Intractable shoulder pain in a patient on chronic hemodialysis.
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Biomedical subjects
Publications and source records attributed to J Bernheim.
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BACKGROUND: The study presented here is the first replica of the Dutch death certificate study on end of life decisions (ELDs). The main objective was to assess the incidence of euthanasia (the administration of drugs with the explicit intention to shorten the patient's life at the explicit request of the patient), physician assisted suicide (PAS), and other ELDs in medical practice in Belgium (Flanders). METHODS: A 20% random sample of 3,999 deaths was selected from all death certificates between January 1 and April 30, 1998. The physicians who signed the death certificates received one mail questionnaire per death case. FINDINGS: The response rate of the physicians was 52%. The results were corrected for the non response bias, and extrapolated to estimated annual incidences after seasonal adjustment for causes of death. It was estimated that 1.3% (1.0-1.6%, CI: 95) of all deaths resulted from euthanasia or PAS. In 3.2% (2.7-3.8%, CI: 95) of all cases, the physician ended the patient's life with lethal drugs without the explicit request of the patient. Alleviation of pain and symptoms with opioids in doses with a potential life shortening effect preceded death in 18.5% (17.3-19.7%, CI: 95) of cases and nontreatment decisions in 16.4% (15.3-17.5%, CI: 95) of cases, of which 5.8% (5.1-6.5%, CI: 95) with the explicit intention of ending the patient's life. INTERPRETATION: ELDs are prominent in medical practice in Belgium (Flanders). The incidence of deaths preceded by an ELD is similar to the Netherlands, but greater than in Australia. However, in Belgium (Flanders) the incidence of ending of patient's life without the patient's explicit request (3.2%, 2.7-3.8% CI: 95) is similar to Australia (3.5%, 2.7-4.3% CI: 95), but significantly higher than in the Netherlands (0.7%, 0.5-0.9% CI: 95).
BACKGROUND: Low birth weight has been shown to be strongly related to hypertension in adult life. OBJECTIVES: To determine whether blood pressure is higher in children with intrauterine growth retardation than in control subjects. METHODS: Blood pressure was measured in 58 children aged 4-6 years with IUGR and in 58 age-matched controls. The control children, whose birth weight was appropriate for gestational age, were also matched for gestational age. RESULTS: The children with IUGR had significantly higher mean values of systolic (P < 0.05) and diastolic blood pressures (P < 0.05) and mean arterial pressure (P < 0.05). Significant differences in blood pressure values were found between preterm IUGR (n = 21) and preterm controls (P < 0.05). CONCLUSIONS: These data indicate that children with IUGR may be at higher risk of hypertension already in childhood.
BACKGROUND: Catheter-based therapeutic ultrasound thrombolysis was recently shown to be effective and safe. The purpose of this work was to study the safety and efficacy of external high-intensity focused ultrasound thrombolysis guided by ultrasound imaging in experimental settings. METHODS AND RESULTS: A therapeutic transducer was constructed from an acoustic lens and integrated with an ultrasound imaging transducer. In vitro clots were inserted into bovine arterial segments and sonicated under real-time ultrasound imaging guidance in a water tank. With pulsed-wave (PW) ultrasound, the total sonication time correlated with thrombolysis efficiency (r(2)=0.7666). A thrombolysis efficiency of 91% was achieved with optimal PW parameters (1:25 duty cycle, 200-micros pulse length) at an intensity (I(spta)) of >35+/-5 W/cm(2). Ultrasound imaging during sonication showed the cavitation field as a spherical cloud of echo-dense material. Within <2 minutes, the vessel lumen evidenced neither residual clot nor damage to the arterial wall. On serial filtration, 93+/-1% of the lysed clot became subcapillary in size (<8 microm). In vitro safety studies, however, showed arterial damage when an I(spta) of 45 W/cm(2) was used for periods of >/=300 seconds. CONCLUSIONS: External high-intensity focused ultrasound thrombolysis using optimal PW parameters for periods of </=300 seconds appears to be a safe and effective method to induce thrombolysis. The procedure can be guided by ultrasound imaging, thereby allowing the monitoring of therapy.
BACKGROUND AND OBJECTIVES: p53, c-erbB-2, and tumor microvascular density have been shown to be potential prognostic tools in female breast cancer. Our objective was to assess the significance of these biomarkers as prognostic factors in infiltrating male breast cancer. METHODS: A retrospective study of expression of p53, c-erbB-2, and tumor microvascular density was done on a group of 26 male breast cancer patients. Biotin-streptavidin immunohistochemical study with specific anti-p53, anti-c-erbB-2, and anti-CD34 antibodies was carried out on paraffin sections of breast carcinoma. The data of expression of the biomarkers were merged with clinicopathological data such as tumor grade, T class, TNM stage, estrogen receptor status, tumor recurrence, and patient survival. RESULTS: p53 and c-erbB-2 were expressed in 46% and 39% of carcinomas, respectively. No correlation was found between positive immunoreactivity of p53, and tumor grade, size, T class, TNM stage, and survival. Nor was any relation found between tumor size, T class, TNM stage, survival, and c-erbB-2 overexpression. c-erbB-2 overexpression was significantly higher in high grade carcinomas. Estrogen receptor (ER) were positive in 21 out of 26 of tumors (81%). No trends were observed between estrogen receptor status and clinicopathological parameters or survival (data not shown). There was a positive correlation between mean microvascular density (MVD), advanced T class, and survival: higher MVD counts were found in patients with advanced tumors and in those who had tumor relapses or died of metastatic disease. CONCLUSIONS: This study suggests that tumor microvascular density may serve as a potential prognostic tool in male breast carcinoma.
BACKGROUND: Cytokeratins are constituents of the intermediate filaments (IFs) of epithelial cells which are expressed in various combinations, depending on the type of epithelium and degree of differentiation. We have reported (R. Zemer, A. Fishman, J. Bernheim, S. Zimlichman, O. Markowitz, M. Altaras, and A. Klein, Gynecol Oncol 70:410-413, 1998) on the determination of cytokeratin-20 (CK-20) by reverse transcription polymerase chain reaction (RT-PCR) in the detection of endometrial cancer cells as a potential biomarker. In that study, we also found that by using immunocytochemistry, most carcinomas were found to be negative for CK-20. The sensitivity and specificity rates obtained by using the RT-PCR method were 94.4 and 91%, respectively. OBJECTIVE: The aim of this study is to investigate the feasibility and potential of the specific mRNA marker, CK-20, to detect endometrial cancer cells-micrometastases (MMs)-by RT-PCR in lymph node (LN) samplings of patients undergoing hysterectomy for endometrial carcinoma. METHOD: We used the RT-PCR method to determine the expression of CK-20 in the LNs of 20 patients [study group (SG)] who were being surgically staged and treated for endometrial carcinoma. The specificity of the mRNA CK-20 marker was examined in LNs obtained from five healthy patients [control group (CG)] who underwent abdominal hysterectomy and bilateral salpingo-oopherectomy for benign gynecologic conditions. The LNs obtained from the SG and CG patients were prepared together before mRNA extraction. RNA of the various cell pellets was extracted and RT-PCR was performed with CK-20 primers. RT-PCR products were analyzed by agarose gel electrophoresis and ethidium bromide staining against PCR size markers. Specificity of the RT-PCR products was examined by Southern blotting. RESULTS: Histopathologic examinations demonstrated the presence of metastases in two (10%) SG patients. These patients were also CK-20 positive. Of the remaining 18 patients with negative histopathologic results, 6 (33%) were CK-20 positive and 12 (67%) were negative. All the CG patients were CK-20 negative (specificity, 100%). CONCLUSIONS: The results obtained in this study suggest that RT-PCR of CK-20 is more sensitive than traditional histopathologic methods in the diagnosis of MMs in LNs of patients with endometrial cancer. Thus, due to the aforementioned characteristics of CK-20, it may be considered a powerful biomarker in the detection of MMs in LNs of patients with endometrial cancer.
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Ductal carcinoma in situ (DCIS) of the breast, a precursor lesion of invasive breast cancer, is a heterogeneous disease in terms of histomorphologic features and biologic behavior. Our aim was to assess the proliferative activity, expressed as topoisomerase IIalpha (Topo IIalpha) immunoreactivity and c-erbB-2 expression in relation to morphologic features and architectural pattern of DCIS. The study included 26 DCIS, which were reclassified according to the recommendations of Consensus Conference. Topo-IIalpha and c-erbB-2 immunoreactivity were detected on paraffin sections. Topo IIalpha was consistently negative in normal ductal epithelium. Topo IIalpha-labeling index (Topo IIalpha-LI) was 0.7+/-0.6% for grade I, 4.3+/-3.9% for grade II, and 13.4+/-8.9 for grade III lesions (P<.01). For mixed nuclear grade DCIS, Topo IIalpha-LI was 6.8+/-4.8. There was no difference in Topo IIalpha-LI between different architectural patterns in low- and intermediate-grade lesions. In high nuclear grade DCIS, there was a progressive increase in Topo IIalpha-LI from solid toward cribriform and comedo-type DCIS. Positive c-erbB-2 immunoreactivity was found in 46% of DCIS, being highest in DCIS with high nuclear grade (78%) and in lesions with extensive necrosis. Topo IIalpha-LI was significantly higher in c-erbB-2-positive lesions (Topo IIalpha-LI- 12.4+/-8.5) as compared with negative lesions (Topo IIalpha-LI- 3.9+/-4.5, P<. 0001). Overexpression of c-erbB-2 and Topo IIalpha is associated with poorly differentiated lesions. Proliferative activity in individual ducts of DCIS depended primarily on the nuclear grade and was independent of architectural patterns of individual ducts in architecturally heterogeneous lesions.
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OBJECTIVE: To provide data on the histopathological and immunohistochemical characteristics of acute sinusitis in humans. STUDY DESIGN: A nonrandomized, retrospective, controlled, qualitative and quantitative study. METHODS: Inflamed sinus mucosal tissues were removed during functional endoscopic sinus surgery from 11 patients with acute sinusitis, of whom 6 had complications with extension of inflammation to the orbit (4) or the meninges (2), 3 had recurrent sinusitis, and 2 had acute exacerbation of chronic sinusitis Normal sinus mucosal tissues were retrieved from four patients with various nasal tumors and served as controls All specimens underwent routine histological processing. Representative sections from each region were stained with hematoxylin and eosin, periodic acid-Schiff, and toluidine blue. Immunohistochemical staining for T and B lymphocytes was also applied. A two-phase examination was designed: low-magnification microscopic assessment (x40) to yield the typical pathological features and high-magnification assessment (x400) to count various inflammatory cells. RESULTS: The lamina propria displayed the most significant changes with edema, extensive infiltration of neutrophils and mononuclear cells, formation of microabscesses, thrombophlebitis, and necrotic foci, whereas the involvement of the epithelial layer in the inflammatory reaction was relatively modest. Immunohistochemistry revealed an increase in the population of T and B lymphocytes. The former were diffusely scattered, whereas the latter also formed distinct clusters: around small venules, adjacent to seromucous glands, and under the epithelium. CONCLUSIONS: The inflammatory reaction of the lamina propria exceeded that of the epithelial layer. It is assumed that the clusters of B lymphocytes around blood vessels may point to the fact that these cells were recruited from the blood during acute sinusitis.
We previously found that chronic exogenous hyperinsulinemia without sugar supplementation does not elevate blood pressure. This may be partially explained by the ability of insulin to release nitric oxide and cause vasodilatation. To test this hypothesis, we studied 4 groups of rats: 9 rats (body weight, 213+/-14 g) treated with a gradual increase of a sustained-release subcutaneous insulin pellet; 9 rats (body weight, 213+/-9 g) treated with N:(G)-nitro-L-arginine methyl ester (L-NAME) in drinking water 50 mg/L; 19 rats (body weight, 217+/-11 g) treated with the combination of L-NAME and insulin; and 9 control rats (body weight, 218+/-11 g). Blood pressure was followed weekly for 6 weeks, and then rats were studied in metabolic cages. Weight gain was not different during the 6 weeks. Renal function did not differ between the 4 groups, but 24-hour urinary nitrite/nitrate excretion was lower (P<0.02) in L-NAME-treated and higher in insulin-treated rats. Plasma insulin doubled (P<0.002) in the insulin-treated rats, but there was no hypoglycemia and, by week 6, fructosamine levels were 2.1+/-0.2, 2.1+/-0.2, 2.3+/-0.1, and 2.3+/-0.2 mmol/L in control rats and rats treated with L-NAME, insulin, and L-NAME plus insulin, respectively. Systolic blood pressure, which did not differ at baseline, at week 3 was 122+/-17, 118+/-17, and 118+/-24 mm Hg in the control, L-NAME, and insulin groups and 136+/-14 mm Hg (P<0.03) in the combination group. At week 6, systolic blood pressure was 128+/-14, 127+/-15, and 118+/-13 mm Hg in the control, L-NAME, and insulin groups, respectively, and 150+/-14 mm Hg (P<0.0005) in the combination group. In a subsequent experiment, L-arginine 2 g/L abrogated the effects of L-NAME and insulin combination. In conclusion, chronic exogenous hyperinsulinemia does not affect blood pressure but may cause hypertension when endothelial function is compromised.
BACKGROUND: Cell-mediated immunity is impaired in uremia. Cell-matrix interactions of immune cells such as CD4+ T lymphocytes with extracellular matrix are an important requirement for an intact immune response. The adherence of CD4+ T cells of healthy subjects (normal T cells) to ECM components is inhibited in the presence of uremic serum. Such decreased adhesive capacity is also found in T cells of dialysis patients. Various chemokines and cytokines affect the attachment of CD4+ T cells to ECM. OBJECTIVE: To evaluate chemokine (MIP-1 beta and RANTES) and tumor necrosis factor-alpha-induced adhesion of CD4+ T cells to ECM in a uremic milieu. METHODS: We examined adhesion of normal CD4+ T cells (resting and activated) to intact ECM in response to soluble or bound chemokines (MIP-1 beta and RANTES) and to TNF-alpha following incubation in uremic versus normal serum. Thereafter, we evaluated the adhesion of resting CD4+ T cells from dialysis patients in a similar fashion and compared it to that obtained from a healthy control group. RESULTS: Addition of uremic serum diminished soluble and anchored chemokine-induced attachment of normal resting and activated CD4+ T cells to ECM compared to a normal milieu (a peak response of 10-11% vs. 24-29% for soluble chemokines, P < 0.001; 12-13% vs. 37-39% for bound chemokines on resting cells, P < 0.01; and 18-20% vs. 45-47% for bound chemokines on activated cells, P < 0.02). The same pattern of response was noted following stimulation with immobilized TNF-alpha (7 vs. 12% for resting cells, P < 0.05; 17 vs. 51% for activated cells, P < 0.01). Adherence of dialysis patients' cells to ECM following stimulation with both bound chemokines was reduced compared to control T cells (15-17% vs. 25-32%, P < 0.0000). In contrast, adherence following stimulation by TNF-alpha was of equal magnitude. CONCLUSIONS: Abnormal adhesive capacity of T lymphocytes to ECM in uremia may, in part, be related to a diminished response to MIP-1 beta, RANTES and TNF-alpha. However, whereas reduced adhesion to chemokines was present in both normal CD4+ T cells in a uremic environment and in dialysis patients' T cells, TNF-alpha-induced adhesion was found to be inhibited only in normal cells in a uremic milieu.
OBJECTIVE: To evaluate the diagnostic accuracy of preoperative transvaginal sonography (TVS) in the detection of deep myometrial invasion in endometrial cancer cases classified by the grade of disease, and in comparison to frozen section analysis in grade 1 cases. METHODS: In a prospective study, 91 patients with confirmed endometrial carcinoma underwent preoperative TVS for evaluation of myoinvasion. Sonographic results were categorized as superficial (less than or equal to 1/2 myometrial depth) and deep invasion (greater than 1/2 myometrial depth). TAH-BSO followed by retroperitoneal lymph node sampling were performed in all patients with grade 2-3 tumors. In patients with grade 1 disease, the surgical specimen was intraoperatively evaluated by frozen section, and lymph node sampling was carried out if deep invasion was determined. The preoperative sonographic findings and the frozen section results were compared to the final histopathology report of myoinvasion. RESULTS: In 77 of the 91 (84.6%) patients, the sonographic assessment of the depth of myoinvasion was in accord with the final histopathologic findings. TVS demonstrated a sensitivity of 87.8% and a specificity of 82.7% in detecting deep invasion in the entire study group (grade 1-3), with positive and negative predictive values (PPV, NPV) of 74.3% and 92.3%, respectively. TVS in grade 1 cases (n=47) showed a sensitivity of 77.7%, a specificity of 79%, PPV of 46.6% and NPV of 93.7%. TVS in cases with grade 2-3 tumors (n=44) showed a sensitivity of 90%, specificity of 91.6%, PPV of 90% and NPV of 91.6%. Thus, the accuracy of TVS in grade 2-3 cases was superior to that achieved in grade 1 cases (91% vs 78.7%; p=.002). The myometrial invasion was assessed by frozen section in 41 out of 47 patients with grade 1 disease and demonstrated a sensitivity of 85.7%, a specificity of 100%, PPV of 100% and NPV of 97.1%. The specificity (100%) and accuracy (97.5%) of the frozen section were found to be superior compared to that of the TVS (79% and 78.7%) in detecting deep invasion in grade 1 cases (p=.008, p=.005, respectively). No statistically significant difference was found between the sensitivity of either technique. CONCLUSIONS: TVS appeared to be a more accurate method for preoperative assessment of myoinvasion in grade 2-3 endometrial cancer patients compared to grade 1 patients. In grade 1 cases, this method achieved lower accuracy in detecting deep invasion compared to the frozen section analysis. Based on these data, the value of preoperative TVS results as the sole criterion in the decision to perform extensive surgical procedures in grade 1 endometrial cancer is questionable and warrants further evaluation.
A 22-year-old woman with a "hot" thyroid nodule who was being treated with minocycline for severe acne vulgaris is presented. A partial thyroidectomy specimen revealed a black adenoma. Microscopically, the black pigment was found in the follicular cells and the colloid of the adenoma. The pigment was bleached with potassium permanganate and was Fontana-Masson stain positive. It was negative for iron, periodic acid-Schiff, and acid-fast Ziehl-Neelsen stains. All these feature suggest a melanin-like pigment. However, electron microscopic examination revealed a dense osmophilic material present within the lysosomes of the follicular cells. No melanosomes were present. Twenty-six previously reported cases are reviewed, and the possible mechanisms for the deposition of the pigment in the adenoma and its relation to minocycline degradation products are discussed.
PURPOSE OF INVESTIGATION: 1) To assess whether endometrial specimens obtained from removed uteri might show an increase in endometrial pathologies which had been previously diagnosed by hysteroscopy in postmenopausal breast cancer tamoxifen-treated patients. 2) To assess whether hysteroscopy is an efficient method of detecting endometrial pathologies in such patients. METHODS: The findings of two consecutive pathological evaluations in 18 postmenopausal breast cancer tamoxifen-treated patients, performed 11.2+/-11.2 months apart, were compared. The first specimen was collected by hysteroscopy and the second was obtained following hysterectomy. RESULTS: The most significant changes observed were three new cancers diagnosed at hysterectomy, one of which was poorly-differentiated. In the first (hysteroscopy) samplings, one patient had atrophic endometrium, a second patient had endometrial proliferation and a third patient had a benign endometrial polyp. Overall, 55.6% of the study patients had various endometrial pathologies in the first sampling, while 83.3% had endometrial pathologies in the second sampling. However, this difference was not statistically significant. CONCLUSION: 1) Endometrial histologic evaluations, performed on removed uteri 11.2+/-11.2 months following previous endometrial samplings of postmenopausal breast cancer tamoxifen-treated patients, showed a non-significant risk of developing overall endometrial pathologies. 2) Hysteroscopy may have missed some endometrial pathologies which were diagnosed later on in specimens obtained by hysterectomy.
BACKGROUND: Endometrial polyps are the most common endometrial pathology described in association with postmenopausal tamoxifen exposure. It is generally accepted that the occurrence of malignancy in endometrial polyps among healthy women is up to 0.5%. However, no one has yet described the incidence of this malignant transformation among postmenopausal breast cancer tamoxifen-treated patients. Objective. The aim of this study was to study the exact rate of malignant changes in endometrial polyps recovered from postmenopausal breast cancer tamoxifen-treated patients. METHODS: We reviewed the pathological results and medical records of all postmenopausal breast cancer patients in whom endometrial polyps were recovered following at least 6 months of tamoxifen treatment in our institute. We also looked for the rate of malignant changes in polyps recovered from all healthy postmenopausal controls with endometrial polyps in our institute during the period of the study. RESULTS: Two (3.0%) of 67 endometrial polyps recovered from postmenopausal breast cancer tamoxifen-treated patients revealed malignant features. None of the clinical variables tested, including risk factors for endometrial cancer, was significantly different between the groups. In the controls only 5 (0.48%) of 1034 polyps were malignant. CONCLUSION: Up to 3.0% of endometrial polyps recovered from postmenopausal breast cancer tamoxifen-treated patients may show malignant changes. This rate is higher than that found in our controls as well as that reported in the general female population.