A Retrospective Analysis of Patients Presenting with Head and Neck Paragangliomas at Two Tertiary Referral Centres in Jamaica / Análisis retrospectivo de pacientes que presentan paragangliomas de cabeza y cuello en dos centros de remisión terciarios en Jamaica

ABSTRACT Objective: Paragangliomas are slow-growing tumours that present with varied clinical spectra. Early recognition is paramount in achieving reduced morbidity and mortality. There is a paucity of data regarding head and neck paragangliomas (HNPGs) in the Caribbean literature. This study aimed to reflect the clinical experience in the management of HNPGs at two Jamaican tertiary referral centres: the Kingston Public Hospital (KPH) and the University Hospital of the West Indies (UHWI). Methods: A retrospective analysis was conducted on all patients presenting to the Ear, Nose and Throat (ENT) departments of the UHWI in 2004-14 and of the KPH in 2012-14 with the diagnosis of a HNPG. Results: There were 15 patients, 1 male and 14 females. The average age at presentation was 47.1 years. The HNPGs in this series included eight patients with glomus tympanicum (GT, 53%), four with glomus jugulare (GJ, 27%), two with carotid body tumours (CBTs, 13%) and one with glomus vagale (GV, 7%). Eight patients underwent surgical resection (two CBTs, four GT and two GJ). Treatment outcomes achieved included: complete resection (four patients), stable with residual disease (two patients), and recurrence (two patients). Seven patients were awaiting definitive treatment, one patient with GJ was referred overseas, and one patient with GV defaulted. Conclusion: Glomus tympanicum is the most common HNPG in this series which contrasts with that of most international series. Despite the limitations within this region, such as limited access to angio-embolization and stereotactic modalities, the management outcomes are similar in some respects to the reported international literature.

RESUMEN Objetivo: Los paragangliomas son tumores de crecimiento lento que se presentan con variados espectros clínicos. Su detección precoz es fundamental para lograr una reducción de la morbilidad y la mortalidad. Hay escasez de datos con respecto a los paragangliomas de cabeza y cuello (PgCC) en la literatura del Caribe. Este estudio tuvo como objetivo reflejar la experiencia clínica en el tratamiento de PgCC en dos centros de remisión terciarios de Jamaica: jamaiquinos: el Hospital Público de Kingston (KPH) y el Hospital Universitario de UWI (HUWI). Métodos: Se llevó a cabo un análisis retrospectivo de todos los pacientes diagnosticados con PgCC que acudieron a los Departamentos de Otorrinolaringología de HUWI en 2004-14 y de KPH en 2012-14. Resultados: Hubo 15 pacientes - 1 varón y 14 hembras. La edad promedio al momento de presentarse fue 47.1 años. El PgCC en esta serie incluyó a ocho pacientes con glomus timpánico (GT, 53%), cuatro con glomus yugular (GY, 27%), dos con tumores del cuerpo carotídeo (TCC, 13%), y uno con glomus vagal (GV, 7%). Ocho pacientes fueron sometidos a resección quirúrgica (dos TCC, cuatro GT, y dos GY). Los resultados logrados con el tratamiento incluyeron: resección total (cuatro pacientes), estables con enfermedad residual (dos pacientes), y recurrencia (dos pacientes). Siete pacientes esperaban un tratamiento definitivo, un paciente con GY fue remitido al extranjero, y un paciente con GV no se presentó. Conclusión: El glomus timpánico es el PgCC más común en esta serie que contrasta con el de la mayoría de las series internacionales. A pesar de las limitaciones dentro de esta región, tales como el acceso limitado a la angioembolización y las modalidades estereotácticas, los resultados del manejo de la enfermedad son similares en algunos aspectos a la literatura internacional reportada.

Long term study into surgical re-exploration of the 'free flap in difficulty'.

BACKGROUND: Free tissue transfers must survive in order to achieve their surgical goals. There is little consensus about managing the 'failing' free flap, and practice is often guided by anecdote. MATERIAL AND METHODS: We have prospectively collected data about all free flaps performed within our department between 1985 and 2008 (2569 flaps). We identified 327 flaps which were re-explored a total of 369 times. We analysed these flaps with regard to indication for re-exploration, operative findings and outcome. RESULTS: Thirteen percent (327) of free flaps were re-explored. Of these, 291 (83%) had a successful outcome. Successful re-explorations took place at a mean 19h post-op and unsuccessful re-explorations at a mean 56h post-op. Clinical diagnosis prior to re-exploration was confirmed operatively in 91% of cases. CONCLUSION: We have considered the factors that allowed us to achieve the salvage rates described over a prolonged period, and identified two key areas. Firstly, we favour a model for free flap monitoring with clinical judgement at its core. Secondly, we feel the facility to recover patients post-operatively in a specialised, warmed environment, and return them to theatre quickly should the need arise, is essential. These two simple, yet institutionally determined factors are vital for maintaining excellent success rates.

The variation in breast density and its relationship to delayed wound healing: a prospective study of 40 reduction mammoplasties.

The proportions of glandular and adipose tissue within the breast vary. This study records the variation in density of breast tissue excised at 40 consecutive bilateral breast reductions. Age, body mass index (BMI), breast size and wound healing problems were related to breast density. The removed breast tissue was weighed and volume determined by water displacement. Delayed wound healing was defined as any breast unhealed after 2 weeks. The density of excised tissue varied between 0.8 and 1.2g/cm(3). There was no correlation between age or BMI and breast density. Delayed wound healing occurred in 32% of patients. There was no correlation between delayed wound healing and breast density. However, there was a direct relationship between increasing BMI and delayed wound healing. In this study, breast density varied by up to 50%. The density of breast tissue cannot be predicted by age, BMI or breast size. There is no relationship between delayed wound healing and breast density.

Phaeochromocytomas presenting as acute crises after beta blockade therapy.

OBJECTIVE: Phaeochromocytoma crisis is a life-threatening emergency that may be undiagnosed because of its numerous, nonspecific manifestations. We analysed, retrospectively, the presentation, management and outcome of patients who were admitted to our institution with phaeochromocytoma crises over a 5-year period. RESULTS: Five patients (two males, three females; mean age 34.6 years, range 19-51 years) who presented as emergencies requiring intensive care, with multiple non-specific manifestations and previously undiagnosed pheochromocytoma, were identified. The initial presentation included features of cardiomyopathy (n = 3), atypical pneumonia with myocarditis (n = 1) and acute abdomen (n = 1). Only one of the five cases had a raised blood pressure at the time of the acute presentation. Initiation of beta blockers in four patients was associated with further deterioration in haemodynamic status, labile blood pressure and cardiac arrhythmias, which led to the diagnosis of the underlying phaeochromocytoma. Following intensive supportive therapy and alpha blockade, all five patients recovered and underwent elective surgical removal of phaeochromocytoma, uneventfully. CONCLUSION: Unexplained cardiopulmonary dysfunction, particularly after the institution of beta blockers, should alert clinicians to the possibility of phaeochromocytoma. A high index of suspicion is essential to reduce morbidity and mortality in these patients through early diagnosis and aggressive management.

The most polymorphic residue on Plasmodium falciparum apical membrane antigen 1 determines binding of an invasion-inhibitory antibody.

Apical membrane antigen 1 (AMA1) is currently one of the leading malarial vaccine candidates. Anti-AMA1 antibodies can inhibit the invasion of erythrocytes by Plasmodium merozoites and prevent the multiplication of blood-stage parasites. Here we describe an anti-AMA1 monoclonal antibody (MAb 1F9) that inhibits the invasion of Plasmodium falciparum parasites in vitro. We show that both reactivity of MAb 1F9 with AMA1 and MAb 1F9-mediated invasion inhibition were strain specific. Site-directed mutagenesis of a fragment of AMA1 displayed on M13 bacteriophage identified a single polymorphic residue in domain I of AMA1 that is critical for MAb 1F9 binding. The identities of all other polymorphic residues investigated in this domain had little effect on the binding of the antibody. Examination of the P. falciparum AMA1 crystal structure localized this residue to a surface-exposed alpha-helix at the apex of the polypeptide. This description of a polymorphic inhibitory epitope on AMA1 adds supporting evidence to the hypothesis that immune pressure is responsible for the polymorphisms seen in this molecule.

The treatment of chronic osteomyelitis: a 10 year audit.

Despite modern surgical techniques and advanced antimicrobial therapy, osteomyelitis remains a difficult and challenging problem. A 10 year audit study from 1990 to 2000 was carried out to assess the outcome of treatment of chronic osteomyelitis. A total of 41 patients with chronic osteomyelitis (26 male, 15 female with an age range of 10-76 years, mean 45.3 years) underwent extirpation and reconstruction with muscle interposition. The duration of osteomyelitis ranged from 1 to 69 years (mean 16.6 years) and many patients had undergone multiple attempted procedures prior to definitive treatment. Thirty-seven patients underwent free microvascular muscle transfer and four patients underwent local transposition muscle flaps. Two of the 41 patients developed recurrent sepsis at 12 months (4.4% recurrence rate). These were treated successfully with elevation of the flap and curettage of the remaining infection and debris and re-insetting of the flap. Only one patient in the series required a below knee amputation and this was as a result of persistent intractable bone pain rather than recurrence of the osteomyelitis.

Pathological implications of iNOS expression in central white matter: an ex vivo study of optic nerves from rats with experimental allergic encephalomyelitis.

Excessive nitric oxide (NO) production from the inducible isoform of nitric oxide synthase (iNOS) has been invoked as a causative factor in many neurodegenerative disorders, including multiple sclerosis. This hypothesis has been supported by in vitro studies showing that glial iNOS expression results in toxic NO concentrations (near 1 microm). To investigate the relevance of such findings, experiments were carried out ex vivo on optic nerves from rats with exacerbated experimental allergic encephalomyelitis, a model of multiple sclerosis. The nerves displayed characteristic immunopathology and expression of iNOS in macrophages and/or microglia and there was overt axonal damage in localized regions of the optic chiasm. The resulting NO levels in the optic nerve were sufficient to cause activation of guanylyl cyclase-coupled NO receptors, resulting in marked cGMP accumulation in axons throughout the nerve. Nevertheless, calibration of cGMP levels against those evoked by exogenous NO indicated that the nerves were not compromised metabolically and that their ambient NO concentration was only approximately 1 nm. Consistent with this observation, electrophysiological tests indicated that there was no ongoing malfunctioning of the type that can be elicited by high exogenous NO concentrations. It is concluded that, with iNOS expressed in physiological locations and levels, the tissue levels of NO remain at concentrations far lower than those shown to have toxic effects, despite continuous NO synthesis. The fact that NO can rise to much higher levels in dispersed cultures in vitro may be attributable to a deficiency in NO inactivation in such preparations.

Drainage in breast reduction surgery: a prospective randomised intra-patient trail.

One hundred and fifty bilateral breast reductions were prospectively randomised intra-operatively to receive a unilateral wound drain. Seven patients required post-operative evacuation of haematoma, three on the drained and four on the undrained sides. There was no statistical difference in haematoma formation between drained and undrained sides (p = 1), or the incidence of wound healing or other complications. We believe that routine wound drainage in breast reduction surgery is an unnecessary intervention.

Management of iatrogenic lower limb ischaemia in children.

An acutely ischaemic lower limb following femoral artery cannulation in children is a problem infrequently encountered by plastic surgeons in the UK. When such a case presented to us, we performed a search of published literature to guide us to the optimum treatment. This included methods for extraperitoneal exposure of the common iliac artery and vein. We describe the surgical technique that we used to salvage an acutely ischaemic lower limb following femoral puncture and a review of the literature.

Pharmacological salvage of a combined distal bypass and free flap with catheter-directed thrombolysis.

With recent improvements in microvascular techniques, the use of combined distal bypass and free-flap transfer has been advocated for salvaging the critically ischaemic limb in extreme conditions. Distal bypass, however, carries an inherent risk of graft failure due to thrombosis, and this may threaten the viability of the free flap and, indeed, the lower limb. We present the case of a 66-year-old man with acute-on-chronic ischaemia of his left leg and rectus abdominis free flap. Despite a prolonged ischaemic time of 72 h, both were successfully salvaged using catheter-directed recombinant tissue plasminogen activator. This is previously unreported in the literature.

Nitric oxide toxicity in CNS white matter: an in vitro study using rat optic nerve.

Excessive nitric oxide formation may contribute to the pathology occurring in diseases affecting central white matter, such as multiple sclerosis. The rat isolated optic nerve preparation was used to investigate the potential toxicity of the molecule towards such tissue. The nerves were exposed to a range of concentrations of different classes of nitric oxide donor for up to 23 h, with or without a subsequent period of recovery, and the damage assessed by quantitative histological methods. Degeneration of axons and macroglia occurred in a time- and concentration-dependent manner, the order of susceptibility being: axons>oligodendrocytes>astrocytes. Use of NONOate donors differing in half-life indicated that nitric oxide delivered in an enduring manner at relatively low concentration was more toxic than the same amount supplied rapidly at high concentration. The mechanism by which nitric oxide affects axons was studied using a donor [3-(n-propylamino)propylamine/NO adduct, PAPA/NO] with an intermediate half-life that produced selective axonopathy after a 2-h exposure (plus 2 h recovery). Axon damage was abolished if, during the exposure, Na(+) or Ca(2+) was removed from the bathing medium or the sodium channel inhibitors tetrodotoxin or BW619C89 (sipatrigine) were added. In electrophysiological experiments, the donor elicited a biphasic depolarisation. The second, larger component (occurring after 7-10 min) was associated with a block of nerve conduction and could be inhibited by tetrodotoxin. Coincident with the secondary depolarisation was a reduction in ATP levels by about 50%, an effect that was also inhibited by tetrodotoxin. It is concluded that nitric oxide, in submicromolar concentrations, can kill axons and macroglia in white matter. The findings lend support to the hypothesis that nitric oxide may be of importance to white matter pathologies, particularly those in which inducible nitric oxide synthase is expressed. The axonopathy, at least when elicited over relatively short time intervals, is likely to be caused by metabolic inhibition. As in anoxia and anoxia/aglycaemia, nitric oxide-induced destruction of axons is likely to be caused by the Ca(2+) overload that follows a reduction in ATP levels in the face of continued influx of Na(+) through voltage-dependent channels.

Pectoralis major "trapdoor" flap for silicone breast implant medial knuckle deformities.

Loss of breast parenchyma through surgery and physiologic involution can lead to problems of subglandular silicone breast implant palpability and even contour irregularities. This can give rise to patient concern and detracts from the aesthetics of the breast augmentation, particularly when it occurs medially. We present a simple solution to this problem on the medial side of the breast in the form of a small segmental medially based pectoralis major "trapdoor" flap that augments the implant soft-tissue cover intracapsularly, at the site where it is deficient. The technique, which has been used with success in five patients over 3 years, is described.

Peri-operative risk factors for acute lung injury after elective oesophagectomy.

Acute lung injury after oesophagectomy is well recognized but the risk factors associated with its development are poorly defined. We analysed retrospectively the effect of a number of pre-, peri- and post-operative risk factors on the development of lung injury in 168 patients after elective oesophagectomy performed at a single centre. The acute respiratory distress syndrome (ARDS) developed in 14.5% of patients and acute lung injury in 23.8%. Mortality in patients developing ARDS was 50% compared with 3.5% in the remainder. Features associated with the development of ARDS included a low pre-operative body mass index, a history of cigarette smoking, the experience of the surgeon, the duration of both the operation and of one-lung ventilation, and the occurrence of a post-operative anastomotic leak. Peri-operative cardiorespiratory instability (measured by peri-operative hypoxaemia, hypotension, fluid and blood requirements and the need for inotropic support) was also associated with ARDS. Acute lung injury after elective oesophagectomy is associated with intraoperative cardiorespiratory instability.

Successful free flap transfer and salvage in sickle cell trait.

The presence of sickle cell haemoglobin is generally regarded as a contraindication to free tissue transfer. We present the case of a 42-year-old male with sickle cell trait who had free transfer of a latissimus dorsi flap to cover a gunshot wound to his thigh. His initial haemoglobin S was 36%. Early flap failure from venous thrombosis was successfully salvaged by re-anastomosis to alternative vessels.

Fix and flap: the radical orthopaedic and plastic treatment of severe open fractures of the tibia.

We performed a retrospective review of the case notes of 84 consecutive patients who had suffered a severe (Gustilo IIIb or IIIc) open fracture of the tibia after blunt trauma between 1990 and 1998. All had been treated by a radical protocol which included early soft-tissue cover with a muscle flap by a combined orthopaedic and plastic surgery service. Our ideal management is a radical debridement of the wound outside the zone of injury, skeletal stabilisation and early soft-tissue cover with a vascularised muscle flap. All patients were followed clinically and radiologically to union or for one year. After exclusion of four patients (one unrelated death and three patients lost to follow-up), we reviewed 80 patients with 84 fractures. There were 67 men and 13 women with a mean age of 37 years (3 to 89). Five injuries were grade IIIc and 79 grade IIIb; 12 were site 41, 43 were site 42 and 29 were site 43. Debridement and stabilisation of the fracture were invariably performed immediately. In 33 cases the soft-tissue reconstruction was also completed in a single stage, while in a further 30 it was achieved within 72 hours. In the remaining 21 there was a delay beyond 72 hours, often for critical reasons unrelated to the limb injury. All grade-IIIc injuries underwent immediate vascular reconstruction, with an immediate cover by a flap in two. All were salvaged. There were four amputations, one early, one mid-term and two late, giving a final rate of limb salvage of 95%. Overall, nine pedicled and 75 free muscle flaps were used; the rate of flap failure was 3.5%. Stabilisation of the fracture was achieved with 19 external and 65 internal fixation devices (nails or plates). Three patients had significant segmental defects and required bone-transport procedures to achieve bony union. Of the rest, 51 fractures (66%) progressed to primary bony union while 26 (34%) required a bone-stimulating procedure to achieve this outcome. Overall, there was a rate of superficial infection of the skin graft of 6%, of deep infection at the site of the fracture of 9.5%, and of serious pin-track infection of 37% in the external fixator group. At final review all patients were walking freely on united fractures with no evidence of infection. The treatment of these very severe injuries by an aggressive combined orthopaedic and plastic surgical approach provides good results; immediate internal fixation and healthy soft-tissue cover with a muscle flap is safe. Indeed, delay in cover (>72 hours) was associated with most of the problems. External fixation was associated with practical difficulties for the plastic surgeons, a number of chronic pin-track infections and our only cases of malunion. We prefer to use internal fixation. We recommend primary referral to a specialist centre whenever possible. If local factors prevent this we suggest that after discussion with the relevant centre, initial debridement and bridging external fixation, followed by transfer, is the safest procedure.

Targeted disruption of an erythrocyte binding antigen in Plasmodium falciparum is associated with a switch toward a sialic acid-independent pathway of invasion.

Erythrocyte invasion by Plasmodium requires molecules present both on the merozoite surface and within the specialized organelles of the apical complex. The Plasmodium erythrocyte binding protein family includes the Plasmodium falciparum sialic acid-binding protein, EBA-175 (erythrocyte binding antigen-175), which binds sialic acid present on glycophorin A of human erythrocytes. We address the role of the conserved 3'-cysteine rich region, the transmembrane, and cytoplasmic domains through targeted gene disruption. Truncation of EBA-175 had no measurable effect on either the level of EBA-175 protein expression or its subcellular localization. Similarly, there appears to be no impairment in the ability of soluble EBA-175 to be released into the culture supernatant after schizont rupture. Additionally, the 3'-cys rich region, transmembrane, and cytoplasmic domains of EBA-175 are apparently non-essential for merozoite invasion. In contrast, erythrocyte invasion via the EBA-175/glycophorin A route appears to have been disrupted to such a degree that the mutant lines have undergone a stable switch in invasion phenotype. As such, EBA-175 appears to have been functionally inactivated within the truncation mutants. The sialic acid-independent invasion pathway within the mutant parasites accounts for approximately 85% of invasion into normal erythrocytes. These data demonstrate the ability of P. falciparum to utilize alternate pathways for invasion of red blood cells, a property that most likely provides a substantial survival advantage in terms of overcoming host receptor heterogeneity and/or immune pressure.

Novel action of BAPTA series chelators on intrinsic K+ currents in rat hippocampal neurones.

1. Whole-cell recordings were made from rat CA1 neurones in brain slices. When electrodes contained diazo-2 (2 mM) or dibromo BAPTA (1 mM) a large steady-state outward current (hundreds of picoamps) developed within 5 min of breakthrough at a VH of -60 mV. BAPTA itself (1 mM) caused qualitatively similar but smaller effects. 2. The outward current was accompanied by increased conductance with a null potential close to the calculated K+ equilibrium potential (EK) of -110 mV. Development of outward current occurred concurrently with progressive loss of slow AHP tail current (IsAHP) evoked by brief depolarizations. The peak latency of IsAHP increased during the onset of chelator action. 3. The persistent outward current was reversibly inhibited by noradrenaline (10 microM) or isoprenaline (2-5 microM), and completely prevented by 8-bromoadenosine 3',5' cyclic monophosphate (8-Br cAMP; 100 microM) or QX-314 (10 mM) in recording electrodes. After development of outward current, diazo-2 photolysis caused inward current and decreased conductance. Both flash- and noradrenergic-sensitive responses were inwardly rectifying outward currents with null potentials close to EK. 4. The outward current induced by dibromo BAPTA was not blocked by internal EGTA (10 mM). However, experiments incorporating Ca2+ influx or Ca2+ loading of the buffer indicate that Ca2+ facilitated the outward current. 5. The outward currents induced by dibromo BAPTA or diazo-2 were not associated with significant changes in resting [Ca2+]i. Regions of the cell contributing to the outward current were deduced from measurements of fura-2 diffusion. These were compared with regions of [Ca2+]i elevation during IsAHP. 6. These results are consistent with the hypothesis that the BAPTA series Ca2+ buffers can activate those Ca2+-activated K+ channels that underlie the slow AHP, without the predicted elevation of bulk [Ca2+]i. Therefore these results cannot be interpreted solely in terms of Ca2+ concentration changes, although the observations illustrate a novel, investigative role for these compounds in the study of Ca2+-dependent processes.

Developing clinical learning sites for undergraduate nursing students.

As health care continues to evolve and take on new shapes, perioperative procedures more often are occurring in nonhospital settings and with fewer opportunities for nursing intervention. Believing that nursing education must prepare nurses at the undergraduate level to provide quality and meaningful perioperative care, nursing specialists and educators at Emory University, Atlanta, developed two new clinical learning sites that allow undergraduate nursing students to learn from preceptors in advanced perioperative roles. These learning sites encourage students to develop and use critical thinking skills that are imperative to perioperative care.

Feminizing genitoplasty for congenital adrenal hyperplasia: what happens at puberty?

PURPOSE: We document the postpubertal outcome of feminizing genitoplasty. MATERIALS AND METHODS: A total of 14 girls, mean age 13.1 years, with congenital adrenal hyperplasia were assessed under anesthesia by a pediatric urologist, plastic/reconstructive surgeon and gynecologist. Of these patients 13 had previously undergone feminizing genitoplasty in early childhood at 4 different specialist centers in the United Kingdom. RESULTS: The outcome of clitoral surgery was unsatisfactory (clitoral atrophy or prominent glans) in 6 girls, including 3 whose genitoplasty had been performed by 3 different specialist pediatric urologists. Additional vaginal surgery was necessary for normal comfortable intercourse in 13 patients. Fibrosis and scarring were most evident in those who had undergone aggressive attempts at vaginal reconstruction in infancy. CONCLUSIONS: These disappointing results, even in the hands of specialists, highlight the importance of late followup and challenge the prevailing assumption that total correction can be achieved with a single stage operation in infancy. Although simple exteriorization of a low vagina can reasonably be combined with cosmetic correction of virilized external genitalia in infancy, we now believe that in some cases it may be best to defer definitive reconstruction of the intermediate or high vagina until after puberty. The psychological issues surrounding sexuality in these patients are inadequately researched and poorly understood.