Celiac disease in children and adolescents with Down syndrome: behavioural, adaptive and sleep profiles.

BACKGROUND: Individuals with Down syndrome (DS) exhibit higher risk for celiac disease (CD) than general population. Although literature suggests CD could be associated with behavioural problems in both paediatric and adult age, such association has been poorly explored in children and adolescents DS. Therefore, the current study aimed to investigate differences in emotional/behavioural difficulties, adaptive skills and sleep problems between children with DS with and without CD. METHODS: Data were retrospectively collected from a database including data from 381 individuals with DS (3-18 years). The final sample included 65 participants, 27 with co-occurring CD and 38 age, IQ, sex and body mass index-matched controls without CD. Emotional/behavioural difficulties, adaptive skills and sleep problems were assessed through parent report questionnaires. RESULTS: No group differences emerged in emotional/behavioural difficulties, whereas participants in the CD group showed better adaptive skills in the practical domain than control group. Weak differences emerged in sleep problems. CONCLUSIONS: Youth with DS and co-occurring CD do not exhibit more emotional and behavioural problems than youth with DS without co-occurring CD but exhibit better adaptive skills in the practical domain.

Medical conditions of children and young people with Down syndrome.

BACKGROUND: The life expectancy of people with Down syndrome (DS) has significantly increased in the last decades. We describe the congenital malformations and main comorbidities of a cohort of children and young people with DS and analyse their differences according to age and gender groups. METHODS: This retrospective cross-sectional study was conducted at DS centre of Bambino Gesù Children's Hospital in Rome (Italy). The period for reviewing all electronic health records ran from July 2016 to September 2017. We collected data on clinical conditions and compared them with the general paediatric population. Moreover, we compared the main comorbidities, dental diseases and body mass index data between age groups. RESULTS: Seven hundred sixty-three children and young people with DS included in this study were aged 7.45 ± 5.49 years. Gender distribution included 58.19% male patients. The majority of our population (71.04%) came from central regions of Italy. Respiratory diseases (19%), congenital heart defects (72.23%), malocclusions (58.62%), astigmatism (20.31%), farsightedness (16.51%), near-sightedness (12.19%) and autoimmune hypothyroidism (3.28%) were more frequent in our population compared with the typical paediatric population. Upper respiratory tract infections and underweight were significantly more frequent in the youngest children, whereas dental diseases, refractive errors, obesity and autoimmune hypothyroidism increased over age. CONCLUSIONS: Children and young people with DS present a high prevalence of potentially treatable medical conditions making multidisciplinary teams a mandatory need for this population.

Increased ß-haemolytic group A streptococcal M6 serotype and streptodornase B-specific cellular immune responses in Swedish narcolepsy cases.

BACKGROUND: Type 1 narcolepsy is a neurological disorder characterized by excessive daytime sleepiness and cataplexy associated with the HLA allele DQB1*06:02. Genetic predisposition along with external triggering factors may drive autoimmune responses, ultimately leading to the selective loss of hypocretin-positive neurons. OBJECTIVE: The aim of this study was to investigate potential aetiological factors in Swedish cases of postvaccination (Pandemrix) narcolepsy defined by interferon-gamma (IFNγ) production from immune cells in response to molecularly defined targets. METHODS: Cellular reactivity defined by IFNγ production was examined in blood from 38 (HLA-DQB1*06:02(+) ) Pandemrix-vaccinated narcolepsy cases and 76 (23 HLA-DQB1*06:02(+) and 53 HLA-DQB1*06:02(-) ) control subjects, matched for age, sex and exposure, using a variety of different antigens: ß-haemolytic group A streptococcal (GAS) antigens (M5, M6 and streptodornase B), influenza (the pandemic A/H1N1/California/7/09 NYMC X-179A and A/H1N1/California/7/09 NYMC X-181 vaccine antigens, previous Flu-A and -B vaccine targets, A/H1N1/Brisbane/59/2007, A/H1N1/Solomon Islands/3/2006, A/H3N2/Uruguay/716/2007, A/H3N2/Wisconsin/67/2005, A/H5N1/Vietnam/1203/2004 and B/Malaysia/2506/2004), noninfluenza viral targets (CMVpp65, EBNA-1 and EBNA-3) and auto-antigens (hypocretin peptide, Tribbles homolog 2 peptide cocktail and extract from rat hypothalamus tissue). RESULTS: IFN-γ production was significantly increased in whole blood from narcolepsy cases in response to streptococcus serotype M6 (P = 0.0065) and streptodornase B protein (P = 0.0050). T-cell recognition of M6 and streptodornase B was confirmed at the single-cell level by intracellular cytokine (IL-2, IFNγ, tumour necrosis factor-alpha and IL-17) production after stimulation with synthetic M6 or streptodornase B peptides. Significantly, higher (P = 0.02) titres of serum antistreptolysin O were observed in narcolepsy cases, compared to vaccinated controls. CONCLUSION: ß-haemolytic GAS may be involved in triggering autoimmune responses in patients who developed narcolepsy symptoms after vaccination with Pandemrix in Sweden, characterized by a Streptococcus pyogenes M-type-specific IFN-γ cellular immune response.

Coinfection in acute gastroenteritis predicts a more severe clinical course in children.

The objectives of this study were to determine the incidence of enteric pathogens causing acute gastroenteritis (AGE) among hospitalized children in a large Italian hospital, to measure the incidence of coinfections, and to compare the clinical characteristics of those infected with one versus multiple agents. A prospective study was conducted from March 2010 to April 2011 at the Bambino Gesù Pediatric Hospital in Rome, Italy. All patients between 1 month and 16 years of age admitted to the Pediatric Department with a diagnosis of AGE were eligible for enrollment. Two stool samples for each patient were tested for gastrointestinal pathogens. We summarized the clinical severity of episodes, describing the duration of diarrhea, duration and frequency of vomiting, fever, and severity of dehydration. All the patients underwent medical evaluation with estimation of dehydration. One or more etiological agents were detected in 151 out of 232 patients (65.1%), while we did not detect any etiological agent in 81 (34.9%). Rotavirus was detected in 96 (63.6%), adenovirus in 17 (11.2%), norovirus in 7 (4.6%), toxin-producing Clostridium difficile in 23 (15.2%), Salmonella spp. in 15 (9.9%, B group in 12/15 and D group in 3/15), C. perfringens in 12 (7.9%), Campylobacter spp. in 6 (4%), and verotoxigenic Escherichia coli (VTEC) in 2 (1.3%). In 27 children out of 151 (17.9%), we found evidence of coinfection. Coinfection with rotavirus and toxin-producing C. difficile was the most common (63%). Children with coinfection had a more severe clinical presentation and had a higher probability to be severely dehydrated, independently of age and living community type.

Fast 3D-EM reconstruction using Planograms for stationary planar positron emission mammography camera.

At the University of Pisa we are building a PEM prototype, the YAP-PEM camera, consisting of two opposite 6 x 6 x 3 cm3 detector heads of 30 x 30 YAP:Ce finger crystals, 2 x 2 x 30 mm3 each. The camera will be equipped with breast compressors. The acquisition will be stationary. Compared with a whole body PET scanner, a planar Positron Emission Mammography (PEM) camera allows a better, easier and more flexible positioning around the breast in the vicinity of the tumor: this increases the sensitivity and solid angle coverage, and reduces cost. To avoid software rejection of data during the reconstruction, resulting in a reduced sensitivity, we adopted a 3D-EM reconstruction which uses all of the collected Lines Of Response (LORs). This skips the PSF distortion given by data rebinning procedures and/or Fourier methods. The traditional 3D-EM reconstruction requires several times the computation of the LOR-voxel correlation matrix, or probability matrix {p(ij)}; therefore is highly time-consuming. We use the sparse and symmetry properties of the matrix {p(ij)} to perform fast 3D-EM reconstruction. Geometrically, a 3D grid of cubic voxels (FOV) is crossed by several divergent 3D line sets (LORs). The symmetries occur when tracing different LORs produces the same p(ij) value. Parallel LORs of different sets cross the FOV in the same way, and the repetition of p(ij) values depends on the ratio between the tube and voxel sizes. By optimizing this ratio, the occurrence of symmetries is increased. We identify a nucleus of symmetry of LORs: for each set of symmetrical LORs we choose just one LOR to be put in the nucleus, while the others lie outside. All of the possible p(ij) values are obtainable by tracking only the LORs of this nucleus. The coordinates of the voxels of all of the other LORs are given by means of simple translation rules. Before making the reconstruction, we trace the LORs of the nucleus to find the intersecting voxels, whose p(ij) values are computed and stored with their voxel coordinates on a hard disk. Only the non-zero p(ij) are considered and their computation is performed just once. During the reconstruction, the stored values are loaded and are available in the random access memory for all of the operations of normalization, backprojection and projection: these are now performed rapidly, because the application of the translation rules is much faster than the probability computations. We tested the algorithm on Monte Carlo data fully simulating the typical YAP-PEM clinical condition. The adopted algorithm gives an excellent positioning capability for hot spots in the camera FOV. To use all of the possible skew LORs in the FOV avoids the software rejection of collected data. Reconstructed images indicate that a 5mm diameter tumor of 37 kBq/cm3, in an active breast with a 10:1 Tissue to Background ratio (T/B), with a 10 min acquisition, for a head distance of 5 cm, can be detected by the YAP-PEM with a SNR of 8.7+/-1.0. The obtained SNR values depend linearly on the tumor volume. The algorithm allows one to discriminate between two hot sources of 5.0 mm diameter if they do not lie on the same axis. The YAP-PEM is now in the assembly stage.

A case of Evans' syndrome in a patient with ulcerative colitis.

The case of a 37-year-old male diagnosed 16 years previously with ulcerative colitis, admitted on account of hemolytic anaemia and thrombocytopaenia that responded to immunosuppressive therapy, is reported. Despite various peculiarities discussed, this may be the first reported case of Evans' syndrome associated with ulcerative colitis.

Treatment of patients with severe burn injuries: the impact of schizophrenia.

Four patients treated in one ward of a psychiatric clinic were admitted to our burn unit within 2 months due to severe burn injuries. The patients showed signs of a self-mutilation epidemic. All four patients were female and the mean age was 28 years. The psychiatric diagnosis was schizophrenia in all patients (ICD 10: F20.9). The ignition of flammable liquid was the most common method and the mean burned TBSA was 33%. The mean severity score (ABSI) was 8 and the median hospital stay was 50 days. All patients were characterised by a prolonged hospital stay in comparison to patients without additional psychiatric pathology (median 31 days). This prolonged stay was based on a delayed wound healing, more operations, extended time for mobilisation and difficulties in co-operation. It is possible that in patients with schizophrenia, changes in nutrition, activity, sleep and drug use could influence their immune system profoundly. Anxiety and depression is also associated with the impairment of cellular and humoural immunity. Poor sleep reduces the production of an anabolic endocrine environment and sleep disturbances can interfere with macrophage and lymphocyte functions. Poor appetite leads to malnutrition, which is also capable of producing delayed wound healing. On the other hand, apathy and a general lack of motivation interfere with therapeutic strategies, because poor appetite and weight loss often occurs after neuroleptic withdrawal, which is correlated with clinical decompensation. Moreover, this "self-destructive" behaviour, which is acting on the immune system, might make a patient more susceptible to infection. All these aspects and side effects of schizophrenia combine to make the treatment of burned patients with schizophrenia a very special and difficult task.

Delivery of high dose VEGF plasmid using fibrin carrier does not influence its angiogenic potency.

Delivery of DNA mixed with a degradable matrix carrier was supposed to improve transgene expression. Using a rabbit hind-limb ischemia model, we tested the angiogenic potency of plasmid encoding human vascular endothelial growth factor (pSG5-VEGF165) entrapped in fibrin sealant. Animals were injected intramuscularly with 500 microg of pSG5-VEGF165 or control plasmid, dissolved in saline (PBS) or fibrin glue. After 14 days, presence of delivered constructs and expression of transgene was confirmed in injected muscles of all animals. There were no significant differences in the levels of human VEGF mRNA and protein between VEGF-PBS and VEGF-fibrin groups (Mann-Whitney test). Accordingly, pSG5-VEGF165 regardless of the way of delivery, induced similar increases in capillary density within treated muscles (ANOVA). Control plasmid did not show any effects. In conclusion, injection of pSG5-VEGF165 into ischemic adductor muscle leads to synthesis of human VEGF and increases the number of capillaries. Fibrin carrier does not influence its angiogenic potential.

[Reconstructive and non-reconstructive procedures in the treatment of the threatened limb]. / Procedure ricostruttive e non ricostruttive nel trattamento dell'arto critico.

Limb threatening ischemia is an acute step in the chronic course of peripheral arterial obstructive disease that requires some form of intervention. The objective of this study is to prove that reconstructive surgery as well as non reconstructive approaches are associated with positive results. Ours is a retrospective analysis of a ten year experience in the treatment of limb threatening ischemia. In the period 1983-93, 139 patients under-went 164 procedures. 67% of patients were diabetics. Early in the observation period the therapeutic strategy was non reconstructive, the procedure of choice was sympathectomy. Later vascular reconstructions have been recognized as the procedures of choice. In the cases not amenable to reconstructive procedures according to our group criteria (absence of a tibial vessel in continuity with a patent pedal arch), we have employed procedures such as prostanoid infusion; thrombolysis and epidural spinal cord stimulation. Reconstructive procedures have been associated with a decrease in the number of major amputations. Alternative procedures, employed in patients not amenable to reconstruction have proven worthwhile in terms of limb salvage even if this trend is limited to a short period of observation.

[Duodenopancreatectomy with conservation of the pylorus]. / Duodenopancreasectomia con conservazione del piloro.

The authors report on their initial experience with pylorus-preserving pancreatoduodenectomy. In the last three years 11 patients with neoplastic disease of the pancreatic head and ampullary region underwent the above mentioned procedure. The surgical technique carefully preserved the blood supply and innervation to the antro-pyloric region and duodenum was transected 2 cm distal to the pylorus. Postoperative mortality was 9%. Postoperative nasogastric suction was required for eight days (median). Long term results are quite good with a satisfactory restoration of intestinal function and a weight gain of 95% of pre-illness weight. At the present time preserving the pylorus appears an usefull modification of Whipple procedure.

[Russell's syndrome: a case of long-term survival and review of the literature]. / Sindrome di Russell: descrizione di un caso clinico a lunga sopravvivenza e revisione della letteratura.

We report the case of a two years old, normally eating child, affected by organic macies and severe dystrophy. After the negative response of blood and laboratory examinations let us exclude a malabsorption syndrome, only the performance of neuro-radiologic exams showed evidence of a subthalamic tumor as the cause of a "Diencephalic syndrome". Diencephalic syndrome or Russell's syndrome is a diencephalic tumor induced disease, which sets in the first time of life. The disease clinical markers are a severe emaciation with appetite preservation and absence or very scarce evidence of any telltale neurological sign. The tumoral histo-pathology most frequently shows a low grade of malignancy astrocytoma, whose eradication is very often difficult because of particular anatomic site. Treatment of choice includes an excisional biopsy with chemotherapy and radiotherapy. We report a clinical case of long-term survival and review of the literature.

[Erdheim-Chester disease: a non-Langerhans cell histiocytosis. A clinical-case and review of the literature]. / La malattia di Erdheim-Chester una istiocitosi a cellule non Langerhans. Rewiew della letteratura e descrizione di un caso clinico.

We make a retrospective evaluation of clinical and radiologic features, treatment, and outcome of Erdheim-Chester disease, a rare non-Langerhans cell histiocytosis. We report a case of Erdheim-Chester disease and review 60 cases from the literature. These cases are consider to have Erdheim-Chester disease when they have either typical bone radiographs (symmetrical long bones osteosclerosis) and/or histologic criteria disclosing histiocytic infiltration with distinctive immunohistochemical phenotype of the non-Langerhans cell histiocytes with positive staining for CD68 and negative staining for S-100 protein and CD1a. Our patient undergoes chemiotherapy according to the LCH-II stratification and therapy plan (Vinblastine, Etoposide and Prednisone) and thereafter receives Carboplatin and Etoposide, and Somatostatin. She is alive and clinically well 33 months after onset of symptoms and the lesions don't appear to progress at imaging examinations. In conclusion, Erdheim-Chester disease may be confused with Langerhans cell histiocytosis as it sometimes shares the same clinical (exophthalmos, diabetes insipidus) or radiologic (osteolytic lesions) findings. However, the characteristics radiological pattern of Erdheim-Chester disease together the immunohistochemical phenotype of hystiocytic infiltration supports the theory that Erdheim-Chester disease is a unique disease entity distinct.

Cosmology with massive neutrinos coupled to dark energy.

Cosmological consequences of a coupling between massive neutrinos and dark energy are investigated. In such models, the neutrino mass is a function of a scalar field, which plays the role of dark energy. The evolution of the background and cosmological perturbations are discussed. We find that mass-varying neutrinos can leave a significant imprint on the anisotropies in the cosmic microwave background and even lead to a reduction of power on large angular scales.

Clinical quality assessment using computer monitor photoimages of optic nerve head cupping.

BACKGROUND: Photo documentation (color slides) of abnormal optic nerve heads enable the clinician to accurately access or estimate the percentage of the optic nerve cupping to quantify the progression of glaucoma. The purpose of this study is to compare cupping estimations using digital images on a computer monitor to those using standard color slides. METHODS: Ten sets of stereo optic nerve head photos from six glaucoma suspects were used in this study. A set is two 35-mm pictures of one optic nerve head. The film was developed as standard color slides using Seattle Filmworks slide developing. The computer monitor photoimages used Seattle Photoworks software for photos on disk. Thirteen experienced examiners estimated cupping on the 10 sets of color slides and on the 10 sets of digital images. Standard criterion was used to estimate the C/D percentage. We used a three-way mixed model ANOVA experimental design to analyze the data. RESULTS: Examiner estimations of C/D differed slightly between color slides and computer monitor photoimages (mean C/D of 61.1% for slides to 63.7% for monitor). This difference was statistically significant (p = 0.033). The differences authors found were not clinically significant (10%) in 7 out of the 10 optic nerve head photos using the accepted standard of interexaminer reliability. The variations of the examiner estimations as well as interexaminer differences will be discussed. CONCLUSION: The use of a computer image photodisplay of an optic nerve head has a potential as an alternative to traditional slide photodocumentation. This study identifies problems which require more work to make these computer images the equivalent of color slides.

Circulatory changes after prolonged ischemia in the epigastric flap.

The circulation system seems to have early encounters with pathophysiologic processes during ischemia and reperfusion, such as overproduction of oxygen radicals, nitric oxide depletion, and leukocyte plugging. The aim of this study was to determine the superficial perfusion and vessel distribution of the epigastric flap with a laser Doppler Imaging (LDI) system during ischemia/reperfusion, and to observe the clinical outcomes 7 days after reperfusion in a separate set of animals. An epigastric flap from male Sprague-Dawley rats (320 to 380 g) was used to assess perfusion in sham animals (n=6) or in 12 hr-ischemia animals (12 hr of ischemia and 3 hr of reperfusion, n = 10) with the LDI system. In a separate experiment, flap size, flap failure index, and histologic sections of the flap from sham animals (n=6) and 12-hr ischemia animals (n=6) were evaluated 7 days after reperfusion. Evaluation of the vessel distribution demonstrated a diffuse picture of flap perfusion after clamp release. Moreover, in the distal portion of the flap, circulation stopped immediately, resulting in a significantly decreased perfusion in the 12-hr ischemia animals during reperfusion, when compared with pre-surgical values (100 percent) or sham animals (77 +/- 26.5 vs. 108 +/- 9.6 percent PU). On day 7, the flaps of animals after ischemia and reperfusion showed significant shrinkage, an increase in flap failure index, as well as necrosis, edema, and leukocyte infiltration. Based on the findings, the authors propose that, after prolonged ischemia, the circulation becomes diffuse, and "no-reflow" occurs in the distal portions of the myocutaneous flap during reperfusion. Perfused areas, assessed with the LDI early during reperfusion, might still become necrotic after several days. In the authors' flap model, edema formation and leukocyte infiltration seem to be related more to ischemia reperfusion damage than to thrombus formation.

Evaluation of total vs. regional blood perfusion with a laser Doppler imaging system in the rat epigastric flap.

Monitoring systems to measure flap survival are either invasive, touch the surface of the tissue, or have problems in reproducibility. The authors sought to determine the efficacy of a laser Doppler imaging (LDI) system to measure perfusion in a myocutaneous flap, by producing a two-dimensional picture of the flap without touching the surface. They compared total flap perfusion with perfusion in selected areas of interest after flap surgery. The perfusion in the left groin of Sprague-Dawley rats was measured before and after surface rubbing, skin injury, and during different lighting conditions. The perfusion of the epigastric flap before and over a period of 60 min after elevation was measured, and values were compared to pre-surgical values and to sham-operated animals. They determined the differences between single and running-suture techniques after flap surgery, as well as between venous and/or arterial occlusion. Surface rubbing, skin injury, and light influenced the LDI image. After flap elevation, total flap perfusion remained stable, while the distal area (area 8, n = 7) of the flap showed a statistically significant decrease in perfusion (71 +/- 5.9 vs. 92 +/- 9.5 percent perfusion units--PU; p < .05). The proximal areas (1 to 3, n = 7) of the flap had a higher perfusion at 60 min after flap surgery, compared with sham-operated (n = 8) animals (118 +/- 12.5 vs. 97 +/- 10.4 percent PU; p < .05). The running-suture technique was followed by decreased perfusion on the peripheral side of the flap, compared with the single-suture technique (73.7 +/- 9.2 vs. 99.2 +/- 4.9 percent PU; n = 2). The LDI was able to visualize venous and/or arterial occlusion after flap surgery. Under standardized circumstances (light, temperature), the LDI was efficient in measuring regional flap circulation experimentally. While total flap perfusion after flap surgery remained stable, perfusion in the distal flap decreased significantly.

Relevance of age on survival of 341 patients with multiple myeloma treated with conventional chemotherapy: updated results of the MM87 prospective randomized protocol. Cooperative Group of Study and Treatment of Multiple Myeloma.

Age could influence the prognosis of multiple myeloma patients treated with conventional chemotherapy. Between January 1987 and March 1990, 341 consecutive previously untreated patients with multiple myeloma received chemotherapy within the prospective, multicentre, randomized Protocol MM87. Survival was evaluated in patients aged > or < or = 66 years (the median age for the whole series) and in a subgroup of patients aged < 55 years. These groups were similar for main clinical characteristics, including results of cytostatic treatment. As of May 1996, 271 (79%) of the 341 patients had died, and median follow-up of the 70 (21%) living patients was 82 months. Overall, younger patients survived longer than older ones. In fact, in patients > and < or = 66 years, median survival was 31 and 44 months (P < 0.00095) and the percentage of patients surviving over 72 months was 17% and 32% (P = 0.0018) respectively; in patients < 55 years, these figures were 57 months and 35% respectively (P = 0.02 and 0.01, with respect to patients aged > 55 years). In all groups, about 50% of the patients surviving over 72 months had stage I disease. For multiple myeloma patients treated with chemotherapy, survival is favourably affected by relatively young age and early stage of disease.

A psoriasis vulgaris protective gene maps close to the HLA-C locus on the EH18.2-extended haplotype.

We determined the molecular haplotypes of the HLA-A, HLA-C and HLA-B loci and the MHC class I-B-related (MIB) microsatellite in 179 unrelated psoriatic patients (72 familial cases) and in 120 controls. The HLA-A*3002-Cw*0501-B*1801-MIB1 haplotype showed a strong negative association with psoriasis vulgaris (PV) and in particular with familial PV, revealing the presence of a PV-protective gene. Analysis of association and linkage disequilibrium of the single alleles and the various two-three-four-locus segments of this haplotype indicated the presence of a protective gene telomeric to the HLA-C locus. This finding was confirmed in 13 informative multiplex PV families, in which at least one parent carried the EH18.2 haplotype. In two families, an affected sibling presented HLA-A/C recombination on the EH18.2 haplotype. A study of 12 polymorphic microsatellites in all members of the informative families, 145 PV patients, 120 controls and 32 EH18.2 homozygous healthy individuals demonstrated that the protection conferred by the EH18.2 haplotype lies within a 170 kb interval between the C143 and C244 loci, most probably in a 60 kb segment between the C132 and C244 loci.

Long-term survival of stage I multiple myeloma given chemotherapy just after diagnosis or at progression of the disease: a multicentre randomized study. Cooperative Group of Study and Treatment of Multiple Myeloma.

We conducted a randomized trial to evaluate whether melphalan-prednisone (MPH-P) treatment administered just after diagnosis improves survival of stage I multiple myeloma (MM). Between January 1987 and March 1993, 145 consecutive previously untreated patients with stage I MM were randomized between treatment with MPH-P (administered for 4 days every 6 weeks) just after diagnosis and treatment only at disease progression. Survival was not influenced by MPH-P treatment either administered just after diagnosis or at disease progression (64 vs 71 months respectively). Comparing the first with the second group the odds ratio of death is 1.17 (95% confidence interval 0.57-2.42; P = 0.64). Disease progression occurred within a year in about 50% of patients who were initially untreated. Response rate was similar in both groups, but duration of response was shorter in patients who were treated at disease progression (48 vs 79 months, P = 0.044). Patients actually treated at disease progression (34/70) survived shorter than those who had neither disease progression nor treatment (56 vs > 92 months; P = 0.005). Starting MPH-P just after diagnosis does not improve survival and response rate in stage I MM, with respect to deferring therapy until disease progression. However, patients with stage I MM randomized to have treatment delayed and who actually progressed and were treated had shorter survival than those with stable disease and no treatment. Biologic or other disease features could identify these subgroups of patients.