125iodine reimplantation for locally progressive prostatic carcinoma

We treated 13 patients with a second 125iodine implant for local recurrence of prostatic carcinoma. All patients had biopsy proved palpable recurrence without evidence of distant metastases. Full doses of irradiation were used (median matched peripheral dose 170 Gy.). Six patients had complete regression of palpable recurrence, 2 had partial regression, 2 had no apparent response and 3 were unevaluable for local response. Actuarial freedom from local disease progression at 5 years was 51%. Despite a relatively high rate of local disease control the actuarial rate of distant metastases reached 100% at 6 years after reimplantation. There were 2 severe rectal complications and 4 instances of mild to moderate urinary incontinence among the 13 patients. Local regression of recurrent prostatic carcinoma may be achieved with 125iodine reimplantation but most patients still had distant metastases.     

Paget-von Schroetter syndrome: case description in the light of the literature

A 27 year old patient with a thrombosis of the subclavian vein (Paget- von Schroetter's-syndrome) was treated successfully with a systemic streptokinase thrombolysis. Indications and success of the different therapeutic ways in current literature (conventional management, systemic and local thrombolysis) are compared to each other. The authors prefer treatment with systemic thrombolysis, patients with contraindications should be treated with conservative management. Nevertheless no final conclusions can be drawn, as there are no controlled studies comparing the different concepts in treatment.     

Initial subcutaneous embedding of the peritoneal dialysis catheter-a critical appraisal of this new implantation technique

Background: The objectives of this open non-randomized study were to evaluate the impact of a new peritoneal catheter placement technique on catheter maintenance, and complications possibly related to the access, e.g. leakage, infectious complications, or drainage failure. Method: In a routine clinical setting, a two-cuff swan-neck catheter was implanted surgically, but its external segment was embedded in a subcutaneous pouch initially without exit site to enable uncontaminated wound healing and tight ingrowth of the cuffs. After 4 weeks at the earliest the distal catheter tip was set free by a small incision under local anaesthesia, and CAPD was started. Results: Using this technique, 26 catheters were implanted in 17 males and nine females (mean age 52.3±17.4, range 19-83 years). The catheters were buried subcutaneously for a median of 79.5 (mean±SD 132.2±157.2, range 28-675) days, and were activated in 21 patients. No leaks were seen, and only one abdominal wall abscess secondary to a haematoma was found. Long-term follow up (mean duration of CAPD 467.0±338.1, range 32-1320 days) revealed a very low overall incidence of infectious complications, i.e. 0.80 per patient-year (1 episode per 14.9 patient-months), and the incidence of catheter-related peritonitis amounted to 0.036 per patient-year (1 episode per 27.2 patient-years), only. However, the postoperative course was complicated by seromas in two of 26, and subcutaneous haematomas in 12 of 26 patients, five of which were revised surgically. At catheter activation, fibrin thrombi were found in nine of 21 patients and two had to be operated. Omental catheter obstruction was diagnosed in four patients, and followed by omentectomy. No relationship was seen between thrombus formation and omental obstruction and duration of subcutaneous embedment (P=0.27 and P=0.5 respectively) or patient age (P=0.06 and P-0.13 respectively; Mann-Whitney-test). There was also no relationship with primary omentectomy or haematoma. Conclusion: We conclude that although the very low incidence of infectious episodes favours the new technique, further improvement is necessary to decrease the unacceptable rate of perioperative complications. Subcutaneous embedding of the catheter may then be considered in patients with expected problems of wound healing, and those who wish to be prepared for peritoneal dialysis in time.     

Effect of cisplatin resistance on cellular radiation response

Cisplatin-resistant tumors of the head and neck are generally resistant to irradiation. To determine whether the association between cisplatin (DDP) resistance and radiation resistance is a cellular phenomenon, we developed DDP-resistant Chinese hamster fibroblasts and studied their response to radiation. DDP resistance did not confer cross resistance to radiation. DDP-resistant cells did not demonstrate altered ability to repair sublethal or potentially lethal radiation damage. However, an isodose concentration of DDP did not inhibit repair of radiation damage in drug-resistant cells as readily as it did in drug-sensitive cells. The results suggest that cross resistance of tumors between DDP and radiation may be a result of the tumor microenvironment, rather than being a cellular phenomenon. Additionally, DDP may not inhibit the repair of radiation damage in DDP-resistant tumors.     

BicD-dependent localization processes: from Drosophilia development to human cell biology

Many eukaryotic cells depend on proper cell polarization for their development and physiological function. The establishment of these polarities often involve the subcellular localization of a specific subset of proteins, RNAs and organelles. In Drosophila, the microtubule-dependent BicD (BicaudalD) localization machinery is involved in the proper localization of mRNA during oogenesis and embryogenesis and the proper positioning of the oocyte and photoreceptor nuclei. BicD acts together with the minus-end directed motor dynein as well as Egl and Lis-1. The finding that the mammalian homologs of BicD function in retrograde Golgi-to-ER transport has supported the view that BicD may be part of a repeatedly used and evolutionary conserved localization machinery. In this review we focus on the various processes in which BicD is involved during Drosophilian development and in mammals. In addition, we evaluate the interactions between BicD, the dynein localization machinery and associated factors.     

A novel 5q35.3 subtelomeric deletion syndrome

We observed a novel 3.5 Mb 5q subtelomeric deletion in a 3-year-old girl with developmental delay, hypotonia and multiple minor anomalies. Comparison of her phenotype with the few published patients with terminal 5q35 deletions revealed several overlapping features, but also showed remarkable differences such as shortness of stature versus macrosomia. After the report of 5q35.3 microdeletions in Sotos syndrome we integrated the published BACs into the public draft sequence and exactly mapped the deletion size in our patient by FISH analysis with 15 BAC probes. We demonstrated that the deletion in our patient is immediately adjacent to the reported Sotos syndrome deletion site. Subtracting the symptoms of Sotos syndrome from the published patients with larger 5q35.3 deletions allowed us to delineate a distinct phenotype of prenatal lymphedema with increased nuchal translucency, pronounced muscular hypotonia and delay of reaching motor milestones, but speech development within normal limits, wide fontanels, failure to thrive with postnatal short stature, and multiple minor anomalies such as mildly bell-shaped chest, minor congenital heart disease, and a distinct facial gestalt, associated with the novel 3.5 Mb cryptic deletion. We further showed in our patient that the deletion of the LCT(4) synthase gene results in a reduction of cysteinyl leukotriene synthesis to about 65% compared to normal values. The prenatal nuchal lymphedema associated with this deletion syndrome my be related to the deletion of the FLT4 gene causing autosomal dominant primary lymphedema and contributes to the differential diagnosis of increased fetal nuchal translucency.     

Activation heat, activation metabolism and tension-related heat in frog semitendinosus muscles

1. Frog semitendinosus muscles were stretched to various lengths beyond the rest length (l(0)) and their initial heat and isometric tension production were measured.2. As the overlap between the thick and thin filaments is reduced, the initial twitch heat and tension decline in a linear manner. At a point at which the twitch tension approaches zero, the initial heat is 30% of that seen at l(0). It is concluded that this heat is the activation heat and reflects the energetics of calcium release and reaccumulation. The initial heat at shorter sarcomere lengths appears to be the sum of the activation heat plus a heat production associated with the interaction of the thick and thin filaments.3. A similar relationship between heat and tension production is seen in tetanic contractions.4. The time course of activation heat production in a twitch can be resolved into two phases: a temperature insensitive (Q(10) < 1.3) ;fast' phase (with a time constant of 45 msec) and a temperature sensitive (Q(10) = 2.8) ;slow' phase (with a time constant of 330 msec at 0 degrees C).5. Measurements of the creatine phosphate (PC) hydrolysis by muscles contracting isometrically at various muscle lengths at and beyond l(0), indicate an enthalpy change of -11.2 kcal/mole PC hydrolysed. The enthalpy change for the ATP hydrolysis by muscles stretched so that little or no tension was produced with stimulation was -9.9 kcal/mole ATP hydrolysed. It is concluded that the net activation heat is produced by the hydrolysis of PC or ATP.