Allele frequency spectrum of known ankylosing spondylitis associated variants in a Swedish population.

Objective: The genetic predisposition to ankylosing spondylitis (AS) has been most widely studied in cohorts with European ancestry. However, within Europe, disease prevalence is higher in Sweden. Given this, we aimed to characterize known AS susceptibility variants in a homogeneous Swedish data set, assessing reproducibility and direction of effect.Method: The power to detect association within an existing Swedish targeted sequencing study (381 controls; 310 AS cases) was examined, and a set of published associations (n = 151) was intersected with available genotypes. Association to disease was calculated using logistic regression accounting for population structure, and HLA-B27 status was determined with direct polymerase chain reaction genotyping.Results: The cases were found to be 92.3% HLA-B27 positive, with the data set showing ≥ 80% predictive power to replicate associations, with odds ratios ≥ 1.6 over a range of allele frequencies (0.1-0.7). Thirty-four markers, representing 23 gene loci, were available for investigation. The replicated variants tagged MICA and IL23R loci (p < 1.47 × 10-3), with variable direction of effect noted for gene loci IL1R1 and MST1.Conclusion: The Swedish data set successfully replicated both major histocompatibility complex (MHC) and non-MHC loci, and revealed a different replication pattern compared to discovery data sets. This was possibly due to population demographics, including HLA-B27 frequency and measured comorbidities.

Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease.

BACKGROUND: Autoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology. METHODS: To understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls. RESULTS: We identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 × 10-15 , MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addison's disease development. We also confirmed the previously known associations with the HLA complex. CONCLUSION: Whilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addison's disease, we have identified BACH2 as a major risk locus in Addison's disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.

Diagnostic value of abdominal drainage in individual risk assessment of pancreatic fistula following pancreaticoduodenectomy.

BACKGROUND: The use of prophylactic abdominal drainage following pancreaticoduodenectomy (PD) is controversial as its therapeutic value is uncertain. However, the diagnosis of postoperative pancreatic fistula (POPF), the main cause of PD-associated morbidity, is often based on drain pancreatic amylase (DPA) levels. The aim of this study was to assess the predictive value of DPA, plasma pancreatic amylase (PPA) and serum C-reactive protein (CRP) for diagnosing POPF after PD. METHODS: Patients undergoing PD with prophylactic drainage between 2008 and 2012 were studied prospectively. DPA, PPA and CRP levels were obtained daily. Differences between groups with clinically relevant POPF (International Study Group on Pancreatic Fistula (ISGPF) grade B/C) and without clinically relevant POPF (no POPF or ISGPF grade A) were evaluated. Receiver operating characteristic (ROC) analyses were performed to determine the value of DPA, PPA and CRP in prediction of POPF. Risk profiles for clinically relevant POPF were constructed and related to the intraoperative pancreatic risk assessment. RESULTS: Fifty-nine (18.7 per cent) of 315 patients developed clinically relevant POPF. DPA, PPA and CRP levels on postoperative day (POD) 1-3 differed significantly between the study groups. In predicting POPF, the DPA level on POD 1 (cut-off at 1322 units/l; odds ratio (OR) 24.61, 95 per cent confidence interval 11.55 to 52.42) and POD 2 (cut-off at 314 units/l; OR 35.45, 14.07 to 89.33) was superior to that of PPA on POD 1 (cut-off at 177 units/l; OR 13.67, 6.46 to 28.94) and POD 2 (cut-off at 98 units/l; OR 16.97, 8.33 to 34.59). When DPA was combined with CRP (cut-off on POD 3 at 202 mg/l; OR 16.98, 8.43 to 34.21), 90.3 per cent of postoperative courses could be predicted correctly (OR 44.14, 16.89 to 115.38). CONCLUSION: The combination of serum CRP and DPA adequately predicted the development of clinically relevant pancreatic fistula following PD.

Effect of Instrument Lubricant on Mechanical Properties of Restorative Composite.

OBJECTIVES: Using a wetting resin or adhesive system as an instrument lubricant when placing composite layers is commonly practiced to improve handling. This study investigated whether instrument lubricants affected strength, stiffness, or hardness. METHODS: Composite beams (TPH Spectra) were fabricated using a stainless steel mold (25×2.5×2 mm) in two steps, where the second half (12.5 mm) was added and cured against a cured first half (n=15). The composite surface at the open end of the first half was smoothed using an instrument lubricated with wetting resin (Ultradent) or universal adhesive (ScotchBond Universal), enough to prevent sticking, or without lubrication. An additional beam of each group was characterized using scanning electron microscopy. Monolithic specimens were also fabricated. After 24 hour storage (37°C, 100% humidity), the beams' flexural strength and stiffness were determined by four-point bending. Vickers surface hardness was measured on 24-hour composite samples in 2 mm deep acrylic cavities, cured after the surface was smoothed with the two instrument lubricants or no lubricant (n=10). Hardness was remeasured after finishing with a series of contouring and polishing discs. Data were statistically analyzed using ANOVA followed by Student-Newman-Keuls post hoc test at 0.05 significance level. RESULTS: There were significant differences (p<0.001) in flexural strength and stiffness among groups. While strength and stiffness were not affected by using a wetting resin as instrument lubricant, use of a universal adhesive increased strength and stiffness significantly, achieving monolithic values. Scanning electron micrographs showed less porosities at the interface when using instrument lubricants. Surface hardness was significantly reduced in groups in which instrument lubricants were used, but finishing/polishing restored original hardness (p<0.001). CONCLUSIONS: Lubricating an instrument with a wetting agent did not adversely affect physical or surface properties, provided the surface was finished and polished. If a universal adhesive was used as lubricant, the strength and stiffness of a layered composite could be increased, reaching monolithic values.

Safety of zoster vaccine in adults from a large managed-care cohort: a Vaccine Safety Datalink study.

OBJECTIVES: The aim of this study was to examine a large cohort of adults who received the zoster vaccine for evidence of an increased risk of prespecified adverse events requiring medical attention. DESIGN: Two self-comparison approaches, including a case-centred approach and a self-controlled case series (SCCS) analysis were used. SETTING: Eight managed-care organizations participating in the Vaccine Safety Datalink project in the United States. SUBJECTS: A total of 193 083 adults aged 50 and older receiving a zoster vaccine from 1 January 2007 to 31 December 2008 were included. MAIN OUTCOME MEASURES: Prespecified adverse events were identified by aggregated International Classification of Diseases, Ninth Revision (ICD-9) codes in automated health plan datasets. RESULTS: The risk of allergic reaction was significantly increased within 1-7 days of vaccination [relative risk = 2.13, 95% confidence interval (CI): 1.87-2.40 by case-centred method and relative rate = 2.32, 95% CI: 1.85-2.91 by SCCS]. No increased risk was found for the following adverse event groupings: cerebrovascular events; cardiovascular events; meningitis; encephalitis; and encephalopathy; and Ramsay-Hunt syndrome and Bell's palsy. CONCLUSIONS: The results of this study support the findings from the prelicensure clinical trials, providing reassurance that the zoster vaccine is generally safe and well-tolerated with a small increased risk of allergic reactions in 1-7 days after vaccination.

[Coverage of chronic osteomyelitis of the ankle and the foot using a soleus muscle island flap, vascularized with retrograde flow on the posterior tibial artery. A seven cases report]. / Couverture des ostéites de cheville et du pied par un lambeau de muscle soléaire pédiculé en îlot rétrograde sur l'artère tibiale postérieure. A propos de sept cas.

AIM OF THE STUDY: The treatment of chronic osteomyelitis with large skin defects at the foot or the ankle is uneasy. In such cases, free muscular flaps are currently advised but they are less reliable in patients with medical diseases. In such difficult cases we have used the distally based soleus island flap, vascularized with retrograde flow on the posterior tibial artery. The technique and the indications of this flap are discussed. PATIENTS AND METHOD: This flap has been used for seven patients with bone infection and skin defects measuring an average of 10 x 7 cm. The preoperative arteriography had to find the whole three arteries at the leg, with a good distal anastomotic arcade. The soleus muscle was raised with the posterior tibial artery, after it was ligated proximally and dissected up to the tarsal tunnel. RESULTS: All of the seven flaps totally survived, except one that a marginal necrosis treated by excision and iterative dissection of the pedicle for a more distal repositioning. No clinical vascular deficiency was found on the legs. At the last review, all the osteomyelitis were cured. DISCUSSION: The soleus island flap, distally vascularized on the posterior tibial artery, is a reliable flap, useful for the coverage of the distal leg, from the ankle to the very distal foot. Harvesting a major artery at the leg should be weighed against the failure of a free flap in high risk patients.

[Gait changes encountered after a total knee prosthesis with or without posterior cruciate ligament preservation]. / Modifications de la marche associées à la présence d'une prothèse totale de genou conservant ou sacrifiant le ligament croisé postérieur.

PURPOSE OF THE STUDY: We wanted to check whether the differences in joint kinematics between the normal and prosthesis knee, with or without preservation of the posterior cruciate ligament, have an effect on knee flexion-extension during gait and on gait performance. MATERIAL AND METHODS: A control group of nine subjects was compared with two groups of subjects with total knee prostheses, with (n = 10 patients) or without (n = 6 patients) preservation of the posterior cruciate ligament. Gait was studied on flat ground at three different walking speeds. We measured the principal temporospatial gait parameters as well as knee flexion and extension angles using continuous electrogoniometry. Non-parametric statistical tests were used to analyze data due to the small number of subjects in each group. RESULTS: The flexion-extension cycles were different between the control group and the prostheses groups, but there was no difference between the two prostheses groups. Measurements made during gait confirmed this result, demonstrating a modification of the temporospatial parameters and a decrease in knee flexion during weight bearing in the prostheses groups compared with the control group. The statistical analysis demonstrated a correlation between these two results. DISCUSSION: The individual nature of gait parameters hindered data analysis. Indeed, there are many different ways to walk "normally". We were however able to demonstrate the following points. The theoretical differences in joint kinematics between prostheses with or without preservation of the posterior cruciate ligament did not have any effect on gait. There were however significant differences between the control group and the prostheses groups, and these differences depended on walking speed. The most interesting results concerned the changes in the weight-bearing phase. Flexion during this phase was related to walking speed and was decreased in amplitude in both prostheses groups. This lesser amplitude in knee flexion probably affected the quality of gait because it was correlated with decreased temporospatial parameters related to gait performance. CONCLUSION: This decreased amplitude of flexion during gait, which cannot be expected from motion measurements without weight bearing, can be explained by an interaction between joint kinematics, the musculoligamentary system and the locomotor schema.

[Knee kinematics in flexion and extension using an electrogoniometric device: results in nine healthy subjects]. / Etude cinématique de la flexion-extension du genou à l'aide d'électrogoniomètre.

PURPOSE OF THE STUDY: We wanted to develop a gait evaluation protocol using an electrogoniometric device allowing simpler measurements than optoelectronic recordings. MATERIAL AND METHODS: Gait was studied in a group of nine healthy subjects, mean age 58 years, walking on flat ground at three different speeds. We recorded the knee flexion and extension angles and the main temporospatial gait parameters. The principal conditions required for considering gait to be normal were taken from the literature. RESULTS: The subjects exhibited gait cycles which were normal in 83% of the cases for both knees at all three walking speeds. In 17% of the cases, the subjects walked with a flexed knee or without flexion during the weight-bearing phase. Knee motion was symmetrical between the right and left knee in all subjects. Increased walking speed was associated with increases temporospatial parameters and greater flexion and extension angles, particularly during the weight-bearing phase. There was a correlation between the weight-bearing flexion phase and stride length. DISCUSSION: The walking distance was moderate but sufficient to avoid the influence of the start and stop cycles. The electrogoniometers were small and did not perturb walking. Certain temporospatial parameters could not be measured directly but could be estimated. We checked that the results corresponded with data in the literature. Lateralization (right, left dominance) did not influence knee movement. Flexion during weight-bearing could influence gait quality by affecting the balance between gravity and quadriceps muscle force, particularly when considering forces used to progress forward. Knee motion varies with walking speed and depends not only on overall knee motion measured without weight bearing, but probably also on the interaction between joint kinematics, the musculoligamentary system, and the locomotor schema.

[Mid-term results of Wallaby I posterior cruciate retaining total knee arthroplasty: a prospective study of the first 425 cases]. / Résultats à moyen terme de la prothèse totale du genou Wallaby I conservant le ligament croisé postérieur: à propos des 425 premiers cas suivis prospectivement.

PURPOSE OF THE STUDY: Posterior Wallaby I is a fixed polyethylene tibial plateau prosthesis enabling preservation of the posterior cruciate ligament (PCL). Its asymmetrical and divergent femoral condyles articulate with also asymmetrical tibial plateaus. The purpose of this prospective study was to analyze outcome of the first 425 Wallaby I prosthesis of the Guepar group implanted for first-intention treatment. MATERIALS AND METHODS: These 425 prostheses were implanted from December 1992 to February 1995 by senior and junior surgeons. Mean patient age at implantation was 70.5 years. 91% had primary or secondary osteoarthritis and only 8.9% had inflammatory rheumatoid disease. The mean preoperative IKS score was 25.34 points and the IKS function score was 29.04. 10.35% of knees were aligned normally (mechanical axis between 2 degrees varus and 3 degrees valgus) according to the IKS criteria (Ewald), 24% presented valgus > or = 4 degrees and 65.6% varus > or = 3 degrees. All tibial and patellar components (except one) were cemented, 5.8% of the femoral pieces were inserted without cement. All but 11 patellae were resurfaced. Clinical outcome was assessed with the IKS score and radiological outcome with the IKS criteria. The patella was considered to be tilted when the alpha angle was > 5 degrees and dislocated when the AA' distance was > 5 mm. The chi-square test was used for comparison of quantitative variables (significance set at 0.05). RESULTS: Early postoperative complications were rare: two infections cured with debridement-lavage and antibiotics without removal of the prosthesis, one peronal nerve palsy which regressed partially, ten late unions without clinical consequence (particularly in the inflammatory rheumatoid patients). Twenty-six prostheses were followed less than one year (eight patients died and eighteen were lost to follow-up) and 84 less than five years (27 patients died and 57 lost to follow-up before five years). 315 prostheses were followed for more than five years (5-9 years) with a mean follow-up of 6.3 years. Among the 399 prostheses followed for one year or more, we noted: four infections including three requiring change of the prosthesis (one cured by arthroscopic lavage), two aseptic loosenings which were revised (one global one tibial), one tibial loosening and three patellar loosenings which were not revised, and two femoral ossifications limiting joint motion but improved by arthrolysis and resection of the ossifications. Three patients experienced anterior pain requiring secondary patellar resurfacing in two and section of the lateral patellar wing in one. Ninteen patellar fractures (4.7%) were noted, including 17 with no significant functional impact which were not revised. The mean IKS knee score among prostheses followed for five years was 90.5 points, with mean motion 110.5 degrees. Mean IKS function score was 61.63 points. 72.9% of the knees were aligned, 22.2% in varus and 4.9% in valgus. The mechanical axis of 94.3% of the knees was between 5 degrees varus and 5 degrees valgus. Prosthesis survival at eight years (Kaplan-Meier method) was 97.7% considering all reasons for prosthesis removal and 98.5% for removal for aseptic loosening. CONCLUSION: This prospective multicentric study demonstrated that the results obtained with the Wallaby I prosthesis are as good as those obtained with other prostheses sparing the PCL and published in the literature. Preservation of the PCL enables better knee stability, correct motion (110.5 degrees in our series) with almost no radiological wear of the tibial polyethylene at eight years. The only worrisome complication is patellar fracture.

An S-mephenytoin cysteine conjugate identified in urine of extensive but not of poor metabolizers of S-mephenytoin.

A conjugate of S-mephenytoin excreted in urine of extensive but not of poor metabolizers of S-mephenytoin has previously been reported. This conjugate, which is easily hydrolysed back to S-mephenytoin, has now been isolated and identified in urine from one extensive metabolizer after a single dose of 100 mg racemic mephenytoin. High performance liquid chromatography purification, followed by gas chromatographic, mass spectrometric and amino acid analyses showed that the isolated compound is a cysteine conjugate of S-mephenytoin. The significant mass spectrometric ions have been confirmed in three additional extensive metabolizers of S-mephenytoin, but were not detectable in urine from three poor metabolizer subjects. The exact structure of the conjugate is unknown, but we suggest that an S-N bond between cysteine and S-mephenytoin is formed via an oxidative radical mechanism catalyzed by CYP2C19.

10-Hydroxylation of nortriptyline in white persons with 0, 1, 2, 3, and 13 functional CYP2D6 genes.

OBJECTIVE: To investigate the disposition and effects of nortriptyline and its major metabolite 10-hydroxy-nortriptyline line in panels of white subjects with different CYP2D6 genotypes, including those with duplicated and multiduplicated CYP2D6*2 genes and to evaluate the contribution of the number of functional C gamma P2D6 alleles to the metabolism of nortriptyline, used here as a model drug for CYP2D6 substrates. METHODS: Oral single doses of 25 to 50 mg nortriptyline were given to five poor metabolizers of debrisoquin (INN; debrisoquine) with no functional CYP2D6 gene, five extensive metabolizers with one functional CY2D6 gene, five extensive metabolizers with two functional CYP2D6 genes, five ultrarapid metabolizers with duplicated CYP2D6*2 genes, and one ultrarapid metabolizer with 13 copies of the CYP2D6*2 gene. Plasma kinetics of nortriptyline and 10-hydroxynortriptyline were analyzed. Anticholinergic effects (inhibition of salivation and accommodation disturbances), sedation, blood pressure, and effect on supine and erect pulse rate were measured. RESULTS: There was a clear relation between the C gamma P2D6 genotype and the plasma kinetics of nortriptyline and 10-hydroxynortriptyline. The proportion between the apparent oral clearances of nortriptyline in the groups with 0, 1, 2, 3, and 13 functional genes was 1:1:4:5:17. The proportions between AUC(nortriptyline) to AUC(10-hydroxynortriptyline) ratios in the groups with 0, 1, 2, 3, and 13 functional genes were 36:25:10:4:1. Oral plasma clearance of nortriptyline and AUC(nortriptyline) to AUC(10-hydroxynortriptyline) ratio both correlated significantly with the debrisoquin metabolic ratio (rS = -0.89, p = 0.0001; rS = 0.92, p = 0.0001). Although ultrarapid metabolizer subjects were given double the nortriptyline dose (50 mg), inhibition of salivation was not more pronounced compared with the other genotype groups given 25 mg nortriptyline. CONCLUSION: The results of this study show the quantitative importance of the CYP2D6 genotype, especially the presence of multiple functional CYP2D6 genes for the pharmacokinetics of nortriptyline and 10-hydroxynortriptyline. Genotyping of subjects with multiple copies of functional genes may be of great value for differentiating ultrarapid metabolizers from patients who do not comply with the prescription and for assuring adequate drug choice and dosage for these patients.

Recurrence of rheumatic fever during prophylaxis with monthly benzathine penicillin G.

A 9-year-old girl had apparent recurrence of rheumatic fever while receiving monthly benzathine penicillin injections. A review of pharmacokinetc studies on the subject suggests that this is a real risk. A need for review of the current recommendations for rheumatic fever prophylaxis is suggested.

Prevalence of excess lead absorption and associated risk factors in children enrolled in a midwestern health maintenance organization.

OBJECTIVE: To assess the prevalence of lead intoxication in children in a defined low-risk population at the new levels recommended by the Centers for Disease Control and Prevention. DESIGN: During an 11-month period, whole blood lead tests were performed on 4678 children at routine well-child visits at 9 months and 2 years of age. For the last 8 months of the study, parents were asked to complete a prescreening risk factor questionnaire at these visits. The questionnaire and blood lead results were then matched. Data were collected from October 1, 1991 through August 31, 1992. SETTING: The study subjects were all enrolled in Group Health, Inc, a large health maintenance organization. Its 17 staff model clinics serve urban and suburban populations in the Minneapolis-St. Paul area. More than 95% of the population had coverage based on employment, not Medicaid. RESULTS: Results indicated that 2.5% (n = 119) of the children had BPb levels > or = 10 micrograms/dL. Urban clinics had rates of elevated BPb levels three to eight times those of suburban clinics (P < .00001), but the number of elevated BPb levels at the suburban clinics was greater than expected. BPb levels were significantly higher in summer and fall (P < .00001). The prescreening questionnaire addressed five areas potentially associated with risk according to the literature: housing, siblings with lead poisoning, parental hobbies or work involving lead, proximity to highways, and use of cultural medicines. Positive correlations were found between elevated BPb levels and residences built before 1950 (P < .00001). For children living in housing built before 1950, positive correlations were found between elevated blood lead levels and peeling paint (P < .01) or remodeling (P < .0001). CONCLUSIONS: Children who are at low socioeconomic risk but who live in housing built before 1950 are at increased risk for lead poisoning. The risk is greater if the house has peeling paint and especially if there is recent or ongoing renovation. Recommendations based on these results and the Centers for Disease Control and Prevention guidelines are made for screening programs in similar populations, and for the need to increase community awareness concerning this issue.

Lead levels in high-risk and low-risk young children in the Minneapolis-St Paul metropolitan area.

OBJECTIVES: To determine distribution of lead levels among children in a low-risk area; to validate a prescreening questionnaire; and to determine if universal lead screening is necessary in children in this area. DESIGN: Blood lead levels and questionnaires were obtained on eligible patients. Data were analyzed using stepwise regression analysis. SETTING: Community clinics and a health maintenance organization (HMO) in the Minneapolis-St Paul metropolitan area. PATIENTS: A total of 9603 children at well-child visits, age 6 months to 6 years at community clinics, and 6 months to 3 years at the HMO. OUTCOME MEASURES: Whole blood lead levels (WBLs) and questionnaires. RESULTS: The total sample rate of WBLs at >/=10 microg/dL was 12%, at >/=15 microg/dL was 31/2%, and at >/=20 microg/dL was 1.2%. At both 10 microg/dL and 15 microg/dL, the non-HMO group was at higher risk. For both groups, risk factors included living in the central cities, and living in housing built before 1950. For the non-HMO group a history of the child eating paint chips, or the child or a sibling having previous lead poisoning were also risk factors. CONCLUSIONS: Not all children need lead screening. Children living in the central cities, or with the risk factors of living in housing built before 1950 or a previous history of lead poisoning should be screened.

Liquid chromatography-tandem mass spectrometry applied to a study of the metabolism of pentamidine. Discussion of possibilities and problems.

Tandem mass spectrometry is usually employed to achieve rapid screening or structure elucidation. We have used liquid chromatography-tandem mass spectrometry in order to detect metabolites of the antiprotozoal drug pentamidine in urine. Samples of urine from rat and man were analysed both by direct injection and after solid-phase extraction. The present paper discusses advantages and disadvantages of using direct injection of urine samples, optimization of chromatographic conditions with regard to the performance of the mass spectrometer, automation and stability of the entire system.

Measurement of stopping power ratios for 60 MeV positive or negative pions.

Pion stopping power ratios are essential parameters for pion radiotherapy treatment planning. The validity of scaling proton stopping powers to pions is called into question since the pion mass is intermediate between the electron and proton masses. Direct measurements of stopping power ratios with respect to water were made for 60 MeV pions of both charges in Teflon, Plexiglas, nylon, paraffin, gelatine, tissue-equivalent plastic (Shonka A150), graphite, aluminium, steel and copper. Corrections for multiple scattering and energy dependence of the stopping power are applied. Measured stopping power ratios at an accuracy of 0.6% are in agreement to within the limits of experimental error with stopping power ratios calculated from the Bethe-Bloch equation using elemental I-values and Bragg additivity.

The vitellin-processing protease of Blattella germanica is derived from a pro-protease of maternal origin.

Proteolytic processing of vitellin in Blattella germanica embryos is accomplished by activation of a yolk-borne cysteine protease (Mr 29 000) derived from a pro-protease precursor of Mr 40 000 (Liu et al., 1997). In the present study, fat body, ovaries and embryos of different developmental stages were examined immuno-cytochemically with purified murine anti-proprotease antibodies (Liu, 1995) to determine the intracellular location of the pro-protease. Proenzyme was detected in discrete secretory granules of the fat body and in large lysosome-like vesicles of both the follicle cell cytoplasm and the cortical ooplasm of previtellogenic ovarian follicles. In vitellogenic oocytes, coated pits and vesicles are scantily labelled for proprotease and no clear gold pattern could be discerned over the yolk granules. During embryonic development, pro-protease is associated with some, but not all, yolk granules. In newlyovulated eggs (day 0), pro-protease is either distributed over the entire granule or confined to some internal vesicles. As development proceeds, it becomes associated with almost every yolk granule and restricted to the superficial layer. By day 6, pro-protease is evident over all yolk granules but the intensity of reaction has greatly diminished, due probably to conversion of the pro-protease to the mature enzyme. Yolk granules are flanked along their margin by vesicles that are stained after zinc-osmium fixation. This observation suggests that the pro-protease may be transferred between yolk granules via vesicular shuttling. B. germanica embryos of different developmental stages were also exposed to [(3)H]-DAMP. Data show that autoradiographic grains are not evenly distributed among closely adjacent yolk granules within vitellophagic cells, a result consistent with the known slight temporal asynchrony of the acidification event.

The isolated scapho-trapezio-trapezoid ligament injury. Diagnosis and surgical treatment in four cases.

Isolated injuries of the scapho-trapezial ligament complex are not well recognized. The ligament complex comprises the stout scapho-trapezial ligament, the floor of the flexor carpi radialis (FCR) tendon sheath and the scapho-capitate ligament. Between August 1991 and May 1992, we diagnosed and treated four cases of partial chronic post-traumatic lesions of this ligament complex. There was chronic pain at the base of the thenar eminence and instability of the thumb-index-middle finger pinch. Standard X-rays were normal. The diagnosis of ligament rupture was confirmed by mid-carpal arthrography showing filling of the sheath of FCR tendon. Surgical exploration showed complete rupture of the tendon sheath of FCR in two cases, associated in the other two cases with complete rupture of the scapho-trapezial ligament. Direct repair of the ligamentous elements was performed in all cases. The tendon of FCR was sutured to the tubercle of scaphoid to protect and to reinforce the ligament repair. The patients have been followed-up for between 6 and 12 months. All four patients recovered normal pinch strength to the middle finger. One patient suffered from chronic pain at work.

[Covering sacral and ischiatic loss of substance with musculocutaneous flaps]. / Recouvrement des pertes de substance sacrée et ischiatique par lambeaux musculo-cutanés.

Eschars located in the sacral and ischiatic areas raise problems of recovering when much tissue has been lost. The usual techniques, such as dermoepidermal grafts or local skin flaps, are difficult to perform and have a high failure rate. In contrast, musculo-cutaneous flaps are excellent both to fill and to cover the raw areas. Three types of flap have been used successfully by the authors in 12 consecutive patients, some of whom had paraplegia. Two of them involve the greatest gluteal muscle which is divided into two heads according to blood supply. The "butterfly" flap uses the upper heads of the two muscles, on either side of the midline, with the corresponding skin territories ; it is most useful to cover wide sacral areas. In the "pendular" flap, the lower head of one of the greatest gluteal muscles is mobilized to cover a moderate loss of tissue in the ischiatic area. Finally, the "kite" flap concept is based on bringing up the ischio-crural muscles to cover wide ischiatic eschars.