Induced pluripotent stem cell clones reprogrammed via recombinant adeno-associated virus-mediated transduction contain integrated vector sequences.

Fibroblasts can be reprogrammed into induced pluripotent stem cells (iPSC) by ectopic expression of key transcription factors. Current methods for the generation of integration-free iPSC are limited by the low efficiency of iPSC generation and by challenges in reprogramming methodology. Recombinant adeno-associated virus (rAAV) is a potent gene delivery vehicle capable of efficient transduction of transgenic DNA into cells. rAAV stays mainly as an episome in nondividing cells, and the extent of integration is still poorly defined for various replicating cells. In this study, we aimed to induce iPSC from mouse and human fibroblasts by using rAAV vector-mediated transient delivery of reprogramming factors. We succeeded in deriving induced pluripotent stem cells from mouse but not human fibroblasts. Unexpectedly, the rAAV vector-mediated reprogramming led to frequent genomic integration of vector sequences during the reprogramming process, independent of the amount of virus used, and to persistent expression of reprogramming factors in generated iPSC clones. It thus appears that rAAV vectors are not compatible with the derivation of integration-free iPSC.

Shall we dance? Spatialization of couple and therapist-patient relationships.

The language of spatial metaphor is both old and familiar: "You seem far away tonight," or "He stands head and shoulders above the crowd." It is vivid and evocative language. When put in the service of therapy, it is capable of clarifying and intensifying aspects of interpersonal relationships which ordinarily remain obscure. This paper explores the deliberate use of space as a metaphor representing interpersonal and emotional realities. Family sculpture, as pioneered by Kantor, Duhl, and Duhl (1973), and elaborated by Simon (1972), Papp (1976) and others, develops a spatial metaphor involving the entire family. This metaphor is both descriptive, clarifying emotional reality, and therapeutic, suggesting avenues for change and growth. We will illustrate the use of this vocabulary as it applies to two-person systems: therapist-patient interactions and the marriage relationship.

[The role of local excision in the surgical treatment of rectal cancer]. / A localis excisio helye a végbélrák sebészi kezelésében.

UNLABELLED: Between 1984 and 1992 authors performed 307 surgical interventions for patients with rectal cancer, of these 199 operations were curative (65%). Local excision of the tumour was carried out in 9 cases: 2 with palliative intent, 7 were considered a curative treatment, that constituted 3.5% of all curative procedures. Five tumours were removed by transanal local excision, 2 located in the upper part of the rectum required laparotomy and rectotomy. No operative mortality. One wound sepsis was registered after laparotomy. There was one local recurrence after removing the primary tumour. At the same time 83 patients suffering abdominoperineal resection or anterior resection had tumour limited to the rectal wall without lymph node metastasis. The mortality was 1.4%, the morbidity 28% and local recurrence rate was 19% in this group. The difference between the the results of the two groups did not achieve statistical significance included the survival too. Of the 83 tumours removed by more radical operations 38 located between 1-8 cm from the anal verge. Excluding tumours poorly differentiated and those with diameter larger than 3 cm, 17 rectal cancer would have been suitable for transanal local excision, that constitutes 8.5% of the curative operations. CONCLUSION: with more accurate preoperative staging the transanal local excision for carcinoma of the rectum can be performed more frequently than earlier. The risk of the operation is lower than those of the abdominoperineal or anterior resection and the late results are comparable if strict selection criteria are implemented.

[The effect of blood transfusion on the late results of the surgical treatment of rectal cancer]. / A transzfúzió befolyása a végbélrák sebészi kezelésének késói eredményeire.

UNLABELLED: Prospectively recorded data of 149 patients undergoing curative resection for rectal cancer between 1985-1992 were evaluated. Survival rate and tumor recurrence were studied in transfused and non-transfused groups of patients. There wasn't statistically significant difference found between the two groups concerning the 5 year survival rate (53 and 59%). Whole blood had more deleterious effect on survival than packed red cells (48 versus 61%), but the difference didn't reach the statistical significance level. The 5 year survival rate of patients without transfusion was significantly higher (p < 0.05) than those received > 800 ml of blood (59 v.s. 33%). The tumor recurrence wasn't associated with transfusion. Neither the quality, nor the amount of blood seems to influence on the recurrence rate significantly. In the group of patients with > 800 ml of transfusion the lower preoperative hematocrit, the higher rate of abdominoperineal resection of the rectum and the longer duration of surgery than those of patients nontransfused reflect the unfavorable tumor stage and the difficulties in removing the tumor. Authors believe these circumstances necessitating the transfusion may be responsible for worse outcome of rectal cancer but the immunosuppressive effect of the blood can't be excluded. CONCLUSIONS: stricter indication than earlier is necessary for administration of blood transfusion to patients with rectal cancer to decrease the risk of transfusion-transmitted infections and to avoid the possible immunosuppressive effect of the blood. Packed red cells is preferable. Decreasing volume of perioperative homologous transfusion by improving surgical technique and clinical application of autologous transfusion should be considered.

Clinical significance and application of anorectal physiology.

During the last decade, interest in anorectal disorders has increased continuously. This review presents the results of Hungarian authors' contributions to a better understanding of anorectal physiology over the last 10 years. It has been demonstrated that the surgical technique of pelvic floor reconstruction can be refined and surgical complication rates reduced through the analysis of anal basal pressure components and exploration of internal anal sphincter function. Objective assessment of anal continence (distinguishing continent from incontinent patients) is a consistent problem in clinical practice. The balloon-retaining test, a special application of manometry, facilitates evaluation of anorectal function in incontinent patients. Constipation is an extremely common symptom. Surgical treatment of these ailments should not be regarded as a first-choice therapy. Disordered defecation due to anismus can be identified by defecometry, and can eventually be treated by biofeedback training. The data presented here demonstrate the enormous impact of sophisticated diagnostic techniques on the therapeutic options in treatment of anorectal diseases.

A structural approach to the single-parent family.

Although the single-parent family is becoming a predominant family structure, there is a surprising scarcity of articles discussing its typical problems or detailing specific therapeutic approaches. This paper attempts, first, to list some core problems encountered by all single parents and, second, to present a sequence of therapeutic approaches geared toward dealing with these problems. Structural theory, with its emphasis on subsystems, generational boundaries, and organizational patterns, provides a framework for viewing the built-in vulnerabilities of the single-parent family unit. Minuchin's (3) emphasis on generational boundaries and the problem of enmeshment underlies the theoretical and therapeutic approach presented here. I have drawn heavily on Haley's (2) idea that the therapist must be an authority, a problem-solver, and a teacher. Finally, the emphasis on creating new organizational patterns is most thoroughly explored in Aponte's (1) discussions of "underorganized families" (many of whom are single-parent families).

One- to three-session therapy with children and families.

Individuals or families occasionally "leave therapy" after only one or several sessions, claiming to have gotten what they needed. Although such experiences are often considered treatment failures, there is growing evidence that such brief contacts can in fact produce changes as thorough and meaningful as those seen in long-term treatment. The few studies exploring such brief encounters suggest the long-range effectiveness of one-session treatment across diagnostic categories. Examples of one- to three-session treatment in the individual and family therapy literature are cited. Three of the author's cases are described, illustrating one style of intervention. Is such treatment merely palliative, or can it deal with "underlying" causal issues? How can significant change occur within the structure of one to three hours? These issues are discussed within the framework of psychoanalytic and family systems theories of symptom formation and symptom maintenance.

An up-to-date method of early postoperative enteral feeding.

A case of early postoperative enteral feeding through a jejunostomically inserted catheter is reported. A child 9 years of age was operated upon for congenital brachyoesophagus. In the course of the operation a Jejunocath (Pfrimmer, Erlangen, FRG) was introduced to provide enteral nutrition with the oligopeptide diet Peptisorb (Pfrimmer). Punp controlled feeding was started on the first postoperative day. The amount of the diet was gradually raised in the first 4 postoperative days reaching a peak amount of 6980 kJoule/24 hours (230 kJ/kg BW). The maximum speed of administration was 80 ml/hour. No deviation in blood or urine was found, intestinal motility was normal. During ten days total and additional four days partial enteral feeding the child's bodyweight and skinfold thickness remained unchanged. It has been concluded that enteral feeding is a useful tool in postoperative nutrition in many cases.

Prognosis of untreated liver metastasis from rectal cancer.

UNLABELLED: Majority of studies based of treatment of liver metastases from colorectal cancer compare their results to historical controls that include patients having untreated secondary liver tumours. The aim of this study was to show the natural history of patients with liver metastasis from rectal cancer. Data of 303 patients underwent laparotomy between 1984 and 1992 were reviewed. 47 of 57 patients who had liver metastasis at the time of surgery fulfilled the criteria of the study. The mean survival time was 8.5 (1-27) months for all patients, 11 months for patients with solitary hepatic tumour (n = 13) and 7.5 months for those with multiple tumours (n = 34). Patients who had liver and other distant metastases simultaneously (n = 9) survived a shorter time than those with hepatic secondaries only (4 and 9 months respectively). The mean survival time for patients in whom the primary tumour was resected (n = 17) was 11 months contrary to 7 months for those who underwent colostomy or exploratory laparotomy, but comparison of survival curves didn't revealed significant difference between the two groups. CONCLUSIONS: The incidence of liver metastases from rectal cancer at the time of laparotomy was 19%. The prognosis was very poor in case of synchronous secondary tumours. Palliative resection of the primary tumour is recommended for selected patients only to control local symptoms.

[Experience with intravenous metronidazole administration in the preoperative care of surgery of the large intestine]. / Erfahrungen mit intravenöser Metronidazolgabe bei der Vorbereitung zu Dickdarmoperationen.

Peroperative intravenous administration of Metronidazole reduces significantly septic complications in surgery of the colon, especially in combination with intravenous Gentamycin. Intravenous Metronidazole was also successful in cases of septic shock.

Ano-rectal physiological changes after rubber band ligation and closed haemorrhoidectomy.

OBJECTIVE: The effect of treatment for haemorrhoids on ano-rectal physiology was studied in a prospective longitudinal follow-up study. METHODS: Thirty-six consecutive patients having II-III degree (Group I, 18 patients) or IV degree (Group II, 18 patients) haemorrhoids were studied. Group I underwent rubber band ligation while Group II underwent closed scissors haemorrhoidectomy. RESULTS: Patients in Group I had significantly lower maximum basal pressure (P < 0.05) and also significantly lower maximum squeeze pressure (P < 0.05) compared to Group II before treatment. Both basal and squeeze pressures dropped after haemorrhoidectomy (P < 0.001) whereas they remained unchanged after rubber band ligation (P > 0.1). The volume of first sensation was higher in Group II before treatment (P < 0.001) and remained so after treatment. Rectal compliance was higher (P < 0.005) in Group I before treatment. It increased significantly in both groups (P < 0.05, Group I; P < 0.001, Group II) after treatment. CONCLUSIONS: The results show a significant increase in anal pressures in constantly prolapsing (IV degree) haemorrhoids. Most of the physiological differences observed between the two groups were abolished after treatment. This suggests that these may be a consequence rather than a cause of haemorrhoids.

[Perineal neoplasms]. / Perineale Neoplasmen.

The literature on perineal neoplasms is reviewed and their incidence, the method and effectiveness of their surgical treatment analyzed. The prognosis of perineal neoplasms is tragic: according to published data 50% of the patients die within two, 92% within four years. The benign or malignant nature of perineal tumours can be judged only on the basis of histological tests. Attention is drawn to the necessity of the early surgical removal of perineal tumours. In the case of a 66-year old woman the histological diagnosis was gelatinous adenocarcinoma. To the best of the knowledge of the authors no similar case has been reported in the literature.

Respiration paralysing and circulatory effects of a new non-depolarizing relaxant, pipecurium bromide, in anaesthetized dogs.

The effect of a new sterane-structure, non-depolarizing muscle relaxant 2 beta,16 beta-bis(4'-dimethyl-1'-piperazino)-3 alpha,17 beta-diacetoxy-5 alpha-androstane dibromide (pipecurium bromide, RGH-1106, Arduan) was studied in 42 mongrel dogs under general anaesthesia (ether, halothane, methoxyflurane, thiobutobarbital, hydroxydione and dehydrobenzperidol-fentanyl (NLA II). Onset and duration of action and the presence of circulatory side effects were examined. It was found that the mean onset of respiration paralysing action was 156.1 s and apnea lasted for 38 min. In the thiobutobarbital group apnea lasted for 74 min. Arterial systolic blood pressure and central venous pressure did not change, but the heart rate was mildly decreased by pipecurium bromide. ECG intervals (PQ, QT and TP) did not change considerably, and the variations ran parallel with the prolongation of RR intervals due to the decrease of heart rate. Pipercurium bromide is a non-depolarizing muscle relaxant of medium duration, without any significant circulatory effects. Its duration of action was prolonged in the presence of thiobutobarbital, indicating a drug interaction between the two preparations.

First clinical experience with a new neuromuscular blocker pipecurium bromide.

The clinical trial of the new non-depolarizing muscle relaxant 2 beta,16 beta-bis-(4'-dimethyl-1'-piperazino)-3 alpha,17 beta diacetoxy-5 alpha-androstane dibromide (pipecurium bromide, RGH-1106, Arduan) was performed on 80 patients who had to undergo medium and major size intraabdominal operation on the basis of chronic surgical indication. Four types of general anaesthetic methods were applied, neuroleptanalgesia, halothane, halothane-fentanyl combination and hydroxydione. The clinical applicability of pipecurium bromide was tried to establish the dose needed for complete muscle relaxation initially and repeatedly and the effect of antagonist drugs on the muscle relaxation. We investigated the duration of the first and repeated dose of the relaxant. Heart rate and arterial blood pressure were measured, mean arterial pressure and pulse pressure were calculated. In 10 patients of the halothane group the behaviour of some haemodynamic parameters was investigated. The changes of acid base parameters, blood gases, serum electrolytes and blood sugar were also observed. The administered doses were initially 3.88 mg/h, repeated doses 2.32 mg/h, this means 0.052 mg/kg body weight initially and 0.026 mg/kg body weight repeatedly The duration of effect after the first dose was 53 min, after the repeated doses 45 min. There were no direct effects on heart rate and arterial blood pressure. It did not affect myocardial contractility or work function, there was no remarkable changes in cardiac output. There were no direct metabolic changes due to pipecurium bromide. The relaxant has no histamine releasing effect. At the end of the anaesthesia the effect can be antagonized with neostigmine. During our observations there were no side effects or allergic reactions caused by pipecurium bromide.

Rectal cancer therapy: decision making on basis of quality of life?

BACKGROUND: As colorectal malignancies are relatively well treatable and show acceptable survival rates, the quality of life indicators are very important in this group of patients. PATIENTS AND METHODS: 372 patients with rectal cancer were included on a voluntary basis in this prospective study. The patient material consisted of two groups, those who underwent sphincter saving operation (64.51 %), and those who underwent Miles operation (35.49 %). The patients answered a colorectal cancer specific questionnaire on quality of life (CRC_QoL) 1 year after surgery. A CRC_QoL was prepared to analyze the correlation between the characteristics of the colorectal cancer and its treatment versus the physical and psychological state, somatic sensations and social connections of the patients. Our QoL questionnaire consists of 62 questions. Internal consistency of each factor was assessed by calculating Cronbach alpha values and was found satisfactory. For the test-retest reliability analysis the questionnaires were re-assessed. Correlation analysis showed that the answers were consistent (p < 0.01 in all cases). Discriminative validity analysis of the factors showed a significant difference in all cases. In self made score system higher numbers mean (9) worse, the smaller mean (0) better quality of life. The scale can also be seen as a percent distribution, where - in turn - the best quality is 100. The CRC_QoL questionnaire, scoring system, and score-to-percent transformation were done in this study. The results were evaluated by question and by patient group too. RESULTS: Our indicator did not show poor QoL for ostomates. Physical function was quite good in both groups: non-ostomates 87.69 +/- 20.85, ostomates: 96.46 +/- 8.25, p = 0.05 respectively. The cumulated converted percentile value for general state was significantly better (p = 0.03) for the ostomates (86.18 +/- 13.43) compared to non-ostomates (69.80 +/- 31.37). The cumulative gastrointestinal problem score did not reveal any significant difference (non-ostomates: 90.19 +/- 12.50, ostomates: 95.62 +/- 9.04, p = 0.11). Non-ostomates and ostomates did not differ regarding the cumulative score of stool-related questions: 83.75 +/- 20.53 versus 89.85 +/- 10.01 respectively, p = 0.14. The score for the peristomal problems was as high as 90.00 +/- 16.12. There was no difference in the cumulative gender specific indicators for both sexes, which showed the value 72.50 +/- 44.35 at non-ostomates and 63.64 +/- 50.45 at ostomates (p = 0.31). None of the patients regarded the chemotherapy problem as a factor diminishing the quality of their life. After calculating the total of all above mentioned functional parameters the score for non-ostomates results 82.50 +/- 19.83, and that of ostomates results 88.60 +/- 8.48, what is about the same, p = 0.12. The cumulative score of the two groups concerning emotional indicators did not really differ (non ostomates 78.69 +/- 24.19, ostomates 84.95 +/- 12.08, p = 0.11). The total cumulative scores among the groups did not show significant difference (non-ostomates 81.67 +/- 31.48, ostomates 87.12 +/- 16.40, p = 0.27). The global QoL was high in both groups with no significant difference among non-ostomates and ostomates (82.00 +/- 24.86 versus 88.60 +/- 8.48, respectively, p = 0.12). CONCLUSION: The quality of life of all patients was poorer than it was prior to the onset of the disease, but most of them could return to their prior way of living with not too many compromises. This process can be well monitored with our score system.

Pre- and postoperative examinations in intestinal tumours of the pelvis.

Pre- and postoperative urological and lower urinary tract urodynamic studies were made in patients operated for intestinal tumours of the pelvis. It was established that urological complications often arise and they often escape detection during the examination or under the conventional surgical care. An examination and a control scheme is recommended for the early detection of the possible complications and for starting an adequate treatment in due time.