Search PubMed⌕ Search

Biomedical subjects

J Marino

Publications and source records attributed to J Marino.

At least 19 recordsLinked to original sources
PubMed2006

Low-coverage vaccination strategies for the conservation of endangered species.

The conventional objective of vaccination programmes is to eliminate infection by reducing the reproduction number of an infectious agent to less than one, which generally requires vaccination of the majority of individuals. In populations of endangered wildlife, the intervention required to deliver such coverage can be undesirable and impractical; however, endangered populations are increasingly threatened by outbreaks of infectious disease for which effective vaccines exist. As an alternative, wildlife epidemiologists could adopt a vaccination strategy that protects a population from the consequences of only the largest outbreaks of disease. Here we provide a successful example of this strategy in the Ethiopian wolf, the world's rarest canid, which persists in small subpopulations threatened by repeated outbreaks of rabies introduced by domestic dogs. On the basis of data from past outbreaks, we propose an approach that controls the spread of disease through habitat corridors between subpopulations and that requires only low vaccination coverage. This approach reduces the extent of rabies outbreaks and should significantly enhance the long-term persistence of the population. Our study shows that vaccination used to enhance metapopulation persistence through elimination of the largest outbreaks of disease requires lower coverage than the conventional objective of reducing the reproduction number of an infectious agent to less than one.

Animals↗
PubMed2001

Association of an RNA kissing complex analyzed using 2-aminopurine fluorescence.

The fluorescent probe, 2-aminopurine-2'-O-methyl riboside (2-AP) has been selectively incorporated at adenosine positions in stem-loops (so called R1inv and R2inv), derived from the ColE1 plasmid encoded RNA I and RNA II transcripts, that interact to form stable loop-loop kissing complexes and bind the RNA one modulator (Rom) protein, such that fluorescence-detected stopped-flow and equilibrium methods could be used to study the detailed mechanism of this RNA-RNA interaction. Formation of loop-loop kissing complexes between R1inv and R2inv hairpins, substituted with 2-AP at positions in the complementary loops, results in a 5-10-fold fluorescence emission decrease (F(max) = 370 nm), which provides a sensitive measure for the binding reaction. The 2-AP substituted complexes are found to have equilibrium binding properties (average K(D) = 2.6 +/- 1.7 nM) and affinity for Rom (average K(D) = 60 +/- 24 nM) that are similar to complexes formed with equivalent unlabeled hairpins. Using stopped-flow experiments, it was found that the 2-AP probes experienced at least three different microenvironments during association of the RNA complex, thus suggesting a kinetic intermediate in the kissing pathway. In contrast, dissociation of the complex was found to fit a single exponential decay (average k(off) = 8.9 x 10(-5) s(-1)). Consistent with these observations, a two-step mechanism for RNA loop-loop complex association is proposed in which the complementary loops of R1inv and R2inv first base pair to form the loop-loop helix (average k(1) = 0.13 microM(-1)s(-1)) in the initial encounter reaction, and subsequently isomerize to the final tertiary fold in a second slower step (average k(2) = 0.09 s(-1)), where the helical stacking around the junctions is optimized.

2-Aminopurine↗
PubMed2001

Irinotecan combined with gemcitabine, 5-fluorouracil, leucovorin, and cisplatin (G-FLIP) is an effective and noncrossresistant treatment for chemotherapy refractory metastatic pancreatic cancer.

BACKGROUND: Single agents have only modest activity as treatment for metastatic pancreatic cancer with response rates of less than 10% and median survivals of less than 6 months. Evaluations of single-agent gemcitabine and rubitecan as second-line treatment for relapsed pancreatic cancer have reported good patient tolerability and median survivals of 3.85 months and 4.7 months, respectively. Regimens incorporating two drugs have demonstrated encouraging activity and clinical impact compared with single-agent therapy. G-FLIP is a regimen designed to incorporate four active single agents into a tolerable and active combination. This analysis is a retrospective evaluation of the efficacy and safety of the G-FLIP regimen as second-line chemotherapy in a series of consecutively treated patients with metastatic pancreatic cancer. METHODS: G-FLIP was administered over 48 hours and repeated every 2 weeks. Day 1 treatment consisted of sequentially administered gemcitabine 500 mg/m(2), irinotecan 80 mg/m(2), leucovorin 300 mg, 5-fluorouracil (5-FU) 400 mg/m(2) bolus followed by infusional 5-FU 600 mg/m(2) over 8 hours. Day 2 treatment consisted of leucovorin 300 mg and 5-FU 400 mg/m(2) bolus, followed by cisplatin 50 to 75 mg/m(2), and then infusional 5-FU 600 mg/m(2) over 8 hours. RESULTS: Thirty-four patients with histologically confirmed metastatic pancreatic cancer were consecutively treated. The median patient age was 64.5 years (range 41-82 years) and all patients had objective disease progression on prior therapy: 32 patients had disease progression with gemcitabine and 31 had disease progression with a gemcitabine/5-fluorouracil/cisplatin combination. Grade 3-4 hematological toxicities included anemia (23%), thrombocytopenia (53%), and neutropenia (38%). There were no grade 3-4 neutropenic fevers, treatment-related mortalities, or withdrawals. Nonhematological grade 3-4 toxicities were rare: nausea/vomiting (3%), neurotoxicity (3%), nephrotoxicity (6%), and diarrhea (3%). Based on RECIST criteria a partial response (PR) was attained in eight patients (24%) and seven patients had stable disease (SD). Seven and six patients who attained a PR or SD, respectively, had disease progression with prior gemcitabine-based therapy. The median time to disease progression for all 34 patients was 3.9 months and 5.9 months for the eight patients who attained a PR. Median overall survival for all 34 patients was 10.3 months. CONCLUSION: Adding a single new drug such as irinotecan to the same first-line chemotherapy combination upon disease progression may be an important alternative to switching to different drug classes for treatment of relapsed/resistant cancer. The promising clinical outcomes and moderate toxicity associated with G-FLIP in this heavily pretreated group warrant development of this novel regimen including tests as first-line therapy in patients with diseases likely to be responsive to the drugs contained in this combination.

Adult↗
PubMed2000

Sensorimotor cortical influences on cuneate nucleus rhythmic activity in the anesthetized cat.

This work aimed to study whether the sensorimotor cerebral cortex spreads down its rhythmic patterns of activity to the dorsal column nuclei. Extracellular and intracellular recordings were obtained from the cuneate nucleus of chloralose-anesthetized cats. From a total of 140 neurons tested (106 cuneolemniscal), 72 showed spontaneous rhythmic activity within the slow (< 1 Hz), delta (1-4 Hz), spindle (5-15 Hz) and higher frequencies, with seven cells having the delta rhythm coupled to slow oscillations. The spindle activity recorded in the cuneate was tightly coupled to the thalamo-cortico-thalamic spindle rhythmicity. Bilateral or contralateral removal of the frontoparietal cortex abolished the cuneate slow and spindle oscillations. Oscillatory paroxysmal activity generated by fast electrical stimulation (50-100 Hz/1-2 s) of the sensorimotor cortex induced burst firing synchronized with the paroxysmal cortical "spike" on all the non-lemniscal neurons, and inhibitory responses also coincident with the cortical paroxysmal "spike" in the majority (71%) of the cuneolemniscal cells. The remaining lemniscal-projecting neurons showed bursting activity (11%) or sequences of excitation-inhibition (18%) also time-locked to the cortical paroxysmal "spike". Additionally, the cerebral cortex induced coherent oscillatory activity between thalamic ventroposterolateral and cuneate neurons. Electrolytic lesion of the pyramidal tract abolished the cortically induced effects on the contralateral cuneate nucleus, as well as on the ipsilateral medial lemniscus. The results demonstrate that the sensorimotor cortex imposes its rhythmic patterns on the cuneate nucleus through the pyramidal tract, and that the corticocuneate network can generate normal and abnormal patterns of synchronized activity, such as delta waves, spindles and spike-and-wave complexes. The cuneate neurons, however, are able to generate oscillatory activity above 1 Hz in the absence of cortical input, which implies that the cerebral cortex probably imposes its rhythmicity on the cuneate by matching the intrinsic preferred oscillatory frequency of cuneate neurons.

Animals↗
PubMed1993

Aggressive natural killer cell lymphoma/leukemia. A recently recognized clinicopathologic entity.

We report a comprehensive study of a case of aggressive natural killer cell lymphoma/leukemia, which is characterized by young male predominance, rapidly progressive clinical course, and presence of lymphadenopathy, hepatosplenomegaly, and bone marrow involvement. The leukemic phase is frequently preceded by pancytopenia. The diagnostic clues are the detection of cytoplasmic granules in tumor cells on Wright-Giemsa-stained tissue imprints or smears and a selective loss of T-cell antigens. Immunophenotyping is decisive in making the final diagnosis by showing positive natural killer cell markers (CD16, CD56, and/or CD57), CD2, CD11c, and Ia, but negative CD3, T-cell receptor heterodimers, terminal deoxynucleotidyl transferase, and B-cell markers. Genotyping always shows germline configuration in both immunoglobulin and T-cell receptor genes. The unique feature in this case is its presentation as a testicular lymphoma, which has not been previously reported. Polymerase chain reaction was performed in this case but failed to detect human T-cell leukemia virus type I/II provirus. It is important to recognize this new entity as it is a highly aggressive disease with a rapidly progressive clinical course and fails to respond to any chemotherapeutic regimen available.

Adult↗
PubMed1992

Use of cisplatin for elderly patients.

The ageing of the population has resulted in a greater emphasis on cancer treatment effects in elderly patients. This population has often had arbitrary dose modification of chemotherapy owing to fear of excessive side-effects. A review was undertaken to evaluate cisplatin toxicity in patients of 70 years of age or older. Thirty-four patients were evaluated. Their mean age was 72.8 years and 85.3% were women. Fourteen of 34 (41%) patients completed the planned therapy. Treatment was terminated because of disease progression (35%), renal toxicity (9%) and non-renal toxicity (15%). Our conclusion is that cisplatin can safely be administered to elderly patients. Arbitrary dose modification or elimination of cisplatin from a treatment programme on the grounds of patient age alone is not justified.

Acute Kidney Injury↗
PubMed1992

Study of the major phenotype of large granular T-cell lymphoproliferative disorder.

Six cases of large granular T-cell lymphoproliferative disorder with a selected immunophenotype (CD3+, CD4-, CD8+, CD16+) were studied to characterize a homogeneous group of patients. It was found that most of these patients did not exhibit the clinical features frequently described in large granular T-cell lymphoproliferative disorder--recurrent infection, rheumatoid arthritis, and splenomegaly. The laboratory tests usually positive in large granular T-cell lymphoproliferative disorder, including rheumatoid factor and anti-nuclear antibodies, also were frequently negative. The pathognomonic features were found to be neutropenia and large granular lymphocytosis with positive killer cell markers. All six cases showed T-cell receptor gene rearrangement that indicated a monoclonal proliferation of lymphoid cells, which were natural killer-like T cells by immunophenotyping. B cells were essentially absent in all cases. It should be emphasized that bone marrow aspirates are as informative as peripheral blood samples for the diagnosis of large granular T-cell lymphoproliferative disorder; indeed, phenotypes of blood and marrow in one case were identical in terms of percentages of markers. In this selected group of patients, the clinical courses were indolent with uncomplicated outcomes. In three patients, chemotherapy did not induce an obvious clinical response, but all patients' conditions remained stable with only supportive care.

Adult↗
PubMed1992

Multifocal choroiditis with evidence of Lyme disease.

A 32-year-old man had multifocal choroiditis without vitreous involvement. The diagnosis of Lyme disease was suggested by serial enzyme-linked immunosorbent assays of his serum and a cerebrospinal fluid specimen. The ocular findings resembled those seen in patients with acute posterior multifocal placoid pigment epitheliopathy (APMPPE). The active lesions resolved after administration of a two-week course of intravenous ceftriaxone. This case suggests that some cases of APMPPE actually may be Lyme disease.

Adult↗
PubMed1991

CD3+, CD4-, CD8- large granular T-cell lymphoproliferative disorder.

Large granular T-cell lymphoproliferative disorder (LGTLD) is a heterogeneous disorder covering a broad spectrum of diseases and requiring further subdivision. Most reported cases emphasized its suppressor phenotype (T gamma cell or CD8+), but we encountered two cases of CD3+, CD4-, CD8- LGTLD. Both cases had a benign clinical course and required no chemotherapy despite persistent lymphocytosis. This unique phenotype has been reported in a few cases of acute lymphoblastic leukemia expressing the T-cell receptor (TcR) gamma chain gene and is considered the counterpart of thymocytes at the intermediate stage between early precursors and mature thymocytes. Our case 1 provides further evidence that the CD3+, CD4-, CD8- phenotype, indeed, expresses the TcR gamma chain gene. However, the negative reaction to terminal deoxynucleotidyl transferase in our case 1 indicates that this phenotype represents proliferation of peripheral T-cells, in which about 2% bear the CD3+, CD4-, CD8- phenotype in the normal population. The selective use of CD3, CD4, CD8, HNK-1 monoclonal antibodies and of cytochemical stains (acid phosphatase and alpha-naphthyl butyrate esterase) for characterization of this disorder is discussed.

Adult↗
PubMed1989

Cognitive mediators in the reduction of pain: the role of expectancy, strategy use, and self-presentation.

Eighty subjects underwent three trials of cold-pressor pain. The first cold-pressor trial served as a baseline. Next, subjects in a neutral (no expectancy information) condition were taught a distraction strategy (shadowing letters) before one cold-pressor trial and an imagery strategy before the other. Subjects in other conditions received positive expectancy information about one of the strategies and negative expectancy information about the other. Negative information reduced expectancy ratings and decreased the magnitude of reported pain reductions. Both pretested levels of social desirability and degree of absorption in strategy use made contributions to the prediction of pain reduction that were independent of expectancy ratings. Theoretical implications are discussed.

Adolescent↗
PubMed1987

Diagnosis of nosocomial pneumonia in intubated, intensive care unit patients.

The clinical distinction between bacterial colonization of the tracheobronchial tree and nosocomial pneumonia is difficult, especially in intubated patients. We studied 51 intubated, intensive care unit patients prospectively by serial examinations of tracheal aspirates for elastin fibers, graded Gram's stains, and quantitative bacterial cultures in conjunction with clinical and radiologic observations in an attempt to develop criteria for the early detection of pulmonary infection. Patients with infection had new or progressive pulmonary infiltrates plus 1 of the following: positive blood culture results, radiographic evidence of cavitation, or histologic evidence of pneumonia, or 2 or more of the following: new fever, new leukocytosis, or grossly purulent tracheal aspirates. Twenty-one patients developed infection, 22 remained colonized, and 8 had an uncertain status. Infiltrates developed in 34 patients (21 infected, 8 colonized, 5 uncertain status). Gram-negative bacilli were most commonly isolated and were more frequent in infected patients (81 versus 47%, p less than 0.05); Pseudomonas aeruginosa and Serratia marcescens were most often associated with infection. No differences were observed between infected and colonized patients in demographic features, smoking history, underlying disease, previous antibiotic therapy, days in hospital before intubation, preexisting pneumonia upon intubation, or highest temperature or leukocyte count during course. By univariate analysis, infected patients had a longer duration of intubation (p less than 0.05), higher Gram's stain grading for neutrophils (p less than 0.05) or bacteria (p less than 0.005), higher bacterial colony counts (p less than 0.05), and more frequent detection of elastin fibers in tracheal aspirates (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1984

Infection caused by vancomycin-resistant Streptococcus sanguis II.

A patient with bacteremia caused by vancomycin-resistant Streptococcus sanguis II is presented. This rare occurrence suggests that vancomycin may not be a completely reliable antibiotic in the treatment of infections due to viridans species of the genus Streptococcus. Gram-positive isolates from blood and otherwise sterile body fluids should be tested for susceptibility to vancomycin.

Anti-Bacterial Agents↗
PubMed1982

Peripheral postcapillary venous pressure--a new hemodynamic monitoring parameter.

Peripheral postcapillary venous pressure (PCVP) appears to be an indicator of peripheral perfusion (cutaneous blood flow) in the experimental animal. Eighteen male mongrel dogs under balanced anesthesia were subjected to either slow, continuous hemorrhage 0.65 ml/kg/min) or plasma expansion with dextran 40 (0.80 ml/kg/min) over a period of 1 hour. Peripheral PCVP, cental venous pressure arterial pressure, cardiac output (CO), mixed venous oxygen saturation, pulmonary arterial pressure, and pulmonary wedge pressure were monitored on a continuous basis. The only parameter that consistently gave a predictable measure of the degree of induced volume change without requiring pulmonary arterial catheterization was PCVP. PCVP showed a close correlation with CO (r = 0.96).

Animals↗
PubMed1978

Bilateral oculomotor paralysis due to neurosyphilis.

Bilateral third nerve paresis attributed to neurosyphilis has not been documented in the absence of associated neurological deficits. We describe a patient with isolated bilateral third nerve paresis, positive serological findings in blood and cerebrospinal fluid, CSF pheocytosis, and increased protein content. Resolution of these abnormalities occurred when the patient was treated with penicillin.

Humans↗