Ocular manifestations in patients with Stevens-Johnson syndrome in Malawi-review of the literature illustrated by clinical cases.

PURPOSE: In Sub-Saharan Africa, manifestations of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are commonly seen in human immunodeficiency virus-infected patients receiving nevirapine-based antiretroviral therapy and/or cotrimoxazole. These patients often face severe ocular complications that lead to moderate to severe visual impairment or blindness. METHODS: Review of the current literature, illustrated by retrospective hospital-based case series: Eight patients at Lions Sight First Eye Hospital, Blantyre, Malawi with severe ocular complications like severe cicatrizing conjunctivitis with symblephara, corneal punctate erosions, corneal vascularization, and corneal ulceration are illustrated after the diagnosis of SJS/TEN. RESULTS: Light perception was reported in six (12 eyes) of them; two patients (4 eyes) had moderate visual impairment (6/36 and 6/18). In one patient, eye problems started after therapy with cotrimoxazole; in seven after therapy, with antiretroviral therapy. CONCLUSION: SJS/TEN in Sub Saharan Africa correlates significantly with moderate visual impairment up to blindness. Early recognition of eye complications and involvement of ophthalmologists in the acute stage, early treatment with local steroids, and close monitoring for up to 6 months after the acute phase are crucial. Severe ocular complications seem to be more severe in dark skin phototype.

Effect of a lateral infraclavicular brachial plexus block on the axillary and suprascapular nerves as determined by electromyography - a cohort study.

We aimed to examine to what extent a lateral infraclavicular brachial plexus block affected the axillary and the suprascapular nerve. We included patients undergoing hand surgery anaesthetised with a lateral infraclavicular brachial plexus block. Our primary outcome was the relative change in surface electromyography during maximum voluntary isometric contraction of the medial deltoid muscle (axillary nerve) and the infraspinatus muscle (suprascapular nerve) from baseline to 30 min after the block procedure. A reduction in electromyography of > 50% defined a successful block. The impact of the block on the shoulder nerves was compared with the surgical target nerves of the arm and hand (musculocutaneous, radial, median and ulnar nerves). Twenty patients were included. The medians of the relative changes in the surface electromyography were significantly reduced (both p < 0.001) with 92% for the deltoid muscle and 30% for the infraspinatus muscle, respectively. In total, 18 out of 20 patients had reductions > 50% for the deltoid muscle, which was significantly different from the infraspinatus muscle, where the proportion was 5 out of 20 (p < 0.001). The medians of the relative reductions in electromyography for the arm and hand muscles were 90-96%, similar to the effect on the deltoid muscle. Our results suggest that a lateral infraclavicular block provides block of the axillary nerve comparable to the block of the surgical target nerves. The suprascapular nerve is blocked to a lesser degree. Combining a lateral infraclavicular brachial plexus block with a selective suprascapular block for shoulder surgery warrants further studies.

Volume of ropivacaine 0.2% and common peroneal nerve block duration: a randomised, double-blind cohort trial in healthy volunteers.

The volume-duration relationship using low concentrations of ropivacaine for peripheral nerve blocks is unknown, even though low concentrations of ropivacaine are increasingly used clinically. We investigated the effect of ropivacaine 0.2% on common peroneal nerve block duration. With ethical committee approval, 60 consenting, healthy volunteers were randomly allocated to receive one of five volumes of ropivacaine 0.2% (2.5, 5.0, 10, 15 or 20 ml) administered by ultrasound-guided, catheter-based injection (at 10 ml.min-1 ) near the common peroneal nerve. Our primary outcome was duration of sensory block, defined by insensitivity to a cold stimulus. Our secondary outcome was duration of motor block. Outcomes were assessed every hour from onset of block to complete remission. Intergroup differences were tested using one-way ANOVA followed by regression analyses using the 20 ml intervention group as reference. Block durations varied significantly (p < 0.0001) between groups. Mean (SD) sensory block durations were 9.2 (3.3), 12.5 (3.0), 15.5 (4.4), 17.3 (3.5) and 17.3 (4.6) h. Mean (SD) motor block durations were 3.3 (2.1), 7.2 (2.5), 9.2 (2.2), 12.7 (2.5) and 12.5 (2.5) h. Regression analysis showed that the effect of volume on block duration was progressively smaller with increasing volume, reaching a threshold volume above which there was no effect on nerve block duration (10 ml for sensory block and 15 ml for motor block). We conclude that there is a ceiling effect of increasing volume of ropivacaine 0.2% on both sensory and motor block duration of the common peroneal nerve.

Initial placement and secondary displacement of a new suture-method catheter for sciatic nerve block in healthy volunteers: a randomised, double-blind pilot study.

We performed a randomised double-blind pilot study in 16 healthy volunteers to investigate the success rate for placing a new suture-method catheter for sciatic nerve block. A catheter was inserted into both legs of volunteers and each was randomly allocated to receive 15 ml lidocaine 2% through the catheter in one leg and 15 ml saline in the other leg. Successful placement of the catheter was defined as a 20% decrease in maximum voluntary isometric contraction for dorsiflexion of the ankle. Secondary outcomes were maximum voluntary isometric contraction for plantar flexion at the ankle, surface electromyography and cold sensation. After return of motor and sensory function, volunteers performed standardised physical exercises; injection of the same study medication was repeated in the same leg and followed by motor and sensory assessments. Fifteen of 16 (94%; 95%CI 72-99%) initial catheter placements were successful. The reduction in maximum voluntary isometric contraction and surface electromyography affected the peroneal nerve more often than the tibial nerve. Eleven of 15 (73%; 95%CI 54-96%) catheters remained functional with motor and sensory block after physical exercise, and the maximal displacement was 5 mm. Catheters with secondary block failure were displaced between 6 and 10 mm. One catheter was displaced 1.8 mm that resulted in a decrease in maximum voluntary isometric contraction of less than 20%. After repeat test injection, 14 of the 16 volunteers had loss of cold sensation. Neither motor nor sensory functions were affected in the legs injected with placebo. We conclude that the suture-method catheter can be placed with a high success rate, but that physical exercise may cause displacement.

A novel concept for continuous peripheral nerve blocks. Presentation of a new ultrasound-guided device.

BACKGROUND: Existing techniques for placing and maintaining the position of peripheral nerve catheters are associated with variable success rates and frequent secondary failures. These factors may affect the clinical efficacy and usefulness of peripheral nerve catheters. METHODS: We developed a new concept and prototype for ultrasound-guided in-plane positioning and readjustment of peripheral nerve catheters (patent pending). The integrated catheter-needle prototype comprises three parts: a curved needle, a catheter with clear echogenic markings attached to the needle tail and a detachable hub allowing injection of local anesthetic while advancing the needle in the tissue. The system works like a suture and is introduced through the skin, passes in close relation to the nerve and exits through the skin. This allows in-plane ultrasound guidance throughout the procedure both during initial positioning as well as during later in-plane readjustment of the catheter. We tested the system in the popliteal region of two fresh cadavers in a preliminary proof of concept study. RESULTS: Both initial placement and secondary readjustment were precise, judged by the catheter orifices placed close to the sciatic nerve in the popliteal fossa. Circumferential spread of 3-ml isotonic saline around the sciatic nerve was observed on ultrasound images in both conditions. CONCLUSION: Preliminary proof of concept of this novel method demonstrates that precise in-plane ultrasound-guided initial placement and secondary in-plane readjustment is possible in fresh cadavers. Future studies should address the clinical efficacy and usefulness of this novel concept.

A novel suture method to place and adjust peripheral nerve catheters.

We have developed a peripheral nerve catheter, attached to a needle, which works like an adjustable suture. We used in-plane ultrasound guidance to place 45 catheters close to the femoral, saphenous, sciatic and distal tibial nerves in cadaver legs. We displaced catheters after their initial placement and then attempted to return them to their original positions. We used ultrasound to evaluate the initial and secondary catheter placements and the spread of injectate around the nerves. In 10 cases, we confirmed catheter position by magnetic resonance imaging. We judged 43/45 initial placements successful and 42/43 secondary placements successful by ultrasound, confirmed in 10/10 cases by magnetic resonance imaging.

Ultrasound-guided block of the suprascapular nerve - a volunteer study of a new proximal approach.

BACKGROUND: The standard approach for the suprascapular nerve block is deep in the supraspinous fossa. However, with this approach, the suprascapular nerve is difficult to visualize by ultrasound. The aim of this study was to describe a new method to visualize and selectively block the suprascapular nerve in a more superficial and proximal location. METHODS: Twelve healthy volunteers were included. We located the brachial plexus in transverse section with ultrasound, and by longitudinal slide, we identified the departure of the suprascapular nerve from the superior trunk. The suprascapular nerve was followed under ultrasound visualization into the subclavian triangle under the inferior belly of the omohyoid muscle. We performed in-plane ultrasound-guided selective suprascapular nerve block by injecting 1 ml of lidocaine, 20 mg/ml close to the nerve. Nerve identification was aided by nerve stimulation. We assessed sensory and motor block of the suprascapular, axillary, radial, median, and ulnar nerves before, 15 and 30 min after performing the block. RESULTS: Eight volunteers demonstrated a selective suprascapular nerve block. Three had block failure and one volunteer did not receive the intervention. CONCLUSIONS: We describe a new ultrasound-guided low-volume local anaesthetic technique to selectively block the suprascapular nerve. The potential clinical role of this new approach remains to be determined.

Ultrasound-guided block of the axillary nerve: a case series of potential clinical applications.

The specific blocking of the axillary nerve has never been investigated clinically. We present four cases illustrating potential applications of the axillary nerve block in the perioperative setting and discuss possible directions for future research in this area. The axillary nerve blocks were all performed using a newly developed in-plane ultrasound-guided technique. In one patient undergoing arthroscopic shoulder surgery, we used the axillary nerve block as the only analgesic combined with propofol sedation and spontaneous breathing. Chronic shoulder pain was eliminated after the axillary nerve block in two patients. The pain score after arthroscopic shoulder surgery in these two patients remained low until termination of the nerve block. In a fourth patient, severe post-operative pain after osteosynthesis of a displaced proximal humerus fracture was almost eliminated after performing an axillary nerve block. These findings warrant larger clinical trials that investigate the pain-mediating role of the axillary nerve in the perioperative setting.

Ultrasound-guided block of the axillary nerve: a volunteer study of a new method.

BACKGROUND: Interscalene brachial plexus block (IBPB) is the gold standard for perioperative pain management in shoulder surgery. However, a more distal technique would be desirable to avoid the side effects and potential serious complications of IBPB. Therefore, the aim of the present study was to develop and describe a new method to perform an ultrasound-guided specific axillary nerve block. METHODS: After initial investigations, 12 healthy volunteers were included. We performed an in-line ultrasound-guided specific axillary nerve block by injecting 8 ml local anesthetic (lidocaine 20 mg/ml) after placing the tip of a nerve stimulation needle cranial to the posterior circumflex humeral artery in the neurovascular space bordered by the teres minor muscle, the deltoid muscle, the triceps muscle and the shaft of the humerus. Needle placement was aided by simultaneous nerve stimulation. We assessed sensory (pinprick and cold stimulation) and motor (active resistive force) block of the axillary nerve before, 15, 30, 60, 90 and 120 min after performing the block and every 30 min until termination of the block. RESULTS: All 12 volunteers demonstrated sensory block of the axillary nerve and 10 volunteers demonstrated complete motor block. Even though it was difficult to directly visualize the axillary nerve, the block was easy to perform with easily recognizable ultrasonographic landmarks. Block duration was approximately 120 min. CONCLUSIONS: We describe a new ultrasound-guided technique to specifically block the axillary nerve. The potential clinical role of this new block remains to be determined.

Physiology of venous return. An unappreciated boost to the heart.

Adequate cardiovascular function depends on the control of venous tone as well as cardiac contractility, heart rate, vascular resistances, and an adequate blood volume. Venous tone is a major determinant of cardiac preload, a clinically important factor influencing cardiac function, especially during cardiac failure. In this review, vascular capacitance, venous tone, and venous return are discussed, and the concepts relating them to cardiovascular function are summarized. Active venoconstriction or dilation provides a rapid compensation, equivalent to a change in blood volume, for cardiovascular homeostasis.

High-throughput generation and engineering of recombinant human antibodies.

The first version of the Human Combinatorial Antibody Library (HuCAL) is a single-chain Fv-based phage display library (HuCAL-scFv) with 2x10(9) members optimised for high-throughput generation and targeted engineering of human antibodies. 61% of the library genes code for functional scFv as judged by sequencing. We show here that since HuCAL-scFv antibodies are expressed in high levels in Escherichia coli, automated panning and screening in miniaturised settings (96- and 384-well format) have now become feasible. Additionally, the unique modular design of HuCAL-genes and -vectors allows the distinctly facilitated conversion of scFv into Fab, miniantibody and immunoglobulin formats, and the fusion with a variety of effector functions and tags not only convenient for therapeutic applications but also for high-throughput purification and detection. Thus, the HuCAL principle enables the rapid and high-throughput development of human antibodies by optimisation strategies proven useful in classical low molecular weight drug development. We demonstrate in this report that HuCAL is a very convenient source of human antibodies for various applications.

Mean circulatory filling pressure: its meaning and measurement.

The volume-pressure relationship of the vasculature of the body as a whole, its vascular capacitance, requires a measurement of the mean circulatory filling pressure (Pmcf). A change in vascular capacitance induced by reflexes, hormones, or drugs has physiological consequences similar to a rapid change in blood volume and thus strongly influences cardiac output. The Pmcf is defined as the mean vascular pressure that exists after a stop in cardiac output and redistribution of blood, so that all pressures are the same throughout the system. The Pmcf is thus related to the fullness of the circulatory system. A change in Pmcf provides a uniquely useful index of a change in overall venous smooth muscle tone if the blood volume is not concomitantly changed. The Pmcf also provides an estimate of the distending pressure in the small veins and venules, which contain most of the blood in the body and comprise most of the vascular compliance. Thus the Pmcf, which is normally independent of the magnitude of the cardiac output, provides an estimate of the upstream pressure that determines the rate of flow returning to the heart.

Association study of serotonin-2A receptor gene polymorphism and panic disorder in patients from Canada and Germany.

The T102C serotonin-2A (5-HT2A) receptor gene polymorphism has been studied extensively in a number of complex psychiatric conditions with mixed results. Recently a genetic association has been described between this polymorphism and panic disorder in a Japanese sample. To evaluate the impact of the T102C polymorphism in panic disorder we genotyped triad families (panic disorder patient and parents), and cases with controls in Canadian and German samples. No significant transmission disequilibrium was observed between the alleles of the T102C 5-HT2A receptor gene polymorphism and panic disorder, nor was a significant excess of either allele found in the case control analysis. Our data suggest thus that this polymorphism is unlikely to play a major role in the pathogenesis of panic disorder.

Healthcare-associated infections in sub-Saharan Africa.

BACKGROUND: Healthcare-associated infections (HCAIs) are the most frequent adverse consequences of healthcare worldwide, threatening the health of both patients and healthcare workers (HCWs). The impact of HCAI is particularly felt in resource-poor countries, with an already overstretched health workforce and a high burden of community-acquired infection. AIM: To provide an overview of the current situation in sub-Saharan Africa with regards to the spectrum of HCAI, antimicrobial resistance, occupational exposure and infection prevention. METHODS: We reviewed the literature published between 1995 and 2013 and from other sources such as national and international agencies. FINDINGS: Sparse data suggest that HCAIs are widespread in sub-Saharan Africa, with surgical site being the dominant focus of infection. Nosocomial transmission of multidrug-resistant tuberculosis is a considerable concern, as is the prevalence of meticillin-resistant S. aureus and resistant Enterobacteriaceae. In HCWs, vaccination rates against vaccine-preventable occupational hazards are low, as is reporting and subsequent human immunodeficiency virus-testing after occupational exposure. HCWs have an increased risk of tuberculosis relative to the general population. Compliance with hand hygiene is highly variable within the region. Injection safety in immunization programmes has improved over the past decade, mainly due to the introduction of autodestruct syringes. CONCLUSIONS: Despite the scarcity of data, the burden of HCAI in sub-Saharan Africa appears to be high. There is evidence of some improvement in infection prevention and control, though widespread surveillance data are lacking. Overall, measures of infection prevention and occupational safety are scarce.