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Biomedical subjects

S L Johansson

Publications and source records attributed to S L Johansson.

At least 19 recordsLinked to original sources

Effect of indomethacin on N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide-induced urinary tract carcinogenesis.

The effects of indomethacin on the urinary bladder and renal pelvis in rats treated with N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) were studied. Two hundred female Sprague-Dawley rats were divided into four groups. Group 1 received control diet without added chemicals. Group 2 was treated with indomethacin (1 mg/kg per day) in the drinking water throughout the experiment. Groups 3 and 4 received 0.2% FANFT in the diet for seven weeks followed by control diet. In addition to FANFT, Group 4 received indomethacin, 1 mg/kg per day, for the entire experiment. The rats were sacrificed after 92 weeks. There were no urothelial tumors in the control group, one renal pelvic tumor in the indomethacin group, 4 tumors in the FANFT group and 10 urothelial tumors in the FANFT + indomethacin group. The difference between Groups 3 and 4 was statistically significant (P < 0.05). Moderate and severe hyperplasia of the renal pelvic and papillary epithelium was found in 15 of 48 rats in Group 2 (indomethacin only) as compared with 6 of 49 control rats (P < 0.05). Moderate and severe hyperplasia was equally frequent in Groups 3 and 4 (14 and 17 animals in each group, respectively). Twenty-four rats in Group 2 had mammary tumors as compared to 12 animals in Group 1 (P < 0.01). Five of the tumors in Group 2 were adenocarcinomas. There was no difference between the number of mammary tumors in Groups 3 and 4 (36 and 32 animals in each group, respectively). The results suggest that indomethacin enhances FANFT-induced urinary tract carcinogenesis. Indomethacin also seems to exert some tumorigenic activity in the mammary gland.

Animals

Primary small cell carcinoma of the bladder: a report of 25 cases.

Primary small cell carcinoma of the bladder is a rare condition with approximately 100 cases reported to date. An incidence of 0.7% small cell carcinoma was found in a total series of bladder tumors diagnosed in Western Sweden during a 2-year period. We describe 22 patients with primary small cell carcinoma followed to death or for at least 6 years. Three additional cases were diagnosed at autopsy. Of 18 patients with stages T2M0 to T4M0 cancer treated with locoregional therapy 5 (28%) had no evidence of disease after a median observation of 10 years (range 6 to 18) and 13 died of disease after 0.5 to 19 months (median 7.3). Two patients with metastatic disease were treated with systemic chemotherapy but died within 15 months. Two patients died shortly after the diagnostic biopsy. Our study and a review of the literature indicate that primary small cell carcinoma of the bladder is less aggressive than its pulmonary counterpart and that some patients can be cured by transurethral resection, or partial or radical cystectomy combined with radiotherapy.

Aged

The relationship among multiple recurrences, progression and prognosis of patients with stages Ta and T1 transitional cell cancer of the bladder followed for at least 20 years.

A retrospective study was done on 176 patients with primary stages Ta and T1 bladder cancer treated between 1963 and 1972. One patient was lost to followup after 6 years, while the remainder were followed to death or for at least 20 years. In 1993, 13 patients had no evidence of disease, 39 died of bladder cancer and 123 died of intercurrent disease. Of 77 patients with a primary noninfiltrating tumor and 99 with a primary lamina propria invasive tumor 9 (11%) and 30 (30%), respectively, died of bladder cancer. Recurrences were noted on 10 or more cystoscopic studies in 16 patients and 10 died of bladder cancer 3.5 to 19 years after the primary transurethral resection. A total of 14 patients received repeated thiotepa instillations, all continued to have recurrences and 10 subsequently died of bladder cancer. Only 1 upper tract tumor was diagnosed on routine followup excretory urography. Invasive transitional cell carcinoma of the bladder developed in only 1 of 59 patients who had been tumor-free for 5 years. The results indicate that patients with recurrences on 10 or more cystoscopic studies will continue to have recurrences until death or cystectomy. Recurrence more than 4 years after the primary tumor operation is another ominous sign. Repeated thiotepa instillations did not influence the course of the disease in patients with a history of multiple recurrences. Followup cystoscopy may be discontinued 5 to 10 years after the last recurrence, at least in patients with a solitary low grade primary tumor. Routine followup urographic studies are neither cost-effective, clinically indicated nor justified in patients with superficial bladder cancer.

Carcinoma, Transitional Cell

Oral histoplasmosis in a patient infected with HIV. A case report.

Histoplasmosis is a frequent complication of HIV infection and is usually the result of reactivation. In the immunocompromised host, histoplasmosis may cause a chronic pulmonary infection or disseminated disease. In the setting of disseminated disease, oral lesions are present in 30% to 50% of patients and may occur in almost every part of the oral mucosa. The most common sites are the tongue, palate, and buccal mucosa. In some cases, oral lesions appear to be the primary or only manifestation of disease. We have been able to find only five case reports in the literature of histoplasmosis in HIV infection with oral lesions. In two of the cases, histoplasmosis was apparently localized to the oral cavity, whereas two cases also had evidence of disseminated disease, the fifth was undetermined. We report one such case of apparently localized oral histoplasmosis in a patient with HIV infection.

AIDS-Related Opportunistic Infections

Pathology of interstitial cystitis.

Morphologic changes, including light microscopy and ultrastructural, immunologic, and immunohistochemical findings in interstitial cystitis are described. The results indicate that biopsies are useful as an aid in the diagnosis of interstitial cystitis.

Adult

Acute urinary tract toxicity of tetraethylorthosilicate in rats.

Acute stomach, kidney, and bladder toxicity was evaluated in F344 rats after gastric gavage of tetraethylorthosilicate (TES) at daily doses of 0, 0.111, 0.223, and 0.333 g. Five rats of each sex at each dose were sacrificed after 1, 2, and 4 days. In TES-treated groups, silicate accumulated in the stomach glands and the muscle layer of the forestomach and glandular stomach. Serum chemistries demonstrated acute onset of renal failure. In the kidneys, acute tubular necrosis, accumulation of silicates, and superficial necrotizing papillitis were observed. In the renal pelvis and bladder, there was urothelial simple hyperplasia, focal erosion of the mucosa, edema, and inflammation. These acute toxic changes were dose and time dependent, but significant sex differences were not observed. The microscopic changes in the urothelium were similar to those observed following administration of high doses of sodium saccharin to male rats in which urinary silicate precipitate and crystals form.

Animals

The effect of cyclophosphamide administration on the kidney of the rat.

In studies primarily designed to evaluate the effectiveness of chitosan as a treatment for cyclophosphamide-induced hemorrhagic cystitis in the rat, renal papillary necrosis and pyelonephritis were observed. Cyclophosphamide alone produced relatively mild renal changes. The combination of cyclophosphamide and intravesical instillation of acetic acid induced renal papillary necrosis (38 to 83% incidence) along with pyelonephritis, hydroureter and hydronephrosis. Chitosan, instilled in place of acetic acid, partially inhibited the induction of renal papillary necrosis. It appears that the presence of vesico-ureteral reflux with or without associated hydroureter and hydronephrosis is a prerequisite for cyclophosphamide-induced renal damage.

Acetates

Penile verrucous carcinoma: a clinicopathologic, human papillomavirus typing and flow cytometric analysis.

The relationship of various verruciform squamous cell proliferations of the penis such as verrucous carcinoma, with or without anaplasia and giant condyloma, is uncertain. We conducted clinicopathologic, flow cytometric, and HPV typing studies on 15 cases of penile verrucous carcinoma to investigate its place in the spectrum of genital squamous proliferations. The results show a high degree of morphologic uniformity with respect to Ackerman's original diagnostic criteria, as well as to several other histopathologic features evaluated. The latter include polygonal squamous cells with glassy cytoplasm, centrally located vesicular nuclei, intercellular edema, well-formed cellular bridges, and absence or paucity of koilocytes, true fibrovascular cores, and keratohyalin granules. Intraepithelial abscesses and crust-formation were present in many cases. Four cases contained microscopic foci of cellular anaplasia. These hybrid verrucous-squamous carcinomas presented and behaved similarly to the pure verrucous carcinomas. Tumor recurrence was correlated with extent of initial surgical management. DNA ploidy analysis by flow cytometry performed on eight pure and two hybrid tumors showed uniform diploid populations with similar G1/G2 fractions in both groups. Eight pure and two hybrid tumors evaluated for HPV by isotopic in situ hybridization were uniformly negative for HPV types 6, 11, 16, 18, and 31. The results show that penile verrucous carcinoma demonstrates characteristic and uniform morphologic features and does not contain the HPV types typically associated with condyloma acuminatum, giant condyloma of Buschke-Löwenstein, and condylomatous carcinoma.

Adult

The relationships among tumor-infiltrating lymphocytes, histopathologic findings, and long-term clinical follow-up in renal cell carcinoma.

The relative abundance of tumor-infiltrating mononuclear cells (TIM) was retrospectively evaluated by immunohistology in nephrectomy specimens from 24 cases of human renal cell carcinoma (RCC). The extent of T-lymphocyte (T-cell) and B-lymphocyte (B-cell) infiltration of the tumors was graded semiquantitatively (0 to 4) in each case. Results of this analysis were correlated with clinical evidence of recurrent RCC, histologic evidence of venous invasion, tumor necrosis, and histologic cell type. Clinical follow-up demonstrated the presence of recurrent tumors in four of the 24 cases (17%), and these cases correlated with higher stage and pathologic grade tumors, as well as significantly increased TIM. Venous invasional and tumor necrosis correlated directly with tumor size, pathologic grade, and extent of TIM. Venous invasion was also associated with advanced stage. The group of cases with mixed or granular histologic cell type was associated with advanced stage, high pathologic grade, and increased T-cell infiltration compared to the clear-cell group of tumors. Overall, the pathologic grade demonstrated the highest correlation coefficients with clinical and TNM stage, but also correlated directly with the extent of T-cell infiltration of the tumor. These results confirm previous findings demonstrating a correlation in RCC between increased T-cell infiltration and both high clinical stage and pathologic grade. In addition, increased T-cell infiltration was found to correlate with tumor recurrence, indicating that such infiltration, along with high pathologic grade, is another indicator of poor prognosis in RCC.

Aged

Epidemiology and etiology of bladder cancer.

Urinary bladder cancer has long been associated with specific etiologic factors, and our knowledge of these factors has increased during this century. The most important factor, even in industrialized societies, is cigarette smoking. Specific chemicals have also been identified as causing bladder cancer, as have a variety of occupational exposures to less well-defined specific agents. In other parts of the world, the association of bladder cancer with Balkan nephropathy, endemic blackfoot disease, and schistosomiasis provides additional leads for investigating, and potentially preventing, the process of carcinogenesis in humans. Many of the critical observations in our understanding of bladder cancer have been made by practicing physicians, and this is likely to continue. It is essential that physicians dealing with bladder cancer patients be attuned to potential etiologic factors, including cigarette smoking, various industrial exposures, or drug exposures to further our understanding of this issue. Bladder cancer is a potentially preventable disease and an important one, as indicated by the total number of cases and the extent of morbidity and death attributable to it around the world.

Caffeine

Promoting effect of snuff in rats initiated by 4-nitroquinoline-N-oxide or 7,12-dimethylbenz(a)anthracene.

A canal was surgically created in the lower lip of male Sprague-Dawley rats and used as a reservoir for moist snuff. A total of 230 animals were randomized into six groups, five containing 40 rats and one containing 30 rats. After 2 wk of recuperation, the animals were treated as follows. Group I was initiated with 7,12-dimethylbenz(a)anthracene 3 times/wk for 4 wk followed by cotton pellet administration. Group II was initiated with 7,12-dimethylbenz(a)anthracene for 4 wk followed by snuff twice a day, 5 days/wk. Group III received snuff twice a day, 5 days/wk. Groups IV and V were initiated with 4-nitroquinoline N-oxide 3 days/wk for 4 wk. Thereafter Group IV received a cotton pellet, and Group V rats were treated with snuff twice a day, 5 days/wk. Group VI received a cotton pellet once a day, 5 days/wk. Treatment of all groups continued for a maximum of 104 wk. Group V rats had a significantly lower mean survival time than did the other groups because of the development of lip sarcomas in 66% of the rats as compared with 23% in Group II and 26% in Group III. One rat in each of Groups IV and VI developed lip sarcomas. The incidence of sarcomas in Group V as compared with the other groups is statistically significant (P less than 0.05 to 0.001). Spindle cell proliferation, a possible precursor lesion of lip sarcoma, was found in five rats of Group II, seven of Group III, and four of Group V. These results show that snuff has strong promoting capability with regard to the development of lip sarcomas after 4-nitroquinoline N-oxide initiation, but not after 7,12-dimethylbenz(a)anthracene initiation. Snuff by itself caused three squamous carcinomas of the palate, two squamous cell papillomas of the lip, and ten lip sarcomas (in 38 rats as compared with one lip sarcoma in 30 control rats), showing snuff to be carcinogenic for the lip and oral cavity.

4-Nitroquinoline-1-oxide

Comparative bladder tumor promoting activity of sodium saccharin, sodium ascorbate, related acids, and calcium salts in rats.

Sodium saccharin and sodium ascorbate are known to promote urinary bladder carcinogenesis in rats following initiation with N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) or N-butyl-N-(4-hydroxybutyl) nitrosamine. Sodium salts of other organic acids have also been shown to be bladder tumor promoters. In addition, these substances increase urothelial proliferation in short term assays in rats when fed at high doses. When they have been tested, the acid forms of these salts are without either promoting or cell proliferative inducing activity. The following experiment was designed to compare the tumor promoting activity of various forms of saccharin and to evaluate the role in promotion of urinary sodium, calcium, and pH as well as other factors. Twenty groups of 40 male F344 rats, 5 weeks of age, were fed either FANFT or control diet during a 6-week initiation phase followed by feeding of a test compound for 72 weeks in the second phase. The chemicals were administered to the first 18 groups in Agway Prolab 3200 diet and the last 2 groups were fed NIH-07 diet. The treatments were as follows: (a) FANFT----5% sodium saccharin (NaS); (b) FANFT----3% NaS; (c) FANFT----5.2% calcium saccharin (CaS); (d) FANFT----3.12% CaS; (e) FANFT----4.21% acid saccharin (S); (f) FANFT----2.53% S; (g) FANFT----5% sodium ascorbate; (h) FANFT----4.44% ascorbic acid; (i) FANFT----5% NaS plus 1.15% CaCO3; (j) FANFT----5.2% CaS plus 1.34% NaCl; (k) FANFT----5% NaS plus 1.23% NH4Cl; (l) FANFT----1.15% CaCO3; (m) FANFT----1.34% NaCl; (n) FANFT----control; (o) control----5% NaS; (p) control----5.2% CaS; (q) control----4.21% S; (r) Control----control; (s) FANFT----5% NaS (NIH-07 diet); (t) FANFT----control (NIH-07 diet). NaS, CaS and S without prior FANFT administration were without tumorigenic activity. NaS was found to have tumor promoting activity, showing a positive response at the 5 and 3% dose levels, with significantly greater activity at the higher dose. CaS had slight tumor promoting activity but without a dose response, and S showed no tumor promoting activity. In addition, NaCl showed weak tumor promoting activity, but CaCO3 was without activity. NH4Cl completely inhibited the tumor promoting activity of NaS when concurrently administered with it. NaCl administered with CaS or CaCO3 administered with NaS showed activity similar to that of NaS. Sodium ascorbate was also shown to have tumor promoting activity, with slightly less activity than NaS. Ascorbic acid showed no tumor promoting activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Transitional cloacogenic carcinoma of the female urethra treated with external irradiation and afterloading with cobalt-60.

A case of transitional cloacogenic carcinoma of the urethra in a 70-year-old woman is reported. Due to incomplete removal of the tumor and reluctancy to undergo extensive surgery, the patient also received external radiation and afterloading with cobalt-60. The patient is alive with no evidence of disease 7 years after the diagnosis, which may suggest that postoperative radiation as outlined should be considered in elderly women with urethral carcinoma.

Aged

A randomized prospective assessment of recombinant leukocyte A human interferon with or without aspirin in advanced renal adenocarcinoma.

We performed a prospective, controlled trial of recombinant leukocyte A interferon (IFN-alpha 2A) with or without aspirin (ASA) in 176 patients with assessable advanced renal cell cancer in light of a 34% response rate (10 of 29 patients) from the two-agent regimen in an earlier nonrandomized trial. This encouraging result was substantially higher than the 15% response rate typically achieved with IFN therapy alone. Eighty-seven patients received IFN-alpha 2A 20 x 10(6) U/m2 intramuscularly three times a week, and 89 received the same IFN therapy with ASA 600 mg orally four times each day. Each group was balanced as to relevant prognostic discriminants. Response rates were 8% for the group receiving ASA in addition to IFN, and 13% for the group receiving IFN alone (P = .30). The median times to progression were 1.9 months for the group receiving IFN with ASA and 2.7 months for the group receiving IFN alone (log-rank P = .36). The median survival durations were 8.8 months for the IFN and ASA group and 8.0 months for the IFN-only group (log-rank P = .60). These figures are also inferior to those typically reported from other studies. Our findings reemphasize the crucial role of randomized trials, admittedly cumbersome and time-consuming, to determine accurately the value of apparently promising therapies. Although some patients may derive benefit from IFN therapy, our findings raise disturbing questions regarding the potential IFN-alpha 2A according to the dose and schedule used in this trial to have any substantive impact on the ultimate outcome of disseminated renal cell cancer.

Adult