The split orbicularis myomucosal flap for lower lip reconstruction

OBJECTIVES: To describe the split orbicularis myomucosal flap and to review our center's experience with this technique for large defects of the lower lip. METHODS: All patients presenting to the senior author (Y.D.) for lower lip reconstruction using this flap were reviewed in a retrospective fashion. RESULTS: A total of 14 patients with a minimum follow-up of 6 months (mean, 3.4 years; range, 6 months to 5 years) underwent lower lip reconstruction using the split orbicularis myomucosal flap from May 1999 to May 2004. Twelve of the defects arose as a result of cancer resection (squamous cell carcinoma [n = 8], basal cell carcinoma [n = 3], and melanoma [n = 1]), and 2 arose secondary to trauma. The defect crossed the vermilion in two thirds of the cases, extending for a variable distance onto the cutaneous portion of the lower lip. The defect size varied from 50% to 80% of the transverse dimension of the lower lip (mean, 68%) and involved the commissure in 4 patients. There were no flap failures, facial nerve palsies or paralyses, oral incompetence, or need for scar revision in any of our study population. CONCLUSION: The split orbicularis myomucosal flap is a reliable method of reconstructing significant defects of up to 80% of the lower lip with minimal risks of microstomia or functional impairment.     

Method for manipulating peak flow measurements producing falsely raised readings

Methods by which patients can artificially produce raised peak flow measurements have been described. We recently observed a patient manipulating the peak flow meter in a way that had not been described before. A study was therefore undertaken to determine if this technique could repeatedly produce clinically significant changes in peak flow readings. Fifteen adults, using a mini-Wright peak flow meter, made five measurements using the correct technique followed by five manipulated measurements under observation. Significant increases in peak flow measurements were observed in 14 of the 15 subjects. The mean increase in peak flow rate using the incorrect technique was 56% (range -4% to 86%). Clinicians should be aware that patients might employ this technique to manipulate measurements which could have consequences for management.     

Isolation of Mycoplasma pneumoniae from synovial fluid samples in a patient with pneumonia and polyarthritis

A patient with a long history of arthritis developed pneumonia. Two weeks into her hospital course, the patient developed effusions in her knee and wrist that yielded cultures positive for Mycoplasma pneumoniae. To our knowledge, this is the third reported case of M pneumoniae isolation from a joint and the first report of isolation of M pneumoniae from two joints in a patient without hypogammaglobulinemia. The evidence suggests that in individuals with atypical pneumonia and joint effusions, M pneumoniae should be considered as a source of infection.     

Mutations disrupting the Kennedy phosphatidylcholine pathway in humans with congenital lipodystrophy and fatty liver disease

Phosphatidylcholine (PC) is the major glycerophospholipid in eukaryotic cells and is an essential component in all cellular membranes. The biochemistry of de novo PC synthesis by the Kennedy pathway is well established, but less is known about the physiological functions of PC. We identified two unrelated patients with defects in the Kennedy pathway due to biallellic loss-of-function mutations in phosphate cytidylyltransferase 1 alpha (PCYT1A), the rate-limiting enzyme in this pathway. The mutations lead to a marked reduction in PCYT1A expression and PC synthesis. The phenotypic consequences include some features, such as severe fatty liver and low HDL cholesterol levels, that are predicted by the results of previously reported liver-specific deletion of murine Pcyt1a. Both patients also had lipodystrophy, severe insulin resistance, and diabetes, providing evidence for an additional and essential role for PCYT1A-generated PC in the normal function of white adipose tissue and insulin action.All living cells are surrounded by a lipid membrane. Eukaryotic cells also contain several internal membrane-bound organelles, which enable them to compartmentalize related biological functions and thereby to enhance the efficiency of these processes. Phospholipids are the predominant component of these membranes. Their hydrophilic head groups interact with the cytosol, whereas their hydrophobic side chains are either buried within the hydrophobic interior of a typical membrane bilayer or interact with the hydrophobic neutral lipid core of lipoproteins and lipid droplets (LDs). Phospholipids are generally defined by their organic head group with phosphatidylcholine (PC) constituting over 50% of all membrane phospholipids. PC was first isolated in the 19th century and the major enzymatic pathway involved in its synthesis was revealed by Kennedy and Weiss (1) in the 1950s. Cells synthesize PC in three consecutive steps (Fig. 1A): choline kinase phosphorylates choline before choline phosphate cytidylyltransferase 1 α (encoded by the PCYT1A gene) generates the high-energy donor CDP-choline in the rate-limiting step of the pathway. In the last step, DAG:CDP-choline cholinephosphotransferase (CPT) uses CDP-choline and diacylglycerol (DAG) to form PC (2, 3).Open in a separate windowFig. 1.Cosegregation of biallelic PCYT1A mutations with fatty liver, low HDL cholesterol levels, lipodystrophy, insulin-resistant diabetes, and short stature. (A) Schematic illustration of the Kennedy PC synthesis pathway. CK, choline kinase; CPT, CDP-choline:1,2-diacylglycerol cholinephosphotransferase; PCYT1A, choline-phosphate cytidylyltransferase A, CTP:phosphocholine-cytidylyltransferase. (B) Family pedigrees of both probands demonstrating that only compound heterozygous carriers of PCYT1A mutations manifest fatty liver (red), low HDL cholesterol (blue), lipodystrophy (yellow), and insulin resistance/type 2 diabetes (T2DM) (green). PCYT1A mutation status, height (Ht.), and body mass index (BMI) are indicated below each individual’s symbol. ND, not determined; WT, wild type. (C) The location of PCYT1A mutations E280del, V142M, and 333fs in relation to known functional domains of PCYT1A. Domain M, membrane binding domain; domain P, phosphorylated region. (D) Conservation around the V142(red*) and E280(red*) mutation sites. Sequence alignment of representative metazoan sequences in the region surrounding the mutated residues. Hydrophobic (blue) and polar (green) residues interacting with V142 are highlighted. Only residues different from the human sequence are shown. Sequence IDs: human (Homo sapiens) {"type":"entrez-protein","attrs":{"text":"P49585","term_id":"166214967"}}P49585, zebrafish (Danio rerio) F1QEN6, sea squirt (Ciona intestinalis) {"type":"entrez-protein","attrs":{"text":"XP_002130773.1","term_id":"198437270"}}XP_002130773.1, sea urchin (Strongylocentrotus purpuratus) H3I3V9, water flee (Daphnia pulex) E9G1P5, Drosophila (D. melanogaster) Q9W0D9, Caenorhabditis (C. elegans) {"type":"entrez-protein","attrs":{"text":"P49583","term_id":"32172439"}}P49583, Trichoplax (T. adherens) B3RI62. (E and F) Structure of the catalytic domain of PCYT1A highlighting the role of V142M in the core packing. The two chains in the dimer are shown in yellow and gray; the residues and the secondary structure units are highlighted in color in the yellow monomer A: loop L3 with V142, red; α-helix, green; and the interacting β-sheet, blue. The residues packing with V142 are shown in ball-and-stick and space-filling representations, the dimer stabilizing R140 is shown in ball-and-stick colored according to the atom type. E is a global view, and F is a zoomed-in view of the catalytic core.Membrane phospholipids are a defining feature of advanced life-forms so it is perhaps not surprising that the pathways involved in their synthesis are ancient, and mutations affecting them are rarely tolerated in evolution. Here, we describe the identification and characterization of pathogenic human loss-of-function mutations affecting the eponymous Kennedy pathway.     

The importance of physics to progress in medical treatment

Physics in therapy is as diverse as it is substantial. In this review, we highlight the role of physics--occasionally transitioning into engineering--through discussion of several established and emerging treatments. We specifically address minimal access surgery, ultrasound, photonics, and interventional MRI, identifying areas in which complementarity is being exploited. We also discuss some of the fundamental physical principles involved in the application of each treatment to medical practice.