Glomerular Capillary Hemorrhage Induced in Rats by Diagnostic Ultrasound with Gas–Body Contrast Agent Produces Intratubular Obstruction

Glomerular capillary hemorrhage (GCH) induced by ultrasonic cavitation during diagnostic imaging represents a unique contrast agent–related nephron injury. Consequences of GCH during 1.5-MHz diagnostic ultrasound with contrast agent were examined by histologic methods in rats. Definity was infused at 10 μl/kg/min for 5 min at the start of 8 min of intermittent image-exposure, with 2.3 MPa in situ peak rarefactional pressure amplitude. Kidney samples were taken for histology at 5 min, 30 min, 4 h, 2 d, 1 week and 4 weeks post exposure. In addition, samples were taken at 4 h from groups treated with heparin or aminocaproic acid. GCH was found in 61% of glomeruli in the center of the scan plane 5 min after exposure, which declined (p < 0.05) to 36.3% after 4 h. The width of Bowman's space was significantly increased for glomeruli with GCH relative to glomeruli without GCH (p < 0.05), consistent with tubular obstruction. Antibody staining revealed fibrin clotting in Bowman's space in 4-h samples and this persisted in the 2-d samples. Heparin reduced and aminocaproic acid increased the GCH seen in 4-h samples. Tubular dilation was evident with injury to the epithelium after 2 d. After one week, areas of inflammatory cell infiltration were present. After four weeks, areas of interstitial fibrosis were revealed by Masson's trichrome stain. The consequences of GCH induced by diagnostic ultrasound with contrast agents include rupture of glomerular capillaries, procoagulant activity resulting in intratubular obstruction, and the potential for progression of the resulting tubular injury toward interstitial fibrosis. (E-mail: douglm@umich.edu)     

Multianalyte profiling of serum antigens and autoimmune and infectious disease molecules to identify biomarkers dysregulated in epithelial ovarian cancer

Ovarian cancer is the deadliest gynecologic cancer in the United States. When detected early, the 5-year survival rate is 92%, although most cases remain undetected until the late stages where 5-year survival rates are 30%. Serum biomarkers may hold promise. Although many markers have been proposed and multivariate diagnostic models were built to fit the data on small, disparate sample sets, there has been no systematic evaluation of these markers on a single, large, well-defined sample set. To address this, we evaluated the dysregulation of 204 molecules in a sample set consisting of serum from 294 patients, collected from multiple collection sites, under a well-defined Gynecologic Oncology Group protocol. The population, weighted with early-stage cancers to assess biomarker value for early detection, contained all stages of ovarian cancer and common benign gynecologic conditions. The panel of serum molecules was assayed using rigorously qualified, high-throughput, multiplexed immunoassays and evaluated for their independent ovarian cancer diagnostic potential. Seventy-seven biomarkers were dysregulated in the ovarian cancer samples, although cancer antigen 125, C-reactive protein, epidermal growth factor receptor, interleukin 10, interleukin 8, connective tissue growth factor, haptoglobin, and tissue inhibitor of metalloproteinase 1 stood out as the most informative. When analyzed by cancer subtype and stage, there were differences in the relative value of biomarkers. In this study, using a large sample cohort, we show that some of the reported ovarian cancer biomarkers are more robust than others, and we identify additional informative candidates. These findings may guide the development of multivariate diagnostic models, which should be tested on additional, prospectively collected samples.     

Spontaneous chylothorax in Noonan syndrome. Treatment with prednisone.

OBJECTIVE--To describe a case of spontaneous chylothorax in a child with Noonan syndrome successfully treated with prednisone. DESIGN--Case report. SETTING--A pediatric cardiology referral center for the Rocky Mountain region. PATIENT--An 18-month-old girl with Noonan's syndrome, pulmonary stenosis, and hypertrophic cardiomyopathy who presented with spontaneous chylothorax. INTERVENTIONS--The child's chylothorax did not respond to thoracic duct ligation, tetracycline pleurodesis, and pleurectomy during a 2-month period. A low-fat diet was helpful but did not eliminate the problem. Prednisone was started orally at 1 mg/kg per dose twice daily and slowly tapered during 3 months. The chylothorax did not recur during 8 months of follow-up. CONCLUSIONS--Prednisone may be useful in the treatment of chylothorax in Noonan syndrome. A controlled clinical trial would be helpful but would be difficult in such a rare complication of an uncommon syndrome.     

Radiotherapy for melanotic freckles

Five patients who received radiotherapy (RT) for 7 melanotic freckles (MF, also known as Hutchinson's freckles, lentigo maligna) were reviewed 8 to 37 months after their treatment by RT. Local control and a favourable cosmetic result occurred in all patients. Treatment toxicity was minimal. Few reports about the use of RT for MF exist. Many other treatments including observation alone have been associated with high rates of recurrence, and in some cases conversion to invasive melanoma has occurred. RT appears to be a safe and effective treatment for this condition, providing that doses equivalent to 44 Gy in 11 fractions or more are given.     

Schizophrenia as a temporal mode of being: an existential "ante-festum" impatience.

We suggest in a phenomenological perspective to consider schizophrenia as a special form of human temporality. From this perspective, we view the symptoms of schizophrenia as actions undertaken by subjects to stabilize themselves in existence. From this vantage, we describe the clinical expression of the disorder as a type of "existential impatience", characterized by a painful and elusive "now". This present time posits the prime moment of the constitution of the person. Existential impatience reflects from our patients the persistence of excessive efforts towards individuation. Schizophrenia. In human life in general, individuation consists in an unceasing dynamic process of building up of the self. This process starts with the non-self and particularly with the other. Therefore, the emergence of any relation within the self is grounded in the relation with the other and is based on the relation the other establishes with himself. Schizophrenia distinctly displays the two constitutive moments of "being oneself." These moments are generally linked for all of us: an "unending coming to oneself" (difference of identity), and a "continuous maintenance of being a self" (identity of difference). Existential impatience is not only an irritability of a formal order. Existence itself is impatient in the schizophrenic experience as it hastens to reach human goals while trampling on an "ante-festum" temporal mode. This "before-the-feast" temporal structure is dominated by the shiver before an unknown future, a sign of a basic quest for a task. Schizophrenic "ante-festum" is both a constant fear of being unable to come to oneself and a desperate effort to reach this unknown future. If psychopathology claims to settle [establish] that "order" and "measure" would constitute the two fundamental anthropological bases of human being, impatience of existence draws the emblematic figure of the disorder of measure as a referential motion of the birth of any temporalisation. Such considerations suggest the value, in treatment and rehabilitation, of praising patience and focusing on building, or re-building, the past. The main objective is to reach a maieutics of the self based on relationships in the community and with care-givers, all within an accompanying structured, daily framework.     

A population-based study of patterns of care for ovarian cancer: who is seen by a gynecologic oncologist and who is not?

OBJECTIVES: To determine the fraction of patients diagnosed with ovarian cancer and seen by a gynecologic oncologist and to compare outcomes with those patients and others who are not seen by a gynecologic oncologist. METHODS: The statewide, population-based Utah Cancer Registry was used to identify 848 patients diagnosed with epithelial ovarian cancer between 1992 and 1998. Differences between selected characteristics of cases seen/not seen by gynecologic oncologists were assessed with chi2 tests, and survival data were analyzed using Kaplan-Meier curves and log-rank testing. RESULTS: Of 848 incident epithelial ovarian cancer cases diagnosed in Utah residents during the period 1992-1998, 333 (39.3%) were seen by a gynecologic oncologist at some time during their cancer diagnosis and/or treatment. The percentage of ovarian cancer cases seen by a gynecologic oncologist varied with age: 35.6% of cases under 40 years of age at diagnosis were seen by a gynecologic oncologist, as were 54.5% of cases 40-59 years of age, 42.6% of cases 60-69 years, and 23.7% of women 70+ years of age (chi2 test, P < 0.01). The percentage of ovarian cancer cases seen by a gynecologic oncologists increased during the study period, from 33.0% in 1992-1993 to 47.5% in 1997-1998 (chi2 test for trend, P < 0.01). The vast majority of the state's population resides within a contiguous, four-county area near the only major city where gynecologic oncology care is available. Ovarian cancer cases that resided within that geographic area were generally more likely to have been seen by a gynecologic oncologist than those who lived in more rural regions of the state (42.7 and 27.1%, respectively; chi2 test, P < 0.01). For ovarian cancer cases diagnosed with local or regional stages of disease, there were no significant differences in survivorship between those treated or not treated by gynecologic oncologists. Among cases diagnosed with advanced disease, those cases seen by gynecologic oncologists had a significant survival advantage when compared to those that were not (median survival 26 and 15 months, respectively, P < 0.01). CONCLUSIONS: Gynecologic oncologists see less than half of ovarian cancer patients. Patients under 40 years of age, over 70 years of age, and in rural areas were significantly less likely to be seen by a gynecologic oncologist in their course of treatment. Patients with advanced disease experienced a significant survival advantage when a gynecologic oncologist was involved in their care.