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Biomedical subjects

M Goldman

Publications and source records attributed to M Goldman.

At least 397 records · Page 22Linked to original sources
PubMed1991

Laser Doppler flowmetry, transcutaneous oxygen tension measurements and Doppler pressure compared in patients undergoing amputation.

The level of amputation continues to present a challenge for surgeons. In view of this, 24 patients who required an amputation of their ischaemic leg were studied prospectively using Laser Doppler flowmetry (LDF), TcpO2 measurements and Doppler ultrasound to assess the best level for amputation. In all patients gangrene of the leg and rest pain were the indication for an amputation. Skin oxygen tension (TcpO2) and skin blood flow (LDF) measurements were obtained the day before surgery on the proposed anterior and posterior skin flaps for below knee amputation and the maximum Doppler systolic pressure was measured. The level of amputation was chosen at surgery by clinical judgement without reference to the measurements mentioned above. A below knee amputation was performed in 17 patients and an above knee in seven. All amputations healed by primary intention. Doppler pressures showed poor discrimination with a median value of 10 mmHg (0-25) in AK patients and 35 mmHg (0-85) in the BK group (p greater than 0.05). In contrast TcpO2 showed a trend. In the BK group the median value was 20 mmHg (4-50) on the anterior and 22 mmHg (2-60) on the posterior flap compared to above knee amputees with median values of 6 mmHg (2-11) and 8 mmHg (3-38), respectively (p greater than 0.05). Laser Doppler seemed more useful. In BK patients the median LDF values were 36 mV (20-85) on the anterior and 34 mV (20-80) on the posterior flap with median LDF values of 10 mV (10-18) on the anterior and 11 mV (8-38) on the posterior flap in the above knee group (p less than 0.01). Laser Doppler flowmetry is a simple objective test, which is a better discriminator of skin flap perfusion than either TcpO2 or Doppler ankle pressures.

Aged↗
PubMed1991

Renal immunopathology in murine host-versus-graft disease.

BALB/c mice neonatally injected with 1 x 10(8) (A/J x BALB/c)F1 hybrid spleen cells develop polyclonal B cell activation and autoimmune features as a consequence of a host-versus-graft (HVG) reaction. In this study, we first analyzed the time-course development of the renal lesions in HVG mice. From week 2 to week 6, linear deposits of IgG were observed by immunofluorescence along the glomerular capillary walls. From week 8 to week 12, the immunofluorescence pattern of IgG changed from linear to granular, and by immunoelectron microscopy, the IgG deposits were located on the epithelial side of the glomerular basement membrane (GBM). In addition, focal glomerulosclerosis complicated this membranous glomerulopathy in about 50% of the 12-week-old HVG mice and albuminuria was increased in most of them. Circulating antibodies to antigens of the GBM (laminin, type IV collagen) and of the renal tubular epithelial (RTE) cells (dipeptidyl peptidase IV, gp330) were already detected at week 2 and were still present at week 12. Immunoglobulins eluted from isolated glomeruli contained antibodies directed against type IV collagen, laminin, and to a lesser degree against gp330. F1 donor B cells were involved in the production of nephritogenic antibodies as indicated by (a) the presence of A/J allotypic determinants on serum anti-laminin antibodies and (b) the abrogation of the in vitro production of anti-GBM, anti-laminin and anti-RTE antibodies when spleen cells from HVG mice were depleted of F1 donor B cells. Finally, mixed lymphocyte culture experiments established that T cells from HVG mice stimulate normal B cells from F1 donor hybrids to produce anti-GBM, anti-laminin, anti-type IV collagen, anti-RTE, anti-gp330 and anti-dipeptidyl peptidase IV antibodies. We conclude that mice neonatally injected with semi-allogeneic spleen cells develop a glomerulonephritis characterized by the transition from a linear to a granular IF pattern, and that the production of nephritogenic antibodies results from the activation of donor B cells by host helper T cells.

Animals↗
PubMed1991

Effect of blood transfusion on survival in a mouse bacterial peritonitis model.

Allogeneic blood transfusions can result in alloimmunization or immunosuppression. A previous study demonstrated a deleterious effect of allogeneic blood transfusion on tumor growth in mice that was dependent, in part, on the dose of tumor cells with which the host animal was inoculated. The current study examined the effect of a similar allogeneic blood transfusion protocol on survival in a mouse bacterial peritonitis model. C57Bl/6J mice were transfused with 0.2 mL of heparinized fresh whole blood from C57Bl/6J (syngeneic) or Balb/c (allogeneic) mice. Transfusions were given on Days -10 and -7. On Day 0, mice were injected intraperitoneally with 10(7) Escherichia coli. Survival at Day 7 was 61 percent in the allogeneic blood transfusion group and 55 percent in the syngeneic blood transfusion group (p = 0.52). Experiments using different strains of mice, different transfusion protocols, and different doses of bacteria also failed to demonstrate an effect of allogeneic blood transfusion on survival. The results demonstrate that blood transfusion does not influence survival after a septic challenge with bacteria. The data obtained in the present study, together with those obtained in the tumor model, suggest that the mechanisms by which the allogeneic blood transfusion impedes host defense against bacterial infections is different from the mechanisms involved in tumor growth.

Animals↗
PubMed1991

High-fiber diet reduces serum estrogen concentrations in premenopausal women.

The effect of dietary fiber on serum estrogen concentrations was studied in 62 premenopausal women. Their estimated daily dietary fiber intake was increased from an average of approximately 15 g to 30 g/d by supplementation with wheat, oat, or corn bran. This was done without any significant decrease in dietary fat consumption. After 2 mo on the high-fiber diets, the wheat-bran-supplemented group showed significant reductions in serum estrone (P less than 0.002) and estradiol (P less than 0.02) but no change in serum progesterone or sex-hormone-binding globulin concentrations. The serum estrogens were unaffected by dietary-fiber supplementation with oat or corn brans.

Adult↗
PubMed1991

Prevention of cyclosporine A-induced vascular toxicity by pentoxifylline.

To determine whether an in vivo treatment with pentoxifylline (PTX) can prevent the vascular toxicity of cyclosporine A (Cx), three groups of rats were studied in parallel. The first group received daily injections of Cx (20 mg/kg intramuscularly) and pentoxifylline (80 mg/kg intraperitoneally) for 7 days, the second group was treated with Cx only, and the third group served as control (vehicle treatment). Cx serum levels were similar in groups 1 and 2. In thoracic aortic rings isolated from Cx group (group 2), the concentration-response curves to phenylephrine were potentiated: there was a significant leftward shift (p less than 0.001 vs. control) in the EC50 values and an increase in the maximal responses (p less than 0.05). After mechanical removal of the endothelium or inhibition of endothelium-derived relaxing factor formation (incubation with NG-monomethyl-L-arginine, L-NMMA), this enhanced responsiveness to phenylephrine persisted. In preparations from the same group (group 2), the endothelium-dependent relaxations to acetylcholine (ACh) were decreased whereas the endothelium-independent relaxations to nitroprusside (NTP 0.01-10 nM) and forskolin (1 nM) were slightly attenuated but without changes in the maximal response. In the group cotreated with Cx and PTX (group 1), the responses to ACh, NTP, and forskolin were not different from controls whereas the greater responsiveness to phenylephrine was only partially attenuated. In vivo cotreatment with PTX may prevent the endothelial dysfunction and the functional changes in smooth muscle cells induced by Cx.

Acetylcholine↗
PubMed1991

Evidence that pentoxifylline reduces anti-CD3 monoclonal antibody-induced cytokine release syndrome.

Pretreatment with pentoxifylline (PTX), a methylxanthine known for its beneficial effects on tissue lesions induced by the injection of endotoxin or recombinant cytokines, was shown to decrease the systemic release of tumor necrosis factor and interleukin 2 occurring after the administration of the anti-CD3 monoclonal antibody 145-2C11 in mice. In parallel, PTX attenuated the hypothermia and the rise in blood urea nitrogen observed in this model. The protective effect of PTX on the toxicity of 145-2C11 was confirmed by the reduction of the mortality among D-galactosamine-sensitized animals. The mitigation by PTX of the release of cytokines did not affect the immunosuppression entailed by 145-2C11 as assessed by the unmodified cytotoxic T lymphocytes (CTL) unresponsiveness against alloantigens measured 48 hr after the injection of the mAb. In vitro experiments on human peripheral blood leukocytes indicated that PTX alone or in synergy with methylprednisolone (m-PDS) also inhibited the release of TNF and IL-2 induced by OKT3. Finally, in a preliminary pilot trial conducted in kidney transplant recipients, we observed that pretreatment with PTX (20 mg/kg i.v.) in addition to m-PDS (2 g i.v.) reduced by half the amount of TNF released in the blood stream after the first injection of OKT3, while no further reduction of the low levels of IL-2 was found.

Animals↗
PubMed1991

Hyper IgE in stimulatory graft-versus-host disease: role of interleukin-4.

Intravenous injection of 2 x 10(8) DBA/2 spleen cells into adult intact (C57BL/6 x DBA/2) F1 mice results in a stimulatory graft-versus-host reaction (GVHR) linked to the recognition by donor CD4+ T cells of Ia alloantigens on host B cells. In the experiments presented here, we found that this GVHR is associated with a major increase in IgE serum levels which was already present 7 days after the cell transfer. At 6 weeks, mean IgE levels were more than 200-fold above the control values. Host B cells were responsible for the hypersecretion of IgE in stimulatory GVHR since it was also observed when the DBA/2 donor inoculum was depleted of B cells but not when the F1 recipients were irradiated. The induction of IgE secretion required donor CD4+ T cells as treatment of the donor inoculum with lytic anti-CD4 monoclonal antibody (MoAb) completely prevented the occurrence of the hyper IgE whereas depletion of CD8+ cells had no influence on this parameter. The role played by interleukin-4 (IL-4) in this model was analysed in vivo by the administration of the 11B11 anti-IL-4 rat MoAb (total dose 36 mg) during the first 12 days following induction of stimulatory GVHR by 8 x 10(7) DBA/2 spleen cells. This treatment completely prevented the development of hyper IgE whereas the administration of a control rat MoAb had no significant effect. We conclude that stimulatory GVHR in mice is associated with a major increase in serum IgE which is mediated by IL-4.

Animals↗
PubMed1991

Modulation of murine host-versus-graft disease by anti-CD3 monoclonal antibody.

BALB/c mice made tolerant to A/J alloantigens by neonatal injection of (A/J x BALB/c)F1 spleen cells develop a host-versus-graft (HVG) disease due to the activation of donor B cells by a subset of host alloreactive helper T cells. We have investigated the effects of a single neonatal injection of the 145-2C11 anti-mouse CD3 monoclonal antibody (MoAb) on the establishment of allotolerance and on the development of the immunopathological features of HVG disease. First, this treatment did not modify the specific anti-donor cytotoxic T lymphocyte (CTL) unresponsiveness or the persistence of circulating immunoglobulins bearing donor allotype. Second, the hyper IgE, the hyper IgG1 and the increased expression of Ia antigens on B cells found in untreated HVG mice were not observed after injection of the 145-2C11 MoAb. Likewise, treated mice displayed lower levels of anti-DNA IgG antibodies and less glomerular immune deposits as compared with untreated HVG mice. We conclude that the administration of the anti-CD3 MoAb did not interfere with the induction of allotolerance but exerts a pronounced inhibitory effect on the associated immunopathological syndrome.

Animals↗
PubMed1991

Increased expression of class II major histocompatibility complex molecules on B cells in rats susceptible or resistant to HgCl2-induced autoimmunity.

Administration of HgCl2 to the susceptible Brown-Norway (BN) rats induces an autoimmune disease characterized by a T-dependent polyclonal activation of B cells responsible for a dramatic increase in serum IgE concentration. The resistant Lewis (LEW) rats injected with HgCl2 do not exhibit such autoimmune manifestations. We show here that, upon HgCl2 injections, major histocompatibility complex (MHC) class II molecule expression is increased very early in lymph nodes and spleen B cells from both strains. So far, it is the earliest marker (day 3) of the effect of HgCl2 on the immune system. In both strains this enhancement is transient, but regulatory mechanisms are much more efficient in the resistant LEW strain than in the susceptible BN strain. In addition, we observed that MHC class II molecule expression on B cells differs according to the organ and the rat strain tested. All these findings are discussed in an attempt to underline the role of MHC class II molecule expression in the occurrence of mercury-induced autoimmunity.

Animals↗
PubMed1991

Overestimation of fetomaternal haemorrhage by the acid-elution technique in mothers with beta-thalassaemia minor.

In Rh-negative women, it is important to quantify the magnitude of an Rh-positive fetomaternal haemorrhage (FMH) so that sufficient Rh immune globulin (RhIg) can be administered early in the post-partum period to prevent alloimmunization. The standard post-partum dose of RhIg varies from 100 micrograms in the UK to 300 micrograms in North America. It is therefore important to identify all Rh-negative women who have had an FMH greater than 10 ml in the UK or greater than 30 ml in North America because an FMH greater than these amounts will affect the dose of RhIg that is administered. As acid-elution techniques can overestimate the magnitude of an FMH in the presence of an elevated maternal haemoglobin F level, we performed a prospective study to determine how often this occurred. Of 1,894 consecutive Rh-negative mothers who delivered Rh-positive infants, whose blood was screened for an FMH greater than 10 ml of fetal blood using an acid-elution procedure, 11 were found to have an FMH over 10 ml. In five of these 11 women, the volume of FMH was less than 10 ml using an alternative technique (rosette test) to assess the FMH size. Six of these women were found to have beta-thalassaemia minor on the basis of a low MCV, and high haemoglobin A2 and/or high haemoglobin F levels. In five of these the FMH was significantly overestimated by the acid-elution technique compared to the rosette technique. Therefore, in the presence of a maternal condition, which may result in an elevated haemoglobin F level, an FMH estimated to be over 10 ml in the UK or 30 ml in North America using an acid-elution procedure, should be confirmed by an alternative technique, which does not involve the estimation, directly or indirectly, of haemoglobin F.

Cell Count↗
PubMed1991

Obstetric complications with GDM. Effects of maternal weight.

Obstetric complications recorded prospectively were assessed retrospectively in 150 women with gestational diabetes mellitus (GDM) and 305 control subjects matched for age, parity, and ethnicity. Intensive diet therapy and self-monitoring of capillary blood glucose were used to obtain postprandial euglycemia; 22% of GDM subjects required insulin. GDM and control subjects were grouped by body mass index to detect any influence of maternal prepregnancy weight on outcome. Polyhydramnios, preterm labor, and pyelonephritis were not more frequent in GDM, but hypertension without proteinuria (7.3 vs. 3.3%) and preeclampsia (8 vs. 3.9%) were more frequent in GDM. The frequency of hypertensive complications in GDM was not totally attributable to being overweight. Abnormalities of labor, birth trauma, and fetal macrosomia were not more common in GDM; 6.7% of the infants of mothers with GDM weighed greater than 4200 g at birth compared with 3.6% of control infants (NS), and 10% were large for gestational age and sex compared with 6.6% of control infants (NS). Despite this, cesarean delivery was more common in GDM (35.3 vs. 22%, P less than 0.01), mostly due to significantly more cesarean births without labor.

Birth Weight↗
PubMed1991

[Nephrotoxicity of anti-CD3 monoclonal antibodies].

The OKT3 monoclonal antibody entails a transient acute nephrotoxicity when used either to prevent or to treat renal allograft rejection. This nephrotoxicity was reproduced experimentally in mice injected with 145-2C11, an anti-CD3 monoclonal antibody which shares many properties with OKT3. Both clinical and experimental data suggest that the renal lesions are due to the systemic release of cytokines that occurs prior to the immunosuppression. Pre-treatment with corticosteroids before the injection of anti-CD3 monoclonal antibody mitigates both the release of cytokines and the nephrotoxicity, in a dose-dependent manner. Experimental data suggest that very high doses of methylprednisolone (50 mg/kg) administered 2 to 3 hours before the monoclonal antibody are necessary to obtain an optimal protection.

Animals↗
PubMed1991

Flash lamp pumped dye laser for rosacea-associated telangiectasia and erythema.

The persistence of facial telangiectasis and erythema in patients with rosacea frequently presents a major cosmetic problem. It may also contribute to relapses of papular and pustular lesions. This study of 27 patients treated for their telangiectasia and erythema with a flash lamp pumped dye laser tuned at 585 nm is described. The laser gave good or excellent reduction of telangiectasia and erythema and overall appearance in 24 of the patients with between one and three treatments. In addition, papule and pustule activity was decreased in 59.2% of the patients, with those with the most severe pre-treatment activity having the most significant improvement. It is suggested that this is a useful additional form of treatment that may improve the telangiectasia and erythematous component of rosacea.

Adult↗
PubMed1991

A comparison of buccal nitroglycerin and sublingual nitroglycerin in the prophylaxis and treatment of exertional (situation-provoked) angina pectoris.

Suscard is a buccally administered formulation which provides rapid introduction of nitroglycerin directly into the systemic circulation and, by virtue of its sustained-release properties, may confer protection against anginal attacks for several hours. Its efficacy has been established in angina pectoris and more recently its usefulness has been extended to include the management of unstable angina and acute heart failure. Buccal nitroglycerin combines the possibilities of short-term treatment and more extended prophylaxis. In a multicentre double-blind study the efficacy of buccal nitroglycerin and sublingual nitroglycerin were compared in patients with proven chronic stable exercise-induced angina as regards anginal attacks and capacity for physical activity. The conclusion is that the two formulations of nitroglycerin have a comparable effect in the treatment of acute attacks of angina pectoris. Buccal nitroglycerin has many advantages when used prophylactically. This is documented by less frequent anginal attacks and a more prolonged duration of effect resulting in an increased physical activity.

Administration, Buccal↗