Digital papillary adenocarcinoma: An important differential diagnosis for digital soft tissue masses.

Digital papillary adenocarcinoma (DPAC) is a rare, aggressive cancer with significant metastatic potential which arises from digital sweat glands. We present a case of a DPAC managed with surgical excision and reconstruction with a reversed homodigital island flap. Level of evidence: V.

Free fibula flap to achieve bone union after congenital pseudoarthrosis of the forearm in neurofibromatosis: Technical report based on 3 cases, and literature review.

Congenital pseudarthrosis of the forearm bones (CPFBs) is rare, with only 106 reported cases, and is frequently associated with neurofibromatosis (NF). Approximately 5% of patients with NF develop pseudarthrosis, and 50% of patients with pseudarthrosis have NF. Achieving bone union is difficult in congenital pseudarthrosis. Many methods have been attempted, including casting, internal fixation with or without grafting, and electrical stimulation, but failure is frequent. Free vascularized fibular flaps (FVFs) have been used to bridge long bone defects since 1975 and in tibial pseudarthrosis since 1979. In CPFB, FVF is more successful than other methods in achieving union and is the current treatment of choice. Here, we presented three cases of forearm pseudarthrosis treated with FVF, reviewed the literature on CPFB, and discussed some technical aspects of FVF treatment. Three cases of congenital pseudoarthrosis were treated with free fibula flaps, diagnosed at ages of 7 years (ulna), 15 months (radius), and 9 years (radius and ulna). Two flaps were stabilized with intramedullary wires and latterly, one with compression plates. One persistent nonunion received revision nonvascularized bone grafting and plating. All patients achieved union by 11 months after index surgery. Reconstruction with vascularized fibula is the treatment of choice because it offers the highest published union rates and good functional results. Complete resection of the affected bone and stable fixation, latterly with compression plates are critical to success. Surgery is technically demanding, and complications are common. Secondary surgery may be required, but outcomes are favorable. LEVEL OF EVIDENCE: IV.

Scintigraphy can be used to compare delivery of sore throat formulations.

AIMS: Sore throat (pharyngitis) is commonly treated with over-the-counter lozenges, tablets, sprays and gargles. While the efficacy of the active ingredients has been examined, less is known about the comparative efficacy of the different delivery formats. METHODS: A pilot study was initially performed, followed by an open-label, four-way crossover study in healthy volunteers to quantitatively assess the delivery efficacy of a lozenge, tablet, spray and gargle, using technetium-99m and scintigraphy as a marker of deposition and clearance of the active ingredients. RESULTS: Initial deposition in the mouth and throat combined was significantly greater for the solid dose forms (lozenge and tablet) than for the spray or gargle. Rates of clearance were initially similar for the tablet and lozenge with low levels of radioactivity present at up to 2 h. At 10 and 20 min, significantly more of the dose remained for the lozenge than for the tablet. The mouth appeared to act as a reservoir for continued clearance to the throat. DISCUSSION AND CONCLUSION: Scintigraphy is an effective means of quantifying the delivery efficiency, and hence availability, of sore throat medications. The results presented here suggest that both lozenges and tablets offer considerable advantages over sprays or gargles, both in terms of proportion of the dose delivered to the mouth and throat, combined, and clearance from these regions. These delivery formats provide fast, effective and prolonged delivery of active ingredients, highlighting their potential benefits for sore throat medication.

Paediatric toe-to-hand transfer: an assessment of outcomes from a single unit.

UNLABELLED: Toe-to-hand transfer is an acceptable treatment option for children born with absent digits. Toe transfer can provide functionally useful digits and may enhance patient wellbeing. A total of 19 children had 31 free second-toe-to-hand microsurgical transfers between 1998 and 2012. The mean age of these children at the time of the first operation was 45 months. All transferred toes survived. The donor site was satisfactory in all 19 patients. Twelve children (19 toes) attended a special review clinic; all children could grasp large objects (Duplo bricks) after toe transfer. The total passive range of motion was greater than total active range of motion by an average of 54 degrees. Static 2-point discrimination was generally excellent (mean = 5 mm). Eleven out of 12 children strongly agreed that their toe transfer had improved hand function. Microsurgical toe-to-hand transfer is a safe and reliable technique that can provide useful function for children with congenital differences. Our series compares favourably with the published literature. LEVEL OF EVIDENCE: IV.

Preoperative management of the amputated limb.

Little literature exists on storage and preparation of an amputated limb prior to transfer to a reconstructive plastic surgical unit for possible macroreplantation. This paper describes practical measures used to prolong ischaemia time allowing macroreplantation, tissue harvesting, or fashioning of a useful stump. A simple protocol is used to summarise these points.

Function of single rat lung isografts after 48-hour cold storage. The effect of treatment with free radical antagonists and prostacyclin PGI2.

Single orthotopic rat lung isografts were carried out in adult male AS rats after 48-hour cold storage (0 degrees C). Grafts were preserved by simple organ flush followed by low-temperature immersion. Hypertonic citrate (HCA) without additives was evaluated as the basic flush solution. In other groups desferrioxamine (an iron chelator), verapamil (a calcium channel blocker) and prostacyclin (PGI2) were added separately to HCA and given intravenously to donor and recipient animals in an attempt to improve the preservation. Baseline controls were fresh HCA-flushed lungs grafted immediately after harvest. Negative controls to the HCA assessment were lungs flushed with isotonic saline (NaCl) stored for 48 hr at 0 degrees C. Functional studies were carried out at weekly intervals until sacrifice (in the fifth postoperative week) and included assessment of blood flow, aeration and gas transfer by perfusion scintigraphy, chest roentgenograms, and blood gas analysis. Of the baseline control animals, 10/10 survived to the end of the study period; all grafts appeared macroscopically normal and blood gas analysis showed good function. Of the animals grafted with HCA-flushed, 48-hr-stored lungs 2/10 died postoperatively; 7/10 grafts appeared macroscopically normal at the end of the study, and one was slightly reduced in size. Blood gas analysis of HCA-flushed, 48-hr-stored lungs showed function similar to that of baseline control grafts. NaCl-flushed lungs (negative controls) survived surprisingly well: 3/10 animals died postoperatively, 6/10 lungs appeared normal, and one was reduced in size. Assessment of graft function showed no significant benefit of HCA flush compared with NaCl. Treatment with desferrioxamine, verapamil or prostacyclin (PGI2) failed to improve the outcome after HCA flush; in fact desferrioxamine gave significantly poorer results. The study has shown that successful 48-hr preservation of rat lung isografts can be achieved by simple organ flush with HCA and storage at 0 degrees C. Contrary to expectation and experience with preservation of other organs, rat lungs were remarkably well preserved after flush with NaCl.

Lipid peroxidation and ultrastructural changes in rat lung isografts after single-passage organ flush and 48-hour cold storage with and without one-hour reperfusion in vivo.

Rat lung isografts were preserved for 48 hr at 0 degrees C using a simple organ flush technique. After storage alone, isotonic saline flush resulted in significantly raised indices of lipid peroxidation in vitro (Schiff bases and thiobarbituric-acid-reactive material [TBAR]). Lungs flushed with hypertonic citrate (HCA) had significantly less oxidative damage than saline-flushed lungs. The addition to the HCA flush of verapamil, a calcium channel blocker, or desferrioxamine, an iron chelator, significantly reduced TBA reactivity in stored lungs compared with HCA alone. After 1-hr reperfusion in vivo, lipid peroxidation was reduced in HCA-flushed lungs compared with saline flush (TBAR alone), but no additional protection from the use of desferrioxamine or verapamil was demonstrated. Electron microscopy after saline flush and storage alone showed gross endothelial swelling and fragmentation. Reperfusion with blood for 1 hr resolved cell swelling, but alveolar/capillary wall rupture occurred. HCA protected against cell swelling, but endothelial vesiculation and widening of the basement membrane were observed. After reperfusion, HCA-flushed lungs developed much endothelial loss that was considerably reduced by the use of desferrioxamine and verapamil. The lipid peroxidation results suggest that iron- and calcium-mediated free radical production may be important mechanisms in oxidative damage to stored rat lungs. Electron microscopy findings correlated with biochemical evidence of free-radical-mediated injury. Reduction of endothelial loss on reperfusion by the use of verapamil and desferrioxamine provides circumstantial evidence that ischemia and reperfusion damage of organs stored for transplantation is partly due to Fe++(+)- and Ca+(+)-dependent mechanisms that probably involve increased free radical production.

Ascorbate treatment prevents accumulation of phagosomes in RPE in light damage.

In dark-reared albino rats, exposure to 2 or 3 hr of intense light interrupted by 2 hr dark periods resulted in extensive degeneration of photoreceptor cells and degeneration of the retinal pigment epithelium (RPE). Ascorbate (ie, vitamin C) administration prior to light exposure protected photoreceptors and the RPE from light damage. In the present study, ascorbate-treated and untreated rats were exposed to various cycles of intermittent light. Immediately after this light exposure, phagosome frequency in the RPE was morphologically evaluated in comparable 50 microns sections. In untreated rats, exposure to 2 or 3 hr of intermittent light resulted in a five- to sixfold increase in phagosome density compared to unexposed controls. In contrast, no increase in phagosome density was observed in ascorbate-treated rats. In these animals, under all lighting regimens, phagosome levels remained essentially identical to those in rats not exposed to light. After a single nondamaging light exposure, phagosome density remained at the level of dark controls in ascorbate-treated and untreated rats. These results indicate that phagosome frequency may serve as an index for light damage and that the protective effect of ascorbate may be linked to its capacity to prevent rod outer segment shedding and phagocytosis under intense light conditions.

Retinal light damage in rats exposed to intermittent light. Comparison with continuous light exposure.

Visible light-induced photoreceptor cell damage resulting from exposure to multiple intermittent light-dark periods was compared with damage resulting from continuous light in albino rats maintained in a weak cyclic-light environment or in darkness before light treatment. The time course of retinal damage was determined by correlative measurements of rhodopsin and visual cell DNA at various times after light exposure, and by histopathological evaluation. The effect of intense light exposures on rhodopsin regeneration and on the level of rod outer segment docosahexaenoic acid was also determined. For rats previously maintained in weak cyclic light, 50% visual cell loss was measured 2 weeks after 12 1 hr light/2 hr dark periods, or following 24 hr of continuous light. A comparable 50% loss of visual cells was found in dark-reared rats after only 5 hr of continuous illumination or 2-3 hr of intermittent light. As judged by histology, cyclic-light-reared rats incurred less retinal pigment epithelial cell damage than dark-reared animals. In both experimental rat models intermittent light exposure resulted in greater visual cell damage than continuous exposure. Visual cell damage from intermittent light was found to depend on the duration of light exposure and on the number of light doses administered. Measurements of rhodopsin and DNA 2 hr and 2 weeks after light exposure of up to 8 hr duration revealed that visual cell loss occurs largely during the 2 week dark period following light treatment. The loss of docosahexaenoic acid from rod outer segments was also greater in rats exposed to intermittent light than in animals treated with continuous light. It is concluded that intermittent light exposure exacerbates Type I light damage in rats (involving the retina and retinal pigment epithelium) and the schedule of intense light exposure is a determinant of visual cell death.

Pharmacoscintigraphic evaluation of lung deposition of inhaled zanamivir in healthy volunteers.

OBJECTIVE: The objective of this study was to determine the sites of zanamivir deposition in the respiratory tract and the pharmacokinetics of zanamivir after oral inhalation from the Diskhaler device and from a prototype of a novel breath-activated device. DESIGN: This was a 2-period block-randomised study in which participants inhaled zanamivir from a Diskhaler and/or the prototype device on separate days. STUDY PARTICIPANTS: 13 healthy volunteers (5 men and 8 women) aged 20 to 42 years (mean age 29 years) and weighing 54.0 to 94.0 kg (mean bodyweight 69.2 kg) entered the study. INTERVENTIONS: Participants were given dry powder zanamivir 10 mg formulated with 99mTc from the Diskhaler or the prototype device on separate days. Scintigraphic images of the chest and oropharynx were recorded. Blood samples for determination of serum zanamivir and urine for excretion studies were taken up to 8 hours after drug administration. Safety was evaluated by monitoring lung function tests, adverse events and laboratory parameters. RESULTS: Orally inhaled zanamivir was well tolerated, as demonstrated by lung function tests. A mean of 13.2% (n = 11) of the 10 mg dose from the Diskhaler was deposited in the bronchi and lungs. The deposition pattern varied between individuals, showing a preferentially central deposition pattern in some and a uniform distribution pattern in others. The major deposition site was the oropharynx (mean 77.6%), with a mean of 1.2% deposited on the trachea and a mean of 3.2% retained in the blister. Similar data were obtained with the prototype device. Inhalation of zanamivir gave a broad peak of systemic absorption with mean maximum serum concentrations of approximately 30 to 40 micrograms/L after 1.5 hours. The rate and extent of absorption were similar irrespective of inhalation device. Less than 5% of drug was excreted unchanged in urine within 8 hours of inhalation, confirming the low bioavailability of zanamivir after pulmonary delivery. A significant correlation existed between systemic exposure and peripheral lung deposition. CONCLUSIONS: The local concentrations of zanamivir that result from oral inhalation via the Diskhaler are estimated to be > 10 mumol/L throughout the respiratory tract, well in excess of the concentrations observed to inhibit influenza virus neuraminidases by 50% (0.64 to 7.9 nmol/L). Similar deposition data were obtained with the Diskhaler and the prototype device, which was consequently not developed further. Pharmacoscintigraphy was confirmed as being a reliable technique for measuring zanamivir deposition in the respiratory tract.

Effect of catecholamines and angiotensin on extracellular water and cation movements and the effect of alpha and beta-adrenoceptor blockade.

1. The extracellular fluid volume (ECFV), as raffinose space, and its content of Na, K and Ca were measured in anaesthetized dogs in acute experiments before and during the vascular response to intravenous injections and infusions of noradrenaline, adrenaline, isoprenaline and angiotensin.2. In male dogs the effect of noradrenaline was unpredictable, the ECFV might increase or decrease. In female dogs noradrenaline caused an increase in the ECFV. The difference between the responses of the two sexes was statistically significant (P<0.001). After phentolamine, noradrenaline exerted no effect at all in either sex. After bretylium the results were like those in normal animals.3. In both males and females adrenaline generally induced an increase in the ECFV. After phentolamine, adrenaline decreased the ECFV in males and caused little change in females. The differences before and after blockade were statistically significant (P<0.001). After bretylium the results in both sexes were like those in normal animals.4. In both male and female dogs isoprenaline induced an increase in the ECFV and the results were the same as in the normal animals after both phentolamine and bretylium.5. In male dogs there was no change in the ECFV as a result of administering angiotensin, either alone or in the presence of phentolamine or bretylium. In normal females angiotensin induced a decrease in ECFV and the difference between the responses of the males and females was statistically significant (P<0.005). In females which had received either phentolamine or bretylium the results were indistinguishable from those in the males.6. Blockade of the beta-adrenoceptors with pronethalol in a few animals did not change the response to the drugs from those seen in normal animals.7. The cation content of the ECF changed in the same direction and to about the same extent as the water, except after noradrenaline when in some experiments the proportionate change in potassium concentration was considerably greater than that of the other substances.8. The inulin space and its Na and K content were measured in several dioestrous, oestrous and pro-oestrous rats and in normal and stilboestrol treated males before and after giving an intravenous injection of angiotensin. There was little difference between the results of control injections of 0.9% saline solution and of angiotensin in dioestrous and oestrous females and normal males. On the other hand, pro-oestrous females and stilboestrol treated males responded alike to angiotensin in the form of a decrease in ECFV which was statistically different from the responses in the other three groups (P<0.0005).9. It is suggested that the various results depend on two factors: the site of action of the drug-for example, whether it increases or decreases capillary pressure and therefore, fluid transfer-and also the sex of the animal. The ground substance of the small blood vessels is probably important in taking up and releasing fluid, and its capacity for so doing may well vary with the amount of available oestrogen. It appears that the effect of oestrogens and events at the alpha-adrenoceptor site are connected in some way.

Effects of angiotensin and noradrenaline on discharge in fibres of the cervical sympathetic nerve in cats and dogs.

1. The effects of angiotensin and noradrenaline on discharge frequency in single and few-fibre preparations of the cervical sympathetic nerve of cats and dogs have been compared.2. When equal changes in blood pressure were produced by intravenous infusion of these drugs, the changes found in sympathetic discharge were similar both in anaesthetized animals and in a decerebrate one.3. Angiotensin and noradrenaline also have similar effects on discharge in sympathetic nerve fibres following complete denervation of the baroreceptor and chemoreceptor nerves.4. It is concluded that when the blood pressure is raised to 200 mmHg by angiotensin, the drug has no central stimulant action on the sympathetic nervous system.

Histopathologic and ultrastructural analysis of congenital corneal staphyloma.

Although the visual prognosis for eyes with congenital corneal staphyloma has been considered hopeless, we successfully treated a 1-month-old girl with this condition. We performed two penetrating keratoplasties, operating on the left eye first and then, one week later, on the right eye. During each procedure, we totally resected the staphyloma and excised the iris which was adherent to the posterior surface of the cornea. We then sutured an 11-mm corneal button into place with 34 interrupted 10-0 nylon sutures. Light and transmission electron microscopy of the Descemet's membrane and endothelium. The left eye had two rejection episodes and underwent a second penetrating keratoplasty. The graft in this eye is now opaque. The child follows objects well with her right eye.

The acute retinal histopathology of MPTP.

The effects of MPTP on the retina have been examined with emphasis on the effects that are apparent within a few hours of administration. Histopathologic changes were found within one day after MPTP administration. These changes were most prominent in the Muller cells, which demonstrated edematous changes in the cellular processes and occasionally pyknotic nuclei in the inner nuclear layer. Capillary endothelial cells also were damaged by MPTP administration as evidenced by disruption of the cellular cytoplasms. This damage may have caused pooling of blood in the blood vessels of the retina. Finally, mitochondria in some retinal layers may have been altered by MPTP administration with swelling and possible rupture seen in some cells. These acute effects of MPTP may be involved in the formation of lesions to dopaminergic amacrine cells found in the retina following MPTP exposure.

A simple technique for maintaining digital hypothermia during replantation surgery.

A simple technique using inexpensive and readily available materials is described for maintaining digital hypothermia during replantation surgery. Direct contact between soft-tissues and ice or water is prevented, and, thus, avoids undesirable maceration and also reduces the risk of cold-thermal injury, which would further prejudice the success of replantation. The technique is intended for use during prolonged replantation procedures, for example, in cases of trans-metacarpal amputation requiring revascularisation of more than one digit. The principle of using a water-tight sleeve could easily be extended to more proximal amputations, such as at the level of the wrist, by placing the entire hand within a double glove sleeve.

David R. Boyd Lecture in Trauma Care and Emergency Medical Systems: upper extremity injuries--past, present, and future.

Since its recognition as a subspeciality soon after World War I, hand surgery has evolved into a highly specialized and sophisticated field of medicine. Enormous advances have been made in the diagnosis and treatment of disorders of the upper limb; primary tenorrhaphy and the application of microsurgical techniques for revascularization, replantation, and free tissue transfer are among the most important innovations. This article reviews the history of flexor tendon surgery and reconstructive microsurgery up to the present time, and makes some predictions for the future direction of these, and other, areas of hand surgery.

The first toe-to-hand transfer: a thirty-year follow-up.

In April 1968 the first successful free toe-to-hand transfer was performed by Mr. J. R. Cobbett at the Queen Victoria Hospital to reconstruct the thumb of a woodworker. Details of the case are discussed and the patient's current level of sensation, power and function are presented over 30 years following reconstruction.

Use of the homodigital adipofascial turnover flap for dorsal cover of distal interphalangeal joint defects.

The homodigital adipofascial turnover flap was originally described by Voche and Merle (1994) for dorsal cover of the proximal interphalangeal joint. We present three patients in whom this flap was used to cover dorsal defects of the distal interphalangeal joint, and describe an adaptation to allow greater flap mobility.