Maggot secretions suppress pro-inflammatory responses of human monocytes through elevation of cyclic AMP.

AIMS/HYPOTHESIS: Maggots of the blowfly Lucilia sericata are used for the treatment of chronic wounds. As monocytes may contribute to the excessive inflammatory responses in such wounds, this study focussed on the effects of maggot secretions on the pro-inflammatory activities of these cells. METHODS: Freshly isolated monocytes were incubated with a range of secretions for 1 h and then stimulated with lipopolysaccharides (range 0-100 ng/ml) or lipoteichoic acid (range 0-5 microg/ml) for 18 h. The expression of cell surface molecules, cytokine and chemokine levels in culture supernatants, cell viability, chemotaxis, and phagocytosis and killing of Staphylococcus aureus were measured. RESULTS: Maggot secretions dose-dependently inhibited production of the pro-inflammatory cytokines TNF-alpha, IL-12p40 and macrophage migration inhibitory factor by lipopolysaccharides- and lipoteichoic acid-stimulated monocytes, while enhancing production of the anti-inflammatory cytokine IL-10. Expression of cell surface receptors involved in pathogen recognition remained unaffected by secretions. In addition, maggot secretions altered the chemokine profile of monocytes by downregulating macrophage inflammatory protein-1beta and upregulating monocyte chemoattractant protein-1 and IL-8. Nevertheless, chemotactic responses of monocytes were inhibited by secretions. Furthermore, maggot secretions did not affect phagocytosis and intracellular killing of S. aureus by human monocytes. Finally, secretions induced a transient rise in the intracellular cyclic AMP concentration in monocytes and Rp-cyclic AMPS inhibited the effects of secretions. CONCLUSIONS/INTERPRETATION: Maggot secretions inhibit the pro-inflammatory responses of human monocytes through a cyclic AMP-dependent mechanism. Regulation of the inflammatory processes by maggots contributes to their beneficial effects on chronic wounds.

Prehospital endotracheal intubation in patients with severe traumatic brain injury: guidelines versus reality.

The international Brain Trauma Foundation guidelines recommend prehospital endotracheal intubation in all patients with traumatic brain injury (TBI) and a Glasgow Coma Scale (GCS)< or =8. Close adherence to these guidelines is associated with improved outcome, but not all severely injured TBI patients receive adequate prehospital airway support. Here we hypothesized that guideline adherence varies when skills are involved that rely on training and expertise, such as endotracheal intubation. We retrospectively studied the medical records of CT-confirmed TBI patients with a GCS< or =8 who were referred to a level 1 trauma centre in Amsterdam (n=127). Records were analyzed for demographic parameters, prehospital treatment modalities, involvement of an emergency medical service (EMS) and respiratory and metabolic parameters upon arrival at the hospital. Patients were mostly male, aged 45+/-21 years with a median injury severity score (ISS) of 26. Of all patients for whom guidelines recommend endotracheal intubation, only 56% were intubated. In 21 out of 106 severe cases an EMS was not called for, suggesting low guideline adherence. Especially those TBI patients treated by paramedics tended to develop higher levels of stress markers like glucose and lactate. We observed a low degree of adherence to intubation guidelines in a Dutch urban area. Main reasons for low adherence were the unavailability of specialized care, scoop and run strategies and absence of a specialist physician in cases where intubation was recommended. The discrepancy between guidelines and reality warrants changing practice to improve guideline compliance and optimize outcome in TBI patients.

Do maggots have an influence on bacterial growth? A study on the susceptibility of strains of six different bacterial species to maggots of Lucilia sericata and their excretions/secretions.

PURPOSE: The maggots of Lucilia sericata are successfully used as a treatment for infected wounds. Many articles are published about possible direct antibacterial properties of maggots and their excretions/secretions (ES), but with different results. The present study reinvestigates the susceptibility of six bacterial strains to maggots and their ES. METHODS: Live maggots were added to a bacterial suspension. After incubation for 16 h, the bacterial growth in this suspension was compared with the growth in a suspension without maggots. We tested Instar-1 and Instar-3 maggots and compared nutrient broths. A turbidimetric assay investigated the antibacterial activity of ES. Finally, we compared the bacterial growth of Gram-positive and Gram-negative bacteria. RESULTS: The test with live maggots showed an increase of bacterial growth. Instar-1 maggots stimulated more bacterial growth than Instar-3 maggots, as well as the use of a more nutritious broth. The turbidimetric assay showed no inhibition of bacterial growth. For all bacteria, except Pseudomonas aeruginosa, an increase in bacterial growth was shown. CONCLUSION: There is no direct antibacterial effect of maggots and/or ES in vitro, however in clinical observations maggot therapy is successful. More research is needed to focus on possible indirect antibacterial activity, such as an immune-related effect.

[Scaphoid fractures: diagnosis and therapy]. / Scafoïdfracturen: diagnostiek en therapie.

An adequate management of scaphoid fractures requires fast and reliable diagnosis. In this, proper history taking and physical examination are essential. Routine scaphoid x-rays miss over 20% of all scaphoid fractures. Therefore, in patients with a clinically suspected scaphoid fracture that cannot be proven by scaphoid x-rays, further diagnostic investigation is indicated. Which supplemental diagnostic tool (bone scintigraphy, MRI, CT) is preferred remains unclear. A below-the-elbow cast without immobilisation of the thumb is an adequate treatment for stable fractures. Unstable fractures and all proximal pole fractures are candidates for open or percutaneous treatment. In addition to the type of fracture, patient-specific requirements are important in deciding which type of management is the most suitable.

A prospective comparison for suspected scaphoid fractures: bone scintigraphy versus clinical outcome.

UNLABELLED: Early diagnosis and treatment of scaphoid fractures limits the number of delayed and non-unions. Bone scintigraphy proved to be a sensitive diagnostic tool for the detection of occult scaphoid fractures. However, the results have to be interpreted with care. OBJECTIVE: To prospectively correlate the results of bone scintigraphy with clinical outcome. METHODS: In a prospective study, we analysed 50 consecutive patients with signs of a scaphoid fracture at physical examination but no evidence of a scaphoid fracture on scaphoid radiographs. All patients had a protocolised follow up at fixed intervals. The clinical outcome was defined according to a standardised algorithm. MAIN RESULTS: Bone scintigraphy revealed 32% (16/50) occult scaphoid fractures and 40% (20/50) occult other fractures. Clinical outcome proved that bone scintigraphy was false positive in five patients and in one case false negative for a scaphoid fracture. CONCLUSION: Bone scintigraphy in combination with protocolised physical examination is the gold standard for patients with signs of a scaphoid fracture that cannot be proven on scaphoid radiographs.

[Basal cell naevus syndrome as the cause of a chronic foot ulcer]. / Basaalcelnaevussyndroom als oorzaak van een chronisch voetulcus.

A 46-year-old man presented to the surgery outpatient clinic with an ulcer on top of his left foot. He had previously been diagnosed with basal cell naevus syndrome but had withdrawn from follow-up. His foot showed a deep ulcerating defect accompanied by profound necrosis extending to the metatarsophalangeal joints. There was a nodular skin defect over the first metatarsophalangeal joint, which was shown by histopathology to be a basal cell carcinoma, and the ulcer was bordered by a raised wall. Further physical examination revealed more than 200 dermal lesions which were identified by the dermatologist who was called in for consultation as basal cell carcinomas; multiple depressions due to abnormal local keratinisation were also seen on the palms of the hands and the soles of the feet. These findings led to a diagnosis of 'basal cell naevus syndrome'. The patient was treated by amputation of the lower leg followed by excision and curettage of the remaining basal cell carcinomas. At the time of the last follow-up, the patient was being checked periodically in the dermatology outpatient clinic. Basal cell naevus syndrome is a rare autosomal dominant hereditary disease. The prevalence is estimated to be between 1 in 57,000 and 1 in 164,000. Basal cell naevus syndrome is generally caused by a mutation in the 'patched homolog' (PTCH)-I gene, located on chromosome 9q22.3. Although the syndrome affects multiple organ systems, the most characteristic of this disorder is the appearance of multiple basal cell carcinomas.

[Maggot therapy for treatment of severe infections in trauma surgery: "back to the future!"]. / Maden: Ein neues Konzept in der Behandlung von Infektionen in der Traumatologie -- "Back to the Future!"

The ancient method of larval therapy for treatment of acute and chronic infections has become a revival and a new dimension with introduction of the Biobag (Vitapad). With use of this therapy trauma patients suffering infectious complications can be treated very effective, which can reduce the overall time needed for treatment and can result in diminished invalidity.

Necrotising fasciitis of the leg following a simple pelvic fracture: case report and literature review.

Necrotising fasciitis is a rare complication following pelvic fracture, but has a high mortality rate. Topical negative pressure and maggot debridement therapy can be used alongside the usual treatment of surgical debridement and antibiotic therapy.

Transcatheter arterial embolization in a hemodynamically unstable patient with grade IV blunt liver injury: is nonsurgical management an option?

The prevalence of liver injury in patients who have sustained blunt multiple trauma was reported to range from 1 to 8%. Because previous mortality rates were as high as 50-80% for severe hepatic injury, the choice of treatment was under intensive investigation. Whereas nonsurgical management was the standard treatment for the hemodynamically stable patient, there is no consensus on how to treat hemodynamically unstable patients. This report details the case of a patient who sustained blunt multiple trauma, resulting in a grade IV liver injury, graded according to the American Association for the Surgery of Trauma (AAST) Liver Injury Scale. With massive fluid and blood resuscitation, the patient was stable enough to be managed nonsurgically. With transcatheter arterial embolization (TAE), the left and right hepatic arteries were embolized with coils, which allowed for a good recovery. We hypothesize that TAE can be used in the hemodynamically unstable patient who responds to rapid fluid resuscitation and blood transfusion. We caution that there is insufficient evidence until now and would therefore not make any recommendations; however, we would question the need for surgery in unstable patients with this kind of injury in the future.

The effects of varying degrees of pressure delivered by negative-pressure wound therapy on skin perfusion.

Vacuum-assisted closure (V.A.C. Therapy) uses 2 distinct types of foams, with different physical characteristics: the black polyurethane (PU) foam and the white polyvinyl alcohol (PVA) foam. This prospective, randomized study evaluates the response of cutaneous blood flow (CBF) in healthy intact forearm skin to varying V.A.C. Therapy negative pressures and both foam types. Continuous negative pressure was used in the range of 25-500 mmHg. Skin blood flow was measured with noninvasive laser Doppler probes incorporated into the foam. Significant increase in CBF was found with both foams up to negative pressure of 300 mmHg, with over 5-fold increase (mean: 5.57; SD: 3.32) with the PU foam and nearly 3-fold increase (mean: 2.87; SD: 1.29) with the PVA foam. Comparison of blood flow at baseline and at a negative pressure of 300 mmHg showed a statistically significant difference (P < 0.001). No decrease in blood flow below baseline was observed during the experiments.

Can laboratory investigations help us to decide when to discontinue larval therapy?

OBJECTIVE: This study investigated retrospectively whether three laboratory investigations--testing for leucocyte levels, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)--can be used to guide the decision of when to discontinue larval therapy. METHOD: Between 1999 and 2002 we administered larval therapy to 16 inpatients. In all cases the decision to discontinue therapy was a clinical one made by the surgeon who headed the trauma department. We retrospectively analysed laboratory investigations, testing for leucocyte levels, CRP and ESR, on the first and last days of therapy to ascertain if the results could have guided this decision. RESULTS: The median leucocyte count on the first day of larval therapy was 10.5 (x 10e9/L) compared with 8.4 (x 10e9/L) on the last day (Friedman test: p < 0.05). CRP and ESR showed a non-significant tendency towards lower values. CONCLUSION: Although the methodological limitations of this open-label non-comparative cohort study preclude a definite conclusion, we believe that laboratory investigations, particularly leucocyte count, can guide the decision of when to discontinue larval therapy. However, this objective parameter cannot replace clinical judgement.

The antimicrobial activity of maggots: in-vivo results.

In the literature maggot therapy is discussed as a promising and potent form of debridement therapy. The number of maggots needed to debride a wound is estimated at 10 per cm2, and more in case of a higher percentage of necrosis or slough. In the authors' hospital, from March 1999 to May 2002, 16 patients were successfully treated with maggot therapy. The average maggot treatment time was 27 days, with an average of seven maggot changes. Most patients were treated for osteomyelitis, with trauma being the leading aetiological factor. In accordance with in-vitro findings, maggot therapy was found to be more effective in gram-positive infected wounds. Gram-negative bacteria are cultured more often after maggot treatment than before it (p=0.001). The opposite effect was found for gram-positive infected wounds (non-significant p=0.07). In vivo maggots seem to be less effective against gram-negative infected wounds. The authors believe that a higher number of maggots is needed not only for a larger wound or a wound with a higher percentage covered with slough, but also for a wound infected with gram-negative bacteria.

Superior efficacy in suppression of heterotopic bone formation using fractionated irradiation of 5 x 2 Gy compared to a single dose of 7 Gy. An experimental study in rats.

Postoperative irradiation of the operative field is an established method to prevent heterotopic ossification in total hip arthroplasty. In this study two theoretical dose-equivalent regimens of radiation therapy were compared. Allogenic bone matrix was implanted in both thighs of 50 adult male Wistar rats to induce heterotopic ossification. Immediately after operation the implants of 40 animals were irradiated using a single-dose of 7 Gy or 5 fractions of 2 Gy each. Ten rats served as a controlgroup and did not undergo irradiation. Radiation therapy with 5 x 2 Gy led to a highly significantly better suppression of heterotopic ossification than irradiation with 1 x 7 Gy (p < 0.001; paired-t-test). Single-dose irradiation reduced the mean calcium contents to 138.87 +/- 22.84 micrograms Ca2+/mg implanted bone matrix; fractionated irradiation obtained a reduction to 63.35 +/- 21.16 micrograms Ca2+/mg implanted bone matrix. In thigh implants not exposed to irradiation the mean calcium content was 191.50 +/- 11.46 micrograms Ca2+/mg implanted bone matrix. Radiographically better suppression of bone formation could be documented after irradiation with 5 x 2 Gy compared to 1 x 7 Gy and non-irradiated implants. The histological aspect of the explanted specimens showed quantitatively more new bone formation in the non-irradiated controls than in both irradiation groups. In view of experimentally demonstrated better effects, as well as the reduced side effects, fractionated irradiation appears preferable.

Amputation-sparing treatment by nature: "surgical" maggots revisited.

Maggots were used as adjunct treatment for infected wounds that showed no response to the classical approach of wound debridement and antibiotic therapy. We summarize findings for 11 patients with necrotic wounds who received treatment with "surgical" maggots (100-2900 applied in 3-10 changes of dressing) for 11-34 days, which apparently aided in tissue remodeling and cure, and describe 2 typical patients in detail.

High stability of the Ilizarov ringfixator in a metacarpal fracture of an Arabian foal.

In a case of I degree open multifragmentary metacarpal fracture of a 4-week-old Arabian foal, an osteosynthesis with the Ilizarov ringfixator was performed. Immediate full weight-bearing (100 kg) was possible, demonstrating the high stability of the Ilizarov ringsystem. After 12 weeks, sufficient bony union was achieved, and the fixator could be removed. At that time, the body weight of the foal was 170 kg. In our opinion, this case proves the high stability and efficiency of the ringsystem under difficult and unusual conditions.