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Biomedical subjects

E Cozzi

Publications and source records attributed to E Cozzi.

At least 73 records · Page 4Linked to original sources
PubMed1992

Changes in circulating B cells and immunoglobulin classes and subclasses in a healthy aged population.

The study of 87 adults of different ages, including 15 centenarians, selected for their healthy status, showed that profound changes of humoral immunity occur throughout life. In particular, a statistically significant age-related increase of the serum level of immunoglobulin classes (IgG and IgA but not IgM) and IgG subclasses (IgG1, 2 and 3, but not IgG4) was detected. A parallel age-related decrease of circulating B cells was also observed. The hypothesis of a complex derangement of B cell function and/or compartmentalization with age is put forward, together with the proposal that healthy centenarians (as representative of successful ageing) may be helpful in identifying the physiological age-related modifications of the immune system.

Adult↗
PubMed1992

Immunotherapeutic approaches with monoclonal antibodies to immunological diseases.

The molecular events triggered by the interaction of the immune system with an antigen and leading to an immune response have been characterized in recent years. This information has provided the background to develop immunotherapeutic approaches to allograft rejection and to autoimmune diseases utilizing monoclonal antibodies to molecules which play a role in the immune response. The clinical trials performed thus far are described. The significance of the results obtained in these trials and the future potential developments are discussed.

Antibodies, Monoclonal↗
PubMed1989

Antiinflammatory action of salicylates: aspirin is not a prodrug for salicylate against rat carrageenin pleurisy.

A current hypothesis postulates that the antiinflammatory effect of aspirin (acetylsalicylic acid) is mediated by its metabolite salicylic acid through inhibition of PGE2 synthesis. We tested this hypothesis in rats with carrageenin-induced pleurisy. Aspirin or salicylate, given orally, reduced exudation and cell migration into the pleural cavity, aspirin being more potent than salicylate. The antiinflammatory effect of aspirin cannot be explained only in terms of salicylate formation. Doses of aspirin and salicylate that inhibit inflammation by 50% result in salicylate levels in the exudate of 70 +/- 12 and 323 +/- 17 micrograms/ml, respectively. At a significant antiinflammatory dose (100 mg/kg), salicylate did not reduce the prostaglandin and thromboxane content of the exudate. This indicates that inhibition of cyclooxygenase is not a likely mechanism for the antiinflammatory effect of salicylate. Salicylate only reduced the amount of 6-keto-PGF1 alpha in the exudate at higher doses (200 mg/kg), while aspirin at an equally antiinflammatory dose (50 mg/kg) reduced the content of 6-keto-PGF1 alpha, TXB2, PGD2 but not of PGE2 in the exudate. It therefore seems unlikely that an inhibition of PGE2 synthesis is the common mechanism by which aspirin and salicylate exert their antiinflammatory effects. These results do not supported the hypothesis that aspirin is a prodrug for salicylate but rather indicate that both compounds may exert their antiinflammatory effects partly by different mechanisms.

Animals↗
PubMed1988

Hemodynamic effects of celiprolol at rest and during exercise; a comparison with enalapril.

The antihypertensive effects of once-daily administration of celiprolol 400 mg were compared with those of once-daily enalapril 20 mg in 20 mild to moderate essential hypertensives in a single-blind study in which the subjects were randomized to 2 weeks' treatment with either drug, preceded by 2 weeks of placebo administration. Supine and standing systolic blood pressure (SBP), diastolic pressure (DBP), and heart rate (HR) were measured at rest and during exercise (exercise bicycle with increasing work loads up to 100 watts) at the end of either period, 20 to 24 hr after drug or placebo administration. Compared to placebo, both celiprolol and enalapril reduced resting supine and standing SBP and DBP to a marked and similar extent; resting HR was unaffected by enalapril, while celiprolol produced modest reductions. During exercise, however, celiprolol significantly attenuated rises in SBP and HR, while enalapril did not. Indexes of cardiac function at rest obtained by echocardiography and systolic time intervals were unaffected by either drug. Thus, despite similar reductions by both drugs in resting blood pressures, celiprolol produced better antihypertensive effects during exercise than enalapril.

Adrenergic beta-Antagonists↗
PubMed1988

Study of some early immunological parameters in aging humans.

We studied the correlation between the in vitro lymphocyte proliferative response and some early parameters of lymphocyte activation in aged people. While a consistent number of elderly subjects showed significantly decreased proliferative responses to mitogen stimulation, interleukin-1 (IL-1) production and IL-2 receptor/DR antigen expression were comparable to those of young controls. The reduction in IL-2 production observed in some aged donors did not correlate with the decreased proliferative activity in response to mitogen. Moreover, addition to the cultures of recombinant IL-2 was not capable of restoring the proliferative response to normal levels. These data on the whole seem to argue against a primary involvement in age-associated lymphocyte hyporesponsiveness of an alteration in the early phases of lymphocyte activation engaging the complex lymphokine/receptor network.

Adult↗
PubMed1988

Comparison of the antihypertensive effects of celiprolol and enalapril.

Muscular exercise is the most common stress imposed on the cardiovascular system and, in hypertensive patients, it causes an exaggerated increase in the already elevated blood pressure. The evaluation of any antihypertensive drug must, therefore, include an investigation of its effects on the haemodynamic response to exercise. For this reason the effects of celiprolol and enalapril were studied in hypertensive patients, both at rest and during an exercise stress test performed on a bicycle ergometer. The haemodynamic changes observed were very similar at rest: both drugs consistently reduced blood pressure without impairing either myocardial geometry or function. The only between drug difference found at rest was slight bradycardia with celiprolol, whereas heart rate was unaffected by enalapril. By contrast, there was a marked difference in the effect on the blood pressure increase caused by muscular exercise: 24 h after dosing, celiprolol continued to attenuate the hypertensive response to exercise while enalapril failed to show any significant antihypertensive effect possibly because after this time there was a reduction in angiotensin converting enzyme inhibiting activity. Thus, celiprolol and enalapril are both effective once-a-day antihypertensive agents, but celiprolol provides a longer lasting protection from hypertensive peaks caused by exercise.

Adrenergic beta-Antagonists↗
PubMed1987

Antibody-mediated extraction/negative-ion chemical ionization mass spectrometric measurement of thromboxane B2 and 2,3-dinor-thromboxane B2 in human and rat urine.

An antibody-mediated extraction method for gas chromatographic-mass spectrometric analysis of thromboxane A2 (TXA2) urinary metabolites is reported. An antibody (Ab) raised against thromboxane B2 (TXB2) (35% cross-reacting with 2,3-dinor-TXB2) was coupled to CNBr-activated Sepharose 4B (Se) and used as stationary phase for simultaneous extraction of both compounds from urine. After addition of deuterium-labeled TXB2 as internal standard, rat or human urine was percolated through a small Ab-Se column. After being washed, the eluate was directly derivatized to the pentafluorobenzyl ester, methyloxime, and trimethylsilyl ether. Quantitation was performed by high-resolution gas chromatography-negative-ion chemical ionization mass spectrometry, monitoring the carboxylate anions. This method was applied to evaluate the urinary excretion of TXB2 and 2,3-dinor-TXB2 in humans and rats. We report on the excretion of 2,3-dinor-TXB2 in the rat. This novel approach to the extraction of urinary thromboxanes is more convenient than currently available methods in terms of simplicity, rapidity, and recovery. This method could be extended to any other prostanoid for which an antibody could be obtained.

Animals↗
PubMed1987

Prostaglandin and thromboxane synthesis by M5076 ovarian reticulosarcoma during growth: effects of a thromboxane synthetase inhibitor.

The five stable metabolites [prostaglandin F2 alpha (PGF2 alpha), prostaglandin D2 (PGD2), prostaglandin E2 (PGE2), thromboxane B2 (TXB2), and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha)] of arachidonic acid (AA) via the cyclooxygenase pathway were measured by high-resolution gas chromatography-mass spectrometry in M5076 ovarian reticulosarcoma (M5) homogenates at various times after tumor implantation (Days 15, 18, 21, and 24). Vegetating tumor showed an active AA overall metabolism, which significantly increased during tumor growth. Synthesis of selected products (TXB2, PGD2, and PGE2) increased markedly over time (up to 10.6, 3.5, and 0.9 micrograms/g, respectively). The overall metabolic profile was TXB2 much greater than PGD2 greater than PGF2 alpha greater than 6-keto-PGF1 alpha greater than PGE2 on Day 15 and TXB2 much greater than PGD2 much greater than PGF2 alpha greater than 6-keto-PGF1 alpha on Day 24. TXB2 was also by far the most abundant product of in vitro-cultured M5 cells. Chronic treatment of M5-bearing mice with dazmegrel (UK-38,485), a selective thromboxane synthetase inhibitor (100 mg/kg p.o. daily, from Day 7 to killing), resulted in incomplete TXB2 synthesis inhibition, AA metabolism diversion toward the other prostaglandins, and no effects of tumor growth and metastasis. More frequent dazmegrel treatment (100 mg/kg p.o. every 8 h from Day 1 to killing) resulted in complete TXB2 synthetase inhibition, AA metabolism diversion, and increased tumor growth and metastasis. These data do not support the hypothesis of thromboxane synthetase inhibitors reducing tumor growth. However, since TXB2 suppression was accompanied by the production of other products possibly interfering in tumor growth, no conclusions on the effective role of TXA2 in malignancy can be drawn.

Animals↗
PubMed1987

Arachidonic acid metabolic profiles in human meningiomas and gliomas.

We determined arachidonic acid (AA) cyclooxygenase metabolic profiles in specimens of human intracranial tumors (gliomas and meningiomas) and, when available, normal brain tissue. Samples were collected at surgery and immediately frozen in liquid nitrogen. The five stable metabolites of AA (PGE2, PGD2, PGF2 alpha, 6-keto-PGF1 alpha and TXB2) were measured by high-resolution gas chromatography-mass spectrometry after ex vivo metabolism of endogenous AA by tissue homogenates. The absolute amounts of AA metabolites varied widely between samples, though meningiomas and gliomas showed characteristic profiles. Compared to the slow-growing benign meningiomas, the rapidly-growing infiltrating gliomas had higher synthesis of TXA2 (reported as a procancer metabolite) and lower synthesis of PGD2 and PGI2 (reported as anticancer metabolites). A higher overall synthesis capacity, preferentially toward TXA2, was found in glioblastomas than in non-pathological brain tissue.

Arachidonic Acid↗
PubMed1984

A totally implanted injection port system for blood sampling and chemotherapy administration.

We evaluated a totally implanted system consisting of a subcutaneous injection port connected to a silicone elastomer central venous catheter for vascular access, including blood drawing, in 35 patients with cancer. All patients lacked peripheral venous access sites and were undergoing aggressive chemotherapy programs. The cumulative duration of successful access exceeded 2,900 days (for individual patients: range, five to 203 days; median, 61 days). In no instance were infusions or injections unsuccessful. Blood-sampling attempts were successful 90% of the time. The system did not require flushing between uses, being filled with heparinized saline after each entry. There were no instances of irreversible catheter occlusion or shear and no system-related infections. Thus, this device appears to have advantages over other central venous catheters in terms of patient acceptance and lack of maintenance between uses.

Adolescent↗
PubMed1984

Regional chemotherapy of colorectal cancer metastatic to the liver.

Ninety-three patients with biopsy-proven colorectal cancer metastatic to the liver were treated with hepatic arterial infusion of 5-fluorodeoxyuridine (FUDR). There were 52 men and 41 women (median age, 60 years). Forty-two patients (45%) had failed prior systemic chemotherapy. Catheters were operatively placed and multiple catheters were used if dictated by hepatic arterial anatomy in order to obtain perfusion of the entire liver. The drug was delivered by a totally implanted INFUSAID model 400 pump and patients received cyclic therapy consisting of 2 weeks of 0.3 mg/kg/d FUDR alternating with 2 weeks of saline. Patients with extrahepatic tumor or patients whose hepatic tumor failed to respond to FUDR were given a 30 minute intraarterial infusion of mitomycin C, 15 mg/m2, every 6 to 8 weeks in addition to FUDR. Fifty of the 93 evaluable patients presented with metastatic tumor confined to the liver. Of these 50 patients, 83% demonstrated a significant reduction in tumor size with a median duration of response of 13 months and a median survival of 25 months from diagnosis of liver metastases. Twenty-four of these 50 patients remain alive. Forty-three patients presented with extrahepatic metastases in addition to their liver tumor, and 74% had a response with a median duration of 6 months and a median survival of 14 months. Only six patients of those presenting with extrahepatic tumor remain alive. None of the 93 patients died solely of uncontrolled liver tumor, and only 9 died as a result of uncontrolled liver metastases and disseminated extrahepatic tumor. The duration of survival for both groups was determined by the uncontrolled progression of extrahepatic tumor. In patients with metastatic colorectal cancer involving only the liver, hepatic arterial FUDR alone and with the addition of mitomycin C provided excellent control of hepatic tumor. Survival appeared to be prolonged in this uncontrolled study.

Antineoplastic Agents↗
PubMed1983

[Clinical study on the antilipemic effect of tiadenol (Eulip)].

The hypolipaemising action of thiadenol (Eulip) was evaluated in a mixed groups of patients with various forms of hyperdyslipidaemia and cardiovascular complications. Mention is made of the administration modalities adopted. The results obtained shows that the drug is significant with regard to blood triglyceride levels in patients in groups IV and II B, and to a lesser, though by no meansnegligible, extent with regard to total cholesterol in II A and II B patients. No signs of intolerance or side-effects were noted, even when anticoagulants were also being administered.

Clinical Trials as Topic↗
PubMed1982

Totally implanted system for intravenous chemotherapy in patients with cancer.

A totally implanted system for improved central venous access has been investigated in 20 patients with cancer (six with solid tumors, four with leukemia, and 10 with lymphomas) who were treated with aggressive chemotherapy regimens and who lacked peripheral venous sites. The system is implanted using local anesthesia and consists of a subcutaneous injection port connected to a Silastic catheter threaded through the subclavian vein into the superior vena cava. Injections and continuous infusions (for up to three weeks) of virtually all classes of antineoplastic agents, antibiotics, blood components, and intravenous solutions were administered through the system. The system was filled with heparinized saline and not otherwise flushed between uses. The system has remained functional for periods exceeding 450 days (mean 235 days). There was no significant local irritation and no system became infected. None of 18 large-bore catheters (0.63 mm lumen) became occluded (seven to 300 days), whereas five of six small-bore catheters (0.38 mm lumen) became occluded (90 to 420 days). Three of the occluded systems were replaced. Acceptance has been excellent, and patients have had no impediment to normal activities. This system appears to be an alternate means of safe and reliable central venous access with improved convenience and cosmetic acceptability.

Antineoplastic Agents↗
PubMed1982

Perfusion scintigraphy (Tc-99m MAA) during surgery for placement of chemotherapy catheter in hepatic artery: concise communication.

In 17 patients receiving regional hepatic chemotherapy, Tc-99m macroaggregated albumin imaging was used to aid arterial catheter placement and to assess perfusion patterns. Intraoperative imaging with a portable gamma camera allowed immediate monitoring of hepatic and extrahepatic perfusion patterns and assisted catheter manipulation when necessary to achieve optimal flow distribution. In all 12 patients with standard hepatic arterial anatomy, complete perfusion of both lobes of the liver was achieved, although three of them required intraoperative catheter manipulation and repeat imaging after initial placement. The remaining five patients had aberrant hepatic arterial anatomy, and complete perfusion was more difficult to achieve; they exemplified the need for dual catheters, ligation of accessory hepatic branches, and repeated imaging.

Adenocarcinoma↗
PubMed1982

Totally implanted venous and arterial access system to replace external catheters in cancer treatment.

A totally implanted venous and arterial access system was tested in 30 cancer patients. The device, an injection port (Infuse-A-Port, Infusaid Corp., Sharon, Mass.), consisted of a 3.5 by 1.5 cm conical chamber with a self-sealing silicone rubber septum connected to a Silastic catheter. Ten patents had the injection port operatively placed for arterial access. A total of 39 bolus injections and 18 continuous infusions lasting an average 5.4 +/- 3.4 days were administered through the port. The total time of arterial access ranged from 70 to 370 days. No special program of heparinization was required to maintain patency. The injection port was used for central venous access in 20 patients. The first six patients had a small lumen catheter of 0.38 mm internal diameter, and five had occlusion between 142 and 447 days. Subsequently, 19 ports with a larger catheter lumen of 0.63 mm were used. These ports functioned for an average of 274 +/- 110 days (23 to 382 days). There were 380 single bolus injections and 64 continuous infusions. A variety of anticancer agents as well as whole blood, blood products, and antibiotics were administered with the device without difficulty. Patient acceptance was excellent.

Adult↗