Hydroxyapatite ceramics as a particulate embolic material: report of the clinical experience

BACKGROUND AND PURPOSE: Our newly developed biocompatible embolic materials, hydroxyapatite ceramic microparticles, have good visibility during injection control and were shown to be capable of producing effective occlusion of the distal arteriocapillary bed in an experimental animal study. The purpose of this present study was to evaluate hydroxyapatite ceramic microparticles for use in human meningioma embolization. METHODS: Thirteen patients with meningiomas underwent preoperative superselective embolization with the use of hydroxyapatite microparticles. Radiologic and histopathologic studies of the surgical specimens were performed. RESULTS: During embolization, no microcatheter clogging was observed and angiographic devascularization was consistently obtained without unexpected proximal occlusions. Histopathologic findings showed that there was mild inflammatory response in the thrombosed lumen. CONCLUSION: Hydroxyapatite microparticles are excellent embolic materials for the treatment of human meningioma. They have excellent biocompatibility and good injection control, which produces occlusion of the distal arteriocapillary bed.     

Scintigraphic progress of the liver in a patient with Alagille syndrome (arteriohepatic dysplasia)

We encountered a 9-year-old Japanese girl with Alagille syndrome. Her scintigraphic examinations of the liver were performed at the ages of 16 months and 9 years. 99mTc-PMT, a hepatobiliary imaging agent, was distributed homogeneously in the liver at the younger age, but unevenly produced an area of focally increased uptake in the medial segment of the liver surrounded by peripheral atrophy at the older age. 99mTc-GSA, a hepatoreceptor binding agent, was highly accumulated in the area, corresponding to the focally increased uptake of 99mTc-PMT. These imaging findings suggest that the pathophysiological and morphological changes of the liver occurred in our patient during the clinical course.     

Effects of counseling on climacteric symptoms in Japanese postmenopausal women

OBJECTIVES: We objectively assessed the effects of counseling on climacteric symptoms in Japanese postmenopausal women. METHODS: Symptoms in 44 women (age, 51.4 +/- 3.4 years; period after menopause, 3.6 +/- 3.4 years) treated with counseling were evaluated according to the Keio modified menopause index. The response to counseling was compared with that to hormone replacement therapy (HRT). RESULTS: Forty cases (90.9%) showed an improvement in index score. There were no significant relationships between improvement and age, the period after menopause, or the severity or type of symptoms before counseling. The most improved symptom was headache, followed by palpitation and insomnia. Physical symptoms accounted for most of the common symptoms. The pattern of improvement with counseling was markedly different from that with HRT. CONCLUSIONS: We suggest that counseling is effective for treating climacteric symptoms, since it improves not only psychological symptoms, but also physical ones. Counseling may deserve evaluation as a complementary treatment to HRT.     

Role of nitric oxide and prostaglandin E2 in acute renal hypoperfusion

Although acute renal ischaemia alters the production of various paracrines, there has been little investigation examining the role of intrarenal vasoactive substances. In the present study, we investigated the role of intrarenal nitric oxide and prostaglandins in modulating the acute renal hypoperfusion-induced alterations in renal function. After a 90% clipping of the left renal artery for 60 min, the clip was released, and the renal haemodynamics and sodium excretion were evaluated in both clipped and non-clipped kidneys of anaesthetized dogs. Furthermore, the changes in renal contents of nitrate/nitrite (NOx) and prostaglandin E2 (PGE2) were assessed by using the renal microdialysis technique. The release of the clipping elicited a gradual recovery of renal plasma flow and glomerular filtration rate, and a sustained increase in fractional sodium excretion (FENa) in the clipped kidney. Renal interstitial NOx was reduced in both the cortex (from 8.2 +/- 1.1 to 2.5 +/- 0.3 micromol/L, P < 0.01) and medulla (from 10.1 +/- 0.9 to 3.1 +/- 0.2 micromol/L, P < 0.01), but the levels gradually elevated after declamping. The treatment with nitro-l-arginine methylester only modestly impaired the recovery of renal plasma flow (RPF; at hour 4) and glomerular filtration rate (GFR; at hours 3 and 4 after declamping), without affecting FENa. Conversely, the renal PGE2 levels increased prominently upon the onset of ischaemia (medulla, from 149 +/- 19 to 378 +/- 39 pg/mL, P < 0.01; cortex, from 107 +/- 13 to 302 +/- 34 pg/mL, P < 0.01). Furthermore, the pretreatment with a non-specific cyclo-oxygenase (COX) inhibitor, sulpyrine, and a COX-2-specific inhibitor, NS398, prominently inhibited the increases in FENa induced by the acute renal arterial clipping in a similar manner. In conclusion, in acute renal hypoperfusion, nitric oxide (NO) plays a permissive role in the recovery of the renal haemodynamics. In contrast, sustained increases in renal PGE2 in both clipped and non-clipped kidneys indicate that the COX-2-mediated PGE2 contributes importantly to the failure of the sodium reabsorption in response to acute renal hypoperfusion.     

Competitive incorporation of arachidonic acid analogs by cultured rat keratinocytes

Arachidonic acid (20:4 n-6) and its metabolic products, such as prostaglandins and leukotrienes, have been known to be associated with skin inflammatory reactions. However, the mechanism of the competitive incorporation of 20:4 n-6 into keratinocytes among polyunsaturated fatty acids (PUFAs) remains uncertain. To investigate the relationship between the molecular structure of PUFAs and the rate of incorporation of PUFAs into cells, a fetal rat skin keratinocyte (FRSK) cell line was used. The cells were incubated for 24 h with any two of the following arachidonic acid analogs: mead acid (20:3 n-9), dihomo-gamma-linolenic acid (20:3 n-6), 11,14,17-cis-eicosatrienoic acid (20:3 n-3), arachidonic acid (20:4 n-6), eicosapentaenoic acid (20:5 n-3) and 5,8,11,14-cis-nonadecatetraenoic acid (19:4 n-5), at the ratio of 1:0, 0.5:0.5, or 0:1; and their incorporation into lipid was measured by capillary gas-liquid chromatography. The experiments indicated that 20:3 n-6 was preferentially incorporated into phospholipids of FRSK rather than 20:3 n-9 or 20:3 n-3, and 19:4 n-5 as well as 20:4 n-6 was preferentially incorporated into total cellular lipid and phospholipids rather than 20:3 n-9 or 20:5 n-3. When two PUFAs were added simultaneously to the medium, 19:4 n-5 most effectively reduced the competitive incorporation of 20:4 n-6 into phospholipids. These results suggest that keratinocytes discriminate 20:4 n-6 from other arachidonic acid analogs by its double bond positions from the carboxyl group.     

Cryopreservation of human sperm in patients with malignancy: First 2 years’ experience

Background  Patients with malignancy (n = 130) participated in the sperm cryopreservation program. Methods  After washing and concentrating, sperm was cryopreserved using KS-VIm cryoprotectant medium. Participant background factors such as age, marital status, underlying disease, presence or absence of previous treatment and semen findings (concentration, motility and morphology) were analyzed to determine parameters associated with the program. Results  Patients in their 20s were most common (64 cases) and 94 cases were unmarried at the first visit. The main underlying diseases were testicular tumor (53 cases), leukemia (43 cases) and malignant lymphoma (13 cases). The program was completed for 118 cases. For leukemia, all semen parameters were closer to normal in patients without previous treatment (untreated group, UG) compared with the treated group (TG). When semen findings in the UG were classified according to underlying disease, sperm concentration was lower in patients with testicular tumor compared with those who had leukemia or malignant lymphoma. Four couples underwent reproductive therapies with the cryopreserved sperm through assisted reproductive technology, and three babies were born to two couples. Conclusion  Sperm cryopreservation liberates patients with malignancy from iatrogenic infertility as a consequence of intensive therapy, allowing them to retain reproductive ability.     

Immunohistochemical studies on tenascin in extrahepatic bile duct remnants of biliary atresia

The expression of tenascin in the extrahepatic bile duct remnants in biliary atresia was investigated using an immunohistochemical method. Tenascin is thought to be a marker of repair of injured tissues based on an immunohistochemical study of a variety of tissues. Twenty-three specimens were obtained from 23 cases (2 correctable type and 21 non-correctable type) of biliary atresia at the time of the definitive operation. Positive tenascin staining was observed in matrices surrounding degenerated epithelium of the bile ductules in the obliterated extrahepatic bile duct. Regarding the correlation between the size of the bile ductule and the degree of positive staining, the larger diameter bile ductules tended to show a higher degree of positive staining. Furthermore, regarding the correlation between the degeneration of epithelium and the degree of staining, the bile ductules with the more significantly denuded epithelium tended to show a higher degree of positive staining. In some specimens classified as non-correctable type, a lumen larger than 1 millimeter in diameter without epithelium was observed. This ductule itself was thought to be the original extrahepatic bile duct because strong tenascin staining was observed surrounding this lumen. These findings suggested that the extrahepatic bile duct might be obliterated after the completion of the hepatobiliary tree system and the bile ductules in the obliterated extrahepatic bile duct might be degenerated in order of their size.     

Multicenter randomized phase II clinical trial of oxaliplatin reintroduction as a third- or later-line therapy for metastatic colorectal cancer—biweekly versus standard triweekly XELOX (The ORION Study)

Background

The aim of this multicenter, open-label, randomized phase II trial was to evaluate the efficacy of a dose-dense capecitabine and oxaliplatin (XELOX) regimen in patients with metastatic colorectal cancer (mCRC) for whom reintroduction of oxaliplatin had been planned as a third- or later-line regimen.

Methods

The patients with mCRC who had received prior chemotherapy including oxaliplatin and were scheduled for reintroduction of oxaliplatin were randomized to capecitabine (1,000 mg/m²) twice daily on days 1–14 and oxaliplatin (130 mg/m²) on day 1 every 21 days (Q3W group) or capecitabine (2,000 mg/m²) twice daily on days 1–7 and oxaliplatin (85 mg/m²) on day 1 every 14 days (Q2W group). The primary endpoint was the time-to-treatment failure (TTF). Other endpoints included overall survival (OS), progression-free survival (PFS) and other adverse events (AEs).

Results

A total of 46 patients were enrolled in the trial—22 patients were randomly assigned to the Q3W group and 23 to the Q2W group. The median TTF was 3.4 months in both groups (hazard ratio [HR] 1.053; p = 0.880). The median PFS and OS were 3.3 and 9.2 months in the Q2W group and 4.3 and 12.1 months in the Q3W group, respectively (HR 1.15; p = 0.153 and 0.672; p = 0.836). The most common grade 3?4 AEs in the Q3W and Q2W groups were fatigue (27.3 vs 21.7), neuropathy (9.1 vs 0 %) and diarrhea (9.1 vs 0 %), respectively.

Conclusion

There was no significant inter-group difference in any of the efficacy and safety endpoints, including TTF, OS, RFS and AEs. The results of this clinical trial were convincingly negative.

     

Tibial tubercle transfer on a medial periosteal pedicle--a report of a new technique

Tibial tubercle transfer is still probably the most widely used procedure of the numerous operative procedures described to realign the patella and extensor mechanism and to prevent a recurrent dislocation. Although this procedure most likely disturbs the blood supply to the tibial tubercle and thus may lead to a delayed union. Tibial tubercle transfer is also considered to play a role in the incidence of a tibial tubercle delayed union. Furthermore, a fracture of the tibial metaphysis has been reported to occur in some cases. We therefore devised a new procedure in which the periosteum of the medial side of the proximal portion of the tibia was left intact when tibial tubercle transfer is performed. The current paper describes the results of new technique in 25 knees with patellar maltracking. Eighty-four percent of the patients had good or excellent results at a mean follow-up time of 49 months. All of the patients achieved complete healing radiographically within 2 months after the operation. Serious complications such as compartment syndrome, infection and skin slough were also completely avoided in all cases. This new procedure that the use of a protective maneuver for the periosteum of the medial side of the tibia may thus reduce the incidence of a delayed union and thereby promote early postoperative rehabilitation after tibial tubercle transfer.