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Biomedical subjects

H Huland

Publications and source records attributed to H Huland.

At least 19 recordsLinked to original sources

Tumor-associated eosinophilia in interleukin-2-treated patients: evidence of toxic eosinophil degranulation on bladder cancer cells.

Blood eosinophilia in tumor patients treated with interleukin-2 (IL-2) is well known and is regarded as evidence of toxicity or as a side-effect [Lotze et al. (1986) Arch Surg 121:1373-1379; West et al. (1987) N Engl J Med 316:898-905]. We recently described a new local IL-2 approach to therapy for advanced bladder carcinoma that allows, for the first time, high-dose continuous administration of natural interleukin-2 (nIL-2) at the tumor site without side-effects [Huland and Huland (1989) Cancer Res 49:5469-5474]. Tumor-associated eosinophilia of up to 65% (i.e. eosinophils constituting 65% of leukocytes) was seen in four of five patients after treatment, but never before treatment or in untreated controls. Activated eosinophils were attached to bladder tumor cells. Local activation was seen only after natural IL-2 treatment and was determined by cytological criteria and by staining with monoclonal antibody (mAb) EG1 directed against all eosinophil granule proteins and mAb EG2 directed against the active secretory granule proteins of the eosinophils. Bladder cancer cells in urinary sediment also stained with these two mAbs, revealing active degranulation of eosinophils on bladder tumor cells. The number of eosinophils in blood increased, however, without signs of activation. These data constitute strong evidence that activated eosinophils in vivo are involved in the IL-2-induced antitumor response.

Administration, Intravesical

Distribution of 486P 3/12 antigen, ABO(H) blood group antigen and T antigen in cystectomy specimens from patients with stage T2 transitional cell carcinoma of the bladder.

We used monoclonal antibody 486P 3/12, anti-ABO(H) antibodies and anti-T antigen lectins to detect malignant transformation in cystectomy specimens from patients with stage T2 transitional cell carcinoma of the bladder. We used an immunoperoxidase technique to do extensive chessboard-like mapping studies in 6 cystectomy bladders with stage T2 lesions and 1 normal bladder from a multiorgan donor as control to characterize antigen expression. Increased 486P 3/12 antigen expression, decreased ABO(H) expression and T antigen deletion were detectable not only in the tumor area but also in tumor-surrounding areas classified as benign. We believe that cells with abnormal antigen expression are a source of tumor recurrence and can be identified with our method of quantitative immunocytology.

ABO Blood-Group System

A test for the identification of relevant sympathetic nerve fibers during nerve sparing retroperitoneal lymphadenectomy.

We present a new intraoperative test for the identification of sympathetic nerve fibers relevant to ejaculation during nerve sparing retroperitoneal lymphadenectomy in patients with nonseminomatous testicular tumors. Electrostimulation of specific isolated postganglionic nerve fibers resulted in intraoperative ejaculation in 9 of 11 patients. Ejaculation was without tumescence in a noneruptive manner and was reproducible in most cases upon repeated stimulation. In 6 patients ejaculation resulted after stimulation of the L3 fiber and in 1 each after stimulation of the L1, L2 and hypogastric plexus. The test seems to be particularly useful in post-chemotherapeutic dissections or otherwise extended dissections when sparing of irrelevant fibers is to be avoided.

Adrenergic Fibers

Interleukin-2 by inhalation: local therapy for metastatic renal cell carcinoma.

We report the use of inhaled natural interleukin-2 in patients with metastatic disease. Six patients with metastatic renal cell carcinoma received 100,000 units natural interleukin-2, 5 times per day by inhalation in addition to a 4-day cycle of intravenous natural interleukin-2 every 2 weeks and subcutaneous interferon 5 days per week. Response was clearly correlated with metastatic site. Distinct tumor burden and the poor condition of the patient did not impair success. Pulmonary metastases responded in 5 of 5 patients. Metastases in the mediastinum, liver, abdomen and pelvis were stabilized in 4 patients. No response was noted in 3 solitary bone metastases, which were successfully removed surgically after several months of therapy, and a pleural metastasis progressed despite a clear response of the pulmonary disease in the same patient. New metastases did not develop in any of the patients during treatment (median followup 183 days of treatment, range 97 to 296 days). The over-all importance of the low toxicity of this novel route of administration (World Health Organization classification not exceeding grade 1) making long-term outpatient treatment possible must be emphasized because limitations of systemic interleukin-2 application are mainly caused by pulmonary side effects, for example pulmonary capillary leakage syndrome and edema. However, this new type of topical natural interleukin-2 application and combination with low dose intravenous interleukin-2 achieved considerable antitumor responses.

Administration, Inhalation

Prostate cancer in nonurological patients with normal prostates on digital rectal examination.

Random systematic ultrasonographically guided transrectal core biopsies of the prostate were performed in 73 patients with pulmonary malignancies to exclude prostate cancer as a primary malignant neoplasm. Of the patients 41 had normal prostates as judged by digital rectal examination, 27 had firm prostates and 5 had clinical stage B nodules. Hypoechoic areas were seen on transrectal ultrasonography in 14 of the 41 patients (34%) with normal prostates. Biopsy of the hypoechoic areas in this subgroup detected only 1 grade II prostate cancer. In another patient with normal transrectal ultrasound grade I cancer was detected by mapping of the prostate with 6 systematic ultrasonographically guided transrectal core biopsies. Of the remaining 39 patients with normal prostates transrectal ultrasound detected no hypoechoic defect in 26, a specificity for the detection of prostate cancer of 67%. Multiple core biopsies revealed prostate cancer in 15 of the 32 cases of palpably abnormal prostates, including 12 that were hypoechoic. Prostate cancer is a rare histopathological finding in men with normal prostates on rectal examination. Transrectal ultrasound detected only 1 of 2 low volume prostate cancers in our study group. Thus, ultrasound seems to have little use in patients with prostates that appear normal on digital examination, and its specificity is low.

Aged

Influence of cause on choice of therapy in 174 patients with erectile dysfunction.

In 174 impotent patients consistent application of modern diagnostic methods, including dynamic color duplex sonography, pharmacocavernosography, nocturnal penile tumescence monitoring and psychological exploration, led to invasive therapy in 38 and to self-injection therapy in 76. Analysis of patients who received penile implants and those who performed self-injection did not show an important effect of etiology of impotence on the choice of treatment. Therefore, if penile vascular surgery is excluded, diagnostic procedures can be limited to a simplified goal-directed panel. Once psychogenic impotence is excluded through nocturnal penile tumescence monitoring, application of vasoactive drugs serves only to select patients to be considered for self-injection therapy. Implant surgery will be reserved for patients who fail to respond to any drug applied.

Adult

Digital rectal examination, imaging, and systematic-sextant biopsy in identifying operable lymph node-negative prostatic carcinoma.

The value of digital rectal examination, computerized tomography, magnetic resonance imaging, prostate-specific antigen, transrectal ultrasonography, and systematic-sextant biopsy in the identification of lymph node-positive patients before radical prostatectomy was analyzed in 103 men who had pelvic lymph node dissection, CT had a sensitivity of only 7% and a specificity of 96% in detecting lymph nodes, whereas magnetic resonance imaging had a sensitivity of 50% and a specificity of 100%. To evaluate the use of tumor volume in predicting lymph node metastasis, we counted the number of positive core biopsies and compared the results with the incidence of positive lymph nodes. If fewer than 5 positive core biopsies were considered negative for predicting lymph node metastasis, the sensitivity would be 67% (12 of 18), and the specificity 94% (50 of 53). To investigate tumor volume more precisely, we measured the extent of tumor volume in every biopsy as a percentage of the total biopsy core and added the percentage for the 6 biopsies. The lowest score was 10% (10% prostatic cancer in 1 of 6 cores), the highest score 580% (4 cores with 100% each and 2 with 90% each). The score was analyzed for sensitivity and specificity in predicting lymph node metastasis. If a score of 280% was used as a cutoff point, the sensitivity was 71% (10 of 14) and the specificity 91% (52 of 57). When we include the grading system by multiplying the percentage of tumor volume with tumor grade, the difference between the lymph node-positive state and lymph node-negative state becomes even more readily apparent.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

[Incidental detection of renal cell cancer].

In the present study, a comparative analysis of clinical-prognostic factors in symptomatic and incidentally found renal cell carcinomas is evaluated. A total of 141 patients with renal cell carcinoma were analyzed according to the TNMG system and involvement of the adrenals. More than 50% of surgically treated renal cell carcinomas are found incidentally. Prognostically, this group has advantageous factors.

Adult

[Nerve sparing retroperitoneal lymphadenectomy with intraoperative electrostimulation in patients with nonseminomatous testicular tumors].

Thirteen patients with nonseminomatous testicular germ cell tumours underwent nerve-sparing retroperitoneal lymphadenectomy (RLA) with prospective isolation and preservation of postganglionic sympathetic nerve fibres. In all ten patients with pathological stage I in whom a unilateral nerve-sparing RLA was performed, ejaculation was preserved. In two of three patients with pathological stage IIa who underwent a bilateral RLA with a nerve-sparing technique on one side, ejaculation was also preserved. In nine patients intraoperative electrostimulation of isolated sympathetic nerve fibres was performed employing Brindley's stimulation device. The result was an immediate and reproducible ejaculation in seven patients. Thus electrostimulation of sympathetic nerves may be a useful intraoperative test for the identification of the nerve fibres that need to be protected for ejaculation. Nerve-sparing RLA seems to be superior to modified (unilateral) RLA with regard to preservation of ejaculation.

Adolescent

[Cytomegalovirus diseases following allogenic kidney transplantation].

Lymphotrophic virus infections, especially when they are caused by the cytomegalovirus, are severe complications after allogenic organ transplantation. First infections are mainly caused by donation of CMV-positive organs to CMV negative recipients. The regular incubation time of 30 to 40 days can be significantly shorter after therapeutic application with high dose prednisone or mono/polyclonal antibodies for treatment of rejection. The spectrum of clinical signs of the CMV-disease after organ transplantation can range between serological alterations and the lethal CMV-syndrome. The early recognition of virus-dependent clinical symptoms and the establishment of the diagnosis are the first conditions for the treatment, consisting in reduction of the immunosuppressive medication and application of ganciclovir, a CMV-specific virusstatic agent. The prophylactic application of CMV-hyperimmunoglobulin is discussed controversially. A very important aspect of CMV-disease in the long-term follow-up is the influence of this virus infection on the development of chronic organ rejection, which could be demonstrated in animal studies by application of the Marek virus and which was seen in pathomorphological samples of transplant biopsies. Future diagnostic and therapeutic strategies, which aim at the prolongation of the patient's survival and the transplant function have to consider the influence of virus infections as a severe risk-factor, as the transplantation of CMV-negative organs to CMV-negative recipients is more the exception than the rule.

Adult

[Polychemotherapy in advanced bladder cancer. Practicality and clinical results].

From 1987 to 1990 a consecutive series of 172 patients were treated for advanced bladder cancer, in our clinic, 48 of whom underwent radical cystectomy. In 80 of the remaining 124 patients polychemotherapy was not possible, because of impaired renal function, poor performance status, cardiovascular disease, second malignancy or other problems. There were 11 patients who refused further treatment and 13 patients with tumor restricted to the pelvis who underwent radiochemotherapy. Thus, 20 patients received polychemotherapy with either methotrexate, vinblastine, Adriamycin and cisplatin (M-VAC) or cisplatin, methotrexate and vinblastine (CMV). In 90% of the M-VAC cycles and 34% of the CMV cycles dose reduction was necessary. Median survival was 10 months. We achieved 2 complete responses lasting 6 months and 19 months and 4 partial responses. The authors conclude that patients who cannot undergo radical surgery for bladder cancer are not good candidates for polychemotherapy either. Only patients with measurable remission of the tumour have a longer survival. New regimens with lower toxicity, and especially with lower renal toxicity, must be developed.

Adult

[The diagnosis of female stress incontinence--the value of the clinical examination, anamnesis and urodynamics].

A prospective study was performed between November 1989 and August 1990 to evaluate 57 consecutive female patients with urinary incontinence. The aim of the study was to determine whether the indication for surgery could be based solely on an anamnestic evaluation and clinical examination or was corrected by an additional urodynamic test. The anamnestic evaluation alone correctly identified all patients with the diagnosis of stress incontinence in our group of selected patients referred by other urologists. The additional clinical examination confirmed this diagnosis in all patients and additionally led to diagnosis of a vesicovaginal fistula in one patient. The urodynamic testing confirmed the clinical and anamnestic diagnosis in all patients and identified urge incontinence as the leading symptom in one patient with an unclear diagnosis. Our results show that urodynamic studies are important to establish a precise indication for surgery but are not necessary in every patient. A possible alternative to routine urodynamic testing in female urinary incontinence is its application only when there is an obvious discrepancy between the carefully evaluated history of incontinence and the findings of the clinical examination.

Evaluation Studies as Topic

[The diagnosis of prostatic carcinoma].

Thanks to the combination of high-resolution transrectal ultrasound and the "Biopty-Gun", it has now become possible for the first time to obtain multiple punch biopsies of the prostate, painlessly and with few complications. "Mapping" of the prostate by 6 randomized punch biopsies permits an evaluation of the sensitivity and specificity of such screening procedures as digital rectal examination (DRE), prostate-specific antigen (PSA) and transrectal ultrasound (TRUS). In addition, randomized biopsies provide reliable information about prostatic carcinomas with a significant volume. The indications and efficacy of the various diagnostic methods are discussed in detail.

Aged

Residual tumor discovered in routine second transurethral resection in patients with stage T1 transitional cell carcinoma of the bladder.

When a second transurethral resection was routinely performed 8 to 14 days after the initial transurethral resection in 46 patients for stage T1 bladder tumors residual disease was found in 20 despite the surgical report of complete resection in 40. In only 13 patients was residual tumor noted at repeat resection by the senior urologist performing the operation and residual tumor was confirmed histologically in 10 of them. The extent of the lesion is easily misjudged even by experienced surgeons. Early cystoscopy cannot exclude residual tumor. Residual tumor is an important cause of early recurrence and repeat resection of stage T1 lesions is recommended.

Carcinoma, Transitional Cell

Comparison of 15 monoclonal antibodies against tumor-associated antigens of transitional cell carcinoma of the human bladder.

Quantitative urinary immunocytology with our monoclonal antibody (mab) 486p 3/12 proved to be valuable for diagnostic use in bladder-cancer patients' urine, especially in the followup of patients with superficial bladder carcinoma. To evaluate the use of other monoclonal antibodies in bladder cancer, we compared 15 mabs directed against bladder-tumor-associated antigens from seven research groups in a broad panel of cellular and tissue specimens (bladder tumor, prostatic adenoma, and kidney stone). Quantitative evaluation was done in cytocentrifuged preparations and tissue specimens. None of the 15 mabs was bladder-tumor-specific. All 15 stained normal urothelium to some extent and six stained granulocytes. Each of the 15 seemed to identify a different cellular antigen, as can be clearly demonstrated by the staining pattern of different regions in the normal kidney. The sensitivity of quantitative urinary immunocytology in bladder-tumor patients can be improved by using a panel, rather than one mab in bladder-tumor patients, but specificity decreases simultaneously. A main reason for the poor specificity of quantitative urinary immunocytology with all 15 mabs is that false-positive results are obtained with all mabs in kidney-stone patients. Our quantitative urinary immunocytology method is a general tool for the diagnostic use of all mabs in bladder-tumor patients. Mabs that have a high sensitivity might be useful in the followup of patients with superficial bladder carcinoma. None of the 15 mabs (because of their poor specificity) seems to be helpful in quantitative urinary immunocytology for screening a population for bladder carcinoma.

Antibodies, Monoclonal

Sensitivity of urinary quantitative immunocytology with monoclonal antibody 486 P3/12 in 241 unselected patients with bladder carcinoma.

We investigated the sensitivity of quantitative immunocytology with our monoclonal antibody 486 P3/12 in 241 unselected patients with transitional cell carcinoma. Immunocytology yielded a sensitivity of 91.8%, 89.4% and 92.9% for grade 1, 2 and 3 tumors, respectively. Standard cytology was positive in 59.2%, 63.8% and 84.7%, respectively. Deoxyribonucleic acid flow cytometry, used in the first 69 patients, was positive in only 27.7%, 48.6% and 57.1%, respectively.

Antibodies, Monoclonal