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Biomedical subjects

G Locatelli

Publications and source records attributed to G Locatelli.

At least 19 recordsLinked to original sources
PubMed2004

A new technical variant for extramucosal pyloromyotomy: the Tan-Bianchi operation moves to the right.

BACKGROUND: Since its first publication in 1986, the Tan-Bianchi procedure for treatment of infantile hypertrophic pyloric stenosis has displayed a growing consensus among pediatric surgeons. However, in up to 30% of cases, the supraumbilical skin fold incision does not allow a comfortable access. Delivery through this route, a large pyloric tumor into the wound to perform a pyloromyotomy, can be fairly difficult and time consuming and may damage the gastric or duodenal serosa by tearing. Other technical variants have been proposed to overcome these limitations, but some are more complicated, some are demanding, and some others can worsen the final cosmetic result. METHODS: The authors present a personal modification to the Tan-Bianchi procedure that they have successfully applied in the last 25 cases of infantile hypertrophic pyloric stenosis. A right semicircular umbilical skin fold incision is performed. The anterior rectus abdominis muscle (RAM) sheath is incised vertically all around the umbilicus, the muscle is laterally displaced, and its posterior sheath and the peritoneal cavity entered in the same line. Because all incisions lay in the same axis, the abdominal cavity is largely opened by 2 retractors without the need for excessive increased traction as it often happens with the supraumbilical approach. RESULTS: This technical variant was particularly useful to deliver a very large hypertrophic pyloric muscle into the wound. There were no complications and excellent cosmetic results were obtained in all patients. CONCLUSIONS: These observations suggest that a right semicircular umbilical skin fold incision is an attractive alternative for pyloromyotomy mostly when facing with a large pyloric tumor.

Digestive System Surgical Procedures↗
PubMed2001

Development of reverse transcriptase PCR assays for detection of active human herpesvirus 6 infection.

We developed reverse transcriptase (RT) PCR assays for the detection of mRNA from three spliced genes of human herpesvirus 6 (HHV-6), the immediate-early genes U16/U17 and U89/U90 and the late gene U60/U66. Sequence analysis determined the splicing sites of these genes. The new assays may be instrumental in investigating the association between HHV-6 and disease.

Genes, Immediate-Early↗
PubMed2000

Real-time quantitative PCR for human herpesvirus 6 DNA.

The diagnosis of human herpesvirus 6 (HHV-6) infection represents a complex issue because the most widely used diagnostic tools, such as immunoglobulin G antibody titer determination and qualitative DNA PCR with blood cells, are unable to distinguish between latent (clinically silent) and active (often clinically relevant) infection. We have developed a new, highly sensitive, quantitative PCR assay for the accurate measurement of HHV-6 DNA in tissue-derived cell suspensions and body fluids. The test uses a 5' nuclease, fluorogenic assay combined with real-time detection of PCR amplification products with the ABI PRISM 7700 sequence detector system. The sensitivity of this method is equal to the sensitivity of a nested PCR protocol (lower detection limit, 1 viral genome equivalent/test) for both the A and the B HHV-6 subgroups and shows a wider dynamic range of detection (from 1 to 10(6) viral genome equivalents/test) and a higher degree of accuracy, repeatability, and reproducibility compared to those of a standard quantitative-competitive PCR assay developed with the same reference DNA molecule. The novel technique is versatile, showing the same sensitivity and dynamic range with viral DNA extracted from different fluids (i.e., culture medium or plasma) or from tissue-derived cell suspensions. Furthermore, by virtue of its high-throughput format, this method is well suited for large epidemiological surveys.

DNA, Viral↗
PubMed2000

Coinfection of SCID-hu Thy/Liv mice with human herpesvirus 6 and human immunodeficiency virus type 1.

Human herpesvirus 6 (HHV-6) has been proposed as a potential cofactor in the progression of human immunodeficiency virus type 1 (HIV-1) disease. We used the SCID-hu Thy/Liv mouse model to evaluate the in vivo interactions between HHV-6 and HIV-1. Our results demonstrate that HHV-6 and HIV-1 can simultaneously replicate in the human thymus in vivo. In this model, however, the presence of one virus appears not to modify the replication or cytopathicity of the other.

Animals↗
PubMed2000

The kidney transplant program at the Bergamo Center.

The kidney transplant program at the Ospedali Riuniti of Bergamo, Italy was established in 1989. Since its inception, 367 patients have been transplanted, including 357 kidney transplants from cadaveric donors and 10 from living-related donors. Overall 8-year patient and graft survival rates were 94% and 77%, respectively. By 1995 our unit co-ordinated the activity of the Department of Immunology and Clinics of Organ Transplantation, Ospedali Riuniti--Mario Negri Institute for Pharmacological Research, Bergamo. The dual "marginal" kidney transplant program in the same recipient was launched in August 1997, as a part of an international cooperative network which established the "Double Kidney Transplant Group" (DKG). To date, 19 dual kidney transplants have been successfully performed in our center. Four combined heart-kidney transplants and 2 combined liver-kidney transplants have also been performed. During the past 4 years several studies involving conventional antirejection drugs were carried out, particularly focussing our attention on cyclosporine (CsA) through pharmacokinetic and pharmacodynamic approaches: 1) a simplified method to evaluate daily exposure to CsA has been set up; 2) the monitoring of calcineurin activity in whole blood samples was evaluated as a way to optimize CsA dosing. As for the new immunosuppressants, studies are ongoing with mycophenolate mofetil (MMF). We are co-ordinating a prospective multicenter randomized trial of steroid sparing in kidney transplant recipients given MMF or azathioprine as a part of their immunosuppression therapy (MY.S.S. study). This involves 9 Italian transplant centers and 2 European centers. Up to now 325 patients have been randomized. Moreover we have set up an HPLC method for measuring plasma mycophenolic acid (MPA), and examined the possibility of optimizing MMF dosing by drug pharmacokinetic monitoring. Further studies have been addressed to chronic allograft nephropathy. The nature and mediators of renal lesions in kidney transplant patients given CsA have been explored taking into account the gene expression of endothelin-1, RANTES and MCP-1 in graft specimens from patients who had evidence of CsA nephrotoxicity, chronic rejection, or no lesions at histological examination. The impact of percutaneous transluminal angioplasty and stenting of posttransplant renal artery stenosis on renal function recovery was also recently examined. From this study we conclude that the procedure is safe and effective to normalize the functional changes sustained by hemodynamically significant artery stenosis. Moreover, Doppler ultrasound scanning is an useful, reliable, non-invasive tool to monitor the renal function response to artery revascularization. Thanks to the long-lasting co-operation with the Negri Bergamo Laboratories, we had in the past and still have an active program in experimental animals to investigate strategies for transplant tolerance and transplant gene therapy, besides addressing some issues related to the immunological barrier of xenotransplantation.

Academic Medical Centers↗
PubMed1999

CD46 is a cellular receptor for human herpesvirus 6.

Human herpesvirus 6 (HHV-6) is the etiologic agent of exanthema subitum, causes opportunistic infections in immunocompromised patients, and has been implicated in multiple sclerosis and in the progression of AIDS. Here, we show that the two major HHV-6 subgroups (A and B) use human CD46 as a cellular receptor. Downregulation of surface CD46 was documented during the course of HHV-6 infection. Both acute infection and cell fusion mediated by HHV-6 were specifically inhibited by a monoclonal antibody to CD46; fusion was also blocked by soluble CD46. Nonhuman cells that were resistant to HHV-6 fusion and entry became susceptible upon expression of recombinant human CD46. The use of a ubiquitous immunoregulatory receptor opens novel perspectives for understanding the tropism and pathogenicity of HHV-6.

Antibodies, Monoclonal↗
PubMed1999

Human herpesvirus 6 (HHV-6) causes severe thymocyte depletion in SCID-hu Thy/Liv mice.

Human herpesvirus 6 (HHV-6) is a potentially immunosuppressive agent that may act as a cofactor in the progression of AIDS. Here, we describe the first small animal model of HHV-6 infection. HHV-6 subgroup A, strain GS, efficiently infected the human thymic tissue implanted in SCID-hu Thy/Liv mice, leading to the destruction of the graft. Viral DNA was detected in Thy/Liv implants by quantitative polymerase chain reaction (PCR) as early as 4 d after inoculation and peaked at day 14. The productive nature of the infection was confirmed by electron microscopy and immunohistochemical staining. Atypical thymocytes with prominent nuclear inclusions were detected by histopathology. HHV-6 replication was associated with severe, progressive thymocyte depletion involving all major cellular subsets. However, intrathymic T progenitor cells (ITTPs) appeared to be more severely depleted than the other subpopulations, and a preferred tropism of HHV-6 for ITTPs was demonstrated by quantitative PCR on purified thymocyte subsets. These findings suggest that thymocyte depletion by HHV-6 may be due to infection and destruction of these immature T cell precursors. Similar results were obtained with strain PL-1, a primary isolate belonging to subgroup B. The severity of the lesions observed in this animal model underscores the possibility that HHV-6 may indeed be immunosuppressive in humans.

Animals↗
PubMed1999

Impact of new treatments for respiratory failure on outcome of infants with congenital diaphragmatic hernia.

UNLABELLED: Term and near-term newborn infants with congenital diaphragmatic hernia (CDH), symptomatic in the first 24 h of life or diagnosed antenatally, without other significant malformations were treated at our hospital with high-frequency oscillatory ventilation (HFOV) as a primary modality of ventilation and elective delay in surgical repair after a period of stabilisation. When unresponsive to HFOV, infants were treated with surfactant, inhaled nitric oxide (iNO) and extracorporeal membrane oxygenation (ECMO) to achieve pre-operative stabilisation. From October 1994 to August 1998, 28 newborn infants with CDH were managed with such treatment; mean birth weight was 3184 +/- 535 g and gestational age 38.5 +/- 1.85 weeks. Age at operation was 68 +/- 35 h. In 9 cases, large diaphragmatic defects required the use of a prosthetic patch (Gore-tex). HFOV was used for primary ventilation in inborn patients (n = 16); outborn infants (n = 12) were placed on HFOV at admittance. A total of 15 patients (53%) were stabilised using only HFOV. Bovine surfactant was administered in 12 infants and 4 responded. iNO was used in eight infants and five responded. ECMO was used in three outborn patients and one survived. Overall, out of 28 infants, 25 survived (89%). Neurological examination (Amiel-Tison and Grenier) of 15 infants showed transient anomalies at 6 months in 40% of infants, while a normal neurological examination was present in all patients at 1 year. The development quotient (Griffiths scales) was within normal values in ten and mildly abnormal in two infants tested at 1 year. CONCLUSION: Management based on early HFOV, eventually associated with surfactant, iNO and ECMO to achieve preoperative stabilisation, resulted in a good survival rate (89%) and good neurodevelopmental outcome at 1 year of age in infants with CDH.

Animals↗
PubMed1998

Cancer procoagulant and tissue factor are differently modulated by all-trans-retinoic acid in acute promyelocytic leukemia cells.

All-trans-retinoic acid (ATRA) downregulates the expression of two cellular procoagulants, tissue factor (TF) and cancer procoagulant (CP), in human promyelocytic leukemia cells. To evaluate whether or not changes of the procoagulant activities (PCAs) may share mechanisms with the ATRA-induced cyto-differentiation process, we have characterized the effect of ATRA on the TF and CP expression by NB4 cells, an ATRA maturation-inducible cell line, and two NB4-derived cell lines resistant to ATRA-induced maturation, the NB4. 306 and NB4.007/6 cells. Next, we evaluated the effect on the PCAs of the NB4 parental cells of three synthetic retinoid analogues, ie: AM580 (selective for the retinoic acid receptor [RAR] alpha), capable to induce the granulocytic differentiation of NB4 cells; and CD2019 (selective for RARbeta) and CD437 (selective for RARgamma), both lacking this capability. Cells were treated with either ATRA or the analogues (10(-6) to 10(-8) mol/L) for 96 hours. The effect on cell differentiation was evaluated by morphologic changes, cell proliferation, nitro blue tetrazolium reduction assay, and flow cytometry analysis of the CD33 and CD11b surface-antigen expression. PCA was first measured in 20 mmol/L Veronal Buffer cell extracts by the one-stage clotting assay of normal and FVII-deficient plasmas. Further TF and CP have been characterized and quantified in cell-sample preparations by chromogenic and immunological assays. In the first series of experiments, ATRA downregulates both TF and CP in NB4 parental cells, as expected. However, in the differentiation-resistant cell lines, it induced a significant loss of TF but had little or no effect on CP. In a second series of experiments, in the NB4 parental cells, the RARalpha agonist (AM580) induced cell maturation and reduced 91% CP expression, whereas CD437 and CD2019 had no cyto-differentiating effects and did not affect CP levels. On the other hand, in the same cells the TF expression was reduced by ATRA and AM580, but also by the RARbeta agonist CD2019, which did not induce cell maturation. These data indicate that in NB4 cells, ATRA modulation of CP occurs in parallel with signs of cell differentiation, while the regulation of TF appears to be at least in part independent from these processes, and involves both alpha and beta nuclear retinoid receptors.

Antineoplastic Agents↗
PubMed1997

Sequential monitoring of urine-soluble interleukin 2 receptor and interleukin 6 predicts acute rejection of human renal allografts before clinical or laboratory signs of renal dysfunction.

BACKGROUND: The significance of noninvasive techniques to the early diagnosis of acute rejection in kidney transplants remains elusive. In this study, we examined whether an early posttransplant increase in serum- and urine-soluble interleukin (IL) 2 receptor (sIL-2R) and IL-6 levels predicted acute rejection. METHODS: Sequential determinations of serum and urine sIL-2R and IL-6 were performed in the first 30 postoperative days in 40 renal transplant patients. Changes during the posttransplant period observed in 26 patients who had one or more episodes of acute rejection (group A) were compared with those recorded in 14 patients who did not experience acute rejection of their graft (group B). RESULTS: Serum sIL-2R was higher than normal in patients of groups A and B without statistical differences between the two groups. In the first 3 days after transplantation, urinary sIL-2R was higher than normal in group A but not in group B. Urinary sIL-2R at days 2 and 3 was significantly higher (P<0.05) in group A than in group B. In the first 5 days after transplantation, urinary IL-6 was persistently higher than normal in group A, whereas it progressively decreased to normal value on day 4 in group B. Sudden increases (doubling within 24 hr) in urine IL-6 preceded clinical diagnosis of acute rejection by a mean period of 2 days, with an 87% sensitivity and a 64% specificity, and also predicted recurrent rejection episodes. CONCLUSIONS: Sequential monitoring of urinary sIL-2R and IL-6 levels does allow very early diagnosis of rejection without invasive procedures. Specifically, high urinary sIL-2R in the first 5 posttransplant days identifies the subgroup of patients at risk. In the subsequent days, a sudden increase in urinary IL-6 occurs in those of the above patients who will indeed reject their graft.

Acute Disease↗
PubMed1995

[Bladder hernia: a clinical case].

The Authors report a case of inguinal bladder hernia and briefly refer about the different kinds of this rare pathology which is often associated to the commonest inguinal hernia. They, moreover, point out the surgical treatment which has to aim to the repositioning of the bladder and to solve the cervicovesical obstruction.

Hernia, Inguinal↗
PubMed1995

Extracorporeal membrane oxygenation with veno-venous bypass and apneic oxygenation for treatment of severe neonatal respiratory failure.

Seven newborn infants with life-threatening respiratory failure were treated with veno-venous (V-V) extracorporeal lung support and apneic oxygenation after maximal ventilatory and pharmacological treatment failed. Diagnosis were meconium aspiration syndrome in 3 cases, respiratory distress syndrome in 2, sepsis in 1, congenital diaphragmatic hernia in 1. Before ECMO 6 infants received tolazoline, 4 surfactant, 3 high frequency ventilation, 1 prostaglandin E, 1 epoprostenol, 2 nitric oxide. Newborns were highly hypoxemic at admission and all but one underwent rescue cannulation. V-V bypass was performed with a single lumen single cannula and tidal flow was generated by an alternating clamp using a non-occlusive roller pump. The mean duration of bypass was 162.4 +/- 162.3 hours and infants were extubated 94.5 +/- 74.8 hours after decannulation. Five newborns survived and two died. Growth and neurologic development of the older children is normal. The extracorporeal lung support with V-V bypass associated with apneic oxygenation was effective in reversing severe neonatal respiratory failure unresponsive to maximal ventilatory and pharmacological support. An early referral, prior to meeting ECMO criteria, is important in order to avoid hypoxic complications preceding ECMO.

Adrenergic alpha-Antagonists↗
PubMed1995

Squamous carcinoma of the epiglottis with sebaceous differentiation. Report of a case.

A case of squamous cell carcinoma with sebaceous metaplasia arising in the epiglottis is reported. Extracutaneous neoplasms that show sebaceous differentiation have been mainly described in the major salivary glands. To date only one case of prominent sebaceous differentiation in a carcinoma arising in the vallecula has been reported. In the present paper we describe a similar case arising in the larynx.

Alcohol Drinking↗
PubMed1994

Endodermal sinus (yolk sac) tumor of the urachus.

A rare case of endodermal sinus (yolk sac) tumor of urachal remnants in a two-year-old infant is described. The tumor was located in the upper part of the bladder and appeared to arise from urachal remnants. The tumor could be entirely removed. The patient is free of tumor after three years and eight months follow-up.

Chemotherapy, Adjuvant↗
PubMed1994

Acute tubular necrosis in a newborn suffering from neonatal necrotizing enterocolitis.

The case history of a newborn who at birth had a necrotizing enterocolitis, worsened by an acute tubular necrosis and anuresis, is presented. A continuous arteriovenous hemofiltration was instituted for the baby, who had previously undergone abdominal surgery with resection of the necrotic bowel. The hypothesis that necrotizing enterocolitis could be the cause of acute tubular necrosis in infancy is discussed.

Enterocolitis, Pseudomembranous↗