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Biomedical subjects

C Marino

Publications and source records attributed to C Marino.

At least 55 records · Page 3Linked to original sources

1-Thio-beta-D-galactofuranosides: synthesis and evaluation as beta-D-galactofuranosidase inhibitors.

Beta-D-galactofuranosidase is a good chemotherapeutic target for the design of inhibitors, since beta-D-galactofuranose is a constituent of important parasite glycoconjugates but is not present in the host mammals. With this aim, we have synthesized for the first time alkyl, benzyl and aryl 1-thio-beta-D-galactofuranosides by condensation of penta-O-benzoyl-alpha,beta-D-galactofuranose with the corresponding thiols, in the presence of SnCl4as catalyst. The complete chemical and spectroscopical characterization of these compounds showed that the reaction was stereoselective. Debenzoylation with sodium methoxide afforded the beta-S-galactofuranosides in high yield. The thioglycosides were tested as inhibitors of the beta-D-galactofuranosidase of Penicillium fellutanum, using for the first time 4-nitrophenyl-beta-D-galactofuranoside as chromogenic substrate. The 4-aminophenyl-1-thio-beta-D-galactofuranoside, obtained by catalytic hydrogenation of the nitrophenyl derivative, was the best inhibitor being then an adequate ligand for the preparation of an affinity phase aimed at the isolation of beta-d-galactofuranosidases from different sources. Also the inhibitory activity of d-galactono-1, 4-lactone was shown.

Chromogenic Compounds↗

Stopping progression to tophaceous gout. When and how to use urate-lowering therapy.

Although the prevalence of tophaceous gout has decreased in the past few years, the disease still exists, and without accurate diagnosis and therapy, it can still result in destructive arthritis. However, use of urate-lowering drugs may reduce plasma urate concentrations enough to allow resorption of tophi and prevent painful tophaceous gout. Some patients may have mechanical problems from tophi, despite adequate control of acute arthritis; in such situations, joint replacement or surgical excision of tophi may be necessary.

Adrenal Cortex Hormones↗

Cancer coverage and tobacco advertising in African-American women's popular magazines.

Mass circulating magazines offer an opportunity to inform large segments of the population about preventive health behaviors relevant for cancer control. We collected information about the number and type of cancer articles from January 1987 through December 1994 in Jet, Ebony and Essence magazines. These magazines each have a principal readership of African-American women and a paid circulation of 1,000,000 or more annually. Cancer articles were counted if the content was gender neutral or specifically targeted for women. There were 84 articles on cancer including 6 on lung cancer and 3 on other tobacco-related cancers. Nine additional references to lung cancer were mentioned under the general cancer category, but lung cancer was not the primary focus of the articles. There were 24 articles on breast cancer and 9 on cervical cancer over the 8 year period. Most of the articles (> 70%) were short fillers of less than one page in length. A prevention focus was included in 42.2%, 75.0%, and 71.0% of the cancer articles in Jet, Ebony, and Essence respectively. Of the 649 health articles, 116 were on cardiovascular disease. In contrast, there were 1,477 tobacco advertisements over the 8 years. The number of cancer articles was not significantly associated with the number of tobacco advertisements. Because tobacco-related cancers are entirely preventable and contribute to the significant cancer burden, the lack of coverage of tobacco-related cancers is a missed opportunity for health promotion among African-American females.

Adult↗

Cancer coverage in women's magazines: what information are women receiving?

BACKGROUND: Women use magazines as sources of health-related information, including information about cancer. Given this reliance on magazines for cancer-related information, it may interest cancer educators to know which cancers are reported on in women's magazines and what types of information are being presented. METHODS: Four widely circulated monthly women's magazines were analyzed for their coverage of cancers during the years 1987-1995. The types of cancers discussed and the frequencies of coverage were noted for each issue of every magazine. Additionally, the content of every cancer-related article was assessed for issues in cancer prevention (primary and secondary), risks, treatment, and genetics. RESULTS: All four magazines in this study reported on breast cancer more often than any other cancer. Lung and colon cancers received very little coverage. The percentages of articles devoted to the six most-discussed cancers (breast, cervical, colon, lung, ovarian, and skin) did not reflect either the mortality rates or the incidence rates of these cancers. CONCLUSIONS: The discussions of cancers in these four women's magazines focused mostly on breast and skin cancers and neglected two very important cancers--lung and colon. If women are indeed receiving much of their cancer information from such media coverage, these findings should alert cancer educators to the possible need to work with these media to help in the dissemination of additional information about cancers to women.

Adolescent↗

Lack of colon cancer coverage in seven women's magazines.

Women's magazines are an important source of health information. To evaluate the relevancy of articles in these publications to known disease risks, seven women's magazines were reviewed to assess their coverage of colon cancer, the third leading cause of cancer mortality in U.S. women. Specifically, the amount of coverage devoted to colon cancer as well as the presentation of issues in the prevention, risks, treatment, diagnosis and genetics of colon cancer were recorded. Twenty articles were published on colon cancer in these magazines during the years 1987-1995. Compared to five other cancers that also affect women, colon cancer was the focus of the fewest articles in the seven magazines analyzed.

Colonic Neoplasms↗

Withdrawal of renal replacement therapy in Newcastle upon Tyne: 1964-1993.

BACKGROUND: Termination of renal replacement therapy (RRT) is common in North America and Australia but is considered to be rare in Europe. METHODS: In order to review the phenomenon of RRT termination in all patients treated in Newcastle upon Tyne between 1964 and 1993 a retrospective study of clinical case notes was undertaken. In all RRT patients sex, age at start of RRT, renal diagnosis and history of RRT were recorded. In addition, mortality data and marital and residential status were recorded in all patients who died, and Karnofsky index, bodyweight, complications, history of bereavement, place of death, overall survival, survival after withdrawal of treatment, other medical problems, higher mental function and surgical history in all patients stopping treatment. RESULTS: 1639 patients started RRT between 1964 and September 1993 inclusive. Eighty-eight patients were identified in whom death was a result of treatment being stopped (17% of all deaths). The first was in 1985. In these patients, age was greater (62 vs 47 years, P < 0.001) and diabetes was more prevalent (15 vs 7%, P < 0.03) than in the total RRT population. The Karnofsky index was 70 at the start and 33 at withdrawal of treatment (P < 0.001). The Karnofsky index at the start of RRT was weakly related to that at withdrawal and overall survival (r = 0.36 and 0.28 respectively, P < 0.01). The Karnofsky index at treatment withdrawal correlated with the following survival (r = 0.40, P < 0.001). The median survival of patients stopping treatment was significantly lower than in all RRT patients (16 vs 74 months, P < 0.001) and the majority survived less than 2 years. After dialysis withdrawal the median survival was 8 days, 15 patients survived 3 days or less and 19 more than 10 days. The majority (80%) received terminal care in hospital. At treatment withdrawal 11 patients were demented and 34 showed signs of early dementia. Seventy-eight patients (89%) stopped treatment as a consequence of multiple medical problems. The possibility of dialysis withdrawal was raised by physicians in 50.5%, the patient in 23.8% and the patients' relatives in 21.9% of cases. Four patients (3.8%) committed suicide. CONCLUSIONS: Death from dialysis termination is a relatively common cause of death in RRT patients in Newcastle upon Tyne. These patients are older with a higher prevalence of diabetes. In 89% of cases the decision to stop treatment was related to multiple medical problems with a recent deterioration. Physicians raised the issue of withdrawal in the majority of cases and most patients subsequently received terminal care in hospital.

Decision Making↗

The impact of diabetes on patients' survival in dialysis patients with non-diabetic renal disease and in patients who develop diabetes during chronic dialysis.

BACKGROUND: It is well known that dialysis patients with diabetic nephropathy have a poor prognosis, but data concerning the survival of dialysis patients with diabetes plus a non-diabetic primary nephropathy or the survival of patients who develop diabetes after the start of regular dialysis are scarce. AIM AND METHODS: We reviewed the survival of two cohorts of dialysis patients in whom diabetes mellitus was associated with non-diabetic primary nephropathy. In the first cohort (18 patients with a primary diagnosis of APKD) diabetes mellitus precede hyperazotaemia, whilst the second cohort of 34 patients developed diabetes after the start of regular dialysis. We compared the survival of each group of patients to the survival of a group of dialysis patients with a primary diagnosis of diabetic nephropathy, and to the survival of each control group of non-diabetic dialysis patients. Within each case series, groups were similar according to age at start of RRT, and place of treatment. All patients were selected among those alive in treatment at 31 December 1986 and were followed up to 31 December 1991. RESULTS: In both case series the survival of patients with diabetes was similar irrespective of the primary diagnosis (Lee-Desu statistics: first cohort P=0.43; second cohort, P=0.08). Moreover, the survival of patients either with diabetic nephropathy or with diabetes in association with non-diabetic primary nephropathy was significantly worse compared to the survival of the non-diabetic patients (Lee-Desu statistics: first case series P=0.02 and P<0.01; second case series P<0.05 and P<0.01). Logistic regression showed that survival was negatively associated to diabetes and age but not to sex, duration of diabetes and diagnosis of diabetic nephropathy. CONCLUSIONS: Our limited data show that the survival of diabetic patients on regular dialysis is poor, irrespective of the primary cause of renal failure and of the duration of diabetes. These data need confirmation and further study.

Cohort Studies↗

Albendazole-induced pseudomembranous colitis.

We report a patient with AIDS and intestinal microsporidiosis. While undergoing treatment with albendazole, he developed worsening diarrhea with abdominal pain and fever. The diagnosis of pseudomembranous colitis was made by flexible sigmoidoscopy and a positive stool specimen for Clostridium difficile toxin. The patient's symptoms resolved with oral vancomycin and his stool C. difficile toxin became negative. Albendazole is an antibiotic that is chemically related to metronidazole. Although a few case reports link metronidazole with the development of pseudomembranous colitis, albendazole has not been associated with the development of this condition. The spectrum of antimicrobial activity of albendazole and its efficacy in the treatment of intestinal microsporidiosis are reviewed. Pathogenic mechanisms for the development of pseudomembranous colitis and the epidemiology of this condition in patients with AIDS are discussed.

AIDS-Related Opportunistic Infections↗

C-tail valine is a key residue for stabilization of complex between potato inhibitor and carboxypeptidase A.

Although the carboxypeptidase A-potato carboxypeptidase inhibitor (CPA-PCI) complex is a well known example of protein-protein interaction, little was known about the basis of its thermodynamic stability. Site-directed mutagenesis has been used to identify key residues in the PCI tail and estimate the contribution of their chemical groups to the binding to CPA. Two deletion mutants were created, one lacking the C-terminal residue of the tail (Gly39) and another one lacking the two C-terminal residues (Val38, Gly39). The last mutant had an inhibition constant for CPA 10(4)-fold higher than that of wild-type PCI, indicating that Val38 is a key residue. The interactions of Val38 with CPA residues contribute 5.4-5.7 kcal mol-1 to the overall stability of the CPA-PCI complex (11.9-12.1 kcal mol-1). A series of PCI point mutants at valine 38 were created, and their inhibition constant for CPA was measured. Two of these mutants with smaller side chains, V38G and V38A, allowed us to estimate that the contribution of the three side chain aliphatic groups of valine 38 to the overall stability of the complex is 3.4-4 kcal mol-1. Another two mutants with larger side chains, V38L and V38I, were constructed, the first being a significantly worse inhibitor than the wild type. These results suggest that only aliphatic groups in positions beta and gamma of residue 38 in PCI (but not those in delta) can establish van der Waals interactions with atoms of the active center of CPA and participate in binding. The energetic contribution of each methyl/methylene group in those positions can be estimated as 1-1.5 kcal mol-1. Our hypothesis is supported by computer simulation analysis.

Carboxypeptidases↗

Analysis of the D4 dopamine receptor gene variant in an Italian schizophrenia kindred.

BACKGROUND: Among the different dopamine receptors, the D4 dopamine receptor is of particular interest in schizophrenia because of its high affinity for the atypical neuroleptic clozapine. Recently, the gene for the D4 dopamine receptor has been cloned and a new and intriguing polymorphism has been described. Different versions of the receptor have varying affinity for clozapine, and thus variant froms of D4 with differing pharmacologic activity exist in the human population. Our hypothesis was that these variants play a role in susceptibility to psychotic illness. Thus, our objective was to test the D4 dopamine receptor genes for linkage to schizophrenia. METHODS: Our genetic linkage study was carried out in a large Italian kindred segregating schizophrenia. Diagnoses were made by using a structured clinical interview and a consensus diagnosis was established. For the computer analysis, 80 members of the family were constructed into a linked set of relatives with 15 of these individuals affected by schizophrenia. The functional variants of the D4 dopamine receptor gene were identified by a combination of Southern blot techniques and the polymerase chain reaction. The gene for tyrosine hydroxylase (TH) was also tested for linkage to schizophrenia in this family. Linkage analyses were done with both a single-locus and a two-locus model. RESULTS: Our results revealed significantly negative lod scores in the region of the D4 dopamine receptor gene and the TH gene. The application of different models of transmission for schizophrenia had an effect on the magnitude of the lod scores, but did not modify the direction of the results. CONCLUSIONS: Our results provide significant evidence for exclusion for linkage between schizophrenia and the dopamine D4 receptor gene and the TH gene under the models specified. Furthermore, we tabulated the distribution of D4 dopamine gene variants in the diseased vs healthy individuals in the family and the results showed that no specific form of the receptor gene is significantly associated with the presence of schizophrenia in the family. Our study does not exclude the possibility that regulatory elements of the D4 dopamine gene located elsewhere in the genome may be involved in the etiology of schizophrenia.

Blotting, Southern↗

Wilms' tumor arising in a multicystic kidney.

We describe a child with Wilms' tumor (WT) which occurred in an unequivocal multicystic dysplastic kidney (MDK). We indicate a current nonsurgical approach to MDK, but stress the probable malignant degeneration of blastemal cells, the need to search carefully for the WT in the MDK, and the necessity on 3-monthly follow-up US studies.

Follow-Up Studies↗

Rhabdomyolysis after exercise.

Rhabdomyolysis should be considered in the differential diagnosis of acute muscle weakness or pain in patients who have recently increased their level of exercise, no matter what their previous level of physical fitness. Measurement of an elevated creatine kinase level confirms the diagnosis. Management of rhabdomyolysis is aimed at avoiding acute renal failure through aggressive fluid replacement to maintain a high urine output.

Acute Disease↗