IMMUNOLOGICAL RECONSTITUTION IN A PATIENT WITH SEVERE COMBINED IMMUNE DEFICIENCY USING NON-SIBLING BONE MARROW DEPLETED OF T CELLS WITH HuLy-m1

Abstract An infant with severe immune deficiency received bone marrow from an HLA-A, -B, -DR matched, mixed leucocyte reaction non-reactive first cousin. The donor marrow was fractionated on a discontinuous Percoll gradient and before infusion was treated with the anti-human T lymphocyte antibody, HuLy-m1, and rabbit serum as a source of complement. Methotrexate was given during the following two weeks. A rise in the peripheral blood lymphocyte count, indicating engraftment, occurred six weeks after transplantation. There was no clinical evidence of graft versus host disease (GVHD). Engraftment has been sustained for one year and the patient is in normal health and has normal in vitro immunological function. In vitro treatment of human marrow with HuL-m1 allows stable engraftment and may be useful in attempting to diminish or prevent GVHD.     

IN-VIVO BIOACTIVITY OF GONADOTROPHIN SURGE ATTENUATING FACTOR (GnSAF)

Gonadotrophin surge attenuating factor (GnSAF) is a nonsteroidal ovarian factor responsible for the attenuation of the endogenous LH surge in superovulated cycles. To study the bioactivity of GnSAF in vivo, the pituitary response to exogenous GnRH was investigated in 13 normally ovulating women during spontaneous and FSH-treated cycles. GnRH experiments were performed at three stages of both spontaneous and FSH cycles, i.e. early (n = 8), mid- (n = 8) and late follicular phase (n = 8). LH response to GnRH increased significantly from the early to late follicular phase in the spontaneous cycles, while in the FSH cycles it decreased significantly in mid- and increased in late follicular phase. A marked attenuation of the LH response to GnRH during both the mid- and late follicular phase was seen in the FSH as compared to the corresponding spontaneous cycles. We conclude that in superovulated cycles small, growing follicles produce GnSAF.     

Urinary oestrogen levels and follicle ultrasound measurements in clomiphene induced cycles with an endogenous luteinizing hormone surge

Summary. Total oestrogen in urine and the ultrasonic size of the follicles were measured in relation to the onset of the endogenous luteinizing hormone (LH) surge (day 0) in 18 cycles induced with clomiphene citrate in an in-vitro fertilization programme. Oestrogen values in urine (μg/24 h) increased progressively during the late follicular phase up to the day of the onset of the surge. The mean maximum follicle diameter (22·3, SD 4·7 mm) estimated by ultrasound was measured on day 0. At the onset of the LH surge, the values of urinary total oestrogen showed a better relation with the total volume of the first three follicles in order estimated by ultrasound ( r = 0·71) than with the mean ultrasonic diameter of the leading follicle ( r = 0·56). A wide range of individual values for both urinary oestrogen and follicle size was found. In another group of 32 women treated with clomiphene for recovery of oocytes used for research purposes, a good correlation was found between the mean ultrasonic follicle diameter 16 h before the laparoscopy and the follicle diameter calculated from the fluid volume at aspiration ( r = 0·80). These results suggest that the decision when to give human chorionic gonadotrophin (hCG) in an in-vitro fertilization programme remains arbitrary in many individual cases. Apart from the oestrogen levels, the calculation of the size of all follicles, instead of only the leading one, may give further help in timing the hCG.     

Beneficial effect of atorvastatin on erythropoietin responsiveness in maintenance haemodialysis patients

Aim: To evaluate the effect of atorvastatin on erythropoietin responsiveness and whether this effect is mediated by C‐reactive protein (CRP) reduction in prevalent dyslipidemic, haemodialysis patients. Methods: We studied prospectively 33 stable, iron‐repleted haemodialysis patients with low‐density lipoprotein cholesterol (LDL) ≥2.58 mmol/L, who received 20 mg atorvastatin aiming to achieve the target of LDL <2.58 mmol/L, over a period of 9 months. Twenty‐five patients completed the study, 15 men, with mean age 66.1 ± 8.2 years. The duration of haemodialysis was 56.6 ± 63.1 months and 5/25 patients were diabetics. Total serum cholesterol, triglycerides, high‐density lipoprotein cholesterol, LDL, haemoglobin, albumin, intact parathyroid hormone, serum iron, ferritin, total iron binding capacity, CRP and weekly dose of erythropoietin/body weight/haemoglobin were analysed. Results: Twenty of the 25 patients (80%) achieved the goal of LDL <2.58 mmol/L. There was a significant decrease in total cholesterol (5.77 ± 0.88 to 4.16 ± 0.96 mmol/L, P < 0.001) and LDL (3.59 ± 0.77 to 1.94 ± 0.77 mmol/L, P < 0.001). Haemoglobin increased from 121 ± 11 to 126 ± 7 g/L (P < 0.05), while weekly dose of erythropoietin/body weight/haemoglobin decreased significantly from 8.34 ± 3.70 to 7.87 ± 3.11 IU/kg per haemoglobin (P < 0.05). CRP decreased not significantly from 7.0 ± 6.1 to 4.5 ± 2.2 mg/L. Conclusion: Dyslipidemia of haemodialysis patients was treated safely and effectively with atorvastatin, but a fifth of the patients failed to achieve the therapeutic target. Statin therapy resulted in a significant increase of haemoglobin levels and improvement of erythropoietin responsiveness without a significant reduction in CRP levels, suggesting that the beneficial effect of statins on erythropoietin responsiveness may be driven by a mechanism other than CRP reduction.     

VJ REARRANGEMENTS OF THE TCRγ LOCUS IN PERIPHERAL T-CELL LYMPHOMAS: ANALYSIS BY POLYMERASE CHAIN REACTION AND DENATURING GRADIENT GEL ELECTROPHORESIS

Using Southern blotting for the diagnosis of clonality in peripheral T-cell lymphomas (PTCLs), analysis of the T-cell receptor (TCR) γ gene rearrangement was shown to be more informative than that of the TCR β gene rearrangement. In order to amplify every VJγ rearrangement, a polymerase chain reaction (PCR) procedure using newly designed GC-clamp primers has been developed. All primers can be mixed in a single multiplex PCR. PCR products are analysed by denaturing gradient gel electrophoresis (DGGE), providing tumour-specific imprints inasmuch as the procedure characterizes N sequence polymorphism at the VJ junctions. In a series of 30 PTCL cases, the PCR procedure demonstrated 27 cases to be clonally rearranged and failed in three cases. PCR was more accurate than Southern blotting, showing 47 rearranged γ alleles, four of which were undetectable on the Southern blot. When lymphomas were studied at different sites and at relapse, the DGGE pattern remained unchanged. In PTCL, the proposed PCR is helpful for the diagnosis and staging of the disease and should improve the follow-up monitoring. The undetectability of clonal rearrangements in a few cases is discussed in the light of concepts of lymphomagenesis and T-cell differentiation.     

Carotid Sinus Hypersensitivity in Patients Undergoing Coronary Arteriography:

Carotid Sinus Hypersensitivity and Atherosclerosis. Introduction: The purpose of the present investigation was to study the precise relationship between carotid sinus hypersensitivity (CSH) and both the severity of carotid atherosclerosis and the extent of coronary artery disease in patients who were referred for evaluation for suspected ischemic heart disease.
Methods and Results: Duplex echocardiography and coronary angiography were used to assess carotid and coronary artery atherosclerosis in 130 consecutive patients. Carotid sinus stimulation was performed before coronary arteriography with simultaneous recordings of the ECG and aortic pressure. Coronary artery disease was present in 103 patients (79%). Thirty patients (23.08%) had one-vessel disease (1-VD), 31 (23.85%) had 2-VD, 29 (22.31%) had 3-VD, and 13 patients (10%) had left main coronary artery disease. Carotid artery atherosclerosis was present in 100 patients (76.92%) and carotid disease (diameter stenosis ≥ 50%) was present in 24 patients (18.46%). CSH was found in 33 patients (25%). The incidence of CSH was 9% in patients with carotid stenosis 1%-15%, 17% in patients with stenosis 16%-49%, 85% in patients with stenosis 50%-79%, and 100% in patients with stenosis ≥ 80%. The incidence of CSH was 11%, 17%, 23%, 34%, and 62% in patients with no VD, 1-VD, 2-VD, 3-VD, and left main coronary artery disease, respectively. Stepwise multiple logistic regression analysis revealed that carotid disease and left main coronary artery disease were the most significant determinants of CSH (P < 0.001 and P = 0.013, respectively).
Conclusion: The incidence of CSH increased in proportion to the severity of carotid and coronary atherosclerosis. These data provide evidence that CSH is closely related to severe carotid atherosclerosis or left main coronary artery disease in patients being evaluated for suspected ischemic heart disease.     

Bare Stent Implantation Through a Side Slot of Another Stent in a Bifurcation Lesion

A case of a patient with significant (≈ 90%) stenosis of the circumflex at its origin from the left main artery and of the first marginal branch, 20 mm after its origin from the circumflex, is described. The case was treated with implantation of two stents, one at the marginal and another at the circumflex through a side slot of the first stent.     

Coronary Angioplasty and Stent Placement by a Single Operator Without the Assistance of a Second Interventional Cardiologist and Nurse

Traditionally, not only the use of several devices, but plain angioplasty is performed by at least two interventional cardiologists and one specialized nurse. The aim of our study was to investigate the feasibility, effectiveness, and safety of angioplasty with stent implantation by a single operator, without the assistance of a second interventional cardiologist or a nurse. A total of 153 patients participated. Angioplasty with stent implantation was performed in 151 consecutive patients. The angioplasty was performed by a single cardiologist in the presence of a backup operator. Angioplasty and stent placement were successful in 151 of 153 cases (success rate = 98.7%). No death occurred and no case of acute stent occlusion was observed. In no case was the backup operator called for assistance. In conclusion, angioplasty with stent placement by a single operator without the assistance of a second interventional cardiologist or a specialized nurse was feasible, effective and safe . (J Interven Cardiol 2000;3-6)     

Impact of long‐term treatment with low‐dose inhaled corticosteroids on the bone mineral density of chronic obstructive pulmonary disease patients: Aggravating or beneficial?

Background and objective: Chronic obstructive pulmonary disease (COPD) is characterized by a low‐level systemic chronic inflammatory activity that is responsible for many of the disease's extra‐pulmonary manifestations, including osteoporosis and fragility fractures. These manifestations are also well‐documented side‐effects of oral corticosteroids. It was hypothesized that low levels of inhaled corticosteroids, due to their anti‐inflammatory properties and their low circulating levels, might preserve the bone mineral density (BMD) of COPD patients. Methods: Two hundred and fifty‐one male ex‐smokers with COPD patients grouped on the basis of their diffusion capacity value as predominantly bronchitic or predominantly emphysematic and 313 male controls with similar age and smoking history were enrolled in the study. Each of the patient's categories was randomized into two separate subgroups. Patients enrolled in subgroups B_neg(n = 91, 36%) and E_neg(n = 37, 14.7%) were treated with long‐acting β2‐agonists and anticholinergics, while subgroups B_ICS(n = 87, 35%) and E_ICS(n = 38, 15.1%) were additionally receiving low‐dose inhaled corticosteroids. Patients and controls were evaluated by clinical examination, lung function testing and BMD measurement every 6 months for 4 years. Results: According to the findings, emphysematic patients demonstrated an increased rate of BMD loss compared with bronchitic patients (P = 0.01). Furthermore, a reduction of the annual BMD loss in bronchitic patients on inhaled corticosteroids (P = 0.02) was measured, without a corresponding benefit for the emphysematics (P = not significant). Conclusions: Long‐term administration of low‐dose inhaled corticosteroids decelerates the annual BMD loss in bronchitic patients, possibly by reducing both pulmonary and systemic chronic inflammation caused by COPD.