Accuracy of Pre- and Postcontrast, 3 T Indirect MR Arthrography Compared with Wrist Arthroscopy in the Diagnosis of Wrist Ligament Injuries.

Background Magnetic resonance (MR) is the most important imaging technique to assess intra-articular pathology of the wrist. Among various MR imaging protocols, the diagnostic performance of indirect MR arthrography needs further investigation. Purpose The purpose of this study was to assess the diagnostic performance of pre- and postcontrast, 3 T indirect MR arthrography in the diagnosis of scapholunate intrinsic ligament (SLIL) and triangular fibrocartilage complex (TFCC) injuries, using wrist arthroscopy as reference standard. Patients and Methods We retrospectively evaluated consecutive patients with suspected SLIL or TFCC injury, who had indirect MR arthrography done before arthroscopy. Images were assessed independently by two senior radiologists. Results Arthroscopy of the 53 wrists demonstrated 16 Geissler stages II and III partial tears and 6 stage IV total SLIL ruptures. Central perforation of the TFCC was found in 24 wrists, and 12 wrists had an ulnar class 1B lesion. To detect any SLIL tear, accuracy was higher for the two observers using postcontrast indirect MR arthrography (0.77 and 0.72) than for precontrast MR imaging (0.60 and 0.60). No difference was found for total SLIL ruptures "0.85 and 0.89" versus "0.85 and 0.89." To diagnose class 1B TFCC injuries, accuracy was higher using postcontrast indirect MR arthrography (0.85 and 0.75) than for precontrast MR imaging (0.70 and 0.72). No difference in accuracy was demonstrated for TFCC central tears "0.75 and 0.75" versus "0.70 and 0.77." Conclusion Postcontrast images at 3 T indirect MR arthrography, compared with precontrast images, have an improved diagnostic performance for the overall detection of SLIL injuries and as well as class 1B TFCC tears. Level of Evidence This is a Level II, diagnostic study.

Cacidases: caspases can cleave after aspartate, glutamate and phosphoserine residues.

Caspases are a family of proteases found in all metazoans, including a dozen in humans, that drive the terminal stages of apoptosis as well as other cellular remodeling and inflammatory events. Caspases are named because they are cysteine class enzymes shown to cleave after aspartate residues. In the past decade, we and others have developed unbiased proteomic methods that collectively identified ~2000 native proteins cleaved during apoptosis after the signature aspartate residues. Here, we explore non-aspartate cleavage events and identify 100s of substrates cleaved after glutamate in both human and murine apoptotic samples. The extended consensus sequence patterns are virtually identical for the aspartate and glutamate cleavage sites suggesting they are cleaved by the same caspases. Detailed kinetic analyses of the dominant apoptotic executioner caspases-3 and -7 show that synthetic substrates containing DEVD↓ are cleaved only twofold faster than DEVE↓, which is well within the 500-fold range of rates that natural proteins are cut. X-ray crystallography studies confirm that the two acidic substrates bind in virtually the same way to either caspases-3 or -7 with minimal adjustments to accommodate the larger glutamate. Lastly, during apoptosis we found 121 proteins cleaved after serine residues that have been previously annotated to be phosphorylation sites. We found that caspase-3, but not caspase-7, can cleave peptides containing DEVpS↓ at only threefold slower rate than DEVD↓, but does not cleave the unphosphorylated serine peptide. There are only a handful of previously reported examples of proteins cleaved after glutamate and none after phosphorserine. Our studies reveal a much greater promiscuity for cleaving after acidic residues and the name 'cacidase' could aptly reflect this broader specificity.

Temporal dynamics in the ruminal microbiome of dairy cows during the transition period.

The transition period in dairy cows refers to the period from 3 wk before calving to 3 wk post-calving and is a critical time for influencing milk production and cow health. We hypothesize that the ruminal microbiome shifts as dairy cows transition from a non-lactation period into lactation due to changes in dietary regimen. The purpose of this study was to identify differences in the ruminal microbiome of primiparous and multiparous (study group) cows during the transition period. Five primiparous and 5 multiparous cows were randomly selected from a herd, and ruminal contents were sampled, via stomach tube, 4 times (study day) at 3 wk before calving date (S1), 1 to 3 d post-calving (S2), and 4 (S3) and 8 wk (S4) into lactation and were evaluated for bacterial diversity using 16S pyrotags. Both groups received the same pre-fresh diet (14.6% CP, 44.0% NDF, 21.9% starch) and 3 different lactation diets (L1, L2, and L3) varying in forage base but not amount and formulated to have similar nutrient specifications (16.8% to 17.7% CP; 32.5% to 33.6% NDF; 26.2% to 29.1% starch) post-calving. Forty bacterial communities were analyzed on the basis of annotations of 100,000 reads, resulting in 15,861 operational taxonomic units grouped into 17 bacterial phyla. The UniFrac distance metric revealed that both study group and study day had an effect on the community compositions (P < 0.05; permutational multivariate ANOVA test). The most abundant phyla observed were Bacteroidetes and Firmicutes across all the communities. As the cows transitioned into lactation, the ratio of Bacteroidetes to Firmicutes increased from 6:1 to 12:1 (P < 0.05; Mann-Whitney U test), and this ratio was greater in primiparous cows than in multiparous cows (P < 0.05). This report is the first to explore the effect of parity on dynamics in the ruminal microbiome of cows during the transition period.

Vibrotactile sense in patients with diabetes and carpal tunnel syndrome.

AIM: To evaluate vibration perception thresholds of patients with and without diabetes, before and after surgical carpal tunnel release. METHODS: In a prospective study, 35 consecutive patients with diabetes and carpal tunnel syndrome were age and gender matched with 31 patients without diabetes having idiopathic carpal tunnel syndrome. Preoperatively, 6, 12 and 52 weeks after surgery, the vibration perception threshold of the index and little finger (median and ulnar nerve, respectively) was measured at seven different frequencies (8, 16, 32, 64, 125, 250 and 500 Hz). RESULTS: At several frequencies, patients with diabetes and carpal tunnel syndrome demonstrated significantly impaired vibration perception thresholds of both the index and the little finger, before as well as after carpal tunnel release, compared with patients without diabetes with idiopathic carpal tunnel syndrome. After surgery, the overall sensibility index improved for the index finger [patients with diabetes and carpal tunnel syndrome (0.79 to 0.91, P < 0.001), patients without diabetes with idiopathic carpal tunnel syndrome (0.91 to 0.96, P > 0.05)] as well as for the little finger [patients with diabetes and carpal tunnel syndrome (0.82 to 0.90, P < 0.008), patients without diabetes with idiopathic carpal tunnel syndrome (0.95 to 0.99, P < 0.05)]. For the index finger, the sensibility index improved to a significantly higher degree for patients with diabetes and carpal tunnel syndrome not having signs of peripheral neuropathy (0.83 to 0.95, P < 0.001) compared with those with neuropathy (0.74 to 0.84, P < 0.02). Vibration perception threshold correlates with age of both patients with diabetes and carpal tunnel syndrome and patients without diabetes with idiopathic carpal tunnel syndrome, while no relationship was found based on duration of diabetes. CONCLUSIONS: Vibrotactile sense is significantly impaired in patients with diabetes before and after carpal tunnel release compared with patients without diabetes. However, patients with diabetes obtained significant recovery of vibration perception threshold, particularly those without peripheral neuropathy.

Health-related quality of life in diabetic patients with carpal tunnel syndrome.

AIMS: To determine health-related quality of life (HRQL) in diabetic and non-diabetic patients with carpal tunnel syndrome (CTS) before and after surgical treatment. METHODS: In a prospective study, 35 consecutive diabetic patients with CTS were age and gender matched with 31 non-diabetic patients with idiopathic CTS. At baseline (preoperatively), 6, 12 and 52 weeks after surgical carpal tunnel release, patients completed the generic Short-Form 36 (SF-36) and the disease-specific Boston Carpal Tunnel Questionnaire (BCTQ). RESULTS: The SF-36 physical component scores at baseline were significantly reduced for diabetic (39+/-7.4) compared with non-diabetic patients (48+/-9.0) (P<0.05). Mixed model analysis demonstrated no differences in post-surgical improvement over time between diabetic and non-diabetic patients. The largest clinical effect was found for bodily pain (effect size 0.8). However, population norms were not reached for the diabetic patients. At baseline, no difference was found in mental component score, which deteriorated over time for diabetic patients. At baseline, BCTQ demonstrated that diabetic patients experienced more pronounced 'numbness in the hand' than non-diabetic patients. Large clinical improvements were found in both symptom severity (effect size 1.98-2.14) and functional status score (effect size 0.89-0.94) for both diabetic and non-diabetic patients, with no difference between the two patient groups. CONCLUSIONS: HRQL is impaired in diabetic patients with CTS compared with non-diabetic patients with CTS and population norms. However, diabetic patients experience similar symptomatic and functional benefits from carpal tunnel release as do non-diabetic patients.

Intraepidermal nerve fibre density at wrist level in diabetic and non-diabetic patients.

AIMS: Myelinated nerve fibre pathology has been demonstrated at wrist level in diabetic patients. We examined if quantification of intra-epidermal nerve fibre density (IENFD) in hairy and glabrous skin at wrist level could detect signs of subclinical small nerve fibre neuropathy. METHODS: In 35 diabetic patients who were age and gender matched with 31 non-diabetic patients, punch biopsies were obtained in conjunction with surgical carpal tunnel release. Biopsies were immunostained with anti-protein gene product (PGP) 9.5. The IENFD was quantified using manual counting by light microscopy. RESULTS: We could not demonstrate significant differences in IENFD between diabetic or non-diabetic patients. Additionally, no differences were found between patients with Type 1 and Type 2 diabetes or in diabetic patients with and without neurophysiologic signs of mild peripheral neuropathy. However, the IENFD was significantly higher in hairy skin compared with glabrous skin. Furthermore, the IENFD was significantly higher in females than in males and correlated with age, but not with duration of diabetes or glycated haemoglobin (HbA(1c)). CONCLUSIONS: In mild neuropathy no difference in IENFD at the wrist level could be detected between diabetic and non-diabetic patients. Independent of diabetes, we found IENFD to be higher in hairy skin compared with glabrous skin and higher in females than in males. These results must be taken into consideration when assessing small nerve fibre pathology in the upper extremity.

Biopsy of the posterior interosseous nerve: a low morbidity method for assessment of peripheral nerve disorders.

AIMS: The sural nerve is the commonest peripheral nerve biopsied to help in the diagnosis of peripheral neuropathy of unknown cause. However, associated complications limit its use. The aim was, as an alternative, to asses biopsy of the terminal branch of the posterior interosseous nerve (PIN) in the forearm. METHODS: PIN pathology was morphometrically quantified in 10 male patients with Type 2 diabetes and compared with six PIN biopsy specimens taken post mortem from male cadavers with no history of neuropathy or trauma. RESULTS: The PIN biopsy procedure provides a long (approximately 3 cm) mono- or bifascicular nerve biopsy with generous epineurial tissue and adjacent vessels. Our results show a significantly lower myelinated fibre density in subjects with diabetes [5782 (3332-9060)/mm(2)] compared with autopsy control material [9256 (6593-12,935)/mm(2), P < 0.007]. No postoperative discomfort or complications were encountered. CONCLUSIONS: A reduction in myelinated fibre density has previously been shown to be a clinically meaningful measure of neuropathy in diabetic patients. We demonstrate similar findings using the PIN biopsy. The PIN biopsy procedure fulfils the criteria for nerve biopsy and was well tolerated by the patients. It may be a possible alternative to sural nerve biopsy to allow for diagnosis of neuropathy.

Combined use of an ibuprofen-releasing foam dressing and silver dressing on infected leg ulcers.

OBJECTIVE: To investigate the effect and safety of an ibuprofen-releasing foam (Biatain-Ibu, Coloplast A/S) combined with an ionised silver-releasing wound contact layer (Physiotulle Ag, Coloplast A/S) on painful, infected venous leg ulcers. METHOD: This open non-comparative study involved 24 patients with painful, exuding, locally infected, and stalled venous leg ulcers. Persistent pain and pain at dressing change were monitored using a 11-point numerical box scale (NBS). The composition of the wound bed, the dressing combination's ability to absorb exudate and minimise leakage, ibuprofen content in the exudate, reduction in wound area and adverse effects were also recorded. RESULTS: Persistent wound pain decreased from a mean of 6.3 +/- 2.2 to 3.0 +/- 1.7 after 12 hours and remained low thereafter. Pain at dressing change also decreased and remained low. Forty-eight hours after the first dressing application, the mean concentration of ibuprofen in the wound exudate reached a constant level of 35 +/- 21 microg/ml. After 31 days, the relative wound area had reduced by 42%, with an associated decrease in fibrin and an increase in granulation tissue. The number of patients with wound malodour decreased from 37% to 4%. No serious adverse events were reported. CONCLUSION: The combined use of the ibuprofen-releasing foam dressing and silver-releasing contact layer reduced wound pain and promoted healing without compromising safety.

Sequelae following sural nerve biopsy in type 1 diabetic subjects.

OBJECTIVES: To detect post-operative sequelae of sural nerve biopsy. MATERIALS AND METHODS: A questionnaire mailed to type 1 diabetic patients (n = 24; male/female 23/1; reply n = 23) 2 years after biopsy. RESULTS: Type 1 diabetic patients (age 56 [11]; median [interquartile range]) had a long duration of diabetes (DM; 20 [19] years) and all had neuropathy. Three out of 24 patients developed infection (two superficial and one deep) and one had a post-operative bleeding. Less frequent pain among the patients were reported from one centre. About one-third or more of the patients still complained of pain, mostly mild, in the biopsy area and paraesthesia in the foot 2 years after surgery. More than two-thirds of the patients were reluctant for further biopsy; a crucial information in drug trial planning. CONCLUSIONS: Sequelae of a sural nerve biopsy occur in type 1 DM. The risk for wound infections should be considered.

Vibrotactile sense in median and ulnar nerve innervated fingers of men with Type 2 diabetes, normal or impaired glucose tolerance.

AIMS: To investigate vibrotactile sense (large fibre neuropathy) at different frequencies in index and little fingers (median and ulnar nerves, respectively) of subjects with diabetes, or impaired (IGT) or normal glucose tolerance (NGT). METHODS: Vibration thresholds (tactilometry at seven frequencies (8, 16, 32, 64, 125, 250 and 500 Hz)) and median nerve function (electrophysiology) were examined in men (age 73.4 +/- 0.12 years; n = 58, mean +/- sd) with persistent NGT (n = 28) or IGT (n = 7) or with Type 2 diabetes mellitus (T2DM) (n = 23) for > 15 years. RESULTS: HbA1c was increased and vibrotactile sense (sensibility index) was impaired in index and little fingers in men with T2DM. Vibration thresholds were particularly increased at 16, 250 and 500 Hz in the little finger (ulnar nerve). T2DM subjects showed electrophysiological (gold standard) signs of neuropathy in the median nerve. Although subjects with persistent IGT had higher HbA1c, vibrotactile sensation and electrophysiology remained normal. HbA1c did not correlate with vibrotactile sense or electrophysiology, but the latter two correlated with respect to Z-score (sign of neuropathy) in forearm (NGT) and at wrist level (NGT and DM). CONCLUSIONS: Vibration thresholds are increased in the finger pulps in T2DM subjects, particularly at specific frequencies in ulnar nerve innervated finger pulps. Neuropathy is not present in IGT. Tactilometry, with a multi-frequency approach, is a sensitive technique to screen for large fibre neuropathy in T2DM. Frequency-related changes may mirror dysfunction of various receptors.

Effect of a new silver dressing on chronic venous leg ulcers with signs of critical colonisation.

OBJECTIVE: To investigate the clinical performance and safety of a new silver-containing wound-contact layer, Physiotulle -Ag (Coloplast), in the treatment of chronic venous leg ulcers with delayed healing and signs of critical colonisation. METHOD: This was an open prospective non-comparative multicentre clinical study. Patients were treated for four weeks with Physiotulle -Ag, which was covered by Alione Hydrocapillary Dressing (Coloplast). RESULTS: Thirty patients were recruited into the study. One ulcer healed after three weeks of treatment. The mean relative ulcer area reduced by 55% after four weeks. Over the study period the mean amount of healthy granulation tissue increased from 26% to 62%, and the mean amount of fibrin decreased from 63% to 32%. The ratio of malodorous wounds was 50% at inclusion, 20% after one week and 3% after four weeks. The dressing was considered easy or very easy to apply in 100% and easy to remove in 89% of dressing evaluations. The dressing combination showed good exudate-management properties. Incidence and severity of maceration, erythema and eczema decreased during the study and no device-related adverse events were recorded. CONCLUSION: Physiotulle -Ag is safe and easy to use in chronic venous leg ulcers in which healing is delayed and with signs of critical colonisation.

Arthroscopy of the proximal interphalangeal joints of the finger.

Cadaveric studies were carried out to evaluate the technique, portals and possible indications for arthroscopy of the proximal interphalangeal joints of the finger. We suggest horizontal placement of the hand instead of using a traction tower, as it is important to be able to flex the joint freely. The recommended arthroscopic portals are either between the central slip and the lateral bands of the extensor mechanism or between the lateral band and the collateral ligament. A blunt technique of introduction is used to avoid iatrogenic cartilage damage and possible digital nerve injury.

Apicomplexan parasites possess distinct nuclear-encoded, but apicoplast-localized, plant-type ferredoxin-NADP+ reductase and ferredoxin.

In searching for nuclear-encoded, apicoplast-localized proteins we have cloned ferredoxin-NADP(+) reductase from Toxoplasma gondii and a [2Fe-2S] ferredoxin from Plasmodium falciparum. This chloroplast-localized redox system has been extensively studied in photosynthetic organisms and is responsible for the electron transfer from photosystem I to NADP+. Besides this light-dependent reaction in nonphotosynthetic plastids (e.g. from roots), electrons can also flow in the reverse direction, from NADPH to ferredoxin, which then serves as an important reductant for various plastid-localized enzymes. These plastids possess related, but distinct, ferredoxin-NADP+ reductase and ferredoxin isoforms for this purpose. We provide phylogenetic evidence that the T. gondii reductase is similar to such nonphotosynthetic isoforms. Both the P. falciparum [2Fe-2S] ferredoxin and the T. gondii ferredoxin-NADP+ reductase possess an N-terminal bipartite transit peptide domain typical for apicoplast-localized proteins. The recombinant proteins were obtained in active form, and antibodies raised against the reductase recognized two bands on Western blots of T. gondii tachyzoite lysates, indicative of the unprocessed and native form, respectively. We propose that the role of this redox system is to provide reduced ferredoxin, which might then be used for fatty acid desaturation or other biosynthetic processes yet to be defined. Thus, the interaction of these two proteins offers an attractive target for drug intervention.

Weilby-Burton arthroplasty of the trapeziometacarpal joint of the thumb.

Twenty-three patients (25 thumbs) were treated by tendon interposition arthroplasty for trapeziometacarpal arthrosis as described by Weilby and modified slightly as described by Burton and Pellegrini. There was good (4/25, 16%) or complete (19/25, 76%) pain relief in 23 (92%) of the cases. Activities of daily living were generally easier. Mobility and strength of the thumb were satisfactory. One patient had signs of instability during a stress test. We conclude that our technique produces a stable and pain-free thumb joint. However, careful selection of the patients for this procedure is essential, and the patient must be given comprehensive information about all stages.

Optimized UVB treatment of psoriasis: a controlled, left-right comparison trial.

In a randomized, controlled, left-right comparison study, 20 patients with chronic plaque psoriasis were treated with UVB. One side of the body received UVB in a conventional regimen with fixed dose increments, the other side was given UVB doses according to measurements of skin pigmentation. Skin pigmentation was quantified by the skin reflectance technique. The relationship between skin pigmentation and sensitivity to UV radiation was used to optimize and individualize the initial UVB exposure dose. Clinical outcome, initial, final and cumulative UVB doses, time to 50% reduction in PASI score, and side-effects were compared. The consequence of the optimization of the UVB doses with a skin reflectance meter was that the initial UVB dose was significantly higher than in the conventional UVB regimen. PASI scoring demonstrated a more rapid improvement during the first 2 weeks of treatment on the half body receiving the optimized treatment compared to the other side (P < 0.05). This new technique offers the same therapeutical advantages and security as a dose regimen guided by minimal erythema dose testing. However, measurement of skin pigmentation by skin reflectance is a quick method which can be operated easily by nurses.

Cloning and functional characterization of the bile acid-sensitive methotrexate carrier from rat liver cells.

We have cloned two complementary DNAs (cDNAs), RL-Mtx-1 and RL-Mtx-2, corresponding to the bile acid- sensitive methotrexate carrier from rat liver by direct full-length rapid amplification of cDNA ends polymerase chain reaction (RACE-PCR) using degenerated primers that were deduced from published sequences of tumor cell methotrexate transporters. When expressed in Xenopus laevis oocytes and cosM6 cells, both clones mediate methotrexate and bumetanide transport. RL-Mtx-1 consists of 2,445 bp with an open reading frame of 1,536 bp. The corresponding protein with 512 amino acids has a molecular weight of 58 kd. RL-Mtx-2 (2,654 bp) differs by an additional insert of 203 bp. This insert is located in frame at position 1,196 of the RL-Mtx-1 and contains the typical splice junction sites at the 5' and 3' end, indicating that the RL-Mtx-2 messenger RNA (mRNA) is generated by alternative splicing. The insert contains a stop codon that shortens the RL-Mtx-2 protein to 330 amino acids (38 kd). Both cDNAs contain the binding site sequence for the dioxin/nuclear translocator responsive element (Ah/Arnt-receptor) in conjunction with a barbiturate recognition sequence (Barbie box). Preliminary results show that the Barbie box acts as a negative regulatory element. The two liver cDNA clones show homologies to the published sequences of folate and the reduced folate carriers, but no homology is found to the transport systems for organic anions like the Ntcp1, oatp1, OAT-K1, and OAT1. Expression of the mRNA for the methotrexate carrier is found in liver, kidney, heart, brain, spleen, lung, and skeletal muscle, but not in the testis as revealed by Northern blot analysis. The highest abundance of the mRNA is found in the kidney.

Structure and interactions of NCAM modules 1 and 2, basic elements in neural cell adhesion.

The structure in solution of the second Ig-module fragment of residues 117-208 of NCAM has been determined. Like the first Ig-module of residues 20-116, it belongs to the I set of the immunogloblin superfamily. Module 1 and module 2 interact weakly, and the binding sites of this interaction have been identified. The two-module fragment NCAM(20-208) is a stable dimer. Removal of the charged residues in these sites in NCAM(20-208) abolishes the dimerization. Modeling the dimer of NCAM(20-208) to fit the interactions of these charges produces one coherent binding site for the formation of two antiparallel strands of the first two NCAM modules. This mode of binding could be a major element in trans-cellular interactions in neural cell adhesion.