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Biomedical subjects

P Rosen

Publications and source records attributed to P Rosen.

At least 19 recordsLinked to original sources

The pathology of abortive neovascular outgrowths from the retina.

Seven abortive neovascular outgrowths (ANVOs) from diabetic retinas were obtained for examination either by biopsy during pars plana vitrectomy (2) or after discovery within enucleated globes (5). Scanning and electron microscopical, histochemical, immunohistochemical and retinal digest techniques were used. The ANVOs consisted of nodules of vessels without an extravascular fibrous component. Two of them contained aneurysm-like dilatations of constituent vessels, and all the specimens showed gross hyaline thickening of the vessel walls. The vascular sclerosis was probably due to accumulation of plasma proteins in the walls of the damaged vessels, which contributes to their involution seen clinically after retinal photocoagulation.

Adult

Management of the subluxed crystalline lens.

There has been a traditional reluctance to remove a subluxed (ectopic) lens because of the high surgical risk. The use of closed intraocular microsurgical techniques, however, now allows greater intraoperative control with few complications. The authors present the results of subluxed lens extraction, by limbal or pars plana lensectomy, in 44 eyes of 24 patients, in which the indication for surgery was lens subluxation causing a reduction in visual acuity or uncorrectable refractive error. Visual acuity was improved in all cases after surgery, with no significant complications. Patients with reduced visual acuity secondary to ectopic lenses have a good visual prognosis after lensectomy using a closed intraocular microsurgical technique.

Adult

A phase I trial of alpha-interferon in combination with pentostatin in hematologic malignancies.

Pentostatin, a novel inhibitor of adenosine deaminase, has shown activity in various lymphoid malignancies of both the T and B cell lineage. This agent has unique side effects and in general myelosuppression has been mild. Interferon has both antiviral and antineoplastic properties. This agent has shown activity in hairy cell leukemia, chronic granulocytic leukemia, low grade lymphoma, and myeloma. Side effects from interferon are in general dissimilar to those that have been seen with pentostatin and in particular myelosuppression has not been a major toxicity with low doses of interferon. This current trial explored the combination of pentostatin and interferon in hematologic malignancies. Fifteen patients were enrolled in this phase I trial at a fixed dose of pentostatin of 4 mg/m2 biweekly and interferon at doses of 0.5, 1, 2, or 4 million units/m2 of interferon. At the first three dose levels of interferon nausea and vomiting were the predominant toxicity and appeared to worsen with time on study. Fatigue also was seen at the lowest level of interferon and was severe enough to cause two individuals to discontinue the study medications. At higher dose levels of interferon, myelosuppression, nausea and vomiting, and fatigue were the predominant toxicities. One patient with hairy cell leukemia had a complete response and a second patient with T cell cutaneous lymphoma had a partial response which lasted for 6 to 7 weeks. The maximum tolerated dose of interferon with pentostatin in this patient population was four million units/m2.

Adult

Effect of varying oxygen concentrations on the proliferation of retinal microvascular cells in vitro.

Microvascular fragments and pure cultures of either retinal microvascular endothelial cells, retinal pericytes or Tenon's capsule fibroblasts were grown on a gas permeable substrate while exposed to varying oxygen concentrations (5, 10, 20, 40 and 95% oxygen). For all three cell types cell proliferation was greatest under the lowest oxygen concentration and decreased as the oxygen concentration increased. The decrease in the proliferative ability of cells exposed to the higher oxygen concentrations could be reversed if the cells were returned to a normoxic environment. Endothelial cells were the most sensitive to changes in oxygen tensions showing a proliferative response after 24 hr exposure as opposed to 48 hr for pericytes and fibroblasts. These results suggest a direct mechanism by which the intra-vitreal and intra-retinal oxygen tension may influence both the development of preretinal new vessels (in response to retinal ischaemia) and also the regression of neovascularization following scatter photocoagulation or vitrectomy.

Animals

Ophthalmological screening for von Hippel-Lindau disease.

Forty seven individuals (from 16 kindreds) without prior evidence of retinal haemangiomas underwent full ophthalmological assessment as part of a comprehensive screening programme for Von Hippel-Lindau disease. Ten were known to be affected on the basis of non-ocular involvement and 37 were at 50% risk of having the abnormal gene. Seventeen angiomas were detected in 14 individuals (six affected patients and eight at risk relatives). Regular detailed ophthalmological assessment is important for all patients with von Hippel-Lindau disease and for relatives at risk of inheriting the abnormal gene.

Adult

Phase I toxicity and pharmacology study of trimethylcolchicinic acid in patients with advanced malignancies.

A phase I study of trimethylcolchicinic acid (TMCA) given orally once daily for 5 days every 3rd week was performed in 19 patients with advanced malignancies. Myelosuppression and mucositis were the major toxicities observed. Serum TMCA levels were monitored and appear to be useful in predicting toxicities. A partial response was seen in one lymphoma patient and stabilization of disease was noted in one patient each with prostatic and ovarian cancer.

Administration, Oral

Breast cancer at Hiroshima and Nagasaki.

A calculation is made of the incidence of breast cancer at Hiroshima and Nagasaki using the dosimetry of Straume and Dobson. Gamma rays cause a mutation in a critical gene. Using a two hit theory, an estimate of the number of target cells and a time period of 24 years, an estimate of the probability of carcinogenesis is obtained which is in good agreement with observation.

Breast Neoplasms

The synergism of gamma-interferon and tumor necrosis factor in whole body hyperthermia.

It is suggested that gamma-interferon (gamma-IFN) can be added to tumor necrosis factor (TNF) to improve therapy in whole body hyperthermia (WBH). The amount of r-HTNF is about 3.5 x 10(6) units per week with about 3.5 x 10(4) units of rH gamma-INF intravenously. The body temperature should be 40 degrees C for one half hour. An i.p. injection of secobarbital (24 mg/kg) should be given as well.

Combined Modality Therapy

Operation outreach: intensive case management for severely psychiatrically disabled adults.

Twenty-eight severely mentally ill adults in an inner-city area of Atlanta participated in a study to determine if intensive outreach by case managers would result in decreased use of mental hospitals and improved community living. The experimental group of 14 clients received intensive support from case managers in the community who helped them anticipate and prevent crises, maintain medication schedules, and address problems in living. Fourteen clients in the control group received some of these same services but at a less intensive level and only at the offices of the case managers. Compared with control clients, experimental clients had an average of ten fewer hospital days and better adherence to medication regimens and agreed-upon service plans during the project.

Community Mental Health Services

Transient focal neurologic deficits complicating interleukin-2 therapy.

We report 2 patients with transient, focal, repetitive, stereotyped episodes of neurologic deficits during treatment with interleukin-2. One patient had recurrent monocular blindness, while the 2nd had recurrent homonymous quadrantanopia. We suggest that these attacks are provoked by endothelial cell activation induced by interleukin-2.

Blindness

Successful whole body hyperthermia for cancer.

It is suggested that whole body hyperthermia at 40 degrees C with immune therapy using recombinant human tumor necrosis factor at about 3.5 million units per week at experimentally determined intervals could eliminate cancer cells.

Animals

Ensuring data quality in a multicenter clinical trial: remote site data entry, central coordination and feedback.

In an ongoing multicenter clinical trial, "Treatment Strategies in Schizophrenia," the five participating sites have the capacity to perform a variety of tasks or study functions independently. These tasks include (a) verification of diagnostic eligibility through the use of computerized decision algorithms; (b) assignment of patients to treatment based on prognostic indicators using a computerized randomization algorithm; (c) entry of data into a microcomputer using a clinical trial data management system that performs simple range and missing data item checks; and (d) regular transfer of all data to the central coordinating team. The clinical trial data management system employed allows for both independent site functioning and assurance of consistency across sites. The integration of a variety of software outside the main data management system provides the central coordinators with the tools to monitor critical data as it is collected, as well as the capacity to assess the flow, quality, and uniformity of the ongoing trial.

Clinical Trials as Topic