Biomedical subjects

J Kirsh

Publications and source records attributed to J Kirsh.

8 recordsLinked to original sources

PubMed1995

Problems of delivery of monoclonal antibodies. Pharmaceutical and pharmacokinetic solutions.

Monoclonal antibodies to tumour-associated antigens have great theoretical potential for the specific targeting of radioactivity and anti-neoplastic agents to tumours. The clinical success of monoclonal antibody-based cancer diagnosis and therapy depends, however, on solving a number of pharmacokinetic delivery problems. These include: (i) slow elimination of monoclonal antibodies from the blood and poor vascular permeability; (ii) low and heterogeneous tumour uptake; (iii) cross-reactivity with normal tissues; (iv) metabolism of monoclonal antibody conjugates; and (v) immunogenicity of murine forms in humans. As a result of extensive pharmaceutical and pharmacokinetic research conducted over the past 10 to 15 years, several potential solutions to these delivery problems have been identified. Blood concentrations of antibody conjugates may be reduced through regional administration, the use of antibody fragments, interventional strategies and various pre-targeting techniques. Tumour uptake may be increased through administration of higher doses, or the use of agents to increase tumour vascular permeability. Tumour retention of antibody conjugates may be improved by inhibition of metabolism, by using more stable linkage chemistry. Alternatively, normal tissue retention may be decreased through the use of metabolisable chemical linkages inserted between the antibody and conjugated moiety. Very small antigen-binding fragments and peptides that exhibit improved tumour penetration and more rapid elimination from the blood and normal tissues have been prepared by genetic engineering techniques. Chimeric (mouse/human) and human monoclonal antibodies have been developed to circumvent the problem of immunogenicity. Future research will continue to be focused on improvements in the design of monoclonal antibodies for tumour targeting, with the ultimate goal of finally uncovering the 'magic bullet' envisioned by Paul Ehrlich almost a century ago.

Animals↗

PubMed1994

Osteopenia in patients with above knee amputation.

Using dual energy x-ray absorptiometry, we studied 16 male patients with unilateral above knee amputations (AKA) with a mean age of 48 years (range, 23 to 66 years) who were full-time prosthetic users for more than 5 years. All prostheses were ischial weight bearing. All 16 subjects were found to have normal bone density in their spines and in the normal femurs when compared to nonamputation controls. However, a significant decrease of mean femoral neck bone density was found on the amputated side (0.68g/cm2, range, 0.52 to 1.01) when compared to the normal side (1.01g/cm2, range, 0.75 to 1.20) (p < .05). The mean bone density percentage difference between the two sides was 28% (range, 4% to 48%). There was a significantly negative correlation between the patient's age at the time of amputation and the severity of osteopenia (-0.73; p < 0.05).

Absorptiometry, Photon↗

PubMed1993

Pre-operative localization of 25 consecutive parathyroid adenomas: a prospective imaging/surgical correlative study.

The successful diagnosis and surgical treatment of primary hyperparathyroidism due to parathyroid adenoma benefits significantly, in our experience, from a process of pre-operative imaging localization of the parathyroid adenoma. This prospective study evaluates a window of 25 consecutive patients who underwent pre-operative imaging localization prior to successful unilateral parathyroidectomy for parathyroid adenoma. All parathyroid adenomas were successfully localized by imaging, and subsequently documented photographically in surgical correlation, and pathologically confirmed. All patients were cured biochemically. Ultrasound accurately localized 92% of adenomas (100% in the neck and extrathyroidal) while radionuclide subtraction scanning identified 60% of a smaller subset. Both DSA and CT were successful in the two cases utilized, and MRI demonstrated four of five adenomas. The high yield of these pre-operative localization studies should make them an important consideration in the routine evaluation of patients undergoing surgery for possible parathyroid adenoma. Their usefulness in directing a conservative unilateral operation may result in time and cost savings, as well as reduced surgical exposure.

Adenoma↗

PubMed1985

Hypertrophic pulmonary osteoarthropathy in four patients with interstitial pulmonary disease.

The association between digital clubbing and idiopathic pulmonary fibrosis has been well established; however, the simultaneous occurrence of hypertrophic pulmonary osteoarthropathy and interstitial fibrosis, in the absence of neoplastic disease, has only been described in two case reports and was not mentioned in any of 336 patients described in several recent reviews. Among 70 patients referred for investigation of pulmonary infiltrates, four were found to have hypertrophic pulmonary osteoarthropathy associated with interstitial pulmonary disease, in the absence of malignant disease. We conclude that the use of bone scans and roentgenographic examination of the extremities may draw attention to an association between hypertrophic pulmonary osteoarthropathy and idiopathic pulmonary fibrosis.

Aged↗

PubMed1984

Pitfall in the investigation of splenic trauma.

A patient with suspected splenic trauma is reported in whom, because of an anatomic variant, both radionuclide and sonographic examinations were misleading and led to the erroneous diagnosis of splenic laceration. Confusion arose because of an overlying left lobe of liver and this was clarified by biliary scintigraphy.

False Positive Reactions↗

PubMed1976

Progressive multifocal leukoencephalopathy.

The radionuclide, radiographic and pathologic findings in a patient with progressive multifocal leukoencephalopathy were correlated. Radionuclide imaging demonstrated the largest two of the many lesions observed at pathology. On repeated studies, one of the lesions developed a "doughnut" sign due to central necrosis. Cerebral angiography disclosed only one lesion which was initially suggestive of tumor encasement, but four weeks later, this deteriorated into an avascular zone. There were no characteristic features of the lesions demonstrated by radionuclide imaging and cerebral angiography that could be specifically attributed to progressive multifocal leukoencephalopathy.

Carotid Arteries↗

PubMed1976

Observations of radionuclide imaging in hypertrophic pulmonary osteoarthropathy.

99mTc pyrophosphate was employed in the study of patients with hypertrophic pulmonary osteoarthropathy. Several facts emerge when comparing the radionuclide, radiographic and clinical findings. Radionuclide imaging reveals the presence and extent of subperiosteal activity with greater clarity than does radiography. Synovitis associated with the syndrome is readily disclosed, and the regression of the skeletal manifestions following excision of the pulmonary lesion can be documented.

Female↗

PubMed1976

Relationship between bone uptake of 99mTc-pyrophosphate and hydroxyproline in blood and urine.

In a group of hospital patients with various diseases, the urinary hydroxyproline-to-creatinine ratio showed a significant correlation (r = 0.63; p less than 0.001) with the 5-hr bone-to-soft-tissue ratio for 99mTc-pyrophosphate uptake. In patients on chronic hemodialysis, a similar correlation was found between the 5-hr bone-to-soft-tissue ratio and hydroxyproline levels in plasma and serum. The findings suggest that 99mTc-pyrophosphate binding by bone is related to collagen metabolism.

Aged↗