Search PubMed⌕ Search

Biomedical subjects

A Rocca

Publications and source records attributed to A Rocca.

At least 37 records · Page 2Linked to original sources

Double-blind, multicenter, randomized trial to compare the effect of two doses of adrenocorticotropic hormone versus placebo in controlling delayed emesis after high-dose cisplatin in adult patients with cancer.

PURPOSE: To compare, in a double-blind, placebo-controlled, randomized trial, the efficacy of two different doses of the depot formulation of adrenocorticotropic hormone (ACTH) in controlling delayed emesis after cisplatin. PATIENTS AND METHODS: One hundred fifty-two patients were enrolled onto the study. On day 1, all patients received cisplatin (60 to 120 mg/m2) and a combination of dexamethasone 20 mg plus ondansetron or metoclopramide to prevent acute emesis. On day 2 (24 hours after cisplatin administration), patients were randomized to receive placebo, or ACTH 1 mg intramuscularly (I.M.), or ACTH 2 mg I.M. plus one additional dose of 1 mg on day 4. Details of vomiting, nausea, and adverse effects were recorded daily for every 24-hour period from day 2 to day 6. In a subset of patients, serum cortisol levels were measured between 20 and 72 hours after cisplatin administration. RESULTS: One hundred fifty patients were assessable. Over the 5 days of the study, delayed vomiting occurred less frequently in the patients treated with ACTH 2 mg plus 1 mg than in those treated with ACTH 1 mg or placebo (28%, 38%, and 65%, respectively; P = .001). The greatest observed differences were seen on days 2 (24 to 48 hours; P = .01) and 3 (48 to 72 hours; P = .01). On days 4, 5, and 6 (96 to 144 hours), no significant differences were observed among the three arms. The severity of delayed emesis expressed as the mean number of emetic episodes per day was 0.48, 0.70, and 0.80, respectively (P = .002). Patients treated with the higher dose of ACTH had the least nausea on day 3 (P = .02) and day 4 (P = .03). Adrenal cortisol secretion rapidly increased after ACTH injection, but was suppressed for approximately 44 hours in the placebo group. Toxicity was mild and transient in all groups. CONCLUSION: ACTH reduces the incidence and severity of delayed vomiting and nausea after cisplatin. A dose of 2 mg 24 hours after cisplatin is better than one of 1 mg. Whether the activity of ACTH is mediated only by adrenal corticosteroids needs to be verified.

Adrenocorticotropic Hormone↗

Abnormal response to exercise in middle-aged NIDDM patients with and without autonomic neuropathy.

The cardiovascular response to exercise in middle-aged non-insulin-dependent diabetes mellitus (NIDDM) patients and the potential role of clinical characteristics and autonomic function were evaluated. One hundred and eight NIDDM patients, aged 40-65 years, were compared with a control group of 112 subjects, matched by age, sex, physical fitness, and presence of hypertension. All subjects performed a maximal exercise test. The diabetic patients completed cardiovascular autonomic neuropathy (CAN) tests: deep breathing, postural hypotension and lying to standing. There were no significant differences in total work capacity, heart rate, and blood pressure, either at rest or at peak exercise between the two groups. Diabetic patients showed significantly lower values of systolic and diastolic blood pressure during exercise, significantly slower recovery of heart rate (at 5th minute the average values were 102.7 +/- 14.1 beats min-1 vs 91.9 +/- 11.1, p < 0.001); and significantly higher proportion of blunted increase of heart rate (9.2% vs 0.9%, p < 0.001) and systolic blood pressure (9.2% vs 0.7%, p < 0.001) during exercise. No correlation between the exercise results and the main clinical characteristic (presence of hypertension, BMI, duration of diabetes, treatment, microalbuminuria, total score of CAN) was observed. These findings suggest that the cardiovascular response to exercise could be impaired also in the absence of signs of CAN. This impairment was higher in patients showing a dysfunction of orthosympathetic activity.

Adult↗

Endovascular treatment of bacterial intracranial aneurysms.

We report three patients with bacterial intracranial aneurysms treated by the endovascular approach: two presented with sudden severe neurological deficits after a diagnosis of endocarditis; the other had suspected vasculitis. CT showed an intracerebral haematoma in all cases; angiography revealed bacterial aneurysms of distal branches of the middle cerebral artery in one. Because of the patients' condition and the location of the aneurysms, endovascular treatment was considered the fastest and safest treatment. Hyperselective catheterisation of the parent branch, close to the aneurysm, was performed with a microcatheter. A small amount of glue was injected to occlude both the aneurysm and a short segment of the diseased vessel. Follow-up angiography revealed occlusion of the aneurysm in all cases. One patient recovered completely; one recovered over some months, with neurological deficit due to the haematoma. The third patient suddenly worsened and died 9 days after treatment for a contralateral haematoma, due to rupture of a new bacterial aneurysm of the middle cerebral artery. Endovascular occlusion of the aneurysm and parent vessel may be an alternative to surgery in selected, severe cases of deep or distal bacterial intracranial aneurysms.

Adult↗

Structural peculiarities of a truncated V kappa III immunoglobulin light chain in myeloma with light chain deposition disease.

We report on the primary sequence of the monoclonal immunoglobulin light chain (LC) REV involved in myeloma-associated light chain deposition disease (LCDD). This sequence was deduced from that of the corresponding complementary (c)DNA in bone marrow plasma cells. Products of three independent amplifications by polymerase chain reaction (PCR) were sequenced and found to be identical. The kappa mRNA encoding this N-glycosylated LC showed an overall normal structure consisting of a V kappa III segment rearranged to J kappa II. Direct N-terminal amino acid sequencing of the circulating monoclonal IgA2, kappa showed identity with the bone marrow-derived sequence. The kappa-chain presented several unusual features affecting both the leader sequence and the variable (V) region. Four unique amino acid substitutions were found at positions -8, -3, -2 and -1 in the leader sequence and probably resulted in an unusual cleavage by signal peptidase, thus making the LC truncated by one residue and accounting for its unique hydrophobic N-terminus: Ile-Ile-Leu. Additional peculiarities were observed in the V region, including a Thr74-->Asn substitution creating a N-glycosylation site, and Thr53-->Ile, which was only reported once among human kappa III chains, in another LCDD case, and may be of special significance at a position usually harbouring a polar amino acid.

Amino Acid Sequence↗

[Usefulness of transvaginal echography in the study of organic pathology of the female urethra].

The Authors describe their experience about the use of vaginal ultrasound in the diagnosis of some organic disease of the female urethra. The ultrasonography was performed with the 5 Mhz endocavitary probe and patients in lithotomy position and filled bladder. With this method has been possible value the urethral and peri-urethral echostructure and urethral calibre during micturition. the Authors visualized 20 urethral diverticula, 6 stenosis, 2 carcinomas and 1 leiomyoma. They show the great reliability of this investigation and argue that it may be present as a first instrumental approach in the clinical suspicion of an organic pathology of the female urethra.

Female↗

[Transvaginal echography in the study of urinary stress incontinence].

Hypermobility of the bladder neck in response to increased intraabdominal pressure is one cause of stress urinary incontinence in women. Vaginal ultrasound (u.s.) is reliable and minimally invasive method for demonstrating bladder neck hypermobility. The Authors studied 50 women with S.U.I. and 40 with no history of S.U.I. measuring the distance from the bladder neck to the midline of the symphysis pubis (P.V.) and the angle between the BP line and the midline of the symphysis pubis (A.I.U.). The continent women were characterized by a median A.I.U. of 70 degrees and mean B.P. of 25.6 mm, at rest, a median A.I.U. of 80 degrees and a mean B.P. of 20 mm. at stress. The incontinent women were characterized by a median A.I.U. of 80 degrees and mean P.V. of 22.5 mm. at rest, and a median A.I.U. of 95 degrees and mean P.V. of 10 mm. at stress. There is a significant difference between the two groups. The Authors recommend the vaginal u.s. as reliable, practical, economical and patient accepted method to study the bladder neck mobility.

Female↗

[Treatment of a solitary renal cyst using percutaneous drainage and repeat alcoholization].

The Authors report their results on the treatment of simple voluminous renal cyst with percutaneous drainage and three times repeated sclerosis with pure alcohol every 24 hours. After a mean follow-up of 28 months They report a 96% of success with only two recurrences. Since the fair results and low invasiveness of the method, the Authors propose the repeated alcoholization in the treatment of simple voluminous renal cysts.

Combined Modality Therapy↗

[Echographic aspects of renal tuberculosis].

In this study the Authors examine the utility of the ultrasonographic investigation in the preoperative evaluation of 22 patients submitted to nephrectomy for tubercular lesions, comparing the informations obtained from this procedure with the histologic report. The renal ultrasonography execute with a Toshiba 3.5 Mhz probe, has been utilized to value morphology, volume, parenchymal echostructure and hydronephrosis. According to the Author's series, the ultrasonography has shown a 100% sensitivity permitting to well value the presence of parenchymal lesions and hydronephrosis. As regards the tubercular renal injuries the ultrasonography is non-specific because it does not allow to have pathognomonic images. The results obtained from the U.S. are overlapping to the Results Related from the literature for abdominal CT. The Authors argue that U.S., rapid and economical investigation is an efficient complement to the urography for an exhaustive preoperative evaluation of patients suffering from renal Tuberculosis.

Humans↗

Role of light chain variable region in myeloma with light chain deposition disease: evidence from an experimental model.

Light chain deposition disease (LCDD) results from a propensity of some human monoclonal L chains to form tissue deposits. We designed an experimental model for in vivo expression of human kappa L chain sequences in mice and compared a somatically mutated LCDD chain with a closely related control kappa chain, both encoded by the unique V kappa IV gene. Mice secreting the LCDD chain but not those producing the control chain showed deposits with a distribution similar to that observed in patients. These data show that discrete changes in V region sequences can play a major role in tissue deposition of human L chains.

Amino Acid Sequence↗

Sequences of V kappa L subgroup light chains in Fanconi's syndrome. Light chain V region gene usage restriction and peculiarities in myeloma-associated Fanconi's syndrome.

Certain monoclonal Ig light chains (LC) are responsible for marked disturbances of proximal tubule cell functions (Fanconi's syndrome, FS). In patients with FS, intracellular crystal-like inclusions containing LC determinants are commonly found in plasma cells, macrophages, and renal tubular cells. In an attempt at understanding the pathogenesis of myeloma-associated FS, we recently determined the first complete primary sequence of a kappa-LC (CHEB) responsible for the disease. We now report on the primary structure of three other kappa-LC of the V kappa l variability subgroup associated with FS (TRE, TRO, and DEL). After PCR amplification, cDNA encoding these LC were sequenced. CHEB, TRE, and TRO LC genes were found to be highly homologous to the same germline gene O2/O12. These patients had numerous intracellular crystals, whereas the fourth patient, DEL, had no detectable crystals. The LC from the latter patient was homologous to another germline gene, O8/O18. Comparison of these LC sequences to previously reported LC of the V kappa l subgroup allowed identification of a number of unusual amino acid substitutions in the V region that had rarely or never been previously described at the corresponding positions. Some of these unusual substitutions affect highly conserved amino acids located either in an external loop (residue 30) or in inner (residues 48 and 55) and outer (positions 63 and 72) beta-sheets that may be important for the structure and binding properties of the kappa-chains. These and several other substitutions, some of them shared with amyloidogenic kappa-LC, could induce conformational alterations and represent a determinant pathogenic factor.

Amino Acid Sequence↗

Protease resistance and binding of Ig light chains in myeloma-associated tubulopathies.

Kidney tubule dysfunction and lesions are frequent complications of myeloma, related to unknown properties of the monoclonal light chain. We have analyzed protease sensitivity and binding properties of urinary light chains from four patients with Fanconi's syndrome, 12 with cast nephropathy, and four control patients without myeloma-associated tubulopathy. All light chains were normal-sized, monomeric and/or dimeric, and none was N-glycosylated. Kinetic studies of light chain digestion by pepsin and the lysosomal enzyme cathepsin B showed the generation of a protease-resistant 12 kDa fragment, corresponding to the V domain of the kappa chain in the four Fanconi's syndrome patients; in two out of four the V domain was also completely resistant to trypsin. Western and dot blots revealed similar patterns of reactivity of light chains from patients with the Fanconi's syndrome towards other light chains. Properties of cast-nephropathy light chains were more heterogeneous but clearly differed from those of Fanconi's syndrome: (i) 9 out of 12 were of the lambda-type; (ii) only four yielded a transient 12 kDa fragment after cathepsin B digestion, but all showed some resistance to proteolysis of the entire molecule or a fragment thereof to at least one protease, at variance with control light chains; (iii) they displayed various patterns of reactivity with other light chains; (iv) 7 out of 12 reacted specifically with Tamm-Horsfall protein (THP) by ELISA, in contrast with those of Fanconi's syndrome. In one patient who presented with cast nephropathy and the Fanconi's syndrome, the light chain exhibited both partial resistance of the V kappa domain to cathepsin B and the highest reactivity with THP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗

[Reconstruction of the skin of the lower eyelid by orbito-nasolabial flap].

The orbitonasolabial flap has been known for a long time. The author considers that it has an important place for the cutaneous reconstruction of the lower lid. The surgical anatomy of the naso-labial area is reviewed before presenting a detailed technical description. This flap was used in 26 cases of repair of defects, usually following resection of a lower lid skin carcinoma. Advantages and drawbacks of this flap, dedicated to the reconstruction of the lower lid skin, are analysed, before a comparative study of other flaps. This method of reconstruction is simple, effective, and can be performed in a one-stage operation. It can therefore be proposed in elderly people and its application can be extended.

Adult↗

Relevance of intravenous cocaine use in relation to prevalence of HIV, hepatitis B and C virus markers among intravenous drug abusers in southern Italy.

The purpose of this study was to analyze the relationship between intravenous (i.v) drug use practices and the prevalence of human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) in 146 heterosexual male i.v. drug users (IVDUs) attending a methadone-maintainance treatment program in Catanzaro, Southern Italy. One hundred and forty-six heterosexual male IVDUs attending a methadone-maintainance treatment program in Catanzaro were interviewed in order to obtain the following information: age, number of drug injections (calculated by multiplying the mean number of daily injections by 365 and then by the number of years of injections), number of injection equipment-sharing partners in the last year, number of sexual partners in the last year and possible IV cocaine use. Their sera were studied for the presence of antibodies to HIV, HBV and HCV by commercial enzyme-linked-immuno-sorbent assays run in duplicate. HIV positive samples were confirmed by Western Blot assay. Sixteen per cent of IVDUs were anti-HIV positive, 40% were anti-HBc positive and 68% were anti-HCV positive. Twenty-three per cent were seronegative and 12% were seropositive for all 3 viral markers. Multiple logistic analysis of HIV, HBV and HCV seropositivities in relation to age, number of drug injections, i.v. cocaine use and presence of injection equipment-sharing partners in the last year, showed that: a) older age (more than 27 years) was significantly associated with all 3 viral infections (mainly with HIV); b) i.v. cocaine use was associated with HBV, but even more with HIV; c) injection equipment-sharing partners in the last year was directly associated with HCV and inversely with HIV. No significant association was observed with the number of drug injections and the number of sexual partners. In conclusion, this study: a) demonstrates a difference of prevalence for HIV, HBV and HCV serum markers in this group of IVDUs from Catanzaro, Southern Italy; b) underlines the importance of i.v. cocaine use in the spreading of HIV; c) emphasizes the need of preventive strategies.

Adolescent↗

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

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

Animals↗

Cross-reactivity among evolutionarily distant major histocompatibility complex class I molecules (HLA-B27 and H-2Kk) revealed by xenoreactive T lymphocytes.

A set of mouse HLA-B27-reactive cytotoxic T lymphocyte clones were found to recognize the HLA-B27 molecule in an H-2-unrestricted manner, i.e. independently of any mouse major histocompatibility complex (MHC) molecule. The reactivity patterns of these clones on HLA-B27 variants (positive only on HLA-B*2702 and HLA-B*2701) allowed the identification of residues N77 and A81 of the HLA-B27 molecule as important for their reactivity. The location of these residues in the peptide-binding groove (specificity pocket F) suggested that the reactivity of the clones is dependent on HLA-B27-bound peptide(s). However, several other class I molecules sharing these residues (N77 and A81) were not recognized, indicating that other residues might also be involved. One of the clones was found to display an interesting cross-reactivity with allogeneic H-2Kk molecules, sharing N77 and A81 with HLA-B*2702. Sequence comparison suggested the involvement of residue H9, located in specificity pocket B of the peptide-binding groove, and revealed some similarity of pockets B in HLA-B27 and H-2Kk. The structural basis of such T cell-mediated MHC cross-reactions across species barriers is discussed.

Amino Acid Sequence↗