Biomedical subjects

D H Johnson

Publications and source records attributed to D H Johnson.

At least 235 records · Page 13Linked to original sources

PubMed1990

The role of hexamethylmelamine in the combination chemotherapy of advanced ovarian cancer: a comparison of hexamethylmelamine, cyclophosphamide, doxorubicin, and cisplatin (H-CAP) versus cyclophosphamide, doxorubicin, and cisplatin (CAP).

To evaluate the contribution of hexamethylmelamine (HMM) to the treatment of advanced ovarian cancer with combination chemotherapy, we compared the results of treatment with HMM, cyclophosphamide, doxorubicin, and cisplatin (H-CAP regimen) to treatment results using cyclophosphamide, doxorubicin, and cisplatin (CAP regimen). The treatment regimens were identical in dosage and schedule with the exception of the addition of HMM to one regimen. Fifty-five patients treated with H-CAP at Vanderbilt University Hospital between August 1977 and March 1980 were compared with a subsequent group of 22 patients who received CAP between October 1984 and October 1987. Following six months of therapy, patients were restaged either with second-look laparotomy or with clinical restaging. Fifty-three of 55 patients (96%) had objective responses to H-CAP compared with 14 of 21 patients (67%) treated with CAP (p = 0.001). The pathologic complete response rate was also higher in the patients who received H-CAP (35% versus 19%). The median survival of patients receiving H-CAP is 47 months compared to 21 months for the CAP patients. When patients with limited residual disease (maximum tumor diameter less than or equal to 3 cm) were compared, the median survival also favored the H-CAP treatment (101 months versus 21 months, p = 0.002). The median time to progression was also greater in patients receiving H-CAP versus those receiving CAP (67 months versus 16 months, p = 0.045). Treatment-related toxicity did not differ substantially between the two regimens. Our findings suggest that the addition of HMM to CAP chemotherapy prolongs the median survival in patients with ovarian cancer and limited residual disease following cytoreductive surgery.

Adult↗

PubMed1990

A new faculty training model for countries developing academic family medicine programs.

Medical schools in many countries wish to start academic programs in family medicine but do not have specifically trained faculty available. When the only medical school in Malta faced this situation, it agreed to try a new model for training potential faculty. This model was an intensive eight-month course for a selected group of ten experienced Maltese general practitioners to train in Malta with a visiting professor of family medicine. These adult learners were heavily involved in designing and contributing to an intensive course in family medicine and in teaching. Maltese teaching resources were used, and training occurred in the context of the society and health care system in which course members would ultimately teach. Subjective and objective measurements of course achievement were made. Results were compared with certification standards of the Canadian College of Family Physicians. This model merits consideration by other medical schools that wish to start academic programs in family medicine.

Communication↗

PubMed1990

Pulmonary venous atrial obstruction after the Senning procedure: relief by catheter balloon dilatation.

Pulmonary venous atrial stenosis developed after a modified Senning procedure in an infant with transposition of the great arteries. The pulmonary venous atrium was surgically revised, but the obstruction recurred. The stenosis was then enlarged by percutaneous balloon catheter dilatation. There was an immediate haemodynamic and echocardiographic improvement. Clinical and echocardiographic improvement persisted nine months after dilatation. The procedure was complicated by staphylococcal endarteritis.

Catheterization↗

PubMed1990

Neonatal mitral valve endocarditis: diagnosis and successful management.

Although still considered to be a rare and mostly fatal illness, the reported incidence of neonatal bacterial endocarditis has increased during the past decade. This parallels the establishment of intensive supportive management of severely ill newborns with multiple medical problems. An extremely difficult diagnostic problem with protean manifestations, the presence of neonatal endocarditis should be vigorously sought in the at risk neonate. The authors report the first known case in America of successfully diagnosed and treated neonatal endocarditis involving the mitral valve.

Endocarditis, Bacterial↗

PubMed1990

Prolonged administration of oral etoposide in patients with relapsed or refractory small-cell lung cancer: a phase II trial.

Twenty-two patients with recurrent small-cell lung cancer (SCLC) were treated with single-agent etoposide 50 mg/m2/d by mouth for 21 consecutive days. Eleven patients had received previous chemotherapy with cyclophosphamide, doxorubicin, and vincristine (CAV) or etoposide (CAE) or both (CAVE). Four of the latter patients also received salvage treatment with cisplatin and etoposide (EP). Nine patients had been treated with EP as induction therapy, while two patients had received high-dose cyclophosphamide, etoposide and cisplatin (HDCEP). Altogether, 18 patients had received previous intravenous etoposide. The median time off chemotherapy was 4.5 months (range, 1 to 28.9 months). Ten patients (45.5%; 95% confidence interval [CI], 27% to 65%) achieved a complete or partial response. Responses were most common in patients who had responded to previous chemotherapy and who had not received any treatment in the 90 days before initiation of oral etoposide. Median response duration was 4 months (range, 1.5 to 9.5 months) and median survival was 3.5+ months (range, 1.0 to 15+ months). Leukocyte and platelet nadirs were 1,800/microL and 160,000/microL, respectively, during cycle 1 of treatment and occurred between days 21 and 28. Overall, total leukocyte count decreased to less than 1,000/microL during 10 of 56 cycles (18%). Five patients required six hospitalizations for neutropenia and fever. There were two toxic deaths due to sepsis. Platelet counts less than 50,000/microL occurred in 14 cycles (25%). Alopecia developed in all patients; gastrointestinal toxicity was uncommon. This schedule of etoposide administration warrants further study in combination with other active agents in previously untreated patients with SCLC.

Administration, Oral↗

PubMed1990

High-dose cisplatin combination chemotherapy in the treatment of advanced epithelial ovarian carcinoma.

We treated 25 newly diagnosed patients with advanced epithelial ovarian cancer with an intensive induction chemotherapy regimen using high-dose cisplatin in combination with cyclophosphamide and doxorubicin. All patients had either stage IIIC or stage IV disease. Two intensive induction courses of chemotherapy were administered at 28-day intervals, which consisted of cisplatin 40 mg/m2 daily for 5 days, cyclophosphamide 500 mg/m2 day 1, and doxorubicin 40 mg/m2 day 1. Four courses of chemotherapy using cisplatin 60 mg/m2, doxorubicin 40 mg/m2, and cyclophosphamide 500 mg/m2 followed the high-dose induction therapy. Two of the first six patients died during high-dose induction therapy (one died of neutropenia and sepsis, one of intercurrent intracerebral hemorrhage). Doxorubicin was subsequently omitted from the induction therapy due to unacceptable myelosuppression; no deaths occurred in the remaining 19 patients, and myelosuppression was manageable. Peripheral neuropathy was the most severe side effect with this regimen. This complication was unpredictable, developed during the third or fourth month of treatment, and was disabling in five patients. Other toxicity included prolonged nausea and vomiting (eight patients), ototoxicity (five patients), and nephrotoxicity (two patients), but these did not compromise therapy. All 23 assessable patients had objective response to therapy. Four of 12 patients who underwent second-look laparotomy had pathologic complete response, while four additional patients had only microscopic residual disease. The median survival for the entire group was 25 months. Four patients remain continuously disease-free 23 to 48 months following completion of therapy. Although this regimen was tolerated by most patients, the unpredictable occurrence of disabling neuropathy may limit its usefulness.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

Etoposide kinetics in patients with obstructive jaundice.

The kinetics and urinary excretion of etoposide and etoposide glucuronide were determined in 11 patients with obstructive jaundice (bilirubin greater than 2.0 mg/dL) and in 23 patients with normal renal and hepatic function. Mean (+/- SE) measurements of clearance (24.5 +/- 2.06 v 26.5 +/- 2.05 mL/min/m2), half-life (5.7 +/- 0.5 v 6.4 +/- 0.5 hours), and volume of distribution (12.4 +/- 1.1 v 13.7 +/- 1.6 L/m2) were not significantly different in patients with jaundice when compared with controls. Similarly, etoposide kinetics in three patients determined during a period of hyperbilirubinemia were not different from measurements made in the same patients following resolution of their obstructive jaundice. In patients with jaundice, 46% of an administered etoposide dose was excreted in the urine as etoposide compared with 35% in controls (P = .15). Urinary excretion of etoposide glucuronide accounted for 29% of an administered etoposide dose in control patients and 15% in those with hepatic obstruction (P = .03). Biliary etoposide excretion measured in four patients with T-tubes was insignificant (less than 2.0% of an administered dose). The calculated renal clearance of etoposide was 11.5 mL/min/m2 in patients with jaundice and 10.4 mL/min/m2 in controls (P = .53). Respective metabolic clearance was 4.9 and 6.9 mL/min/m2 in these two study groups (P = .13). Although hepatic metabolism of etoposide may be slightly decreased in patients with obstructive jaundice, a modest increase in renal etoposide excretion appears to compensate for this change, so that total clearance is similar in the patients with jaundice when compared with controls. No etoposide dose reductions appear to be needed in treating patients with obstructive jaundice who have normal renal function.

Biliary Tract↗

PubMed1990

Glycosaminoglycans of human trabecular meshwork in perfusion organ culture.

The synthetic profile of glycosaminoglycans (GAGs) of human trabecular meshwork in perfusion organ culture was studied in a series of 34 human eyes. The anterior segments of these eyes were cultured for periods of two to 28 days and received medium containing 3H-glucosamine and 35S-sulfate during the final 48 hours of culture. The meshwork was then dissected and the GAGs isolated and subjected to sequential enzyme digestion. Active labelling of hyaluronic acid, chondroitin sulfate, dermatan sulfate, keratan sulfate, and heparan sulfate was found in all time periods. Eyes cultured seven and 14 days had similar incorporation profiles to "fresh" eyes (cultured 48 hours to allow for labelling). Eyes cultured 21 days showed an increase in dermatan sulfate labelling and a slight decrease in keratan sulfate labelling when compared with "fresh" eyes. Light microscopic autoradiography confirmed the trabecular meshwork incorporation of the radiolabelled precursors at all time periods. Thus, the trabecular meshwork remains metabolically active and GAG synthetic profiles remain reasonably similar to fresh eyes for up to three weeks in a perfusion organ culture system. This system may serve as a model for future studies of human trabecular meshwork GAGs.

Adult↗

PubMed1990

Staging non-small cell carcinoma of the lung using technetium-99m-labeled monoclonal antibodies.

A technetium-labeled monoclonal antibody was administered to 52 patients with non-small cell lung carcinoma, either to stage the mediastinum preoperatively or to detect distant metastases. Results from planar and tomographic imaging are compared to CT and histologic confirmation. Differences in detection rates and predictive values between imaging modalities are discussed. The authors conclude that imaging with a technetium-labeled monoclonal antibody is safe and accurate and may be useful for staging patients with either operable or inoperable non-small cell lung cancer.

Adult↗

PubMed1990

The effect of dexamethasone on glycosaminoglycans of human trabecular meshwork in perfusion organ culture.

The effect of dexamethasone treatment on glycosaminoglycans (GAG) in the human trabecular meshwork was studied by placing 20 pairs of eyes in perfusion organ culture. One eye received 550 nM dexamethasone in addition to culture medium; the fellow eye received culture medium only. 3H-glucosamine and 35S-sulfate were added to the medium for the final 48 hr of culture. The meshwork was then dissected, and the GAGs were isolated and subjected to sequential enzymatic degradation. Active labeling of hyaluronic acid, chondroitin sulfate, dermatan sulfate, keratan sulfate, and heparan sulfate was found in both control and steroid-treated eyes. Dexamethasone-treated eyes had an average 92% increase in the 3H-glucosamine incorporation rate in the undigestible GAG residue fraction after 14-21 days treatment (20.6% versus 10.7%, P = 0.03). This change was not apparent in eyes treated for 7 days. In this preliminary study, dexamethasone appeared to cause a time-dependent increase in the undigestible GAG incorporation profile in human trabecular meshwork.

Adult↗

PubMed1990

Chronic daily administration of oral etoposide.

Etoposide is a useful antineoplastic drug, but its optimal dose and schedule of administration remain unknown. In small cell lung cancer (SCLC), an intravenous dose given on a 5-day schedule is clearly superior to the same dose given over 1 day. The standard dose has been in the range of 300 to 500 mg/m2 divided over 3 to 5 days. Whether this schedule dependency (superiority) extends beyond 5 days is unknown. We have investigated patients with several refractory neoplasms who were given oral etoposide over a long-term period (21-day cycles) in a phase 1 trial. The maximum tolerated dose is 50 mg/m2/d for 21 days. The major toxicity is myelosuppression, which usually resolves by days 28 to 35. Responses were seen in several patients. Phase II trials are under way, and it appears that the long-term daily administration of etoposide is more active than the standard schedule. Responses have been seen in refractory germ cell tumors, lymphomas, and SCLC in patients who have progressed on the standard dose and schedule of etoposide. In addition, the drug may be active in soft tissue sarcoma. Preliminary results of combination chemotherapy with cisplatin show good tolerance and activity. The long-term daily administration of etoposide may prove to be a superior schedule and, as such, may be incorporated into combination chemotherapy for several neoplasms.

Adult↗

PubMed1990

Overview of ifosfamide in small cell and non-small cell lung cancer.

The alkylating agent ifosfamide, an analogue of cyclophosphamide, has undergone extensive testing in the treatment of bronchogenic carcinoma. Available data indicate that ifosfamide as a single agent can effect a 50% objective response rate in small cell lung cancer (SCLC) and a 25% response rate in non-small cell lung cancer (NSCLC). With mesna uroprotection, the primary dose-limiting toxicity is myelosuppression. In combination with other active agents, ifosfamide has yielded high response rates in both SCLC and NSCLC. Results of recent trials indicate that ifosfamide can be used safely in combination chemotherapy. Determination of the precise role of this agent in overall management of bronchogenic carcinoma requires additional study, however.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1990

Chemotherapy for unresectable non-small cell lung cancer.

The treatment of unresectable non-small cell lung cancer remains a frustrating clinical dilemma. Objective response rates with single agents are brief and rarely complete. Although response rates are higher for combination chemotherapy regimens, they remain disappointing. Since patients with more advanced disease typically have a greater tumor burden, with concomitant decreases in performance status and weight, few studies have demonstrated a survival benefit with chemotherapy. Nevertheless, selected patients should be offered the option of treatment with combination chemotherapy. Candidates for chemotherapy include individuals with good performance status, minimal weight loss, and minimal bulk disease. Patients should understand the limitations of cisplatin-based chemotherapy. Treatment should be discontinued after two to three cycles in the absence of obvious improvement.

Antineoplastic Agents↗

PubMed1990

Primary brain lymphoma in the immunocompetent host: relation to Epstein-Barr virus.

Epstein-Barr virus has been implicated in the pathogenesis of primary brain lymphoma in patients with congenital or acquired immunodeficiency states. To examine its role in central nervous system (CNS) lymphoma in the immunocompetent host, Epstein-Barr virologic studies were performed in six consecutive cases seen at our institutions. Virus DNA sequences were detected in only one of three tumor specimens studied by Southern blot hybridization. Serologic studies from the entire cohort disclosed past virus infection; however, antibody reactivity to virus-specific antigens in cerebrospinal fluid was limited to the patient harboring genome-positive tumor. Immunologic studies revealed hyperimmunoglobulin-E (range, 720 to 1040 micrograms/ml) in each of four patients tested. Our findings suggest that Epstein-Barr virus is an infrequent pathogen in nonimmunosuppressed patients with primary CNS lymphoma. Abnormalities in isotype-specific regulation of IgE production are common in such patients and may have pathogenetic implications.

Aged↗

PubMed1990

Human trabecular meshwork phagocytosis. Observations in an organ culture system.

Perfusion organ culture of the trabecular meshwork was used to study the phagocytic ability of human trabecular cells. Cultured eyes were challenged with blood, latex microspheres, or zymosan particles for periods of 1 hour to 7 days. Trabecular cells were capable of ingesting all three types of particles. The presence of a foreign particle did not necessarily induce a phagocytic response, however, as free particles were seen in the intertrabecular spaces and Schlemm's canal. In contrast to studies in animals which indicate trabecular cell migration from the eye may play a role in the removal of foreign debris, limited human trabecular cell migration was observed. The effect of the culture process on trabecular cell phagocytosis was also studied, using adult cats. One eye received a phagocytic challenge in vivo with the fellow eye later receiving the phagocytic challenge in vitro. Phagocytosis was demonstrated in each eye, although more cells were involved with phagocytosis in vivo. The additional cells involved in vivo may have been recruited by an accompanying inflammation. Organ culture of human trabecular meshwork may be useful in the study of trabecular cell phagocytosis, and it allows separation of the effects of inflammation from the potential effects of phagocytosis itself.

Aged↗

PubMed1990

Effect of aging on hepatic biotransformation in female Fischer 344 rats: changes in sulfotransferase activities are consistent with known gender-related changes in pituitary growth hormone secretion in aging animals.

The effect of aging on hepatic drug conjugation in 5- to 6-, 12- to 13- and 22- to 23-month-old female Fischer 344 rats was examined. The overall disposition of acetaminophen including the formation and elimination kinetics of its sulfate and glucuronide metabolites were used as in vivo probes. The effects of aging on selected in vitro drug metabolizing enzyme activities and on the pattern of phenol and bile salt sulfotransferase isoenzymes were also determined. Aging decreased the total clearance of acetaminophen and the partial clearance of acetaminophen to acetaminophen sulfate by 36 and 47%, respectively. Increasing age also resulted in a reduced partial clearance of acetaminophen to the glucuronide- (24%) and to the glutathione-derived conjugates (29%). UDP glucuronosyltransferase activity toward 1-naphthol, morphine and testosterone was unaffected by advanced age, whereas there was a significant correlation between increased age and increased UDP glucuronosyltransferase activity toward estrone. Cytochrome P-450 concentration and glutathione-S-transferase activity toward 1-chloro-2,4-dinitrobenzene were unchanged by aging. Oxidative demethylase activity toward p-nitroanisole was decreased 18% and sulfotransferase activities toward p-nitrophenol, acetaminophen and glycolithocholate were decreased 27, 12 and 12%, respectively, in the 22- to 23-month-old rats, compared to the 5- to 6-month-old animals. In contrast to the age-related feminization in the pattern of sulfotransferase isoenzyme activities that occurs in male rats, there was no effect of aging on the pattern of phenol and bile salt sulfotransferase isoenzyme activities in female rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗

PubMed1990

Stimulation of cell division by argon and Nd:YAG laser trabeculoplasty in cynomolgus monkeys.

Although laser treatment of the trabecular meshwork is the most common form of surgery for glaucoma, the tissue response to this therapy is still incompletely understood. We applied argon or Nd:YAG laser to the trabecular meshwork of six monkeys. Cell division was identified by injecting tritiated thymidine into the anterior chamber 24 hr after laser application. Autoradiography of tissue sections revealed significantly more labelled cells in eyes treated with laser than in the untreated controls. In addition, cells in neighboring tissues such as iris, ciliary body and sclera showed labelling in association with laser application. Furthermore, comparison of argon-induced lesions with those caused by pulsed Nd:YAG suggests that there are quantitative and qualitative differences in the response of trabecular meshwork and surrounding tissues to these two forms of laser energy.

Animals↗

PubMed1990

Trabecular meshwork cellularity. Differences between fellow eyes.

The difference in trabecular meshwork cellularity between fellow eyes was determined in a series of seven pairs of normal human eyes. Variations in cellularity between different quadrants of individual eyes also were determined. Characterization of these differences and development of appropriate sampling techniques to determine trabecular cellularity has become important in light of recent studies that find a decrease in trabecular cell numbers with age and with primary open-angle glaucoma, and the apparent stimulation of trabecular cell division by laser trabeculoplasty. The difference in absolute cell numbers (nuclei per section) between fellow eyes was 12.8% +/- 4.3% (standard error of the mean, SEM). The difference in cellularity (nuclei per solid tissue area) was 9.4% +/- 4.5% (SEM) in a subgroup of five pairs of these eyes. The coefficient of variation between different quadrants of an eye was 18.4% for absolute cell numbers and 17.3% for cellularity for the entire group of eyes. Sample size calculations indicate that for future studies, four pairs of eyes would be needed to detect a 20% difference in absolute cell numbers between fellow eyes and three pairs needed for detecting a similar difference in cellularity (alpha = 0.05, beta = 0.1). At least two quadrants per eye should be examined.

Aged↗