Evaluation of Results of Open Reduction and Internal Fixation (ORIF) of Fracture of Distal End of Femur with Intra-Articular Extension.

INTRODUCTION: Fractures of the distal femur account for 0.4% of all fractures. They involve about 7% of all femur fractures, with bimodal age distribution, commonly occur during high-velocity trauma of motor vehicle accidents in the younger group of patients and are frequently associated with other skeletal injuries. The treatment of distal femoral fractures has evolved from conservative treatment to more aggressive operative treatment. The aim is to achieve and maintain a good reduction of the joint to allow early active mobilisation, thus minimising the joint stiffness and severe muscular atrophy encountered in the conservative treatment. MATERIALS AND METHODS: This is a retrospective study of 25 patients with distal femur fracture with intra-articular extension treated with open reduction and internal fixation with DFLP, admitted at our institute between 2016 to 2019, with a minimum follow-up of six months. RESULTS: In our study, 19 (76%) patients had excellent to good results. Three (12%) patients had fair outcomes, and three (12%) patients had poor outcomes according to Neer's score. The average time for bone union in closed fractures was earlier (4.25 months) than open fractures, averaging 5.86 months. The outcome was almost similar between closed and open fractures. There were 2 (8%) cases of infection in the early post-operative period, 7 (12%) patients suffered from knee stiffness, and there were 3 (12%) cases with a pre-operative bone loss that required bone grafting. CONCLUSION: Management of complex intra-articular distal femur fracture has always been a challenge. Anatomical reduction of articular fragments and rigid fixation of these fractures are a must. DFLP provides angular stability with multiple options to secure fixation of both metaphyseal and articular fragments with the restoration of the joint congruity, limb length, alignment and rotation, allowing early mobilisation and aggressive physiotherapy without loss of fixation, resulting in gratifying functional outcome and low complication rate.

Clinical research and diagnostic efficacy studies in the oral and maxillofacial radiology literature: 1996-2005.

OBJECTIVES: The aim of this study was to determine the level of evidence that is published in the oral and maxillofacial radiology (OMR) literature. METHODS: OMR papers published in Dentomaxillofacial Radiology and Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontology between 1996 and 2005 were classified using epidemiological study design and diagnostic efficacy hierarchies. The country of origin and number of authors were noted. RESULTS: Of the 725 articles, 384 could be classified with the epidemiological study design hierarchy: 155 (40%) case reports/series and 207 (54%) cross-sectional studies. The distribution of study designs was not statistically significant across time (Fisher's exact test, P = 0.06) or regions (P = 0.89). The diagnostic efficacy hierarchy was applicable to 246 articles: 71 (29%) technical efficacy and 166 (67%) diagnostic accuracy studies. The distribution of efficacy levels was not statistically significant across time (P = 0.22) but was significant across regions (P < 0.01). Authors from Japan produced 26% of the papers with a mean ± standard deviation of 5.78 ± 1.98 authors per paper (APP); American authors, 23% (3.78 ± 1.72 APP); and all others, 51% (3.76 ± 1.51 APP). CONCLUSION: The OMR literature consisted mostly of case reports/series, cross-sectional, technical efficacy and diagnostic accuracy studies. Such studies do not provide strong evidence for clinical decision making nor do they address the impact of diagnostic imaging on patient care. More studies at the higher end of the study design and efficacy hierarchies are needed in order to make wise choices regarding clinical decisions and resource allocations.

Melanoma in solid organ transplant recipients.

This manuscript outlines estimated risk and clinical course of pretransplant MM, donor-transmitted MM and de novo MM posttransplantation and includes an analysis of risk factors for metastasis, data from clinical studies and current and proposed management. MM in situ and thin melanoma (<1 mm) in the transplant population has similar recurrence and survival estimates to those in the general population. A minimum wait time of 2 years prior to transplantation is suggested for MM with a Breslow depth <1 mm and no clinical evidence of metastasis. More advanced MM may adopt a more aggressive course in transplant recipients. Sentinel lymph node biopsy may be of additional prognostic benefit. Revision of immunosuppression in the management of de novo melanoma in collaboration with the transplant team should be considered. Larger studies utilizing uniform staging criteria or at minimum Breslow depth, are required to assess true risk and outcome of MM in the immunosuppressed transplant population. Emphasis remains on patient education and regular screening to provide early detection of MM.

Prevention of non-melanoma skin cancer in organ transplant patients by regular use of a sunscreen: a 24 months, prospective, case-control study.

BACKGROUND: Skin cancers represent a major challenge within the ever growing group of long time surviving organ transplant recipients (OTR) world wide. Especially UV-induced non-melanoma skin cancers (NMSC) like invasive squamous cell carcinomas (SCC) and actinic keratoses (AK), and basal cell carcinoma (BCC), outnumber every other form of cancer in organ transplant recipients. Despite encouraging reports of protective effects of broad-spectrum sunscreens in immunocompetent patients, evidence for the prevention of NMSC in immunocompromised patients is still missing. OBJECTIVES: To assess preventive effects of regular sun-screen use on AK, SCC and BCC in chronically immunocompromised organ transplant recipients. METHODS: Hundred and twenty matched (age, sex, skin type, graft, transplant duration, previous post-transplant skin malignancies) organ transplant recipients (40 heart, 40 kidney, 40 liver grafted) were recruited for this prospective, single-center study. Both groups received equally written and oral information on sun protection measures. Sixty patients were provided with a free broad spectrum study-sunscreen (SPF>50, high-UVA absorption) for daily application of 2 mg cm(-2) to the head, neck, forearms, and hands. RESULTS: All 120 patients completed the 24 months study. Within this 24 month study interval 42 of the 120 patients developed 82 new AK (-102 sunscreen group vs. +82 control; P<0.01), 8 new invasive SCC (0 vs. 8; P<0.01) and 11 BCC (2 vs. 9; ns). In spite of equal numbers of AK at baseline, a marked difference in favor of the intent-to-treat sunscreen group was recorded after 24 months (89 vs. 273; P<0.01, mean difference 3.07 [1.76-4.36]) and the lesion count was significantly lower as compared to the initial visit (89 vs. 191; P<0.01, mean difference 1.7 [0.68-2.72]). With an average of 5.6 applications per week throughout the 24 months the study sunscreen was generally well tolerated. Serum 25-hydroxy vitamin D levels as marker for vitamin D status were decreased in all patients without adequate substitution and 25(OH)D was found to be lower in the sunscreen-group as compared to the control group (mean value 53 ng mL(-1) vs. 60 ng mL(-1)). INTERPRETATION: Regular use of sunscreens, as part of a consequent UV-protection strategy, may prevent the development of further AK and invasive SCC and, to a lesser degree, BCC in immune-compromised organ transplant recipients.

Skin cancer and the solid organ transplant recipient.

Organ transplant recipients (OTRs) are living longer in setting of improved medical immunosuppression. The most common late post-transplant complication includes a variety of malignant and premalignant cutaneous tumors. Aggressive skin cancers are common in this population. Clinical and pathologic correlation is essential in choosing the appropriate treatment for the various subtypes of skin cancer in OTR. Approaches include risk assessment for other skin tumors, treatment of malignancy, and prevention. Few prospective or retrospective studies with multivariate analysis exist and therefore opinion largely dominates treatment recommendations. Treatment aims: (i) The mainstay of treatment focuses on total removal (excision) or mechanical destruction of the tumor. In the appropriate clinical scenario, a skin cancer should be removed or treated fully. (ii) Treatment modality is dependant upon low- vs high-risk tumors and tumor type. (iii) Utilize excision with margin control, either by permanent or frozen (Mohs) technique, for large tumors and tumors in high-risk sites. (iv) New treatment modalities include immune modulators, topical photodynamic therapy, and drugs targeting genetic defects. (v) Education on skin cancer prevention should target all the age groups.

Actinic keratosis is an early in situ squamous cell carcinoma: a proposal for reclassification.

The term actinic keratosis (AK) describes a sun-induced, clinical erythematous lesion covered with scale, but does not provide an understanding of the biology or histopathology of the lesion. Consequently, several classification systems for AK have been suggested, but as yet no consensus has been reached. These systems strive to correlate the pathological and clinical features to better provide physicians with the most accurate information to enable correct decisions to be made regarding treatments, Prognosis and metastatic potential. AK is a clinical description that has a histological diagnosis consistent with squamous cell carcinoma (SCC) in situ. We recommend an AK classification system that describes these lesions as squamous cell carcinomas (SCCs), using the terminology 'early in situ SCC Type AK I', 'early in situ SCC type AK II' and 'in situ SCC Type AK III', there by giving clinicians better guidance for diagnosis and specific treatment recommendations.

Does progression from actinic keratosis and Bowen's disease end with treatment: diclofenac 3% gel, an old drug in a new environment?

Progression from actinic keratosis (AK) and Bowen's disease (BD) to invasive disease involves a complex cascade of events. The preparation of diclofenac 3% gel (Solaraze; Shire Pharmaceuticals) has been shown to be efficacious and well tolerated in AK. The inhibition of the COX enzymes results in a decrease in downstream by-products of arachidonic acid metabolism. These metabolites have been shown to play a pivotal role in promoting epithelial tumour growth. Given its mechanism of action, we hypothosize that diclofenac 3% gel may have potential to halt the progression of actinic keratoses (AKs) in the setting of field cancerisation and BD. We report a series of five patients with BD, all treated with diclofenac 3% gel with clinical and histological clearance.

Genetically determined susceptibility to COX-2 inhibitors: a report of exaggerated responders to diclofenac 3% gel in the treatment of actinic keratoses.

Diclofenac 3% gel is an effective treatment for actinic keratoses (AKs) and is reported to be generally well tolerated with only mild local reactions. However, there is a subset of patients that seem to be susceptible to developing severe local reactions following application of diclofenac 3% gel. Although some of these reactions can be explained as being allergic contact dermatitis and/or photoallergic contact dermatitis, others cannot. We report a series of 10 patients who all developed severe local reactions following application of diclofenac 3% gel, despite negative diclofenac patch testing. This raises the question as to whether there is a subset of patients with skin cancer or AK lesions that are highly/more susceptible to local reactions caused by cyclo-oxygenase-2 (COX-2) inhibitors and peroxisome proliferator-activated receptor (PPAR) agonists? We speculate that underlying molecular differences exist in these patients that make the skin more susceptible to COX-2 inhibitors.

From embryos to embryonic stem cells: biopolitics and therapeutic potential.

The inner cell mass of the preimplantation blastocyst, from which all the cells of the body develop, is a source of embryonic stem cells. These cells can be maintained in their undifferentiated state over long periods in culture and yet retain their pluripotency. The generation of human stem cells capable of differentiating into all the cell types of the human body opens the way for the use of these cells in therapeutic transplantation for a myriad of diseases. However, as discussed here, there are a number of logistical, biological, and clinical hurdles that must be overcome prior to the use of these cells in routine clinical practice.

From embryos to embryonic stem cells: biopolitics and therapeutic potential.

The inner cell mass of the preimplantation blastocyst, from which all the cells of the body develop, is a source of embryonic stem cells. These cells can be maintained in their undifferentiated state over long periods in culture and yet retain their pluripotency. The generation of human stem cells capable of differentiating into all the cell types of the human body opens the way for the use of these cells in therapeutic transplantation for a myriad of diseases. However, as discussed here, there are a number of logistical, biological, and clinical hurdles that must be overcome prior to the use of these cells in routine clinical practice.

Liquid phase migration in the extrusion and squeezing of microcrystalline cellulose pastes.

Extensive movement of the liquid phase relative to the solids in solid-liquid pastes during extrusion forming is an undesirable process phenomenon. The impact of formulation and flow pattern on liquid phase migration (LPM) during extrusion of model pharmaceutical pastes (40-50 wt% microcrystalline cellulose/water) has been investigated by ram extrusion through square-entry and 45 degrees conical-entry dies, and by lubricated squeeze flow (extensional flow). Threshold velocities for LPM were observed in both configurations. Squeeze flow testing showed that dilation during extension can cause LPM, while ram extrusion featured both dilation effects and drainage due to compaction. The threshold velocities observed in the two configurations agreed when presented as characteristic shear rates. The threshold velocity increased with paste solids content.

Skin manifestations in vasculitis and erythema nodosum.

Cutaneous lesions are frequent in medium-sized and small vessel systemic vasculitides. The classic cutaneous manifestation of vasculitis is palpable purpura; however the clinical manifestations greatly depend on the size of the vessels affected. They usually do not affect prognosis but relapsing or intractable forms have been described. When skin manifestations are only one of the clinical signs of vasculitis, treatment with corticosteroids and, when indicated, an immunosuppressant, is mandatory, which usually leads to the rapid disappearance of cutaneous lesions. Conversely, when skin lesions are isolated, the diagnosis can be more challenging, but initial treatment may be less aggressive, e.g., dapsone or colchicine, reserving corticosteroids only for those patients in whom the former are ineffective. Erythema nodosum (EN) is the most frequent septal panniculitis. In general it is characterized by the sudden eruption of one or more erythematous and tender nodules or plaques located mainly over the extensor sides of lower extremities. EN resolves with complete "restitutio ad integrum" of the skin in 3-6 weeks. Relapses are uncommon but in patients with idiophatic, streptococcal or EN associated with other upper respiratory tract infections they are more frequent. The main treatment of EN is that of the underlying associated conditions, if demonstrated. Aspirin and other NSAIDs in full doses are often sufficient.

Use of the Self-Administered Eczema Area and Severity Index by parent caregivers: results of a validation study.

BACKGROUND: The Eczema Area and Severity Index (EASI) is used by dermatological investigators world-wide to assess eczema disease severity. EASI measures are, however, time-consuming and require trained personnel, thereby limiting its application to large-scale epidemiological studies. Additionally, the use of self-assessed severity indices in dermatology is restricted to adult subjects and conditions, thereby not addressing the needs of paediatric patients. OBJECTIVES: To develop and validate an instrument for a caregiver's self-assessment of the severity of his/her child's atopic dermatitis (AD), the Self-Administered EASI (SA-EASI). METHODS: Trained investigators performed a modified EASI assessment on the same day as an SA-EASI was obtained from 47 caregivers of children with AD. RESULTS: The SA-EASI was found to be a valid measure of the severity of AD. Total, acute and chronic SA-EASI scores predicted total, acute and chronic modified EASI scores (P < 0.0001). SA-EASI body surface area (BSA) scores predicted EASI BSA scores (P < 0.0001). SA-EASI pruritus scores correlated with the acute, chronic and total EASI scores (P = 0.0001). CONCLUSIONS: The SA-EASI may provide caregivers the means to report the severity of their child's skin disease objectively. The high correlation with the EASI score observed in this sample implies that statistical inferences with the SA-EASI will be valid for large populations. In future studies, this will permit analysis of the relationship of skin disease severity to such measures as quality of life, disability, patient satisfaction and the costs of various therapies. Moreover, this SA-EASI instrument may allow older children, over 12 years old, to assess the severity of their AD.

Comparative efficacy and pharmacokinetics of racemic bupivacaine and S-bupivacaine in third molar surgery.

PURPOSE: To compare the efficacy and pharmacokinetics of racemic bupivacaine (rac-bupivacaine) with S-bupivacaine as primary local anesthetic agent in bilateral impacted third molar extractions. METHOD: A randomised, double blind, two period cross-over design was employed. Six subjects (2 males, 4 females; age 19-25 years; weight 69.2+/-9.4 kg) received bupivacaine hydrochloride injection (6.6 ml) as rac-bupivacaine (0.5% as salt) or S-bupivacaine (0.5% as base) prior to extraction of impacted third molars on one side and three weeks later on the other side. Anesthesia, blood loss associated with surgery and post-operative pain experience were evaluated. Plasma samples were analysed for bupivacaine enantiomers by chiral HPLC. RESULTS: In 7/12 operations, anesthesia adequate for surgery was delayed (>10 min) or unsatisfactory requiring lidocaine rescue medication. Despite this, there were no significant differences in onset and duration of anesthesia, blood loss or post-operative pain experience between the two arms of the study. Pharmacokinetic parameters were not significantly different and there was no evidence of chiral inversion after dosing with S-bupivacaine. CONCLUSIONS: Both study drugs were inadequate as single anesthetic agent for third molar surgery. Any decision to use S-bupivacaine for oral surgery must rest on evidence that it is less toxic than the racemic drug.

Bone and joint complications related to Gaucher disease.

There is a broad spectrum of Gaucher disease-related skeletal complications, ranging from asymptomatic osteopenia to osteonecrosis (of the shoulders and hips) with secondary degenerative joint disease. Characterization of the pattern and severity of bone involvement in the individual patient requires the application of conventional and advanced radiographic techniques. The introduction of enzyme replacement therapy (ERT) for this inborn error of glycosphingolipid metabolism has focused great interest in determining the nature and extent of the bone responses with this mode of treatment. The multifactorial etiology of the bone complications necessitates a multifaceted approach, combining pharmacologic strategies with physical therapy and orthopedic intervention. As bone disease can lead to chronic pain and debility with a resultant adverse impact on quality of life, it is important that patients be monitored closely and that early intervention with ERT prior to established bone disease (infarction and fibrosis) be considered.

Analysis of cross-linked human hemoglobin by conventional isoelectric focusing, immobilized pH gradients, capillary electrophoresis, and mass spectrometry.

Diaspirin cross-linked hemoglobin (DCLHb), a hemoglobin-based oxygen carrier exhibiting near physiological oxygen binding capability and devoid of nephrotoxic side effects, was previously found, by gel permeation, reversed-phase high performance liquid chromatography (RP-HPLC) and mass spectrometry, to consist of ca. 94% cross-linked product (reacted on the Lys 99 of two alpha-chains), accompanied by ca. 6% cross-linked Hb, which also reacted on the Lys 132 and/or Lys-144 of the beta-chains and a small amount of intermolecularly cross-linked dimers. However, conventional isoelectric focusing in carrier ampholyte buffers (CA-IEF) gave an unexpected spectrum of four major, almost equally represented, pI species in the pH range of 6.82-7.01, a band of mid-intensity with a pI of 7.11, and two minor components with pls of 6.73 and 6.77. This extraordinary polydispersity was reevaluated by other surface charge probes, such as immobilized pH gradients (IPG) and capillary zone electrophoresis (CZE) of native and denatured globin chains. IPGs of DCLHb gave the expected spectrum of bands, consisting of a main component (92%) with pl 7.337 and three additional minor bands, with lower pIs, representing ca. 8% of the total. These data were in agreement with CZE profiles of native DCLHb, which resolved, in addition to the main DCLHb peak, 3-4 minor components representing ca. 10% of the total. Also, CZE of denatured, heme-free globin chains gave the expected pattern with only traces of minor, extrareacted species. The latter technique, in addition to resolving alpha- and beta-globin chains in a 1:1 ratio in control Hb, resolved a free beta- and the alpha-alpha-dimer in DCLHb. In a 1:1 mixture of control and DCLHb, three peaks were observed, eluting in the order alpha-, alpha-alpha- and beta-globin chains. The identity of the major DCLHb and of the minor species was ascertained by mass spectrometry.

Absence of immunogenicity of diaspirin cross-linked hemoglobin in humans.

Diaspirin cross-linked hemoglobin (DCLHb) is an intramolecularly cross-linked hemoglobin-based oxygen carrier being developed as a therapy for acute blood loss. We report here the absence of immunogenicity of DCLHb in patients enrolled in phase II and III clinical trials of DCLHb. Two very sensitive immunoassays, an enzyme-linked immunosorbent assay (ELISA) and a Western blot assay, were developed and validated for this assessment. The DCLHb-antibodies used in these assays were raised in monkeys, had similar affinities for DCLHb and native human hemoglobin (SFHb), and showed cross-reactivity for subunits of DCLHb and SFHb on the Western blot, suggesting that these antibodies were elicited as a xenogenic response to the protein. In the ELISA, the optical density of a patient sample exposed to DCLHb-coated wells was compared with that of the patient sample exposed to carbonate buffer-coated wells; an optical density ratio of 1.4 was established for discriminating between a positive (reactive) or negative DCLHb antibody response. To date, all of the more than 300 patient specimens (preinfusion and postinfusion) from clinical trials have exhibited a ratio of less than 1.4, confirming the lack of preexisting antibodies to DCLHb and clearly showing the absence of DCLHb antibodies after exposure to this new biologic entity. There has been no requirement for use of the confirmatory Western blot assay. Taken together, the results from this study indicate DCLHb is not immunogenic in humans at doses evaluated clinically.

Spinal leptomeningeal hemangioblastomatosis in von Hippel-Lindau disease: magnetic resonance and pathological findings.

A 55-year-old man with von Hippel-Lindau disease presented with quadriparesis. Multiple enhancing cervical and thoracic spinal masses were seen on magnetic resonance imaging (MRI). A rim of diffuse, nodular enhancement linking all of the discrete masses was apparent on the surface of the cervical and thoracic regions of the cord. Surgical exploration revealed multiple extramedullary-intradural and intramedullary masses, extending to and infiltrating the cord; the leptomeninges contained numerous small tumor seeds at several levels. The excised spinal masses were diagnosed as capillary hemangioblastomas, which infiltrated the pia mater. Diffuse, intense, spinal leptomeningeal enhancement on MRI associated with multiple hemangioblastomas has not been previously reported and may be referred to as spinal "leptomeningeal hemangioblastomatosis."

Structural characterization of human hemoglobin crosslinked by bis(3,5-dibromosalicyl) fumarate using mass spectrometric techniques.

Diaspirin crosslinked hemoglobin (DCLHb) was analyzed by mass spectrometric-based techniques to identify the protein modifications effected by the crosslinking reaction with bis(3,5-dibromosalicyl) fumarate. DCLHb consists of two principal components. These components were isolated by size-exclusion chromatography and identified by measurement of their molecular weight using electrospray mass spectrometry and subsequent peptide mass mapping and mass spectrometric sequence analysis of their individual digests. Three major RP-HPLC fractions were observed from the major hemoglobin in DCLHb. Their MWs matched the MW of heme, intact hemoglobin beta-chain, and two hemoglobin alpha-chains crosslinked by a fumarate moiety, respectively. The minor HPLC peaks of DCLHb were also separated, and characterized by mass spectrometric methods. These minor components revealed additional details of the structural nature of covalent modification of DCLHb.

Secretion of cyclic GMP by cultured epithelial and fibroblast cell lines in response to nitric oxide.

LLC-PK1 epithelial cells and RFL-6 fibroblasts secreted both cyclic AMP (cAMP) and cyclic GMP (cGMP) when costimulated with forskolin and 3-morpholinosydnonimine (a chemical nitric oxide generator). Intracellular cAMP levels as high as 1100 and 12,000 pmol/10(6) cells were achieved for the two cell types, respectively. These levels were high enough to reach approximately 50% saturation of the cAMP transporter and inhibited transport of cGMP to an equal extent, suggesting that the two cyclic nucleotides compete for a common transport system. The rates of secretion of cGMP and cAMP from LLC-PK1 cells increased in proportion to their rates of synthesis as concentrations of stimulant were varied, but increased only 25% relative to intracellular concentrations in response to inhibition of phosphodiesterases by 3-isobutylmethylxanthine. It is proposed that secretion of cyclic nucleotides is not simply proportional to the total intracellular pool in these cells, but rather is coupled to synthesis. In support of this model, oxyhemoglobin was used to trap nitric oxide and block activity of guanylate cyclase in cells treated with 3-morpholinosydnonimine. As a result, secretion of cGMP ceased within 1 min, whereas intracellular levels decreased slowly over 60 min. Probenecid [p-(dipropylsulfamoyl)benzoic acid] is a nonselective antagonist of anion transport that inhibited secretion of cAMP in both cell types but, unexpectedly, blocked synthesis of cGMP, and this was reflected in direct inhibition of soluble guanylate cyclase in cell lysates. Two heat-stable, high molecular weight factors that confer sensitivity to probenecid were identified, and these factors increased the sensitivity of guanylate cyclase to nitric acid by an order of magnitude.