Biomedical subjects
Publications and source records attributed to J Bernheim.
Two cases of bilateral ureteral obstruction in malignant lymphoma are reported. In one case, primary infiltration of the ureters by Hodgkin's disease was demonstrated, while in the other the obstruction was due to ureteral compression by enlarged lymph nodes. The diagnostic procedures and the management of such cases are discussed.
We describe the third documented case of Listeria monocytogenes pericarditis. This occurred in a 54-year-old woman with end-stage renal failure on chronic hemodialysis. Her initial presentation was one of Listeria monocytogenes bacteremia, which apparently responded to two weeks of cefazolin sodium therapy. After cessation of therapy the patient returned with Listeria monocytogenes pericarditis, this responding completely to four weeks of erythromycin therapy. We could not rule out coexisting endocarditis, especially since we found high levels of circulating immune complexes which subsided as the patient's condition improved. Further immunological studies displayed a decrease in cellular functions. This case illustrates the importance of Listeria monocytogenes as a human pathogen in immunocompromised patients. Listeria should be included among the potential causative agents of pericarditis in such patients.
The term cutaneous T-cell lymphoma (CTCL) has recently been coined to describe a group of rare lymphoproliferative T-cell disorders classically beginning in the skin and pursuing a chronic, progressive, and indolent course eventually followed by visceral involvement. This term encompasses the spectrum of the traditional mycosis fungoides and Sézary syndrome. A unique case of CTCL that developed a fulminant course leading to death within a few months following the initial symptoms is presented. The clinical course bears a striking similarity to a group of acute T-cell malignancies, while the cytologic-pathologic findings favor the diagnosis of Sézary syndrome. Regardless of the exact classifications, this entity appears to be a highly malignant T-cell disorder, resistant to chemotherapy.
AIM: To study the effect of sociodemographic and attitudinal determinants of physicians making end-of-life decisions (ELDs). METHODS: The physicians having signed 489 consecutive death certificates in the city of Hasselt (Belgium) were sent an anonymous questionnaire regarding their ELDs and another on their attitudes toward voluntary euthanasia (EUTH) and physician-assisted suicide (PAS). RESULTS: 55% response rate. Nontreatment decisions occurred in 16.7% of all death cases; in 16%, there was potentially life-shortening use of drugs to alleviate pain and symptoms; in 4.8% of cases, death was deliberately induced by lethal drugs, including EUTH, PAS, and life termination without explicit request by the patient. In their attitudes toward EUTH and PAS, the 92 responding physicians clustered into 3 groups: positive and rule oriented, positive rule-adverse, and opposed. Cluster group membership, commitment to life stance, years of professional experience, and gender were each associated with specific ELD-making patterns.
Molecular alterations in the mismatch repair system suggest that this mechanism may be important in the evolution of cutaneous melanoma. Our current study evaluated the expression of two mismatch repair proteins, hMLH1 and hMSH2, in dysplastic nevi (DN) and cutaneous melanoma (CM). Immunohistochemical staining of these proteins was performed on 55 CM and 30 DN specimens. The staining results were divided into three groups: negative, partially positive and strongly positive. Normal adjacent skin cells served as an internal control for positive immunostaining. Altered immunoreactivity of one of the proteins was found in four (13.4%) DN and seven (12.7%) CM. Lack of staining for hMLH1 was observed in two (6.7%) cases of DN and five (9.1%) cases of CM; staining for hMSH2 was absent in two (6.7%) of the DN and two (3.6%) of the CM specimens. Partially positive staining was found in 33.3% and 53.3% for hMLH1 and hMSH2, respectively, in DN, and in 54.5% and 69.1%, respectively, in CMM. Our study shows that complete or partial loss of MMR protein expression occurs in a subset of both DN and CM and may represent a distinct pathway in the development of some DN and CM.
BACKGROUND: Genetic aberrations observed in the large bowel during the neoplastic progression have a cumulative effect and are responsible for the propagation of the multistep malignant process. In the present study we evaluated the immunoreactivity of c-fos, ras, bcl-2 and p53 in aberrant crypt foci (ACF) and minute polyps of the large bowel obtained from patients with colorectal cancer. METHODS: ACF and minute polyps were collected from macroscopically normal colonic mucosa. Protein immunoreactivity was detected on parafin sections utilizing the biotin-streptavidin method on 25 hyperplastic, 10 dysplastic ACF, 5 hyperplastic and 10 dysplastic adenomas. RESULTS: 41% of the lesions displayed positive ras immunoreactivity. bcl-2 immunoreactivity was positive in six minute polyps of which five were neoplastic. fos immunoreactivity was detected in five ACF and seven minute polyps, mainly in dysplastic lesions. Two neoplastic polyps were positive for p53 immunoreactivity. Coexpression of two or more oncoproteins was found with increasing frequency in dysplastic versus hyperplastic lesions and in polypoid lesions versus ACF. CONCLUSION: Abnormal expression and coexpression in oncoproteins can be identified in the earliest stages of colorectal tumorigenesis and may contribute to the progression of selected lesions during ACF-adenoma-carcinoma sequence.
OBJECTIVE: Glucose-based dialysate induces non enzymatic glycation within the peritoneal cavity. To evaluate the relationship between the formation of advanced glycation end-products (AGEs) and peritoneal transfer for small solutes and macromolecules, we developed a model of simulated peritoneal dialysis (PD) in normal rats. METHODS: Male albino rats of the Charles River strain were divided into two sets of 3 groups (15-25 rats in each group). In the experimental (E) group, the rats were intraperitoneally (i.p.) injected daily with a commercially available 4.25% dextrose solution. In the control puncture (CP) group, the peritoneum was punctured daily, but no PD solution infused. In an age-matched control (CC) group, no intervention was given. Two study protocols were used. Protocol A (duration 20 weeks) consisted of a daily i.p. injection of 10 mL PD solution per 100 g body weight. In protocol B, a double volume of PD solution was introduced (20 mL per 100 g body weight). At 9, 16, and 20 weeks in protocol A, and at 9 weeks in protocol B, urea, creatinine, microalbumin [(MAL) measured using specific anti-rat albumin monoclonal antibody], and AGEs (measured by fluorescent assay with excitation at 370 nm and emission at 440 nm) were measured in peritoneal effluent and serum. RESULTS: At no time during the study were AGEs detected in serum from any group in either protocol. In both protocols, no differences were found between the control groups (CP, CC) with respect to all parameters. In protocol A, the dialysate-to-plasma ratio (D/P) of urea was significantly higher in the experimental group as compared with the control groups at 9, 16, and 20 weeks [9 weeks: 0.59 +/- 0.03 (E) vs 0.39 +/- 0.02 (CP) vs 0.46 +/- 0.02 (CC), p < 0.0004 and p < 0.002, respectively; 16 weeks: 0.71 +/- 0.08 (E) vs 0.42 +/- 0.01 (CP) vs 0.46 +/- 0.01 (CC), p < 0.0001 and p < 0.02, respectively; 20 weeks: 0.57 +/- 0.03 (E) vs 0.39 +/- 0.01 (CP) vs 0.41 +/- 0.02 (CC), p < 0.002 and p < 0.004, respectively]. At 16 and 20 weeks, dialysate MAL levels were significantly increased in group E [16 weeks: 354.00 +/- 80.35 microg/mL (E) vs 134.75 +/- 14.36 microg/mL (CP) vs 110.69 +/- 7.83 microg/mL (CC), p < 0.04 and p < 0.03, respectively; 20 weeks: 283.17 +/- 14.71 microg/mL (E) vs 105.14 +/- 12.11 microg/mL (CP) vs 135.50 +/- 19.03 microg/mL (CC), p < 0.00001 and p < 0.0001, respectively]. In protocol B, at completion of the study (week 9), D/P urea, effluent MAL, and AGEs were significantly higher in the experimental group as compared with the control groups [D/P: 0.67 +/- 0.04 (E) vs 0.46 +/- 0.07 (CP) vs 0.41 +/- 0.02 (CC), p < 0.0002 and p < 00001, respectively; MAL: 336.8 +/- 63.30 microg/mL (E) vs 125.71 +/- 16.77 microg/mL (CP) vs 119.00 +/- 39.75 microg/mL (CC), p < 0.008 and p < 0.007, respectively; AGEs: 265.77 +/- 33.49 U/mg creatinine (E) vs 163.10 +/- 21.99 U/mg creatinine (CP) vs 83.17 +/- 22.66 U/mg creatinine (CC), p < 0.02 and p < 0.001, respectively]. Peritoneal effluent AGEs were found to be significantly correlated with D/P urea and dialysate MAL (r = 0.42, p < 0.04, and r = 0.7, p = 0.00001, respectively). CONCLUSIONS: In situ generation of AGEs constitutes the chief origin of peritoneal AGEs. Advanced glycation end-products affect peritoneal permselectivity for both small and large solutes. The rat model of simulated peritoneal dialysis developed in this experiment provides a reliable method for studying peritoneal AGE formation and effect on peritoneal transfer of small solutes and macromolecules.
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OBJECTIVE: To evaluate the effect of advanced glycation end-products (AGEs) and the inhibitor of their formation, aminoguanidine, on tumor necrosis factor-alpha (TNFalpha) production (as a functional marker) by rat peritoneal macrophages (PMphi). DESIGN: Charles River rats underwent a daily intraperitoneal injection of peritoneal dialysis solution [(PDS), 4.25 g/dL dextrose; Dialine, Travenol, Ashdod, Israel] for a 2-month period (group E). Another group of rats was subjected to the same protocol with the addition of 25 mg/kg aminoguanidine (group A). Three control groups were utilized: (1) rats that were injected daily with aminoguanidine only (group AO), (2) rats that were injected with Dulbecco's phosphate-buffered saline (group D), and (3) rats in which no intervention was carried out (group C). After 2 months, PMphi were isolated from rat peritoneal effluent and their TNFalpha production measured by ELISA in cell-free culture supernatants, in both the basal state and after 24-hour stimulation with lipopolysaccharide (LPS). The concentrations of AGEs in peritoneal effluent were assayed and correlated to TNFalpha levels. PMphi obtained from normal rats were then incubated for 24 hours with (1) the peritoneal effluent of each of the above respective groups, with or without LPS; (2) increasing concentrations of AGEs (0-250 microg/mL); and (3) increasing concentrations of aminoguanidine (0-7.5 mg/mL), and TNFalpha secretion again determined. RESULTS: After 2 months of daily intraperitoneal injection of PDS, in the basal state, TNFalpha production was significantly higher in PMphi isolated from the peritoneal effluent groups (groups E, A, and AO) compared to controls (group C). Following LPS stimulation, a further increase in TNFalpha secretion was seen, with a significantly greater response in group AO versus groups E, A, and D. Effluent AGEs were markedly elevated only in group E. No correlation was found between TNFalpha secretion by these PMphi and the concentration of AGEs. On incubation with the respective peritoneal effluents (groups E, A, and AO), in both the basal and stimulated state, TNFalpha production by PMphi from normal rats was significantly enhanced compared to group C. Incubation with increasing concentrations of AGEs or aminoguanidine resulted in an increase of TNFalpha secretion by these PMphi. CONCLUSIONS: Following intermittent intraperitoneal administration of glucose-based PDS, rat PMphi are chronically activated, as evidenced by increased basal TNFalpha secretion. The peritoneal effluent of such treated animals is capable of stimulating TNFalpha production by normal rat PMphi. These data suggest that glucose-based PDS acts as a primer of PMphi, which retain their ability to further stimulation by LPS. Although, in vitro, AGEs promote TNFalpha secretion by normal rat PMphi, in vivo, their influence is probably modulated by other factors. Aminoguanidine has a specific inducing effect on rat PMphi, independent of glucose-based PDS.
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Immunosuppressed patients are known to be susceptible to infectious agents. Association of allograft rejection and herpes virus infection (high incidence of cytomegalovirus) was yet reported after renal transplantation. Authors studied 19 rejection episodes on 24 renal transplantation performed for 17 months, cytomegalovirus infection being associated in 7. Because of the therapeutic difficulties observed in these cases, a preventive attitude is necessary.
Auricular asystoly (A.A.) was the electrocardiographic pattern of 6 patients admitted for electrolytic disorders secondary to either renal failure or inadequate treatment. A rapid increase of blood potassium was the unique commun abnormality found to explain the dysrhytmia. Bradycardia (between 25 and 55 beats/mn) was present in each case with or without clinical symptoms. Temporary prophylactic pace maker insertion was performed in 4/7 patients. Recovery appeared after dialysis treatment in 6 cases, medical treatment in one, sinus rhythm being present in 6 and chronic atrial fibrillation in one. Prognosis of A.A. due to hyperkaliemia is good when hydroelectrolytic disorders are rapidly corrected. Follow up of blood electrolytes and electrocardiogram must be regular to prevent reccurencies.
Ninety postmenopausal women with advanced breast cancer were randomly assigned to be treated with HD-MPA administered either by oral route (daily dose 900 mg) or by intramuscular injections (1 g IM daily X 5 q w during 4 consecutive weeks followed by maintenance with 1 g twice weekly). Among 78 evaluable cases, most heavily pretreated, remissions, lasting for a median duration of 11 months, were more frequent on oral (8/37 = 22%) than on IM therapy (5/41 = 12%). In both arms, high estrogen receptor levels and various clinical factors were associated with higher response rates i.e., age greater than 60, Karnofsky greater than 70, light prior systemic treatment. Side-effects, consisting mainly of weight gain, hypertension and tremor occurred with equal frequency on oral or IM treatment. Five patients complained of pain at the sites of IM injections. Thus, we recommended that, whenever possible, the oral route should be preferred. During the same study, in 20 patients (11 on oral and 9 on IM therapy), blood was drawn at 0, 30, and 60 days of treatment for the assessment of MPA and hormone levels. In both arms, at 60 days, comparable levels of circulating MPA were obtained, with a very significant drop of cortisol, androstenedione, and estrone. These endocrine results, together with our clinical data, indicate that HD-MPA therapy is active on estrogen-dependent tumors with the same specificity as that of other modalities aiming to suppress the adrenal function. Its antineoplastic action in humans could be ascribed at least in part to its suppressive action on the adrenals, resulting in a severe estrogenic deprivation in postmenopausal women.
We report a neonate who manifested type II (proximal) renal tubular acidosis (RTA). Hypoventilation secondary to hypothalamic dysfunction led to carbon dioxide retention. The consequent changes in acid base regulation are detailed and discussed.
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Enlarged Brunner glands (EBG) are an occasional finding in upper gastro-intestinal barium studies. The clinical manifestations vague upper abdominal symptoms or bleeding are rare. Brunner gland secretion is stimulated by different stimuli but especially by secretin. In our report E.B.G. has been observed in 9/15 chronically hemodialysed patients. This uncommon frequence of E.B.G. can be related to the high blood levels of secretin found in patients with chronic renal failure. E.B.G. could explain some of the gastro-intestinal complications occuring in these patients.