Mutant Phosphodiesterase 3A Protects From Hypertension-Induced Cardiac Damage.

BACKGROUND: Phosphodiesterase 3A (PDE3A) gain-of-function mutations cause hypertension with brachydactyly (HTNB) and lead to stroke. Increased peripheral vascular resistance, rather than salt retention, is responsible. It is surprising that the few patients with HTNB examined so far did not develop cardiac hypertrophy or heart failure. We hypothesized that, in the heart, PDE3A mutations could be protective. METHODS: We studied new patients. CRISPR-Cas9-engineered rat HTNB models were phenotyped by telemetric blood pressure measurements, echocardiography, microcomputed tomography, RNA-sequencing, and single nuclei RNA-sequencing. Human induced pluripotent stem cells carrying PDE3A mutations were established, differentiated to cardiomyocytes, and analyzed by Ca2+ imaging. We used Förster resonance energy transfer and biochemical assays. RESULTS: We identified a new PDE3A mutation in a family with HTNB. It maps to exon 13 encoding the enzyme's catalytic domain. All hitherto identified HTNB PDE3A mutations cluster in exon 4 encoding a region N-terminally from the catalytic domain of the enzyme. The mutations were recapitulated in rat models. Both exon 4 and 13 mutations led to aberrant phosphorylation, hyperactivity, and increased PDE3A enzyme self-assembly. The left ventricles of our patients with HTNB and the rat models were normal despite preexisting hypertension. A catecholamine challenge elicited cardiac hypertrophy in HTNB rats only to the level of wild-type rats and improved the contractility of the mutant hearts, compared with wild-type rats. The ß-adrenergic system, phosphodiesterase activity, and cAMP levels in the mutant hearts resembled wild-type hearts, whereas phospholamban phosphorylation was decreased in the mutants. In our induced pluripotent stem cell cardiomyocyte models, the PDE3A mutations caused adaptive changes of Ca2+ cycling. RNA-sequencing and single nuclei RNA-sequencing identified differences in mRNA expression between wild-type and mutants, affecting, among others, metabolism and protein folding. CONCLUSIONS: Although in vascular smooth muscle, PDE3A mutations cause hypertension, they confer protection against hypertension-induced cardiac damage in hearts. Nonselective PDE3A inhibition is a final, short-term option in heart failure treatment to increase cardiac cAMP and improve contractility. Our data argue that mimicking the effect of PDE3A mutations in the heart rather than nonselective PDE3 inhibition is cardioprotective in the long term. Our findings could facilitate the search for new treatments to prevent hypertension-induced cardiac damage.

Reorganization of inter-chromosomal interactions in the 2q37-deletion syndrome.

Chromosomes occupy distinct interphase territories in the three-dimensional nucleus. However, how these chromosome territories are arranged relative to one another is poorly understood. Here, we investigated the inter-chromosomal interactions between chromosomes 2q, 12, and 17 in human mesenchymal stem cells (MSCs) and MSC-derived cell types by DNA-FISH We compared our findings in normal karyotypes with a three-generation family harboring a 2q37-deletion syndrome, featuring a heterozygous partial deletion of histone deacetylase 4 (HDAC4) on chr2q37. In normal karyotypes, we detected stable, recurring arrangements and interactions between the three chromosomal territories with a tissue-specific interaction bias at certain loci. These inter-chromosomal interactions were confirmed by Hi-C. Interestingly, the disease-related HDAC4 deletion resulted in displaced inter-chromosomal arrangements and altered interactions between the deletion-affected chromosome 2 and chromosome 12 and/or 17 in 2q37-deletion syndrome patients. Our findings provide evidence for a direct link between a structural chromosomal aberration and altered interphase architecture that results in a nuclear configuration, supporting a possible molecular pathogenesis.

Phosphodiesterase 3A and Arterial Hypertension.

BACKGROUND: High blood pressure is the primary risk factor for cardiovascular death worldwide. Autosomal dominant hypertension with brachydactyly clinically resembles salt-resistant essential hypertension and causes death by stroke before 50 years of age. We recently implicated the gene encoding phosphodiesterase 3A (PDE3A); however, in vivo modeling of the genetic defect and thus showing an involvement of mutant PDE3A is lacking. METHODS: We used genetic mapping, sequencing, transgenic technology, CRISPR-Cas9 gene editing, immunoblotting, and fluorescence resonance energy transfer. We identified new patients, performed extensive animal phenotyping, and explored new signaling pathways. RESULTS: We describe a novel mutation within a 15 base pair (bp) region of the PDE3A gene and define this segment as a mutational hotspot in hypertension with brachydactyly. The mutations cause an increase in enzyme activity. A CRISPR/Cas9-generated rat model, with a 9-bp deletion within the hotspot analogous to a human deletion, recapitulates hypertension with brachydactyly. In mice, mutant transgenic PDE3A overexpression in smooth muscle cells confirmed that mutant PDE3A causes hypertension. The mutant PDE3A enzymes display consistent changes in their phosphorylation and an increased interaction with the 14-3-3θ adaptor protein. This aberrant signaling is associated with an increase in vascular smooth muscle cell proliferation and changes in vessel morphology and function. CONCLUSIONS: The mutated PDE3A gene drives mechanisms that increase peripheral vascular resistance causing hypertension. We present 2 new animal models that will serve to elucidate the underlying mechanisms further. Our findings could facilitate the search for new antihypertensive treatments.

Reliability and validity of the Brachial Plexus Outcome Measure in children with obstetric brachial plexus palsy.

STUDY DESIGN: Clinical measurement and cross-sectional study. INTRODUCTION: Numerous scales have been developed to examine activities of daily living and function in children with brachial plexus palsy. The Brachial Plexus Outcome Measure (BPOM) scale was developed in 2012 by Emily S. Ho and contains 14 items that measure activity and self-evaluation. PURPOSE OF THE STUDY: The aim of the study was to cross-culturally translate the BPOM scale into Turkish and test its measurement properties in children with brachial plexus palsy. METHODS: The scale was translated into Turkish using standard cross-cultural translation procedures. Forty-eight children with obstetric brachial plexus palsy (OBPP) were included in psychometric evaluations. Internal structure consistency and test-retest reliability were measured for reliability analyses. For each item on the scale, Cronbach alpha coefficient and item-total score correlations for all subscales were calculated. The scale was administered at baseline and 1 week later by 2 different physiotherapists to evaluate test-retest reliability. Concurrent construct validity was assessed using Pearson correlations between the OBPP and the Mallet classification system. RESULTS: Eighteen (37.5%) girls and 30 (62%) boys, in total 48 children, whose mean age was 8.7 ± 2.4 (minimum-maximum = 5-14) years were included in the study; 9 (18.9%) have a history of both early microsurgery and tendon transfers and 39 (81.3%) have a history of only tendon transfer. Cronbach alpha ranged from 0.89 to 0.96, and for the whole scale, it was calculated as 0.938. DISCUSSION: Test-retest reliability was high. Moderate correlations were observed between the measures. CONCLUSION: The Turkish BPOM scale is a valid and reliable measurement for assessing function in children with OBPP in the Turkish population.

Distally based subcutaneous veins for venous insufficiency of the reverse posterior interosseous artery flap.

BACKGROUND: The reverse posterior interosseous artery flap (PIAF) provides soft, thin, and pliable tissue for upper extremity reconstruction without sacrificing any major arteries of the hand. The authors performed a new technique that included one extra distally based subcutaneous vein within the pedicle to diminish venous insufficiency and they aimed to present the results of reconstruction with this technique. PATIENTS AND METHODS: Twelve patients with a mean age of 30 years (range 5-52 years) underwent reverse PIAF surgery. The defects were located on the hand and wrist, with a mean area of 57.8 cm2 (range 20-99 cm2) . After the skin between the distal edge and the pivot point of the flap was elevated, the most reliable subcutaneous vein was chosen, chased, and included within the flap. RESULTS: The average size of the PIAF was 6 × 5 cm to 12 × 9 cm (mean area: 64.4 cm2 ) and the median follow-up time was 13 months (range 4-16 months). The mean quick Disabilities of the Arm, Shoulder and Hand (DASH) score was 21.4, indicating a low degree of disability. Of the 12 patients, ten were very satisfied and two were satisfied with the result of the reconstruction. All but one flap survived completely. One flap was nearly totally lost due to arterial insufficiency after hemodialysis. We observed no venous congestion or insufficiency in the patients. CONCLUSIONS: Subcutaneous veins may be reliable and useful for overcoming major drawbacks associated with reverse flow posterior interosseous artery flap and for diminishing flap loss due to venous insufficiency. © 2016 Wiley Periodicals, Inc. Microsurgery 36:384-390, 2016.

A Novel Operation Technique for Forearm Deformities in Patients with Brachial Plexus Birth Injury: Retrospective Analysis of 14 Patients.

Background: We aimed to evaluate the effectiveness of our novel operation technique that included radial shaft shortening plus supination producing osteotomy and transfer of the biceps brachii tendon to the brachialis tendon in patients with chronic radial head dislocation secondary to brachial plexus birth injury (BPBI). Methods: Fourteen patients with chronic radial head dislocation resulting from BPBI were included in this study, with a minimum 1-year postoperative follow-up period. All patients underwent the same surgical procedure. The range of motion of affected elbow was measured with a standard goniometer. The Mayo Elbow Performance Score (MEPS) was used to measure for evaluation of functional result of these patients. The affected elbow radiograph also obtained in the last visit for evaluation of compatibility of the radiocapitellar joint. Results: Fourteen patients (10 males and 4 females) were included in the study. The average age at the time of surgery was 7.2 (5-8) years and average follow-up was 73.2 ± 19 (36-131) months. Although the forearm active-passive pronation decreased, active-passive supination significantly improved postoperatively (p < 0.001). Ten patients had excellent MEPS results (90 and above), two patients with good results (75 and 80), one patient with fair (65) and one patient with poor result (55). Radiocapitellar reduction was achieved in 78.5% (11/14) of the patients. Conclusions: The novel surgical techniques that included radial shaft shortening plus supination producing osteotomy and transfer of the biceps brachii tendon to the brachialis tendon improved the functional outcomes of patients with chronic radial head dislocation secondary to BPBI. Level of Evidence: Level IV (Therapeutic).

ADAM19 cleaves the PTH receptor and associates with brachydactyly type E.

Brachydactyly type E (BDE), shortened metacarpals, metatarsals, cone-shaped epiphyses, and short stature commonly occurs as a sole phenotype. Parathyroid hormone-like protein (PTHrP) has been shown to be responsible in all forms to date, either directly or indirectly. We used linkage and then whole genome sequencing in a small pedigree, to elucidate BDE and identified a truncated disintegrin-and-metalloproteinase-19 (ADAM19) allele in all affected family members, but not in nonaffected persons. Since we had shown earlier that the extracellular domain of the parathyroid hormone receptor (PTHR1) is subject to an unidentified metalloproteinase cleavage, we tested the hypothesis that ADAM19 is a sheddase for PTHR1. WT ADAM19 cleaved PTHR1, while mutated ADAM-19 did not. We mapped the cleavage site that we verified with mass spectrometry between amino acids 64-65. ADAM-19 cleavage increased Gq and decreased Gs activation. Moreover, perturbed PTHR1 cleavage by ADAM19 increased ß-arrestin2 recruitment, while cAMP accumulation was not altered. We suggest that ADAM19 serves as a regulatory element for PTHR1 and could be responsible for BDE. This sheddase may affect other PTHrP or PTH-related functions.

Psychological adjustment, maternal distress, and family functioning in children with obstetrical brachial plexus palsy.

PURPOSE: To examine emotional and behavioral characteristics of children with obstetrical brachial plexus palsy (OBPP), psychological distress of their mothers and their family functioning, and compare them with healthy peers. METHODS: Participants included 42 children with OBPP (22 boys, 20 girls; age range, 4-16 y; mean, 7 y 0 mo; SD, 3 y 3 mo) and 43 healthy controls (24 boys, 19 girls; age range, 4-15 y; mean, 8 y 0 m; SD, 3 y 0 mo). Childhood Behavior Checklist, Symptom Checklist 90, and Family Assessment Device were filled in by the mothers. RESULTS: Participants with OBPP displayed higher problem scores than the comparison children in most of the domains, including internalizing and externalizing problems. Maternal distress was higher in the OBPP group, and few differences in family functioning were noted. Maternal distress and having the diagnosis of OBPP were the strongest predictors of children's total problem scores and explained 26% of the variance when the effect of age, sex, and family functioning were controlled. CONCLUSIONS: Children with OBPP and their mothers are at increased risk for a variety of psychological problems. Professionals should be aware of these children's and their caregivers' psychological adjustment and refer them for further psychological support when needed. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

An unusual cause of posterior interosseous nerve palsy and contribution of ultrasonography to electromyography in a patient with neurofibroma.

Neurofibroma, a benign peripheral nerve sheath tumor, represents a rare cause of posterior interosseous nerve syndrome. Electrodiagnostic studies may not identify the exact site of nerve compression, a possible lesion that compresses the nerve and do not provide information about the morphological changes. Ultrasound is a cost-effective, practical modality that provides the opportunity for dynamic tracking in the peripheral nerves, and it is widely considered as the initial imaging modality for peripheral nerves. Herein, we report a case of posterior interosseous nerve palsy in a 13-year-old boy with neurofibroma of posterior interosseous nerve diagnosed with ultrasound. The benefit of ultrasound in localizing and determining the etiology of the posterior interosseous nerve palsy is emphasized in this case report. A meticulous ultrasound examination is recommended in suspected peripheral nerve lesions, regardless of the results of electrophysiological and imaging modalities.

The effect of botulinum toxin application on latissimus dorsi and teres major muscles in patients with brachial plexus birth palsy: An electron microscopic and clinical study.

BACKGROUND: In brachial plexus birth palsy (BPBP), botulinum toxin may be utilized to prevent glenohumeral dysplasia and to maintain the stable growth of the glenohumeral joint. Repeated injections may cause muscular atrophy and their functional effects are uncertain. The aim of this study was to compare the microstructure and the function of the muscles that received two injections before transfer with the muscles that were not injected. METHODS: BPBP patients that were operated between January 2013 and December 2015 were included in the study. Latissimus dorsi and teres major muscles were transferred to humerus in standard fashion. Patients were divided in two groups according to bo-tulinum toxin status. Group 1 was toxin negative whereas Group 2 was toxin positive. For each patient, mean latissimus dorsi myocyte thickness (LDMT) was measured with electron microscopy and pre-operative and post-operative active shoulder abduction, flexion, external and internal rotation, and Mallet scores were evaluated with goniometry. RESULTS: Fourteen patients (seven patients per group) were evaluated. Five patients were female whereas nine were male. Mean LDMT was not affected significantly (p>0.05). The operation improved shoulder abduction, flexion, and external rotation significantly (p<0.05), independent of the toxin status. The internal rotation decreased significantly only in Group 2 (p<0.05). The Mallet score increased in both groups, but it was not significant (p>0.05), independent of the toxin status. CONCLUSION: Botulinum toxin that was applied twice prevented glenohumeral dysplasia and it did not cause permanent latissimus dorsi muscle atropy and function loss in late period. It augmented upper extremity functions by alleviating internal rotation contracture.

A cis-regulatory site downregulates PTHLH in translocation t(8;12)(q13;p11.2) and leads to Brachydactyly Type E.

Parathyroid hormone-like hormone (PTHLH) is an important chondrogenic regulator; however, the gene has not been directly linked to human disease. We studied a family with autosomal-dominant Brachydactyly Type E (BDE) and identified a t(8;12)(q13;p11.2) translocation with breakpoints (BPs) upstream of PTHLH on chromosome 12p11.2 and a disrupted KCNB2 on 8q13. We sequenced the BPs and identified a highly conserved Activator protein 1 (AP-1) motif on 12p11.2, together with a C-ets-1 motif translocated from 8q13. AP-1 and C-ets-1 bound in vitro and in vivo at the derivative chromosome 8 breakpoint [der(8) BP], but were differently enriched between the wild-type and BP allele. We differentiated fibroblasts from BDE patients into chondrogenic cells and found that PTHLH and its targets, ADAMTS-7 and ADAMTS-12 were downregulated along with impaired chondrogenic differentiation. We next used human and murine chondrocytes and observed that the AP-1 motif stimulated, whereas der(8) BP or C-ets-1 decreased, PTHLH promoter activity. These results are the first to identify a cis-directed PTHLH downregulation as primary cause of human chondrodysplasia.

Quadruple salivary duct diversion for drooling in cerebral palsy.

Drooling complicates many neurologic disorders including cerebral palsy. It is socially debilitating for the patient and very tedious for the caregiver. Surgical treatment consists mainly of ablative (excision/ligation) or physiological (diversion) methods; combined techniques have also been proposed. We have applied bilateral diversion of both submandibular and parotid ducts in 12 cerebral palsy patients (age range, 7-15 years). Preoperative drooling severity was grade 4/5 in 10 cases and grade 5/5 in 2 of the cases. All patients underwent physiotherapy for a minimum of 6 months and were consulted with a dentist, otolaryngologist, and a speech therapist before surgery. No bleeding, hematoma, or infection has been observed in any of the patients. Two patients had early postoperative tongue edema that regressed with conservative treatment. All patients except one regressed to grade 2/5 drooling by the first postoperative month. In 1 patient who had previously been classified as grade 5/5, surgery provided limited improvement with only 1 grade of step-down. Satisfactory results for the patients and their families could be achieved and sustained for a median 18 months (7-20 months) of follow-up. In conclusion, the quadruple duct diversion method is an effective physiological surgical method in the control of drooling in cerebral palsy.

Quality of upper extremity skills and disability inventory via manual ability classification in children with neonatal brachial plexus palsy.

PURPOSE: The aim of study was to investigate the relationship between upper extremity skill quality and disability inventory according to manual ability classification system in children with neonatal brachial plexus palsy (NBPP). MATERIALS AND METHODS: Children with NBPP were included between the ages of 4-7.5 years. Children were classified in Manual Ability Classification System (MACS). Upper extremity skill quality was evaluated with Quality of Upper Extremity Skills Test (QUEST), disability status was assessed with Pediatric Evaluation of Disability Inventory (PEDI). RESULTS: Total of 63 children (girls:31/boys:32), and mean age was 6.32 ± 1.73 years. 37 (58.73%) of children were at MACS Level-2. According to MACS classification, significant differences were noted in PEDI scores (p = 0.001), dissociated movements (p = 0.016) and grasp (p = 0.002) domains of QUEST. However, no significant differences between QUEST total scores (p = 0.079). PEDI (ROC; AuC = 0.762) and QUEST total score (ROC; AuC = 0.714) were sensitive to difference between groups across MACS in children with NBPP. CONCLUSION: The PEDI and QUEST are sensitive in distinguishing the disability of children with NBPP at different MACS levels. Assessment of children with NBPP is not limited to functionality, disability, and quality of movement, it is multidimensional. Outcomes measures studies of movement's quality in children with NBPP are needed.

Functionality evaluation in children with neonatal brachial plexus palsy is multidimensional.Appropriate assessment of functionality in children with neonatal brachial plexus palsy provides accurate information about daily living activities and disability levels.We propose using Quality of Upper Extremity Skills Test (QUEST) and Pediatric Evaluation of Disability Inventory (PEDI) to evaluate the relationship between the quality of upper extremity movements and disability in school-aged children with neonatal brachial plexus palsy at different Manual Ability Classification System (MACS) levels.

Beta-2 adrenoreceptor gene polymorphisms and sympathetic outflow in humans.

OBJECTIVES: Previous association studies suggested that common polymorphisms of the beta-2 adrenoreceptor gene leading to glycine for arginine substitution at position 16 or glutamic acid for glutamine substitution at position 27 affect blood pressure. We reasoned that measurements of resting sympathetic nerve traffic could increase the sensitivity of defining a gene phenotype relationship. METHODS: We studied 111 Caucasian subjects (70 men, 41 women) with blood pressure<140/90 mmHg. We measured electrocardiogram, beat-by-beat finger blood pressure, brachial blood pressure, and muscle sympathetic nerve activity (MSNA) using microneurography. We genotyped the functionally relevant polymorphisms of the beta-2 adrenoreceptor gene by means of allele-specific polymerase chain reaction. RESULTS: Sympathetic nerve traffic was similar regardless of genotypes. We obtained similar results when we quantified sympathetic nerve traffic as bursts/100 heart beats or as normalized burst area or when we adjusted resting sympathetic nerve traffic for gender, age, and blood pressure. The polymorphism at position 27 affects sympathetic regulation in men. Men with a Glu/Glu genotype had a significant positive correlation between blood pressure and MSNA. INTERPRETATIONS: While our study was not sufficiently powered to detect subtle influences of genetic variability in the beta-2 adrenoreceptor gene on resting sympathetic nerve traffic, a large effect is unlikely. However the observation that beta-2 adrenoreceptor genotype may affect coupling between resting sympathetic nerve traffic and systolic blood pressure deserves to be tested in larger populations.

Does primary brachial plexus surgery alter palliative tendon transfer surgery outcomes in children with obstetric paralysis?

BACKGROUND: The surgical management of obstetrical brachial plexus palsy can generally be divided into two groups; early reconstructions in which the plexus or affected nerves are addressed and late or palliative reconstructions in which the residual deformities are addressed. Tendon transfers are the mainstay of palliative surgery. Occasionally, surgeons are required to utilise already denervated and subsequently reinnervated muscles as motors. This study aimed to compare the outcomes of tendon transfers for residual shoulder dysfunction in patients who had undergone early nerve surgery to the outcomes in patients who had not. METHODS: A total of 91 patients with obstetric paralysis-related shoulder abduction and external rotation deficits who underwent a modified Hoffer transfer of the latissimus dorsi/teres major to the greater tubercle of the humerus tendon between 2002 and 2009 were retrospectively analysed. The patients who had undergone neural surgery during infancy were compared to those who had not in terms of their preoperative and postoperative shoulder abduction and external rotation active ranges of motion. RESULTS: In the early surgery groups, only the postoperative external rotation angles showed statistically significant differences (25 degrees and 75 degrees for total and upper type palsies, respectively). Within the palliative surgery-only groups, there were no significant differences between the preoperative and postoperative abduction and external rotation angles. The significant differences between the early surgery groups and the palliative surgery groups with total palsy during the preoperative period diminished postoperatively (p < 0.05 and p > 0.05, respectively) for abduction but not for external rotation. Within the upper type palsy groups, there were no significant differences between the preoperative and postoperative abduction and external rotation angles. CONCLUSIONS: In this study, it was found that in patients with total paralysis, satisfactory shoulder abduction values can be achieved with tendon transfers regardless of a previous history of neural surgery even if the preoperative values differ.

Microwave assisted synthesis, experimental and theoretical characterization and antibacterial activity screening of novel azomethine compounds containing thiophene and aminophenol functionality.

Eight new azomethine compounds (3a-3h) containing thiophene and aminophenol functionality were synthesized in excellent yields by using conventional heating and microwave assisted synthesis methods. The structures of newly synthesized compounds were characterized by spectroscopic techniques such as UV-Vis, FTIR, 1H and 13C NMR and elemental analysis. UV-Vis and 1H NMR results show that all compounds prefer the phenol-imine tautomer form in solvent media. The chemical structure of 3a, 3b and 3g was also confirmed by single crystal X-ray diffraction method. The molecular conformations of 3a, 3b and 3g are stabilized by an N+-H⋯O- type intramolecular hydrogen bond in zwitterionic form in the crystalline solid state. The optimized molecular structures, 1H and 13C NMR chemical shift values, UV-Vis spectroscopic parameters, HOMO-LUMO energies, Mulliken (MPA) and natural (NBO) atomic charges, Natural bond orbitals (NBO), molecular electrostatic potential (MEP) maps and solvent accessible surfaces (SASs) for 3a-3h were calculated by using DFT/B3LYP/6-311G(2d,p) approach. The theoretical spectroscopic features obtained by DFT calculations show a very good agreement with the experimental data. In addition, the synthesized compounds (3a-3h) were screened for their antibacterial activities against Bacillus cereus (NRRL-B3711), Bacillus subtilis (NRRL-B4378), Escherichia coli (NRRL B-3008), Staphylococcus aureus (ATCC-6538) and Salmonella typhimurium (ATCC-13311). The results show that investigated compounds have either moderately active, slightly active or inactive among the tested microorganisms. 3a exhibited the stronger antibacterial activity against all test bacteria than other compounds. It also has been observed that compounds with relatively low HOMO-LUMO energy gaps exhibit better antibacterial effects.

[Donor site sequela of class III B vascular anomaly following reconstruction of the mandible with free osteoseptocutaneous fibula flap: a case report]. / Serbest fibula osteoseptokutan flep ile mandibula rekonstrüksiyonundan sonra verici sahada sinif III B vasküler anomaliye bagli sekel: Olgu sunumu.

Free transfer of the fibula for mandibular reconstruction provides desirable functional and aesthetic results. However, unexpected donor- and recipient-site complications may be encountered with most free flap transfer procedures. A 62-year-old woman underwent wide resection and segmental mandibulectomy for low-grade squamous cell carcinoma of intraoral location. Reconstruction of the defect was performed at the same session with an osteoseptocutaneous free flap from the right fibula. A class III B vascular malformation was detected intraoperatively at the donor site, which resulted in restriction of foot inversion and abduction, and of toe extension during the follow-up.

[Reconstruction of the head and neck with free osteoseptocutaneous flap in elderly heavy smokers]. / Agir sigara içici yasli hastalarin bas-boyun rekonstrüksiyonunda serbest osteoseptokutan flep uygulamalari.

OBJECTIVES: We evaluated complications of free flap reconstruction following oncological head and neck surgery in elderly patients who smoked heavily. PATIENTS AND METHODS: The study included eight patients (2 females, 6 males; mean age 68.5 years; range 65 to 74 years) over 65 years of age, who smoked heavily (at least 1 pack/day). All cases but one with mandibular ameloblastoma had intraoral squamous cell carcinoma. Two patients underwent reconstruction with free radial forearm osteoseptocutaneous flap following bilateral maxillary resection, and six patients with free fibular osteoseptocutaneous flap following mandibular resection. Postoperative complications, in particular those associated with the donor and recipient sites were evaluated. RESULTS: No partial or total flap loss was observed. Wound healing problems were seen in three patients (37%), which were at the donor site in two patients, and at the recipient site in one patient. Psychogenic disorders were observed in two patients (25%). No other complications were encountered. CONCLUSION: Aside from some recipient- and donor-site-related healing problems, heavy smoking and advanced age cannot be regarded as contraindications for free flap reconstruction.

[Nonvascular phalangeal transfer from toes to hand in congenital aphalangia]. / Dogustan afalangiali olgularda ayaktan ele nonvasküler falanks transferi.

OBJECTIVES: Free transfer of the toe phalanges to the hand without vascular anastomosis is a proposed option for reconstruction of congenital aphalangia. We evaluated the growth behavior of the phalanges in patients after transfer. METHODS: Six patients with congenital aphalangia underwent 18 nonvascular phalangeal transfers from toes to the hand. The anomaly was bilateral in one patient. Except for one patient who was 11.5 years old, the mean age at the time of surgery was 27 months (range 14 to 48 months). The patients were followed-up for a mean of 2.5 years (range 2 to 4 years) with respect to functional results, yearly longitudinal growth, epiphysial closure, bone resorption or necrosis, digital tip necrosis, fracture, angulation, subluxation, infections, and donor site morbidity. RESULTS: The mean yearly longitudinal growth rate of transferred phalanges was 2.4 mm. On final radiographic examinations, epiphysial closure was not completed in 14 phalanges (78%). Functional improvements included stabilization using the affected digit in three patients, and performing further movements in three patients. One patient underwent reoperation for postoperative subluxation. No fractures or angulation above 15 degrees were seen. Bone resorptions were partial in three patients (16%), and total in one patient (5%). Concerning soft tissue complications, digital tip necrosis developed in one patient (5%). No infections were encountered during the follow-up. All the patients exhibited minimal donor digit shortening. CONCLUSION: Nonvascular phalangeal transfer is an alternative rehabilitation method by which use of prosthetics may be facilitated and functional capacity may be increased in congenital hand anomalies such as congenital aphalangia, in which vascular phalanx transfer is not suitable.