Intracellular pH regulation in human SW-620 colon cancer cells

Intracellular pH (pHi) regulation is essential for basic functioning of the cell and activation of pHi regulatory mechanisms appears to be involved in the initial stage of cell division. Little is known about pHi regulation in human colonic carcinoma cells. We investigated SW-620 (CCL 227) cells, a cell-line derived from a human colonic adenocarcinoma. pHi changes were recorded by computer-assisted spectrofluorimetric monitoring of the pH-sensitive, fluorescent dye BCECF (2',7'-bis(carboxyethyl)- 5(6)carboxyfluorescein). Resting pHi in HEPES (N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid) buffered solution was 7.53 +/- 0.01. Intracellular acidification after an ammonium prepulse produced a pHi decline of 0.5 units and pHi returned to normal value in NaCl Ringer's. Both 1 mM amiloride and Na-free solution completely inhibited recovery for 8 minutes. This inhibition was reversible in NaCl Ringer's. Na-free solution led to a pHi decrease to 7.39 +/- 0.04 after 16 min, pHi was also lowered by 8 minute incubation of cells with 1 mM amiloride (7.40 +/- 0.02). In HCO3/CO2-buffered solution resting pHi was 7.42 +/- 0.01 (n = 35). Recovery from an acute acid load, induced by NH4 prepulse or switching from HEPES- to bicarbonate-buffered solution, was Na dependent, Cl independent, reversible and only partially blocked by 1 mM amiloride - pHi slowly recovered from 6.83 +/- 0.03 to 7.00 +/- 0.06 in 8 minutes. In the presence of amiloride and 200 microns H2DIDS (dihydro-4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid) pHi recovery was completely inhibited for 8 minutes. In Na-free solution pHi decreased from 7.44 +/- 0.04 to 7.29 +/- 0.03 within 8 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Technique and results of laparoscopic conservative organ-preserving myoma enucleation

Myoma is one of the most common benign diseases of the female genital tract. The surgical management of this entity has been altered over the last years from complete hysterectomy to conservative enucleation of the myomas. We retrospectively compared our data concerning laparoscopic or open myomectomies. Over a period of 2 years, we operated 207 myomas in 102 patients. Of this collective, 69 (67.6%) were operated on laparoscopically and 33 (32.4%) via an open approach. In both groups, the median number of myomas was 2 (1-7). The mean diameter of the largest myoma was 5.1 +/- 2.4 cm (laparoscopy) and 6.2 +/- 2.6 cm (laparotomy), respectively. The additive diameter of myomas was 7.7 +/- 5.1 cm (laparoscopy) and 9.8 +/- 4.1 cm (laparotomy), respectively. There was no relevant difference between the groups in terms of operating time and blood loss. Four (3.9%) laparoscopies had to be converted to an open approach. In three cases (2.9%) a laparoscopically assisted enucleation had to be performed, requiring a mini-laparotomy 4 to 5 cm in length. We encountered no severe complications. Given appropriate indication, laparoscopic myomectomy is an easy-to-perform and minimally invasive technique with a low complication rate.     

Prevalence of cytomegalovirus antibody in hemophiliacs and homosexuals infected with human immunodeficiency virus type 1

We determined the prevalence of antibody to cytomegalovirus (CMV) in the sera of non-homosexual hemophilia patients and homosexual men infected with the human immunodeficiency virus type 1 (HIV-1). CMV antibody testing by latex agglutination revealed 33 of 58 HIV-1 infected hemophiliacs (57%) were antibody-positive compared with 54 of 54 HIV-1 infected asymptomatic non-hemophiliac homosexuals (100%) (p less than .001). Nine of 15 hemophiliacs (60%) with symptomatic HIV-1 infection were CMV antibody-positive. We also tested 22 HIV-1 antibody-negative hemophiliacs who had received non-heat treated factor concentrates. 14 of these 22 (64%) were CMV antibody-positive compared with 57% of HIV-1 antibody-positive hemophiliacs. We conclude 1) there is little correlation between transmission of HIV-1 and CMV by factor concentrates, 2) the presence of CMV antibody does not appear to be associated with clinical stage of HIV-1 infection in hemophiliacs, and 3) there may be a significant number of CMV antibody-negative hemophiliacs with HIV-1 infection at risk for primary infection and subsequent disease if CMV seronegative blood products are not provided for future transfusions.     

Mycophenolate mofetil in patients with Crohn's disease

Objective: Intolerance to azathioprine is a rare but important problem in treating chronically active Crohn's disease. We performed this study to evaluate mycophenolate mofetil as an alternative immunosuppressive therapy for patients with Crohn's disease who did not tolerate azathioprine.
Methods: Four patients with highly active perianal Crohn's disease and two patients with chronically active, steroid-dependent Crohn's disease were included. All patients consumed 2 g/day of mycophenolate mofetil for a median of 8 months (range, 6–12 months). Disease activity was measured by the Perianal Crohn's Disease Activity Index in patients with perianal disease and by the Crohn's Disease Activity Index in patients with chronically active Crohn's disease.
Results: Azathioprine-induced side effects disappeared after the drug was discontinued. All patients improved during treatment with mycophenolate mofetil, as shown by a remarkable reduction in the respective clinical scores. Five patients showed no side effects during treatment with mycophenolate mofetil. After 4 months' treatment one patient developed diarrhea that was probably not due to mycophenolate mofetil.
Conclusions: Mycophenolate mofetil could be an alternative therapy to azathioprine in patients with Crohn's disease.     

Modelling of the oxygen enhancement ratio for ion beam radiation therapy

The poor treatment prognosis for tumours with oxygen-deficient areas is usually attributed to the increased radioresistance of hypoxic cells. It can be expressed by the oxygen enhancement ratio (OER), which decreases with increasing linear energy transfer (LET) suggesting a potential clinical advantage of high-LET radiotherapy with heavy ion beams compared to low-LET photon or proton irradiation. The aim of this work is to review the experimental cell survival data from the literature and, based on them, to develop a simple OER model to estimate the clinical impact of OER variations. For this purpose, the standard linear-quadratic model and the Alper-Howard-Flanders model are used. According to our calculations for a carbon ion spread-out Bragg peak at clinically relevant intermediate oxygen levels (0.5-20 mmHg), the advantage of carbon ions might be relatively moderate, with OER values about 1%-15% smaller than for protons. Furthermore, the variations of OER with LET are much smaller in vivo than in vitro due to different oxygen partial pressures used in cell experiments or measured inside tumours. The proposed OER model is a simple tool to quantify the oxygen effect in a practical way and provides the possibility to do hypoxia-based biological optimization in treatment planning.     

Possible role of MDR1 two-locus genotypes for young-age onset ulcerative colitis but not Crohn’s disease

Background The role of the single nucleotide polymorphisms (SNPs) on positions 2677G>T/A and 3435C>T of the multi-drug-resistance gene 1 (MDR1) in inflammatory bowel disease (IBD) remains unclear. Aims To further elucidate the potential impact of MDR1 two-locus genotypes on susceptibility to IBD and disease behaviour. Patients and methods Three hundred eighty-eight German IBD patients [244 with Crohn’s disease (CD), 144 with ulcerative colitis (UC)] and 1,005 German healthy controls were genotyped for the two MDR1 SNPs on positions 2677G>T/A and 3435C>T. Genotype–phenotype analysis was performed with respect to disease susceptibility stratified by age at diagnosis as well as disease localisation and behaviour. Results Genotype distribution did not differ between all UC or CD patients and controls. Between UC and CD patients, however, we observed a trend of different distribution of the combined genotypes derived from SNPs 2677 and 3435 (χ² = 15.997, df = 8, p = 0.054). In subgroup analysis, genotype frequencies between UC patients with early onset of disease and controls showed significant difference for combined positions 2677 and 3435 (χ² = 16.054, df = 8, p = 0.034 for age at diagnosis ≥25, lower quartile). Herein the rare genotype 2677GG/3435TT was more frequently observed (odds ratio = 7.0, 95% confidence interval 2.5 – 19.7). In this group severe course of disease behaviour depended on the combined MDR1 SNPs (χ² = 16.101, df = 6, p = 0.017 for age at diagnosis ≥25). No association of MDR1 genotypes with disease subgroups in CD was observed. Conclusions While overall genotype distribution did not differ, combined MDR1 genotypes derived from positions 2677 and 3435 are possibly associated with young age onset of UC and severe course of disease in this patient group.     

Testicular microlithiasis: The importance of self‐examination

Aim: To explore the issue of appropriate management of testicular microlithiasis. We report the third ever case of tumour arising from a testis previously known to have microlithiasis in childhood and review the literature to provide an evidence‐based approach to management of testicular microlithiasis. Methods: Case report and review of previous literature. Results and Conclusions: Although there is a strong association between testicular microlithiasis and testicular malignancy at diagnosis, there are only three reported cases of subsequent tumour development in childhood. Testicular microlithiasis is an increasingly recognised entity. There is insufficient evidence in the current literature to support any regime of clinical surveillance. Self‐examination is the most important factor in the early detection of testicular malignancy.     

Conservative management of early endometrial adenocarcinoma with repeat curettage and hormone therapy under assistance of hysteroscopy and laparoscopy

We report a rare case of early-stage endometrial adenocarcinoma in a 22 year old nullipara with polycystic ovaries undergoing conservative treatment. Pretreatment evaluation including tumour grade, depth of myometrial invasion, tumour size, hormone receptor status and flow cytometric analysis indicated a favourable prognosis. The patient underwent repeat endometrial curettage and a 6 month period of therapy with megestrol acetate and tamoxifen. A combination contraceptive pill was then prescribed to ensure withdrawal of the menstrual cycle thereafter. Now, 1 year after the last curettage, there is no evidence of disease. During the treatment period, hysteroscopy allowed for a more precise approach in panoramically examining the tumour nest in the endometrial cavity, and the subsequent endometrial response to hormone therapy. Laparoscopy using bulldog clamps applied to the isthmic portion of the Fallopian tubes prevented i.p. spread of endometrial tissue from retrograde regurgitation during hysteroscopy. Laparoscopic ovarian electrocautery resulted in the reduction of abnormal hypervascularization on the surface of polycystic ovaries postoperatively but caused a peri-ovarian adhesion complication. It is interesting that this case posed a unique opportunity to demonstrate the tumour regression under the assistance of laparoscopy and hysteroscopy.      

Frontocentral DC-potential shifts predicting behavior with or without a motor task.

This study was designed to investigate the predictive value of the event-related potentials (ERPs) preceding the initiation of a difficult perceptual-memory task and to investigate whether these ERPs require a motor movement on the part of the subject for their occurrence. Across 4 conditions the DC-potential shifts were recorded from 23 right-handed subjects using DC amplifiers. Although the start of each trial began with a ready signal, the conditions differed in that the subjects initiated the task by a button press in 2 conditions and the computer initiated it in 2 others without a press. The results showed that, especially in the frontocentral electrode sites, the DC-potential shifts which began those trials ending in correct performance were more negative relative to those trials ending in an incorrect response. Those conditions which required the subjects to self-initiate the trial and those which were initiated by the computer showed similar results indicating that the negative DC-potential shifts preceding correct performance are neither produced by nor depend on a task initiating motor movement. The onset of the DC-potential shifts preceded task initiation by up to 4.1 sec indicating that they were more than the Bereitschaftspotential.