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Biomedical subjects

R L Richardson

Publications and source records attributed to R L Richardson.

At least 19 recordsLinked to original sources
PubMed1992

A phase II study of recombinant human alpha-interferon in advanced hormone-refractory prostate cancer.

To determine the efficacy of recombinant human leukocyte alpha-interferon (IFL-RA) in advanced hormone-refractory prostate cancer, the authors treated 40 patients with IFL-RA administered intramuscularly at a dose of 10 x 10(6) U/m2 three times weekly. Toxicity was substantial and necessitated at least a 50% dose reduction in all but five patients during the first 1-2 months of therapy. No responses were observed in patients with bone metastases, but complete and partial regression of nodal disease were observed in two patients with extraosseous disease (overall response rate, 5%; 95% confidence interval, 0.64-17.75%). The authors conclude that IFL-RA cannot be recommended at this dose and schedule in patients with advanced prostate cancer, but additional study of its use in patients with nodal disease may be warranted.

Adenocarcinoma↗
PubMed1992

Expression of transforming growth factor-beta (TGF-beta 1) and insulin-like growth factor II (IGF-II) messenger RNA in the developing subcutaneous tissue (SQ) of the fetal pig.

Studies (in situ hybridization) were performed on the developing subcutaneous tissue (SQ) of the pig fetus to determine sites of synthesis of TGF-beta 1 and IGF-II. Tissues from 50, 70, 90, 110-day-old pig fetuses and 7-day-old postnatal pigs were Bouin's fixed, paraffin embedded and hybridized with biotin labelled cDNA probes. The expression of TGF-beta 1 messenger RNA was detectable primarily in the dermis, hair follicle fat lobule, outer and inner SQ areas at all ages. Cells adjacent to adipocyte clusters and some small adipocytes were positive for TGF-beta 1. There was no positive hybridization of TGF-beta 1 probes in the developing muscle below the SQ. The expression of IGF-II was evident in the developing muscle below the SQ at 50 d and 70 d, and could be detected in the outer and inner SQ at 70 d. Much lower levels of IGF-II expression were observed in 90 and 110 d fetuses, but an increase in IGF-II expression was evident in the muscle of 7d postnatal pigs. Our results suggest that paracrine and autocrine regulatory systems may be operative for developing adipocytes (TGF-beta 1) and muscle (IGF-II), with specific areas and times of TGF-beta 1 and IGF-II expression being evident in developing pig SQ tissue.

Animals↗
PubMed1990

Phase I and clinical pharmacological evaluation of pirozantrone hydrochloride (oxantrazole).

Pirozantrone hydrochloride, an anthrapyrazole analogue, was selected for clinical evaluation based on broad antitumor activity against murine tumor systems and on potentially less cardiotoxicity when compared to anthracyclines. This anthrapyrazole analogue is currently under clinical evaluation, and we now report results on a Phase I clinical trial incorporating a pharmacologically guided dose-escalation scheme. Dose escalation was designed to proceed by factors of 2 until the patient drug exposure (concentration x time) was 40% of the murine exposure at the LD10 dose (90 mg/m2). Thereafter, more moderate dose escalations were employed. The target concentration x time value (59 micrograms-min/ml) derived from preclinical pharmacology data was exceeded in all three patients at a dose of 90 mg/m2. A dose of 160 mg/m2 was found to reproducibly result in appropriate myelosuppression. This dose is recommended for further testing in Phase II studies. Nonhematological toxicities encountered in this trial were mild, the most notable being phlebitis at the infusion site. Objective responses were observed in two patients, one with metastatic breast cancer and another with metastatic melanoma. Following a 60-min infusion, pirozantrone hydrochloride plasma elimination was monoexponential, with a half-life of approximately 30 min, mean total body clearance of 1.29 liters/min/m2, and mean steady state volume of distribution of 29 liters/m2.

Adult↗
PubMed1990

Cranial nerve lesions due to base of the skull metastases in prostate carcinoma.

We studied 11 patients with prostate cancer metastatic to the base of skull that caused cranial nerve deficits. Patients with occipital condyle, jugular foramen, middle fossa, parasellar, and orbital syndromes are described. Other patients had combinations of these syndromes or other cranial nerve involvements. Two patients had 6th nerve palsies secondary to prepontine cistern and clivus lesions. The median survival time from the diagnosis of cranial nerve involvement was 4 months. Two patients had cranial nerve involvement and, on subsequent investigation, were found to have carcinoma of the prostate. Interestingly, these patients are still alive at 42 and 84 months after diagnosis.

Aged↗
PubMed1990

Synchronous and metachronous bilateral testicular tumors. Mayo Clinic experience.

The authors report a retrospective review of their experience with bilateral testicular cancers over two 10-year periods, one each from the prechemotherapy era (1935-1944) and the postchemotherapy era (1977-1986). Three of 295 patients (1.02%) evaluated at Mayo Clinic (Rochester, MN) for testicular germ cell malignancy between 1935 and 1944 had evidence of bilateral testicular malignancy. Two of these were synchronous and one metachronous occurring 3 years after the first diagnosis. In all three, the histology was pure seminoma. None of these three had a history of undescended testes. Both patients with synchronous tumours died within 2 years (6 months and 2 years, respectively) in spite of appropriate treatment at that time, and the one with metachronous tumor survived long-term (47 years). During the modern chemotherapy era, 16 of 500 (3.2%) patients evaluated at the Mayo Clinic Rochester between 1977 and 1986 for testicular germ cell malignancy had evidence of bilateral testicular cancers (four of these were synchronous and 12 metachronous [eight seminomas, four non-seminomas]) occurring between 1 to 15 years after the first diagnosis. Only two of 16 had a history of undescended testes surgically corrected while the patients were in their teens. All patients did well after appropriate treatment. This study reemphasizes the small but definite risk for development of a second testicular malignancy and suggests a recent increase in incidence of bilateral testicular tumors as possibly related to improved treatment modalities with a higher cure rate of the original tumor.

Adolescent↗
PubMed1990

Phase I and clinical pharmacological evaluation of a parenteral hexamethylmelamine formulation.

Hexamethylmelamine has been evaluated in single agent and combination regimen studies for many years, but only following p.o. administration. Pharmacological studies in animals and humans have shown that systematic availability of parent drug following p.o. administration is relatively low and variable due to extensive first-pass metabolism rather than due to poor absorption. Two Phase I clinical trials, with accompanying pharmacokinetic studies, have been conducted by using a parenteral formulation in which hexamethylmelamine was prepared by Intralipid 10%. The parenteral formulation was well tolerated by all patients receiving hexamethylmelamine by 1-day and by daily for 5-days schedules. Nausea and vomiting were the dose-limiting toxicities. Maximally tolerated doses on the 1-day and daily for 5-days schedules were approximately 850 mg/m2 and 630 mg/m2/day, respectively. No responses were observed in either study. Following i.v. administration of 540 mg/m2 hexamethylmelamine, plasma elimination was best described by a three-compartment open model with terminal half-life, total body clearance, and steady-state volume of distribution values of 10.4 h, 0.75 liter/min/m2 and 460 liters/m2, respectively. Twenty-four h urinary recoveries of parent drug were less than 1% for all patients. Accumulation of hexamethylmelamine during the 5-day treatment at 945 mg/m2 suggested possible saturation of parent drug elimination at that dose. Phase II studies are currently under way with the parenteral formulation of hexamethylmelamine.

Altretamine↗
PubMed1990

Familial testicular cancer: report of six cases and review of the literature.

The cause of testicular cancer, like most other cancers, is unknown. Certain risk factors such as cryptorchidism, carcinoma in situ, and a preceding contralateral testicular germ cell neoplasm are known to predispose a person to the subsequent development of a testicular malignant lesion. Familial testicular cancer has been debated as a potential and possibly independent risk factor. Evidence in favor of such a hypothesis, based on various genetic studies reported during the past few decades, is reviewed. We add to the existing literature our experience with six cases of familial testicular cancer encountered during a 10-year period, consisting of four father-and-son pairs, one pair of nontwin brothers, and a 23-year-old man who had a maternal uncle with a history of testicular cancer.

Adult↗
PubMed1990

Observation after orchiectomy in clinical stage I nonseminomatous germ cell tumor of testis. Mayo Clinic experience.

We report a retrospective review of our experience with close observation after orchiectomy in clinical stage I nonseminomatous germ cell tumors (NSGCT) of the testis during a 10-year period. Twenty-four patients were followed between 1977 and 1986 for a median duration of 47 months (24-112 months). Six of 24 (25%) relapsed at a median of 3.5 months (2-46 months) after orchiectomy; all of these were treated with chemotherapy and are in complete remission at a median of 55 months (27-69 months) after diagnosis of recurrence. Eighteen other (75%) who did not relapse are without evidence of disease at a median of 39 months (24-112 months) after orchiectomy. Orchiectomy alone followed by close observation in clinical stage I NSGCT is a reasonable approach in reliable patient populations at well-equipped centers where adequate follow-up is possible.

Adolescent↗
PubMed1990

Life-threatening bleomycin pulmonary toxicity with ultimate reversibility.

A 60-year-old man with advanced seminoma was treated with four cycles of a cisplatin, etoposide and bleomycin. He then developed severe pulmonary toxicity with diffuse infiltrates as evidenced on a chest x-ray film. The room air PaO2 value was 32 mm Hg. The patient was treated with steroids and oxygen supplementation, including a high FIo2 for several days, and survived and eventually experienced marked improvement in his pulmonary status. Aggressive management of severe bleomycin-induced pneumonitis appears justified.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1979

Small cell lung cancer. Complete remission and improved survival.

Thirty-two patients with limited-stage small cell lung cancer were treated with combined supervoltage radiotherapy and a combination of cyclophosphamide, doxorubicin and vincristine chemotherapy. The goal of obtaining a complete remission, the necessary step which precedes improved survival, was successful in 26 of 27 of completely re-evaluated patients. Fiberoptic bronchoscopy was useful in substantiating complete remission status. Seventeen of the 32 patients remain alive from 8+ to 28+ months (median 16+ months). Ten patients are alive and relapse-free from 12+ to 28+ months (median 19+ months). Transient granulocytopenia (mean nadir 650 cells/mm3) during induction therapy and the associated risk of infection were the most serious toxicities encountered. This therapy produces complete remission on roentgenography and bronchoscopy, symtomatic improvement and improved survival in the majority of patients with limited-stage small cell lung cancer. A portion of these patients may have their disease eradicated.

Adult↗
PubMed1979

Traumatic rupture of the thoracic aorta.

Our experience with 36 cases of traumatic rupture of the aorta has prompted an aggressive investigative and surgical approach. Age range, mechanism of injury, and associated injuries are quite variable. Aortogram is essential for diagnosis and should be done with any evidence of mediastinal abnormality following a deceleration injury. The preferred method of repair is graft interposition for the transected aorta, using femoral vein to femoral artery bypass with an oxygenator in the system. The salvage rate is good if an aggressive surgical approach is used.

Accidents, Traffic↗
PubMed1978

Treatment of oat cell carcinoma of the lung: complete remissions, acceptable complications, and improved survival.

Oat cell lung cancer is a common disease which is usually disseminated by the time it is diagnosed. Treatment with cyclic combination chemotherapy (cyclophosphamide, doxorubicin, vincristine) administered concurrently with radiotherapy to the chest lesion and subsequent prophylactic brain irradiation was investigated in 36 patients with oat-cell carcinoma of the lung. Complete remissions occurred in 26 of the patients (15 of the 16 with limited-stage disease and 11 of the 20 with extensive-stage disease). Symptomatic improvement occurred in all patients. Twelve of the 16 patients with limited disease remained well and free of disease for over a year. The results were equivalent to those of a similar though more intensive regimen, but the toxicity was much less (there were no treatment-related deaths). Transient granulocytopenia with the risk of infection was the most serious complication. Survival and quality of life have been improved for all patients, particularly those with limited disease, who have previously responded poorly to treatment.

Aged↗
PubMed1978

High-dose methotrexate with citrovorum factor rescue in non-small-cell lung cancer.

Nineteen patients with non-small-cell carcinoma of the lung were treated with high-dose methotrexate and leucovorin rescue. Two partial responses (10.5%) were observed, lasting 13 and 17 weeks. Toxicity was acceptable. It is concluded that the occasional benefit of high-dose methotrexate with leucovorin rescue at this dose and according to the schedule described for these patients does not warrant further study.

Adult↗
PubMed1978

An inexpensive color display for computed tomography scanners and other imaging systems.

The use of color pictures and displays for interpreting images obtained from computed tomography scanners, scintillation cameras, and ultrasound equipment is an interesting possibility. As currently supplied, color television monitors may add significantly to the cost of a system. A relatively simple way of converting an entertainment grade color television receiver to color monitor operation is described. The display system is significantly lower in cost than vendor supplied monitors and produces images of similar quality.

Color↗
PubMed1978

Effect of signaled versus unsignaled stress of rat myocardium.

Foot-shock stress resulted in a threefold increase in myocardial uptake of technetium-99m-methylene diphosphonate (Tc-99m-MDP) in rats compared to unstressed controls. The introduction of a 4-sec signal prior to each shock resulted in a two-thirds reduction in this stress-induced Tc-99m-MDP myocardial uptake, suggesting that most of the stress-induced myocardial damage was psychologically mediated.

Animals↗