[Health status and quality of life in ß-thalassemia adults in Marseille, France]. / État de santé et qualité de vie des patients ß-thalassémiques adultes à Marseille, France.

INTRODUCTION: The life expectancy of ß-thalassemia patients has increased over the last 20 years. In this study, we evaluated the current health status and quality of life of these patients managed in a reference center in Marseille. METHODS: This is a single-center, descriptive study conducted between June and August 2019 in patients over 18 years of age with ß-thalassemia major or intermedia. Clinical and paraclinical data were collected retrospectively and the SF-36 health survey questionnaire was proposed to each patient. RESULTS: 43 of 64 selected patients were included and divided into 2 groups: 35 patients with transfusion-dependent ß-thalassemia and 8 patients with non-transfusion-dependent ß-thalassemia. Liver iron overload is the most frequent complication, present in 80% of transfusion-dependent and 62.5% of non-transfusion-dependent patients. Cardiac iron overload is present only in the transfusion dependent ß-thalassemia group (20%). Hypogonadotropic hypogonadism remains the most common endocrine disorder (41.9%) followed by osteoporosis (37.2%). Among the 31 patients who completed the SF-36 questionnaire, physical and mental quality of life scores were lowered in transfusion dependent (respectively 42.7 and 46.8) as in non-transfusion-dependent patients (respectively 43.8 and 28.9). CONCLUSION: Despite an improvement in medical care, our patients with ß-thalassemia show an alteration in their quality of life that will need to be characterized in the entire French cohort.

Radiopathological correlations: masses, non-masslike enhancements and MRI-guided biopsy.

MRI-guided biopsy is a recent interventional breast technique. Validating the procedure poses a new problem because the signal targeted is created by the injection of a paramagnetic contrast agent and is thus transitory. In the first instance, the procedure is validated by the radiologist, who checks that targeting is accurate and inserts a clip at the end of the procedure, and secondly by analysis of the histopathological results, which should be representative of the lesion. The pathologist needs to know the nature of the image, i.e. whether it is of mass or non-masslike enhancement, and its BI-RADS classification. The objective is that the image and the pathological result should concur. If the result is non-specific and benign, a follow-up MRI is required six months later.

Rapid onset of diabetic nephropathy in three renal allografts despite normoglycemia.

Diabetes mellitus is the leading cause of end-stage renal disease in the United States. Renal transplantation is currently the treatment of choice for diabetic patients on renal replacement therapy. Current immunosuppression includes medications that are diabetogenic and place nondiabetic transplant recipients at risk for developing posttransplant diabetes mellitus and subsequent de novo diabetic nephropathy in the allograft. Here we present three patients who underwent a deceased donor renal transplant and developed posttransplant diabetes mellitus. In all three patients despite excellent glycemic control (HbA(1c) < or = 7%) and average tacrolimus trough levels less than 10 ng/ml, clinical and histologic de novo diabetic nephropathy developed within 2 years of the diagnosis of posttransplant diabetes mellitus. This is in contrast to other reported data in which the average time to onset of de novo diabetic nephropathy was approximately 10 years. Additionally, in other case series the average HbA(1c) was 8.4% in patients who developed diabetic nephropathy. It is possible that the metabolic milieu of transplant recipients warrants tighter glycemic control. The allograft is also susceptible to hyperfiltration injury which may accelerate the diabetic lesions even at normal glucose levels. Further studies are warranted to determine the optimum glycemic control in posttransplant diabetes mellitus.

Primary mediastinal anaplastic alk-1-positive large-cell lymphoma of T/NK-cell type expressing CD20.

We describe an unusual case of ALK-1-positive primary mediastinal lymphoma with the morphology of an anaplastic large-cell lymphoma (ALCL) of T/NK cell type but expressing CD20. This tumour had T/NK morphology and immunophenotype, as demonstrated by its expression of CD30, EMA, ALK-1, CD7 and TiA-1 and the lack of expression of B-cell markers other than CD20. The significance of such a co-expression of a B cell-associated antigen in a case of ALCL of T/NK cell type is discussed.

Non-traditional cardiovascular disease risk factors in end-stage renal disease: oxidate stress and hyperhomocysteinemia.

Studies in experimental animals have shown that oxidative stress and hyperhomocyst(e)inemia culminate in abnormal vascular and endothelial regulation, functional nitric oxide deficiency, vascular hypertrophy, and atherosclerosis. Oxidative stress is accompanied by increased advanced glycation endproducts and oxidized low density lipoproteins. Studies of patients with end-stage renal disease provide extensive indirect, evidence of increased oxidative stress and more than ninety percent are hyperhomocyt(e)inemic. Presently, only uncontrolled or observational studies are available to assess the effects of anti-oxidant therapy for oxidative stress or folate therapy for hyperhomocyst(e)inemia in these patients. Promising developments include the reports of beneficial effects of a vitamin E coated dialyzer, and the reduction in homocyst(e)ine levels in patients with end-stage renal disease given an intravenous folate metabolite. However, there is presently no therapy available to reverse fully oxidative stress or hyperhomocyst(e)inemia. Therefore, the causative role of these nontraditional risk factors of cardiovascular disease remains untested.

Maintenance immunosuppression: new agents and persistent dilemmas.

Since the approval of cyclosporine in 1983, only 3 drugs, mycophenolate mofetil, tacrolimus, and sirolimus, have been approved for maintenance immunosuppression in renal transplant recipients. All 3 agents decrease the incidence of early acute allograft rejection. An increase in intermediate and long-term graft survival has not been shown. However, survival data from these clinical trials should be interpreted with caution because the studies were not designed for this purpose. All 3 drugs have significant, albeit different, safety profiles. It remains to be seen whether, the lower incidence of hypertension and hyperlipidemia seen in tacrolimus-treated patients will reduce the incidence and severity of the cardiovascular disease experienced by renal transplant recipients. Sirolimus causes severe hyperlipidemia, and the long-term consequences both on the pathogenesis of cardiovascular disease and on lipid-associated renal injury have yet to be determined. Tacrolimus and mycophenolate mofetil appear to increase graft survival in pancreas-kidney recipients but their efficacy in another high-risk group, African-American recipients, has not yet been clearly shown. However, the trend toward improved graft survival in African-American recipients treated with tacrolimus is encouraging. Steroid-withdrawal remains a goal in the posttransplant period. The available data from steroid-withdrawal and steroid-avoidance clinical trials are mixed. Steroid withdrawal can be achieved in about 50% of patients on a cyclosporine-based immunosuppression regimen. Steroid-withdrawal under coverage of tacrolimus, mycophenolate mofetil or Neoral (Novartis Pharmaceuticals, East Hanover, NJ) may be more successful than that achieved in patients receiving Sandimmune (Novartis Pharmaceuticals). Further studies are needed in this area.

Determination of reduced and oxidized homocysteine and related thiols in plasma by thiol-specific pre-column derivatization and capillary electrophoresis with laser-induced fluorescence detection.

A new sensitive and rapid capillary electrophoresis (CE) assay for measuring reduced and oxidized thiols in human plasma has been developed. To prevent oxidation of the thiols, whole blood was immediately centrifuged after collection and the plasma proteins were precipitated with perchloric acid. The reduced thiols in the supernatant were derivatized quantitatively at 25 degrees C, pH 7.5 with a fluorescent reagent, fluorescein-5-maleimide (FM). The total plasma concentration of thiols, including the fraction coupled to proteins, was assayed after an initial reduction of the disulfide linkage in plasma with dithiothreitol. The separation of FM-thiols was performed in an acetonitrile/10 mM sodium phosphate-50 mM SDS buffer [25:75 (v/v); pH 7.0] using a fused-silica capillary (57 cm x 75 microm I.D.) at 45 degrees C. A 3-mW argon-ion laser (lambda(ex) 488 nm/lambda(em) 520 nm) was employed for FM-thiol detection. With the electric field of 530 V/cm, the time needed for the separation of FM-homocysteine, FM-glutathione and FM-N-acetylcysteine was less than 8 min. The lower limit of detection was 3 microM for the total thiols and 10 nM for the reduced thiols. The method was applied to, the determination of homocysteine levels in plasma from patients with end-stage renal disease.

The level of lipopolysaccharide-binding protein is significantly increased in plasma in patients with the systemic inflammatory response syndrome.

Currently, there is no way to predict with a high degree of sensitivity and specificity which patients are likely to develop systemic inflammatory response syndrome (SIRS) following systemic infection, trauma, organ rejection, or blood loss. The level of human lipopolysaccharide-binding protein (LBP) was determined in the plasma of 22 patients with a clinical diagnosis of early SIRS. Twenty-nine plasma samples from healthy volunteers were used as controls. The mean level of LBP in the plasma of healthy volunteers was 7.7 micrograms/ml (standard deviation, 6.2 micrograms/ml). Twenty-one of 22 patients (95%) with SIRS had an LBP level on admission at least 2 standard deviations above the mean LBP level for a healthy volunteer control group (range, 4.9 to 114.2 micrograms/ml; mean, 36.6 micrograms/ml; standard deviation, 22.2 micrograms/ml; P < 0.0001). The level of LBP in the plasma of the majority of patients with early SIRS is significantly increased compared to that in healthy controls. The sensitivity, specificity, and predictive value of elevated plasma LBP levels in patients with SIRS remain to be determined.

Successful and unsuccessful approaches to imaging carcinoids: comparison of a radiolabelled tryptophan hydroxylase inhibitor with a tracer of biogenic amine uptake and storage, and a somatostatin analogue.

A mouse mastocytoma model was used to determine the biodistribution and tumour uptake of four radiopharmaceuticals developed to target the serotonin synthetic pathway in carcinoid tumours. Three of the compounds were competitive inhibitors of the rate-limiting enzyme of serotonin synthesis, tryptophan hydroxylase. Radiolabelled iodo-dL-phenylalanine (iodine-131 PIPA) was found to have the highest uptake and tumour-to-liver ratio. Four patients with known carcinoid tumours were then injected with 0.5 mCi 131I-PIPA and imaged at 1, 4, 24 and 48 h post-injection. The radiopharmaceutical, however, failed to localize in the known tumour sites. This result was in contrast to the authors experience of 131I- and 123I-MIBG imaging of carcinoid tumours. Seven patients with known metastatic carcinoid tumours, two patients with symptoms of recurrence following tumour resection, one patient with completely resected disease, and two patients with a flushing syndrome of uncertain aetiology were studied with 131I-MIBG. Three of the seven patients with known metastatic disease had positive 131I-MIBG scans. Both patients with clinical evidence of recurrent disease had negative scans, as did the patient who was considered to have had complete resection of her primary tumour. The two patients with idiopathic flushing syndrome also had negative scans. Among seven patients imaged with 123I-MIBG there were four true-negative scans and one false-negative, the latter in a patient with biochemical and CT evidence of recurrence. In a seventh patient with distant metastases there was variable uptake in some of the lesions. Four patients were studied with indium-111 pentetreotide . Two patients with metastatic carcinoid disease had positive scans, although hepatic metastases were not seen in one. Another two with idiopathic flushing syndrome had normal studies. The literature suggests that up 50% of carcinoid tumour cases are detected with 131I-MIBG, compared to a sensitivity of 87% reported with somatostatin receptor imaging using 111In-pentetreotide. The experience with 123I-MIBG is much less extensive. The mechanisms of carcinoid tumour localization for each of the three classes of radiotracers are discussed and contrasted to their varying sensitivities. The relative success of 131I-MIBG and 111In-pentetreotide relative to 131I-PIPA may be related to the fact that 131I-MIBG is actively taken up and stored by the enterochromaffin cells of the tumours and 111In-pentetreotide binds to cell surface receptors, whereas 131I-PIPA binds to tryptophan hydroxylase, which may be present in quantities too small to permit tumours to be imaged.

Plasma substance-P in neuroendocrine tumors and idiopathic flushing: the value of pentagastrin stimulation tests and the effects of somatostatin analog.

We examined the role of the potent vasoactive kinin substance-P (SP) in flushing derived from various causes. SP was measured in plasma after acetone/ether extraction using an antiserum directed at the carboxy-terminal 5-11 amino acid region of undecapeptide SP. The antiserum had less than 1% cross-reaction with the other neurokinins, neurokinin-A and neuropeptide-K, that derive from the beta-preprotachykinin gene and share carboxy-terminal residues. Basal and pentagastrin-stimulated SP levels were measured in 22 healthy controls, 11 patients with histologically proven carcinoid tumors, 8 patients with tumors other than carcinoid, and 7 patients with idiopathic flushing (IF). Basal SP levels were less than 10 pg/mL in normal subjects. All patients with midgut carcinoid tumors had SP levels greater than 25 pg/mL, as did 7 of 8 patients with noncarcinoid tumors and 5 of 7 patients with IF. Using 50 pg/mL as the cutoff point, the sensitivity was 63% for detection of a tumor, and 100% of nontumor patients were excluded. Pentagastrin administration uniformly induced flushing and caused a rise in SP levels greater than 150 pg/mL in 5 of 10 patients with carcinoid tumors, 3 of 8 with noncarcinoid tumors, and 0 of 7 with IF, i.e. a SP rise of more than 100 pg/mL suggests a tumor. Administration of somatostatin (150 micrograms) 0.5 h before the pentagastrin abolished flushing in all carcinoid patients and reduced SP levels, but not into the normal range. Long term treatment with SMS significantly reduced flushing and lowered SP levels, but did not restore these to normal. We conclude that 90% of patients with carcinoid/noncarcinoid tumor have raised COOH-terminal SP levels. A basal level above 50 pg/mL or a pentagastrin-stimulated rise of more than 100 pg/mL distinguishes carcinoid from IF. The dissociation between SP concentrations and flushing suggests that SP may not be the only kinin involved in the flushing associated with carcinoid tumors.

Corrected Q-T interval prolongation as diagnostic tool for assessment of cardiac autonomic neuropathy in diabetes mellitus.

A simple method for evaluating alterations in cardiac sympathetic innervation may be measurement of the Q-T interval. Seventy-three diabetic patients (46 insulin dependent and 27 non-insulin dependent) were separated into four groups based on the presence and degree of cardiac autonomic neuropathy (CAN) with noninvasive cardiovascular reflexes and blood pressure responses. None of the patients had evidence of ischemic heart disease, kidney disease, or the idiopathic long Q-T-interval syndrome. The corrected Q-T interval (Q-Tc) was determined at rest with Bazett's formula. As a group, diabetic patients with greater than or equal to 2 abnormalities of cardiac autonomic function had a longer Q-Tc interval than those with no evidence of CAN. Diabetic patients with greater than or equal to 1 abnormality had a prolonged Q-Tc interval compared with a control group of 96 healthy nondiabetic subjects (mean +/- SD 397 +/- 18). The frequency of prolonged (greater than 433 ms, normal mean + 2SD) resting Q-Tc intervals increased with the increasing number of abnormalities (0, 1, 2, greater than or equal to 3): 11, 25, 41, and 75%, respectively. Twenty-three of 25 (92%) patients with a Q-Tc greater than 433 ms had evidence of CAN. However, 57% (31 of 54) of the patients with CAN had a normal Q-Tc interval. These data provide further evidence of a relationship between the presence and severity of CAN and degree of Q-Tc interval prolongation.(ABSTRACT TRUNCATED AT 250 WORDS)

Demonstration by iodine-131-hippurate renography of a marked sensitivity of some transplanted kidneys to volume contraction.

Incidental observations made in a canine renal transplant model in which both native and transplanted kidneys were present revealed that abnormal I-131-iodohippurate renograms were derived from some of the transplanted kidneys in the presence of mild dehydration. In these cases, the renogram normalized with fluid administration. In contrast, the renograms derived from the native kidneys were unaffected by the mild dehydration of the animals. These findings demonstrate a greater sensitivity to dehydration of some transplanted kidneys when compared to normal kidneys.

Syphilis--an appraisal of the Groote Schuur Hospital antenatal screening programme.

Syphilis is a major public health problem in pregnant women. Since congenital syphilis is preventable, an adequate screening programme is an essential facet of antenatal care. At Groote Schuur Hospital, Cape Town, the Venereal Disease Research Laboratory and Treponema, pallidum haemagglutination tests are employed for antenatal screening. A survey of the current literature on serological testing for syphilis does not reveal clear guidelines for an optimal antenatal screening programme. The high prevalence of syphilis in pregnant women is confirmed by this study, which shows the current programme to be very effective in excluding women without disease.

[Septo-optic dysplasia with antidiuretic hormone deficiency and central adrenocortical insufficiency. Three cases report in infants (author's transl)]. / La dysplasie septo-optique avec déficit en hormone antidiurétique et insuffisance surrénale centrale. Trois nouvelles observations chez le nourrisson.

Three cases of septo-optic dysplasia are related in infants. A neurogenic diabetes insipidus and an central adrenocortical insufficiency is proved. An growth hormone deficiency is founded in one case. The other anterior pituitary functions are normal. The pneumo-encephalography with congenital absence of septum lucidum and the ophtalmologic anomalies are typical. The treatment is envisaged. In one case an autopsy sustains the radiologic aspect.