Antitumor activity of five new platinum complexes having a glycolate leaving ligand.

In an attempt to develop a new anticancer platinum complex with greater or equivalent antitumor activity but reduced side effects compared with cisplatin (CDDP), a series of new platinum complexes having a glycolate leaving ligand was synthesized. Among them, five complexes were selected for further development on the basis of adequate water solubility, low nephrotoxicity and high antitumor activity in a murine system. The chemosensitivity of these five complexes was examined in MTT assay against two human pulmonary adenocarcinoma cell lines, PC-9 and PC-14, and two human stomach adenocarcinoma cell lines, MKN-45 and KATO III. Their IC50 and relative antitumor activity (RAA) values were compared with those of CDDP and 254-S, a second-generation platinum complex with a glycolate leaving ligand under phase III clinical trial. The lowest mean IC50 value was observed in CDDP, followed by SKI 2034R and SKI 2033R. In this study, the antitumor activity was evaluated in terms of RAA values and SKI 2034R showed the highest RAA value. The order of RAA values was SKI 2034R > CDDP > SKI 2032R > SKI 2033R > SKI 2030R > SKI 2029R > 254-S. Based on the RAA order, we have recommended SKI 2034R as the most promising candidate for further development of a clinically useful platinum complex.     

Ultrasensitive analysis of the intestinal absorption and compartmentalization of aluminium in uraemic rats: a 26Al tracer study employing accelerator mass spectrometry

BACKGROUND: Developments in accelerator mass spectrometry (AMS) now permit the determination of femtogram amounts of 26Al in blood and in various tissues with good precision and free of external contamination. METHODS: In the present study we used trace quantities of 26Al to investigate the intestinal absorption and compartmentalization of aluminium in rats with renal failure (Nx, 5/6 nephrectomy) and in pair- fed controls (C). Single oral doses of 20 ng 26Al were administered to six animals in each group and, subsequently, 24-h post-load 26Al was analysed in serum, urine, bone, liver, and spleen by means of AMS. RESULTS: Serum concentrations of 26Al were significantly lower in uraemic rats compared to controls, whereas urinary excretion was comparable (Nx, 7.11 +/- 5.78 pg/day vs C, 9.46 +/- 6.10 pg/day), suggesting a higher fraction of ultrafiltrable serum 26Al in uraemia. The target tissues of cellular transferrin-mediated 26Al uptake, liver and spleen, tended to show a larger degree of aluminium accumulation in controls (0.26 +/- 0.31 pg/g vs Nx, 0.14 +/- 0.10 pg/g and 0.37 +/- 0.27 pg/g vs Nx, 0.25 +/- 0.27 pg/g respectively). In contrast, in bone, a site of extracellular aluminium deposition, 26Al concentrations were more elevated in uraemia (1.22 +/- 0.59 pg/g vs C: 0.68 +/- 0.30 pg/g). Estimated total 26Al accumulation in all measured target tissues was significantly higher in uraemic rats (28.15 +/- 9.90 pg vs C: 17.03 +/- 7.03 pg) and total recovery of 26Al from tissue and urine was 26.58 +/- 6.74 pg in controls and 35.75 +/- 7.03 pg in uraemic animals, suggesting a fractional absorption of 0.133% and 0.175% respectively. CONCLUSIONS: Our data suggest that fractional absorption from a dietary level dose of 26Al is about 0.13%. Compartmentalization occurs in transferrin-dependent target tissues such as liver and spleen; however, in quantitative terms extracellular deposition in bone is more important. Uraemia has a significant effect on the intestinal absorption and compartmentalization of aluminium. It enhances fractional absorption and increases subsequent extracellular deposition of aluminium in bone. However, at the same time uraemia does not increase transferrin-dependent cellular accumulation of aluminium in liver and spleen.      

Molluscum contagiosum occurring in an epidermal cyst--report of 3 cases.

We present three unusual cases of molluscum contagiosum occurring in epidermal cysts. All of them are asymptomatic, elevated, oval nodules diagnosed clinically as epidermal inclusion cyst or prurigo nodularis. Histology showed true epidermal cysts containing molluscum bodies throughout the cyst wall and some type of laminated material within the cyst itself. The lesion, in all three cases developed in the pubic area of young adult men.     

Mitogenic, chemotactic, and synthetic responses of rat periodontal ligament fibroblastic cells to polypeptide growth factors in vitro.

The mitogenic, chemotactic, and synthetic responses of rat periodontal ligament (PDL) fibroblastic cells to epidermal growth factor (EGF), transforming growth factor-beta (TGF-beta), recombinant human platelet-derived growth factor (rhPDGF)-AB, rhPDGF-BB, natural (n) PDGF-AB, and insulin-like growth factor-I (IGF-I) were examined in vitro using PDL cells obtained from the coagulum of healing tooth sockets. PDGFs and IGF-I have potent and comparable mitogenic effects on PDL fibroblastic cells. The maximum mitogenic effect of PDGFs was observed at the concentration of 10 ng/ml, whereas that of IGF-I was seen at concentrations higher than 100 ng/ml. In contrast, EGF induced moderate, and TGF-beta inhibitory mitogenic responses. The combination of rhPDGF-AB with either EGF or TGF-beta demonstrated comparable mitogenic potency, equivalent to the level of PDGF alone regardless of the mitogenic effect of other growth factors. The combination of rhPDGF-AB and IGF-I, however, showed a synergistic effect revealing the highest mitogenic effect among all individual growth factors as well as any combinations of the growth factors tested. Similarly, PDL fibroblastic cells demonstrated strong chemotactic responses to both IGF-I and PDGFs. The maximum effect was observed by IGF-I at concentrations higher than 10 ng/ml, followed by rhPDGF-BB at 0.1 ng/ml, rhPDGF-AB and nPDGF at concentrations ranging from 0.1 to 1 ng/ml. TGF-beta revealed no, and EGF slightly increased, chemotactic effects. IGF-I slightly enhanced the synthesis of total protein, whereas other factors had no significant effect. However, both rhPDGF-AB and TGF-beta stimulated collagen synthesis. On the other hand, IGF-I showed no effect on collagen synthesis, while EGF suppressed collagen synthesis. These findings suggest that rhPDGF-BB and IGF-I stimulate proliferation and chemotaxis of PDL fibroblastic cells. In addition, the combination of these growth factors further increases the mitogenic effect. rhPDGF-AB also stimulates collagen synthesis by PDL fibroblastic cells. Thus, rhPDGF-BB and IGF-I may have important roles in promotion of PDL healing, and consequently, may be useful for clinical application in periodontal regenerative procedures.     

Arthroscopic all-inside repair techniques of lateral meniscus anterior horn tear: a technical note

Although the conventional outside-in technique is especially useful for repairing tears in the anterior portion of the meniscus, it has a disadvantage of making an additional 1–2 cm sized skin incision and tying knots subcutaneously over the capsule. Therefore we devised two all-inside repair techniques of lateral meniscus anterior horn tear according to the site of meniscal tear, meniscosynovial junction or red–red zone. Because these techniques are modified methods of the outside-in meniscal repair using a spinal needle, they are as simple as conventional outside-in technique. In addition they have advantages of vertical mattress suture, which is an important characteristic of the all-inside repair, and no additional incision. We recommend these techniques as an alternative method for repairing an anterior horn tear of the lateral meniscus.     

Comparison of the APACHE III, APACHE II and Glasgow Coma Scale in acute head injury for prediction of mortality and functional outcome

Objectives: This study examines the efficacy of the predicting power for hospital mortality and functional outcome of three different scoring systems for head injury in a neurosurgical intensive care unit (NICU). Design: On the day of admission, data were collected from each patient to compute the Acute Physiology, Age, and Chronic Health Evaluation (APACHE) II and III, and Glasgow Coma Scale (GCS) scores. Hospital mortality was defined as the deaths of patients before discharge from hospital. Early mortality was defined as death before the 14th day after admission. Late mortality was defined as death after the 15th day from admission. Functional outcome was evaluated by Index of Independence in Activities of Daily Living (Index of ADL). Setting: An 8-bed NICU in a 1270-bed medical center in Taichung Veterans General Hospital. Patients and participants: Two hundred non-selected patients with acute head injury were included in our study in a consecutive period of 2 years. Patients less than 14 years old were not included. Interventions: None. Measurements and results: Sensitivity, specificity and correct prediction outcome were measured by the chi-square method in three scoring systems. The Youden index was also obtained. The best cut-off point in each scoring system was determined by the Youden index. The difference in Youden index was calculated by Z score. A difference was also considered if the probability value was less than 0.05. The area under Receiver Operating Characteristic (ROC) curve was computed. Then the area under ROC of each scoring system was compared by Z score. There was statistical significance if p was less than 0.05. For prediction of hospital mortality, the best cut-off points are 55 for APACHE III, 17 for APACHE II and 5 for GCS. The correct prediction outcome is 82.4% in APACHE III, 78.4% in APACHE II and 81.9% in the GCS. The Youden index has best cut-off points at 0.68 for APACHE III, 0.59 for APACHE II, and 0.56 for GCS. The area under Receiver Operating Characteristic (ROC) curve is 0.90 in the APACHE III, 0.84 in the APACHE II and 0.86 in the GCS. There are no statistical differences among APACHE III and II, and GCS in terms of correct prediction outcome, Youden Index and the area under the ROC curve. Other physiological variables excluding GCS in APACHE III and II (AP III-GCS, AP II-GCS) have less statistical value in the determination of mortality for acute head injury. For the prediction of late mortality, APACHE III and II yield significantly better results in the area under the ROC curve, correct prediction and Youden index than those of GCS. Other physiological variables (AP III-GCS and AP II-GCS) play an important role in the prediction of late mortality in APACHE scores. For prediction of the functional outcome of surviving patients with acute head injury, the APACHE III yields the best results of correct prediction outcome, Youden index and the area under the ROC curve. Conclusion: The APACHE III and II may not replace the role of GCS in cases of acute head injury for hospital or early mortality assessment. But for prediction of the late mortality, the APACHE III and II have better accuracy than GCS. Other physiological variables excluding GCS in the APACHE system play a crucial contribution for late mortality. GCS is simple, less time-consuming and economical for patients with acute head injury for the prediction of hospital and early mortality. The APACHE III provides better prediction for severe morbidity than GCS and APACHE II. Therefore, the APACHE III provides a good assessment not only for hospital and late mortality, but also for functional outcome. Received: 22 May 1995 Accepted: 2 September 1996     

Immunoscintigraphy in the detection of tuberculosis with radiolabelled antibody fragment against Mycobacterium bovis bacillus Calmette-Guérin: a preliminary study in a rabbit model.

Immunoscintigraphy with radiolabelled monoclonal antibodies is widely used to detect solid tumours, but only a few trials have been carried out concerning the specific in vivo localization of an inflammatory process. The purpose of this study was to investigate the detectability of tuberculous foci utilizing this method with radiolabelled bacillus Calmette-Guérin (BCG)-specific F(ab')2 in rabbits. All of the tuberculous lesions (n = 8) were clearly visualized on serial scintigraphy for up to 48 h after injection of the antibody. Immunohistochemical and Ziel-Neelson staining of the tuberculous lesions confirmed the presence of the tuberculous antigens and bacilli. It failed to demonstrate any sustained retention of the BCG-specific antibody fragment in the control group with syphilitic orchitis (n = 2). Therefore, the specific in vivo localization of tuberculosis is feasible by immunoscintigraphy.     

Lateral position prevents respiratory occlusion during surgical procedure under general anesthesia in the patient of huge anterior mediastinal lymphoblastic lymphoma

Lymphoblastic lymphoma, an aggressive mediastinal mass, is recognized as serious threat to the patient in developing cardiac tamponade or airway obstruction. Surgical procedure is often required to relieve clinical emergency and to establish prompt pathological diagnosis. However, in such a patient, acute respiratory occlusion in the spine position can be a life-threatening complication during general anesthesia. We describe a 17-year-old man whose cardiac tamponade was treated by pericardial-pleural window through a left anterior thoracotomy in the lateral position. The patient recovered from hemodynamic compromise without showing respiratory occlusion during general anesthesia and remained in the lateral position until extubation. Pathological diagnosis was precursor T-lymphoblastic lymphoma. There were no complications attributable to the operative procedure. Further chemotherapy reduced the mediastinal mass in size after two weeks when the patient developed sepsis and died. Lateral position prevents respiratory occlusion during surgical procedure under general anesthesia in the patient of huge anterior mediastinal tumor with airway obstruction.     

Umbilical portion of recipient's left portal vein: a useful vascular conduit in dual living donor liver transplantation for the thrombosed portal vein.

We considered performing living donor liver transplantation (LDLT) in a larger-size recipient. When the recipient was large-sized, or when the donor liver was severely steatotic or had a right-to-left volume discrepancy. We devised dual living donor liver transplantation (DLDLT) to make up for graft size insufficiency and to secure the donor's safety. However, portal vein thrombosis (PVT) presented a challenge for DLDLT because of the need for intact right and left portal veins for the implantation of both liver grafts. Our 52-year-old male patient with hepatitis B cirrhosis had suffered from repeated esophageal and gastric variceal bleeding and underwent 2 trials of a transjugular intrahepatic portosystemic shunt (TIPS). He developed TIPS occlusion and PVT involving the area just above the spleno-mesenteric confluence to the right and left PV. Also, the right PV orifice was destructed and difficult to isolate because of severe periportal inflammation and neointima growth in the TIPS mesh. The patient's two sons were inadequate for donation because of right-to-left volume discrepancy. Therefore, DLDLT using 2 left lobes was necessary to compensate for graft-size insufficiency and to secure donor safety, and we substituted an intact umbilical portion of recipient's left PV for the destroyed right PV. The patient recovered well, and liver function has been normal for more than a year. In conclusion, the umbilical portion of recipient's left PV can be a useful vascular substitute for the reconstruction of a thrombosed main portal branch in DLDLT.