TEMPORAL LOBE HERNIATION AND CHIASMOPATHY DURING DOPAMINE AGONIST THERAPY FOR PROLACTINOMA.

Background: Dopamine agonists (DA) are first line treatment for prolactinomas. Optic chiasm herniation can rarely occur during therapy, while brain herniation is very uncommon. Case Reports: A 34 yo woman presented with headaches and vision changes. Prolactin (PRL) was 4300 ng/mL. MRI showed a 4.5 cm pituitary adenoma with chiasm compression. After 3 months, PRL decreased to 201 ng/mL while patient was taking CAB 0.75 mg twice a week. MRI showed ~30% tumor reduction with medial temporal lobe herniation and encephalocele. CAB was stopped and she underwent surgical debulking and encephalocele repair. Histopathology confirmed prolactin tumor. CAB 0.75 mg twice a week was resumed.A 50 yo man had incidental detection of a sellar mass after trauma. MRI showed 3.6 cm tumor with minimal contact of right optic nerve, and PRL 3,318 ng/ml. He received CAB 0.5mg twice a week with PRL improvement to 26 ng/mL after 1 month. After 2 months ophthalmology exam showed new left superotemporal depression. PRL was 68 ng/mL and MRI showed 35% mass reduction and new inferior displacement tethering of the chiasm. CAB dose was decreased to 0.25 mg twice a week. Conclusion: Our cases illustrate that rapid biochemical and radiographic response to DA therapy in large prolactinomas warrants close clinical and neuro-ophthalmologic follow-up. We recommend repeating the MRI 3 months after initiation of DA therapy or sooner in case of new mass effect manifestations. Decision regarding DA dose reduction or chiasmopexy for visual field deficits needs to be multi-disciplinary and on a case-to-case basis.

Is there a role for FDG-PET for the assessment of treatment efficacy in Wilms' tumor? A case report and literature review.

BACKGROUND: The role of FDG-PET in Wilms' tumor has not been well established. The aim of this report is to describe the role of FDG-PET to assess chemotherapy efficacy and to show potential correlations between different Standardized Uptake Values (SUVs) and histopathological features in a patient with persisting metastatic disease. CASE DESCRIPTION: A 3-year-old boy was diagnosed with Wilms' tumor without anaplasia. The patient underwent treatment as according to the AIEOP-TW-2003 protocol, for stage III tumors. Therapy was discontinued with no evidence of disease, yet 9 months later thorax metastases were found. Although second and third line treatments were administered, conventional imaging demonstrated stable disease. Metronomic chemotherapy as well was employed for 44 months and FDG-PET was annually performed basing on responsible local physician choice trying to better describe the disease status. Four months after fourth line treatment was stopped, the patient manifested clinical symptoms; lesions began to increase their metabolic activity inhomogeneously. Therapy was hence restarted and SUVs decreased. Metastasectomies were then performed and histology revealed a correlation between viable disease shown by higher FDG-PET uptake and viable tumor areas. CONCLUSIONS: Our case discussion demonstrates that FDG-PET is potentially valuable in Wilms' tumor correlating SUV values and histological features of the tumor after chemotherapy. This case suggests that FDG-PET is a valid tool to assess chemotherapy response in relapsed Wilms' tumor even in case of no evidence of significant dimensional changes under conventional imaging.

Analysis of immune reconstitution in children undergoing cord blood transplantation.

OBJECTIVE: The aim of this study was to investigate and compare immune reconstitution in allogeneic cord blood transplantation (CBT) and bone marrow transplantation (BMT) recipients. MATERIALS AND METHODS: Twenty-three children underwent CBT from either human leukocyte antigen-identical siblings (11 cases) or unrelated donors (12 cases) were enrolled in the study, together with 23 matched children receiving BMT. Patients were analyzed 2-3 and 12-15 months after transplant. Recovery of T-, B-, and NK-lymphocyte subsets, proliferative in vitro response to mitogens, as well as cytotoxic activities, were investigated. RESULTS: CBT recipients showed a marked increase in the number of B lymphocytes as compared with patients who underwent BMT (p < 0.001). The absolute number of CD3(+) and CD8(+) T cells, as well as the proliferative response to T-cell mitogens, recovered with time after transplantation, irrespective of the source of stem cells used. Recipients of unrelated CBT had a better recovery of CD4(+) T lymphocytes (p < 0.01). Among patients experiencing acute graft-versus-host disease (GVHD), children given CBT had a much greater production of CD4(+) CD45RA(+) T cells than BMT recipients (p < 0.005). Recovery of NK cell number and innate cytotoxic activities was fast, irrespective of the source of stem cells used. CONCLUSIONS: Despite the much lower number of lymphocytes transferred with the graft, recovery of lymphocyte number and function toward normal in CBT recipients was rapid and comparable to that observed after transplantation of bone marrow progenitors. This prompt immune recovery possibly was favored by the reduced incidence and severity of GVHD observed in children who underwent CBT.

Vancomycin-resistant Enterococcus faecium infection in three children given allogeneic hematopoietic stem cell transplantation: clinical and microbiologic features.

BACKGROUND AND OBJECTIVES: The emergence of vancomycin-resistant enterococci (VRE) as nosocomial pathogens is a major problem in the US; in Europe, VRE nosocomial infections are uncommon and only rarely have been reported in Pediatric or Neonatal Units. The aim of this study is to report on the clinical and microbiological features of VRE infections in 3 children given hematopoietic stem cell transplantation (HSCT). PATIENTS AND METHODS: Five episodes of vancomycin-resistant Enterococcus faecium (VREF) infection were diagnosed in 3 children given an allogeneic HSCT. Molecular methods, such as random amplification of polymorphic DNA (RAPD) fingerprinting and automated ribotyping, were used in order to define the circulation of strains. RESULTS: All the isolates were resistant to all commercially available agents and showed the VanA genotypic profile. All children were successfully treated with the combination of quinupristin/dalfopristin (QD) plus teicoplanin (TEC), although treatment was not sufficient to eradicate the micro-organism promptly from the gastrointestinal tract. All our children are still alive. After the first isolation of VRE, a surveillance protocol was started and we documented that the rate of colonization in children and their mothers was less than 1.5%. The RAPD method demonstrated the possible nosocomial transmission of one strain. INTERPRETATION AND CONCLUSIONS: Our experience demonstrates that VRE infection is a life-threatening complication in children given HSCT. Prompt diagnosis of this infection and its treatment with the combination of QD and TEC can successfully manage this severe infection in profoundly immunocompromised patients.

Cytohistochemical Analysis of Malus domestica Borkh. Seeds from Shedding and Nonshedding Fruits.

A histological, cytochemical, and ultrastructural investigation of seeds of control (nonshedding) and shedding fruits of Malus domestica Borkh. showed differences in the pattern of nutrient distribution. The kind and amount of storage compounds in the two seeds also differed. Protein bodies and starch were abundant in the control seeds and nearly absent in the seeds of shedding fruit. In the latter, there was a great abundance of phenols that exhibited a specific distribution in different tissues of the chalazal region. A cuticle was present on the inner side of the inner integument of the seeds of both control and shedding fruits. This cuticle was interrupted in the chalaza and formed a pathway for nutrient translocation, what we termed the "window." Cell wall changes observed in the chalazal window were probably associated with the different distribution pattern of storage compounds and with the control of nutrient routing. The delayed and variable development of the embryos of seeds in shed fruits may be related to both the altered pattern of storage substances and their translocation to the embryo.

Graft versus host disease prophylaxis with low-dose cyclosporine-A reduces the risk of relapse in children with acute leukemia given HLA-identical sibling bone marrow transplantation: results of a randomized trial.

Leukemia relapse is a major cause of treatment failure for patients with acute leukemia given allogeneic bone marrow transplantation (BMT). This study evaluated whether a reduction of the dosage of cyclosporine-A (Cs-A) used for graft versus host disease (GVHD) prophylaxis could reduce relapse rate (RR) in children with acute leukemia given BMT. Fifty-nine children who had transplantation from HLA-identical siblings were randomized to receive Cs-A intravenously at a dosage of 1 mg/kg/d (Cs-A1) or of 3 mg/kg/d (Cs-A3) until patients were able to tolerate oral intake. Subsequently, both groups received Cs-A orally at a dosage of 6 mg/kg/d, with discontinuation 5 months after BMT. The probability of developing grade II-IV acute GVHD was 57% for the Cs-A1 group versus 38% for the Cs-A3 group (P =.06); the probability of developing chronic GVHD was 30% for the Cs-A1 group and 26% for the Cs-A3 group (P = NS). Three patients died of grade IV acute GVHD: 2 were in the Cs-A1 and the third in the Cs-A3 group. The RR was 15% for the Cs-A1 group and 41% for the Cs-A3 group (P =.034); 1-year transplant-related mortality estimates were 17% and 7%, respectively (P = NS). With a median observation time of 44 months from BMT, the 5-year event-free survival for children belonging to Cs-A1 and Cs-A3 groups was 70% and 51%, respectively (P =.15). Our data demonstrate that the use of low Cs-A doses is associated with a statistically significant reduction of leukemia relapse, probably due to an increased graft versus leukemia effect. (Blood. 2000;95:1572-1579)

Resolution of immune haemolytic anaemia with allogeneic bone marrow transplantation after an unsuccessful autograft.

Autologous transplantation of lymphocyte-depleted peripheral blood stem cells (PBSC) has been proposed for treatment of patients with severe autoimmune disease. However, several patients have been reported to achieve only transient remissions. We report on a child with thalassaemia intermedia and immune-mediated haemolytic anaemia, given an autologous lymphocyte-depleted PBSC transplant, who relapsed 7 weeks after transplant. A complete remission, lasting 18 months to date, was obtained with allogeneic bone marrow transplantation (BMT) from an HLA-matched unrelated donor. This experience indicates that, in selected cases, allogeneic BMT may be the treatment of choice for life-threatening autoimmune disease. A graft-versus-autoimmunity effect may favour the eradication of the recipient autoaggressive lymphocytes.

Mobilization and selection of peripheral blood hematopoietic progenitors in children with systemic sclerosis.

BACKGROUND AND OBJECTIVE: Autologous transplant of lymphocyte-depleted peripheral blood stem cells has been proposed for treatment of patients with severe autoimmune disease. However, until now, no data are available on the safety and feasibility of both stem cell collection and selection in pediatric patients with these disorders. We report on three children affected by systemic sclerosis with lung involvement, who received chemotherapy and granulocyte colony-stimulating factor (G-CSF) to mobilize autologous peripheral blood progenitors. DESIGN AND METHODS: The priming regimen consisted of cyclophosphamide (CY, 4 g/m(2)) and G-CSF (lenograstim, 10 microg/kg/day starting 2 days after cyclophosphamide administration until stem cell collection). Leukapheresis was performed when WBC and CD34+ cell count were at least 2 x 10(9)/L and 0.03 x 10(9)/L, respectively. In the first patient, positive selection of CD34+ cells was performed through the Ceprate SC stem cell concentrator (CellPro, Bothell, WA, USA). In the remaining 2 children, progenitor cells were also purged with negative selection of CD4+ and CD8+ lymphocytes performed by means of the Isolex 300i device (Baxter). RESULTS: All patients tolerated the priming regimen well and did not present any sign of autoimmune disease exacerbation. Collection was successful in all children and the number of CD34+ cells before selection ranged between 10.7 x 10(6) and 17.6 x 10(6)/kg of patient body weight. The selection of haematopoietic stem cells in the 3 patients resulted in at least 2. 6-log T-cell depletion of the cell content, with a recovery of the initial value of CD34+ cells comprised between 21 and 44%. After, a preparative regimen consisting of CY (200 mg/kg over 4 days) and Campath-1 G in vivo (10 mg/day for 2 consecutive days), patients were transplanted using cryopreserved lymphocyte-depleted progenitor cells. In all cases, a prompt hematopoietic engraftment was observed. INTERPRETATION AND CONCLUSIONS: Taken together these data suggest that mobilization, collection and selection of hematopoietic progenitors are safe and feasible in children with autoimmune disease.

A model for analysing the cost of autologous peripheral blood progenitor cell (PBPC) transplantation.

Data from autologous peripheral blood progenitor cell (PBPC) transplant recipients were used for cost analysis and modelling so as to link the main intervention procedures and clinical events to resource use and costs. This cohort consisted of 64 patients from 4 to 62 years old at transplantation (mean, 36.9 years) who underwent a first transplant between August 1994 and May 1997. The main indications for transplantation were non-Hodgkin's lymphomas (47%), multiple myeloma (30%) and Hodgkin's lymphomas (15%). The course of a patient during the whole transplant procedure was modelled using a Markov chain of six states of health: (1) mobilisation and recovery of PBPC; (2) post-mobilisation phase; (3) conditioning and transplant; (4) critical haematological reconstitution; (5) non-critical haematological reconstitution; (6) death. The probability of transition between the different health states, together with the estimated costs, were the input for the Markov model. The model also managed transition probabilities depending both on the current health state and on various demographic, clinical and procedure-related covariates unique to the patient. The expected time spent in each clinical state and the expected total cost were, therefore, estimated. This analysis gave an actual total cost per transplanted patient of $26,600 (95% range: $24,700 to $43,500) while mean duration was 197 days. The expenses for in-hospital stay accounted for 80% of the costs. Both the probability of staying in the different states, and the consequent cost were dependent on the number of CD34-positive cells collected, the phase and the type of the disease, the subset of patients (either children or adults), and the post-transplant G-CSF prophylaxis. The sensitivity of the estimates to alternative assumptions was studied, and the method of comparing alternative future scenarios by the model was explored.

Does the emergence and persistence of donor-derived leukaemia-reactive cytotoxic T lymphocytes protect patients given an allogeneic BMT from recurrence? Results of a preliminary study.

The frequency of CTL precursors (CTLp) directed towards recipient-derived pre-transplant leukaemic blasts (LB) was measured in the peripheral blood of nine children with acute leukaemia and given BMT from either an HLA-identical sibling or a matched unrelated donor (MUD). Patients were evaluated at various time points between 1 month and more than 2 years after transplantation. A high frequency of donor-derived LB-reactive CTLp was detectable 2-6 months after BMT in all children and persisted for at least up to 18 months in the eight patients in haematological remission, while it rapidly declined in the only patient who relapsed. Generation of LB-reactive T cell clones obtained from some of these patients demonstrates that various T lymphocyte subsets, either HLA class I-restricted/TCR-dependent or HLA-unrestricted, contribute to this phenomenon. The in vitro GVL effect here described seems to be at least partially separated from GVHR, since no correlation was observed between the emergence of LB-reactive CTLp and the development and/or severity of GVHD. Development of LB-reactive CTL in the patients was independent of the frequency of these cells in the donor. These data suggest that donor-derived CTL activity specifically directed towards leukaemic blasts may develop in patients given allogeneic BMT and contribute to the maintenance of a state of haematological remission.

Plasma neurotensin levels in prepubertal children and adults: possible involvement in the regulation of growth hormone secretion.

The present study investigated a possible relationship between plasma neurotensin (NT) and serum growth hormone (GH) levels after GH-stimulation provocative tests in humans. Samples were obtained from twelve prepubertal children and sixteen normal adult volunteers. Basal plasma NT levels were higher in children with growth delay (19.02 +/- 4.01 fmol/ml) (mean +/- SEM) than in normal adults (6.13 +/- 1.1 fmol/ml) (p < 0.001). Basal GH levels in children (1.52 +/- 0.06 ng/ml) were not different from those in adults (0.60 +/- 0.41 ng/ml). After stimulation of GH secretion, NT values decreased when GH peaked, and increased when GH levels diminished. These data suggest that plasma NT levels may be involved in the regulation of GH secretion, as a peripheral signal, probably through modulation of somatostatin release from the median eminence.

Frequency of donor cytotoxic T cell precursors does not correlate with occurrence of acute graft-versus-host disease in children transplanted using unrelated donors.

Bone marrow transplantation (BMT) from unrelated volunteers is frequently associated with both increased incidence and increased severity of acute graft-versus-host disease (GVHD). In the last years, it has been suggested that the analysis of the frequency of cytotoxic T lymphocyte precursors (CTLp) of unrelated HLA-matched donors can be used to detect disparity for HLA class I antigens and as a predictive test for development of severe GVHD. In this report, we summarized our experience regarding 20 pediatric patients affected by various hematological disorders, receiving allogeneic BMT from unrelated donors. HLA class I and II antigens of donor/recipient pairs were determined by means of serological typing, whereas molecular typing of HLA-class II antigens of patients and their potential donors was performed using PCR-SSP and PCR-fingerprinting techniques. CTLp values, estimated using limiting dilution analysis, were high (range, 1:7000-1:40,000) in 9 of 20 patients, while the other 11 children had low or undetectable levels (< 1:100,000) of CTL precursors. CTLp frequency was compared with the incidence and severity of GVHD observed after BMT. Our data demonstrate that the frequency of donor CTLp does not statistically correlate either with the occurrence of clinically significant acute GVHD or with disparity for HLA-class II molecular typing between donor and recipient. In particular, 4 of the 10 evaluable patients with an undetectable CTLp frequency developed grade IV, III, II, and IV acute GVHD, respectively. Although the limited number of subjects studied does not allow us to draw any firm conclusion, our data suggest a certain caution in considering this test suitable for the selection of potential donors.

Distribution of 5-methylcytosine-rich regions in the metaphase chromosomes of Vicia faba.

The DNA methylation pattern of Vicia faba metaphase chromosomes was examined with a specific monoclonal antibody. 5-methylcytosine (5-mC) residues are present in different chromosomal sites, and are particularly abundant in telomeric and/or subtelomeric regions and in certain intercalary bands. Chromosomal localization of methylated regions enables a better knowledge of the lengthwise differentiation of this chromosome complement. Our results also indicate that there may be differences in monoclonal antibody binding between corresponding regions of homologous chromosomes in V. faba. This behaviour is detectable in specific regions with different frequencies. The data support results previously obtained for Allium cepa metaphase chromosomes using the same monoclonal antibody.

[Iopentol in varix radiography. Double blind comparison with iohexol]. / Iopentolo nella varicosografia. Confronto in doppio cieco con Iohexolo.

This trial was aimed at comparing the tolerance and the safety of Iopentol, a new nonionic monomeric contrast agent, with Iohexol, a reference compound already on the market and commonly used in similar trials. Sixty adult patients (41 women and 19 men, aged 23 to 76 years, mean age: 51.4 years) referred to our Department of Radiology for varicography 24 hours before surgery were examined; the trial was designed as a double-blind, parallel two-group comparison of Iopentol 300 mg/ml and Iohexol 300 mg/ml with 30 patients in each treatment group. No adverse reactions were observed in our series of patients. Only slight and not clinically significant changes were observed in heart rate and blood pressure values. The immunohistochemical parameters were studied for postvaricography anatomopathologic complications of the injected veins (A-Actin ML, Vimentin, Factor VIII, CD31, CD68, CK, Ulex Europaeus I, Lecitin, Desmin, Laminin) and no statistically significant differences were observed between the two groups. The histologic specimens showed only venous wall changes, as diagnosed on admission. All radiographs were classified as technically adequate and contrastographic efficacy was defined as "good" in all patients by two independent radiologists. To conclude, our trial on the efficacy and safety of the two nonionic monomeric radiographic contrast agents Iopentol and Iohexol proved the two contrast agents to be equally effective and well tolerated, which makes Iopentol a good alternative to Iohexol in varicography.

[Color Doppler and phlebography in the Paget-Schroetter syndrome]. / Color Doppler e flebografia nella sindrome di Paget-Schroetter.

The authors compared the adequacy of phlebography and color-Doppler US in the diagnosis of subclavian-axillary thrombosis, or Paget-Schroetter syndrome. Ten patients with subclavian-axillary thrombosis (8 men and 2 women, aged 16 to 55 years, mean age: 30 years) were examined over a two-year period. All of them underwent color-Doppler US and conventional phlebography in the same session. US findings were in agreement with phlebographic results in all cases as to thrombosis presence and site. The thrombosis involved the subclavian-axillary vein in 8 cases, the subclavian-innominate vein in 1 case and both veins in 1 case. Color-Doppler US, however, yielded no information relative to the superior vena cava; these data were always obtained with phlebography even though in 4 cases that segment had to be studied with phlebographic opacification via contralateral route. Furthermore, US failed to clearly demonstrate the thrombosis involving the last axillary valve; preserving this valve is indeed the main aim of fibrinolysis since its integrity, at this level, prevents venous reflux independent of subclavian-axillary trunk recanalization, thus reducing the severe symptomatologic sequelae following postphlebitic damage. Phlebography showed the valve and its possible involvement in all cases. In 4 cases phlebography also demonstrated compressive thoracic inlet syndrome, which had been missed by US, yielding the main anatomic elements for following surgery. To conclude, the authors suggest noninvasive color-Doppler US as the screening method of choice, while phlebography remains the gold-standard technique to be performed in all Doppler positive cases: in fact, the latter method yields more pieces of information and is more panoramic than the former, besides allowing fibrinolysis effects to be studied and the possible presence of an associated thoracic inlet syndrome to be investigated.

[Subpopliteal muscular venous thrombosis in aching calf syndrome]. / Le trombosi venose muscolari sottopoplitee nella sindrome del polpaccio dolente.

The lower limbs of 84 consecutive patients (48 women and 36 men, age range: 16-75 years, average: 38 years) suffering from acute aching calf symptoms were examined with conventional and color Doppler US. Thirteen cases of muscular thrombosis in the calf were observed, together with 19 cases of deep venous thrombosis, 7 post-phlebitic syndromes, 9 lymphatic obstructions, 6 muscular hematomas and 7 popliteal articular cysts. Case history, clinical signs and phlebography do not allow the former condition to be differentiated definitely from the latter ones--especially hematomas and Baker's cysts which require different treatment protocols. The authors stress the value of conventional and color Doppler US imaging in the aching calf syndrome for its differential diagnostic capabilities. The other more complicated and expensive radiologic and laboratory techniques should be used in case of negative US findings only.

[Deep venous thrombosis of the legs. Diagnostic results comparing the duplex and the color-Doppler methods]. / Trombosi venosa profonda localizzata agli arti inferiori. Risultati diagnostici a confronto fra sistema duplex e color-Doppler.

Thirty-eight patients (45 limbs on the whole) with clinical suspicion of deep venous thrombosis in the lower limbs were examined with duplex US and color-Doppler flow mapping. The results were compared with those of ascending phlebography used as a reference. Disease sites included distal localizations, limited to the leg, with no involvement of the popliteal vein, and proximal localizations, involving the popliteal vein to the iliac segment. In case of proximal thrombosis, duplex US had 81% sensitivity, 93% specificity, 86% positive and 90% negative predictive values. Color-Doppler flow mapping had 87% sensitivity, 96% specificity, 93% positive and negative predictive values. In case of distal localizations, the results were poorer with both methods; duplex sensitivity decreased to 60% and specificity to 83% with 64% positive and 80% negative predictive values. Color-Doppler results were slightly higher, with 80% sensitivity, 93% specificity, 85% positive and 90% negative predictive values. Thus, the authors believe color-Doppler flow mapping to be adequate as the imaging method of choice when deep venous thrombosis is suspected. Color-Doppler imaging yields better results in distal localizations and makes the examination easier, quicker and more panoramic. Phlebography should be employed in questionable cases and is required for the diagnosis of limited thromboses, which are at risk for embolism, as those we observed in the adductor canal, which are difficult to diagnose with US.

[Hemorrhage caused by lipoma of the mesocolon protruding into the intestinal lumen]. / Hémorragie par lipome du mésocôlon proéminant dans la lumière intestinale.

Investigation of a patient with rectal bleeding showed the hemorrhage to be due to a lipoma of mesocolon protruding into the transverse colon. A literature review failed to discover a report of a similar case.