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Biomedical subjects

D Albert

Publications and source records attributed to D Albert.

At least 19 recordsLinked to original sources
PubMed1992

Prevention of metastasis of intraocular melanoma in mice treated with difluoromethylornithine.

The antimetastatic potential of a novel chemotherapeutic agent, alpha-difluoromethylornithine (DFMO), was evaluated in a murine model of intraocular melanoma. In vivo studies demonstrated that DFMO retarded the growth and spontaneous metastasis of murine intraocular melanomas. Further studies indicated that oral DFMO also exercised antimetastatic effects against the blood-borne stage of melanoma metastases. In vitro studies revealed that DFMO exerted impressive antiproliferative effects on three murine melanoma cell lines, four human cutaneous melanoma cell lines, one human uveal melanoma cell line, and one conjunctival melanoma cell line. DFMO inhibited in vitro DNA synthesis in human cutaneous melanoma cell lines by 84%-98% and that in two human ocular melanoma cell cultures by 62% and 86%, respectively. DFMO possesses several characteristics that render it an attractive chemotherapeutic agent for potential use in the management of uveal melanoma. These include its antiproliferative effect against a wide range of murine and human melanomas, its extremely low toxicity, and its ease of administration.

Administration, Oral↗
PubMed1992

The discovery and development of zileuton: an orally active 5-lipoxygenase inhibitor.

The enzyme 5-lipoxygenase is a key target in the effort to discover drugs which inhibit the pathophysiology associated with the formation of leukotrienes. The research efforts of these laboratories have focused on the discovery of direct enzyme inhibitors of 5-lipoxygenase. In particular, compounds with hydroxamate or N-hydroxyurea functionalities have proven to be potent inhibitors of leukotriene biosynthesis in vitro and more importantly in vivo. One of these compounds, zileuton (N-(1-benzo-[b]-thien-2-ylethyl)-N-hydroxyurea) has been shown recently to be an effective leukotriene inhibitor in man. The critical approaches and breakthroughs in the discovery and development of zileuton are described. In addition, some recent results with zileuton in animals and man are detailed.

Animals↗
PubMed1992

Five DNA tumor viruses undetectable in human retinoblastomas.

Retinoblastoma (RB) is a childhood eye cancer that arises when a retinal cell lacks a functional RB gene. Recent data indicate the transforming proteins of adenovirus, papillomavirus, and the polyomaviruses BK and JC all can bind to the product of the RB gene. Furthermore, adenovirus 12, JC virus, and simian virus 40 are able to induce RB-like tumors in rodents. In view of these findings, 50 human RBs were tested for the presence of five human DNA tumor viruses: adenovirus 12, BK virus, JC virus, and human papillomaviruses 16 and 18. Using the polymerase chain reaction, no viral sequences were detected in 50 RB DNAs. These data provide no evidence that these viruses have an etiologic role in human RB.

Base Sequence↗
PubMed1991

Phase I-II evaluation of intravesical novantrone (mitoxantrone) in superficial bladder cancer.

The objective of this study was to determine the safety and efficacy of intravesical novantrone in refractory superficial bladder cancer. The eligibility criteria included proven carcinoma in situ or superficial transitional cell carcinoma of the bladder at stage Ta or T1 that was proven refractory to or in relapse after the use of at least one other standard anti-cancer agent. The patient was to have received no prior radiotherapy or intravesical therapy for at least 4 weeks prior to entry. Patients also did not suffer significant cardiac dysfunction, such as angina, congestive heart failure, or uncompensated cardiomyopathy. All patients were given 4-6 doses of intravesical novantrone at the same dose level at weekly dosing interval. Patients were required to retain the drugs in the bladder for 2 h. Baseline study included history/physical, hematology, blood chemistry, cystoscopy, bladder barbotage, urine cytology, cystometrogram to assess the bladder capacity, and finally, chest X-ray, EKG, and MUGA scan, if indicated. Weekly assessment involved toxicity notation, blood chemistry, hematology and urinalysis. Monthly assessment included physical examination, toxicity notation, hematology, urinalysis and blood chemistry. Within 4 weeks of completion of the last dose, patients underwent repeat cystoscopy to assess disease status. Patients who responded to the 4-6 week induction phase were entered in a monthly dose regimen for up to 5 months. A total of 23 patients were enrolled: 22 males and 1 female. One patient dropped out before receiving medication because of a protocol violation for entry criteria. Twenty-two patients were eligible for assessment of safety and 20 were eligible for assessment of efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Diastolic potentials recorded by surface electrocardiographic signal averaging during sustained ventricular tachycardia: possible origin from the reentrant circuit.

ECG signal averaging can detect low amplitude diastolic potentials in sinus rhythm. We, therefore, recorded signal-averaged ECGs during eight episodes of inducible uniform sustained VT with coincident atrial pacing to look for continuous diastolic electrical activity. Simultaneous AV pacing in seven patients served as controls. The number of QRS complexes averaged (187 +/- 47 vs 183 +/- 63), the noise level (1.26 +/- 0.88 vs 1.39 +/- 0.47) and cycle length (385 +/- 52 vs 404 +/- 40) did not differ between VT and paced recordings. In each lead the difference in onset between the unfiltered surface recording and the filtered data (40 Hz bidirectional) was significantly greater in VT than the paced recordings (25 +/- 16 vs 11 +/- 8 msec, P = 0.0012). These late diastolic (pre-QRS) potentials were greater than 15 msec duration in 65% of the leads in VT versus 20% of paced recording (P = 0.021). The maximum value was greater than 20 msec in six VT (75%) versus one (14%) paced recording (P = 0.019). The earliest filtered onset in any lead preceeded the earliest surface activity by greater than 12 msec, in 6 VT versus one paced recording (P = 0.019). Early diastolic (post-QRS) potentials were also longer in VT than pacing (49 +/- 40 versus 5 +/- 20, P = 0.001) and exceeded 38 msec in seven of the VTs but none of the paced recordings (P = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Atrioventricular Node↗
PubMed1991

Pharmacokinetics, safety, and ability to diminish leukotriene synthesis by zileuton, an inhibitor of 5-lipoxygenase.

Zileuton is a potent and specific inhibitor of 5-lipoxygenase, the first dedicated enzyme in the metabolism of arachidonic acid to the leukotrienes. The leukotrienes have been implicated in numerous pathological conditions. Zileuton was given to normal human volunteers in single doses of 200 mg to 800 mg. Results of these studies indicated that zileuton was well absorbed orally with an elimination half-life of approximately 2.5 hours. Leukotriene B4 production by ex vivo calcium ionophone stimulated whole blood was inhibited by up to 80% of baseline and correlated with plasma concentrations. Zileuton did not significantly inhibit cyclooxygenase as demonstrated by thromboxane B2 levels. There were no safety concerns that would preclude development.

Adolescent↗
PubMed1991

Standardized data collection and coding in eye disease epidemiology: the Uveal Melanoma Data System.

The Uveal Melanoma Data System of the Massachusetts Eye and Ear Infirmary is a computerized data-base designed for data management and analysis with a broad range of clinical research applications. The system was created in 1980 and has evolved to include standardized data collection forms for all aspects of uveal melanoma patient care such as initial examination, treatment, and follow-up, as well as precoded forms for computer entry, which facilitate quality control measures and data analysis. Excerpts from current versions of these forms are presented. The Uveal Melanoma Data System has been used for a variety of clinical epidemiologic investigations. Examples of its application, including descriptive studies, prognostic factor studies, and treatment evaluations, are discussed. The model has potential broad application for clinical ophthalmic research in other specialty areas.

Data Collection↗
PubMed1990

The dose dependent effect of cyclic AMP on ribonucleotide reductase in mitogen stimulated mononuclear cells.

Cyclic adenosine monophosphate arrests proliferating T lymphocytes in the G1 phase of the cell cycle. Here we demonstrate that exogenous and endogenous elevations in cyclic AMP concentration result in diminished mitogen stimulation, cell cycle arrest, and decreased ribonucleotide reductase messenger RNA concentrations in peripheral blood mononuclear cells. At lower concentrations (less than 1mM) of dibutyryl cyclic AMP that do not generate cell cycle arrest there is inhibition of ribonucleotide reductase activity without decreased messenger RNA concentration for the M2 subunit of ribonucleotide reductase. However, at higher concentrations of dibutyryl cyclic AMP there is G1 cell cycle arrest and reduced M2 specific messenger RNA concentration. Thus, cyclic AMP inhibition of lymphocyte activation may occur by different mechanisms that are dose dependent.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗
PubMed1990

Acoustic reflectometry as an aid to the diagnosis of glue ear.

In assessing the usefulness of the acoustic reflectometer we have evaluated its performance on a selected group of patients, finding it to be of equivalent predictive value to those screening tests in common use. We feel that the advantages of the instrument combined with its performance will provide the general practitioner with a useful diagnostic aid.

Acoustic Impedance Tests↗
PubMed1989

Sebaceous carcinoma of the ocular adnexa: radiotherapeutic management.

A total of 30 patients with histologically confirmed sebaceous carcinoma of the ocular adnexa were evaluated at our institution from 1974-1986. There were 18 women and 12 men in the series with a median age of 61 years. Ten cases received radiotherapy with curative intent. Four patients were treated definitively with doses ranging from 45-63.0 Gy over 4-7 weeks. Six patients received post-operative radiotherapy to the parotid bed and ipsilateral cervical lymph node chain for parotid metastases developing within 36 months of initial surgical treatment. Patients with lower lid lesions and significant pagetoid histologic components were more likely to develop parotid lymph node metastases. Local control at the primary site after radiation and/or surgery was 90% with follow-up ranging from 2-10 years. Overall disease specific actuarial survival at 5 years was 96%. Radiation therapy is an effective treatment modality in adnexal sebaceous carcinoma. With employment of careful technique and state-of-the-art technology, long term local control and survival with satisfactory cosmetic and functional results can be anticipated.

Adenocarcinoma↗
PubMed1988

Connective-tissue disease following breast augmentation: a preliminary test of the human adjuvant disease hypothesis.

It has been proposed that scleroderma in particular or connective-tissue diseases in general may be caused by exposure to silicone-containing materials used for breast augmentation. We performed a historical cohort study to estimate the point prevalence of this potential complication sometimes referred to as "human adjuvant disease." Three-hundred and seventy-eight patients who underwent augmentation mammaplasty with silicone-containing envelope-type prostheses from 1970 through 1981 were surveyed. Regional musculoskeletal syndromes, fibrositis, or osteoarthritis occurred in a third (38 of 125) of our responders. No patient developed an inflammatory systemic rheumatic disease during the period of observation (mean 6.8 years for the 125 subjects). Using calculations based on risk for development of rheumatic disease, it does not appear likely that augmentation mammaplasty is a significant or major inducer of inflammatory connective-tissue diseases in general. However, the number of patients surveyed was small, and our results must be considered preliminary. We could not exclude a specific risk for the development of scleroderma.

Adult↗
PubMed1988

Cobalt plaque versus enucleation for uveal melanoma: comparison of survival rates.

Two hundred and twenty-three patients treated by cobalt plaque for uveal melanoma were compared with 416 patients treated by enucleation for uveal melanoma in terms of patient survival. The median follow-up time for the patients treated by cobalt plaque was 4.3 years. Kaplan-Meier survival curves were calculated up to five years following treatment based on time to tumour-related deaths. Cox's proportional hazards multivariate analysis was performed to determine which variables were related to melanoma-related deaths while controlling for age, size, and location of the tumours. Statistically significant predictive factors were location of tumour and largest tumour dimension. There was not a statistically significant difference in survival between patients treated by cobalt plaque and those treated by enucleation.

Adolescent↗
PubMed1987

Lectin receptors of amyloid in corneas with lattice dystrophy.

We analyzed lectin binding patterns of amyloid glycoconjugates in patients with lattice dystrophy of the cornea. Results of paraffin and frozen sections differed in some instances. With paraffin sections, three lectins--wheat germ agglutinin (WGA), Ricinus communis agglutinin I (RCA-I), and concanavalin A (Con A)--stained the abnormal deposits. In frozen sections, the abnormal deposits were stained by five lectins--WGA, RCA-I, Con A, peanut agglutinin (PNA), and soybean agglutinin (SBA). In paraffin sections, PNA and SBA did not stain amyloid deposits. In both paraffin and frozen sections, some lectin-positive deposits corresponded to the Congo red-positive material, whereas others were present surrounding and encroaching on the Congo red-reactive material. This study demonstrates that WGA-, RCA-I-, Con A-, PNA-, and SBA-positive abnormal deposits are present in corneas with lattice dystrophy. Since lectins bind to specific sugar residues, we conclude that the abnormal deposits consist, at least in part, of glycoconjugates and that these glycoconjugates contain oligosaccharides with N-acetylglucosamine/sialic acid, mannose/glucose and terminal beta-galactose residues and chains with terminal beta-galactose-N-acetylgalactosamine disaccharides.

Adult↗
PubMed1987

Relationship of stressful housing conditions to the onset of diabetes mellitus induced by multiple, sub-diabetogenic doses of streptozotocin in mice.

The effect of the stress of crowded housing conditions (10 mice/cage) on the onset of diabetes after multiple, sub-diabetogenic doses of streptozotocin (MSZ) in male C57BL/KsJ mice was investigated. Prior to MSZ treatment, the group-housed and individually-housed animals had similar plasma glucose levels, while the former group's plasma corticosterone (CS) levels were elevated (54 +/- 8 ng/ml, p less than 0.03; 166% of the latter group). The group-housed animals became hyperglycemic (253 +/- 23 mg/dl) 2 days after the MSZ (day 7), with maximum hyperglycemia (506 +/- 23 mg/dl) developing by day 10. The individually housed animals did not become hyperglycemic until day 10 (303 +/- 24 mg/dl, p less than 0.001), and did not reach maximal hyperglycemia until between days 31 and 46, when plasma glucose levels were no longer different from the group-housed mice (507 +/- 37 mg/dl). There was a significant and progressive rise in CS levels of the stressed animals, reaching 218 +/- 25 ng/ml at day 46. The rise in CS of the unstressed animals was not significant until day 46, when the mean value reached 96 +/- 19 ng/ml (p less than 0.001 vs. basal). However, even at the conclusion of the experiment, the mean CS in the stressed animals was still 227% of that in the unstressed group (p less than 0.001). These studies demonstrate that the effects of stress (biochemically documented as an increase in CS levels) act synergistically with streptozotocin to promote an earlier onset of diabetes mellitus in males of this murine strain.

Animals↗
PubMed1986

A method for assessing potential bias among cancer patients recorded as "dead of other causes." Application to cases of intraocular melanoma.

By applying the Cox regression model to 226 cases of intraocular melanoma, the authors detected a statistical association between tumor-related measurements and 42 deaths that were recorded as due to causes other than melanoma within 10 years of follow-up. This association may reflect a number of events, including errors in assignment of cause of death and confounding from any one of several sources.

Eye Neoplasms↗