Search PubMed⌕ Search

Biomedical subjects

J E Tomaszewski

Publications and source records attributed to J E Tomaszewski.

At least 145 records · Page 8Linked to original sources

Paget's disease primarily involving the scrotum.

Three cases of Paget's disease primarily involving the scrotum are reported. One case exhibited positive staining for prostate specific antigen (PSA) and was associated with an underlying, invasive poorly differentiated adenocarcinoma of unknown primary. The other cases were not associated with any underlying or visceral malignancy. The literature on Paget's disease primarily involving the scrotum including clinical presentation, differential diagnosis, treatment, prognosis, and possible histogenetic mechanisms of this disease is discussed.

Adenocarcinoma↗

A comparison of three nucleoside analogs with anti-retroviral activity on immune and hematopoietic functions in mice: in vitro toxicity to precursor cells and microstromal environment.

A number of 2'3'-dideoxynucleosides have been reported to markedly inhibit the in vitro growth of HIV, the causative agent of acquired immunodeficiency syndrome (AIDS). Clinical trials have shown that the continued therapeutic use of these nucleoside derivatives can be associated with adverse side effects. Since these side effects include myelotoxicity, as occurs in many patients treated with zidovudine (AZT; 3'-azido'3-deoxythymidine), and AIDS patients already represent an immunologically compromised population, we examined the immunological effects of three nucleoside inhibitors, including zidovudine, 2'3'-dideoxycytidine, and 2'3'-dideoxyadenosine (DDA) in a mouse model. Additional studies were conducted to further determine and characterize the potential toxic effects associated with these drugs on the hematopoietic system. Of the three dideoxynucleosides examined, only DDA altered immune functions following a 30-day subchronic exposure in mice. This was evidenced by a marked suppression of the antibody plaque-forming cell response and a slight alteration in macrophage function. None of the nucleoside derivatives affected bone marrow function following in vivo exposure, although AZT produced a mild macrocytic anemia in vivo and was myelotoxic when added in vitro to bone marrow cell cultures. In vitro studies indicated that AZT was capable of affecting both proliferating stem cells as well as the stromal cell microenvironment, both of which play a role in hematopoiesis. These data indicate that, although the mice may not develop the identical toxicities associated with nucleoside therapy in humans, certain adverse immunological and hematological effects were readily discerned which could have relevance to humans.

Acquired Immunodeficiency Syndrome↗

Testicular plasmacytoma.

The case of a sixty-five-year-old man with multiple myeloma and a testicular plasmacytoma is described. This represents the thirty fourth reported case of testicular plasmacytoma and the first in which immunoperoxidase histochemistry has been used to demonstrate that the testicular plasma cells contain immunoglobulin of the same isotype as the patient's paraprotein. The clinical and morphologic features of previously reported testicular plasmacytoma are reviewed.

Aged↗

Prostatic carcinoma and benign prostatic hyperplasia: correlation of high-resolution MR and histopathologic findings.

High-resolution magnetic resonance (MR) imaging of 24 fresh radical prostatectomy specimens was performed on an experimental 1.9-T system. Direct correlation between the findings in 7-micron-thick macrosections and their corresponding MR images was possible. Fourteen patients had macroscopic evidence of cancer. In all 14 cases, the carcinoma nodules appeared as areas of low signal intensity on images obtained with a repetition time of 2,500 msec and an echo time of 80 msec. Ten of 14 nodules had well-defined margins and consisted of densely packed glandular elements, which displaced the surrounding normal glandular material of higher signal intensity. Ten specimens displayed benign prostatic hyperplasia (BPH). The MR characteristics of this entity were quite variable but relatively predictable, depending on the distribution and size of the glandular elements, as well as the composition of the surrounding stroma. In BPH, the changes began in the central portion of the gland. The areas of highest signal intensity corresponded to dilated glandular elements (cystic ectasia), while the areas of lowest signal intensity corresponded to collagen (scar) and fibromuscular stroma. Nodules of mixed glandular BPH and fibromuscular BPH were found to have signal intensities similar to those of well-differentiated nodules of prostatic adenocarcinoma.

Aged↗

Natural killer-cell activity in cyclosporine-treated renal allograft recipients.

We prospectively studied natural killer (NK)-cell activity in 16 cyclosporine-treated renal transplant recipients. NK function remained intact in the group as a whole in the initial 6 months following transplantation. The percentage of CD16-positive cells within the peripheral blood mononuclear-cell population was highly correlated with NK activity both prior to and following transplantation in the absence of rejection. During rejection, the correlation was poor. A marked increase in NK activity occurred during 9 of 12 rejection episodes; similar increases in NK activity were rarely observed in the absence of rejection. Significant infiltrates of NK cells, as determined by expression of CD16, were not demonstrated in stained biopsy specimens obtained from rejecting allografts. Pretransplant NK activity did not predict clinical outcome of the allograft. Our results indicate that NK cells are activated during allograft rejection in cyclosporine-treated patients, but their exact role in the rejection process is unknown.

Adolescent↗

Treatment of bladder cancer with interstitial iridium-192 implantation and external beam irradiation.

Although interstitial implantation of invasive carcinoma of the bladder has been shown to be an effective treatment in Europe, there has been little experience with this method in the U.S. During the past 6 years, 14 patients at the Hospital of the University of Pennsylvania with single bladder tumors less than 5 cm and no evidence of carcinoma in situ on random bladder biopsies have been treated by a combination of external beam radiation and iridium wire implant. The iridium wire is inserted by an afterloading technique following tumor exposure via suprapubic cystotomy. Following delivery of the prescribed dose, the sources are removed percutaneously. Three patients with recurrent or high grade T1 lesions and 11 patients with T2-T3A lesions have been treated. With a median follow-up of 22 months (range 17 to 65 months), 9 patients are currently NED, 4 patients have died of disease, and 1 patient has died of intercurrent disease. There have been two isolated bladder recurrences, both non-invasive, one having been treated with cystectomy and one being treated locally. In addition, one patient developed regional failure, two developed distant metastases only, and one developed local recurrence following distant failure. The 2-year actuarial local control rate is 84%, with an overall 2-year actuarial survival of 66%. Complications have been minimal. Bladder implantation by this method is technically simple and produces excellent local control with acceptable morbidity.

Adult↗

Small renal cell carcinomas: resolving a diagnostic dilemma.

Thirty-nine patients with pathologically proved renal cell carcinomas 3 cm or les in diameter were examined. Results of intravenous urography (n = 30) were true positive in 20 patients and false negative in ten (sensitivity, 67%). Renal ultrasound (US) (n = 29) had true-positive results in 23 patients and false-negative results in six (sensitivity, 79%); computed tomography (CT) (n = 36) had true-positive results in 34 and false-negative results in two (sensitivity, 94%). For selective renal angiography (n = 35%), the results were true positive in 26 and false negative in nine (sensitivity, 74%), with typical hypervascular renal cell carcinomas demonstrated in 17. Finally, the findings of percutaneous fine-needle aspiration biopsy were true positive in one of five patients when US guidance was used (sensitivity, 20%) and in five of eight when CT guidance was used (sensitivity, 62%). Small renal cell carcinomas are more frequently encountered in clinical practice than heretofore realized, and they are best imaged by CT.

Adult↗

Recurrent sickle cell nephropathy in a transplanted kidney.

Of patients who developed end-stage renal disease secondary to sickle cell anemia (SCA), some have undergone renal transplantation with reasonable success. We recently cared for a patient with SCA and a functioning, transplanted kidney who experienced a permanent decline in renal function three and one-half years following transplant. The evaluation of his renal dysfunction revealed multiple features to support recurrence of sickle cell nephropathy as the cause for the deterioration.

Adult↗

Prevention of diabetes in BB rats by intermittent administration of cyclosporine.

The successful prevention of spontaneous autoimmune diabetes in biobreeding (BB) rats--the closest animal model to human type I diabetes mellitus--by daily administrations of cyclosporine (CsA) has prompted clinical trials of CsA immunosuppression in human diabetes. Although remissions from hyperglycemia have been achieved in human subjects, nephrotoxicity and recurrence of diabetes after discontinuation of CsA have been observed. Therefore we studied the biologic efficacy of intermittent administration of CsA, a theoretically less dangerous immunosuppressive protocol, in the prevention of spontaneous diabetes in the BB rat. Beginning at 30 to 49 or 50 to 55 days of age, treated animals (n = 86) received daily injections of CsA (15 mg/Kg) for 2 weeks (induction phase) and then twice weekly (maintenance phase) until 160 days of age. A third group of animals (n = 31) received daily CsA for 14 days only. Control littermates (n = 121) were not injected. All animals were followed to 275 days of age. Intermittent administration of CsA was determined to be a biologically effective regimen in the prevention of spontaneous diabetes in the BB rat. Blood levels of CsA and the major CsA metabolites were undetectable intermittently during the course of therapy. Major complications associated with CsA immunosuppression (nephrotoxicity, malignancy, and infection) were not associated with the intermittent CsA protocol. We conclude that spontaneous diabetes can be delayed and often permanently prevented by intermittent administration of CsA. This immunosuppressive regimen deserves further consideration as a biologically effective, but theoretically less toxic, therapeutic regimen.

Animals↗

Invasive carcinoma of prostate presenting as rectal carcinoma.

Prostate carcinoma occasionally can present with rectal obstructive symptoms and an annular constricting lesion of the rectum. Discriminating between primary rectal carcinoma and prostate carcinoma locally invasive to the rectum is of obvious importance because of the different treatments and prognoses. History and physical examination play only a marginal role in differentiating between these two lesions. The diagnosis of prostatic malignancy in patients in this circumstance can be supported by an elevated serum acid phosphatase as well as a bone scan that demonstrates a pelvic/vertebral distribution of bony metastases. The rectal mucosa is usually spared, and a barium enema often will demonstrate tapered margins as opposed to a tumor edge in primary rectal malignancy. Excretory urography often demonstrates hydronephrosis. Rectal biopsy with immunohistochemical staining for prostate specific antigen can direct the origin of a poorly differentiated adenocarcinoma to the prostate. Treatment involves hormonal manipulation with estrogen therapy or orchiectomy. Radiation therapy to the obstructed rectum has provided satisfactory palliation when hormonal manipulation fails.

Adenocarcinoma↗

Penicillamine-induced rapidly progressive glomerulonephritis in patients with progressive systemic sclerosis: successful treatment of two patients and a review of the literature.

Although D-penicillamine has been used effectively in the management of a variety of diseases such as cystinuria, Wilson's disease, rheumatoid arthritis, and progressive systemic sclerosis, several toxic drug reactions have been observed with prolonged administration of this agent. One of the most serious side effects is the renal changes that occur following several months of use. We now report two patients with scleroderma who developed serologic evidence of lupus and crescentic glomerulonephritis during treatment with D-penicillamine. Both patients responded to pulse methylprednisolone and subsequent daily steroids. We also review the current information available on the variety of penicillamine nephropathies.

Adolescent↗

Long-term renal responses to high dietary protein in dogs with 75% nephrectomy.

It has been proposed that ingestion of large amounts of dietary protein leads to sustained renal hyperperfusion and progressive glomerulosclerosis in rats. This hypothesis was tested in dogs, with 75% reduction in renal mass, maintained for 4 years on either 56, 27, or 19% dietary protein. Twelve of 21 dogs survived 4 years, and death due to renal failure was not correlated to diet. Dogs fed 56 and 27% protein had increased GFR and CPAH before and after reduction of renal mass compared to the 19% group. A pattern of deterioration of renal function, including proteinuria, was not found in any diet group. Nine of 11 dogs, fed 56, 27, or 19% protein had minimal glomerular lesions, including mesangial proliferation, GBM irregularities, adhesions, and sclerosis. Two other dogs, fed 56% protein, had more severe glomerular lesions. No significant ultrastructural differences were found in glomeruli among the three diet groups. These results do not support the hypothesis that high protein feeding had a significant adverse effect on either renal function of morphology in dogs with 75% nephrectomy.

Animals↗

Cell surface antigen identification by a modified fluorescein immunosphere method.

Fluorescein immunospheres may be used in an indirect technic to label lymphocyte cell surface antigens. Wright's counter-staining allows simultaneous identification of fine morphology and surface antigen properties. Studies designed to determine methods for separating cells with bound immunospheres from free immunospheres revealed that removal of unbound immunospheres by flotation over cold protein solution creates excessive numbers of false negatives. Glutaraldehyde cross-linking of the primary and secondary antibodies linking immunospheres to the lymphocyte stabilizes the complex. This modification of the fluorescein immunosphere method compares favorably with flow cytometry.

Adult↗

The "intelligent workstation" for cell-surface phenotyping based on principles of pattern recognition and image analysis.

Technical advancements in computer hardware and the associated computerized architectures allow the design and fabrication of dedicated, modestly expensive computerized workstations to aid humans in complex decision-making tasks. We refer to these as "Intelligent Workstations" because they accommodate the hypothesis-driven reasoning ability of the user into the system. Concomitant with the rapid developments in computers, diagnostic and therapeutic technologies related to cell analysis have undergone growth. Combining these technologies requires careful formulation and analysis of the diagnostic model involving image cytometry. Here we present a model of the intelligent workstation for image cytometry and illustrate its advantages in cell-surface phenotyping. Combining cell morphology with cell-surface phenotyping has clear diagnostic utility that no other widely available methods can supply. Although the reported results are based on samples of peripheral blood, cell suspensions of disaggregated cells can also be analyzed.

Aged↗

Two-year inhalation toxicity study of propylene in F344/N rats and B6C3F1 mice.

Chronic toxicity studies of propylene were conducted by exposing groups of 50 F344/N rats and 50 B6C3F1 mice of each sex in chambers to air containing the chemical in concentrations of 5000 and 10,000 ppm, 6 hr per day, 5 days per week, for 103 weeks. Groups of 50 rats and 50 mice of each sex in similar chambers received clean air only on the same schedule and served as controls. Survival and mean body weights of exposed and control male and female rats and mice were similar. In exposed rats, increased incidences of nonneoplastic lesions were observed in the nasal cavity. These consisted of epithelial hyperplasia in female rats exposed to the high concentration, and squamous metaplasia in female rats exposed to both concentrations and in male rats exposed to the low concentration. In addition, inflammatory changes characterized by an influx of lymphocytes, macrophages, and granulocytes into the submucosa and by granulocytes into the lumen occurred in male rats of both exposure groups. There was no evidence of nasal cavity lesions in exposed mice, suggesting a species difference in sensory irritation to propylene. There were no treatment-related increases or decreases in tumor incidence in the exposed groups relative to controls for either rats or mice. These data suggest that inhaled propylene induces signs of nasal cavity toxicity in rats but not in mice, and that the chemical is not carcinogenic to either species at the concentrations tested.

Alkenes↗