First experience of the use of a generic of plerixafor in peripheral blood stem cell mobilization in multiple myeloma and lymphoma patients.

Mobilization failure in patients is a major therapeutic concern which makes subsequent ASCT impossible. A new growth factor called Plerixafor (Mozobil®) developed by the pharmaceutical industry (Sanofi-aventis, France), is a chemoreceptor antagonist, CXCR4 type, which disrupts the interaction of SDFI and CXCR4, thereby enhancing the effect of G-CSF mobilization and is especially indicated for mobilization failure. Currently, there is a generic of plerixafor developed by the pharmaceutical industry (Hetero Drugs Ltd, India). The brand name of this medicine is Mozifor®. The objective of this study was to evaluate if generic plerixafor has the same efficacy and safety as originator plerixafor when used with G-CSF in the mobilization of PBSCs for autologous ASCT in multiple myeloma (MM) and lymphoma failure patients. The 32 patients received plerixafor were divided in two groups. The first group concerns the 11 consecutive patients prospectively received generic plerixafor (Mozifor®) in the period between January to July 2020. These were compared with a retrospective control cohort (second group n = 21) who had been treated between 2009 and 2019 with originator plerixafor (Mozobil®). For the Mozifor® group, the mean CD34+ was 4.54x106/kg(1.56-6.79), the median time to achieve an absolute neutrophil count >0.5 G/L was 13 days (range: 8-21). The median time to self-sustained platelet count >20 G/L was 15 days (range: 8-24). For the Mozobil® group, the mean CD34+ was 3.1x106/kg (0.56-8.91) (p=0.86), the median time to achieve an absolute neutrophil count >0.5 G/L was 10 days (range 7-23). The median time to self-sustained platelet count >20 G/L was 13 days (range: 7-29). Our study showed that the generic of plerixafor was practically identical to that of the originator (Mozobil®) with no significant difference (p = 0.52). This study demonstrates the safety and feasibility of mobilization PBSC with generic plerixafor in ASCT in MM and lymphoma. Although these outcomes are encouraging, prospective comparison with other traditional auto-HCT regimens used for patients with MM and lymphoma is warranted.

Arterial stiffness is elevated in normotensive type 2 diabetic patients with peripheral neuropathy.

BACKGROUND AND AIMS: Arterial stiffness, a measure of macrovascular damage predictive of poor cardio-vascular outcomes, is strongly related to age and hypertension (HT). In diabetic patients peripheral neuropathy (PN) has been found to be associated with increased arterial stiffness, which might be due to the concomitant presence of HT. The aim of this study was to examine in type-2 diabetic patients, the relationship between arterial stiffness and presence or absence of PN and HT separately. METHODS AND RESULTS: Arterial stiffness was measured with the gold standard carotid-femoral pulse wave velocity (PWV) in 447 type-2 diabetic subjects of whom 66% were hypertensive, 53% had PN, and 40% had both. Patients with PN were older, more often hypertensive and had higher PWV than those free of PN. Patients were separated according to the presence or absence of PN and HT. PWV values above the 90th percentile age- and blood pressure-adjusted reference range (PWV+) were different across these groups (p < 0.005) with the following respective prevalences: 27.2%, 53.4%, 33.3% and 30.6%. Only PWV+ was significantly associated with PN and hypertension in the interaction analysis. CONCLUSION: Well controlled hypertensive patients did not have elevated arterial stiffness compared to normotensive patients. This might be due to anti-hypertensive treatment although our study design does not allow us to confirm it. A strong association between PN and arterial stiffness was only present in normotensive patients, suggesting that normotensive type 2 diabetic patients with PN and elevated arterial stiffness should be carefully managed to prevent future macrovascular complications.

A simplified method for autologous stem cell transplantation in multiple myeloma.

BACKGROUND AND OBJECTIVES: We evaluated the efficacy and safety of non-cryopreserved storage of autologous hematopoietic stem cells with no post-transplant granulocyte colony-stimulating factor (G-CSF) support in adult patients undergoing autologous stem cell transplantation (ASCT) for multiple myeloma (MM). DESIGN AND SETTING: Retrospective review of patients undergoing ASCT from May 2009 to July 2011. PATIENTS AND METHODS: Autologous stem cell were mobilized using G-CSF. Leukapheresis to harvest stem cells was performed on day -2 and -1. The grafts were kept in a conventional blood bank refrigerator at 4°C until reinfusion on day 0. The conditioning regimen consisted of melphalan 200 mg/m2 in all patients. The post-chemotherapy myeloablative phase was managed without growth factors. RESULTS: Between May 2009 to July 2011, 54 adults with MM were treated in our center in Oran. The median age at ASCT was 55 years (range, 35-65). There were 37 males and 17 females. The median harvested CD34+ cell count was 3.60X106/kg (range, 1.90 to 10.52). All patients had neutrophil engraftment on the median of day 10 (range, 6-17) and platelet transfusion independence on the median of day 13 (range 9-24). In the 47 evaluable patients the median post-transplant overall survival had not been reached; the estimated overall survival at 30 months was 93.8% (0.05%) , and the estimated disease-free survival at 27 months was 93.6% (0.05%). CONCLUSION: High-dose chemotherapy and ASCT using non-cryopreserved stem cells and no G-CSF support is safe and feasible in the treatment of MM under our work conditions in developing countries.

[Computerized temperature monitoring of the vaccine cold chain in a tropical climate, Chad]. / Surveillance informatisée de la chaîne du froid en milieu tropical (Tchad).

Because new EPI liquid vaccines are highly sensitive to freezing and overheating, close monitoring of the cold chain is mandatory. The new Testostore 171-1 electronic thermometer (Testo) provides more reliable monitoring of cold chain temperature than freezer indicators, vaccine vial monitors and color strips that only indicate if vaccines are out-of-date. The Testo thermometer uses a probe placed in refrigeration units to periodically measure and store temperature readings. Temperature curves are displayed via a USB connection on a laptop computer running special software (Comfort software light). Testo temperature data can easily be communicated to all management levels by e-mail. The first experience using the Testo system in Africa involved regional EPI supervision in Mondou, Logone Occidental, Chad. After a preliminary mission in Chad in 2006 showed the feasibility of using this method to manage the national cold chain at all levels, a nurse was appointed as EPI supervisor and given a refresher course in Chad's capital Ndjamena in March 2009. In April-May 2009, the supervisor was sent back to the Logone Occidental Region to monitor, by himself, refrigeration units making up the regional and district cold chain for vaccine storage in five health centers (rural and urban). Temperature curve readings were performed on site in the presence of the medical staff and results were compared to those recorded twice a day on conventional temperature charts using lamellar thermometers installed in refrigerators doors. Testo curves showed that liquid vaccine storage temperatures fell below freezing too frequently and that temperatures readings of door thermometers were often inaccurate. Testo readings also detected power outages in refrigeration units used in urban settings and flame extinctions in kerosene lamp refrigerators due to refrigerator breakdown or windy weather conditions before the rainy season. The main advantage of this monitoring method is to provide reliable data as a basis not only for detection of possible freezing of liquid vaccines but also for discussion of cold chain management and improvement with medical staff.

How we assess adequacy of fine-needle aspiration materials intended for flow cytometric analysis.

Many articles have been published on the subject of FNAFNA, highlighting the usefulness of flow cytometry in the diagnosis and classification of lymphomas. But occasionally, flow cytometric evaluation fails to detect an abnormal population in a FNAFNA specimen involved by lymphoid neoplasm. Sampling errors (poor viability, peripheral blood contamination and hypocellular specimens) are the major reasons of this failure. In our laboratory we use a simple, fast and cost-effective approach to assess adequacy of FNAFNA materials and in this paper, we describe this procedure with giving some examples of interpretations of our results.

[Myofibroma of the mandibule: a case report]. / Myofibrome de la mandibule: à propos d'un cas.

INTRODUCTION: Myofibromatosis is a rare tumor. Two forms are described, solitary and multicentric, the solitary type is more common and is localized mainly on the head and the neck, mandible involvement is rare. The recent observation of a patient with a myofibrome of the mandible has given the opportunity to conduct an analysis and review of the literature of this disease rarely encountered. MATERIALS AND METHODS: We report a case illustrating solitary myofibroma of the mandible in a 16 year old man. RESULTS: The histological diagnosis was done on the identification of the spindle-shaped tumoral proliferation and the positive expression of the anti-vimentine, anti-smooth, muscle actin anti desmin. The treatment was surgical. DISCUSSION: myofibromatosis often presents as a painless, well-circumscribed, solid nodule. Imagery is very useful to assess lesion extension and for the therapeutic followup. The diagnosis is made on anatomopathological findings and immunohistochemical assessment. The treatment of the solitary myofibromatosis is primarily surgical and its prognosis is excellent contrary to the multicentric form.

[The fight against rabies in Africa: from recognition to action]. / Lutte contre la rage en Afrique: du constat à l'action.

As a follow-up to the first AfroREB (Africa Rabies Expert Bureau) meeting, held in Grand-Bassam (Côte-d'Ivoire) in March 2008, African rabies experts of the Afro-REB network met a second time to complete the evaluation of the rabies situation in Africa and define specific action plans. About forty French speaking rabies specialists from Northern, Western and Central Africa and Madagascar met in Dakar (Senegal), from March 16th to 19th, 2009. With the participation of delegates from Tunisia, who joined the AfroREB network this year, 15 French speaking African countries were represented. Experts from the Institut Pasteur in Paris, the Alliance for Rabies Control, and the Southern and Eastern African Rabies Group (SEARG, a network of rabies experts from 19 English speaking Southern and Eastern African countries) were in attendance, to participate in the discussion and share their experiences. AfroREB members documented 146 known human rabies cases in all represented countries combined for 2008, for a total population of 209.3 million, or an incidence of 0.07 cases per 100,000 people. Even admitting that the experts do not have access to all reported cases, this is far from the WHO estimation of 2 rabies deaths per 100,000 people in urban areas and 3.6 per 100,000 in rural Africa. It was unanimously agreed that the priority is to break the vicious cycle of indifference and lack of information which is the main barrier to human rabies prevention.

[Two cases of Lactobacillus rhamnosus infection and pancreatitis]. / Infection àLactobacillus rhamnosus et pancréatite:deux cas.

Lactobacilli rhamnosus infections are rare and occur in patients with severe conditions causing immunosuppression and/or in those who have received intense antibiotic treatment such as with teicoplanin and vancomycin. We report two cases which occurred within a period of 48 hours, during regression of pancreatitis in two women aged 35 and 70 years old, hospitalized in the same department. Several criteria pointed towards two independent infections but the rarity and chronology of the appearance of these infections raised the question of possible cross-contamination. Lactobacillus rhamnosus was isolated in intra-abdominal samples from both patients, and in blood cultures from one of them. Specimens were monomicrobial. The description of these observations shows the limits of molecular biology for identifying the Lactobacillus rhamnosus strain: it was not possible to determine whether a single clone or two different clones were involved.

[Microalbuminuria, a marker of artery rigidity and cardiac dysfunction]. / La microalbuminurie, un marqueur de rigidité artérielle de dysfonctionnement cardiaque.

INTRODUCTION: Microalbuminuria is considered as a marker of endothelial dysfunction and is associated with an increase in cardiovascular risk. The aim of this study was to evaluate this parameter as a potential marker of artery rigidity and left ventricle (LV) function. SUBJECTS AND METHODS: We included 375 subjects referred to a health assessment center. They were 228 men and 147 women aged in means of 52.7 and 53.1 years, respectively. Among this population, 57 had type 2 diabetes, 28 of them with hypertension, 65 were hypertensive but free of diabetes, and 39 were free of diabetes but exhibited a metabolic syndrome (NCEP-ATP III). Urinary albumin excretion rate (UAER) was determined. Artery rigidity was evaluated by pulse pressure of the brachial artery (plethysmographic method), pulse pressure of the radial artery and aorta and pulse wave velocity (PWV) measured by aplanation tonometry (SphygmoCor). LV afterload was appreciated by LV telesystolic pressure and coronary perfusion by the diastolic area/systolic area ratio for aortic pressure curve (Buckberg index). RESULTS: UAER correlated with PWV in the overall population (p<0.0001) and in the diabetic sub-group (p<0.001). In the overall population UAER correlated with LV telesystolic pressure (p=0.006) but not with Buckberg index. In the overall population and the diabetic subgroup, the artery rigidity indexes correlated strongly with LV telesystolic pressure, and radial and aortic pulse pressure correlated negatively with Buckberg index. CONCLUSION: These data suggest that 1) microalbuminuria may be considered as a marker of artery rigidity, in line with experimental data which indicate the deleterious role of endothelial dysfunction on artery compliance; 2) artery rigidity is a potent determinant of LV afterload and coronary perfusion, in particular in diabetic patients.

[Role of vagosympathetic balance in obesity-induced hypertension]. / Rôle de la balance vagosympathique dans l'hypertension associée à l'obésité.

A sympathetic hyperactivity is a common feature in hypertension, type 2 diabetes (T2D), ageing and obesity-induced hypertension. This increase in sympathetic activity may lead to an elevation of arterial rigidity. By contrast, cardiac parasympathetic impairment is observed in these pathologies. Recently we showed in a model of rats with massive obesity (ventromedial hypothalamic lesions) that an enhanced vagal activity may be protective against hypertension. The aim of the present study was to evaluate the influence of an increase in sympathetic activity and a change in vagal activity on arterial rigidity and hypertension in T2D patients. Fourteen hypertensive T2D patients aged 54 +/- 2 years were compared to 22 elderly normotensive subjects (75 +/- 1 years: 11 controls and 11 T2D) and 34 middle aged normotensive subjects (43 +/- 1 years; 17 controls and 17 T2D). Cardiovascular vagosympathetic activity was investigated by spectral analysis of heart rate (HR) and blood pressure (BP) (Finapres) during 6 min at a controlled breathing rate (12 cycles/min). BP and the low frequencies of systolic BP (LF-SBP) were significantly (p<0.01) higher in hypertensive T2D and elderly patients. Pulse pressure (PP) and the high frequencies of HR (HF-HR) were lower in hypertensive T2D patients. PP was positively correlated to LF-SBP (r=0.58; p=0.03) only in hypertensive T2D patients. Diastolic BP was negatively correlated to HF-HR in elderly control subjects (r=-0.63; p=0.03) but not in hypertensive T2D patients. The present results suggest that: sympathetic nervous system activity is enhanced in subjects over 70 years without any aggravating effect of T2D and in middle-aged hypertensive patients with type 2 diabetes; the increase in pulse pressure, an index of arterial rigidity, in elderly subjects may result from sympathetic override; the decrease in the cardiac sympathovagal balance, mainly due to a high vagal activity, may be protective against the occurrence of hypertension in patients with type 2 diabetes.

[Amyloidosis and pleural calcification]. / Amylose et calcinose pleurale.

INTRODUCTION: Pulmonary diseases during the course of generalised amyloidosis are principally represented by tracheobronchial involvement and diffuse parenchymal localizations. CASE REPORT: The authors report the case of a 66-year-old woman presenting with pleural amyloidosis in the context of generalised amyloidosis. Thoracoscopy performed in the investigation of recurrent transudative pleural effusions found evidence of an inflamed parietal pleura with areas of calcification. Pleural biopsies confirmed amyloid infiltration pleural ossification. Talc pleurodesis was performed. CONCLUSIONS: The authors' conclusion is that, meeting an unexplained pleural effusion even transudative during the course of a generalised amyloidosis, the thoracoscopy is the diagnosis key test as it allows moreover a pleural pleurodesis to be performed.

[Relationship between vasosympathetic activity and insulin resistance in normotensive and mildly hypertensive obese patients]. / Relations entre activité vagosympathique et insulinorésistance chez les obèses normotendus et modérément hypertendus.

Several studies have well demonstrated that obesity is associated with changes in cardiovascular vagosympathetic activity. The aim of the present work was to evaluate this activity in normotensive and in mildly hypertensive obese patients, and to correlate this activity with clinical and biological indexes of insulin resistance. Heart rate (HR) and systolic blood pressure (sBP) were examined by spectral analysis in 70 normotensive obese patients (group 1), 32 mildly hypertensive obese patients (group 2), and 21 controls. The high frequency peak of HR variations at a controlled breathing rate (vagal activity) was significantly reduced in both groups (p < 0.001). The mid frequency peak of sBP in the standing position (sympathetic activity) was similar in both groups and in the control group. In groups 1 and 2, the high frequency peak correlated negatively with age (p = 0.005 and 0.034 respectively). In group 1, the mid frequency peak correlated positively with fat mass, fasting plasma insulin and triglyceride levels, and insulin resistance index (p < or = 0.03). In group 2, the mid frequency peak correlated positively with fasting insulin and insulin resistance index (p = 0.006 and 0.007 respectively). This study shows that, in obese patients: 1. cardiac vagal activity is reduced in normotensive and mildly hypertensive subjects; 2. vascular sympathetic activity is unchanged in means but may be increased as a consequence of adiposity, hyperinsulinemia and insulin resistance, and this increase is likely to be involved in the increase of blood pressure.

[Arterial rigidity and cardiovascular vagosympathetic activity in normotensive and hypertensive obese patients and type 2 diabetics]. / Rigidité artérielle et activité vagosympathique cardiovasculaire chez les obèses et les diabétiques de type 2 normotendus et hypertendus.

An increase in arterial rigidity is associated with a poor cardiovascular prognosis. Several studies have suggested that an increase in sympathetic activity may be involved in essential hypertension. We have recently shown that vagal control of heart rate (HR) variations during standardised tests is altered in normotensive obese and diabetic patients. The aim of the present study was to compare cardiovascular vagosympathetic activity in obese and type 2 diabetic patients, either normotensive or hypertensive, and to investigate the relationship between pulse pressure (an index of arterial rigidity) and sympathetic activity in this population. Seventy normotensive obese and 32 mildly hypertensive obese patients, 18 normotensive type 2 diabetic patients and 14 mildly hypertensive type 2 diabetic patients were compared with 21 control subjects. Finapres studied HR and blood pressure variations. In the four groups, during a 6-min period at a controlled breathing rate, the high frequency peak of HR variations was significantly reduced (p < 0.001). The mid-frequency peak of systolic BP variations in the standing position, which depends on sympathetic activity, did not differ significantly between the four groups and control subjects. In obese and diabetic hypertensive patients, this peak correlated significantly with pulse pressure measured in the lying position (r = 0.379; p = 0.043 and r = 0.81; p < 0.0001, respectively). This study 1, confirms that vagal control of HR variations is reduced to a similar extent in obese and diabetic patients; and 2, suggests that cardiovascular sympathetic activity is relatively increased in these patients without significant difference between normotensive and hypertensive patients, but interestingly that the increase in arterial rigidity is associated with a higher sympathetic activity.

Impact of pulse pressure on degree of cardiac hypertrophy in patients with chronic uraemia.

OBJECTIVE: To evaluate the degree of cardiac hypertrophy in patients with end-stage renal disease (ESRD) in comparison with that in patients with uncomplicated hypertension and in patients with peripheral vascular disease (PVD), at the same values of mean blood pressure. DESIGN: Thirty-six ambulatory hypertensive patients were investigated, 11 with ESRD, 14 with PVD and 11 with uncomplicated hypertension, matched for age, sex, mean arterial pressure and antihypertensive drug treatment. METHODS: Cardiac mass was determined using M-mode echocardiography together with measurement of systemic blood pressure and the ratio between ankle and arm systolic blood pressures. RESULTS: At the same mean arterial pressure, patients with ESRD developed a greater degree of cardiac hypertrophy in comparison with those with uncomplicated hypertension (P < 0.01) and patients with PVD (P < 0.05). The pulse pressure was significantly greater in patients with ESRD than in those with uncomplicated hypertension (P< 0.01) and those with PVD (P< 0.05). Multiple regression analysis showed that only pulse pressure was positively correlated to cardiac mass (r= 0.62, P< 0.001), suggesting a predominant impact of pulse pressure on left ventricular mass in patients with ESRD. CONCLUSIONS: In patients with chronic uraemia, left ventricular hypertrophy seems to be strongly and independently associated with pulse pressure.

Dynamics of rabies virus quasispecies during serial passages in heterologous hosts.

To understand the mutations and genetic rearrangements that allow rabies virus infections of new hosts and adaptation in nature, the quasispecies structure of the nucleoprotein and glycoprotein genes as well as two noncoding sequences of a rabies virus genome were determined. Gene sequences were obtained from the brain and from the salivary glands of the original host, a naturally infected European fox, and after serial passages in mice, dogs, cats and cell culture. A relative genetic stasis of the consensus sequences confirmed previous results about the stability of rabies virus. At the quasispecies level, the mutation frequency varies, in the following order: glycoprotein region (21.9 x 10(-4) mutations per bp), noncoding sequence nucleoprotein-phosphoprotein region (7.2-7.9 x 10(-4) mutations per bp) and nucleoprotein gene region (2.9-3.7 x 10(-4) mutations per bp). These frequencies varied according to the number, type of heterologous passages and the genomic region considered. The shape of the quasispecies structure was dramatically modified by passages in mice, in which the mutation frequencies increased by 12-31 x 10(-4) mutations per bp, depending on the region considered. Non-synonymous mutations were preponderant particularly in the glycoprotein gene, stressing the importance of positive selection in the maintenance and fixation of substitutions. Two mechanisms of genomic evolution of the rabies virus quasispecies, while adapting to environmental changes, have been identified: a limited accumulation of mutations with no replacement of the original master sequence and a less frequent but rapid selective overgrowth of favoured variants.