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Biomedical subjects

K Kahn

Publications and source records attributed to K Kahn.

At least 37 records · Page 2Linked to original sources

Near infra-red interactance for nutritional assessment of dialysis patients.

BACKGROUND: Malnutrition is a common problem in dialysis patients and may affect up to one-third of patients. Near-infrared interactance (NIR) is a novel approach to estimate body composition and per cent total body fat. METHODS: We used near-infrared interactance (Futrex 5000) to estimate the body composition including body fat percentage, as well as subjective global assessment (SGA), anthropometric measurements including mid-arm circumference (MAC), triceps and biceps skinfold thickness, calculated mid-arm muscle circumference (MAMC), body mass index (BMI), and laboratory values. NIR score, SGA assessment and anthropometric parameters were measured shortly after the end of a dialysis session. NIR measurement was made by placing a Futrex sensor on the nonaccess upper arm for several seconds. Serum albumin, transferrin (reflected by total iron binding capacity), and total cholesterol concentrations were performed as well. RESULTS: Thirty-four patients (20 men and 14 women) were selected from a pool of 120 haemodialysis patients. Their ages ranged from 26 to 86 years (58+/-14 years). Time on dialysis ranged from 8 months to 19 years (4.5+/-4.6 years). NIR scores were significantly different in three SGA groups: (A) well-nourished, 32.5+/-6.9%; (B) mildly to moderately malnourished, 29.2+/-5.3%; and (C) severely malnourished, 23.2+/-10.2% (P<0.001). Pearson correlation coefficients (r) between the NIR score and nutritionally relevant parameters were significant (P<0.001) for body mass index (r=+0.81), mid-arm circumference (r=+0.74), triceps skin fold (r=+0.54), biceps skin fold (r=+0.55), and mid-arm muscle circumference (r=+0.54). An inverse correlation was also found between NIR and years dialysed (r=-0.49, P=0.004), denoting a lesser body fat percentage according to NIR for patients dialysed longer. NIR was correlated with serum transferrin (r=+0.41, P=0.016) and cholesterol (r=+0.39, P=0.022) and marginally with serum albumin (r=+0.29, P=0.097). CONCLUSIONS: We conclude that NIR, which can be performed within seconds, may serve as an objective indicator of nutritional status in haemodialysis patients. More comparative and longitudinal studies are needed to confirm the validity of NIR measurements in nutritional evaluation of dialysis patients.

Adipose Tissue↗

Stroke in rural South Africa--contributing to the little known about a big problem.

OBJECTIVES: To describe the extent of mortality from cerebrovascular accident (CVA) in a rural South African population. DESIGN: Annual demographic and health surveillance with verbal autopsy of all deaths, 1992-1995. OUTCOME MEASURES: Stroke mortality rate by age and sex. RESULTS: Stroke mortality increased with age and is higher in men than women over age 35. Proportionate mortality ratio from CVA: 10.3% of deaths in the 35-64-year age group. CONCLUSION: Cerebrovascular disease is an important cause of death in South Africa's rural north-east. Community-based research is needed to inform policy and practice.

Adult↗

The Agincourt demographic and health study--site description, baseline findings and implications.

OBJECTIVES: To present baseline results from first-phase demographic and health surveillance in the Agincourt field site, Bushbuckridge. To contrast findings with international data, and comment on their relevance to health development. DESIGN: Multi-round, prospective community-based study. Baseline census, 1992. SETTING: A subdistrict in South Africa's rural north-east, adjacent to the border with Mozambique. SUBJECTS: Entire population of the Agincourt subdistrict. OUTCOME MEASURES: Baseline variables for each resident included age, sex, months spent at home during 1991, mother alive/dead, highest educational standard achieved, and refugee status. A full demographic profile was constructed. RESULTS: In 1992 the subdistrict contained 57,609 persons, 26.4% of whom were Mozambican, with a population density of 148 persons per km2. Forty-four per cent were under 15 years of age, and the dependency ratio was 93%. Fertility was declining, along with a moderate decline in adult female mortality. The approximate total fertility rate was 4.0; teenage parenting was common and almost 40% of 19-year-olds had at least one child. Over 60% of men and 14% of women in the 30-49-year age group were migrants, resulting in a high proportion of single-parent households. Despite improvements, most children experienced delays in reaching primary school, and less than half made the transition to secondary school. Educational levels among Mozambican children were lower than those of local children. CONCLUSIONS: Agincourt contains a complex mix of communities comprising migrant workers, Mozambicans and a more stable permanent population. The area shares features with sub-Saharan Africa, although the mortality and fertility transitions have progressed further. Reliable, local information is essential for managing decentralised health systems.

Adult↗

Spectroscopic characterization of intermediates in the urate oxidase reaction.

The oxidation of urate catalyzed by soybean urate oxidase was studied under single-turnover conditions using stopped-flow absorbance and fluorescence spectrophotometry. Two discrete enzyme-bound intermediates were observed; the first intermediate to form had an absorbance maximum at 295 nm and was assigned to a urate dianion species; the second intermediate had an absorbance maximum at 298 nm and is believed to be urate hydroperoxide. These data are consistent with a catalytic mechanism that involves formation of urate hydroperoxide from O2 and the urate dianion, collapse of the peroxide to form dehydrourate, and hydration of dehydrourate to form the observed product, 5-hydroxyisourate. The rate of formation of the first intermediate was too fast to measure accurately at 20 degreesC; the second intermediate formed with a rate constant of 32 s-1 and decayed with a rate constant of 6.6 s-1. The product of the reaction, 5-hydroxyisourate, is fluorescent, and its release from the active site occurred with a rate constant of 31 s-1.

Energy Transfer↗

Limulus amebocyte lysate assay for detection of endotoxin in patients with sepsis syndrome. AMCC Sepsis Project Working Group.

Clinical predictions alone are insufficiently accurate to identify patients with specific types of bloodstream infection; laboratory assays might improve such predictions. Therefore, we performed a prospective cohort study of 356 episodes of sepsis syndrome and did Limulus amebocyte lysate (LAL) assays for endotoxin. The main outcome measures were bacteremia and infection due to gram-negative organisms; other types of infection were secondary outcomes. Assays were defined as positive if the result was > or = 0.4 enzyme-linked immunosorbent assay units per milliliter. There were positive assays in 119 (33%) of 356 episodes. Assay positivity correlated with the presence of fungal bloodstream infection (P < .003) but correlated negatively with the presence of gram-negative organisms in the bloodstream (P = .04). A trend toward higher rates of mortality in the LAL assay-positive episodes was no longer present after adjusting for severity. Thus, results of LAL assay did not correlate with the presence of bacteremia due to gram-negative organisms or with mortality after adjusting for severity but did correlate with the presence of fungal bloodstream infection.

Bacteremia↗

Cyanobacterial transposons Tn5469 and Tn5541 represent a novel noncomposite transposon family.

A noncomposite transposon, designated Tn5541, was isolated from strain Fd33 of the filamentous cyanobacterium Fremyella diplosiphon UTEX 481. Sequence analysis showed that Tn5541 is structurally and genetically very similar to Tn5469, which is also endogenous to F. diplosiphon. Both Tn5469 and Tn5541 encode homologous forms of an unusual composite transposase and a protein of unknown function. DNA hybridization analysis showed that like Tn5469, Tn5541 was not widely distributed among cyanobacterial genera. A similar analysis showed that Tn5469 and Tn5541 were equally limited to and present as multiple genomic copies in three of six distinct strains comprising the Tolypothrix 1 cluster of heterocyst-forming filamentous cyanobacteria. These and other distinguishing features suggest that Tn5469 and Tn5541 represent a novel noncomposite transposon family.

Amino Acid Sequence↗

Kinetic mechanism and cofactor content of soybean root nodule urate oxidase.

The kinetic mechanism of urate oxidase isolated from soybean root nodules has been determined by initial velocity kinetic studies monitoring oxygen uptake, in order to avoid potential artifacts in the spectrophotometric assay which arise from absorbance due to unidentified products of the enzymatic reaction. Urate and O2 bind to the enzyme sequentially; xanthine is a competitive inhibitor versus urate and a noncompetitive inhibitor versus O2, which suggests that urate binds to the enzyme before O2. This kinetic mechanism was confirmed by an 18O isotope-trapping experiment, which demonstrated that O2 does not bind productively to the enzyme in the absence of urate. The pH dependence of V and (V/K)urate reveal the presence of an ionizable residue on the enzyme with a pK of approximately 6.2, which must be unprotonated for the catalytic reaction to occur. The (V/K)O2 profile is pH independent; these data are accomodated by a model in which a unimolecular step intervenes between the binding of urate and O2. The pKi profile for 9-methylurate, a competitive inhibitor versus urate, is pH independent, confirming that the protonation state of the ionizable residue is not important for binding. The pKi profile for xanthine defines a pK of 7.4, which demonstrates that the monoanion of xanthine binds to the enzyme; by analogy, the monoanion of urate is predicted to be the substrate. The four isomeric N-methylurates were examined as potential inhibitors of urate oxidase. Only 9-methylurate showed significant inhibition suggesting that ionization at N9 of urate is not required for binding; it is proposed that the N3-deprotonated urate monoanion is the species which binds to urate oxidase. The gene encoding urate oxidase was cloned from soybeans and expressed in Escherichia coli. The metal content of the recombinant enzyme was examined by inductively coupled argon plasma emission spectroscopy, and only trace quantities of copper were found. The molecular mass of the protein was determined by MALDI-TOF mass spectrometry and found to be 35,059.8 Da. The calculated molecular mass of urate oxidase is 35,052 Da; therefore, these data suggest that there is no covalently bound cofactor in urate oxidase.

Cloning, Molecular↗

What is the role of timing in the surgical and rehabilitative care of community-dwelling older persons with acute hip fracture?

OBJECTIVE: To determine the relationship of surgical repair of acute hip fracture within 2 days of hospital admission, followed by more than 5 sessions per week of physical and occupational therapy (PT/OT), to outcomes after acute hip fracture. DESIGN: Comparison of hip fracture outcomes via secondary analysis of data obtained by retrospective medical record review according to timing of surgical repair and frequency of PT/OT, adjusted for patient, medical care, and hospital characteristics. SAMPLE: The study included the medical records of 1880 elderly Medicare recipients admitted from the community to 284 acute care hospitals in 5 states during 1981 and 1982 or 1985 and 1986 with a primary diagnosis of acute hip fracture who underwent surgical repair and received PT/OT. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The postoperative day when ambulation first occurred, the length of hospital stay, and return to the community. RESULTS: Earlier surgical repair was associated with a shorter length of hospital stay (5 fewer days, P < .001) without a statistically significant increase in medical complications. High frequency PT/OT was associated with earlier ambulation (odds ratio [OR], 1.76; 95% confidence limits [CL], 1.50, 2.07). Patients who ambulated earlier [corrected] had shorter lengths of stay (6.5 fewer days, P < .001), were more likely to return to the community (OR, 1.45; 95% CL, 1.16, 1.81), and had better 6-month survival (OR, 2.8; 95% CL, 2.06, 3.88), and patients younger than 85 years had fewer in-hospital complications (11% vs 4%, P < .001). CONCLUSION: Surgical repair within the first 2 days of hospitalization and more than 5 PT/OT sessions per week were associated with better health outcomes in a nationally representative sample of elderly patients with hip fracture.

Acute Disease↗

Predicting bacteremia in patients with sepsis syndrome. Academic Medical Center Consortium Sepsis Project Working Group.

The goal of this study was to develop and validate clinical prediction rules for bacteremia and subtypes of bacteremia in patients with sepsis syndrome. Thus, a prospective cohort study, including a stratified random sample of 1342 episodes of sepsis syndrome, was done in eight academic tertiary care hospitals. The derivation set included 881 episodes, and the validation set included 461. Main outcome measures were bacteremia caused by any organism, gram-negative rods, gram-positive cocci, and fungal bloodstream infection. The spread in probability between low- and high-risk groups in the derivation sets was from 14.5% to 60.6% for bacteremia of any type, from 9.8% to 32.8% for gram-positive bacteremia, from 5.3% to 41.9% for gram-negative bacteremia, and from 0.6% to 26.1% for fungemia. Because the model for gram-positive bacteremia performed poorly, a model predicting Staphylococcus aureus bacteremia was developed; it performed better, with a low- to high-risk spread of from 2.6% to 21.0%. The prediction models allow stratification of patients according to risk of bloodstream infections; their clinical utility remains to be demonstrated.

Adult↗

rpbA controls transcription of the constitutive phycocyanin gene set in Fremyella diplosiphon.

Three gene sets encode alpha and beta subunits of the phycobiliprotein phycocyanin (PC) in the filamentous cyanobacterium Fremyella diplosiphon. The cpcB1A1 set (encodes PC1) is constitutively expressed, whereas the cpcB2A2 set (encodes PC2) is expressed only in red light and the cpcB3A3 set (encodes PC3) is expressed only during sulfur-limited growth. Primary pigment mutant strain FdBM1 is characterized by elevated levels of PC. DNA hybridization analysis showed that like many pigment mutants in our strain collection, strain FdBM1 harbors an extra genomic copy of endogenous transposon Tn5469. By direct cloning from FdBM1 genomic DNA, the extra copy of Tn5469 was localized to an open reading frame, which we have designated the rpbA gene. Complementation experiments correlated rpbA activity to the phenotype of strain FdBM1. The predicted RpbA protein contains two regions resembling the characterized helix-turn-helix motif which is involved in DNA recognition by many bacterial and phage transcription regulator proteins. RNA hybridization analysis showed that relative to the parental strain Fd33, the level of transcripts from cpcB1A1, but not cpcB2A2 or cpcB3A3, was significantly elevated in strain FdBM1. Introduction of the intact rpbA gene into strain FdBM1 restored the cpcB1A1 transcript level to that of strain Fd33. These results suggest that the rpbA gene product functions in controlling constitutive transcription from the cpcB1A1 gene set, possibly as a DNA-binding transcriptional repressor element.

Amino Acid Sequence↗

A role for cpeYZ in cyanobacterial phycoerythrin biosynthesis.

Pigment mutant strain FdR1 of the filamentous cyanobacterium Fremyella diplosiphon is characterized by constitutive synthesis of the phycobiliprotein phycoerythrin due to insertional inactivation of the rcaC regulatory gene by endogenous transposon Tn5469. Whereas the parental strain Fd33 harbors five genomic copies of Tn5469, cells of strain FdR1 harbor six genomic copies of the element; the sixth copy in FdR1 is localized to the rcaC gene. Electroporation of FdR1 cells yielded secondary pigment mutant strains FdR1E1 and FdR1E4, which identically exhibited the FdR1 phenotype with significantly reduced levels of phycoerythrin. In both FdR1E1 and FdR1E4, a seventh genomic copy of Tn5469 was localized to the cpeY gene of the sequenced but phenotypically uncharacterized cpeYZ gene set. This gene set is located downstream of the cpeBA operon which encodes the alpha and beta subunits of phycoerythrin. Complementation experiments correlated cpeYZ activity to the phenotype of strains FdR1E1 and FdR1E4. The predicted CpeY and CpeZ proteins share significant sequence identity with the products of homologous cpeY and cpeZ genes reported for Pseudanabaena sp. strain PCC 7409 and Synechococcus sp. strain WH 8020, both of which synthesize phycoerythrin. The CpeY and CpeZ proteins belong to a family of structurally related cyanobacterial proteins that includes the subunits of the CpcE/CpcF phycocyanin alpha-subunit lyase of Synechococcus sp. strain PCC 7002 and the subunits of the PecE/PecF phycoerythrocyanin alpha-subunit lyase of Anabaena sp. strain PCC 7120. Phycobilisomes isolated from mutant strains FdR1E1 and FdR1E4 contained equal amounts of chromophorylated alpha and beta subunits of phycoerythrin at 46% of the levels of the parental strain FdR1. These results suggest that the cpeYZ gene products function in phycoerythrin synthesis, possibly as a lyase involved in the attachment of phycoerythrobilin to the alpha or beta subunit.

Amino Acid Sequence↗

Rehabilitation after hip fracture--equal opportunity for all?

OBJECTIVES: To determine whether factors unrelated to clinical appropriateness affect use of physical and occupational therapy (PT/OT) in elderly Medicare patients with acute hip fracture. DESIGN: Bivariate and multivariate analysis of detailed clinical data retrospectively gathered from medical records and of nonclinical variables obtained through linkage with the American Hospital Association data base. SETTING: 297 randomly selected hospitals from 5 states. PATIENTS: 2,762 elderly Medicare patients hospitalized with a primary diagnosis of acute hip fracture who were hospitalized during 1981-1982 or 1985-1986. INTERVENTION: Observational study. MAIN OUTCOME MEASURES: Initiation and intensity of PT/OT while in the acute hospital. RESULTS: We found evidence that factors not relevant to clinical appropriateness, such as race, hospital size, and state, significantly affect whether patients receive any PT/OT after acute fracture, as well as the intensity of PT/OT. For example, after controlling for patient clinical characteristics, we found that 63% of African-American patients received low-intensity PT/OT in comparison to 43% among non-African-American, and we found threefold differences among states both in initiation of PT/OT and in the intensity of its use. Overall, clinical characteristics had relatively greater influence on whether patients started PT/OT, whereas factors not relevant to clinical appropriateness had relatively greater influence on how much rehabilitation was provided. CONCLUSION: There are significant disparities in use of rehabilitation after hip fracture, only partially explained by patient clinical characteristics. Factors without obvious relevance to the clinical appropriateness of PT/OT exert a significant influence on use of rehabilitation services, particularly on the intensity of their use.

Black or African American↗

Quality of care for depressed elderly patients hospitalized in the specialty psychiatric units or general medical wards.

BACKGROUND: Studies to assess quality of care have become increasingly important for research and policy purposes. OBJECTIVE: To evaluate the difference in quality of care between elderly depressed patients hospitalized in specialty psychiatric units and those hospitalized in general medical wards. METHODS: We reviewed retrospectively the medical charts of 2746 patients with depression hospitalized in 297 general medical hospitals in five different states. Quality of care was assessed by clinical review of explicit and implicit information contained in the medical records of patients in specialty psychiatric units (n = 1295) and general medical wards (n = 1451). We also used other secondary data sources to determine postdischarge outcomes. RESULTS: We found that (1) a higher percentage of admissions on the psychiatric units were considered appropriate, (2) overall psychological assessment was better on the psychiatric unit, (3) patients were more likely to receive psychological services on the psychiatric wards but more likely to receive traditional general medical services on medical wards, (4) there were more inpatient general medical complications on the psychiatric wards, and (5) implicit measures of clinical status at discharge were better for those on the psychiatric unit. CONCLUSIONS: Although limited by reliance on medical record abstraction and a retrospective study design, our data indicate that the quality of care for the psychological aspects of the treatment of depression may be better on psychiatric units, while the quality of general medical components of care may be better on general medical wards.

Aged↗

A meta-analysis of infant outcomes after breech delivery.

OBJECTIVE: To estimate the risks of neonatal morbidity and mortality associated with a trial of labor and with elective cesarean for the term breech infant. DATA SOURCES: Using the terms "breech," "malpresentation," and "external cephalic version," we used the MEDLINE and Health Planning and Administration data bases to search the English-language literature from January 1981 to June 1993. The search was supplemented with a review of the reference lists of key articles and text chapters. METHODS OF STUDY SELECTION: We included randomized trials or cohort studies that specified selection criteria for a vaginal delivery, provided detailed outcome data, and allowed for analysis by intended mode of delivery. DATA EXTRACTION AND SYNTHESIS: Nine studies met the inclusion criteria. We pooled the weighted results from these studies to estimate the risks of birth injuries and perinatal death, and the risk differences between trial of labor and no trial of labor groups. The pooled risk for any injury was 1.00% after a trial of labor and 0.09% after elective cesarean. For any injury or death, the risk was 1.23% after a trial of labor and 0.09% after elective cesarean. The risk differences for injury and injury or death were 0.89 and 1.10%, respectively. These are significantly different from zero, suggesting an increased risk of injury and injury or death after a trial of labor. CONCLUSION: When management decisions are made, the potential increased risk of neonatal morbidity after a trial of labor should be considered along with the increased maternal risk from cesarean delivery.

Birth Injuries↗

Characterization of transposon Tn5469 from the cyanobacterium Fremyella diplosiphon.

A transposon, designated Tn5469, was isolated from mutant strain FdR1 of the filamentous cyanobacterium Fremyella diplosiphon following its insertion into the rcaC gene. Tn5469 is a 4,904-bp noncomposite transposon with 25-bp near-perfect terminal inverted repeats and has three tandemly arranged, slightly overlapping potential open reading frames (ORFs) encoding proteins of 104.6 kDa (909 residues), 42.5 kDa (375 residues), and 31.9 kDa (272 residues). Insertion of Tn5469 into the rcaC gene in strain FdR1 generated a duplicate 5-bp target sequence. On the basis of amino acid sequence identifies, the largest ORF, designated tnpA, is predicted to encode a composite transposase protein. A 230-residue domain near the amino terminus of the TnpA protein has 15.4% amino acid sequence identity with a corresponding domain for the putative transposase encoded by Lactococcus lactis insertion sequence S1 (ISS1). In addition, the sequence for the carboxyl-terminal 600 residues of the TnpA protein is 20.0% identical to that for the TniA transposase encoded by Tn5090 on Klebsiella aerogenes plasmid R751. The TnpA and TniA proteins contain the D,D(35)E motif characteristic of a recently defined superfamily consisting of bacterial transposases and integrase proteins of eukaryotic retroelements and retrotransposons. The two remaining ORFs on Tn5469 encode proteins of unknown function. Southern blot analysis showed that wild-type F. diplosiphon harbors five genomic copies of Tn5469. In comparison, mutant strain FdR1 harbors an extra genomic copy of Tn5469 which was localized to the inactivated rcaC gene. Among five morphologically distinct cyanobacterial strains examined, none was found to contain genomic sequences homologous to Tn5469.

Amino Acid Sequence↗

Effects of Medicare's prospective payment system on service use by depressed elderly inpatients.

OBJECTIVE: To determine the effects of Medicare's prospective payment system (PPS) on hospital care, changes in length of stay and intensity of clinical services received by 2,746 depressed elderly patients in 297 acute care general medical hospitals were studied. METHODS: A pre-post design was used, and differences in sickness at admission were controlled for. Data on length of stay and use of specific clinical services were obtained from the medical record using a medical record abstraction form. Care provided on units exempt from PPS was compared with care provided in nonexempt units. RESULTS: After implementation of PPS, the average length of stay fell by up to three days within the different types of acute care settings studied, but this decline was partially offset by proportionately more admissions to psychiatric units, which had longer lengths of stay. Intensity of clinical services increased after PPS implementation, especially in nonexempt psychiatric units. CONCLUSION: Despite financial incentives for hospitals to reduce clinical services under PPS, its implementation was not associated with a marked decline in length of stay, when averaged across all treatment settings, and was associated with an increase in the intensity of many clinical services used by depressed elderly patients in general hospitals.

Aged↗

Intravesical RTNF therapy of superficial bladder cancer. A phase I study of recombinant tumor necrosis factor administered intravesically to patients with superficial bladder cancer.

OBJECTIVE: A phase I/II study was initiated in patients with refractory localized superficial bladder cancer to establish the tolerance and toxicity of recombinant tumor necrosis factor (rTNF) given intravesically. A preliminary evaluation of patient responses to therapy was noted; however, the small trial size precluded extensive statistical assessment of the data. SETTING: A large teaching hospital, where patients were referred for treatment of recurrent superficial bladder cancer. PATIENTS: A referred sample consisting of 16 patients with a primary diagnosis of histologically documented superficial bladder cancer (stage Ta, T1, TIS), refractory to at least 1 previous therapy, were entered on the study. Eligibility criteria Included: 1) cystoscopy in last 42 days, 2) no contraindications to chemotherapy, 3) life expectancy of 3 months, and 4) informed consent. INTERVENTION: Patients were given rTNF intravesically twice weekly for 4 weeks at doses ranging from 10 to 500 mcg/m2. MAIN OUTCOME MEASURES: Adverse effects were recorded as minimal, moderate, severe, or intolerable. Patient responses were measured on the basis of clinical and laboratory signs, symptoms, and tumor size. RESULTS: We observed no severe or intolerable toxicities associated with the treatment. Two patients had complete responses, 9 had partial responses, 2 had minor responses, 1 was diagnosed with progressive disease, and 2 were not evaluated. No maximum tolerated dose was determined because rTNF was well tolerated at a maximum dose of 500 mcg/m2. CONCLUSIONS: The study drug rTNF was well tolerated up to a dose of 500 mcg/m2 and exhibited some antitumor effects against transitional cell carcinoma, but a biologically active dose was not determined. On the basis of this trial, further studies of intravesical treatment of superficial bladder cancer with rTNF appear warranted.

Administration, Intravesical↗