Significance of serum CrossLaps as a predictor of changes in bone mineral density during estrogen replacement therapy; comparison with serum carboxyterminal telopeptide of type I collagen and urinary deoxypyridinoline

The newly developed Elecsys -CrossLaps/serum assay measures C-terminal telopeptide of type I collagen and has thus been proposed as a reliable serum marker for bone resorption. We investigated its usefulness for monitoring the therapeutic effect of estrogen replacement therapy on bone turnover and bone mineral density (BMD) in patients with postmenopausal osteoporosis. Serum -CTx decreased by 43.2% ± 9.2% (mean ± SD), and 55.1% ± 7.0% at 3 and 6 months, respectively, after initiation of estrogen replacement therapy (ERT), which was significantly greater than the respective value of urinary excretion of deoxypyridinoline (DPD) (27.8% ± 4.1%, 34.1% ± 4.9%, respectively) or pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) assay (14.5% ± 4.1%, 13.1% ± 5.0%, respectively). The percent reduction in serum -CTx at 1, 3, and 6 months after initiation of ERT was significantly correlated in a negative manner with the percent increase in spinal BMD at 6 months. Further, ROC analysis to determine the significance of the percent change in bone resorption markers after 3 months of ERT in predicting the gain in spine BMD after 6 months suggested that serum -CTx and urinary DPD might provide a more discriminating indicator than serum ICTP. In conclusion, the findings suggest that the Elecsys -CrossLaps/serum assay provides a sensitive, and thus useful, tool for assessing bone resorption state in Japanese patients.     

The effects of prolonged controlled hypotension induced by prostaglandin E1 on renal tubular function

The effects of the prolonged 3-hour and 6-hour controlled hypotension induced by prostaglandin E₁ (PGE₁) on renal tubular function have been comparatively studied with trimethaphan (TMP; 3-hour hypotensive anesthesia) and enflurane deep anesthesia (6-hour hypotensive anesthesia), using the urine N-acetyl--D-glucosaminidase (NAG index) and the serum and urine ₂-microglobulin (fractional clearance of ₂-m; Fc-₂-m) as markers. During 3-hour and 6-hour controlled hypotension PGE₁, NAG index and Fc-₂-m and urine volume could be maintained without remarkable changes. In the group with TPM, NAG index and Fc-₂-m significantly increased. The increasing trend was also noted over time in deep anesthesia with enflurane. On 1st postoperative day, Fc-₂-m significantly increased in PGE₁ group in both 3-hour and 6-hour hypotensive anesthesia, whereas it restored to normal on 2nd postoperative day. Also, in TMP and enflurane deep anesthesia, Fc-₂-m significantly increased on 1st postoperative day. With the latter, significant increase was also observed on 2nd postoperative day. These results suggest that, in 3-hour and 6-hour controlled hypotension induced by PGE₁, renal tubular function is normally maintained and that it is useful for prolonged controlled hypotensive anesthesia. However, further study is necessary because tubular dysfunction might appear on 1st postoperative day.(Fukusaki M, Shibata O, Fujigaki T et al.: The effects of prolonged controlled hypotension induced by prostaglandin E₁ on renal tubular function. J Anesth 4: 197–205, 1990)     

The changes in arterial keton bodies during upper abdominal surgery

The relationship between the arterial keton body ratio (AKBR: acetoacetate/-hydroxybutyrate) and the plasma hormone activities were studied under a general anesthesia using enflurane group (group G) and a GO + Epidural group (group E) with continuous glucose loading (10g·hr^–1) during partial gastrectomy. In both groups, the AKBR increased significantly during the operation. The plasma insulin activity was significantly positively correlated with the AKBR and it was negatively correlated with log (-hydroxybutyrate) in both groups. We could not find any significant difference of the AKBR between group G and group E. Our results indicate that the plasma insulin activity affects the arterial keton body ratio and that the AKBR must be evaluated considering the plasma hormone activity, especially insulin activity during the operation.(Ogata M, Obata K, Matsumoto et al.: The changes in arterial keton bodies during upper abdominal surgery. J Anesth 4: 131–137, 1990)     

Quantitative ultrasound of bone and clodronate effects in thalassemia-induced osteoporosis

Osteoporosis in -thalassemia major has emerged as a topic of interest since optimized transfusion regimens have increased life expectancy and quality in these patients. Although the pathogenesis of thalassemic osteopathy is multifactorial, the evidence of an increased resorption phase suggests that the use of antiresorptive drugs such as bisphosphonates can be considered a valuable therapeutic strategy to reduce bone turnover and the risk of fragility fractures. We compared the effects of long-term cyclical clodronate therapy (300mg intravenous infusion every 3 weeks for 2 years) and of an active placebo (calcium 1 vitamin D) on bone mass and bone turnover in 30 male patients with -thalassemia major. We also tested the possibility of using quantitative ultrasound (QUS) for assessing bone involvement in thalassemic osteopenia and in monitoring the response to antiresorptive therapy. Broadband ultrasound attenuation (BUA) was significantly reduced in patients with -thalassemia major as compared to healthy controls. In calcium and vitamin D-treated patients, a significant decline in spine, femoral, and total body areal bone density was observed. In the patients given intravenous clodronate we measured a substantial stability of bone mass, which was not significantly changed at the end of the study. The urinary excretion of deoxypyridinoline (a marker of bone resorption) showed a progressive significant decline throughout the study period in clodronate-treated patients. No significant change was observed in BUA values in both groups of patients. These results indicate that intermittent intravenous clodronate administration was not able to increase areal bone density in our thalassemic patients. Moreover, this is the first study to have assessed the usefulness of broadband ultrasound measurements in -thalassemia major.     

Controlling mesenchymal stem cell differentiation by TGFΒ family members

Mesenchymal stem cells can differentiate into various tissue types including bone, cartilage, fat, and muscle. Transforming growth factor- (TGF) family members, including TGFs and bone morphogenetic proteins (BMPs), play important roles in directing fate decisions for mesenchymal stem cells. TGF can provide competence for early stages of chondroblastic and osteoblastic differentiation, but it inhibits myogenesis, adipogenesis, and late-stage osteoblast differentiation. BMPs also inhibit adipogenesis and myogenesis, but they strongly promote osteoblast differentiation. TGF family members signal via specific serine/threonine kinase receptors and their nuclear effectors, termed Smad proteins. In this review we discuss recent advances in our understanding of the molecular mechanisms by which TGF family members control mesenchymal stem cell differentiation.Presented at the 17th Annual Research Meeting of the Japanese Orthopaedic Association, Aomori, Japan, October 2002     

Effect of tumor necrosis factor-α and interferon-γ on the growth of human prostate cancer cell lines

Human recombinant tumor necrosis factor- (rTNF-, 10^-12–10^-8 M) inhibited the proliferation of androgen-dependent LNCaP cells by 32–56%. In contrast, proliferation of androgen-independent PC-3 and JCA-1 cells was only slightly inhibited, or not inhibited at all, respectively. Human recombinant interferon- (rIFN-, 500 U/ml) decreased proliferation of PC-3 and JCA-1 cells by 35% and 53%, respectively, but had no effect on LNCaP cells. Interestingly, the combination of rIFN- and TNF- had greater antiproliferative effects on JCA-1 cells than treatment with either cytokine alone. However, the antiproliferative effects of this combination were similar to those observed for PC-3 or LNCaP cells treated with rIFN- or TNF- alone, respectively. These data suggest that some forms of androgen-independent prostate cancer may benefit from a combination therapy of IFN- and TNF-, while the use of IFN- alone may be more efficacious in others.     

An in vitro method for comparing the efficacy of two preservation solutions in one canine liver using the 5′-nucleotidase assay

The activity and localization of the plasma membrane-bound enzyme 5-nucleotidase (5-NT) in liver tissue are sensitive parameters of ischemic damage. The value of 5-NT as a marker of liver graft viability was studied in relation to liver preservation. In six mongrel dogs, the main right and left branches of the portal vein were cannulated and flushed separately in situ with cold University of Wisconsin (UW) solution and Euro-Collins (EC) solution, respectively. After hepatectomy, the right and left liver lobes were split and stored at 5°C in either of the two solutions. 5-NT activity was demonstrated in cryostat sections of liver tissue using the lead salt method. After 48 h of storage in EC solution, the 5-NT score had decreased to 31%±16% (n=6), whereas in UW solution the 5-NT score was 76%±10% (n=6). Significantly (P<0.05) higher 5-NT scores were also found after 24-h and 72-h preservation times in UW versus EC solutions. This result is in keeping with the higher preservation tolerance of liver grafts preserved in UW solution. The 5-NT assay was studied in relation to graft function in orthotopic liver transplantation experiments in dogs. All dogs with liver grafts preserved in UW solution for 24 h (n=4) and 48 h (n=3) survived (>5 days). pretransplant 5-NT scores ranged from 61% to 100%. The 72-h-preserved livers (n=5) did not show life-supporting function. Pretransplant 5-NT scores (33%±12%, n=5) were significantly (P<0.05) decreased. The 5-NT score pretransplantation was a more reliable indicator of graft function than peak SGOT values post-transplantation. In conclusion, the 5-NT assay, in conjunction with the double flush method through the portal vein, provides a simple and rapid in vitro method to test solutions for liver preservation.     

Changes in the productivity of cytokines and active-oxygen in peripheral blood cells following surgery

An investigation was carried out on the productivity of cytokines and active-oxygen by peripheral blood cells during the pre- and post-operative periods. While the preoperative production of tumor necrosis factor (TNF) and interleukin-l (IL-1) was elevated, that of lymphotoxin (LT) and interferon- (IFN-) were slightly suppressed. In the postoperative period the peak TNF and IL-1 and active-oxygen productivity was elevated, while LT and IFN- productivity was suppressed in patients with an intraoperative bleeding volume of more than 1,000 ml compared to those with that of less than 1,000 ml. Thus, stress stimulates the TNF and IL-1 and active-oxygen producing system, that is, the macrophage-neutrophil system, and suppresses the LT and IFN- system, being, the inflammatory helper T cell system, in the early postoperative period.     

Receptor function studies in specimens from the proximal human urethra obtained by transurethral resection

Summary During transurethral resection (TUR) for prostatic hyperplasia, specimens were taken from the proximal urethra. Muscle strips thus obtained were mounted in an organ bath and muscle contraction was induced by adding increasing concentrations of noradrenaline (NA), methoxamine (₁-agonist) and clonidine (₂-agonist). NA and methoxamine induced a dose-dependent muscle contraction, but clonidine had no effect. The influence of prazosin (₁-antagonist) and yohimbine (₂-antagonist) on the NA-induced muscle contraction was also evaluated. Both antagonists had an inhibitory effect,which was much more potent with prazosin. The specimens taken during TUR were found to be suitable for in vitro receptor function studies. The -adrenergic receptor function in the proximal human urethra was found to be mainly of the -type.     

Serum α1-microglobulin and β2-microglobulin for the estimation of fetal glomerular renal function

As proteins cannot cross the placenta levels of the microproteins ₁-microglobulin (₁MG) and ₂-microglobulin (₂MG) can be used to assess fetal glomerular renal function. ₁MG, ₂MG and creatinine were routinely determined in cord and maternal blood of 133 newborns [gestational age (GA) 25–42 weeks]. Twenty-nine patients with suspected impaired maternal or fetal renal function were studied separately and two fetuses were studied in utero. The mean fetal ₂MG concentration fell from 3.87±0.56 mg/l in the 25–31 weeks GA group to 2.60±0.50 mg/l in the mature newborn group. ₁MG concentration fell from 3.10±0.51 to 2.25±0.49 mg/dl. In contrast, the mean maternal ₁MG concentration rose from 1.73±0.69 mg/l in the 25–31 weeks GA group to a mean of 1.83±0.48 mg/l in the mature newborn group; ₁MG rose from 3.96±0.58 to 4.33±1.6 mg/dl. Maternal and fetal creatinine levels were identical. Fetal microprotein levels fall during intra-uterine development as glomerular filtration rate (GFR) rises. There is no correlation between cord blood and maternal ₁MG or ₂MG concentrations. In 13 children with urological anomalies only 1 had elevated microprotein levels and he later developed renal insufficiency. Determination of microprotein levels in fetal serum can be used to detect severe renal function disturbances and to estimate GFR independently of maternal renal function.     

Anastomotic insufficiency in small bowel surgery —incidence and treatment

Summary In the period 1977–1981 234 small bowel anastomoses were constructed in 143 patients. Eight anastomoses showed leakage (3.4%) and from nine anastomoses a fistula developed (3.8%): a total rate of disturbed healing of small bowel anastomoses (7.3%). In the presence of intra-abdominal infection this rate was 14.8%, in the absence of infection 0.8%. The results of treatment with oversewing and with resection and immediate anastomosis were disappointing. Better results were obtained by dismantling of the anastomosis, establishment of a split-enterostomy and reestablishment of continuity in a second stage. Mortality was 3/17 (18%). The literature is reviewed.

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Insuffizienz von Dünndarmanastomosen — Ineidenz und Therapie

Zusammenfassung In dem Zeitraum 1977–1981 wurden bei 143 Patienten 234 Dünndarmanastomosen angelegt. Acht Anastomosen zeigten eine Nahtleckage (3,4%), bei neun entwickelte sich eine Fistel (3,8%): die Gesamthäufigkeit von Wundheilungsstörungen bei Dünndarmanastomosen war 7,3%. Bei gleichzeitigem Vorliegen intraabdominaler Infektionen betrug die Häufigkeit 14,8%, ohne diese 0,8%. Die Resultate einer Therapie durch Übernähung oder Resektion mit sofort anschließender Reanastomosierung waren enttäuschend. Befriedigendere Ergebnisse wurden durch Aufheben der Anastomosen, Anlage einer split enterostomy unter Wiederherstellung der Kontinuität in einer zweiten Sitzung erzielt. Die Mortalität betrug 3/17 (18%). Ein Literaturüberblick wird gegeben.

     

The diagnosis and treatment of the ‘mixed’ type of depressed fractures of the calcaneum

Summary The mixed type of depressed fractures of the calcaneum is described and a classification proposed. During a six year period, 78 patients with fractures of the calcaneum were seen. Of these 32 were of the mixed type and 23 were treated by sub-talar arthrodesis and restoration of the calcaneal outline. Very good or good results were obtained in all patients subjected to operation.

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Résumé L'auteur décrit un type de fracture du calcanéum par enfoncement «mixte» (i. e. à la fois vertical et horizontal) et il en propose une classification. Sur 78 fractures du calcanéum observées en six ans, 32 étaient de ce type «mixte» et 23 d'entre elles furent traitées par arthrodèse sous-astragalienne avec reconstitution de la forme du calcanéum. D'excellents ou de bons résultats ont été obtenus chez tous les blessés qui ont bénéficié de cette intervention.

     

Association of meningiomas with dural “tails”; Surgical significance

Summary Intracranial meningiomas are characteristically benign tumours with a tendency to recur following surgical resection. Our group is investigating the pathogenesis of meningioma recurrence. In our initial studies we identified two cases of dural tails associated with intracranial meningiomas. Gadolinium-enhanced magnetic resonance images were utilized to identify the dural tails preoperatively. These images aided us in performing a more complete surgical resection of the meningiomas. Histopathological confirmation of meningotheliomatous cell infiltration into the dural tails demonstrates their surgical significance.     

Surgical remodeling of the silhouette by aspiration lipolysis or selective lipectomy

The author, a pioneer in originating the technique of suction lipectomy, discusses in detail the pathophysiology of the fat cell and fat metabolism. In addition, he describes the surgical means by which, since 1977, he has popularized this innovative new approach to the treatment of unsightly fat deposits in many sites in the body, including the thighs, buttocks, abdomen, hips, arms, ankles, breasts, and submental regions.     

Urinary unconjugated 5α-androstane-3α, 17β-diol in patients with prostatic tumours

Summary A sensitive and reliable radioimmunoassay (RIA) for urinary unconjugated 5-androstane-3, 17-diol is described. The mean overall recovery of unconjugated 5-androstane-3, 17-diol was found to be 57.4%. The sensitivity of the assay was 79 fmol per assay tube and the intra and inter-assay variations ranged between 7.2% and 11.4%. The mean ± SEM for the concentration of this androgen in the urine of normal men was 339.6±66.8 nmol/24h. The corresponding values for patients with benign prostatic hypertrophy (BHP) and carcinoma of the prostate (Ca) were 297.8±44.7 and 1592.1±622.7 respectively. The mean value for Ca patients was significantly higher than either BPH (p<0.05) or normal subject (p<0.02), suggesting a differential urinary excretion pattern for unconjugated 5-androstane-3, 17-diol between BPH and Ca patients. It is concluded that the combined measurement of this androgen in the plasma and urine provides a more accurate assessment of the profile of this hormone than a single plasma estimation.     

Deformation: Its application to cosmetic facial surgery

The principles of deformation have come to our attention through the study of technical skills in art. It creates emphasis on the motif of a work by transformation and results in the illusionary phenomenon that makes the total appearance more harmonious and impressive. With this artistic technical concept compounded with our surgical experiences, we designed the deformation technique for facial corrective surgery. Introducing some distinctive cases applying this technique, we show its advantages over the see a defect, correct the defect limitations to present surgical techniques and the good effect of the patient's mind and attitudes.Presented at the 17th Annual Meeting of the American Society for Aesthetic Plastic Surgery, Los Angeles, California, April 20, 1983     

“Tear-Drop Augmentation Mastopexy”: A Technique to Augment Superior Pole Hollow

Breast ptosis classification systems focus on the inferior descent of the nipple, as well as the descent and distribution of the breast parenchyma below the inframammary fold. Common problems, such as development of a superior pole hollow and an excessive width of the superior pole, extending into the axilla, are not addressed. Few procedures specifically address these deficiencies, and even less information is available in terms of preventative maneuvers when augmentation is desired as an adjunct. Round implants worsen the problem by creating a superior pole shelf, and anatomic implants are unreliable alternatives. Here, we present a technique—tear-drop augmentation mastopexy—that addresses superior pole hollow, excess superior pole width, as well as breast ptosis and hypomastia. Patients with moderate to severe breast ptosis (Regnaults classification), tubular breast deformity, and deformities secondary to previous breast surgery are included in the study. Skin is deepithelialized through a circumareolar incision, and a skin-fat flap is elevated completely encircling the breast. A 2-cm area of parenchyma is left attached to the skin in the lower half of the breast. Breast parenchyma in the superior half of the breast is then advanced and plicated in a superiomedial direction to move the nipple areolar complex to the desired new position. Care is taken to redefine the pectoralis major muscle at its axillary border. A 3-cm incision is then placed in the inferior part of the parenchyma at the 6 oclock position to create a subpectoral pocket for placement of the implant. The tunnel is then closed to separate the implant pocket from the subcutaneous dissection. Residual dermal flap is used to define, and add durability to the parenchyma reshaping procedure. A 3-0 mersiline (Ethicon, Somerville, NJ) blocking suture is used for a uniform circumareolar skin closure. Patients (n:35), ages 17–48, underwent tear-drop augmentation mastopexy between January 1999 and September 2002 for correction of the breast ptosis, tubular breast deformity, and deformities secondary to previous aesthetic breast surgery. The average follow-up was 2 years. All patients displayed type 1 or 2 (Baker classification) capsules. One subcutaneous hematoma and one subcutaneous seroma were seen, which were both treated by percutaneous aspiration. No submuscular hematomas, infections, skin or nipple losses, or hypertrophic scars were noted. Patient satisfaction was high. A more natural tear-drop breast shape was created with an improvement in the superior pole hollow and narrowing of the superior breast. The smallest breasts did not benefit from this technique for elimination of the superior pole shelf, as correction was proportional to the amount of breast tissue available for superior advancement. The tear-drop augmentation mastopexy is a novel technique for correction of the breast ptosis with augmentation, avoiding problematic development of superior pole hollow and excess superior width. This technique is also well applied to tubular breast deformity as well as to secondary breast procedures. Long-term follow-up demonstrates a safe and reproducible result with high patient satisfaction. This technique may solve several problems associated with breast ptosis surgery, which before were not specifically addressed, and the technique warrants further investigation.     

170. Operative Korrektur der Phimose im Kindesalter mit der Plastibell-Methode

Zusammenfassung Auf der Basis von Bildern der verschiedenen Operationsphasen und -ergebnissen wird die Technik der Plastibell-Methode gezeigt. Sie bedeutet eine einfache, komplikationslose Möglichkeit zur Korrektur der angeborenen oder erworbenen Phimose und ist ebenso verwendbar bei routinemäßiger Beschneidung Neugeborener. Postoperativer Heilverlauf und Nachuntersuchungsergebnisse bei über 400 Fällen sind als gut zu bezeichnen. Das Plastibell-Verfahren, besonders gut im ambulanten Bereich durchführbar, wird als Methode der Wahl empfohlen.