neurological symptoms and another mild nausea and agitation, probably as toxic reaction to the contrast medium. A single local hematoma developed after unsuccessful puncture of the brachial artery. CONCLUSION: Transbrachial selective carotid DSA is safe, reliable and well-tolerated in outpatients and achieves a superimposition-free CCA visualization.

[Evolution of inflammatory parameters after fibroid embolization]. / Entwicklung der Entzündungsparameter nach Myomembolisation.

PURPOSE: To describe the rise of classical laboratory tests for inflammation following transarterial uterine fibroid embolization (UFE) in order to monitor the normal course following UFE. MATERIALS AND METHODS: In 20 females, white blood cell (WBC) count and C-reactive protein (CRP) were determined before and up to 5 days after UFE. With the exception of one noninflammatory complication, the post-procedure course was uneventful in all patients. The measured values were correlated with both the total uterine volume and the amount of instilled embolizing agent. RESULTS: Following UFE, an increase in the WBC count to an average maximum of 10.8 +/- 3.5/wL (range 5.9 - 18.6/wL) was found. In 13 of 20 patients, the WBC count was above normal on at least one day following UFE. The increase reached the maximum on the third post-interventional day and subsided within 5 days after the UFE. The CRP values increased significantly to an average maximum of 41.9 +/- 28.8 mg/l. The maximum was found on the 2nd post-interventional day in 8 patients, on the 3rd day in 11 patients and on the 4th day in one patient. No correlation to the total uterine volume or to the amount of the instilled embolizing agents was detected. CONCLUSION: Following uncomplicated UFE, a steep increase in CRP occurs with no or only a mild increase in the WBC count, which does not indicate an infected fibroid. The maximum is reached on the 3rd or 4th post-interventional day, followed by a decline in CRP and normalization of the WBC count.

Central hemodynamic monitoring in a woman with acute respiratory insufficiency after evacuation of a complete molar pregnancy. A case report.

BACKGROUND: The incidence of hydatiform moles in the United States is approximately 1 in 1,200 pregnancies. Acute respiratory insufficiency is a known complication of molar pregnancies, occurring in 8-11%. While there have been numerous case reports and retrospective studies describing respiratory complications following evacuation of hydatiform moles, only a limited number of reports provide data from central hemodynamic monitoring in patients with this complication. CASE: A 16-year-old, Hispanic woman, gravida 1, para 0, presented to the emergency room at 13 weeks' gestational age by menstrual dating with complaints of vaginal bleeding for two days. The serum quantitative beta-hCG level was 1 x 10(6) mIU/mL, and a bedside sonogram was consistent with hydatiform mole. After informed consent was obtained, the patient underwent dilation and suction curettage. Approximately five minutes after evacuation of the uterus was begun, the patient developed pulmonary edema in the setting of oliguria. A pulmonary artery catheter was inserted to determine the etiology of the edema. The initial pulmonary capillary wedge pressure was > 18 mm Hg, consistent with hydrostatic pulmonary edema. Volume overload in association with a reduced colloid osmotic pressure to wedge pressure gradient was primarily responsible for the pulmonary edema in this patient. CONCLUSION: The majority of case reports of pulmonary complications after evacuation of a hydatidiform mole were either presumed or documented to be due to trophoblastic pulmonary embolism. Thyrotoxicosis, fluid overload with dilutional anemia, preeclampsia, sepsis, hypoalbuminemia or a combination of these factors may be more common than trophoblastic embolization.

Pigmented Bowen's disease (squamous cell carcinoma in situ): a mimic of malignant melanoma.

BACKGROUND: Darkly pigmented individuals may manifest unusual or uncharacteristic presentations of various skin conditions, including heavy pigmentation of cutaneous tumors. OBJECTIVE: To increase the awareness of an unusual presentation of Bowen's disease in a darkly pigmented individual. METHODS: We report the case of a 52 year old black woman that presented with a lesion clinically consistent with malignant melanoma. However, histopathologic examination revealed pigmented Bowen's disease. RESULTS: A biopsy is almost always indicated to confirm the diagnosis of lesions in darkly pigmented individuals. CONCLUSION: This case is presented to reinforce the idea that pigmented Bowen's disease should be considered in the differential diagnosis of malignant melanoma.

Verrucous carcinoma of the foot associated with human papillomavirus type 16.

BACKGROUND: We present 2 patients with verrucous carcinoma (VC) of the foot, a malignancy of unknown origin. OBJECTIVE: Molecular studies from the VCs were undertaken to determine the presence, type, and physical state of human papillomavirus (HPV) as well as the expression levels of certain oncogenes and antioncogenes. METHODS: Synthetic consensus and type-specific primers were used to determine the HPV type from both VCs via polymerase chain reaction (PCR). Verification of fragments was accomplished by means of specific isotope-labeled oligonucleotide probes. The physical state of HPV DNA was determined by two-dimensional gel electrophoresis. Quantitative oncogene and antioncogene expression studies were performed with the use of reverse transcriptase PCR. RESULTS: HPV type 16 was identified in episomal and integrated forms in both tumors. Expression studies revealed increased messenger RNA levels of c-Ki-ras oncogene and the p53 antioncogene and decreased messenger RNA levels of the Rb antioncogene in both VCs. CONCLUSION: Episomal and integrated forms of HPV-16 DNA were found in VCs of the foot, along with alterations of c-Ki-ras, p53, and Rb genes.

Pedal interdigital condylomata lata: a rare sign of secondary syphilis.

BACKGROUND: Condylomata lata of the toe webs are uncommon manifestations of secondary syphilis. Considering the recent decline in the incidence of syphilis in the United States, such lesions are likely to present infrequently. In some cases, this phenomenon may be the only physical sign of syphilis; therefore, it is important that a high index of suspicion is maintained when evaluating toe web lesions in patients at epidemiologic risk for syphilis. GOALS: A case of secondary syphilis presenting solely with interdigital condyloma lata in the toe web spaces is reported, and similar cases reported in the literature are reviewed. STUDY DESIGN: This article documents the diagnosis of secondary syphilis based on a positive serology in conjunction with the development of interdigital condyloma lata as the only physical finding suggestive of lues. RESULTS: The latter lesions resolved after appropriate, adequate antibiotic therapy. CONCLUSIONS: A case of condylomata lata of the toe webs without other pertinent physical findings is presented. Analogous to lesions typically seen in the anogenital region, moist exophytic toe web plaques may represent condyloma lata and thereby be a sign of secondary syphilis. The differential diagnosis includes tinea pedis, erythrasma, macerated corns, verrucae, and several tropical mycoses (chromomycosis, mycetoma).

Factitious disease of the breast of a male due to injection of liquid plastic.

BACKGROUND: Factitious disease involving the breast is unusual. The rarely reported cases of this entity have been encountered in middle-aged women. In general, factitious disease can be distinguished on clinical and/or psychological grounds from self-induced disorders seen in malingerers and among those demonstrating Munchausen's syndrome. METHODS: We report herein a male patient displaying factitious disease of the breast due to injection of a high viscosity liquid plastic material. RESULTS: Establishment of the proper diagnosis was greatly delayed due to a lack of suspicion of this entity. Only direct confrontation of the patient with the biopsy results (lipogranulomatosis) led to a reluctant and then only partial admission of the self-induced nature of this patient's illness. CONCLUSION: The clinician should remain vigilant for factitious disease when confronted with chronic or recurrent lesions of a bizarre or atypical morphology. Any body site can be involved, including the breast. Management is difficult and is best accomplished in conjunction with an appropriate mental health professional. Continued dramatic surgical interventions are contraindicated.

Cost of illness in adult patients with hypopituitarism.

OBJECTIVE: To compare the healthcare costs of patients with hypopituitarism with those of individuals from the general population. DESIGN: A retrospective study of costs over 1 year. Estimates of direct and indirect health-related costs were calculated for patients from the general population using existing databases, and for patients with hypopituitarism using records of all patients eligible to participate on 31 December 1989 who could be traced, were willing to participate and had not been treated for acromegaly or Cushing's disease. SETTING: The catchment area of the Endocrine Unit, Sahlgrenska Hospital, Gothenburg. The study was conducted from the societal perspective. Reference data were collected from official regional and national registries. PATIENTS: 199 patients with adult-onset hypopituitarism in whom replacement therapy was given to maintain the adrenal, thyroid and gonadal (but not the somatotropic) axes. MAIN OUTCOME MEASURES AND RESULTS: Direct and indirect costs incurred by patients with hypopituitarism were higher than those incurred by individuals from the general population. The total direct costs per patient were Swedish Crowns (SEK)22,920 vs SEK12,080 (p < 0.003) in the general population, and the highest costs were related to inpatient care. Of the patients aged 16 to 64 years, 22% had drawn a disability pension versus the expected 11.3% (p < 0.003) in the general population, and the patients had a mean sick leave of 38.4 days vs 23.5 (p < 0.001). Total excess costs for all patients with hypopituitarism were SEK 35,768 per patient (p < 0.007). CONCLUSIONS: Patients with hypopituitarism incur more health-related costs than individuals from the general population. They also take more sick leave days and are more likely to claim a disability pension than members of the general population. Further cost analyses are needed to determine whether improvements in diagnostic and surgical procedures, and hormone replacement therapy, can reduce the healthcare costs of patients with hypopituitarism.

Treatment of keratoderma blennorrhagicum with tazarotene gel 0.1%.

We report near clearing of keratoderma blennorrhagicum following topical application of tazarotene gel 0.1%. This is the first report detailing the use of tazarotene gel for this purpose.

Growth hormone (GH) effects on bone and collagen turnover in healthy adults and its potential as a marker of GH abuse in sports: a double blind, placebo-controlled study. The GH-2000 Study Group.

The effects of GH on bone remodeling in healthy adults have not been systematically investigated. An analysis of these effects might provide insights into GH physiology and might yield data useful for the detection of GH doping in sports. The aim of this study was to evaluate the effects of GH administration on biochemical markers of bone and collagen turnover in healthy volunteers. Ninety-nine healthy volunteers of both sexes were enrolled in a multicenter, randomized, double blind, placebo-controlled study and assigned to receive either placebo (40 subjects) or recombinant human GH (0.1 IU/kg day in 29 subjects and 0.2 IU/kg x day in 30 subjects). The treatment duration was 28 days, followed by a 56-day wash-out period. The biochemical markers evaluated were the bone formation markers osteocalcin and C-terminal propeptide of type I procollagen, the resorption marker type I collagen telopeptide, and the soft tissue marker procollagen type III. All variables increased on days 21 and 28 in the two active treatment groups vs. levels in both the baseline (P < 0.01) and placebo (P < 0.01) groups. The increment was more pronounced in the 0.2 IU/kg-day group and remained significant on day 84 for procollagen type III (from 0.53 +/- 0.13 to 0.61 +/- 0.14 kU/L; P < 0.02) and osteocalcin (from 12.2 + 2.9 to 14.6 +/- 3.6 UG/L; P < 0.02), whereas levels of C-terminal propeptide of type I procollagen and type I collagen telopeptide declined after day 42 and were no longer significantly above baseline on day 84 (from 3.9 +/- 1.2 to 5.1 +/-1.5 microg/L and from 174 +/- 60 to 173 +/- 53 microg/L, respectively). Gender-related differences were observed in the study; females were less responsive than males to GH administration with respect to procollagen type III and type I collagen telopeptide (P < 0.001). In conclusion, exogenous GH administration affects the biochemical parameters of bone and collagen turnover in a dose- and gender-dependent manner. As GH-induced modifications of most markers, in particular procollagen type III and osteocalcin, persist after GH withdrawal, they may be suitable markers for detecting GH abuse.

Treatment of pyoderma faciale with isotretinoin in a patient with ulcerative colitis.

The explosive onset of fluctuant facial papulonodules, usually in young women, is characteristic of pyoderma faciale. This disorder is neither a true pyoderma nor a variant of acne, but rather a severe form of rosacea. The most effective therapeutic modality appears to be isotretinoin, especially if preceded by a brief course of oral corticosteroids or a short interval of application of potent topical corticosteroids. Despite our concern about the potential adverse effects of systemic retinoids on underlying inflammatory bowel disease, isotretinoin was given to a patient with refractory pyoderma faciale. Response was dramatic, and no ill effects were encountered.

Multiple primary melanoma.

BACKGROUND: Incidence rates of cutaneous malignant melanoma (CMM) have been increasing for decades among Caucasian populations worldwide. Multiple factors identify persons at increased risk of CMM, including those with a family history of melanoma and those with atypical moles. Approximately 6-12% of melanomas are familial and approximately 12% of patients with familial melanoma have multiple primary melanomas. OBJECTIVE: To report a case of a patient with atypical moles and with 17 multiple primary melanomas. To review the literature on multiple primary melanomas as well as to review the genetics and treatment of melanoma. CONCLUSION: Patients with numerous atypical moles and a family or personal history of melanoma are at greatest risk for developing CMM. Patients from this population tend to develop CMM approximately 10 years earlier than the general population and have an increased risk for developing multiple primary melanomas. Since genetic tests capable of detecting individuals with an inherited susceptibility to CMM are not available, it is important to identify those patients with an increased risk and monitor them closely with regular total-body examinations.

Assessment of coagulation system activation using spot urine measurements.

Coagulation system activation is most commonly assessed by measuring levels of one or more proteins in peripheral blood. Because faulty blood-drawing can cause activation of the coagulation system, artifactual elevations of such markers have been reported. We have therefore investigated the possibility of using randomly collected ('spot') urine samples as a non-invasive means of assessing the state of coagulation system activation. Using a commercially available enzyme-linked immunosorbent assay kit designed to measure plasma levels of fragment 1 + 2, we found immunoreactive fragment 2 in healthy control subjects, and significantly increased levels in diabetic and non-diabetic pregnant subjects, and patients with venous thromboembolism, prostate cancer, and diabetes. Measurements of excretion of immunoreactive fragment 2 are worth further study as an adjunct or alternative to plasma-based assays designed to detect or quantify coagulation system activation.

The antifungal agent butenafine manifests anti-inflammatory activity in vivo.

BACKGROUND: Dermatophyte infections are often accompanied by a striking inflammatory reaction, alleviation of which has often been achieved by the concomitant but controversial use of topical steroidal agents. Recent investigations have suggested the presence of inherent anti-inflammatory properties associated with certain antifungal agents, particularly those within the allylamine class. Butenafine, the first and only approved representative of the benzylamine antifungals, possesses a chemical structure and antifungal activity similar to the allylamines. Although several studies have demonstrated excellent antimycotic efficacy, none has addressed anti-inflammatory properties associated with butenafine. OBJECTIVE: This study was designed to determine whether butenafine, a benzylamine antifungal, expresses anti-inflammatory activity in vivo. METHODS: A randomized single-blinded control investigation comparing the attenuation of UVB irradiation-induced erythema by butenafine, its proprietary base cream, and no application (negative control) was performed in humans. RESULTS: Butenafine demonstrated a significant and marked decrease in UVB-induced erythema as compared with both the base cream and the unaltered control. CONCLUSION: The benzylamine antifungal agent butenafine demonstrates inherent anti-inflammatory properties, in vivo, as demonstrated by reduced cutaneous erythema response after UVB irradiation.