István Csízy

High-throughput live-cell imaging reveals differential inhibition of tumor cell proliferation by human fibroblasts

Increasing evidence indicates that cancer development requires changes both in the precancerous cells and in their microenvironment. To study one aspect of the microenvironmental control, we departed from Michael Stokers observation (Stroker et al, J Cell Sci 1966;1:297–310) that normal fibroblasts can inhibit the growth of admixed cancer cells (neighbour suppression). We have developed a high‐throughput microscopy and image analysis system permitting the examination of live mixed cell cultures growing on 384‐well plates, at the single cell level and over time. We have tested the effect of 107 samples of low passage number (<5) primary human fibroblasts from pediatric and adult donors, on the growth of six human tumor cell lines. Three of the lines were derived from prostate carcinomas, two from lung carcinomas and one was an EBV‐transformed lymphoblastoid line. Labeled tumor cells were grown in the presence of unlabeled fibroblasts. The majority of the tested fibroblasts inhibited the proliferation of the tumor cells, compared to the control cultures where labeled tumor cells were co‐cultured with unlabeled tumor cells. The proliferation inhibiting effect of the fibroblasts differed depending on their site of origin and the age of the donor. Inhibition required direct cell contact. Mouse 3T3 fibroblasts inhibited the growth of SV40‐transformed 3T3 cells and human tumor cells, showing that the inhibitory effect could prevail across the species barrier. Our high‐throughput system allows the quantitative analysis of the inhibitory effect of fibroblasts on the population level and the exploration of differences depending on the source of the normal cells.

Atresia of the ileocecal junction with agenesis of the ileocecal valve and vermiform appendix: report of a case.

Intestinal atresia involving the ileocecal region is a very rare intestinal malformation, and the presence or absence of the ileocecal valve influences its surgical management. We report the case of a male newborn with a provisional diagnosis of distal ileal atresia, in whom laparotomy revealed that the entire ileocecal region was atretic with an absent ileocecal valve and appendix vermiformis. We resected the dilated terminal ileum together with the atretic segment and performed an ileocolic anastomosis between the terminal ileum and the transverse microcolon without valve reconstruction. When last seen, 8 months after the operation, the baby was developing normally. Ileocolic anastomosis without valve replacement appears to be sufficient if an ileocecal valve is completely absent and only a short segment of the terminal ileum is lost.

Urinary Homogentisic Acid in Alkaptonuric and Healthy Children

Abstract To detect and follow-up the metabolic status of patients with alkaptonuria (AKU), urinary homogentisic acid (HGA) was measured by gas chromatography. These results were close to values we obtained by colorimetric method (linearity: up to 700 mg/l, detection limit: 1 mg/l, within-run imprecision (CV): 1.2% at 100 mg/l HGA, 4.9% at 10 mg/l, between-run CV: 6.8% at 100 mg/l). To determine urinary reference ranges of HGA, 84 healthy children (age: 2months–18 years) were divided into five age groups. HGA and creatinine were measured in their morning urine. Statistical analysis proved that urinary HGA/creatinine ratio is age-dependent. The ratio is relatively high between 1 and 6 years of age, with large scatter (upper limit of reference ranges given as mean + 2 SD: 5.5–7.2 mg/mmol = 0.03–0.04 mmol/mmol creatinine), and it decreases with age. Approximately at the age of 7 years, HGA/creatinine ratio becomes constant, and later it is similar to the adult value (upper limit: 2.8 mg/mmol = 0.017 mmol/mmol creatinine). We monitored a patient during her 1–5th year of life, and her urinary HGA was 80–200 times higher than the upper limit of the age-matched reference ranges. The measurement of HGA supports the decision for starting restricted protein diet and is useful for the evaluation of the effectiveness of therapy.

Decreased Incidence of Appendix Testis in Cryptorchidism with Intraoperative Survey

Objective: Several authors have investigated the background of the process of testicular descent, but the role of the appendix testis has not been studied. The human appendix testis was found to express both estrogen and androgen receptors. We determined and compared the occurrence of testicular appendices intraoperatively in descended and undescended testes. Methods: The number of appendix testis was evaluated retrospectively in 208 boys who underwent uni- or bilateral orchiopexy, hydrocele or hernia repair and the testis was visible during operation. Results: The incidence of appendix testis was 76% (78 in 103) in descended and 24% (30 in 125) in undescended testes. Mean age at orchiopexy was lower in patients without appendix testis (39 months) compared to those patients who were found with appendix (61 months). Conclusion: The incidence of appendix testis was significantly lower (p < 0.05) in undescended testes, suggesting that the appendix testis might play a role in the process of testicular descent.

Reliability of colour Doppler ultrasound in the differential diagnosis of acute scrotum

Az akut scrotum hattereben allo heretorzio a here rapid irreverzibilis ischaemias karosodasa miatt surgős, szinte azonnali műteti exploraciot igenyel. Ugyanakkor a lenyegesen gyakoribb herefuggelek- (appendix testis) torzio es az epididymitis akar konzervativan is kezelhető. A fizikalis vizsgalaton alapulo elkulonitő korisme bizonytalansaga miatt sok esetben kerul sor felesleges exploraciora. A color Dopplerrel (CD) kiegeszitett here-ultrahangvizsgalat egyre nepszerűbb a gyermekkori akut scrotum differencialdiagnosztikajaban, ugyanakkor megbizhatosagat meg sokan vitatjak. Anyag es modszer: A szerzők tanulmanyukban osszevetettek a Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum Gyermekgyogyaszati Intezeteben az elmult 10 ev soran akut scrotum diagnozissal kezelt 124 beteg 129 esetenek a fizikalis vizsgalat, a klinikai lefolyas es a 111 műteti exploracio alapjan megallapitott vegleges diagnozisat, valamint az első here-ultrahangvizsgalat eredmenyet. Eredmenyek: A vegleges diagnozis 100 esetben herefug...

Pyloric atresia associated with Dieulafoy lesion and gastric dysmotility in a neonate

In this case study, we report a male infant with pyloric atresia, extreme gastric distension, and a caliber-persistent gastric artery (Dieulafoy lesion) with massive gastric bleeding. After a transverse pyloroplasty and endoscopic hemoclip application to the caliber-persistent gastric artery, very slow gastric emptying developed, which required repeated surgical interventions. Gastroduodenostomy failed to promote gastric emptying. The intraoperative and postmortem histologic examinations of the gastric wall revealed a loss of interstitial cells of Cajal, which possibly explains the extreme motility disorder.

Excessive pediatric fasciitis necrotisans due to Pseudomonas aeruginosa infection successfully treated with negative pressure wound therapy

The case of a 10‐year old female child is described with a history of myeloproliferative disorder having skin, bone and visceral involvement. Bone marrow biopsy revealed histiocytosis X. During chemotherapy necrotizing fasciitis of the lower abdominal wall was diagnosed. Multiple microbiological cultures taken from the wound base revealed Pseudomonas aeruginosa infection. Surgical necrectomy and application of negative pressure wound therapy (NPWT) was started together with intensive care treatment for sepsis. As both wound and general condition of the patient improved, autologous split thickness skin grafting was carried out in two sitting under continuing NPWT application. The applied skin grafts showed excellent take, the perilesional subcutaneous recesses resolved and complete healing was achieved after 28 days of NPWT treatment. Proper dermatological diagnosis and immediate escharectomy complemented with application of NPWT can be life‐saving in the treatment of necrotizing fasciitis.

Double unfurled dartos flap technique in the surgical treatment of recurrent urethrocutaneous fistulas.

Background: The management of recurrent urethrocutaneous fistula (RUCF) is a challenging problem that poses a serious difficulty for the hypospadias surgeon. We report here a novel technique in which a double unfurled dartos subcutaneous flap is utilized in the treatment of patients with RUCF. Methods: We retrospectively reviewed the records of all our patients who underwent surgical treatment of urethrocutaneous fistula with this new operative method after previously failed fistula repair. The main novelty of this technique is the use of two opposite medium thickness flaps, unfurled from the inner surface of the dartos fascia and spread over the fistula and each other so as to cover the urethral suture line completely, and fixed to the surrounding corporal tissue. Results: Eight patients with 11 RUCFs (with localizations varying from subcoronal to penoscrotal fistula opening) underwent surgical correction with the new method. There had previously been at least 3 recurrences in 6 of these patients, and different closure techniques had been used. RUCF diameter was <4 mm in all patients. Surgery was performed at the earliest following a 6-month healing period since the last fistula repair attempt. All of the RUCFs were repaired successfully with the technique. After a follow-up of at least 6 months, none of the 8 patients had developed recurrence of the fistula, and there were no postoperative complications. Conclusion: The double unfurled dartos subcutaneous flap method appears to be a simple and appropriate procedure with which to repair recurrent mid-shaft and proximal urethral fistulas after failed hypospadias repair.

Endocrine and anatomical findings in a case of Solitary Median Maxillary Central Incisor Syndrome

Solitary Median Maxillary Central Incisor Syndrome (SMMCI) is a rare malformation syndrome consisting of multiple, mainly midline defects. Some authors suggest that it is a mild manifestation of the wide spectrum of holoprosencephaly, others classify it rather as a distinct entity. Authors report a case of SMMCI presenting with growth retardation, mild intellectual disability and absence of puberty. Cytogenetic and molecular cytogenetic investigations could identify no abnormalities. The presence of a single maxillary incisor called for further investigations to clarify hidden anomalies, these were empty sella, panhypopituitarism, hypothyroidism, and hypoplasia of the inner genitals. Based on the above findings, growth hormone, estrogen, and L-thyroxine substitution was introduced, which resulted in satisfactory longitudinal growth and onset of sexual maturation. We suggest genetic counselling and if needed, invasive investigations in female patients with short stature and absent/delayed puberty, with or without sex chromosomal anomalies, as the adequate therapy and even the quality of life of patient depends largely on the knowledge of their anatomical and endocrine status.

Early introduction of peritoneal dialysis may improve survival in severe sepsis.

Objectives: Acute renal failure is a serious complication of sepsis and is associated with a very high mortality. Recent evidence suggests that proinflammatory cytokines (interleukins 1 and 6 and tumor necrosis factor &agr;) released into the circulation in response to sepsis can be removed from the blood via hemofiltration and appear in the dialysate in times of peritoneal dialysis as well. Methods: An infant who developed acute renal failure in full-blown sepsis is presented. Peritoneal dialysis was initiated on the fourth day after admission. Changes in clinical and laboratory parameters were monitored. Results: Urine output (1.13 mL/kg per hour) began to improve on the sixth day after admission (second day after the introduction of peritoneal dialysis); normalization of serum creatinine level was achieved on the 30th day after admission. Parallel with the serum creatinine level (255 &mgr;mol/L on day 5 after admission vs 208 &mgr;mol/L by day 9 after admission, fifth day of PD), serum procalcitonin, C-reactive protein, and lactate dehydrogenase levels decreased dramatically (procalcitonin >500 vs 261 &mgr;g/L; C-reactive protein, 203 vs 25.9 mg/L; and lactate dehydrogenase, 3092 vs 1744 U/L on days 5 and 9 after admission, respectively). Conclusions: Considering that there are no guidelines defined for the management of acute renal failure with accompanying sepsis in children, authors point out that peritoneal dialysis is an easy-to-perform and effective renal replacement modality in low body weight, critically ill patients. Early initiation of peritoneal dialysis does not only improve fluid and electrolyte imbalance but also may significantly reduce the destructive effect of systemic cytokine storm in sepsis and contribute to a more favorable outcome, even in cases of critical cardiovascular and hemostaseological status.