The clinical usefulness of the renal allograft biopsy in the cyclosporine era: a prospective study

BACKGROUND: The renal allograft biopsy is generally accepted as the gold standard for clarifying the cause of renal dysfunction. However, the clinical usefulness of this procedure has rarely been studied prospectively, nor have most studies included follow-up of patients to delineate the influence of the biopsy on clinical outcome. In this study, we evaluated prospectively the clinical usefulness of the allograft biopsy in renal transplant recipients receiving cyclosporine (CyA). METHODS: During a 21-month period, 82 biopsies were performed. In 54 instances (47 patients), we outlined a presumed diagnosis and tentative treatment plan before the procedure. After the biopsy, a definitive diagnosis was made and an appropriate patient management approach was instituted. We analyzed the incidence of change in patient management that resulted from histological findings. All patients were followed to monitor their response to treatment and allograft survival. In cases of biopsy-proven acute cellular rejection (ACR) or cyclosporine (CyA) toxicity, clinical and laboratory data from the day of the biopsy were reviewed to determine their diagnostic value. RESULTS: One biopsy specimen was inadequate for definitive interpretation. The biopsy findings resulted in a change in patient management in 22 (41.5%) of the remaining 53 cases (change group). The incidence of altered patient management was 38.7% in biopsy specimens taken in the first month, 55.6% between 1 and 12 months, and 38.5% after 1 year posttransplantation. A change in management was required in 2 of 2 patients with chronic allograft dysfunction, in 44.4% of the 45 patients with acute allograft dysfunction, and in none of the patients with delayed graft function (n=6). Within the first week of treatment 19 of 22 (86.4%) in the change group and 25 of 31 (80.6%) in the no change group had a positive response to therapy. The 1-year allograft survival rate was also similar between the two groups. None of the clinical and laboratory data was useful in distinguishing ACR from CyA toxicity. CONCLUSIONS: Renal allograft biopsy findings alter patient management recommendations in approximately 40% of patients in whom a presumptive diagnosis had been made on the basis of clinical and laboratory findings. Patients who had a change in patient management because of biopsy findings demonstrated a response to therapy and allograft survival similar to those of patients who had no alteration in management plan after the biopsy.     

Dorsal adipofascial turn-over flap for fingertip amputations

We designed a dorsal adipofascial pedicled flap to cover amputations of the tip of the same digit. This flap includes all the adipofascial tissues from the dermis to the paratenon of the extensor tendons. After elevation of the skin, the adipofascial tissues are raised as a flap and turned over to resurface the exposed bone or joint and then covered with a split thickness skin graft. Ten digital amputations between the distal phalanx proximal to the nail matrix and the mid portion of the middle phalanx were successfully resurfaced with dorsal adipofascial turn-over flaps. All flaps survived completely and the mean follow-up was 11 months. This one-step procedure would seem to be a relatively simple way of achieving early recovery because it does not require the use of distant flaps immobilization of adjacent digits, or homodigital flaps that might jeopardize an already injured finger.     

Distribution of proteoglycans in the human trabecular meshwork: histochemical electron microscopic findings with cuprolinic blue

The distribution of sulfated proteoglycans (PGs) in the normal human trabecular meshwork was studied by histochemical electron microscopy using the cationic dye, cuprolinic blue (CB).. The trabecular meshwork was obtained from human enucleated eyes and incubated for three days. After incubation, they were stained with 0.2% CB at a critical electrolyte concentration and prepared for histochemical electron microscopy. Ultrastructurally, PG-CB complexes were found as small punctate or filamentous structures, and were associated with collagen fibrils in the cores of the trabecular beams and the basal laminae of trabecular endothelial cells. In addition, large filamentous PG-CB complexes were mainly associated with areas of amorphous extracellular matrix between the collagen fiber bundles and in the fine fibrillar material near the basal laminae of endothelial cells of Schlemm's canal. This investigation resulted in an illustration of the ultrastructural distribution of PGs in the human trabecular meshwork. Further studies will be needed to specify the nature of PGs and their role in the aqueous outflow system.     

Penetrating keratoplasty in patients with corneal scarring due to trachoma

BACKGROUND AND OBJECTIVE: Trachoma remains the leading cause of preventable corneal blindness. The outcome of penetrating keratoplasty (PK) in these patients is usually poor because of the extensive corneal vascularization, adnexal and ocular surface problems. We evaluated the long-term results of PK in patients with corneal scarring due to trachoma. PATIENTS AND METHODS: The fiels of 16 eyes of 13 patients who underwent PK due to late sequel of trachoma were reviewed. RESULTS: Preoperative visual acuity ranged from light perception to finger counting levels. Preoperatively, dry-eyes, meibomian gland dysfunction, trichiasis and cicatricial entropion were treated. Over a mean postoperative follow-up of 26.1 +/- 15.6 months (range of 14-61 months), eyes required redrafting due to graft rejection and failure, and corneal ulceration (12.5%). Fourteen eyes remained clear grafts (87.5%), and 13 eyes (81.3%) achieved 0.1 or better visual acuity. CONCLUSIONS: These results suggest that although patients with corneal scarring due to trachoma are at high risk, PK may be helpful for visual rehabilitation.     

Early intracellular signalling pathway of ethanol in vascular smooth muscle cells

1. ERKs belong to MAP kinase family and are activated by several growth and stress factors. Although ethanol has been shown to modulate ERK1 and ERK2 (p44(mapk) and p42(mapk)) activity, it can also act as an antiproliferative agent in various mammalian cells. Since the nature of the antiproliferative effect of ethanol in VSMCs has not been defined, we examined its effects on growth and on early intracellular events normally induced by growth factors in VSMCs. 2. Measurement of cytosolic Ca(2+) and pH in cell monolayers was performed using fura-2/AM and BCECF/AM, respectively. The effect of ethanol on VSMCs growth was assessed by [(3)H]-thymidine incorporation, by cell counting and by determination of the caspase 3 activity. Stimulation of ERK1 and ERK2 was examined by the chemiluminescence Western blotting method. The expression of c-fos was quantitated by Northern blotting. Determination of inositolphosphates was performed after labelling of VSMCs with myo-[2-(3)H]-inositol and separation of inositolphosphates by HPLC. 3. Ethanol (0.3 - 1.0% v v(-1), 17 - 170 mM) induced a dose-dependent maximal stimulation of p44(mapk)/p42(mapk) at 30 min and expression of c-fos mRNA with a maximum at 120 min. Intracellular events upstream to MAP kinase, like an increase in [Ca(2+)](i), activation of the Na(+)/H(+) exchanger and formation of phosphoinositol metabolites were also markedly activated by ethanol. Treatment of VSMCs with ethanol for 3 - 5 min induced an increase in DNA synthesis whereas treatment of the cells for more than 30 min was toxic. Caspase 3 activity was not modulated by ethanol treatment of VSMCs. 4. We may postulate that the activation of these mitogenic signals including the elevation of DNA synthesis reflects a cell effort to protect itself against the toxic effects of ethanol.     

Aggregation inhibitory activity of minor acetophenones from Paeonia species

Two minor acetophenones, 2,5-dihydroxy-4-methoxy-acetophenone (2) and 2,5-dihydroxy-4-methylacetophenone (7) from Paeonia species were found to selectively inhibit the aggregation of rabbit platelets induced by arachidonic acid. They were more potent than the major compound, paeonol (1), and 7 also inhibited the formation of TXA2 and PGD2 from arachidonic acid.     

In vitro inducible nitric oxide synthesis inhibitory active constituents from Fraxinus rhynchophylla

Bioassay-guided fractionation of an H2O extract of the barks of Fraxinus rhynchophylla has furnished two inducible nitric oxide synthase (iNOS) inhibitory compounds, ferulaldehyde (1) and scopoletin (3) together with a coumarin, fraxidin (2). Compounds 1 and 3 showed inhibition of nitric oxide (NO) synthesis in a dose-dependent manner by murine macrophage-like RAW 264.7 cells stimulated with interferon-gamma (IFN-gamma) plus lipopolysaccharide (LPS). The inhibition of NO synthesis of 1 was reflected in the decreased amount of iNOS protein, as determined by Western blotting.     

Pathogenesis and prevention of stomach cancer.

In many Western developed countries, the incidence of stomach cancer has declined dramatically. This decrease was an extraordinary, "unplanned triumph", especially when compared to other cancers. Stomach cancer is still the most prevalent malignant tumor in Korea. Most Koreans carry Helicobacter pylori in their stomach. Thus, a new hypothesis, based on the relationship between the host and Helicobacter pylori, is presented as the carcinogenesis of human stomach cancer. The reasons for why the N-nitrosamide hypothesis should be dismissed as the etiology of stomach cancer, and why the contemporarily available principles and practice of intervention strategies to rapidly decrease the surprisingly high prevalence rate of Helicobacter pylori infection are impractical at this moment, are explained. In order to introduce an alternative provisional strategy of the "planned triumph" for the population vulnerable to stomach cancer, vitamin C is defined as an anti-inflammatory agent on the basis of the pathogenesis of Helicobacter pylori infection.     

Doppler velocimetry of intraplacental fetal arteries

Doppler velocimetry of the umbilical and intraplacental fetal arteries was studied by color flow mapping in 39 normal pregnancies. The systolic-diastolic ratio (S/D) and pulsatility index of the intraplacental fetal artery downstream to the umbilical artery decreased significantly with advancing gestational age, and its S/Ds were persistently lower than those of the umbilical artery. The difference in the S/D between the umbilical artery and its intraplacental downstream branches decreased with advancing gestational age and approached zero as the pregnancy progressed to term. We conclude that intraplacental fetal arteries, possibly fetal arteries in main stem villi, can be imaged by color flow mapping and that there is a significant "resistance gradient" between the intraplacental fetal artery and the umbilical artery. Intraplacental fetal artery velocimetry using color flow mapping may give further insights into the umbilical-placental circulation.     

Differentiation of various Propionibacterium species from acne-vulgaris efflorescences]

Samples of pustules taken from 37 patients with acne (a. vulgaris, a. papulopustulosa, a. conglobata) were examined using different culture mediums for the growth of anaerobic to microaerophilic coryneforms. We identified 46 isolates of Propionibacteria which were tested according to their morphological, biochemical, serological, and phagelysotopic reactions. Three types of Propionibacteria were found: P. acnes (33), P. granulosum (11) and P. avidum (2). Nine samples showed P. acnes combined with P. avidum, four samples from patients with acne conglobata showed P. granulosum or P. avidum only. Tests from 37 patients are too limited to reach definite conclusions. We are not able to suggest any correlation between type and degree of clinical acne, and the isolated Propionibacteria. These data indicate that pustules from patients with acne of all clinical degrees can contain P. acnes as well as other anaerobic coryneforms. Therefore, other species of anaerobic bacteria, particularly those of the "propionibacteria type", should be included in any discussion about the aetiological factors of acne.