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Biomedical subjects

J Bernheim

Publications and source records attributed to J Bernheim.

At least 91 records · Page 5Linked to original sources
PubMed1998

A second primary malignancy in a cohort of patients with epithelial ovarian cancer--characteristics of diagnosis.

As the life expectancy of cancer patients has been extended because of earlier diagnosis and improved therapeutic modalities, second primary tumors are being diagnosed more frequently. We have examined the clinical characteristics of 38 second primary tumors in a cohort of patients diagnosed with epithelial ovarian cancer in our department over a 6-year period. The most frequent neoplasm associations were in decreasing order of occurrence: ovary-breast, ovary-endometrium, and ovary-gastro-intestinal tract. Most heterochronous second primary tumors have been diagnosed following patient symptoms and not during routine follow-up of patients with a known primary cancer. Family history was obtained for 30/38 patients (19 with full pedigrees and 11 with partial information). Two of these 30 patients (6.6%) had one affected first degree relative-one with ovarian cancer and one with breast cancer. With an increased risk of developing a second malignancy after having a previous tumor, closer surveillance of patients posttreatment for cancer is warranted.

Adult↗
PubMed1998

A 30s PAS stain for frozen section analysis of surgical margins of vulvectomy in Paget's disease.

Application of a modified periodic-acid Schiff's procedure (PAS) technique in frozen section analysis of surgical margins of vulvectomy specimen in Paget's disease is described. The reaction obtained using a microwave procedure takes only 30 seconds. This method was found to be useful in identifying Paget cells on the margins thought to be free of disease by conventional histological evaluation.

Aged↗
PubMed1997

Estrogen and progesterone receptors in the endometrium of postmenopausal breast cancer patients treated with tamoxifen and progestogens.

Postmenopausal breast cancer patients who were treated with tamoxifen and progestogens showed a uniform decidual reaction of the endometrium. It is well established that progestogens antagonize the estrogen effect on the endometrium by reducing its receptors in the endometrium. To assess in vivo such a possible effect of progestogens on endometrium primarily exposed to tamoxifen, we analyzed estrogen and progesterone receptors (ER, PR) on endometrial specimens showing decidualization from nine postmenopausal breast cancer patients on tamoxifen and progestogen treatment and on endometrial polyps with areas of decidualization from two other similar patients. ER was weakly detected in the endometrial glands of four (36.4%) patients and in the endometrial stroma of one (9.1%) patient. PR was detected in the endometrial gland of only one (9.1%) patient. No PR was detected in the endometrial stroma. There was no correlation between the length of tamoxifen treatment, the tamoxifen dosage, or the length of progestogen treatment and the ER or PR content, although progestogens were administered for more than 3 consecutive months in all patients. This relatively very low ER and PR content may be attributed to the antagonistic effect of progestogens on the "priming" estrogen-like effect of tamoxifen on the endometrium.

Adult↗
PubMed1997

Proliferating cell nuclear antigen as a marker of cell kinetics in aberrant crypt foci, hyperplastic polyps, adenomas, and adenocarcinomas of the human colon.

BACKGROUND: One of the first steps in multistage colonic carcinogenesis is increased cell proliferation and an upward shift of the proliferation zone of colonic crypts. In the present study, progression in cell kinetics was followed up at all sequential stages of colonic carcinogenesis, starting with aberrant crypt foci (ACF), the earliest putative preneoplastic lesions, hyperplastic and dysplastic polyps, and invasive carcinomas. MATERIALS AND METHODS: Colonic tissue and tumor specimens were prospectively obtained from 65 patients treated at our hospital for adenocarcinoma or malignant polyps. For identification of ACFs, dissected mucosal strips obtained from patients with colorectal cancer were stained with 0.1% methylene blue and scanned under dissecting microscope. Paraffin-embedded ACFs and macroscopic lesions were serially sectioned, deparaffinized, and stained with a monoclonal antiproliferating cell nuclear antigen (PCNA) antibody. The PCNA-labelling index (PCNA-LI), expressed as a ratio of positively stained nuclei to total nuclei counted, was calculated separately for basal, middle, and upper colonic crypt compartments. A comparison of the PCNA-LI was made for each compartment in normal mucosa, and hyperplastic and dysplastic lesions. RESULTS: A stepwise increase in the PCNA-LI was observed during neoplastic progression of colonic lesions. The two most important variables of increased cell proliferation, expressed as PCNA-LI per crypt compartment, were the presence of dysplasia and the size of dysplastic lesions. CONCLUSIONS: In colorectal carcinogenesis, hyperproliferation with upward expansion of proliferative compartment is a characteristic feature at all stages of malignant progression.

Adenocarcinoma↗
PubMed1997

Nitric oxide and vascular reactivity in pregnant rats with adriamycin nephropathy.

1. In previous studies we have shown that, after the administration of adriamycin, hypertension developed in rats who became pregnant (adriamycin-pregnant rats), whereas virgin animals remained normotensive. Subsequently, we showed that this hypertension was prevented by administration of L-arginine, suggesting that deficient synthesis of nitric oxide may be pathogenetic in this model. 2. To further assess the role of nitric oxide in this model, we measured mean arterial blood pressure after administration of L-arginine to adriamycin-pregnant rats or of NG-nitro-L-arginine-methyl ester (L-NAME) to normal pregnant rats. In other experiments, we assessed the response of isolated perfused arterial mesenteric vessels, precontracted with noradrenaline, to acetylcholine, L-arginine or L-NAME. 3. Blood pressure was decreased in normal pregnant rats, whereas it was elevated in adriamycin-pregnant rats. L-NAME treatment increased blood pressure in normal pregnant rats and L-arginine decreased it in adriamycin-pregnant rats. 4. Mesenteric vessels of adriamycin-pregnant rats exhibited an exaggerated vasoconstrictory response to noradrenaline, when compared with the blunted response observed in normal pregnancy. The addition of L-NAME in vitro induced a further contraction, significantly greater in normal pregnant rats. The vasodilatory response to acetylcholine and L-arginine was greater in vessels from adriamycin-pregnant rats. In contrast, responses to either nitroprusside or diazoxide were similar in all groups. 5. The results suggest a state of reduced nitric oxide synthesis in rats with adriamycin nephropathy, leading to vascular maladaption and hypertension in pregnancy.

Acetylcholine↗
PubMed1997

Diminished adhesion of CD4+ T cells from dialysis patients to extracellular matrix and its components fibronectin and laminin.

BACKGROUND: Cell-mediated immunity is impaired in uraemia. The recognition and ensuing interactions of immune cells, such as CD4+ T lymphocytes, with adhesive glycoproteins of the extra-cellular matrix (ECM) are mediated by integrins of the beta 1 subfamily. We have previously demonstrated that uraemic sera inhibit the proliferation and adhesion of normal CD4+ T cells to ECM components. In the present study, the adhesive capacity of CD4+ T lymphocytes of dialyzed patients (both haemodialysis [HD] and continuous ambulatory peritoneal dialysis [CAPD] was evaluated. METHODS: Adhesion of CD4+ T cells from dialysis patients to intact ECM and its immobilized moieties, fibronectin (FN) and laminin (LN) was measured following phorbol-12-myristate-13-acetate (PMA) stimulation. In addition, cell surface expression of beta 1 integrins (VLA 4-6) was determined by FACScan analysis. RESULTS: Compared to normal cells, CD4+ T cells of dialysis patients demonstrated a significantly reduced adhesion to ECM, FN and LN (27-28 vs 52-55%, P < 0.001). This decreased adhesive capacity was not normalized upon incubation of the cells with normal sera. Cell surface expression of beta 1 integrins was not modified. The inhibition of cell adhesion was more pronounced in CAPD patients (23-24% vs 29-30% in HD, P < 0.02). Serum albumin correlated directly with cell adhesion. Aged HD patients' T cells demonstrated increased adhesion to ECM and its ligands, whereas a reverse trend was demonstrated in the CAPD group. CONCLUSIONS: T cells of dialysis patients exhibit abnormal adhesive activity, which may be due to an acquired cellular defect induced by uraemic milieu. CAPD patients show a greater degree of adhesion impairment, possibly due to their lower concentrations of serum albumin.

Adult↗
PubMed1997

Pefloxacin in adriamycin induced nephrotic syndrome in the rat.

BACKGROUND: Pefloxacin, a fluorinated 4-quinolone, has recently been advocated as a first-line treatment for minimal-change nephropathy (MCN) or focal segmental glomerulosclerosis (FSGS). To further evaluate this issue we have utilized an animal model resembling human MCN, namely adriamycin-induced nephrotic syndrome in Wistar male rats. METHODS: Adriamycin at a dose of 7 mg/kg was injected intravenously to all rats at day zero. Rats were divided into two groups: group A (n = 20) given only water served as the control group while group B (n = 19) was administered pefloxacin at 150 mg/kg. At days 7, 14, 21 and 28, the rats were placed in metabolic cages and daily proteinuria determined. RESULTS: The nephrotic syndrome developed in all rats within 7 days of adriamycin administration. At day 7, proteinuria in group B was 173 +/- 78 vs 423 +/- 626 mg/day in group A, P < 0.02, but thereafter at days 14, 21 and 28, no significant difference in urinary protein excretion was noted. CONCLUSIONS: These results suggest that in this animal model of NS mimicking human MCN, pefloxacin's antiproteinuric effect is only of a mild and transitory nature. In view of the above data and the overall results in human patients (detailed herein), the use of pefloxacin as definitive treatment of the NS cannot be recommended.

Animals↗
PubMed1997

Orthostatic hypoxaemia in dialysed adult polycystic kidney disease patients.

BACKGROUND: Recently we observed a unique clinical phenomenon, namely, orthostatic or postural hypoxaemia in a 72-year-old female adult polycystic kidney disease (APKD) patient, maintained on CAPD. Extensive investigations failed to yield a satisfactory explanation for her ambulatory hypoxaemia. METHODS: To validate our observation, 15 dialysed patients underwent blood gases analyses in both the supine and ambulatory positions (SpO2 and ApO2 respectively). Patients were divided into two groups: group 1 (n-7) whose end-stage renal failure (ESRF) was due to APKD and group 2 (n-8) in whom ESRF was due to other causes. Both haemodialysed (HD) and CAPD patients were included. ApO2 was determined as the pO2 immediately upon standing up. Readings in HD patients were taken at the end of the dialysis session, that is, at the patients' dry weight. RESULTS: Respective SpO2 and ApO2 of the two groups were 85 +/- 17.1 and 78 +/- 20.5 vs 85.8 +/- 19 and 91 +/- 21 mmHg. Delta change in pO2 defined as the mean decrease (negative value) or mean increase (positive value) of ApO2 in relation to SpO2 was -7.85 (group 1) vs + 5.2 mmHg (group 2), P < 0.005. In group 1, six of seven patients demonstrated a negative delta. In group 2, four of eight showed a positive delta whilst the remaining four had no change in the delta value. CONCLUSION: Orthostatic hypoxaemia may occur in dialysed patients whose ESRF is due to APKD.

Adult↗
PubMed1997

Characterization of smoking-induced nasopharyngeal lymphoid hyperplasia.

The frequency of smoking-induced nasopharyngeal lymphoid hyperplasia in heavy smokers and its potential clinical implications are still unknown. Precise criteria to differentiate this entity from other types of nasopharyngeal lymphoid hyperplasia are needed. A prospective clinicopathological study of smoking-induced nasopharyngeal lymphoid hyperplasia was conducted in 17 heavy smokers. Ten nonsmoking patients, five of them with chronic sinusitis, three with adult-onset adenoid hypertrophy, and two children with adenoidal hypertrophy served as a control group. Both in smokers and in nonsmokers, lymphocytic infiltration of the mucosa was characterized immunohistochemically as T cells. In smokers, semithin (1 micron) sections revealed deformed and migrating cytotoxic lymphocytes in the nasopharyngeal mucosa. The lymphocytes were attached to epithelial, ciliated, and goblet cells, resulting in cell damage. Transmission electron microscopy of biopsies from smokers revealed emperipolesis, characterized by mucosal invasion and epithelial cell damage by an unusual population of migrating T lymphocytes that penetrate them. These findings confirm a direct effect of smoking on the nasopharyngeal lymphoid tissue, which forms part of the immune system. It is concluded that the diagnostic evaluation and therapeutic approach of heavy smokers with otological and airway symptoms should be based on thorough endoscopic examination of the nasopharynx. When the diagnosis is not clear-cut, selective tele-endoscopic biopsy and electron microscopic examination are recommended. This entity should be added to the list of known clinical manifestations of the smoking habit.

Adenoids↗
PubMed1997

Hypertension in pregnancy.

Normal pregnancy is characterized by a marked reduction in peripheral vascular resistance. Blood pressure is diminished, while cardiac output, blood volume, renal blood flow and the glomerular filtration rate are increased. These hemodynamic changes are reversed in preeclampsia-eclampsia (PE-E), a condition considered to be related to a dysfunction of the endothelium. Decreases in the production of nitric oxide (NO) and prostacyclin (in association with an increased synthesis of thromboxane A2) may play a role in the pathogenesis of PE-E. Recent reports have supported the concept that an imbalance between vasodilators and vasoconstrictors may explain the clinical, laboratory and hemodynamic disturbances observed in PE-E. Particular attention has been given to the fact that a state of L-arginine NO deficiency may be present. The control of hypertension, rest, and close clinical and laboratory surveillance remain the gold standard to minimize the severity of the complications of PE-E. However, on the basis of its physiology and pathophysiology, low-dose aspirin has been recommended in pregnancies at risk to prevent or, at least, to delay the occurrence of PE-E. Although initial reports showed promising results, recent conclusions from large trials have moderated this optimism. The use of supplemental L-arginine may be considered another possibility of treatment, and experimental data have given convincing results, but there are no reports on PE-E. Therefore, the practical management of PE-E requires prudence, careful follow-up and prompt decisions on the precise moment for delivery (which remains the most effective therapeutic procedure).

Adult↗
PubMed1997

High frequency of adenomyosis in postmenopausal breast cancer patients treated with tamoxifen.

Pathologic evaluation for adenomyosis in uterine specimens as well as demographic characteristics, health habits and risk factors for endometrial cancer were compared in 28 postmenopausal breast cancer patients with tamoxifen (TAM) treatment and in 11 similar patients without TAM treatment in order to determine the association between postmenopausal TAM exposure and the frequency of adenomyosis. The same comparison was also made between TAM-treated patients with adenomyosis and TAM-treated patients without adenomyosis. Adenomyosis was histologically diagnosed in 53.6% TAM-treated patients and in 18.2% non-TAM patients. Overall, there were no significant statistical differences in all parameters tested between the 2 groups, as well as between the TAM-treated patients with adenomyosis and the TAM-treated patients without adenomyosis. It can be concluded that adenomyosis was significantly more common among postmenopausal breast cancer patients who were treated with TAM as compared to similar patients without TAM treatment (p = 0.0186). This significant high rate of adenomyosis may be attributed to the continuous and unopposed exposure to TAM. It is, however, impossible to predict which postmenopausal breast cancer patient will develop adenomyosis after treatment with TAM.

Aged↗
PubMed1997

Pregnancy-induced hypertension in rats with adriamycin nephropathy is associated with an inadequate production of nitric oxide.

Hypertensive complications are relatively common in pregnancy, particularly in the presence of preexisting renal disease. Although the pathogenesis of such complications is still unknown, recent animal studies have suggested that it may be related to impaired synthesis of nitric oxide (NO). Rats with adriamycin nephropathy develop a "preeclamptic-type" pregnant state characterized by elevated blood pressure, lack of hyperfiltration, and enhanced proteinuria. Preliminary studies with this model have implicated inadequate NO synthesis in the development of preeclamptic-like pregnancy. The aim of the present study was to confirm this hypothesis. Pregnant rats, both normal (PREG) and those with adriamycin nephropathy (AN-PREG), received 100 mg/L N omega-nitro-L-arginine methyl ester PO from the middle of gestation to term (day 11, term approximately 22 days). One group of AN-PREG rats received either L-arginine or D-arginine (2 g/L) from midpregnancy. At term, systolic pressure, mean arterial pressure, urinary metabolites of NO, creatinine clearance, and urinary protein were assessed. At term, compared with virgin rats with adriamycin nephropathy, untreated AN-PREG rats had increased systolic pressure, mean arterial pressure, and proteinuria (mean arterial pressure, 124 +/- 2.5 versus 99.7 +/- 1.6 mm Hg [P < .05]; proteinuria, 434 +/- 58 versus 216 +/- 63 mg/d [P < .05]). Creatinine clearance did not change (1.68 +/- 0.23 versus 1.35 +/- 0.09 mL/min, P = NS). In PREG rats, urinary metabolites of NO increased approximately threefold at term pregnancy compared with control. By contrast, in AN-PREG rats, excretion of urinary metabolites of NO increased only by approximately 1.7-fold (P < .01) versus PREG rats. With the exception of AN-PREG rats, inhibition of NO synthesis with N omega-nitro-L-arginine methyl ester enhanced blood pressure and decreased creatinine clearance but did not influence proteinuria. Excretion of urinary metabolites of NO was similarly inhibited in all rats. In AN-PREG rats, L-arginine normalized blood pressure (91 +/- 2.15 mm Hg) and lowered proteinuria partially but significantly. D-Arginine had no effect. In summary, AN-PREG rats are unable to adequately increase NO synthesis when physiologically required. Correction of this deficit by L-arginine treatment induced a significant clinical improvement.

Animals↗
PubMed1996

Renal osteodystrophy in rats with reduced renal mass.

The rat remnant kidney, a popular model of experimental renal failure, has also been used to assess the histological bone changes associated with reduction in renal mass. The suitability of this model has been challenged, especially with regard to the standardization of animals from different age groups and various degrees of renal failure. The present study was undertaken: (1) to better evaluate the histomorphometric changes associated with reduction in renal mass; (2) to assess these changes over a longer follow-up period as compared to those of matched intact animals; (3) to define the response to pharmacological doses of calcitriol. Male rats were evaluated 4 and 8 weeks after induction of renal failure (5/6 nephrectomy) and compared with age-matched control rats with intact kidneys. Plasma biochemistry, creatinine clearance and parathyroid hormone (PTH) were obtained from normal rats and from the rats with chronic renal insufficiency. Histomorphometric studies were performed in all animals on the right tibial bone. Induction of renal failure of 4 weeks' duration (short-term study, age 16 weeks) was associated with increased PTH and bone resorption, but suppressed bone formation. At long-term follow-up (rats aged 20 weeks), the suppression in bone formation was even more prominent. These changes were assessed considering normal bone histomorphometry during the process of growing. Calcitriol administration was associated with a significant suppression of bone resorption and a spectacular increase in all osteoid parameters. The bone formation rate, however, remained in the same low range as that in untreated animals. This model of renal osteodystrophy is similar to human secondary hyperparathyroidism with regard to the enhanced bone resorption, but differs by the marked decrease in bone formation. There was a remarkable similarity between the response of rats with renal failure and that of patients with severe secondary hyperparathyroidism to large doses of calcitriol, leading in both to adynamic bone disease. Keeping in mind the species differences, the bone changes developing in the uraemic rats may be useful in understanding certain aspects of human renal osteodystrophy.

Animals↗
PubMed1996

Frequent involvement of the internal cuff segment in CAPD peritonitis and exit-site infection - an ultrasound study.

BACKGROUND: The extent of involvement of the subcutaneous Tenckhoff catheter tract in CAPD peritonitis and catheter-related infections is of major therapeutic importance. By definition, both peritonitis and exit-site infections do not involve the catheter tract. However, diagnosis of these infections as well as the more sinister tunnel infection is based mainly on clinical signs. METHODS: We examined the usefulness of ultrasound examination (US) of the catheter tract in delineating catheter-related (exit-site and tunnel) infections, and their relationship to each other and to peritonitis. CAPD patients with no evidence of peritonitis or catheter-related infections for 6 months prior to examination served as controls. US were performed by one of two experienced radiologists using the Acuson 128XP/10 scanner with a 7-MHz linear transducer. A positive US was defined as an area of hypoechogenicity (indicative of fluid collection) >2 mm in width along any portion of the catheter tract. Findings were localized into segments(S) as follows: S1, limited to external cuff; S2, intercuff segment adjacent to the external cuff; S3, intercuff segment adjacent to the internal cuff; S4, limited to the internal cuff; and S5, involvement extending throughout the catheter tract. RESULTS: Between March 1993 and January 1995, 39 CAPD patients, all with a double-cuff straight Tenckhoff catheter with the exit site situated above the point of entry into the peritoneum were studied. A total of 56 US were performed divided among 26 episodes of peritonitis, four tunnel infections, 13 exit-site infections,and 13 controls. There were 30 positive US distributed among 16 peritonitis, four tunnel, eight exit site infections and two control patients. The two positive controls went on to develop peritonitis within 1 month of the US. The majority of the US findings (13/16 in episodes of peritonitis and 5/8 exit site infections were localized to segment 4, that is, to the internal cuff region. Apart from a significant increase in width in all infected segments versus a normal tunnel, no differences in size were seen between peritonitis, exit-site, or tunnel infections, nor were there any differences in size and localization in these infections when comparing the offending organism (Gram-positive, negative, or culture negative). CONCLUSIONS: We conclude that peritonitis and exit-site infections are frequently accompanied by involvement of the catheter tract. The localization of infection to the internal cuff region in cases of exit-site infection probably occurred as a result of downward migration along the catheter tract. This supports the notion that ideally the exit site should be pointing caudally or that the peritoneal catheter have a swan-neck configuration. With regard to peritonitis, infection within the peritoneal cavity appears to extend and involve the internal cuff region. Thus both the internal and external cuffs do not seem to pose an effective barrier against the spread of infection.. Based on our data, we recommend that US be performed as a routine investigation in all cases of exit-site infection and in cases of refractory or relapsing peritonitis.

Adult↗