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Biomedical subjects

G S Johnston

Publications and source records attributed to G S Johnston.

At least 19 recordsLinked to original sources
PubMed1996

Pharmacokinetics of dacarbazine in the regional perfusion of extremities with melanoma.

BACKGROUND: The pharmacokinetics of dacarbazine (DTIC), which has been shown to be an effective therapeutic agent against metastatic melanoma, has not been extensively studied. However, to improve the clinical use of the drug, more information on the kinetics is required. METHODS: A pharmacokinetic study was undertaken in six patients with melanoma of an extremity who were undergoing hyperthermic isolation perfusion with DTIC in order to understand better its clinical pharmacokinetics. Plasma was sampled from the arterial and venous lines of an extracorporeal pump during the perfusion with the systemic vein and urine sampled postperfusion. Samples were analyzed for DTIC. 2-azahypoxanthine (2-AZA), and aminoimidazole carboxamide (AIC). 99(m)Tc (Technetium) human serum albumin (HSA) was used in the perfusion circuit to monitor the crossover of the perfusate into the systemic circulation during the procedure. The data were analyzed using a compartmental model of sampled body compartments incorporating the isolated extremity. RESULTS: High tissue DTIC levels were maintained throughout the perfusion, whereas in the systemic circulation, plasma DTIC concentrations, when observed, were 40-100-fold less than those in the perfusate. Almost 70% of the DTIC administered was not recovered in the perfusate after the washout of the extremity. CONCLUSIONS: High levels of DTIC can be maintained in an extremity (i.e., arm or leg) during perfusion.

Antineoplastic Agents↗
PubMed1995

Radioiodine therapy for thyroid cancer.

A small abut important subset of patients with differentiated thyroid cancer will die of disease. Our approach to therapy treats almost all patients similarly, with aggressive surgery and I-131 therapy. Meticulous follow-up should include multiple I-131 diagnostic scans using at least 5 to 10 mCi of I-131 with attention to proper patient preparation and good quality procedures. Thyroglobulin levels should be monitored, and other radiographic diagnostic procedures, including thallium scans and MR imaging, should be used as needed. Until screening tests are discovered which will accurately pinpoint patients at high risk for aggressive, recurrent thyroid cancer, the best course of action appears to be aggressive management, including radioiodine therapy.

Female↗
PubMed1990

Effect of histocompatibility factors on pulmonary retention of indium-111-labeled granulocytes.

Granulocyte transfusions are associated with a number of side effects including febrile transfusion reactions and occasionally pulmonary infiltrates. There is evidence that the presence of preformed antibodies may be a cause of these complications. In this study, allogeneic 111Indium-labeled granulocytes were used to evaluate the pulmonary retention of radioactivity in alloimmunized and non-alloimmunized patients in an attempt to assess antibody effect on granulocyte migration. After injection of labeled allogeneic granulocytes into neutropenic patients, the ratios of lung to heart activity were calculated for the first 30 min of scanning. There was significantly greater retention of radioactivity from cells in the lungs of patients who were alloimmunized, having both lymphocytotoxic (anti-HLA) and leuko-agglutinating antibodies, compared to the activity in the lungs of non-alloimmunized patients (P less than .001) or of patients receiving autologous granulocytes (P less than .001). This study demonstrates that labeled, mismatched granulocytes may be retained in the lungs for a significantly longer time in patients with preformed antibodies. This implies that transfusion of large numbers of such mismatched granulocytes, i.e., granulocyte transfusions, may also be retained in the lungs of alloimmunized patients, which could lead to pulmonary compromise. Therefore, granulocyte transfusions from random donors should not be given to alloimmunized patients.

Blood Transfusion↗
PubMed1990

Cytomegalovirus (CMV) titers among acquired immunodeficiency syndrome (AIDS) patients with and without a history of Kaposi's sarcoma (KS).

The relationship between a history of Kaposi's sarcoma (KS) and serum titers to cytomegalovirus (CMV) among homosexual patients with acquired immunodeficiency syndrome (AIDS) was studied. Individuals with a history of AIDS and biopsy-proven or clinically confirmed KS were identified and compared with AIDS patients who did not have a history of KS. By demographic parameters and level of immunosuppression, the two groups were similar. Titers to CMV among the 53 AIDS patients (using an indirect fluorescent antibody [IFA] system) demonstrated a median titer for the first group of 1:512 and 1:2048 for the second. The two groups, however, did not differ in a matched study using a McNemar's test for correlated proportions. Wilcoxon ranked sum test performed on the data also demonstrated that the two groups did not differ with respect to the distribution of CMV titers. Serologic data failed to demonstrate a role for CMV infection in the pathogenesis of KS.

Acquired Immunodeficiency Syndrome↗
PubMed1989

External accumulation of radionuclide in hepatic hydrothorax.

Hepatic hydrothorax is a complication in approximately 5% of patients with cirrhosis. Ascites is almost always present and helps to suggest the correct diagnosis. However, when ascites is absent, radionuclide imaging has proven to be helpful in establishing that the pleural effusion originated from ascitic fluid. When pleural fluid is rapidly removed, such as by thoracostomy tube drainage, the radioisotope may accumulate outside the thorax and produce a negative scan of the chest. When the radionuclide scan is nondiagnostic and the pleural space is being rapidly drained, the pleural fluid collecting system should always be imaged before rejecting a diagnosis of hepatic hydrothorax.

Drainage↗
PubMed1989

Right-to-left shunting via persistent left superior vena cava identified by perfusion lung scintigraphy.

A right-to-left shunt was demonstrated following a left antecubital injection of [99mTc]MAA but was not seen after a right antecubital injection. This was because of the presence of a persistent left superior vena cava draining into the left atrium. Recognition of the presence of this anatomic variant is of importance in perfusion imaging, in patients with otherwise unexplained systemic embolization.

Adult↗
PubMed1988

Clinical significance of radionuclide angiographically-determined abnormalities following acute blunt chest trauma.

Abnormalities of right and left ventricular ejection fraction and segmental wall motion may be detected by radionuclide angiography (RNA) following blunt chest trauma. Of 111 patients with blunt chest trauma who were admitted to a large regional shock trauma center and underwent combined first-pass and equilibrium gated RNA, abnormalities were present in 40 (36%). These abnormalities were confined to the right ventricle in 33 patients. There was a positive association between RNA abnormalities and the presence of right bundle branch block (10 of 40, p less than 0.05) and a negative association between RNA abnormalities and the finding of rib fractures (6 of 40, p less than 0.05). The in-hospital death rate of these patients was low (3 of 40 patients with an abnormal RNA and 2 of 71 patients with a normal RNA). Follow-up RNA was performed at 10 +/- 4 days in 26 of the 40 patients with initially abnormal scans, and 22 (85%) of the 26 had reverted to normal. Thus although RNA abnormalities appear common following blunt chest trauma, among patients who survive for more than 24 hours and who undergo subsequent RNA, the complication rate is low despite an abnormal scan. We conclude that routine RNA adds little to clinical management following acute blunt chest trauma.

Adult↗
PubMed1988

Frequency of hepatic visualization during I-131 imaging for metastatic thyroid carcinoma.

Sixty-one total body I-131 scans performed on 29 patients who were post-thyroidectomy for differentiated thyroid cancer were retrospectively reviewed to determine the frequency of hepatic visualization. The liver was seen in 52% of the patients. Diffuse liver uptake was present on 5 of 38 (13%) diagnostic (10 mCi) scans and on 12 of 23 (52%) post-therapy (80-150 mCi) scans. None of these patients showed clinical or laboratory evidence of hepatic metastases during a mean follow-up period of 18 months. We conclude that physiological diffuse liver activity is seen frequently on I-131 total-body scans.

Adenocarcinoma↗
PubMed1987

Collateral ventilation of obstructed lung during high-frequency oscillation in dogs and pigs.

To determine if collateral ventilation (CV) occurs in pigs and dogs during intermittent positive-pressure ventilation (IPPV) and high-frequency oscillation (HFO), seven pigs and seven dogs were studied by measuring Xenon 133 washout (XeW) from an occluded subsegmental bronchus. The rate constant/min (K) for Xe blood uptake (KXeb) was derived, and when subtracted from K for XeW (KXeW) gave K for removal of Xe by CV (KXecv). Pig XeW were single exponentials with mean KXew = 0.25/min during IPPV and 0.12/min with HFO. In pigs, mean K of XeW was no different from KXeb so that all XeW occurred by blood uptake and none by CV. XeW in dogs had two exponentials. Dogs had over 11 times greater mean KXeW than pigs during IPPV and over 24 times greater during HFO. In dogs, on average, 79% (IPPV) and 87% (HFO) of XeW occurred by CV. CV is a means of gas exchange during HFO and IPPV in dogs but not in pigs.

Animals↗
PubMed1987

The significance of gastric bile reflux seen at endoscopy.

We evaluated the significance of bile seen in the stomach at the time of endoscopy. Twenty-three percent of 110 consecutive patients undergoing elective panendoscopy were found to have bile in their stomachs. Gastric biopsies were obtained from these patients. To assess the significance of bile reflux, the patients underwent a quantitative gastric bile analysis on two separate days. On day 1, gastric juice was aspirated by nasogastric suction, and bile acid concentrations were measured. On day 2, bile reflux into the stomach was quantitated by scintiscan measurement of gastric nucleotide after intravenous administration of 99mTc-DISIDA. Approximately half the patients with bile reflux showed histologic evidence of mucosal injury. However, fewer than half with histologic injury had significant bile reflux when measured by quantitative methods. There was no correlation among the gastric bile acid concentration, degree of histologic injury, or severity of endoscopic changes. We conclude that finding bile reflux at endoscopy is probably of no clinical significance.

Bile Reflux↗
PubMed1986

Toxicity and complications of vascular isolation and hyperthermic perfusion with imidazole carboxamide (DTIC) in melanoma.

The authors have used imidazole carboxamide (DTIC) in vascular isolation and hyperthermic perfusion for melanoma. The regional and systemic toxicity and complications of this procedure were studied in 40 cases with Stage III (15) and Stage I (25) melanoma. Technetium 99m-labelled serum albumin crossover and pharmacokinetic studies were done simultaneously to see if these correlate with toxicity. Local toxicity on muscles, nerves, skin, and arteries was conspicuously absent despite using dosages of 2 g/m2 (40-45 mg/kg) for the lower extremity and 1.2 g/m2 (24-28 mg/kg) for the upper extremity. Skin and core temperature were raised to 39 degrees C to 40 degrees C. Deep vein thrombosis was noted in three patients. No death or gangrene of the extremities occurred. Local infection was noted in only one patient. Fourteen patients (35%) manifested bone marrow toxicity (leukocyte count of 4000/mm3 or platelets of 100,000/mm3) in the second or third week after perfusion. Severe hematologic toxicity was seen in two instances. Dosages of DTIC greater than 40 mg/kg were associated with toxicity in 65% of the patients. No bleeding complications occurred in seven patients with thrombocytopenia. Measurement of crossover and recovery of radionuclide were not reliable indicators of subsequent systemic toxicity. Perfusion fluid balance data also were of no predictive value. Forty-seven percent of the administered DTIC was recovered in washout fluid. Of this, less than 2% was converted to its metabolites, that is aminoimidazole carboxamide and 2-azahypoxanthine. Thirty-five of 40 patients experienced mild nausea and vomiting. Transient and mild hepatotoxicity was noted in seven patients. It appears that DTIC hyperthermic isolation perfusion is a safe procedure, however, the total dosage should be below 40 mg/kg to avoid hematologic toxicity.

Adult↗
PubMed1986

Posttraumatic cardiac dysfunction: assessment with radionuclide ventriculography.

The authors studied 54 patients with multisystem trauma, including blunt chest injury, using combined dynamic first-pass and electrocardiographically (ECG) gated radionuclide ventriculography (RNV) to evaluate for posttraumatic myocardial dysfunction. Twenty-six of 54 (48%) patients had abnormalities of ventricular wall motion. The ventricular dysfunction was confined to the right ventricle in 92% of cases. In general, abnormalities consisted of right ventricular dilatation and diffuse hypokinesia, although in seven cases there were localized wall-motion abnormalities. The right ventricular ejection fraction of those patients with wall-motion abnormalities was significantly lower than those with normal studies. Left ventricular ejection fraction did not differ significantly between these groups. ECG changes were not associated with the cardiac dysfunction demonstrated scintigraphically, nor was there a relationship between the number or type of extrathoracic or thoracic injuries demonstrated by RNV. Follow-up studies obtained in 15 cases showed a significant overall improvement in cardiac function by 3 weeks after injury. Combined first-pass and ECG-gated RNV is useful for the identification and follow-up of patients with posttraumatic cardiac dysfunction.

Adolescent↗
PubMed1986

The diagnosis of acute acalculous cholecystitis: a comparison of sonography, scintigraphy, and CT.

The clinical and laboratory diagnosis of acute acalculous cholecystitis is difficult, and the reliability of various diagnostic imaging techniques has not been established. The results of several imaging procedures performed over a 6-year period on 56 patients with clinically suspected acute acalculous cholecystitis were evaluated retrospectively. Sonography and CT were both highly sensitive (92% and 100%, respectively) and specific (96% and 100%, respectively). Hepatobiliary scintigraphy was compromised by frequent false-positives; the result was a specificity of only 38%. Percutaneous bile aspiration was insufficiently sensitive (33%) for diagnosis. Sonography was as sensitive as hepatobiliary scintigraphy and was more specific in establishing the diagnosis. Because sonography is relatively inexpensive and can be performed at the bedside, it should be regarded as a satisfactory screening procedure. However, CT is a good alternative in an easily transported patient when other intraabdominal disease is suspected.

Accidents↗
PubMed1985

Use of 111In-bleomycin for combining radiotherapy and chemotherapy on glioma-bearing mice.

Mice bearing transplanted glioma received 0.9% NaCl, 0.1 mg of BLM, or 200-250 microCi of 111In-BLM (0.1 mg BLM) daily for 5 days intraperitoneally. After therapy, tumor sizes were in the order NaCl greater than BLM greater than 111In-BLM. On the 11th day after the first injection, tumor size (mm3) in the 111In-BLM group was 1,220; in the BLM group, it was 2,310 (P less than .025). After intratumor injection of a total dose of 0.1 mg of BLM/gm tumor weight, or of 1 mCi/gm tumor weight of 111In-BLM (carried by 0.1 mg of BLM/gm tumor weight), the tumor size decreased in the 111In-BLM group more than in the BLM group. On the 5th day after the 2nd dose therapy, the tumor size in the 111In-BLM group was 2,020; in the BLM group it was 4,220 (P less than .05). Host weights for these two groups were similar. The necrotic area in the tumor was much greater in the 111In-BLM group than in the BLM group. These results suggest the use for radiotherapy and chemotherapy.

Adenocarcinoma↗
PubMed1985

A new 111In-bleomycin complex for combined radiotherapy and chemotherapy.

Six days after tumor transplantation three daily intraperitoneal doses of 0.9% NaCl, bleomycin (BLM), or a new 111In-bleomycin complex (BLMC, 15 microCi/g body weight) were administered to glioma-bearing mice. After therapy, tumors in mice treated with 111In-BLMC were smaller than those treated with BLM. Sixteen days after the first injection tumor size for 111In-BLMC-treated mice was 560 (240-1,030) mm3, 1,980 (1,400-3,290) mm3 for BLM (P less than 0.025), and 4,830 (2,580-9,180) mm3 for NaCl (0.1 less than P less than 0.2). Thirteen days after tumor transplantation glioma-bearing mice received single intratumor injection of 0.9% NaCl, BLM, or 111In-BLMC (1.5 mCi, carried by 0.5 mg BLM/g tumor weight). The average tumor size for 111In-BLMC was smaller than that for BLM by a factor of 2.5-3.7. Host weights for these two groups were similar, and morphologic abnormalities were not found in kidney or liver.

Animals↗
PubMed1985

Differentiation of jaundice in infancy: an application of radionuclide biliary studies.

Atresia and hypoplasia of the bile ducts are the most common congenital biliary anomalies of clinical importance. Surgical correction can help about 10% of these infants. However, surgery should be performed within the first month of life to avoid irreversible liver parenchymal changes. It is difficult to separate the surgical condition, biliary atresia, from conditions in which the trauma of laparotomy should be avoided, such as neonatal hepatitis and other clinically indistinguishable causes of obstructive jaundice. Radionuclide imaging with the 99mTc-labeled N-substituted iminodiacetic acids (HIDA, PIDIDA, DISIDA, etc) have been helpful in the differential diagnosis of biliary atresia.

Bile Ducts↗