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Biomedical subjects

L Lamki

Publications and source records attributed to L Lamki.

At least 37 records · Page 2Linked to original sources
PubMed1994

Scintigraphic manifestations of "sternal cupping".

Sternal abnormalities in sickle-cell disease have been documented by bone scintigraphy and radiography in patients with homozygous sickle-cell anemia, but not in patients with sickle-thalassemia. We present here two unusual cases of sternal abnormalities in complicated sickle-cell disease. One is an infant with radiographic findings of "sternal cupping" and transient hypo-ossification of the sternum and sickle-thalassemia. The other patient is also a male infant with unusual, persistent under-ossification of bone, in association with radiographic findings of "sternal cupping." The second patient also had a 4P-chromosomal defect (Wolf-Hirschhorn syndrome) in which sternal hypo-ossification was described.

Abnormalities, Multiple↗
PubMed1991

Clinical pharmacology, metabolism, and tissue distribution of 90Y-labeled monoclonal antibody B72.3 after intraperitoneal administration.

B72.3 is a murine monoclonal antibody that recognizes a high-molecular-weight tumor-associated glycoprotein (TAG-72). Nine patients with TAG-72-positive ovarian carcinoma or papillary serous carcinoma of the peritoneum received an intraperitoneal infusion of 2, 4, or 10 mg B72.3 labeled with 0.5-1.2 (mean, 0.8) mCi 90Y. All patients had laparotomy, with multiple tissue and tumor samples removed 3-7 days later. The concentration of the total 90Y label in peritoneal fluid cleared with an extrapolated half-life of 68.6 +/- 4.5 hours. A low-molecular-weight 90Y-labeled species of metabolite was identified by high-performance liquid chromatography. The concentration of this low-molecular-weight species initially increased in the peritoneal fluid, with a half-life of 0.9 hour, and was rapidly cleared from the peritoneal cavity, with a half-life of 23.1 hours. Both the 90Y-labeled metabolite and the 90Y-labeled B72.3 were absorbed into the plasma, with half-lives of 16 +/- 2.2 hours and 25 +/- 5 hours, respectively. The clearance half-lives for these agents in plasma were 25 +/- 3 hours for the metabolite and 42 +/- 17 hours for B72.3. Approximately 8%-11% of the total injected 90Y label appeared in urine over 72 hours. Most of the label (about 70%) was present as the 90Y-labeled metabolite, but about 30% of the 90Y label in urine appeared identical to the authentic 90Y-labeled B72.3 standard when assayed by chromatography. Tissue distribution studies showed that normal tumor tissue and omentum contained the highest content of 90Y (about 0.017% of the injected dose per gram), followed in descending order by liver, normal lymph nodes, peritoneum, bone, and fascia. The lowest concentrations of 90Y were found in rectus abdominis muscle, bone marrow, and fat. There was substantial heterogeneity in the uptake of the 90Y label into tumor sites among patients and among different sites within the same patient. No correlation could be demonstrated between the TAG-72 content and the amount of 90Y label found in tumor sites. Preliminary radiation dosimetry estimates suggest that the tumor sites received about 82.8 cGy for each millicurie of 90Y administered. Thus, if an adequate total radiation dose can be achieved, 90Y-labeled B72.3 should be therapeutically useful for treating diffuse intraperitoneal disease.

Adult↗
PubMed1991

Regression of hepatic metastases from gastrointestinal leiomyosarcoma after hepatic arterial chemoembolization.

Two patients with gastrointestinal leiomyosarcoma metastatic to the liver were treated by hepatic chemoembolization with cisplatin and polyvinyl sponge followed by hepatic arterial infusion of vinblastine. Effective palliation in terms of durable tumor regression was achieved in both patients after two chemoembolization-infusion procedures. These results suggest that regional therapy may offer new hope for the subset of sarcoma patients who have liver metastases resistant to combination systemic chemotherapy.

Aged↗
PubMed1989

Sequential use of indium-111 labeled monoclonal antibodies 96.5 and ZME-018 does not increase detection sensitivity for metastatic melanoma.

Two indium-111 labeled anti-melanoma murine monoclonal antibodies (MAb), 96.5 and ZME-018, each recognizing separate antigens on melanoma cells, were administered intravenously to 17 patients with melanoma in a sequential fashion to determine whether: 1) additional tumor sites could be imaged with the combination compared to a single Mab; 2) the first MAb influenced the biodistribution and tumor localization of the second; and 3) significantly toxicity occurred with the combination. Patients were randomized to receive either 96.5, followed by ZME-018, ZME-018 followed by 96.5, or each MAb followed by itself (controls). Infusions of the second MAb occurred 10 days after the first infusion. Gamma camera images were obtained 72 hours after each antibody infusion. There were 139 known metastatic sites of which 72 lesions were localized by either MAb for an overall sensitivity of 52%. The detection rate was higher when lesions only greater than 1.5 cm were considered. Imaging results were independent of MAb administration sequence. When ZME-018 was given as the first infusion, when ZME-018 was given as a second infusion (p = NS). However, mean sensitivities using 96.5 as the first or second infusion were 48% and 66% respectively (p = NS). There was not a significant number of sites detected by MAb 2 that were missed by MAb 1. Human anti-murine antibody (HAMA) response occurred in seven of eight patients studied; two patients who experienced toxicity had levels of HAMA greater than 2000 ng/ml. We conclude that the use of these two murine anti-melanoma monoclonal antibodies given in sequential fashion did not significantly change the imaging sensitivity from that seen with each individual antibody. Moreover, with the exception of one patient, mean plasma half-life of the MAb did not change significantly, suggesting that overall clearance mechanisms were not saturated by the consecutive doses of monoclonal antibody or significantly altered by the presence of HAMA.

Adult↗
PubMed1987

Comparative clinical pharmacology of [111In]-labeled murine monoclonal antibodies.

Patients with metastatic melanoma received either the murine antimelanoma antibody ZME-018 (20 patients) or antibody 96.5 (26 patients) at doses ranging from 1 to 20 mg and coupled to 2.5 or 5 mCi of [111In]. The pharmacokinetics and tissue disposition of these antibodies were measured at various times after infusion of the radiolabel. The clearance of the [111In]label from plasma closely fit (r2 greater than 0.90) an open, one-compartment mathematical model after administration of antibody 96.5. Clearance of [111In] from plasma after administration of ZME-018 fit a one-compartment model in some patients and a two-compartment model in others. The terminal phase half-lives of 96.5 and ZME-018 antibodies at the 20-mg dose were almost identical (27 +/- 2 h and 29 +/- 5 h, respectively). The half-lives calculated for 96.5 were not dependent upon the total antibody dose; however, with increasing doses of ZME-018 there was a dose-dependent increase in t 1/2 (from 17.8 +/- 2 h at the 2.5-mg dose to 29 +/- 5 h at the 20-mg dose). For 96.5 antibody, the apparent volume of distribution (Vd) approximated the total blood volume (7.8 +/- 0.71) at the 1-mg dose and decreased significantly at the 20-mg dose, suggesting saturation of extravascular antigen sites. In contrast, the Vd calculated for ZME-018 did not appear to be dependent upon the administered dose. Improved imaging occurred with increasing doses of unlabeled 96.5 above 2 mg, a finding not observed with ZME-018. The cumulative urine excretion of [111In] after administration of 96.5 or ZME-018 was 10%-14% of the total dose. These studies show that murine monoclonal antibodies of the same subtype but recognizing different surface antigens can exhibit markedly different in vivo pharmacokinetic behavior, which may partially explain differences in imaging noted with increasing doses of monoclonal antibody.

Antibodies, Monoclonal↗
PubMed1987

Clinical parameters related to optimal tumor localization of indium-111-labeled mouse antimelanoma monoclonal antibody ZME-018.

Radioimmunolocalization of an 111In-labeled mouse antimelanoma monoclonal antibody (MoAb), ZME-018, was examined in 21 patients with metastatic malignant melanoma. Each patient received a single. i.v. infusion of MoAb at concentrations ranging from 1 mg to 20 mg, coupled to 5 mCi 111In by the chelating agent DPTA. No toxicity was observed in any patient. Total-body and regions of interest scans performed at 4, 24, and 72 hr following MoAb administration revealed uptake in 63 out of 105 previously diagnosed metastases for an overall sensitivity of 60%. Uptake was consistently observed in liver/spleen, and less frequently in bowel, testes, axillae and bone. Sensitivity of detection increased significantly at doses of MoAb above 2.5 mg, with 74% of lesions imaging at 20 mg/5 mCi compared with 29% at 2.5 mg/5 mCi (p less than 0.005). A significant correlation was observed between tumor uptake of 111In-MoAb conjugate and increasing tumor size. Soft-tissue lesions such as skin and lymph node metastases were imaged to a greater extent (76%) than visceral metastases (19%). In five of six patients, biopsies obtained from 3 days to 14 days after MoAb administration showed antibody present on tumor cells as demonstrated by flow cytometry and/or radioimmunoassay. Human anti-murine immunoglobulin responses were observed in seven of 17 patients studied. Mean plasma clearance of ZME-018 was prolonged with a T1/2 of 24.7 hr and increased slightly with increasing MoAb dose. Urinary excretion of 111In averaged 12.4% of the injected dose over 48 hours. Radioimmunolocalization of melanoma with 111In-labeled ZME-018 appears feasible. The sensitivity of the technique was related to dose, tumor size, and disease site.

Antibodies, Monoclonal↗
PubMed1987

Radioimmunoimaging in malignant melanoma patients with the use of indium-111-labeled antimelanoma monoclonal antibody (ZME-018) to high-molecular-weight antigen.

Radioimmunolocalization of an 111In-labeled, mouse antimelanoma monoclonal antibody (MAb), ZME-018, was examined in 30 patients with metastatic malignant melanoma. Each patient received a single iv infusion of MAb at concentrations ranging from 0.6 to 40 mg, coupled to 5 mCi 111In by the chelating agent pentetic acid. No toxicity was observed in any patient. Total-body and region of interest scans performed at 4, 24, and 72 hours following MAb administration revealed uptake in 110 of 171 previously diagnosed metastases for a sensitivity of 64%. Nonspecific uptake of radioactivity was consistently observed in the liver and spleen, and less frequently in the bowel, testes, axillae, and bone. Sensitivity of detection increased significantly at doses of MAb above 2.5 mg, with 74% of the lesions imaging at 20 mg/5 mCi compared with 29% at 2.5 mg/5 mCi (P less than .005). Sensitivity actually decreased slightly at the 40-mg dose. There was a significant correlation between tumor uptake of MAb-111In-conjugate and increasing tumor size. Soft tissue lesions, such as skin and lymph node metastases, were imaged to a greater extent (77%) than were visceral metastases (40%). Mean plasma clearance of ZME-018 was prolonged with a half-life of 33.6 hours in patients receiving 40 mg, compared with 17.8 hours in patients given 2.5 mg (P less than .01). Urinary excretion of the isotope averaged 11.4% of the injected dose over 48 hours. Hence radioimmunolocalization of melanoma with 111In-ZME-018 appeared feasible. The sensitivity of the technique varies with MAb dose, specific activity of 111In-MAb conjugate, tumor size, and disease site.

Antibodies, Monoclonal↗
PubMed1986

Effect of non-steroidal anti-inflammatory drugs on control of hypertension by beta-blockers and diuretics.

The effect of sulindac on renal function and blood pressure was compared with those of placebo, piroxicam, and naproxen in 20 patients with primary hypertension being treated with a diuretic and a beta-blocker. Although the three non-steroidal anti-inflammatory drugs (NSAIDs) did not differ in their effect on renal function (weight, glomerular filtration rate, creatinine clearance) or on serum thromboxane and plasma 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha), blood pressure was significantly lower with sulindac than with placebo, piroxicam, or naproxen. These differences were associated with less renal cyclooxygenase inhibition by sulindac (reflected by urinary thromboxane B2 and 6-keto PGF1 alpha) than by other NSAIDs. The findings suggest that the blood pressure differences reflect vasodilation due to differences in the balance between systemic and renal effects of the NSAIDs.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Differential glomerular filtration rate in diagnosis of renovascular hypertension and follow-up of balloon angioplasty.

Two hundred nine hypertensive patients with high stimulated plasma renin levels were screened for renovascular hypertension using Tc-99m DTPA renal scintigraphy. Differential glomerular filtration rate (Diff-GFR) was obtained by integrating the area under the background-subtracted renogram of each kidney between 1 and 3 minutes. 50 patients who also had undergone selective renal angiography were divided into four groups according to Diff-GFR contribution by one of the kidneys. If one kidney contributed 45-50% of total GFR, this was regarded as normal. A Diff-GFR of less than 45% was very considered to be very suggestive of renovascular hypertension in the appropriate clinical setting, while a Diff-GFR of less than 20% indicated that the renal artery might not be amenable to successful balloon angioplasty. Diff-GFR following balloon angioplasty closely reflected the early clinical response of the patients--and in some cases progressive Diff-GFR improvement was observed several months later. Diff-GFR as a scintigraphic criterion for renovascular hypertension has a sensitivity of 93%, specificity of 74%, and accuracy of 85%.

Adolescent↗
PubMed1986

Reduction by morphine of human postprandial insulin release is secondary to inhibition of gastrointestinal motility.

The effect of morphine (0.1 mg/kg) on insulin secretion stimulated by oral, intraduodenal, or intravenous administration of glucose was studied in seven healthy volunteers. When glucose was given intravenously, morphine had no effect on plasma glucose, insulin, glucose-dependent insulinotropic polypeptide (GIP), or pancreatic glucagon. Following oral glucose, morphine slowed gastric emptying and reduced plasma concentrations of glucose, insulin, and GIP. During intraduodenal infusion of glucose, insulin concentrations in plasma were also decreased by morphine, an effect best explained by decreased small intestinal transit with delayed absorption of glucose and delayed release of GIP. We conclude that clinically relevant doses of morphine have no direct effect on insulin secretion and that the changes observed were secondary to slowed gastric emptying and small intestinal transit.

Adolescent↗
PubMed1985

Baker's cyst. Radionuclide arthrographic findings.

Radionuclide arthrography of the knee is described using Tc-99m sulfur colloid, which is injected into the synovial cavity following partial distension of the joint space with saline. The preliminary findings in Baker's cyst are described. There appear to be four patterns: 1) a herniation or cyst that can be posterior, inferior, medial or lateral to the knee synovial space; 2) a limited leak inferiorly toward the calf or superiorly toward the thigh; 3) extensive leak: giant cyst found in patients with rheumatoid arthritis; 4) multiple "cysts" or communications with the knee synovial space. The series is small, and more work is needed before these preliminary findings can be used as firm categories. Radionuclide arthrography should be considered in patients with unexplained calf pain or pain behind the knee, especially with a history of previous internal knee derangement, or rheumatoid arthritis in whom ruptured cysts can closely mimic acute thrombophlebitis. Radionuclide arthrography has certain advantages over contrast arthrography and also arthroscopy in the diagnosis of Baker's cyst.

Humans↗
PubMed1985

Radioimmunoimaging in malignant melanoma with 111In-labeled monoclonal antibody 96.5.

A radiolabeled monoclonal antibody (96.5) reactive with an Mr 97,000 antigen found on over 80% of melanoma cell lines and tissue extracts was examined for its ability to detect malignant melanoma metastases in vivo. For imaging purposes, it was conjugated with diethyltriaminepentaacetic acid and subsequently labeled with 111In by chelation. Thirty-one patients with metastatic melanoma received single injections of monoclonal antibody 96.5 at concentrations ranging from 0.5 to 20 mg and at specific activities of 111In ranging from 0.125 to 4 mCi/mg. Total-body scans were performed at various time intervals following administration. No serious side effects were observed. Of a total of 100 previously documented metastatic sites, 50 imaged for a specificity of 50%. The number of sites imaged increased significantly as the amount of antibody administered increased relative to the average radiation dose. Considerable background uptake of isotope was observed in blood pool and other organs with gradual acquisition of label in tumor sites by 48 to 72 h. Hence, tumor imaging of melanoma using 111In-labeled monoclonal antibody 96.5 appeared feasible, especially at antibody doses above 2 mg.

Adult↗
PubMed1983

A study of gastrointestinal opiate receptors: the role of the Mu receptor on gastric emptying: concise communication.

Animal and in vitro experiments suggest that opiates exert their actions by interaction with possibly five different subtypes of opiate receptors, identified as mu, kappa, sigma, delta, and epsilon. As yet there is no conclusive evidence for their existence in man. Our experiments on morphine and the enkephalin analog DAMME have suggested at least two types of opiate receptors involved in gastric secretion. In this study we have used the very powerful and nonselective opiate agonist etorphine to stimulate as many of the different opiate receptors as possible. We have then attempted to block selectively the mu receptor by administering a small dose of naloxone. Etorphine delayed gastric emptying whereas naloxone alone had no effect. In combination, the inhibitory effect of etorphine on gastric emptying was incompletely prevented while the subjective effects of etorphine were completely abolished. These results may indicate that mu receptors are important in the regulation of gastric emptying, but that other (non-mu) receptors are also involved. The radionuclide study of gastric emptying, as used here, is a potentially powerful tool in physiological research on the gastrointestinal tract.

Adult↗
PubMed1983

The effect of a synthetic enkephalin analogue on postprandial gastrointestinal and pancreatic hormone secretion.

The effect of the synthetic enkephalin analogue Sandoz FK33-824 (DAMME) on gastric emptying and the postprandial secretion of upper gastrointestinal and pancreatic hormones was investigated in six healthy subjects. Gastric emptying was delayed as was the postprandial rise in glucose. There was significant blunting of insulin and gastric inhibitory polypeptide secretion, with complete abolition of the normal postprandial increases in pancreatic polypeptide and motilin. The secretion of gastrin was prolonged. These results demonstrate that pharmacological doses of opiate peptides inhibit gastric emptying and may have direct and indirect effects on gastrointestinal and pancreatic hormone secretion.

Adult↗