Five-year follow-up of persons with brain injury entering the French vocational and social rehabilitation programme UEROS: Return-to-work, life satisfaction, psychosocial and community integration.

BACKGROUND: Social and vocational reintegration of persons with brain injury is an important element in their rehabilitation. AIMS: To evaluate the 5-year outcome of persons with brain injury included in 2008 in the Aquitaine Unit for Evaluation, Training and Social and Vocational Counselling programme (UEROS). METHOD: 57 persons with brain injury were recruited from those who completed the 2008 UEROS programme. Five years later, an interview was done to assess family and vocational status, autonomy and life satisfaction. These results were compared with those from persons completing the 1997-1999 programme. RESULTS: The typical person entered the 2008 UEROS programme 6 years after a severe brain injury (42%) and was male, single and 35 years. At the 5-year follow-up, more persons lived with a partner (+23%) and lived in their own home (+21%). 47% were working vs 11% on entering the programme. Approximately half were satisfied or very satisfied with their quality of life. Having a job in 2013 was associated with a high education level, less cognitive sequelae, having a job in 2008 and no health condition. CONCLUSIONS: The UEROS programme is effective with regard to return-to-work and improvement of autonomy in persons with brain injury, irrespective of length of time from injury.

Immunoglobulin genes undergo legitimate repair in human B cells not only after cis- but also frequent trans-class switch recombination.

Immunoglobulin (Ig) genes specifically recruit activation-induced deaminase (AID) for 'on-target' DNA deamination, initiating either variable (V) region somatic hypermutation, or double-strand break intermediates of class switch recombination (CSR). Such breaks overwhelmingly undergo legitimate intra-Ig repair rather than rare illegitimate and potentially oncogenic junctions outside of Ig loci. We show that in human B cells, legitimate synapsis and repair efficiently join Ig genes whether physically linked on one chromosome or located apart on both alleles. This indicates mechanisms faithfully recognizing and/or pairing loci with homology in structure and accessibility, thus licensing interchromosomal trans-CSR junctions while usually preventing illegitimate interchromosomal recombination with AID off-target genes. Physical linkage of IgH genes in cis on the same allele just increases the likelihood of legitimate repair by another fourfold. The strongest force driving CSR might thus be recognition of legitimate target genes. Formation of IgH intra-allelic loops along this process would then constitute a consequence rather than a pre-requisite of this gene-pairing process.

Complexes between nuclear factor-κB p65 and signal transducer and activator of transcription 3 are key actors in inducing activation-induced cytidine deaminase expression and immunoglobulin A production in CD40L plus interleukin-10-treated human blood B cells.

The signal transducer and activator of transcription 3 (STAT3) transcription factor pathway plays an important role in many biological phenomena. STAT3 transcription is triggered by cytokine-associated signals. Here, we use isolated human B cells to analyse the role of STAT3 in interleukin (IL)-10 induced terminal B cell differentiation and in immunoglobulin (Ig)A production as a characteristic readout of IL-10 signalling. We identified optimal conditions for inducing in-vitro IgA production by purified blood naive B cells using IL-10 and soluble CD40L. We show that soluble CD40L consistently induces the phosphorylation of nuclear factor (NF)-κB p65 but not of STAT3, while IL-10 induces the phosphorylation of STAT3 but not of NF-κB p65. Interestingly, while soluble CD40L and IL-10 were synergistic in driving the terminal maturation of B cells into IgA-producing plasma cells, they did not co-operate earlier in the pathway with regard to the transcription factors NF-κB p65 or STAT3. Blocking either NF-κB p65 or STAT3 profoundly altered the production of IgA and mRNA for activation-induced cytidine deaminase (AID), an enzyme strictly necessary for Ig heavy chain recombination. Finally, the STAT3 pathway was directly activated by IL-10, while IL-6, the main cytokine otherwise known for activating the STAT3 pathway, did not appear to be involved in IL-10-induced-STAT3 activation. Our results suggest that STAT3 and NF-κB pathways co-operate in IgA production, with soluble CD40L rapidly activating the NF-κB pathway, probably rendering STAT3 probably more reactive to IL-10 signalling. This novel role for STAT3 in B cell development reveals a potential therapeutic or vaccine target for eliciting IgA humoral responses at mucosal interfaces.

Definition and epidemiology of mild traumatic brain injury.

BACKGROUND/OBJECTIVES: The definition of mild traumatic brain injury (mTBI), also known as concussion, has been a matter of controversy, which makes comparison between studies difficult. Incidence varies greatly from one country to another. The present article reviews definitions and epidemiology. METHODS: Literature review. RESULTS: According to the Mild TBI Committee of the American Congress of Rehabilitation Medicine, revised by the World Health Organization (WHO), mTBI is defined by a Glasgow Coma Scale score between 13 and 15 at 30minutes post-injury, and one or more of the following symptoms: <30min loss of consciousness; <24hours post-traumatic amnesia (PTA); impaired mental state at time of accident (confusion, disorientation, etc.); and/or transient neurological deficit. If a focal lesion is found on computed tomography (CT) or magnetic resonance imaging (MRI), the term "complicated mild TBI" has been proposed. Incidence of mTBI is 200-300/100,000 persons per year for hospitalized patients and probably twice as high if non-hospitalized patients are included. However, a few recent population-based studies reported a much higher rate (>700/100,000). A changing pattern of epidemiology has been found in high-income countries, related to a decrease in road-accident injuries in young adults, while conversely the proportion of falls has increased with population aging. CONCLUSION: Mild TBI is a major public health concern, the epidemiology of which has greatly changed in the last twenty years.

Management of unfavorable outcome after mild traumatic brain injury: Review of physical and cognitive rehabilitation and of psychological care in post-concussive syndrome.

INTRODUCTION: Mild Traumatic Brain Injury (mTBI) is a public health issue with approximately 42 million people worldwide affected yearly. Most patients have a favorable short-term recovery but 10-20% are likely to develop post-concussive syndrome (association of physical, cognitive, and psychological difficulties after injury). Post-concussive syndrome can be associated with Post-Traumatic Stress Disorder (PTSD). There is to date no recommendation on the interventions that could be done to reduce post-concussive syndrome. The present review aims at summarizing the effect of therapeutic education, physical and cognitive rehabilitation and of psychological care in mTBI patients with post-concussive syndrome. METHODS: In the current international literature, we investigated the effects of therapeutic education, physical and cognitive rehabilitation and of psychological care in this population using the Medline database and we discussed the results of these studies. RESULTS: The application of a therapeutic education intervention within 3 months after mTBI has been found appropriate and effective to prevent post-concussion syndrome in several studies but the timeline of this intervention differs among the existing studies. Concerning physical disabilities, several pharmacological, rehabilitative and non-pharmacological techniques have shown some efficacy in reducing headache and vertigo; rTMS seems also promising in this context. The management of fatigue is also crucial and requires a multidisciplinary approach. We did not find any intervention in mTBI patients with post-concussive syndrome suffering from dysosmia and/or dysgueusia. No pharmacological treatment is currently recommended to reduce the cognitive symptoms of post-concussive syndrome after mTBI. Rehabilitation and brain-stimulation techniques have already proven their efficacy to reduce the cognitive impairment in this population. Even if the use of Virtual Reality software seems well tolerated in this population, its efficacy and additional value needs to be demonstrated in larger studies. Concerning the psychological care after mTBI, Cognitive and Behavioral Therapy interventions are the most frequently reported in this population, followed by psychoeducational interventions. PTSD management seems crucial in overall recovery of patients with post-concussive syndrome. CONCLUSION: Many studies have sought to demonstrate the effectiveness of various rehabilitation techniques, including different cognitive rehabilitation programs, technology-assisted rehabilitation, different types of brain stimulation and some pharmacological treatments. However, most of these studies are of a low level of scientific evidence and it would be necessary to carry out well-conducted prospective randomized trials in order to offer an appropriate and effective multidisciplinary management for patients with post-concussive syndrome after mTBI.

Structure of a monoclonal kappa chain of the V kappa IV subgroup in the kidney and plasma cells in light chain deposition disease.

That structural abnormalities may be responsible for nonamyloid immunoglobulin (Ig) light chain deposition disease (LCDD) is suggested by previous results of Ig biosynthesis studies, but this hypothesis was not documented at the molecular level. We report on the first complete primary sequence deduced from cDNA analysis of a kappa light chain responsible for LCDD associated with an apparently nonsecretory myeloma. Bone marrow myeloma cells contained intracellular kappa chains and no heavy chains by immunofluorescence. Kidney biopsy showed typical nonamyloid PAS-positive kappa chain deposits. SDS-PAGE analysis of material extracted from a kidney biopsy specimen and of Ig produced by the myeloma cells revealed kappa chains of abnormally high apparent molecular mass (30,000). Comparison of the NH2-terminal aminoacid sequence of the kappa chain deposited in the kidney and of the complete sequence of several identical kappa cDNA clones from bone marrow cells showed the identity of the tissue deposited and plasma cell kappa chain. The kappa mRNA had an overall normal structure and corresponded to the V kappa IV gene rearranged to J kappa 1 and followed by a normal constant exon of the Km(3) allotype. The variable sequence differed from the V kappa IV germline gene by nine point mutations, including an Asp----Asn substitution at position +70 resulting in a potential N-glycosylation site. In vitro biosynthesis experiments and treatment with N-glycosidase provided evidence for the intracellular glycosylation of the monoclonal kappa chain. The peculiar sequence and the glycosylation of a kappa chain of the rare V kappa IV subgroup might be responsible for structural abnormalities leading to tissue deposition.

Eµ and 3'RR IgH enhancers show hierarchic unilateral dependence in mature B-cells.

Enhancer and super-enhancers are master regulators of cell fate. While they act at long-distances on adjacent genes, it is unclear whether they also act on one another. The immunoglobulin heavy chain (IgH) locus is unique in carrying two super-enhancers at both ends of the constant gene cluster: the 5'Eµ super-enhancer promotes VDJ recombination during the earliest steps of B-cell ontogeny while the 3' regulatory region (3'RR) is essential for late differentiation. Since they carry functional synergies in mature B-cells and physically interact during IgH locus DNA looping, we investigated if they were independent engines of locus remodelling or if their function was more intimately intermingled, their optimal activation then requiring physical contact with each other. Analysis of chromatin marks, enhancer RNA transcription and accessibility in Eµ- and 3'RR-deficient mice show, in mature activated B-cells, an unilateral dependence of this pair of enhancers: while the 3'RR acts in autonomy, Eµ in contrast likely falls under control of the 3'RR.

The contribution of virtual reality to the diagnosis of spatial navigation disorders and to the study of the role of navigational aids: A systematic literature review.

INTRODUCTION: Spatial navigation, which involves higher cognitive functions, is frequently implemented in daily activities, and is critical to the participation of human beings in mainstream environments. Virtual reality is an expanding tool, which enables on one hand the assessment of the cognitive functions involved in spatial navigation, and on the other the rehabilitation of patients with spatial navigation difficulties. Topographical disorientation is a frequent deficit among patients suffering from neurological diseases. The use of virtual environments enables the information incorporated into the virtual environment to be manipulated empirically. But the impact of manipulations seems differ according to their nature (quantity, occurrence, and characteristics of the stimuli) and the target population. METHODS: We performed a systematic review of research on virtual spatial navigation covering the period from 2005 to 2015. We focused first on the contribution of virtual spatial navigation for patients with brain injury or schizophrenia, or in the context of ageing and dementia, and then on the impact of visual or auditory stimuli on virtual spatial navigation. RESULTS: On the basis of 6521 abstracts identified in 2 databases (Pubmed and Scopus) with the keywords « navigation ¼ and « virtual ¼, 1103 abstracts were selected by adding the keywords "ageing", "dementia", "brain injury", "stroke", "schizophrenia", "aid", "help", "stimulus" and "cue"; Among these, 63 articles were included in the present qualitative analysis. CONCLUSION: Unlike pencil-and-paper tests, virtual reality is useful to assess large-scale navigation strategies in patients with brain injury or schizophrenia, or in the context of ageing and dementia. Better knowledge about both the impact of the different aids and the cognitive processes involved is essential for the use of aids in neurorehabilitation.

Regulatory elements of the mb-1 gene encoding the Ig-alpha component of the human B-cell antigen receptor.

The mb-1 gene encodes the Ig-alpha component of the B-cell antigen receptor. It is specifically expressed in pre-B and mature B cells but not in plasma cells losing membrane Ig (mIg) expression. We looked for transcriptional regulatory elements within a 12 kb genomic fragment. A strong promoter activity was found in a 591 bp fragment harboring consensus binding sites for known transcription factors including Ets, EBF/BlyF, LyF1/micro B and Spl. It was able to drive transcription of a reporter gene in the absence of any additional enhancer and was mostly active in B lymphocytes not in plasma cells or T cells. Although no fragment from the mb-1 gene displayed enhancer activity in combination with either the SV40, a Ig VH or a Ig VL promoter, a 1078 bp fragment corresponding to the 5' part of the gene behaved as a strong enhancer in either orientation in constructs driven by the mb-1 promoter itself. Deletions within this fragment allowed to delineate shorter sequences with enhancer activity upstream the first exon. The tissue-restricted, promoter-restricted and stage-specific activity of this 5' flanking region suggests that it is the main regulatory element of the mb-1 gene.

Production of an abnormal mu chain with a shortened VHIV subgroup variable region in a Burkitt's lymphoma cell line.

The Burkitt's lymphoma cell line Ly66 produces a short mu chain which lacks 4 kDa in apparent molecular mass. Study of the corresponding messenger RNA showed it to be 0.3 kb shorter than normal mu transcripts. The cDNA sequence of the mu transcripts began by a short VH region consisting of the first one-third of a VHIV subgroup gene segment. It was followed by a normal mu constant region. This VH region coded for 38 amino acids, thus differing from two truncated VHIV regions previously reported in other Burkitt's lymphoma cell lines, which were interrupted at codon +26 by an alternate splicing event. In addition, the Ly66 variable sequence bore several point mutations and contained two potential N-glycosylation sites.

Three year follow-up of acromegalic patients treated with intramuscular slow-release lanreotide.

Somatostatin analogs are an alternative treatment to pituitary surgery and radiotherapy in acromegalic patients. Recently, a depot long-lasting formulation of slow release (SR) lanreotide has been shown to be effective in the short-term control of GH hypersecretion in acromegalic patients. We report the long-term follow-up of a cohort of 22 acromegalic patients treated with SR lanreotide during 1-3 yr. Thirteen females and 9 males, age 51 +/- 3 yr, presented with macroadenomas (n = 12), microadenomas (n = 8), or empty sella (n = 2). Seven patients previously had undergone a partial surgical removal of their adenomas, and 21 of them had mean plasma GH levels less than 5 micrograms/L during a previous octreotide treatment. According to GH values recorded after 3 months of twice monthly 30 mg SR lanreotide im injection, SR lanreotide was administered every 14 days (n = 13) or every 10 days (n = 9). At the 6-month visit, mean GH values were 5 micrograms/L or less in 68% and 2.5 micrograms/L or less in 27% of patients, and these results remained unchanged during the 1-3 yr follow-up period. During SR lanreotide treatment, the mean insulin-like growth factor I (IGF-I) concentrations remained in the normal range in 63% of patients. No escape from the treatment occurred in any of the cases. A significant decrease of the pituitary tumor volume was observed in 3 (13%) patients. The main side effect consisted of minor digestive problems during 48 h after each injection and was reported by 13 patients. Biannual gallbladder echographies revealed the occurrence of gallstones in 4 (18%) patients. In conclusion, these data confirm the efficacy and the tolerance of the long-term SR lanreotide administration (30 mg im every 10-14 days) in the control of acromegaly.

Insertion of the IgH locus 3' regulatory palindrome in expression vectors warrants sure and efficient expression in stable B cell transfectants.

We have explored the effect of inserting 3' immunoglobulin heavy chain (IgH) locus transcriptional regulatory elements in stable expression vectors driven by a heavy chain variable gene promoter (pVH). A cassette was constructed, associating three enhancer elements from the palindromic part of the 3' IgH regulatory region, namely Calpha3'/hs3 reverse, alpha3'E/hs1-2, and hs3. As regard to stable expression, this cassette carried some features of a locus control region (LCR) and conferred expression to an associated cat reporter gene in the majority of B cells having integrated the transgene. The palindromic cassette was inserted in an expression vector carrying Ig light chain coding sequences. In this construct, transcription driven by a pVH promoter/Emu cassette upstream of the transcription initiation site was boosted by the palindromic cassette located downstream of the coding sequence. This potent expression plasmid mimicking the architecture of endogenous Ig loci, definitely manifested a potent stimulatory activity for stable transcription, outscoring conventional ubiquitous or B-cell specific expression vectors.

The effect of intron sequences on expression levels of Ig cDNAs.

Several cDNA expression vectors were constructed and tested by stable transfection into a murine lymphoid cell line in order to compare secretion rates of a human immunoglobulin (Ig) light chain (LC). When the cDNA was under transcriptional control of the SV40 promoter and enhancer and preceded by the SV40 19S late mRNA intron, a weak LC production was detected. Secretion rate was not improved by replacing the SV40 promoter and enhancer by a combination of a murine Ig heavy chain (HC) gene promoter and enhancer even with insertion of additional Ig enhancers. In contrast, replacement of the 19S intron by a large intron derived from a human Ig HC gene and containing the intronic enhancer dramatically increased the secretion rate. High-level production was also obtained with the same enhancer-containing intron placed downstream from the LC cDNA. Stable transfectants were obtained that secreted the human LC in amounts comparable to those obtained with Ig genes. Our results suggest that the SV40 19S late mRNA intron used in several expression vectors is not appropriate when the purpose is to produce large amounts of antibody molecules. By providing transcriptional, splicing and polyadenylation signals, the presently described vectors will be useful for easy cloning and high-level expression in lymphoid cells of cDNAs or PCR products encoding antibody molecules.

An elevation in the concentration of HLA class I molecules in human blood due to ageing.

The quantification of plasmatic HLA class-I molecules (sHLA-I) was realized by a sandwich ELISA using a monomorphic mAb (W6/32). sHLA-I concentration is significantly increased in the elderly group (>50 years, 0.429+/-0.301 microg ml(-1)) as compared to the young group (<50 years, 0.126+/-0.085 microg ml(-1)). The variation of sHLA-I content could contribute to the unresponsiveness of ageing immune system.

Modification of HLA expression on peripheral lymphocytes and monocytes during aging.

Immunosenescence involves modifications of humoral and cellular immunity. Here we report the analysis of human leukocyte antigen (HLA) expression on T lymphocytes, B lymphocytes and monocytes of 58 healthy subjects aged 23-95 years old. Using a double staining immunofluorescence and flow cytometry analysis, we have determined the percentages of cells expressing HLA class-I and HLA-DR antigens. The number of antigenic sites expressed per cell were evaluated for HLA-ABCw, HLA-A, HLA-B, HLA-DR locus with a flow cytometry quantification technique. With advancing age, we observed: (i) a significant decrease of the percentage of T cells and B cells expressing HLA-A products; (ii) a decrease of the number of HLA class-I antigenic sites expressed per cell on the three populations tested, predominantly on B cells and in a locus-dependent fashion; (iii) a decrease of the number of HLA-DR molecules expressed per T cell, although the percentage of T cells expressing DR products was increased; (iv) a significant diminution of the percentage of B cells expressing HLA-DR molecules, without changes of the number of HLA-DR antigenic sites per cells. These changes in HLA expression with increasing age could contribute to the decreased level of immunologic responsiveness observed with ageing and contribute to the modification of antigen recognition.

Complete variable region deletion in a mu heavy chain disease protein (ROUL). Correlation with light chain secretion.

In a patient affected with chronic lymphocytic leukemia with lymphocyte surface mu and kappa determinants and vacuolated bone marrow plasma cells, the serum contained polymers of a truncated mu chain and normal-sized kappa chains. These light chains were present as monomers and covalent dimers in studies performed under dissociating conditions, but they were linked by non-covalent bridges to a portion of the serum short mu chains. The patient's urine contained a kappa type Bence-Jones protein. Study of a messenger RNA and complementary DNA from blood cells showed the abnormal mu chain to lack the entire variable region, likely due to a direct splicing of the leader peptide exon onto the CH1 exon. The production of light chains, a rare event in heavy chain diseases, appears to correlate with the occurrence of a heavy chain deletion restricted to the variable domain, likely because the non-covalently linked light chains allow these unusual heavy chains to be secreted.

Variable growth hormone profiles following withdrawal of long-term 30mg slow-release lanreotide treatment in acromegalic patients: clinical implications.

OBJECTIVE: Intramuscular injections of 30mg slow-release (SR) lanreotide (every 10 to 14 days) are an effective treatment in acromegalic patients. Because of an ongoing need to assess the efficacy and the tolerance of a new formulation of a depot preparation of lanreotide, we have evaluated prospectively GH profiles following withdrawal of 30mg slow-release lanreotide in a cohort of acromegalic patients. PATIENTS: Fifty-one acromegalic patients, controlled during long-term 30mg SR lanreotide treatment (GH: 1.44 +/- 0.64 microgram/l, IGF-I: 316 +/- 145ng/ml) (mean +/- s.d.), were studied following the withdrawal of the drug. MEASUREMENTS: Mean GH (half-hour samples, 0800-1200h), IGF-I and lanreotide levels were evaluated 14, 28, and 42 days following the last 30mg SR lanreotide injection. RESULTS: Mean GH levels remained below 2.5 microgram/l in 32 patients (group 1) twenty-eight days following SR lanreotide withdrawal. In these patients, mean GH and IGF-I levels had increased from 1.2 +/- 0.6 to 1.7 +/- 0.5 microgram/l (P < 0001), and from 283 +/- 138 to 359 +/- 168ng/ml (P < 0.001) respectively. In the 19 other patients (group 2), mean GH concentrations had risen above 2.5 microgram/l at 28 days following SR lanreotide withdrawal. Mean GH and IGF-I levels had increased from 1.9 +/- 0.4 to 5.1 +/- 2.8 microgram/l (P < 0.001), and from 371 +/- 143 to 568 +/- 206ng/ml (P < 0.001) respectively. Patients of groups 1 and 2 were comparable with regard to age, sex, tumoral status, mean GH levels before somatostatin analogue treatment, and previous treatments such as radiotherapy and duration of somatostatin analogue therapy, but 75% of group 1 patients underwent surgery compared with 37% of group 2 patients (P < 0.01). Twenty-eight days following SR lanreotide withdrawal, mean lanreotide levels in group 1 and group 2 had decreased from 1.6 +/- 0.7 to 0.6 +/- 0.3ng/ml (P < 0.001), and from 2.7 +/- 2.0 to 0.7 +/- 0.7ng/ml (P < 0.001) respectively. A negative correlation was observed between the lanreotide levels and GH and IGF-I concentrations in the two groups of patients, but the inhibition of GH/IGF-I concentrations by lanreotide levels was higher in group 1 patients than in those of group 2. Six patients of group 1 were treated with 30mg SR lanreotide injected at monthly intervals. During monthly follow-up, mean GH levels increased above 2.5 microgram/l in 2 patients. After 12 months follow-up, mean GH and IGF-I levels from 4 other patients were similar to those obtained with previous therapeutic sequence (i.e. intramuscular injections every 14 days). CONCLUSION: The degree of responsiveness to lanreotide and the duration of somatotroph suppression following lanreotide withdrawal are variable in acromegalic patients controlled during long-term 30mg SR lanreotide treatment. In patients displaying high sensitivity to lanreotide, the interval between i.m. 30mg SR lanreotide injections can be increased to one month, thus reducing the cost of the therapy, without altering its efficacy upon GH/IGF-I control.

Intramuscular injections of slow-release lanreotide (BIM 23014) in acromegalic patients previously treated with continuous subcutaneous infusion of octreotide (SMS 201-995).

Nine acromegalic patients (five females and four males), mean age 50 +/- 4 years, presented macroadenomas (N = 7), microadenoma (N = 1) or normal computed tomography scans (N = 1). Patients were treated with continuous subcutaneous infusion of octreotide (range 200-600 micrograms/day). Following a washout period of 7 days, the patients were injected im with 30 mg slow-release lanreotide every 10 days for the first month and then twice monthly. In case of elevated growth hormone (GH) levels at 3 months, the patients were injected every 10 days for the next three months. Plasma GH and insulin-like growth factor I (IGH-I) decreased in all patients during octreotide treatment. After 6 months of octreotide treatment, seven patients were considered as well controlled (mean 8 h GH < 5 micrograms/l, IGF-I normal) whereas in two patients the mean 8-h GH and/or IGF-I levels remained increased. Serum GH and IGH-I increased after octreotide withdrawal. In one patient, serum GH and IGF-I increased during slow-release lanreotide administration and injections were stopped after 45 days. After 3 months of lanreotide, three patients were well controlled while in five patients GH or IGF-I levels were not normalized. At 6 months, five patients were injected twice monthly and three patients had one injection every 10 days. Six patients were well controlled and in two patients the mean 8-h GH level remained increased. The pituitary tumor volume decreased by 20-30% in two patients during octreotide, as well as in one other during slow-release lanreotide therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Molecular remission after allogeneic bone marrow transplantation for chronic lymphocytic leukemia.

A 51-year-old man with previously treated CLL received an allogeneic sex mismatched BMT after total body irradiation and high dose chemotherapy. Residual disease was studied at phenotypic and molecular levels including Y chromosome DNA amplification by PCR assay. The patient was clinically disease-free 20 months after BMT with disappearance of the leukemic clone assessed by the most sensitive methods of detection. Long-term follow-up is necessary to ascertain the relevance of Y DNA amplification in predicting outcome in this patient.