University Hospital Financial Status Does Not Influence Subjective Perception of General Surgery Residents on Training Adequacy.

BACKGROUND: Surgical residency training is a complex and costly task. Hospital economic health is dependent on different variables, but it is especially linked to the country macroeconomics that may be extremely fluctuating, especially in underdeveloped countries. This study analyzed the correlation between a single-center university hospital financial status and subjective perception of general surgery residents on program support and adequacy. METHODS: We surveyed former residents that started general surgery residency program in a tertiary university hospital between 1999 and 2017. Individuals answered a questionnaire about the perception of the influence of the hospital´s financial status on training. Hospital´s financial status was estimated yearly by the current liquidity ratio (CLR) that measures whether or not a company has enough resources to meet its short-term obligations. RESULTS: Two hundred and fifty-seven (96%) were still in surgical practice; 242 (93%) were satisfied with their residency training; 210 (78%) believed training was affected by financial status; 183 (68%) believed they were prepared for independent practice; 180 (67%) practiced in an academic environment; 146 (54%) felt the need to complete specialty training beyond residency; and 56 (21%) believed hospital financial status was adequate. The rate of positive or negative answers did not correlate with the current liquidity ratio, except for the need to complete specialty training that was indirectly related to CLR. CONCLUSIONS: University hospital financial status did not influence subjective perception of general surgery residents on training, program support and adequacy.

Prevalence and risk factors of domestic violence in women attending the National Guard Primary Health Care Centers in the Western Region, Saudi Arabia, 2018.

BACKGROUND: Domestic violence (DV) is considered a public health issue in Saudi Arabia as well as a violation of a fundamental human right. DV causes many acute and chronic physical and mental health consequences. Cultural taboos and lack of awareness regarding the appropriate support services can increase the number of cases annually. The objective of the study was to assess the prevalence and risk factors of DV in women attending the National Guard Primary Health Care Clinics in the Western Region of Saudi Arabia. METHODS: A cross-sectional study was conducted with patients attending five Primary Health Care Centers in Jeddah from August 2017 to February 2018. A convenient sampling method was used. In total, 1845 participants were invited to complete a self-report validated Arabic version of the Norvold Domestic Abuse Questionnaire (NORAQ) to determine the prevalence and risk factors of DV. All women between 18 and 65 years who met the inclusion criteria were included. The data were analyzed using SPSS (Statistical Package Social Sciences) version 24.0. RESULTS: The lifetime prevalence of DV in the study sample was 33.24%, with psychological abuse the most prevalent (48.47%), followed by physical abuse (34.77%) and sexual abuse (16.75%). A small proportion (4.1%) suffered from all three types of abuse. Risk factors for being a victim of abuse include being single or divorced, having a postgraduate level of education, employed, and being financially independent of the husband. CONCLUSION: DV is prevalent in Saudi Arabia. Modernization has shifted the risk factors, identifying the risk factors and victim characteristics would support the development and implementation of preventive and screening programs to facilitate the early identification of cases as well as the initiation of empowerment programs for Saudi women.

Post-treatment endodontic pain following occlusal reduction in mandibular posterior teeth with symptomatic irreversible pulpitis and sensitivity to percussion: a single-centre randomized controlled trial.

AIM: This randomized, prospective, controlled trial assessed the effect of occlusal reduction on post-treatment endodontic pain and medication intake following root canal treatment of mandibular posterior teeth with symptomatic irreversible pulpitis with sensitivity to percussion treated in two visits. METHODOLOGY: Three hundred and eight patients were randomly assigned into two equal groups according to whether occlusal reduction was done or not (n = 154). For all patients, root canal treatment was carried out in two visits without intracanal medication. Patients assessed their pain using the 0-10 numerical rating scale (NRS) 6, 12, 24 and 48 h after the first visit (post-instrumentation) and 6 and 12 h following root canal filling (post-obturation). Patients, also, recorded their medication intake (sham or analgesic), post-instrumentation and post-obturation; patients initially received a sham capsule, but, if pain persisted, an analgesic was prescribed. Data were analysed using Mann-Whitney U-test, Friedman's test, Wilcoxon's rank test and chi-square (χ2 ) test. The relative risk (RR) and its 95% confidence interval (CI) were calculated for binary data. RESULTS: Occlusal reduction was associated with lower pain intensity than no occlusal reduction at 12 and 24 h post-instrumentation (P < 0.05). Pain intensity significantly and gradually decreased with both groups at all post-instrumentation and post-obturation time-points compared to preoperative pain (P < 0.05). The RR of moderate-to-severe pain was 0.61 (95% CI: 0.41, 0.91) 12 h post-instrumentation, and the RR of pain incidence, regardless of its level, was 0.75 (95% CI: 0.61, 0.92) 24 h post-instrumentation. There was no significant difference in medication intake (sham or analgesic) between groups (P > 0.05). CONCLUSIONS: Occlusal reduction was effective in reducing the intensity of postoperative pain 12 h and 24 h after root canal instrumentation in the first visit in patients with symptomatic irreversible pulpitis with sensitivity to percussion. Occlusal reduction lowered the risk of moderate-to-severe pain by about 40% 12 h post-instrumentation and the overall risk of pain by 25% 24 h post-instrumentation; yet, it did not affect medication intake.

Clinical characteristics of women diagnosed with carcinoma who tested positive for cervical and anal high-risk human papillomavirus DNA and E6 RNA.

High-risk human papillomavirus (hrHPV) is an essential cause of cervical carcinoma and is also strongly related to anal cancer development. The hrHPV E6 oncoprotein plays a major role in carcinogenesis. We aimed to evaluate the frequency of hrHPV DNA and E6 oncoprotein in the anuses of women with cervical carcinoma. We analyzed 117 women with cervical cancer and 103 controls for hrHPV and the E6 oncogene. Positive test results for a cervical carcinoma included 66.7 % with hrHPV-16 and 7.7 % with hrHPV-18. One case tested positive for both HPV variants (0.9 %). The samples from the anal canal were positive for HPV-16 in 59.8 % of the cases. Simultaneous presence of HPV in the cervix and anal canal was found in 53.8 % of the cases. Regarding expression of E6 RNA, positivity for HPV-16 in the anal canal was found in 21.2 % of the cases, positivity for HPV-16 in the cervix was found in 75.0 %, and positivity for HPV-18 in the cervix was found in 1.9 %. E6 expression in both the cervix and anal canal was found in 19.2 % of the cases. In the controls, 1 % tested positive for HPV-16 and 0 % for HPV-18. Anal samples from the controls showed a hrHPV frequency of 4.9 % (only HPV16). The presence of hrHPV in the anal canal of women with cervical cancer was detected at a high frequency. We also detected E6 RNA expression in the anal canal of women with cervical cancer, suggesting that these women are at risk for anal hrHPV infection.

Perspectives of tele-orthodontics in the COVID-19 emergency and as a future tool in daily practice.

AIM: The aim of our study was to explain how tele-orthodontics represents the only way to perform orthodontics during a period of restriction as the one subsequent to COVID-19 emergencies: To do this, we report a case study and explore the proposal of a model of tele-orthodontics, considering the advantages of this modality in the immediate post-emergency phase and in the future daily practice. MATERIALS AND METHODS: Study design: Our study involves 30 patients, who had undergone different orthodontic therapies in a traditional way, and that the clinician continued to follow by means of tele-orthodontics. Given the obvious limitations of tele-practice, a comparison with patients who did not undergo any follow-up or underwent only in-office follow-ups could not be possible. The communication tools used in our study and proposed in our model of tele-orthodontics are videocalls, dedicated applications, intraoral and extraoral photos taken by the patients and instant messaging. RESULTS: Tele-orthodontics allowed to perform some orthodontic follow-ups with less chairside time, reduced time spent by the patients in the dental office from up to 45 min, less risk of infection, fewer to no missed appointments, specific troubleshooting solutions, and more follow-ups with odontophobic patients. Overall, tele-orthodontics balanced the disadvantages of less personal contacts and in-office visits. CONCLUSIONS: The need to respect safety distance and the fears patients have about the risk of infection make tele-orthodontics a fundamental tool during a pandemic lockdown and in its immediate post-emergency phase. Tele-orthodontics demonstrated to be a viable tool to continue at least some orthodontic care in times of emergency, but it may be considered an appropriate solution and addition even in normal times to ease therapy demands for both the orthodontist and the patient, while reducing time and money spent, without an excessive decrease in orthodontic quality.

Serum C-reactive protein is a useful marker to exclude anastomotic leakage after colorectal surgery.

Anastomotic leakage is a complication of colorectal surgery. C-reactive protein (CRP) is an acute-phase marker that can indicate surgical complications. We determined whether serum CRP levels in patients who had undergone colorectal surgery can be used to exclude the presence of anastomotic leakage and allow safe early discharge. We included 90 patients who underwent colorectal surgery with primary anastomosis. Serum CRP levels were measured retrospectively on postoperative days (PODs) 1 - 7. Patients with anastomotic leakage (n = 11) were compared to those without leakage (n = 79). We statistically analysed data and plotted receiver operating characteristic curves. The incidence of anastomotic leakage was 12.2%. Diagnoses were made on PODs 3 - 24. The overall mortality rate was 3.3% (18.2% in the leakage group, 1.3% in the non-leakage group; P < 0.045). CRP levels were most accurate on POD 4, with a cutoff level of 180 mg/L, showing an area under the curve of 0.821 and a negative predictive value of 97.2%. Lower CRP levels after POD 2 and levels <180 mg/L on POD 4 may indicate the absence of anastomotic leakage and may allow safe discharge of patients who had undergone colorectal surgery with primary anastomosis.

Metalloproteinase-1, metalloproteinase-7, and p53 immunoexpression and their correlation with clinicopathological prognostic factors in colorectal adenocarcinoma.

AIM: The aim of this study was to analyze the immunoexpression of metalloproteinase-1, metalloproteinase-7, and p53 in colorectal adenocarcinoma, and to correlate this with clinicopathological prognostic factors. MATERIAL AND METHODS: Formalin-fixed paraffin-embedded tumor tissue from 82 patients was analyzed by means of immunohistochemistry, using the streptavidin-biotin method and the tissue microarray technique. Protein tissue expression was correlated with the variables of the degree of cell differentiation, stage, relapse-free survival, recurrence, survival, and specific mortality. RESULTS: All of the tumors were positive for metalloproteinase-1, while 50 (61%) were positive for metalloproteinase-7, and 32 (39%) were negative for the latter. For p53, 70 (85.4%) of the tumors were positive and 12 (14.6%) were negative. Correlation of the marker expressions separately and in conjunction did not produce any statistically significant data. CONCLUSION: The immunoexpression of metalloproteinase-1, metalloproteinase-7, and p53 did not correlate with recurrence, mortality, relapse-free survival, survival, degree of cell differentiation, or staging of colorectal cancer.

Study on the prevalence of human papillomavirus in the anal canal of women with cervical intraepithelial neoplasia grade III.

OBJECTIVE: The objective was to evaluate the prevalence of human papillomavirus (HPV) in the anal canal of women with cervical intraepithelial neoplasia (CIN) grade III. STUDY DESIGN: Two groups were compared. In group I (study group), 40 women who had undergone cervical biopsy with a histopathological result indicating CIN III were evaluated. Group II (control) consisted of 40 women with normal results from colposcopic examination and colpocytological tests. The women in group I who presented high-grade neoplasia in colpocytological tests underwent collection of material from the uterine cervix and anal canal for investigating HPV DNA using the Hybrid Capture II technique. Colposcopy and cervical biopsy were then performed. If CIN III was confirmed, HPV DNA was investigated in the material collected. In group II, colpocytological tests and colposcopy were performed and, if normal, the procedure was similar to that followed for group I, except that no biopsy was performed. RESULTS: In group I, 39 women (97.5%) were positive for HPV in the uterine cervix and 14 women (35%) in the anal canal. In group II, only four women (10%) had a positive HPV test, for both the uterine cervix and the anal canal. CONCLUSIONS: The prevalence of HPV in the anal canal of the women with CIN III was greater than in the women without CIN III.

Value of carcinoembryonic antigen and cytokeratins for the detection of recurrent disease following curative resection of colorectal cancer.

AIM: To evaluate the efficacy of postoperative serial assay of carcinoembryonic antigen (CEA) and cytokeratins for the detection of recurrent disease in patients with colorectal adenocarcinoma after radical surgery. METHODS: Between 1993 and 2000, 120 patients with colorectal adenocarcinoma underwent radical surgery in the Department of Surgical Gastroenterology, Federal University of Sao Paulo-Escola Paulista de Medicina, Sao Paulo, Brazil. Periodic postoperative evaluation was performed by assaying markers in peripheral serum, colonoscopy and imaging examination. Presence of CEA was detected using the Delfia method with 5 microg/L threshold, and cytokeratins using the LIA-mat TPA-M Prolifigen method with 72 U/L threshold. RESULTS: In the first postoperative year, patients without recurrent disease had normal levels of CEA (1.5 +/- 0.9 microg/L) and monoclonal tissue polypeptide antigen-M (TPA-M, 64.4 +/- 47.8 U/L), while patients with recurrences had high levels of CEA (6.9 +/- 9.8 microg/L, P < 0.01) and TPA-M (192.2 +/- 328.8 U/L, P < 0.05). During the second postoperative year, patients without tumor recurrence had normal levels of CEA (2.0 +/- 1.8 microg/L) and TPA-M (50.8 +/- 38.4 U/L), while patients with recurrence had high levels of CEA (66.3 +/- 130.8 microg/L, P < 0.01) and TPA-M (442.7 +/- 652.8 U/L, P < 0.05). The mean follow-up time was 22.3 mo. There was recurrence in 23 cases. Five reoperations were performed without achieving radical excision. Rises in tumor marker levels preceded identification of recurrences: CEA in seven (30%) and TPA-M in eleven individuals (48%). CONCLUSION: Intensive follow-up by serial assay of CEA and cytokeratins allows early detection of colorectal neoplasm recurrence.

Endogenous and exogenous polyamines in support of tumor growth.

The combination of inhibitors of ornithine decarboxylase and polyamine oxidase and of antibiotics suitable for the (partial) decontamination of the gastrointestinal tract with a polyamine-deficient diet reduced the growth rate of Lewis lung carcinoma by more than 80%. The formation of lung metastases was prevented by 70 to 100%, depending on the treatment. The reduction of tumor growth was accompanied by a decrease of tissue polyamine concentrations, a reduced rate of tumor cell proliferation, and protein synthesis. The comparison of the ornithine decarboxylase inhibitors Eflornithine [D,L-2-(difluoromethyl)ornithine] and (E)-2-(fluoromethyl)dehydroornithine ethylester confirmed the greater in vivo potency of the latter compound. Our method of growth inhibition by systematic polyamine deprivation is not tumor specific, but presumably generally applicable to rapid growth.

Primary perineal posterior hernia: an abdominoperineal approach for mesh repair of the pelvic floor.

Spontaneous development of perineal hernias is a very rare condition and many techniques have been described for repairing the floor defect. The authors describe the use of a combined approach in the surgical treatment of primary perineal hernias, by reconstructing the muscle pelvic floor and restoring the rectum to its sacral position with mesh repair. The case of one patient with a huge primary perineal hernia is reported, with clinical manifestations of progressive bulging in the buttock area, obstipation and fecal incontinence. Long-term follow-up has shown no recurrence of the condition and normal bowel function. It is concluded that primary perineal hernia can be repaired by a combined surgical approach, by using prosthetic material.

Effects of basic fibroblast growth factor on the development of GABAergic neurons in culture.

Six-day-old neuronal cultures derived from 14-day-old embryonic rat cerebral hemispheres were highly enriched in GABAergic neurons, as was demonstrated by immunocytochemistry using an anti-glutamate decarboxylase antiserum. They contained about 64% glutamate decarboxylase-positive neurons. About 8% of these neurons proliferated, as shown by a combination of glutamate decarboxylase immunocytochemistry and [3H]thymidine incorporation into cell nuclei. The proliferative activity of GABAergic precursor cells and changes in the cellular concentrations of the non-essential amino acids, including GABA under the effect of basic fibroblast growth factor were studied. When basic fibroblast growth factor was added to the cultures 4 h after seeding, the proliferation of the GABAergic neurons was stimulated about threefold. Under this culture condition, the concentration per cell of all amino acids increased, except those of GABA and beta-alanine. When basic fibroblast growth factor was added to cultures only on day four, the proliferation of the neuronal cells was no more enhanced. Under this condition of treatment, the concentrations of all non-essential amino acids, including those of GABA and beta-alanine were enhanced. Under both basic fibroblast growth factor treatments the concentration of GABA per GABAergic cell was increased. In contrast, the specific activity of glutamate decarboxylase was not stimulated under these conditions. We hypothesize that under the effect of basic fibroblast growth factor the capabilities of the cells to store GABA are improved.

Chain-fluorinated polyamines as tumor markers. II. Metabolic aspects in normal tissues.

The objective of this work was to study certain metabolic aspects of fluorine-substituted analogues of natural polyamines in healthy experimental animals, with the aim of exploring their potential application as tumor markers. Tissue polyamine concentrations were more effectively depleted by combined treatment with D,L-alpha-difluoromethylornithine, an irreversible inhibitor of ornithine decarboxylase, and N1,N4-bis-allenylputrescine, an inactivator of polyamine oxidase, than with either inhibitor alone. This suggests the general importance of polyamine interconversion as a metabolic source of putrescine. Administration of 2,2-difluoroputrescine after 2 weeks pretreatment with the two inhibitors caused the formation of 6,6-difluorospermidine and 6,6-difluorospermidine in nearly all tissues. Highest concentrations of the chain-fluorinated polyamines were observed in the small intestine. At 24 h after 2,2-difluoroputrescine administration the amount was about 8% of the normal endogenous polyamine pool in the small intestine, but lower in all other tissues. Replenishment of endogenous polyamine pools is a relatively slow process. Approximately 9 days after cessation of treatment with the two inhibitors normal values had been reestablished. The rate of formation of endogenous polyamines was not affected by the presence of their difluoro analogues. Elimination of the chain-fluorinated polyamines from tissues seems not to follow normal polyamine metabolic patterns. Their most rapid elimination coincides with the enhancement of endogenous polyamines, indicating that the fluoro analogues are displaced by the natural polyamines. Most of the 2,2-difluoroputrescine was rapidly excreted in the urine, and formation of a conjugate was detected. 6,6-Difluorospermidine was also a urinary excretion product. However, the metabolic fate of 6,6-difluorospermine could not be clarified. It was not found in urine, either free or as conjugate. The relatively low accumulation of chain-fluorinated polyamines, together with their rapid elimination from normal tissues are characteristics which together with their previously established selective uptake into rapidly proliferating tissues recommend them as potential tumor markers that can be determined by 19F-NMR spectroscopy.

On the formation of gamma-aminobutyric acid from putrescine in brain.

Gamma-aminobutyric acid is not formed in significant amounts from putrescine by incubation with rat brain homogenates. However, it is formed if acetyl-CoA is added to the incubation medium. This is taken as further evidence for the existence of a metabolic pathway in mammalian brain which comprises acetylation of putrescine to monoacetyl putrescine and oxidative deamination of monoacetyl putrescine by MAO. Nerve cells and glia cells have comparable capacities for putrescine degradation along this pathway.

Metabolic routes of GABA formation in chick embryo brain.

Sobue and Nakajima (1978) reported that GABA formation from putrescine is significant in chick embryo brain between days 6 and 8 of incubation. They attributed an important functional role to the putrescine-derived GABA. We found that depletion of putrescine and spermidine in chick embryos by inhibition of ornithine decarboxylase activity did not decrease the in vivo rate of GABA formation, showing that putrescine is, from a quantitative point of view, a negligible source for GABA in chick embryo brain. The changes of brain GABA levels obtained after administration of glutamate decarboxylase inhibitors and in vitro determinations of glutamate decarboxylase activity were compatible with the assumption that GABA is mainly formed by decarboxylation of l-glutamate, even during early brain development. Participation of the NAD(+)-dependent, aerobic transformation of glutamate into GABA (Seiler and Wagner, 1976) in the overall GABA production of chick embryo brain could, however, not be excluded.

Comparative antipsychotic profiles of neurotensin and a related systemically active peptide agonist.

Several lines of evidence have shown that neurotensin can modulate dopamine neurotransmission. It has been suggested that neurotensin has potential antipsychotic activity because it reduces dopaminergic activity preferentially in the nucleus accumbens. In the present study, the effects of neurotensin and NT1 (N alpha Me-Arg-Lys-Pro-Trp-TIe-Leu or Eisai hexapeptide), a metabolically stable and systemically active neurotensin agonist, were examined in several models of antipsychotic activity and side effect liability in mice; analgesic and hypothermic effects of both compounds also were determined. Up to high doses, neurotensin (5.0 and 10.0 micrograms, i.c.v.) and NT1 (10.0 and 20.0 mg/kg, i.p.) did not produce catalepsy. A much lower dose of neurotensin (0.03 microgram, i.c.v.) significantly reduced amphetamine- and phencyclidine-stimulated locomotor activity; NT1 also diminished amphetamine- and phencyclidine-stimulated locomotion with ED50 values of 0.3 and 0.4 mg/kg, i.p., respectively. Neurotensin (0.01-0.3 microgram, i.c.v.) and NT1 (0.1-1.0 mg/kg, s.c.) also produced dose-dependent analgesia in the paw pressure test and decreased body temperature; these effects were insensitive to pretreatment with naloxone (10.0 mg/kg, i.p.). Together, the results support the hypothesis that neurotensin agonists have antipsychotic and analgesic activity. Moreover, the data suggest that such compounds may not produce extrapyramidal side effects.

Developmental changes of putreanine in vertebrate brains.

A method for the determination of putreanine has been developed, based on the separation of ion pairs with octanesulfonic acid on a reversed phase column. The method has been used to determine the developmental pattern of this amino acid in chick and rat brain.

Synapse formation and development of neurotransmitter functions in neuronal cells from chick brain cultured in a serum-free, defined medium.

Cells dissociated from cerebral hemispheres of 8-day-old chick embryos were seeded on poly-L-lysine coated Petri dishes in serum-containing medium. After 24 hr the culture medium was switched to a serum-free, chemically defined medium. These cultures contain mainly neuronal cells until day 14, characterized by the presence of acetylcholinesterase activity and neurofilament proteins. After 2 weeks glial cells progressively contaminated the neuronal culture. Cultures were maintained for a period of 4 weeks. From day 6 on numerous synapses with clear vesicles were observed. The activity of choline acetyltransferase remained low throughout the culture period, while GABA levels increased in parallel with synaptogenesis. Our observations indicate that chick cerebral hemisphere neuronal cultures grown in serum-free, chemically defined medium contain GABAergic neurons that undergo maturation.

Synergistic anticonvulsant effects of GABA-T inhibitors and glycine.

The anticonvulsant effect of inhibitors of GABA-T (R/S-gamma-vinyl-GABA, ethanolamine-O-sulfate, gabaculine, aminooxyacetic acid) was enhanced by 10 mmol/kg glycine in animal seizure models which are based on a functional GABA deficit. Similar to glycine in their action, although less effective, were its close structural analogues (sarcosine, N,N-dimethylglycine) and homologous omega-aminoacids (beta-alanine, taurine, gamma-aminobutyric acid, delta-aminovaleric acid). It is assumed that glycine and its structural analogues act on supraspinal glycine receptors as glycine agonists. Our observation is the first example of the synergistic interaction of two inhibitory neuronal systems resulting in the amplification of the anticonvulsant effect. Combined treatment with GABA-T inhibitors and glycine may turn out to be of practical importance in the therapy of seizure disorders and other diseases, for which treatment with GABA-T inhibitors is considered a potentially useful therapeutic approach.

The gastrointestinal tract as polyamine source for tumor growth.

It has previously been demonstrated that decarboxylation of ornithine in tumors, and the oxidative splitting of N1-acetylspermidine in tumor and normal tissues, are important sources of putrescine. Both these sources are utilised by tumors and other tissues with a high demand for polyamines to ensure their polyamine requirement. Consequently, combined treatment of tumor-bearing animals with an inhibitor of ornithine decarboxylase (e.g. alpha-difluoromethylornithine) and polyamine oxidase (e.g. N,N'- bis-allenylputrescine) has an antitumoral effect superior to that of either drug alone. In the present work, it was demonstrated that the alimentary tract is a third important source of polyamines which maintains tumor growth. Gastrointestinal polyamines are of alimentary origin, and are also formed by aerobic and anaerobic microorganisms. They can be reduced by feeding a polyamine deficient diet together with antibiotics that are suitable for decontaminating the gastrointestinal tract. This treatment combined with the administration of the mentioned inhibitors of ornithine decarboxylase and polyamine oxidase completely prevents Lewis lung carcinoma from growing, and prolongs considerably the average life span of L1210 leukemia mice. The results of the polyamine analyses of tumors, leukemia cells and tissues are compatible with the notion that the effective blocking of the three main putrescine sources (intracellular decarboxylation of ornithine, formation of putrescine from N1-acetylspermidine, and the gastrointestinal tract) produces a very strong cytostatic effect. It is expected that the clinical efficacy of polyamine antimetabolites can be considerably improved by measures analogous to those applied in this pilot study.