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Biomedical subjects

D Marino

Publications and source records attributed to D Marino.

At least 19 recordsLinked to original sources
PubMed2000

Cardiovascular remodeling, apoptosis, and drugs.

Apoptosis, a form of programmed cell death, mediates the controlled deletion of so-called "unwanted" cells. This review deals with the key features of this cell death program, showing that apoptosis is regulated by factors extrinsic and intrinsic to the dying cell. The elucidation of the possible interactions between these factors may be of major interest in preventing the progression to cardiovascular remodeling in patients with hypertensive disease. New pathways of research are emerging for drugs, such as beta-blockers, ACE inhibitors, the calcium-antagonists, and the receptor antagonist of angiotensin II, all of which have beneficial effects on cardiovascular remodeling. This may be due to the direct effect of these drugs on the cell proliferation/apoptosis balance.

Adrenergic beta-Antagonists↗
PubMed1999

Pro-apoptotic effect of fluvastatin on human smooth muscle cells.

The antiatherosclerotic effect of statins has been attributed to their hypocholesterolemic action. We therefore evaluated the effect, in vitro, of the addition of the serum of patients taking fluvastatin on human smooth muscle cells in order to ascertain the effect of the drug on cell proliferation and apoptosis. We found that the addition of serum from patients treated with fluvastatin for 6 days caused a significant reduction in cell proliferation, increased cell apoptosis and reduced the B cell leukemia-2 (bcl-2) concentration. It is concluded that the induction of apoptosis by statins could be a supplementary mechanism in the prevention of atherosclerotic lesions in humans.

Adult↗
PubMed1999

Potent, orally bioavailable somatostatin agonists: good absorption achieved by urea backbone cyclization.

Backbone cyclization of urea-based somatostatin agonists resulted in novel, orally bioavailable agonists. Binding assays confirmed that the resulting conformationally constrained cyclic ureas retained the potency of their acyclic counterparts. SAR studies subsequently led to highly potent analogs, selective for receptor subtype 2, and having good oral bioavailability.

Administration, Oral↗
PubMed1999

Does captopril have a direct pro-apoptotic effect?

The beneficial effect of ACE inhibitors on cardiovascular remodelling from hypertension and ischemic disease may be due to the effect of these drugs on the proliferation/cell death balance. We therefore investigated the effect of the addition of captopril in vitro, on the onset of apoptosis in human vascular myocytes, by using a propidium iodide fluorescence analysis and a morphological analysis using the acridine orange technique. Captopril (0.23 mM) caused an increase in apoptotic phenomena that was more than 3. 5-fold than in controls both at the 24th (7.7 vs. 2%) and the 48th h (10.1 vs. 3.8%). The addition of propranolol strengthened the effect on apoptosis. The induction of apoptotic phenomena may be a mechanism by which ACE inhibitors affect cardiovascular remodelling and it might also explain the favorable effect these drugs have on diseases such as IgA nephropathy and diabetic nephropathy.

Adrenergic beta-Antagonists↗
PubMed1998

Effect of target gene CpG content on spontaneous mutation in299 transgenic mice.

Transgenic mutation assays utilizing bacterial target genes display a high frequency of spontaneous mutation at CpG sequences. This is believed to result from the fact that: (1) the prokaryotic genes currently being used as transgenic mutation targets have a high CpG content and (2) these sequences are methylated by mammalian cells to produce 5-methylcytosine (5MC), a known promutagenic base. To study the effect of CpG content on the frequency and type of spontaneous mutation, we have synthesized an analogue of the bacterial lacI target gene (mrkII) that contains a reduced number of CpG sequences. This gene was inserted into a lambda vector and used to construct transgenic mice that undergo vector rescue from genomic DNA upon in vitro packaging. Results on spontaneous mutation frequency and spectrum have been collected and compared to those observed at the lacI gene in Big Blue transgenic mice. Spontaneous mutations at the mrkII gene occurred at a frequency in the mid-10-5 range and were predominantly base pair substitutions, similar to results seen in Big Blue. However, mrkII mutations were distributed toward the carboxyl end of the gene instead of the bias toward the amino terminus seen in lacI. Unexpectedly, 23% of the spontaneous mrkII mutations were GC-->AT transitions at CpG sequences (compared to 32% in lacI), despite the reduction in CpG number from 95 in lacI to only 13 in mrkII. Nine of the CpG bases undergoing transition mutations in mrkII have not been recorded previously as spontaneous sites in Big Blue. Therefore, substantial reduction of the number of CpG sequences in the lacI transgene did not significantly reduce the rate of spontaneous mutation or alter the contribution of CpG-related events. This suggests that other factors are also operating to establish frequency and composition of spontaneous mutations in transgenic targets.

Animals↗
PubMed1997

Simple enzymatic method for rapid identification of a Staphylococcus aureus subspecies aureus biovar.

In order to correctly identify a new biovar of Staphylococcus aureus subsp, aureus, (NBSA) a simple, rapid, and reliable enzymatic assay was developed. The assay was based on the detection of the production of three enzymes: alpha-glucosidase, beta-glucosidase and beta-N-acetyl-glucosaminidase. Of a total of 46 isolates of Staphylococcus aureus subsp. aureus from clinical specimens, the new assay correctly identified 19 as NBSA and 27 as typical Staphylococcus aureus subsp. aureus. Among the 19 NBSA isolates, 15 (79%) showed a clear biochemical profile while only four isolates (21%) showed a less well-defined enzymatic combination, due to a phenotypic alteration caused by subculturing. Since this assay is both simple to perform and inexpensive, it is potentially applicable in the laboratory.

Acetylglucosaminidase↗
PubMed1995

Comparison of cocaine and opiate exposures between young urban and suburban children.

OBJECTIVE: To determine the prevalence of cocaine and opiate metabolites in the urine of young urban and suburban children. DESIGN: Survey. SETTING: Urban and suburban emergency departments and private pediatric practices. PATIENTS: A convenience sample of 1469 children between 1 and 60 months of age who required a urinalysis for investigation of the chief complaint. INTERVENTION: None. MAIN OUTCOME MEASURES: Urine was screened for benzoylecogonine and opiates using an enzyme-multiplied immunoassay technique and a fluorescence-polarization immunoassay, both with a sensitivity of 50 ng/mL. RESULTS: Benzoylecogonine was identified in the urine of 45 children (3.1%) (95% CI, 2.2% to 3.9%) and opiates in the urine of 38 children (2.6%) (95% CI, 1.8% to 3.4%). No difference was observed between urban and suburban health care facilities in the percentage of patients whose urine tested positive for benzoylecgonine (29 of 1011 vs 16 of 458, P = .6) or opiates (28 of 1011 vs 10 of 458, P = .6). CONCLUSION: Exposure to illicit drugs, as reflected by urinary metabolites, is similar for urban and suburban children.

Child, Preschool↗
PubMed1995

Occult cocaine and opiate exposure in children and associated physical findings.

We determined the prevalence of cocaine and opiate exposure and the association of exposure with objective physical findings in children presenting to an urban pediatric emergency department. The study included 942 children between one and 60 months of age who required urinalysis for investigation of their chief complaint. Anonymously and without informed consent, urine was screened for benzoylecgonine (BE) and opiates, using an enzyme multiplied immunoassay technique (EMIT) with sensitivity of 50 ng/ml. EMIT-positive samples were rescreened using a fluorescence polarization immunoassay (FPIA). Specimens positive by both EMIT and FPIA were confirmed by gas chromatography/mass spectrometry (GC/MS) if sufficient quantity of urine was available. BE was identified in 41 (4.4%) and opiates in 46 (4.9%) patients by both EMIT and FPIA. The presence of BE or opiate was confirmed by GC/MS in all 34 cases where sufficient urine was available. The age- and sex-adjusted systolic and diastolic blood pressure percentiles were greater, and head circumference and weight percentiles were lower in BE-positive patients compared to those with negative drug screens. There were no associations between opiate exposure and any of these variables. We conclude that occult postnatal cocaine exposure is associated with measurable physical and physiologic differences.

Blood Pressure↗
PubMed1995

Improving materials management through re-engineering.

Activities related to the purchase, distribution, and management of supplies account for about one-third of the operating costs of healthcare facilities. Under a free-for-service reimbursement system, the use of supplies generates revenue; there is little motivation to control supply costs, and the goal in most facilities is to ensure abundant availability of supplies to both patient care staff and patients. As the reimbursement picture changes, however, and supplies become expenses instead of revenue generators, facilities are being forced to scrutinize all activities, including materials management, that influence operating costs and to identify and seize cost-reduction opportunities. One approach to improving materials management to reduce the cost of supplies is re-engineering. A successful re-engineering effort involves six basic steps: 1) recognizing the need for change, 2) establishing guidelines, 3) forming a team, 4) analyzing current processes and costs, 5) redesigning processes, and 6) implementing and managing the changes. In this article, a case study illustrates the possible benefits of re-engineering materials management processes.

Cost Control↗
PubMed1992

Modulation of monocyte functions by muramyl tripeptide phosphatidylethanolamine in a phase II study in patients with metastatic melanoma.

BACKGROUND: Muramyl tripeptide phosphatidylethanolamine (MTP-PE) is a synthetic analogue of muramyl dipeptide (MDP), a component of bacterial cell walls that has potent in vitro monocyte-activating properties. We conducted a phase II clinical trial of MTP-PE in 30 patients with metastatic melanoma. PURPOSE: Our purpose was to define a clinical response rate for this agent in patients with advanced melanoma and to evaluate the agent's immunomodulatory properties. METHODS: Patients were randomly assigned to 1- or 4-mg dose levels of MTP-PE and received the drug intravenously once a week for 12-24 weeks. Immunological monitoring consisted of measurement of plasma tumor necrosis factor-alpha (TNF-alpha), neopterin, interleukin-1-beta, interleukin-6 (IL-6), and beta 2-microglobulin levels; phenotyping analysis of expression of human HLA-DR, CD-14 on mononuclear cells; and measurement of in vitro monocyte cytotoxicity against SKMel28 targets cells. RESULTS: MTP-PE was well tolerated; fever and chills were the major toxic effects. Plasma TNF-alpha levels increased 16-fold 2 hours after the first MTP-PE treatment. Increases in TNF-alpha levels after MTP-PE administration continued through week 12, but changes were of a lower magnitude after week 1. Plasma neopterin levels were significantly increased 24 hours after treatment at weeks 1, 6, and 12. A marked increase in IL-6 and a modest rise in beta 2-microglobulin levels were also seen at week 1. No significant changes from baseline IL-1 beta were observed. In the cytotoxicity assay, monocyte cytotoxic activity was significantly increased at weeks 4 and 6. Surface immuno-phenotyping revealed a consistent transient reduction in the number of circulating monocytes 2 hours after MTP-PE was administered. In addition, we observed a down-regulation (i.e., a decrease) in the expression of Leu M3 and HLA-DR on monocytes, 2 hours after MTP-PE treatment, followed by a recovery 24 hours after treatment. No objective clinical responses were seen in this advanced disease population. CONCLUSIONS: We conclude that MTP-PE has pleiotropic and potentially beneficial biologic effects and that further clinical investigations of MTP-PE are justified. IMPLICATIONS: In view of the clear immunomodulatory actions seen in our study and in earlier clinical trials, we believe that MTP-PE deserves further study in the adjuvant setting.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1992

Seizures associated with meningitis.

The records of 187 patients with bacterial meningitis were reviewed. Seizures were a presenting manifestation in 25 (13%). Seven (28%) of the patients with a presenting seizure had been taking antibiotics prior to the diagnosis. Four of seven pretreated patients did not have additional signs or symptoms with the seizure, while all 18 patients without treatment had additional findings (P less than 0.01). Patients developing seizures while hospitalized had a poorer outcome than those without seizures. Patients with bacterial meningitis may present with only a seizure if they have been taking oral antibiotics; therefore, all patients taking antibiotics who develop a seizure require a lumbar puncture to exclude meningitis.

Child, Preschool↗
PubMed1989

Frequency of suspected abuse/neglect in burn patients.

This study was conducted to determine the frequency of suspected abuse/neglect in pediatric patients with burns presenting to an emergency department. Criteria were established for the suspicion of abuse/neglect. During a 12-month period, 431 patients were evaluated. Eighty-four (19.5%) were suspected of being abused or neglected. The frequency of suspected abuse/neglect in single-parent families was 22%, compared to 10% for married couples (P = 0.027). There was no significant difference in the rate of suspected abuse/neglect in patients seen fewer than or more than 24 hours after the injury occurred. Seventy-five children (17%) had more than two burn sites, with 24 (32%) appearing to be a result of abuse/neglect (P = 0.01). One hundred twenty-eight patients (30%) were admitted to the hospital, with 34% suspected of being abused/neglected, compared to 13% who were treated on an ambulatory basis (P = 0.00005). Fifty-eight (69%) of the suspected abused/neglected patients were diagnosed based on the history and/or physical examination. The medical records of 31% revealed previous abuse/neglect, ingestion, failure to thrive, or old burns. We conclude that abuse or neglect is a significant factor in pediatric burn patients and that the child's previous medical record must be reviewed. Other associated factors include a single parent family or the child with greater than two burn sites. The actual incidence of abuse/neglect could not be determined, owing to laws regarding confidentiality.

Burns↗