Biomedical subjects
Publications and source records attributed to A Neri.
Combined congenital anomalies of the Müllerian and Wolffian duct systems are a rare phenomenon. We report a case of bicornuate uterus and infected right Gartner duct cyst, associated with agenesis of the left kidney and a left ovarian cyst. The case is discussed in view of its unknown occurrence.
This study reports on the urinary albumin to creatinine ratio during normal pregnancy, with special emphasis on the pre-delivery and labour periods. Albumin was determined in single voided urine specimens obtained from healthy non-pregnant women (n = 16) and healthy pregnant women (n = 203; Groups A and B, 133 females examined during clinic visits and presentation at obstetric department; Group C, 70 females examined during labour) by radioimmunoassay (RIA). The mean ratio (+/- SD) for albumin/creatinine (A/Cr) in non-pregnant women was 1.46 +/- 0.32 mg mmol-1 Cr. Thus, 2.10 mg mmol-1 Cr (mean+2 SD) was considered to be the upper limit of normo-albuminuria. During pregnancy, 73% of the women (97 out of 133, Groups A and B) excreted less than or equal to 2.10 mg mmol-1 Cr. During the first 35 weeks of gestation, 30 of 34 pregnant women (88%) excreted less than or equal to 2.10 mg mmol-1 Cr, the mean being 0.93 +/- 0.64 mg mmol-1 Cr (median 1.0 mg mmol-1). During 36-42 weeks of gestation, the median A/Cr was 1.93 mg mmol-1 Cr (range 0.43-12.16) and 32 of 99 (32%) had values greater than 2.10 mg mmol-1 Cr, an increase of more than two-fold (p less than 0.031) compared with the first 35 weeks. During labour, 61% of non-haematuric urines (33 of 54, Group C) were greater than 2.10 mg mmol-1 Cr, being 125% greater (p less than 0.006) than that observed during pregnancy. Thus in normal pregnancy, A/Cr is increased during the late period of pregnancy and during labour.
In a retrospective study on 100 female patients (mean age 52 years), with a menopause lasting for 3.5 years, referred to the Menopausal Clinic of Beilinson Medical Center, we studied the pretreatment, clinical and laboratory work-up before administration of hormone replacement therapy (HRT). The work-up consisted of clinical and medical examination and history. Mammography is a necessary test for malignancy exclusion, and also the assessment of lipid metabolism. Pap smear is not so important since cervical cancer is a rare event in Jewish women and pelvic sonography cannot be a decisive diagnostic tool for ruling out malignancy. We conclude that HRT for prevention of osteoporosis and cardiovascular disease should be administered in a menopausal clinic by a gynecologist, after performing a few tests: confirmation of menopause by follicle-stimulation hormone (FSH) and E2, excluding malignancy by mammography, and confirmation of normal lipid metabolism.
A case of association between pheochromocytoma and homolateral stenosis of renal artery is discussed. Until now, this is the first notification of such an association. The authors examine the possibility of a link between the two pathologies on the basis of congenital or physical factors. This association could have been so rarely just only due to the difficulty to prove it.
A 24-year-old woman in her 20th week of pregnancy sustained a severely displaced acetabular fracture. Skeletal traction failed to achieve reduction. Open reduction and internal fixation were performed through an extended iliofemoral approach without affecting the pregnancy. At full term, she had a normal delivery. Four years after the injury, the patient had a pain-free hip with full range of motion and a healthy child. The potential benefit or danger of surgery to the patient and her pregnancy was thoroughly considered.
A B cell lymphoma-associated chromosomal translocation, t(10;14)(q24;q32), juxtaposes the immunoglobulin C alpha 1 locus to a novel gene, lyt-10. The normal lyt-10 cDNA codes for a 98 kd protein which displays amino-terminal homology with the rel (DNA-binding) domain of the NF-kappa B-rel family of transcription factors and carboxy-terminal homology with the NF-kappa B p50 precursor protein, including the putative proteolytic cleavage domain (poly-G) and the ankyrin-like repeat domains. The lyt-10 protein can bind to kappa B sequences in vitro, although with different specificity from NF-kappa B p50, and in vitro DNA-binding is activated by removal of the ankyrin domain. Chromosomal translocation generates an lyt-10-C alpha 1 fusion gene coding for a protein that retains the rel effector domain, lacks the ankyrin regulatory domain, and binds kappa B sequences in vitro, suggesting its constitutive activation in vivo. Analogous rearrangements of the lyt-10 gene have been found in an additional three cases of lymphoid neoplasia. The lyt-10 gene defines a new subfamily (rel/poly-G/ankyrin) of NF-kappa B-rel transcription factors with potential for oncogenic activation in human cancer.
The Authors report their clinical experience in superior mesenteric artery embolism: 10 arterial embolisms (71%) collected from a series of 14 obstructions of the superior mesenteric artery. The main interval from the beginning of the symptomatology to hospital admission was 48 h. Laparotomy was performed in all ten patients; gangrenous bowel was resected in 2 and 2 had an embolectomy of the superior mesenteric artery without intestinal resection. The remaining 6 patients had laparotomy alone and died. The Authors emphasize the difficulty in recognizing the disease at an early stage and suggest to contemplate in patients at risk with a persistent abdominal pain, the possibility of a superior mesenteric artery embolism.
Clinical follow-up of 71 patients subjected to major amputation of the lower extremities for atherosclerotic arteriopathy has been analysed for the purpose of ascertaining real possibilities of functional recovery and quality of life. Research results show that only a small number of patients (38%) can achieve an acceptable quality of life. The reasons have been identified in the objective difficulty of adequate physical and psychotherapeutic rehabilitation owing to structural shortcomings or the presence of associated pathology or the advance in the basic condition which does not permit application or frustrates results.
We have investigated the frequency of p53 mutations in B- and T-cell human lymphoid malignancies, including acute lymphoblastic leukemia, the major subtypes of non-Hodgkin lymphoma, and chronic lymphocytic leukemia. p53 exons 5-9 were studied by using genomic DNA from 197 primary tumors and 27 cell lines by single-strand conformation polymorphism analysis and by direct sequencing of PCR-amplified fragments. Mutations were found associated with (i) Burkitt lymphoma (9/27 biopsies; 17/27 cell lines) and its leukemic counterpart L3-type B-cell acute lymphoblastic leukemia (5/9), both of which also carry activated c-myc oncogenes, and (ii) B-cell chronic lymphocytic leukemia (6/40) and, in particular, its stage of progression known as Richter's transformation (3/7). Mutations were not found at any significant frequency in other types of non-Hodgkin lymphoma or acute lymphoblastic leukemia. In many cases, only the mutated allele was detectable, implying loss of the normal allele. These results suggest that (i) significant differences in the frequency of p53 mutations are present among subtypes of neoplasms derived from the same tissue; (ii) p53 may play a role in tumor progression in B-cell chronic lymphocytic leukemia; (iii) the presence of both p53 loss/inactivation and c-myc oncogene activation may be important in the pathogenesis of Burkitt lymphoma and its leukemic form L3-type B-cell acute lymphoblastic leukemia.
We have examined, by Southern blotting, the patterns of chromosomal breakpoint locations in 55 cases of Burkitt's lymphoma (BL) with respect to geography and Epstein-Barr virus (EBV) association. We have confirmed the association between chromosome 8 breakpoint and geography: 74% of endemic (eBL) but only 9% of sporadic BL (sBL) had breakpoints outside the HindIII fragment encompassing the c-myc gene (P2 less than .00001). Conversely, not only did 91% of sBL manifest a rearranged HindIII fragment, but at least 56% of these cases, in contrast to 17% of eBL cases, had a breakpoint within the first exon or intron of c-myc (P2 less than .004). Breakpoints outside the switch mu (S mu) region (ie, the HindIII fragment encompassing S mu) on chromosome 14 were twice as common overall (73%) as those within S mu (27%), but in the 15 tumors with S mu breakpoints, 13 (87%) had a rearranged c-myc gene. Breakpoints outside the HindIII fragment encompassing c-myc on chromosome 8 were predominantly associated with non-S mu breakpoints on chromosome 14 (85%) and this was the combination most frequently associated with eBL (65%; 6% of sBL, P2 less than .00001). In sBL, the most frequent breakpoint combination was a rearranged c-myc gene with a non-S mu breakpoint (63%; 13% of eBL). Twenty-eight percent of sBL and 13% of eBL had breakpoints both within c-myc and within S mu. EBV DNA was present in 19 of 20 tumors with breakpoints outside c-myc, in none of 7 with a breakpoint in the immediate 5' region of c-myc, in 4 of 5 tumors with breakpoints in the first exon, and in 7 of 12 tumors with breakpoints in the first intron. These data suggest that the pathogeneses of eBL and sBL differ with regard to the mechanism of c-myc deregulation, and probably also with regard to the state of differentiation of the target cell for malignant transformation. We have formulated a testable hypothesis regarding the potential role of EBV in pathogenesis: that it is required to contribute to the deregulation of c-myc in the presence of some, but not all, types of c-myc damage arising from the chromosomal translocations.
The Epstein-Barr virus (EBV) is associated with distinct forms of human lymphoid malignancies, including the endemic (eBL) and sporadic forms of Burkitt's lymphoma (sBL) and acquired immunodeficiency syndrome-associated non-Hodgkin lymphoma (AIDS-NHL). However, whether EBV has a pathogenetic role in these tumors or is a passenger virus has not been conclusively demonstrated. One element to distinguish between these two possibilities is to determine whether EBV infection has preceded and, thus, possibly contributed to clonal expansion, or whether infection has occurred after clonal expansion and thus is unlikely to contribute to pathogenesis. Toward this end we analyzed the structure of the heterogeneous genomic termini of EBV as markers of clonal infection in a panel of eBL (11 cases), sBL (9 cases), and AIDS-NHL (10 cases) biopsies. We show that EBV termini are uniformly clonal in sBL, eBL, and AIDS-NHL, strongly suggesting that EBV infection has preceded and, thus, most likely contributed to clonal expansion in these malignancies.
The ability of tumor cells to express elevated levels of proteinases capable of degrading tissue matrix and basement membrane components in vitro has been correlated to their invasive and metastatic potential. Many in vitro invasion assays have been performed either in the presence of serum or with tumor cells that had been previously grown in serum. Since serum contains large amounts of active proteinase inhibitors, their presence could complicate interpretations. We have, therefore, attempted to measure the amounts of serine proteinase inhibitors released into culture medium by two rat mammary adenocarcinoma metastatic variants selected in vitro for serum-independent growth and differing in their in vivo metastatic behavior. Concentrated spent media (CSM) derived from cultures of poorly metastatic MTLn2(T42D) and highly metastatic MTLn3(T17D) tumor cells, grown in the presence and absence of fetal bovine serum (FBS) for 20-24 h, were compared for the presence of serine proteinase inhibitors capable of inactivating alpha-chymotrypsin. Our results show that when MTLn2(T42D) and MTLn3(T17D) tumor cells were exposed to FBS, the CSM of MTLn2(T42D) exhibited nearly 5-fold greater amounts of active proteinase inhibitors than that of MTLn3(T17D). The amount of proteinase inhibitory activity detected in the CSM of tumor cells not exposed to FBS was not eliminated but declined by 82% and 37% for MTLn2(T42D) and MTLn3(T17D), respectively. Analysis for enzyme-inhibitor (E-I) complex formation by nonreducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by autoradiography confirmed the kinetic results and revealed that the major inhibitor present in CSM/FBS of both variants forms a heat- and sodium dodecyl sulfate-stable E-I complex with an apparent molecular weight of approximately 79,000, identical to that formed when FBS or purified alpha 1-proteinase inhibitor is incubated with [alpha-125I]chymotrypsin. E-I complexes with apparent molecular weights of 44,000 and 50,000 were formed from CSM/bovine serum albumin of MTLn3(T17D) and MTLn2(T42D), respectively, that were not detected when [alpha-125I]chymotrypsin was incubated with bovine serum albumin. We infer from these observations that, in culture, poorly metastatic MTLn2(T42D) tumor cells, as compared to their highly metastatic MTLn3(T17D) counterparts, exhibit an increased capacity to retain and subsequently release significantly greater amounts of serum-derived active proteinase inhibitors. Moreover, the detection of proteinase activity by kinetic analysis and E-I complexes by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography in CSM prepared from cultures not exposed to FBS indicates that both variants have the capacity to produce their own inhibitors.(ABSTRACT TRUNCATED AT 400 WORDS)
The search for bone marrow clone neoplastic precursors in the peripheral blood of multiple myeloma (MM) patients has been the subject of a number of studies which, using different methodological approaches, have led to conflicting results. With the aim of contributing toward resolving this controversy, immunoglobulin (Ig) gene rearrangement in the bone marrow mononuclear cells (BMMC) and B-lymphocyte enriched peripheral cells (BePBC) of 11 appropriately selected advanced MM patients was studied by means of Southern blotting. Peripheral mononuclear cells (PBMC) and BePBC were studied immunophenotypically by evaluating the presence of cytoplasmic Ig positive cells (CyIg+) and CD19/PCA-1 reactivity. A pattern of Ig gene rearrangement identical to that observed in the respective BMMC was found in only two patients who, moreover, had a significant number of CyIg+ cells. Ig gene rearrangement was not found in any of the remaining patients who showed no evidence of the presence of CyIg+ cells, although there were CD19/PCA-1 positive cells. Consequently, the significance of the presence of malignant pre-plasma cell peripheral B-lymphocytes needs to be reconsidered and, in any case, these cells should be looked for in cell populations greatly enriched in B-lymphocytes and, above all, completely lacking in plasma cells or CyIg+ cells.
The familial occurrence of hypertrophic cardiomyopathy is well known; familial dilated cardiomyopathy has so far received less attention. Ten families with two or more members affected by dilated cardiomyopathy were studied by echocardiography. In 3 out of 10 families, a transverse study extended to even apparently healthy subjects was carried out, which included a total of 45 subjects. In 19 out of the 45, dilated cardiomyopathy (either symptomatic or asymptomatic) was diagnosed at echocardiography. Three more relatives, already dead of the disease, were identified through hospital records. A clinical and echocardiographic longitudinal study, lasting up to 11 years, was carried out in 5 of the 10 families. During the follow-up, 8 out of 19 patients who, at first examination were affected by dilated cardiomyopathy, died, one improved, 3 remained in stable condition and 7 were lost at follow-up. One of two patients who presented echocardiographic findings suggestive of border-line dilated cardiomyopathy returned to normality and the other developed dilated cardiomyopathy. The clinical and echocardiographic findings in our patients, and in their relatives, suggest the possibility that idiopathic dilated cardiomyopathy may be a multifactorial disease in which genetic factors might play a variable role.
The adhesive property of white blood cells is essential for a normal immune response. We examined the state of leukocyte adhesiveness/aggregation (LAA) in the peripheral blood of 31 mothers and their newborns by means of a direct slide test and found it to differ significantly, the respective per cents of aggregated leukocytes found in the peripheral blood being 15 +/- 6.4 and 5 +/- 3.3 (mean +/- SD). However, the particle concentration of white blood cells in the peripheral blood did not differ significantly (14.2 +/- 4.4 and 13.6 +/- x 10(9) l-1). By incubating a mother's plasma with her newborn's whole blood we could induce a significant (p less than 0.0001) increment in the state of LAA. We conclude that deficiency of a plasma factor that does not cross the placenta is responsible for the low LAA in the newborn's peripheral blood.
Healthy men, 20 to 60 years old, drank a moderate dose of ethanol in the morning after an overnight fast. They consumed either neat whisky in amounts corresponding to 0.34, 0.51, 0.68, 0.85, or 1.02 g of ethanol per kilogram of body weight or 0.80 g/kg ethanol solvent diluted with orange juice. The peak blood-ethanol concentration (BEC) increased with the dose administered, but the time required to reach the peak was not markedly influenced over the range of doses studied. At a dose of 0.68 g/kg, the peak BEC ranged from 52 to 136 mg/dL (N = 83), and slow absorption (a late-occurring peak) produced a lower peak BEC. The peak BEC was reached between 0 and 45 min for 77% of the subjects (N = 152) and between 0 and 75 min for 97% of them. The time of peaking in venous blood occurred, on average, 10 min later than in capillary (fingertip) blood although the peak BEC was not appreciably different; the mean venous BEC was 97.0 mg/dL (range, 76 to 112 mg/dL), and the mean capillary BEC was 99.6 mg/dL (range, 75 to 123 mg/dL). When subjects drank 0.80 g/kg ethanol diluted with orange juice over 30 min, the average BEC increment between the end of drinking and the peak was 33 mg/dL (range, 0 to 58 mg/dL). The rate of absorption of ethanol was 1.78 mg/dL/min (range, 0.52 to 4.8 mg/dL/min), and the peak BEC occurred within 60 min after the end of drinking in 92% of the trials. The largest BEC increment (mean, 21 mg/dL; range, 0 to 44 mg/dL) was seen during the first 15 min after the drinking period.
The Authors report a 68% overall success rate in a three years follow-up study of 45 "complementary" profundoplasties. The key factors with a significant prognostic effect on the clinical surgical results are the early postoperative increase of the resting ankle pressure index (I.W.) and the angiographic preoperative patency of the tibial arteries. An early postoperative increase of I.W. has been always associated with good results whereas an unchanged postoperative I.W. has always been associated with poor results; an angiographic tibial run-off (one or two or three patient tibial arteries) has been associated with significant better clinical results (p less than 0.001).
A case of lymphomatoid granulomatosis of lung that occurred in a patient with the acquired immunodeficiency syndrome (AIDS) was studied by light microscope, electron microscope, cell surface markers, and Southern blot test. Clonal selection of two clones of B-cells was seen. Two clones were infected with Epstein-Barr virus. There was no c-myc rearrangement. Lymphomatoid granulomatosis in patients with AIDS may represent multiclonal selection of B-lymphocytes in association with Epstein-Barr virus infection.