The value of cardiac MRI versus echocardiography in the pre-operative assessment of patients with Duchenne muscular dystrophy.

BACKGROUND/PURPOSE: Duchenne Mmuscular Ddystrophy (DMD) related cardiomyopathy is associated with significant perioperative mortality. Cardiac MRI (CMR) has not previously been systematically evaluated as pre-operative assessment tool for heart function in DMD. Our aim was to establish whether CMR versus echocardiography contributes to pre-operative DMD assessment. METHODS: Case records were retrospectively reviewed of 35 consecutive DMD boys who underwent evaluation for surgical procedures between 2010 and 2013. RESULTS: Echocardiography revealed a median left ventricular (LV) shortening fraction (SF) of 29/% (range: 7-44). 37% of boys (13/35) had abnormal SF <25%, 66% (23/35) showed hypokinesia and 26% (9/35) had LV dilatation. CMR revealed a median left ventricular ejection fraction (LVEF) of 52% (range: 27-67%). 57% of boys (20/35) had abnormal LVEF <55%, 71% (25/35) had hypokinesia, and 82% late gadolinium enhancement. Extensive versus minimal late gadolinium enhancement was associated with reduced left ventricular ejection fraction (48% vs 58%; p = 0.003) suggesting more severe cardiomyopathy. Although echocardiography shortening fraction correlated with CMR ejection fraction (rs = 0.67; p < 0.001), three-quarter of echocardiography studies had suboptimal scanning windows and in 26% measurements significantly over- or underestimated left-ventricular function compared to CMR. CONCLUSION: Our findings clearly demonstrate the added value of CMR versus echocardiography in assessing DMD-cardiomyopathy. Particularly when echocardiographic scanning windows are suboptimal, CMR should be considered to allow accurate pre-operative cardiac assessment.

Thinking outside of the blue box: a case presentation of neonatal methemoglobinemia.

We report the case of a full-term neonate who presented with cyanosis from birth secondary to methemoglobinemia precipitated by the obstetric use of bupivacaine in a spinal anaesthetic for caesarean delivery.

The influence of shoe sole's varying thickness on lower limb muscle activity.

BACKGROUND: The lateral ligament injury of the ankle is acknowledged to be the most common ankle injury sustained in sport. Increased peroneus longus muscle contraction in the shod population has already been documented. This study aimed to quantify the effect of shoe sole's varying thickness on peroneus longus muscle activity. METHODS: Electromyographic recordings of the peroneus longus muscle activity following unanticipated inversion of the foot from 0° to 20° in a two-footplate tilting platform were collected from 38 healthy participants. The four test conditions were: barefoot, standard shoe, and shoes with 2.5 cm and 5 cm sole adaptation respectively. RESULTS: Compared to the barefoot condition, there is an increase in the magnitude of muscle contraction on wearing shoes, which further increases with thickening shoe soles. The peroneus longus was responding earlier in the shod conditions when compared to the barefoot, although the results were variable within the three shod conditions. CONCLUSION: Footwear with increasing shoe sole thickness evokes a correspondingly stronger protective eversion response from the peroneus longus to counter the increasing moment at the ankle-subtalar joint complex following sudden foot inversion. Hence, fashion footwear with thicker sole is likely to increase the risk of lateral ligament injury of the ankle when such protective response is overwhelmed. Similarly, the clinicians need to be cautious regarding the amount of shoe raise that they could provide for patients with limb length discrepancy without any detrimental untoward side effects.

Osteochondritis dissecans of the knee; long-term clinical outcome following arthroscopic debridement.

We reviewed 32 knees in 26 patients who had previously undergone arthroscopic debridement for symptomatic osteochondritis dissecans (OCD) of the knee. The patients were followed up at a minimum of 11 years following surgery and were evaluated clinically using the American Knee Society Clinical Rating Score. Additional evaluation was performed using the Hughston Scale to include radiographic assessment. The mean American Knee Society Score was 179 (out of 200), indicating good clinical function. Radiographically, however, only 29% scored excellent or good on the Hughston Scale. Younger patients with a small, stable (and therefore preserved), medial femoral condyle lesion had the best prognosis. Whilst more novel and complex options such as chondrocyte implantation are being assessed for the treatment of OCD, it is clear that within this study group careful debridement with removal of loose tissue can achieve good clinical results in the long term. There was however radiographic evidence of early degenerative joint disease in 17/24 (71%) of patients reviewed. Patients undergoing excision of OCD fragments did worse than those in whom the fragment was preserved, however the risk of further surgery is raised if a fragment is left in situ at initial surgery.

A comparison of bilateral uncemented total knee arthroplasty: simultaneous or staged?

In a series of 1304 patients (1867 knees), the results of simultaneous and staged bilateral total knee arthroplasty were compared with each other and with unilateral total knee arthroplasty. The bilateral procedures had a significantly higher rate of complications than unilateral procedures, almost entirely because of thromboembolic problems. However, this did not correspond to an increase in mortality. If a bilateral procedure was indicated, then a simultaneous procedure had no increased risk over a staged procedure. There was no increase in cardiovascular complications, the rate of deep-vein thrombosis or pulmonary embolism or mortality. The rate of infection was lower with a bilateral procedure and the overall revision rate was less than 1% in all groups. The prosthesis functioned as well in all groups in the medium and longer term periods. We feel that simultaneous bilateral total knee arthroplasty is a safe and successful procedure when compared with a staged bilateral procedure. It also has the added benefit of single anaesthetic, reduced costs and decreased total recovery time when compared to a staged bilateral procedure. For these reasons it should be considered as an option in the presence of bilateral knee joint disease.

Results of open arthrolysis for the treatment of stiffness after total knee replacement.

Stiffness is an uncommon but potentially debilitating complication following total knee replacement (TKR). The treatment of this condition remains difficult and controversial. We present the results of 13 patients who underwent open arthrolysis for stiffness. The mean time between TKR and arthrolysis was 14 months. The mean follow-up was 7.2 years (2 to 10). The mean range of movement prior to arthrolysis was 55 degrees . This increased to 91 degrees , six months after arthrolysis (p < 0.005). The improved range of movement was maintained during the follow-up period. No patient has required revision of their components. We have found arthrolysis to be a useful and successful approach to post-TKR stiffness.

A hydroxyapatite-coated total knee replacement: prospective analysis of 1000 patients.

We prospectively reviewed 1000 consecutive patients who underwent a cementless, hydroxyapatite-coated, stemless, total knee replacement over a period of nine years. Regular post-operative clinical follow-up was performed using the Knee Society score. The mean pre-operative score was 96, improving to 182 and 180 at five and ten years, respectively. To date, there have been seven (0.5%) cases which required revision, primarily for septic loosening (four cases), with low rates of other post-operative complications. The cumulative survival at ten years with revision as the end-point, was 99.14% (95% confidence interval 92.5 to 99.8). These results support the use of hydroxyapatite in a cementless total knee replacement since it can give reliable fixation with an excellent clinical and functional outcome.

Hydroxyapatite-coated, cementless total knee replacement in patients aged 75 years and over.

We have carried out a prospective study comparing the results at five years in patients older than 75 years of age undergoing hydroxyapatite-coated, cementless total knee replacement (TKR) with those who were younger. The Knee Society clinical rating scores were recorded before and after operation. Of 559 patients undergoing TKR, 135 were in the elderly age group. The knee scores at five years or more showed comparable results, with patients under 75 years of age reaching a score of 183 and those aged 75 years or over reaching 174. These differences were predominantly due to the functional component of the score. We conclude that elderly patients do just as well as the younger group using this prosthesis.

Arthroscopic debridement in the treatment of the infected total knee replacement.

Infection is a potentially disastrous complication of total knee replacement (TKR). Retention of the prosthesis has been associated with high rates of persistent infection. Our study shows that in selected situations, arthroscopic debridement may allow retention of the prosthesis and eradication of the infection. However, the prosthesis must be stable, the surgical technique must be meticulous and specific antibiotics must be taken for a lengthy period. Arthroscopic debridement should be considered as an alternative to an open technique, or revision, for the infected TKR.

Meniscal bearing uncemented total knee arthroplasty: early clinical results at a minimum 2-year review.

A prospective study of early clinical and radiologic outcome of the Motus (Osteo, Selzach, Switzerland) meniscal bearing total knee arthroplasty was performed. We reviewed the first 75 consecutive prostheses in 62 patients, implanted over a 4-year period. The mean follow-up was 2.5 years. Average preoperative knee score was 97 out of 200 (Knee Society score, 43; functional score, 54) and at 2-year review was 179 out of 200 (Knee Society score, 87; functional score, 92). Average postoperative flexion at 2 years was 113 degrees. No meniscal bearing subluxation, dislocation, or breakages occurred. Radiologically, there was no evidence of subsidence or osteolysis. Our results support the continued use of this meniscal bearing knee prosthesis. It is important to confirm, however, an equal flexion and extension gap without proximal joint line migration.

Ability to kneel after total knee replacement.

We have investigated the ability to kneel after total knee replacement. We asked 75 patients (100 knees) at least six months after routine uncemented primary total knee replacement, to comment on and to demonstrate their ability to kneel. Differences between the perceived and actual ability to kneel were noted. In 32 knees patients stated that they could kneel without significant discomfort. In 54 knees patients avoided kneeling because of uncertainties or recommendations from third parties (doctors, nursing staff, friends, etc). A total of 64 patients was actually able to kneel without discomfort or with mild discomfort only and 12 of the remainder were unable to kneel because of problems which were not related to the knee. Twenty-four patients therefore were unable to kneel because of discomfort in the knee. There was no difference between the 'kneelers' and 'non-kneelers' with regard to overall knee score, range of movement and the presence of patellar resurfacing.

A new chemical synthesis of 5alpha-cholest-8(14)-en-3beta,5alpha-diol.

Reduction of 3beta-benzoyloxy-14alpha,15alpha-epoxy-5alpha-cholest-7-ene with lithium in ethylenediamine gave 5alpha-cholest-8(14)-en-3beta, 5alpha-diol in high yield. This procedure offers an alternate synthesis through the reductive rearrangement of an alpha,beta-unsaturated steroidal epoxide.

Design and synthesis of new steroidal inhibitors of estrogen synthase (aromatase).

The estrogen synthase (aromatase) enzyme system is responsible for the biosynthesis of estrogen hormones in human females. Estrogens are vital for normal growth and development, but will promote the growth of certain breast cancers. Approximately 30-50% of breast cancers are considered to be hormone-dependent. Consequently regulation of estrogen biosynthesis has advanced as a potential therapeutic strategy. This has led to the development of active-site inhibitors, which may have potential for the control of breast cancer. We have recently prepared a number of new steroidal inhibitors that have been evaluated as aromatase inhibitors. These include steroidal A/B-ring isoxazoles and a series of A/B-ring pyrazoles with alkyl- and aryl-substituted nitrogen. In addition, we have developed new chemical procedures for the synthesis of 6beta-hydroxy steroids, which could be key intermediates in the preparation of C-19 inhibitors of aromatase activity.

Pneumocysterol [(24Z)-ethylidenelanost-8-en-3beta-ol], a rare sterol detected in the opportunistic pathogen Pneumocystis carinii hominis: structural identity and chemical synthesis.

Pneumocystis carinii pneumonia (PcP) remains among the most prevalent opportunistic infections among AIDS patients. Currently, drugs used clinically for deep mycosis act by binding ergosterol or disrupting its biosynthesis. Although classified as a fungus, P. carinii lacks ergosterol. Instead, the pathogen synthesizes a number of distinct Delta7, 24-alkylsterols, despite the abundance of cholesterol, which it can scavenge from the lung alveolus. Thus, the pathogen-specific sterols appear vital for organism survival and proliferation. In the present study, high concentrations of a C32 sterol were found in human-derived P. carinii hominis. The definitive structural identities of two C-24 alkylated lanosterol compounds, previously not reported for rat-derived P. carinii carinii, were determined by using GLC, MS, and NMR spectroscopy together with the chemical syntheses of authentic standards. The C31 and C32 sterols were identified as euphorbol (24-methylenelanost-8-en-3beta-ol) and pneumocysterol [(24Z)-ethylidenelanost-8-en-3beta-ol], respectively. The identification of these and other 24-alkylsterols in P. carinii hominis suggests that (i) sterol C-24 methyltransferase activities are extraordinarily high in this organism, (ii) 24-alkylsterols are important components of the pathogen's membranes, because the addition of these side groups onto the sterol side chain requires substantial ATP equivalents, and (iii) the inefficacy of azole drugs against P. carinii can be explained by the ability of this organism to form 24-alkysterols before demethylation of the lanosterol nucleus. Because mammals cannot form 24-alkylsterols, their biosyntheses in P. carinii are attractive targets for the development of chemotherapeutic strategies against this opportunistic infection.

Synthesis of new steroidal isoxazoles: inhibitors of estrogen synthase.

A novel class of steroidal A/B ring isoxazoles have been prepared by two independent reaction schemes using 3 beta,17 beta-diacetoxyandrost-5-ene (1) and 3 beta,17 beta-diacetoxyandrost-4-en-6-one (4) as synthetic precursors. The key common intermediate in these syntheses, 3 beta,17 beta-diacetoxyandrost-4-eno[6,5,4-c,d] isoxazole (3), was prepared by synthetic methods described in both schemes. Further chemical modification of 3 yielded 3 beta,17 beta-dihydroxyandrost-4-eno[6,5,4-c,d] isoxazole (6), androst-3,17-dione-4-eno[6,5,4-c,d] isoxazole (7), and 17 beta-hydroxyandrost-3-one-4-eno[6,5,4-c,d] isoxazole (9). Human placental estrogen synthase (aromatase) bioassays were conducted to obtain the following IC50 values resulting from a 50% reduction of enzymatic activity: 6, 120.5 microM; 7, 1.889 microM. 9, 18.57 microM.

Remote functionalization of the steroid side-chain.

By using classical methods of organic synthesis, the introduction of chemical modifications into the saturated side-chains of steroids usually requires a multistep synthesis to construct new side-chains to be added to the steroid nucleus. In order to circumvent these earlier methods, new procedures have been developed to directly introduce functionality onto the steroid side-chain to produce useful products. These initial products may also provide an entry toward the further modification of the side-chain to produce steroids which could previously be obtained only with great difficulty.

Identification of C31 and C32 sterols in Pneumocystis carinii hominis-infected human lungs.

Two sterols in autopsied whole lung specimens obtained from Pneumocystis carinii pneumonia patients were detected by gas-liquid chromatography and their structures were elucidated by mass spectrometry and nuclear magnetic resonance spectrometry. Both were in the lanosterol series; the C31 sterol, with a methyl group at C-24, was identified as euphorbol, and the more abundant C32 sterol, with an ethyl group at C-24, is given the trivial name pneumocysterol.