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Biomedical subjects

P J Cozzi

Publications and source records attributed to P J Cozzi.

At least 19 recordsLinked to original sources
PubMed2004

Immunohistochemical characterisation of the monoclonal antibody BLCA-38 for the detection of prostate cancer.

BACKGROUND: Monoclonal antibodies (MAbs) can be used to detect, image and treat cancers. This study aimed to characterise the binding of BLCA-38 MAbs to human prostate cancer cell lines, human prostate cancer biopsy samples and normal tissues to enable future targeted studies. METHODS: BLCA-38 antigen expression on cancer lines was determined by flow cytometry; that on patient specimens from normal tissues and cancers was tested by immunohistochemistry using fresh frozen tissues or paraffin-embedded tissues that had undergone antigen retrieval. RESULTS: Cell surface BLCA-38 antigen expression was seen on DU-145, PC-3, PC-3 M and PC-3 M-MM2 prostate cancer lines, but LNCaP, MDA PCa 2a or MDA PCa 2b lines were negative. Other human lines, including 8/12 bladder cancer and A431 vulval epidermoid cells, but not breast cancer lines, expressed BLCA-38 antigen. Staining occurred in glandular epithelial cells in the majority of frozen, and paraffin-embedded prostate cancer tissues and was occasionally seen in prostatic intraepithelial neoplasia (PIN). No staining was observed in normal cadaver tissues or in benign areas from various other cancer tissues. CONCLUSIONS: The BLCA-38 antibody binds to the majority of human prostate cancers but not to normal cells, and has potential for targeting novel therapies in patients with this disease.

Animals↗
PubMed1999

A fellowship in the USA: essential information for the Australasian medical graduate.

BACKGROUND: There have been many recent changes to the immigration and educational requirements necessary to obtain both clinical and research positions in the USA. This paper describes these requirements in detail and examines the cost of obtaining a position. METHODS: An extensive review of Medline and relevant documents from educational and immigration bodies is undertaken in addition to personal and peer experience of the processes necessary to fulfil educational and immigration requirements for funded medical positions in the USA. A cost analysis is performed based upon the latest charges for exam requirements and visa fees. A 'minimum' cost for fulfilling exam and visa requirements only and a 'likely' cost (which represents a more realistic appraisal of the expenses likely to be incurred) are investigated. RESULTS: This review shows that many recent changes have made the attainment of a position difficult and expensive. Much foresight and planning is required to obtain the necessary requirements for medical licensure and to obtain working visa status in addition to the application for the position itself. The cost analysis reveals that the minimum cost is $4050 (AU$) and the 'likely' cost is $8600 (AU$). CONCLUSION: Australasian trainees and Fellows need to be fully aware of the difficulties and expenses likely to be encountered in order to make an informed decision with regard to overseas training in the USA.

Asia↗
PubMed1999

Cyclophosphamide in the treatment of pulmonary diseases: survey of use, training, and practitioner knowledge base.

OBJECTIVE: To assess pulmonologists' use, training in the use, and knowledge base of the drug cyclophosphamide. DESIGN: Survey through questionnaire. Testing of knowledge base before and after instructional conference. PARTICIPANTS AND METHODS: Pulmonologists (94 attendings, 31 fellows), selected randomly at the 1996 and 1997 annual meetings of The American Thoracic Society, completed surveys of their use and training in the use of cyclophosphamide. Thirty-five attending at the 1998 meeting completed a test of knowledge base of the drug. Members of the pulmonary teaching service at The University of Chicago Hospitals completed the test before and after a case-based conference designed to educate pulmonologists in the use of the drug. RESULTS: Forty-three percent of the attending pulmonologists and 55% of the fellows were currently using the drug in the management of their patients; 77% of the attending pulmonologists had prescribed the drug in the past. Nonmalignant diseases for which the drug was prescribed included usual interstitial pneumonitis/desquamative interstitial pneumonitis, vasculitis, collagen vascular disease, constrictive bronchiolitis, sarcoid, and Goodpasture's disease. Sixty-eight percent of attending pulmonologists and 81% of fellows had no training in the drug's use. Of the attending pulmonologists who made use of the drug, 64% were prescribing and managing its use themselves. Of those who prescribed and managed the drug's use themselves, 65% had had no training in its use. Of those fellows who prescribed and managed the drug's use themselves, 73% had had no training in the drug's use. On knowledge-based testing, the average correct score was 30 +/- 10%. With an educational conference, average pre- and post-test scores rose from 40 +/- 10% to 80 +/- 10% (p < 0.001). CONCLUSION: Cyclophosphamide had been used by the vast majority of pulmonologists, either currently or in the past, for a wide variety of lung diseases. Its use is commonly managed by physicians who have no specific training relevant to this agent. Practitioner knowledge base of the drug is poor, and case-based conferences in fellowship may be an effective means of imparting information concerning this drug.

Congresses as Topic↗
PubMed1999

Toxicology and pharmacokinetics of intravesical gemcitabine: a preclinical study in dogs.

More active and well-tolerated agents are needed for the treatment of superficial bladder cancer. This study investigated intravesical gemcitabine to establish the toxicology and pharmacokinetics necessary for clinical trials. Beagle dogs (in groups of 2; n = 6) received 100 mg, 350 mg, or 1 g of drug by intravesical administration on alternate days three times/week for 4 weeks. Animals were observed for clinical signs of toxicity; gemcitabine levels and peripheral blood counts were taken three times weekly. The dogs were euthanized, and a full necropsy was performed at days 1 and 14 after the last dose. Intravesical gemcitabine was given at 100 mg (n = 2), 350 mg (equivalent to the 1000 mg/m2 human dose; n = 3), and 3.5 g (n = 1). i.v. gemcitabine was given at 350 mg (n = 2). Plasma samples drawn at time points up to 8 h were analyzed for systemic absorption and clearance of drug. Doses of 100 and 350 mg were well tolerated with no clinical side effects. Necropsies revealed normal bone marrow cellularity and normal bladder histology. At 1 g, signs of severe clinical toxicity were evident, and after only three doses, necropsies demonstrated severe bone marrow hypoplasia, cystitis, and intestinal necrosis. At all intravesical doses, significant systemic absorption was seen. The T1/2 (+/- SD) for intravesical and i.v. administration of 350 mg was 328 (+/-6.8) min and 99.3 (+/-5.2) min, respectively (P<0.001). Intravesical gemcitabine is well tolerated and has no direct bladder toxicity at doses up to 1000 mg/m2. Higher doses result in gastrointestinal, bladder, and bone marrow toxicity.

Absorption↗
PubMed1998

Cryotherapy for neuroendocrine liver metastases.

While the prognosis for patients with untreated liver metastases from neuroendocrine primaries is rather good, they often suffer disabling symptoms due to syndromes of hormonal excess. Thirteen patients with metastatic neuroendocrine tumours were treated by hepatic cryotherapy; seven patients were symptomatic and five of these had elevated levels of hormonal tumour markers. Twelve patients are alive and mostly asymptomatic with a median follow up of 13.5 months; one patient died after 45 months of bronchopneumonia without evidence of tumour recurrence. All patients with elevated preoperative tumour markers have had a significant fall in markers postoperatively. Two patients were returned to the operating theatre for coagulopathy-associated bleeding: one patient each developed acute renal failure and pulmonary embolism, but there was no mortality. This study shows that hepatic cryotherapy offers a useful treatment option for this group of patients, alleviates symptoms and may have an impact on survival.

Adult↗
PubMed1997

Cryosurgery.

The in situ destruction of malignant tissue by freezing is a relatively new addition to the list of treatment options for patients with cancer in solid organs. Although skin cancers have long been treated by cryosurgery, the lack of suitable equipment for both delivering and monitoring the freezing process hindered further development of the treatment of more inaccessible lesions until the 1960s. At this time, Cooperz developed cryosurgical machines which enabled the destruction of CNS lesions in patients with Parkinson's disease and stimulated renewed interest in the application of cryosurgery to the treatment of cancer.

Journal Article↗
PubMed1997

Renal cryotherapy in a sheep model; a feasibility study.

PURPOSE: This study was designed to evaluate the safety and efficacy of renal cryotherapy as a possible treatment of renal malignancy with preservation of renal parenchyma. MATERIALS AND METHODS: Ten Merino sheep were anaesthetised and the right kidney was exposed through a retro-peritoneal approach. A 5 mm. cryotherapy probe (LCS 3000 Cryotec UK) was inserted into the lower pole of the kidney and freezing was undertaken to form an iceball 5 cm. in diameter. RESULTS: There was no mortality and no complications were observed. A transient rise in creatinine was observed post-operatively. The sheep were euthenased at 4 weeks and at necropsy macroscopic examination revealed a contracted, fibrotic wedge shaped lesion of 3 cm in diameter. Histological examination of the "cryolesion" revealed a central area of coagulative necrosis and a 5 mm rim of partial necrosis with preservation of renal tubules. CONCLUSION: We conclude that renal cryotherapy is safe and can achieve effective renal necrosis in the sheep model.

Animals↗
PubMed1996

In vitro and in vivo assessment of urethral warming catheters for the transperineal cryoablation of prostatic carcinoma.

OBJECTIVE: To evaluate the two most common urethral warming catheters currently available for their effectiveness in preventing urethral injury in an animal model and thus during transperineal cryosurgery for the treatment of prostate cancer. PATIENTS, MATERIALS AND METHODS: The warming efficiency of the variable-diameter thin latex-balloon catheter (Cook, Australia) and the fixed-diameter PVC catheter (Candela, USA) were evaluated in a water-bath. A sheep model was then used for subsequent experiments to further evaluate the better catheter. The technique used for the insertion of the Cook catheter in a series of 33 patients treated with prostate cryosurgery is also described. RESULTS: In vitro, the Cook catheter was more effective (P < 0.01) than the Candela catheter in preventing localized cooling. In vivo, results in five animals showed that the urethral epithelium was viable in all sections that had been protected by the catheter and focally denuded or necrotic in those sections not protected, with each animal used as its own control (P < 0.01 Fisher's exact test). The 33 patients treated while using the Cook catheter had no subsequent complications. CONCLUSION: The urethral warming catheter currently in use for prostatic cryosurgery in Australia is more effective in vitro than its competitor and is effective in preventing urethral injury in vivo.

Catheterization↗
PubMed1996

Critical temperature for in vivo cryoablation of human prostate cancer in a xenograft model.

OBJECTIVES: To assess the in vivo sensitivity of human prostate cancer cells (PC3) to cryoablation and thus define the minimum temperature needed to prevent the recurrence of cancer after percutaneous transperineal radical prostatic cryoablation. MATERIALS AND METHODS: Twenty-five male nu/nu mice were inoculated by a subcutaneous injection with 5 x 10(5) PC3 cells. After 3 weeks the tumours (mean area 60.4 mm2, SEM 5.7) were frozen using a 3 mm cryotherapy probe (LCS 3000 Cryotech UK) to temperatures ranging from 0 degrees to -40 degrees C. RESULTS: No tumours recurred in seven mice which had tumours frozen to < -15 degrees C. There were eight recurrences in 15 mice which had tumours frozen to between 0 degree and -15 degrees C, and all were confirmed histologically. CONCLUSIONS: The minimum temperature required to prevent recurrence of tumours from human prostate cancer cells was < -15 degrees C in this in vivo mouse model.

Animals↗
PubMed1996

Two cases of spontaneous liver rupture and literature review.

Spontaneous liver rupture is uncommon, difficult to diagnose and carries a universally high mortality. It has been well documented to occur as a complication of primary or secondary hepatic malignancy. Similarly, there are 28 cases of ruptured haemangiomata described in the world literature. It is also well described in severe pregnancy-induced hypertension and is said to carry a mortality of 18% for patients treated by packing and drainage of the haematoma and 75% for patients treated with liver resection. Two female patients aged 60 and 61 presented to our accident and emergency department. One had a history of hypertension only and the other a history of a bleeding diathesis from the lupus anticoagulant. Both presented with hypotension and abdominal pain and both were diagnosed by abdominal CT scan. One was treated with hepatic artery ligation and tamponade and the other with liver resection and correction of the coagulopathy. Neither had any evidence of a ruptured hemangioma or tumor at laparotomy or on histological examination, and both are alive and well. The conclusions to be drawn from this review and our own recent experience is that the treatment of choice for ruptured haemangiomata is liver resection and, for rupture during pregnancy, is tamponade with packs and evacuation of the haematoma. Hepatic arteriography and embolisation, if possible, is a useful adjunct. Correction of any coagulopathy is essential. We can only speculate that the aetiology in our patients was uncontrolled hypertension in one and coagulopathy in the other.

Female↗
PubMed1996

Laparoscopic vs open ultrasound of the liver: an in vitro study.

Intra-operative contact ultrasound is a sensitive method of detecting liver tumours. The aim of this study was to compare the sensitivity of open contact ultrasound (OUS) of the liver with laparoscopic contact ultrasound (LUS). Hypoechoic "lesions" were created in 5 fresh pig livers by inserting 28 grapes via small incisions in the inferior surface. The size (range 8-25 mm) and location of each grape was recorded. Scanning was undertaken in random order by two experienced independent observers with no knowledge of the size, number or position of the lesions, using an Aloka 650 series scanner and 7.5 MHz probes. The crude sensitivity with OUS was 96% and 100% respectively for the two observers, and 92% for each with LUS. One grape was interpreted as 2 separate grapes on LUS by one observer. Absolute sensitivity (grapes identified in the correct location) was 86% and 93% respectively with OUS and 79% for each observer with LUS. LUS was almost as sensitive as OUS in this model of hepatic metastases.

Animals↗
PubMed1995

Cryotherapy treatment of patients with hepatic metastases from neuroendocrine tumors.

BACKGROUND: Liver metastases from neuroendocrine tumors often present with disabling symptoms due to syndromes of hormonal excess. A locally destructive technique such as hepatic cryotherapy not only alleviates symptoms but may improve survival in this group of patients. METHODS: Six patients with metastatic neuroendocrine tumors were treated with hepatic cryotherapy. Four patients were symptomatic and three of these had elevated tumor markers from ectopic hormone production. RESULTS: All patients are alive and asymptomatic, with a median follow-up of 24 months (range, 6 months to 6 years). All have had a complete radiologic response. All with elevated preoperative markers have had a greater than 89% decrease in tumor markers. Coagulopathy occurred in two patients necessitating additional surgery, but there was no other morbidity attributable to the cryotherapy. CONCLUSION: To the authors' knowledge, this study demonstrates for the first time that hepatic cryotherapy offers supportive treatment for patients with neuroendocrine tumors metastatic to the liver. Cryotherapy alleviates symptoms and may improve survival.

Adenoma, Islet Cell↗
PubMed1995

Bioactivity of recombinant feline interleukin-2 on human and feline leukocytes.

Interleukin (IL)-2 is a 16,000 Da protein product of T lymphocytes which is the principle cytokine responsible for clonal expansion of T lymphocytes as a response to antigen exposure. Deficiency of functional IL-2 plays a pivotal role in the pathogenesis of human immunodeficiency syndrome and may be important in the pathogenesis of feline immunodeficiency syndrome as well. Additionally, IL-2 may enhance secretion of interleukin-5 from the TH2 subset of CD4+ T cells, promote peripheral and systemic eosinophilia, and contribute to the eosinophilia which characterizes the inflamed airways of human beings and cats with asthma. We recently reported the sequence of feline IL-2 and the synthesis of recombinant feline IL-2. The purpose of the present study was to evaluate the bioactivity of recombinant feline IL-2 on human and feline leukocytes. We established dose-response relationships between recombinant feline IL-2 and radiolabeled proliferating human and feline leukocytes using thymidine incorporation as a marker of bioactivity. We found that recombinant human IL-2 promotes proliferation of both human and feline leukocytes. However, recombinant feline IL-2 promotes proliferation of feline cells, but not human cells.

Animals↗
PubMed1995

Pulmonary artery diastolic-occlusion pressure gradient is increased in acute pulmonary embolism.

OBJECTIVE: To assess the pulmonary artery (PA) diastolic-occlusion (wedge) pressure gradient in patients with acute pulmonary embolism and to evaluate this variable's diagnostic utility. DESIGN: Retrospective, clinical review. SETTING: Intensive care and cardiac catheterization units of a university medical center. INTERVENTIONS: None. PATIENTS: A series of 19 acute pulmonary embolism patients with concurrent right heart catheterization. Control groups consisted of 19 age-, sex-, and heart rate-matched critically ill controls who also underwent right heart catheterization, eight patients suspected of having pulmonary embolism who had negative pulmonary angiography and concurrent right heart catheterization, and 255 patients with a primary diagnosis of coronary artery disease who underwent right heart catheterization at the time of left heart catheterization. MEASUREMENTS AND MAIN RESULTS: Initial hemodynamics (systolic, diastolic, and mean systemic and pulmonary arterial pressures, occlusion pressure, PA diastolic-occlusion pressure gradient, cardiac output, systemic and pulmonary vascular resistances) were compared between cohorts. Other than differences in the PA diastolic-occlusion pressure gradients, no significant differences were identified between cohorts. Pulmonary embolism patients were found to have increased PA diastolic-occlusion pressure gradients (10 +/- 5 vs. 3 +/- 2 mm Hg for the critically ill controls [p < .0002], and 4 +/- 4 mm Hg for the coronary artery disease cohort [p < .0005]). However, no significant difference in PA diastolic-occlusion pressure gradient values was identified when patients with proven pulmonary embolism were compared with patients in whom pulmonary embolism was clinically suspected yet not confirmed by angiograms (10 +/- 9 mm Hg; NS). For three of 19 pulmonary embolism patients, no occlusion pressure could be obtained due to an inability to wedge the balloon tip; 13 of 16 patients had PA diastolic-occlusion pressure gradients of > or = 8 mm Hg. In the pulmonary embolism cohort, PA diastolic-occlusion pressure gradient correlated well with pulmonary vascular resistance (r2 = .50; p < .05), but not with cardiac output or heart rate. CONCLUSION: In the large number of patients with right heart catheters in whom the question of pulmonary embolism is raised, an increased PA diastolic-occlusion pressure gradient (especially > or = 8 mm Hg) may provide a clue to the diagnosis of pulmonary embolism, but is not specific for this diagnosis.

Acute Disease↗
PubMed1993

Sequence and functional characterization of feline interleukin 2.

Since the discovery of its involvement in the pathogenesis of feline immunodeficiency virus infection ("cat AIDS") and feline leukemia virus infection, the role of feline interleukin 2 (IL-2) has been a focus of particular interest. The purpose of this study was to clone feline IL-2 cDNA, as well as synthesize bioactive recombinant feline IL-2. The isolation of cDNA encoding feline IL-2 was carried out using a PCR-based strategy and screening of a feline leukocyte cDNA library. Feline IL-2 consists of 154 amino acids including a putative signal sequence and has 81%, 69%, 60% and 64% identity to human, bovine, murine and rat IL-2, respectively. Feline IL-2 cDNA was expressed in COS-7 cells. The secreted protein has CTLL-4 murine cytotoxic T cell proliferative activity characteristic of authentic IL-2. These data confirm the synthesis of bioactive recombinant feline IL-2.

Amino Acid Sequence↗
PubMed1993

Activation of tracheal smooth muscle responsiveness by fMLP-treated HL-60 cells and neutrophils.

We assessed the effects of cultured human promyelocytic leukemia (HL-60) cells and polymorphonuclear leukocytes (neutrophils) isolated from peripheral human blood on tracheal smooth muscle responsiveness in 40 male Hartley guinea pigs. Undifferentiated HL-60 cells (16-25 passages) were activated in vitro by incubation with 1 microM f-Met-Leu-Phe (fMLP), and force of contraction was measured isometrically using an in situ preparation of tracheal smooth muscle. Increasing concentrations of acetylcholine (ACh; 10(-10) to 10(-6) mol/cm2 tracheal surface) were applied topically to the epithelial surface pretreated with 4 x 10(6) fMLP-activated HL-60 cells, 4 x 10(6) fMLP-activated neutrophils, 4 x 10(6) sham-activated HL-60 cells, fMLP+vehicle, or vehicle control. Topical application of fMLP-activated HL-60 cells caused a maximum active tension (AT) of 1.13 +/- 0.2 g/cm after 5 min; fMLP-activated neutrophils, sham-activated HL-60 cells, or fMLP+vehicle had no effect. The fMLP-activated HL-60 cells also caused substantial augmentation of tracheal contraction to ACh (P < 0.05 vs. sham-activated cells for all concentrations > 10(-9) mol/cm2). Although fMLP treatment caused 247 +/- 28% increase from baseline level in O2-. production, neither direct contraction nor augmentation of muscarinic stimulation was demonstrated after topical application of 4 x 10(6) neutrophils. In 12 other preparations, fMLP-activated HL-60 cells were pretreated with either 10 microM indomethacin (Indo) or 100 microM A63162, a 5-lipoxygenase inhibitor. Pretreatment with Indo caused complete blockade of direct tracheal contraction and 88 +/- 13% blockade of muscarinic augmentation; there was no effect after A63162.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetamides↗