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Biomedical subjects

G Ruggeri

Publications and source records attributed to G Ruggeri.

At least 19 recordsLinked to original sources

Effects of K(ATP) channel blockade by glibenclamide on the warm-up phenomenon.

AIMS: The increased tolerance to myocardial ischaemia observed during the second of two sequential exercise tests, i.e. the warm-up phenomenon, has been proposed as a clinical model of ischaemic preconditioning. As ATP-sensitive K+ channels appear to be a mediator of ischaemic preconditioning in both experimental and clinical studies, the aim of this study was to investigate the role of K(ATP) channels in the warm-up phenomenon. METHODS AND RESULTS: Twenty-six patients with coronary artery disease were randomized to receive 10 mg oral glibenclamide, a selective ATP-sensitive K+ channel blocker, or placebo. Sixty minutes after glibenclamide or placebo administration, patients were given an infusion of 10% dextrose (8 ml x min(-1)) to correct glucose plasma levels or, respectively, an infusion of saline at the same infusion rate. Thirty minutes after the beginning of the infusions, both patient groups underwent two consecutive treadmill exercise tests, with a recovery period of 15 min to re-establish baseline conditions. Before exercise tests, blood glucose levels were similar in placebo and glibenclamide groups (96 +/- 10 vs 105 +/- 22 mg x 100 ml(-1), P=ns). After placebo administration, rate-pressure product at 1.5 mm ST-segment depression significantly increased during the second exercise test compared to the first (220 +/- 41 vs 186 +/- 29 beats x min(-1) x mmHg x 10(2), P<0.01), but it did not change after glibenclamide (191 +/- 34 vs 187 +/- 42 beats x min(-1) x mmHg x 10(2), P=ns), with a significant drug-test interaction (P=0.0091, at two-way ANOVA). CONCLUSIONS: Glibenclamide, at a dose previously shown to abolish ischaemic preconditioning during coronary angioplasty, prevents the increase of ischaemic threshold observed during the second of two sequential exercise tests. These findings confirm that ischaemic preconditioning plays a key role in the warm-up phenomenon and that in this setting is, at least partially, mediated by activation of ATP-sensitive K+ channels.

Adenosine Triphosphate

Prenatal diagnosis of bladder exstrophy: what counseling?

PURPOSE: Bladder exstrophy has recently become one of the several congenital malformations detectable prenatally by fetal ultrasonography, which implies the necessity of a correct prognostic evaluation of quality of life on which therapeutic termination of pregnancy may depend within the temporal limits stated by the law. While maintaining a preeminently informative role, prenatal counseling has gained increasing relevance for the quality of life long-term prognosis in adults affected by bladder exstrophy, particularly in regard to urinary continence, and sexual and reproductive problems in male and female individuals. We report a case of bladder exstrophy diagnosed at 22 week of gestation, and comprehensively review the literature on prenatal diagnostic tools and procedures as well as long-term followup in such cases. MATERIALS AND METHODS: At week 22 of gestation a woman underwent prognostic counseling due to the diagnosis of fetal bladder exstrophy made by prenatal ultrasound. After counseling the parents elected pregnancy termination. In addition, literature data were analyzed in regard to quality of life and bladder exstrophy. RESULTS: We believe that the rarity of the prenatal diagnosis of this abnormality has resulted in the lack of a comprehensive review of necessary counseling criteria. CONCLUSIONS: We suggest what we consider to be a valid counseling approach for parents after a prenatal diagnosis of bladder exstrophy.

Adult

Histopathological changes in bone marrow biopsies from patients with chronic myeloid leukaemia after treatment with recombinant alpha-interferon.

AIMS: Recombinant alpha-interferon (r-IFN) is an effective therapy for chronic myeloid leukaemia (CML), inducing haematological and major cytogenetic response in 70% and 30% of patients, respectively. In this study we have evaluated the significance of bone marrow (BM) histology on the subsequent response to r-IFN therapy, as well as the morphological changes induced by r-IFN within BM. METHODS AND RESULTS: 73 BM biopsies were studied from 21 patients with Ph1-positive CML in chronic phase at diagnosis and at different times during r-IFN treatment. At diagnosis the probability of achieving a major or complete cytogenetic response was significantly higher in patients with a total marrow cellularity lower than 90% (P = 0.02). During therapy with r-IFN, significant BM changes included disappearance of the CML pattern (P = 0.0002), reduction of M:E ratio (P = 0.0009) and total cellularity (P = 0.0027), and increase in number of terminal megakaryocytes (P = 0.0009) and of fatty tissue regeneration (P = 0.037); only after long-term therapy (mean 20 months), did reticulin fibrosis increase significantly (P = 0.032). CONCLUSIONS: The overall BM morphology in response to treatment displayed different pictures, ranging from persistence of CML (25 biopsies out of 51), to reversion to normal histology (14 out of 51). Persistence of diffuse morphological abnormalities was associated with lack of cytogenetic responsiveness (P = 0.025).

Adolescent

A case of non-functioning antiperistaltic retrosternal colic conduit replaced in situ and substituted with an isoperistaltic segment of ileum-caecum.

The authors report the case of a female patient, affected by long-gap oesophageal atresia, who, at 5 months old, was operated on for retrosternal substitution with a right-transverse antiperistaltic colic segment, in her local district hospital. Due to the anomalous position the neooesophagus never worked, and the baby was seriously dysphagic and failed to thrive. For this reason, when she was 11 months old, she was reoperated in our department. Through a medium sternolaparotomy the antiperistaltic colon was removed and replaced between the left and right colon; reconstruction was carried out with a retrosternal and isoperistaltic segment of ileo-caecum. The reoperation resolved her problems. This case is reported to confirm the author's opinion that all intestinal conduits must be positioned in the isoperistaltic direction.

Cecum

Continuous infusion of carboplatin during conventional radiotherapy treatment in advanced squamous carcinoma of the cervix uteri IIB-IIIB (UICC). A phase I/II and pharmacokinetic study.

OBJECTIVE: A prospective, single-arm phase-I/II trial performed to assess the efficacy and toxicity of the concomitant use continuous infusion of low-dose carboplatin and pelvic conventional radiotherapy in patients with locally advanced squamous cell carcinoma of the cervix. MATERIALS AND METHODS: Between January and July 1994, a total of 12 patients consecutively diagnosed to have squamous cell carcinoma of the cervix uteri stages IIB-IIIB UICC-TNM (five patients, IIB; and seven patients, IIIB) entered the study. All patients were evaluated by a gynecologist and a radiation oncologist and were submitted to standard pretreatment staging procedures. Radiation was delivered with 10-MeV photon beams with the shrinking-field technique. The patients received 2 Gy radiotherapy daily, 5 fractions per week, up to a planned total of 60 Gy in 6 weeks to the primary tumor and 46 Gy in 4 weeks to the whole pelvis. Irradiation was performed using four fixed orthogonal fields. One intracavitary insertion, 8 Gy to point A (dose rate, 1.1 Gy/h), was performed immediately after external pelvic irradiation. Carboplatin (12 mg/m2/day) was also administered in a continuous infusion, starting 1 day before the first fraction of radiotherapy. The platinum in plasma and urine, as well as the platinum concentration in the cytosols of lymphocytes and tumor, was measured weekly. RESULTS: A complete response was seen in nine (75%) of the 12 patients. Of the nine patients who achieved a complete remission, only one had subsequent failure in the pelvis. The total pelvic failure rate was 33.3% (four of 12 patients). With a median follow-up time of 20 months, the actuarial survival rate at 24 months was 64.8%. All patients completed the treatment without major protocol violations. Grade-2 leukopenia (in nine patients) and grade-1 nausea and vomiting (in five) were the most common acute toxicities. There was one grade-3 hematologic toxicity. Grade-3 late complications were observed in 16.6% of cases (two of 12 patients). On days 28 and 42 of the treatment, the mean total platinum plasma concentrations were 491 micrograms/L (SD = 129) and 672 micrograms/L (SD = 160), and the ultrafilterable fraction was 8-10%. At the same time points, the concentration in lymphocytes was constant at 21 picograms (pg) platinum/lymphocyte. The levels of platinum concentration measured on days 14 and 28 in the cytosols of tumor cells were 0.3 microgram/g (SD = 0.1) and 0.93 microgram/g (SD = 0.2). CONCLUSION: The combination of continuous infusion of carboplatin and radiotherapy at the aforementioned doses in patients with locally advanced cervical carcinoma resulted in a relatively low frequency of significant acute and late complications. Platinum in normal tissue (picograms per lymphocyte) was stable from week 1 of treatment, whereas the platinum steady state in plasma and in tumor cells was not reached in 6 weeks and was below that required in vitro to produce radiopotentiation. Further studies to determine the optimal dose of carboplatin and irradiation are needed prior to the initiation of phase-III studies.

Adult

Effects of A1 adenosine receptor blockade on the warm-up phenomenon.

The increased tolerance to myocardial ischemia observed during the second of two sequential exercise tests, i.e. the warm-up phenomenon, has been proposed as a clinical model of ischemic preconditioning. Adenosine appears to be a mediator of ischemic preconditioning in both experimental and clinical settings. The purpose of this study was to investigate the role of A1 adenosine receptors in the warm-up phenomenon. A double-blind, placebo-controlled, cross-over design was used. Twelve patients with coronary artery disease and positive exercise test were randomized to receive either bamiphylline, a selective A1 adenosine receptor antagonist, or placebo, immediately prior to two consecutive treadmill exercise tests carried out on day 1. Then, on day 2 all patients underwent two consecutive exercise tests immediately after administration of the remaining treatment. During the first exercise test, bamiphylline, compared to placebo, increased the time to and rate-pressure product at 1.5 mm ST-segment depression (from 317 +/- 118 to 423 +/- 127 s, p < 0.05 and from 199 +/- 38 to 230 +/- 36 b/min.mmHg.10(2), p < 0.05, respectively). After both placebo and bamiphylline infusions, time to 1.5 mm ST-segment depression during the second exercise test was greater than that during the first test (445 +/- 121 vs 317 +/- 118 s, p < 0.001 and 483 +/- 128 vs 423 +/- 127 s, p < 0.05, respectively), as was rate-pressure product at 1.5 mm ST-segment depression (228 +/- 40 vs 199 +/- 38 b/min.mmHg.10(2), p < 0.01 and 253 +/- 42 vs 230 +/- 36 b/min.mmHg.10(2), p < 0.05, respectively). In conclusion, bamiphylline, at a dose able to increase ischemic threshold and exercise tolerance compared to placebo, does not prevent the warm-up phenomenon. These findings suggest that, in the setting of the warm-up phenomenon, A1 adenosine receptor blockade is insufficient to prevent ischemic preconditioning.

Aged

Ectopic cervical thymus: case report.

Ectopic cervical thymus is rarely considered in the differential diagnosis of cervical masses: this lesion is essentially asymptomatic and generally occupies a position in the neck along the carotid sheath, underneath the sterno-cleido-mastoid muscle. It is supposed that most of these masses arise as a consequence of migration defects during glandular embryogenesis. Ectopic thymus rarely invades contiguous structures but in the literature some cases of malignant transformation of aberrant cervical thymus have been reported. Some non-invasive investigations (MRI, ultrasonography) are useful but accurate diagnosis depends eventually on surgical excision and histologic examination.

Choristoma

[Relationship between prenatal and postnatal echographic diagnosis of uropathy: is mass screening useful?].

Urinary tract malformations have a 1-2% incidence. An early diagnosis of these defects allows to realize as fast as possible the best medical and/or surgical treatment, preventing or at least slowing down the evolution toward chronic renal failure. Urinary tract malformations are particularly suitable for a "prevention" program due to their elevated incidence, to the "silent period" preceding complications and to the therapeutic possibilities strictly related to an early diagnosis. Ultrasound screening can easily identify congenital urinary tract abnormalities, especially obstructive ones, but unfortunately almost half of the cases escape even the most expert "eye". It is necessary a complete check-up right after birth. We tried to compare the method and the results of prenatal screening with the postnatal one, already used in many hospitals. We believe, even following our experience, that the screening for urinary tract malformations of all the neonatal population is a goal to pursue and achieve as soon as possible for its high sensitivity and specificity.

Cost-Benefit Analysis

Lumbar hernia as congenital aplasia of lumbo-dorsal muscle.

A newborn with congenital aplasia of the dorso-lumbar muscles is described. The lesion seemed to be a congenital lumbar hernia and is a very uncommon feature. The child underwent surgery and although it was a very large bilateral defect, it was repaired without using prosthetic patch. The surgical technique and the results are discussed. The function of the region was conserved as demonstrated at the check-up of the child at 6 and 12 months of age.

Hernia

[Critical review of the diagnostic protocol in patients with head injury].

The results of a retrospective review of the conventional radiographs performed on head injury patients are reported. Skull radiography findings were compared with clinical symptoms and CT results, when CT was performed, to investigate the presence of intracranial lesions. The radiographs of 2,285 adult patients of both sexes were evaluated: skull fractures were observed in 21/2,285 patients (0.9%) only. CT was positive for an intracranial lesion in 18 of 21 patients (85.71%). Clinical symptoms were divided into three groups according to lesion severity and to neurologic impairment. 979 patients were asymptomatic and 1,306 were symptomatic: 1,114 patients were included in group I, their symptoms being nausea, vomit and loss of consciousness for less than ten minutes, 124 were included in group II (epistaxis and loss of consciousness for more than 10 minutes) and 68 were included in group III (coma and focal neurologic signs). All the patients in groups II and III and 30 patients in group I were submitted to CT--222 CT exams on the whole. Thirty-five patients in group III and 9 in group II had an intracranial lesion on CT, while CT findings were normal in all group-I patients. Thus, we conclude that the presence of a skull fracture is not always correlated with the presence of intracranial lesions. The latter are more likely to be correlated with clinical symptoms, especially coma and neurologic impairement. Therefore, the higher value is confirmed of the clinical examination than of conventional radiographs in head injury patients.

Adolescent

Antibodies for denatured human H-ferritin stain only reticuloendothelial cells within the bone marrow.

Human H-ferritin homopolymer was denatured in sodium dodecyl sulphate and injected in mice to obtain antibodies for dissociated H-subunit. The antisera and Moabs obtained were specific for the denatured H-chain with no cross-reactivity with assembled ferritins in immunoblotting experiments. In contrast the Moabs for native recombinant H-ferritin are specific for the assembled ferritin molecules with weak cross-reactivity with the denatured H-subunits. The epitope recognized by one of the anti-denatured H-chain Moabs was mapped on the C-terminal helix of ferritin. The antibodies were used to study H-ferritin conformation in cells. In immunocytochemistry experiments the antibodies for denatured H-ferritin stained HeLa and K562 cells weakly, with a different intensity and pattern to those obtained with anti-native H-ferritin antibody. In human bone marrow smears the anti-denatured ferritin antibodies stained only reticuloendothelial cells, and did not recognize the H-ferritin rich immature erythroblasts. It is concluded that assembled and denatured H-ferritins are immunogenically distinct, and that erythroid and reticuloendothelial cells within the bone marrow contain H-ferritin in different conformations.

Antibodies, Monoclonal

A mutational analysis of the epitopes of recombinant human H-ferritin.

Murine monoclonal antibodies were elicited by the recombinant human H-ferritin overexpressed in Escherichia coli. They had a specificity analogous to that of the antibodies elicited by natural human H-chain, and all of them showed low additivity in binding the recombinant ferritin. Four antibodies of each group were challenged with four H-ferritin mutants overexpressed in E. coli, altered in different accessible areas of the molecule. They consisted of deletions of the first 13 and last 22 amino acids, a duplication of an 18 amino acid sequence in the loop region, and a substitution of a 5 amino acid stretch in the three-fold symmetry axis region. Double diffusion, immunodot analyses and inhibition plots indicated that: (1) all the mutants were recognized by at least one antibody; (2) the deletion of the N-terminus and the duplication in the loop region had the strongest effect on antibody binding; and (3) epitope boundaries of the various antibodies could not be recognized. The antibodies were tested with H-containing ferritins from rat and hen hearts, and showed low or absent reactivities despite their high structural homology with human ferritin. Comparison of the amino acid sequences of human, mouse, rat and hen H-chains, together with mutational data, suggested that; (i) ferritin epitopes are large, probably encompassing a large portion of the subunit surface and (ii) Thr-5 and Cys-90 have a role in H-ferritin immunogenicity.

Amino Acid Sequence

Immunocytochemical detection of ferritin in human bone marrow and peripheral blood cells using monoclonal antibodies specific for the H and L subunit.

We have used the monoclonal antibodies 2A4 (specific for the H subunit of human ferritin) and LO3 (specific for the L subunit) for immunocytochemical detection of ferritin in bone marrow and peripheral blood cells from normal subjects and patients with various haematological disorders. Formalin-fixed slides were stained by the immunoalkaline phosphatase procedure (APAAP). In normal subjects, ferritin could be found only in bone marrow smears and appeared to be largely confined to erythroid precursors and reticuloendothelial cells. The more immature erythroid precursors contained higher concentrations of cellular ferritin. Although evaluation could be only semiquantitative, erythroblast ferritin appeared to be more reactive with the monoclonal 2A4 (15 +/- 7% positive erythroblasts) than with the monoclonal LO3 (6 +/- 5% positive erythroblasts), indicating that H-type ferritin was predominant, particularly in proerythroblasts and basophilic erythroblasts. By contrast, the ferritin present in reticuloendothelial cells appeared to be predominantly of L-type. Patients with iron deficiency showed low levels of positive erythroblast, whereas the reverse was true in patients with transfusional iron overload. Intense positivity for reticuloendothelial cell ferritin was found in patients with anaemia of chronic disease. In myelodysplastic syndromes and acute myeloid leukaemia (AML), ferritin positivity was generally very strong at any stage of erythroblast development, particularly with the monoclonal antibody 2A4. Perls-positive perinuclear granules of ring sideroblasts were not stained, confirming that mitochondrial iron deposition is not in the form of ferritin. In AML and myelodysplastic syndromes with excess of blasts, ferritin could be detected also in immature myeloid cells. These data indicate that: (a) in normal conditions ferritin is mainly expressed in red cell precursors and reticuloendothelial cells, and this is in keeping with the peculiar role of these cells in iron metabolism; (b) abnormal cell ferritin contents can be observed in both iron overload and malignancy.

Antibodies, Monoclonal

[New technic for the treatment of high intraabdominal cryptorchism: testicular autotransplantation with venous anastomosis only].

A new technique in the treatment of high intraabdominal cryptorchidism is proposed: testicular autotransplantation with venous anastomosis only. The technique consists in performing microsurgical anastomosis of the spermatic vein and homolateral inferior epigastric vein only for adequate venous drainage, leaving irrigation of testis to the deferential artery alone. We have utilized this technique in 16 cases and excellent results have been achieved. It has permitted performing surgery in younger patients (2 years). Surgical trauma and the duration of the operation are less compared to the Silber technique. There is a higher success rate and the procedure is easy to perform.

Anastomosis, Surgical

[Sex change in children with Morris syndrome].

Eleven boys with Morris syndrome underwent feminizing genitoplasty utilizing a segment of the sigmoid colon for neovaginal reconstruction. Bilateral orchiectomy was performed for cosmetic reasons and to prevent neoplasms. Patient follow-up ranging from 6 months to 13 years have demonstrated good results were obtained. No intra- or postoperative complications were observed. Patient psycho-social-sexual identification and satisfaction were achieved.

Adolescent

Development of an immunoassay for all human isoferritins, and its application to serum ferritin evaluation.

Calibrated mixtures of anti-H and anti-L ferritin subunit monoclonal antibodies were used in a sandwich enzyme-immunoassay for the evaluation of all isoferritins. The assay was designed to have overlapping calibration plots for human liver (95% L-chain) and recombinant human H-chain ferritin (100% H-chain). It appeared to recognize all the heart isoferritins including the ones in the middle of the isoferritin spectrum. By direct comparison it was shown that these isoferritins are under-evaluated by the assays for H- and L-subunit-rich ferritins, based on the two separated antibodies. The three assays (for total, H-rich and L-rich ferritins) provide an index of the presence of the isoferritins with intermediate H/L composition. Sera from 30 tumor and non-tumor patients were analyzed. Intermediate isoferritins were found in 2 non-tumor subjects and in none of the 14 patients with Hodgkin's disease or mammary carcinoma. It is concluded that the evaluation of the total and intermediate isoferritins is possible, but does not have an evident clinical significance for tumor monitoring.

Adult

Immunohistochemical evidence for a lack of ferritin in duodenal absorptive epithelial cells in idiopathic hemochromatosis.

Patients with idiopathic hemochromatosis exhibit an unexplained increase in intestinal iron absorption. The aim of this work was to study immunohistochemical H- and L-ferritin distribution in duodenal mucosal cells of patients with idiopathic hemochromatosis, and of subjects with various degrees of iron loading. Biopsy sections of gastrointestinal mucosa from 24 patients with idiopathic hemochromatosis, 10 patients with secondary iron overload, 6 normal subjects, and 13 iron-deficient subjects were analyzed with monoclonal antibodies for the presence of immunohistochemical H and L ferritin types, and with Perls' stain for hemosiderin. Ferritin content of duodenal homogenates was evaluated in 5 cases. The absorptive duodenal cells were found to contain ferritin, mostly of the L type, in apical granules; these ferritin granules were present in all normal, iron-deficient, and iron-over-loaded subjects, but were absent in 21 (87%) of the patients with established idiopathic hemochromatosis. In cells other than those of the duodenal epithelium, such as lamina propria or antral mucosa, ferritin and hemosiderin contents were related to iron loading and no difference was evident between primary and secondary iron overload. These findings indicate that (a) idiopathic hemochromatosis is associated with an altered ferritin expression in the duodenal absorptive epithelial cells, (b) this alteration cannot be detected by analysis of duodenal homogenates, (c) idiopathic hemochromatosis does not affect ferritin accumulation in the other cell types analyzed, and (d) ferritin in absorptive duodenal cells may have a regulatory role in iron absorption.

Antibodies, Monoclonal

[Acute enteritis and dietetic errors in the first 6 months of life].

The dietary habits of 174 infants under 6 months old and suffering from enteritis were analysed revealing a high incidence of feeding errors (almost always feeding with artificial formulas, wrong concentration of milk powder, failure to sterilise the bottle and the water used to dilute the milk, too early administration of undiluted, unboiled bottled cow's milk, too early and incorrect weaning). Such mistakes appeared to be linked to the poor economic and sociocultural conditions of the families concerned. It is claimed that dietary errors conditioned by the poor economic and sociocultural conditions encountered may have favoured the onset of enteritis and that the adequate prophylaxis of acute infantile enteritis will depend on improving people's dietary habits and living conditions.

Acute Disease