Optimal position of a long-term central venous catheter tip in a pediatric patient with congenital diseases.

Progress in medical and scientific research has increased the chances of survival for young patients with congenital diseases, children who, in the past, would not have had any chance of survival. Nowadays, congenital diseases can be treated with appropriate replacement therapies. These treatments can be difficult to administer in young patients because of the high frequency of administration (sometimes more than a dose per week), the use of intravenous infusion and the long-term or life-term requirement.

Proinflammatory modulation of the surface and cytokine phenotype of monocytes in patients with acute Charcot foot.

OBJECTIVE: Despite increased information on the importance of an inappropriate inflammatory response in the acute Charcot process, there has been no previous attempt to define the specific pathways that mediate its pathogenesis. Here, the role played by monocytes was analyzed. RESEARCH DESIGN AND METHODS: The immune phenotype of peripheral monocytes was studied by fluorescence-activated cell sorter analysis comparing patients with acute Charcot (n = 10) in both the active and recovered phase, diabetic patients with neuropathy (with or without osteomyelitis), and normal control subjects. RESULTS: When compared with diabetic control subjects and healthy subjects, monocytes from acute Charcot patients showed a proinflammatory immune phenotype characterized by increased production of proinflammatory cytokines, reduced secretion of anti-inflammatory cytokines, increased expression of surface costimulatory molecules, and increased resistance to serum withdrawal-induced apoptosis. In addition, the pattern of circulating cytokines confirmed activation of proinflammatory cytokines. No modulation of the monocyte phenotype was documented in diabetic control subjects and healthy subjects, thus indicating that the proinflammatory alterations of monocytes are specific and causative of acute Charcot. CONCLUSIONS: Together, these data provide evidence for the role of proinflammatory changes in the immune phenotype of monocytes in the pathogenesis of acute Charcot. These alterations may explain the abnormally intense and prolonged inflammatory response that characterizes this disorder and may represent a potential therapeutic target for specific pharmacological interventions.

Bilateral orbital roof fracture.

Bilateral orbital roof fractures are rare events usually associated with high-energy impact trauma. The clinical picture is often multiple because of involvement of cranial, cerebral, and facial injuries. The primary diagnostic and therapeutic approaches aim to safeguard the cerebral state and to intercept the consequences of severe orbital trauma. The latter may present dramatic events and determine permanent ocular bulb or optic nerve damage, even vision impairment and blindness. Immediate intraorbital decompression decreases the pressure exerting directly or indirectly on the optic nerve. Surgical decompression of the orbit was performed in a young man showing almost complete blindness after bilateral orbital roof fracture. The final result showed good recovery of vision and functional motility of the bulbs.

1Alpha,25-dihydroxyvitamin D3 inhibits CD40L-induced pro-inflammatory and immunomodulatory activity in human monocytes.

CD40 ligand (CD40L) stimulation induces proinflammatory and immunomodulatory activity in monocytes. Here, we report on the effects of the steroid hormone 1alpha,25-dihydroxyvitamin D3 (1,25D3) on human blood monocytes that have been stimulated with the CD40L ligand. Co-treatment of CD40L-stimulated monocytes with 1,25D3 resulted in reduced production and secretion of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta, as well as in reduced expression of the surface co-stimulatory molecules CD80 and CD86. In addition, costimulation of CD4+ T lymphocytes by monocytes co-treated with CD40L and 1,25D3 resulted in reduced cell proliferation and diminished interferon (IFN)-gamma but enhanced IL-10 production by CD4+ T cells. Finally, 1,25D3 interfered with the ability of CD40L to rescue monocytes from apoptosis induced by serum withdrawal. These findings suggest that 1,25D3 may regulate the interaction of monocytes with T cells or other cell types that express CD40L, thus influencing the outcome of the immune or inflammatory response.

Downregulation of CD40 ligand response in monocytes from sepsis patients.

It has been suggested that a defective adaptive immune response contributes to septic immunosuppression. Here, the response of monocytes to CD40 ligand (CD40L) for patients with sepsis due to infection with gram-negative organisms has been analyzed. Compared to cells from controls, monocytes from septic patients showed significantly reduced production of tumor necrosis factor alpha, interleukin-1beta (IL-1beta), and IL-12 and were unable to acquire high levels of CD80 and CD86 molecules. These alterations were observed at the onset of sepsis and persisted at day 7. However, the ability of monocytes to respond to CD40L stimulation was partially but significantly restored in cells from patients who recovered from sepsis. In addition, costimulation of autologous CD4+ T lymphocytes by CD40L-activated monocytes from septic patients failed to induce cell proliferation and gamma interferon production. Finally, the ability of CD40L to rescue monocytes from apoptosis was severely impaired. We conclude that downregulation of the CD40L response may be an appropriate model for the monocyte alteration observed during septic immunosuppression and may help in the development of novel therapeutic strategies.

Extra central nervous system metastases from cerebral glioblastoma multiforme in elderly patients. Clinico-pathological remarks on our series of seven cases and critical review of the literature.

AIMS AND BACKGROUND: The aim of the study was to evaluate the treatment of the extracranial metastases from glioblastoma multiforme in the elderly, discussing their uncommon occurrence and their pathogenesis. METHODS: The authors report seven cases of elderly patients (mean age, 69 years), with an initial diagnosis of cerebral glioblastoma multiforme, treated by a grossly total surgical removal and followed by adjuvant radiotherapy (64 Gy in 6 weeks, using Linac) and adjuvant chemotherapy (temozolomide both concomitant and sequential to radiotherapy). RESULTS: All patients presented a postoperative course characterized by good functional and clinical conditions (Karnofsky performance scale > or =70), which remained unchanged for a mean period of about 21 months (range, 16-23), with no neuroradiological signs of lesion regrowth. After this interval, new clinical signs occurred, and their clinical and radiological investigation showed metastatic repetitions in different sites: lung, liver, humerus and lymph nodes. All the metastases were surgically treated, but regrowth of the brain tumor and progression to deep important neural structures caused the patients' exitus after a mean interval of about 10 months (range, 8-12) from the diagnosis of metastasis. CONCLUSIONS: We found 128 cases of extra CNS metastases in the English literature. The main features of the patients of the previous reports and of those of the present series were analyzed. The main modalities of glioblastoma multiforme spread, the few theories about the rarity of metastasis, and the probable biological, histological and immunogenetic mechanisms involved in the pathogenesis are described. Although several studies have reported a poor outcome in elderly patients, they affirm that the treatment of those with a Karnofsky performance status >60 should be just as aggressive as in younger patients. This allows them to obtain a longer survival time and to also treat metastases, which are uncommon particularly in the elderly.

Lipopolysaccharide desensitizes monocytes-macrophages to CD40 ligand stimulation.

Polymicrobial sepsis induces the suppression of macrophage function as determined by a reduction of pro-inflammatory cytokine production upon re-exposure to lipopolysaccharide (LPS) in vitro. Here, we examined whether macrophages were refractory to only LPS or if they were unable to respond to other stimuli such as CD40 ligand (CD40L). Monocytic cells exposed in vitro to LPS showed a dose-dependent reduction of their ability to produce interleukin-12 and tumour necrosis factor-alpha upon subsequent CD40L stimulation, as compared to cells stimulated with CD40L alone. Similarly, LPS interfered with the up-regulation of CD40, CD80 and CD86 induced by CD40L in monocytic cells. The effect of LPS on the response of monocytes to CD40L was similar whether these cells were directly exposed to LPS or cocultured with LPS-pretreated cells, indicating that soluble factors released by LPS stimulation could mediate tolerance to CD40L. We also show that the functional alterations induced by LPS in monocytes can be reversed by indomethacin, thus suggesting a role for inducible cyclooxygenase in mediating the LPS-induced hyporesponsive state of monocytes to CD40L. In conclusion, we propose that in vitro CD40L tolerance may be an appropriate model of monocyte alteration observed during septic immunosuppression and may help in the development of novel therapeutic strategies.

Membranectomy in organized chronic subdural hematomas: indications and technical notes.

BACKGROUND: The aim of the present study is to present our operative method of removing organized CSDHs and to structure the criteria for choosing this approach as first treatment. METHODS: Between 1991 and 1999 at our Institution, 14 consecutive patients with organized CSDHs required 16 craniotomies with membranectomy. They represent 5.8% of all patients (243) treated for CSDHs in the same period. All the patients had preoperative contrast-enhanced CT, and 9 patients also had contrast MRI. RESULTS: Initially, 9 patients underwent one burr hole or twist-drill hole. Of these 9 patients, 3 were treated at the same surgery with craniotomy and membranectomy as second treatment, 3 underwent a second burr hole and then membranectomy at the same surgery, and 3 patients underwent a second burr hole 3, 4, and 21 days after the first one and then membranectomy. Five patients underwent immediate craniotomy and membranectomy. There were no morbidity or mortality associated with this procedure. All patients had a full recovery without recurrence. CONCLUSIONS: Contrast-enhanced MRI has greatly improved opportunities for discovering neomembrane before surgical intervention. We believe that MRI detection of thick and extensive membranes or solid clot with mass effect makes an immediate craniotomy to remove CSDH necessary.

Craniofacial trauma in adolescents: incidence, etiology, and prevention.

BACKGROUND: The lack of a common agreement on the precise meaning of the term "adolescence" makes it difficult to interpret the literature regarding fractures in this age group. METHODS: The records of all patients with craniofacial trauma admitted to the Division of Maxillo-Facial Surgery of the Rome "La Sapienza" University Hospital between February 2001 and August 2004 were reviewed retrospectively. Besides the anatomical site of the fracture, the authors also reviewed in the group of adolescent fractures the cause, complications, and the safety devices employed and their effectiveness. RESULTS: Of 601 patients admitted after facial or craniofacial fractures, 96 were between 11 and 19 (15.97%). The most frequent cause of fracture in this age group was motorcycle crash (39/96), followed by car crash (26/96), sporting accident (15/96), attacks (11/96), microcar crash (2/96), accidental fall (2/96), and firearm trauma (1/96). Only three patients wearing a full-face helmet suffered facial fractures; the most severe fractures with neurosurgical complications occurred in patients without a helmet; the majority of facial fractures occurred in patients wearing an open-face helmet. CONCLUSIONS: It is universally agreed that the primary cause of fracture is road collisions and, although car crashes prevail in all other age groups, motorcycle crashes are more frequent in adolescents. It is necessary to emphasize the need for protective devices capable of avoiding not only neurosurgical complications but also maxillofacial fractures (full-face helmet).

Multilevel oblique corpectomy without fusion: our experience in 48 patients.

STUDY DESIGN: The authors provide their results in performing multilevel oblique corpectomy for degenerative spondylotic myelopathy in 48 patients. OBJECTIVE: To demonstrate the efficacy and safety of the multilevel oblique corpectomy when applied in selected cases. SUMMARY OF BACKGROUND DATA: The technique of multilevel oblique corporectomies for treatment of cervical spondylogenetic myeloradiculopathies allows anterolateral access to the cervical spine so that the spinal canal and conjugate foramen can be widened at more than one level, without the need for vertebral stabilization. METHODS: During a 7-year period, multilevel oblique corpectomy was performed in 48 consecutive patients for degenerative spondylotic myelopathy. The outcomes were analyzed according to the Japanese Orthopaedic Association classification modified to Western customs, and according to Nurick's scale 1 month, 1 year, and 2 years after surgery. Spinal stability was evaluated in all patients by plain radiograph films of the cervical spine, lateral views in flexion and extension, on discharge, 1 month and 1 year after operation. RESULTS: Significant clinical improvement occurred in 29 patients with a complete functional recovery in 22; moderate improvement was achieved in 12 patients; neurological status remained stable in 5, and it worsened in 2. All patients showed spinal stability. CONCLUSIONS: Multilevel oblique corpectomy was found to be a safe technique that guarantees good results in terms of both regression of clinical symptoms and long-term spinal stability.

Traumatic epidural hematoma in children.

The purpose of this study was to investigate the characteristics of childhood acute epidural hematoma and to report our experience in recent years. A series of 35 patients below the age of 15 years treated for acute epidural hematoma at our institution between June 1991 and December 2000 was analyzed in detail. Pediatric epidural hematoma presents both age-related and atypical features when compared with epidural hematoma in adults. In selected cases, prompt surgical evacuation of the hematoma results in an excellent outcome. Outcomes seem to be directly related to the patient's preoperative neurologic status and the presence of associated intracranial lesions.

Severe craniofacial fractures with frontobasal involvement and cerebrospinal fluid fistula: indications for surgical repair.

BACKGROUND: The management of posttraumatic cerebrospinal fluid (CSF) fistulae is a controversial topic. Although recent literature shows that endoscopic repair of CSF fistula is efficacious and minimally invasive, in specific conditions open operative approach remains imperative. METHODS: A series of 36 patients underwent surgery for posttraumatic CSF fistula according to specific selection criteria. These criteria included: bone displacement more than 1 cm (5 cases), location of fracture in proximity to the midline (6 cases), involvement of cribriform plate (12 cases), presence of encephalocele (3 cases), and failure of the conservative treatment (10 cases). The dural defect was closed using vascularized pericranium and fibrin glue. Closure of the basal bone defect was necessary in very large fractures or in special localization of the fistula, such as near the optic nerve. Mean clinical follow-up was 5.7 years. RESULTS: Two patients presented meningitis without sequelae, and 12 with hyposmia. One patient died of the severity of the primary brain injury and associated extracranial lesions. None of the patients had recurrence. CONCLUSIONS: Our results indicate that surgical dural repair in selected cases is related to low morbidity and mortality preserving from delayed risks such as recurrence and infections.

Occipital condyle fractures: report of five cases and literature review.

Occipital condyle fractures (OCFs) are uncommon and potentially fatal lesions. After the advent of CT, prompt diagnosis can be readily made and consequently better prognosis of these patients is expected. Early recognition of some types of OCF is imperative to avoid fatal results. We analyzed 121 cases of OCF (116 from the literature and five of our own). Rarely patients with a deficit of the lower cranial nerves make a complete recovery. However, quoad vitam prognosis of patients with "pure OCFs" remains good. Immobilization provides good recovery of most OCFs, but delay of treatment can lead to serious morbidity. We want to emphasize that not only an OCF with instability of O-C1-C2 can be a fatal injury unless prompt surgical intervention, but a displacement and migration of the fractured condylar fragment can also result in a fatal outcome. A high level of suspicion is fundamental for the early diagnosis of these fractures, so that when a posterior basal cranial or occipital squama fracture occurs, a CT study of the occipital condyles becomes imperative.

Anti-gene peptide nucleic acid targeted to proviral HIV-1 DNA inhibits in vitro HIV-1 replication.

Highly active antiretroviral therapy (HAART) is unlikely to affect reservoirs of HIV in latently infected cells. Anti-gene compounds, such as peptide nucleic acids (PNAs), which block transcriptional activity via sequence-specific invasion of double-stranded DNA may be an effective strategy to target cells harbouring proviral HIV DNA. Here we show that a PNA oligomer (PNA(HIV)), 15 bases in length, linked to a nuclear localization signal (NLS), substantially suppressed HIV-1 replication in chronically infected lymphocytes and macrophages and efficiently prevented mitogen-induced HIV-1 reactivation in lymphocytes, as determined by HIV-p24 antigen production in supernatants and FACS analysis for intracellular HIV accumulation. In contrast, a mismatched PNA did not show any effect on HIV expression. Semi-quantitative RT-PCR and quantitative real-time RT-PCR demonstrated a decrease of HIV RNA expression in infected cells treated by PNA(HIV) indicating that inhibition of HIV-1 replication occurred at the transcription step. In conclusion, the use of anti-gene PNA to target the HIV-1 proviral DNA in the quest for new antiretroviral agents appears quite promising.

Post-traumatic glioma. Report of four cases and review of the literature.

AIMS AND BACKGROUND: To add a further contribution to the literature supporting the relationship between previous head trauma and development of glioma. METHODS: We report on four patients who developed brain gliomas in the scar of an old brain injury. RESULTS: All cases fulfilled the widely established criteria for brain tumors of traumatic origin. In all of our cases there was radiological evidence of absence of tumor at the time of the injury. CONCLUSIONS: We believe that in specific cases it is reasonable to acknowledge an etiological association between a severe head trauma and the development of a glioma. This assumption is further sustained if there is radiological and surgical documentation of the absence of neoplasia at the moment of the trauma.

Management of the entered frontal sinus.

The opening of the frontal sinus is a common occurrence in surgical practice. It may involve many surgical disciplines. The complications that may derive from incorrect treatment of an opened frontal sinus are potentially fatal. Unfortunately, the treatment of patients with injured frontal sinus is not uniform and standardized. Here, we describe our technique of treatment. We propose our treatment modality on the basis of our personal experience, which has been excellent in the past 20 years, that is from the time of the technique's introduction and routine application.

Hypophosphaturic mesenchymal tumor of the ethmoid associated with oncogenic osteomalacia.

Oncogenic osteomalacia is an uncommon syndrome characterized by bone pain, proximal muscle weakness, hypophosphatemia, hyperphosphaturia, and a low plasma concentration of 1,25-dihydroxy-vitamin D. The disease affects both sexes at around 40 years of age, although it can sometimes affect children and adolescents. Generally, the syndrome is associated with a tumor, usually benign, of mesenchymal origin and is resolved after removal of the tumor; this syndrome can sometimes be associated with malignant tumors. These tumors seem to be histologically heterogeneous and are generally localized in soft tissues and bone. In this article, a case of oncogenic osteomalacia associated with a hypophosphaturic mesenchymal tumor of the ethmoid is reported in a 24-year-old man. After surgical and radical removal of the tumor, the patient noted a decrease in the clinical symptoms and signs.

Inflammation markers and risk factors for recurrence in 35 patients with a posttraumatic chronic subdural hematoma: a prospective study.

OBJECT: To evaluate the role of local inflammation in the pathogenesis and postoperative recurrence of chronic subdural hematoma (CSDH), the authors conducted an investigation in a selected group of patients who could clearly recall a traumatic event and who did not have other risk factors for CSDH. Inflammation was analyzed by measuring the concentration of the proinflammatory and inflammatory cytokines interleukin (IL)-6 and IL-8. The authors also investigated the possible relationship between high levels of local inflammation that were measured and recurrence of the CSDH. METHODS: A prospective study was performed between 1999 and 2001. Thirty-five patients who could clearly recall a traumatic event that had occurred at least 3 weeks previously and who did not have risk factors for CSDH were enrolled. All patients were surgically treated by burr hole irrigation plus external drainage. The concentration of inflammatory cytokines was very high in the lesion, whereas it was normal in serum. In five cases in which recurrence occurred, concentrations of both IL-6 and IL-8 were significantly increased (p < 0.01) in comparison with cases without a recurrence. In a layering hematoma, the IL-6 and IL-8 concentrations were significantly higher (p < 0.05). Layering CSDHs were also significantly correlated with recurrence. Trabecular hematoma had the lowest cytokine levels and the longest median interval between trauma and clinical onset. The interval from trauma did not significantly influence recurrence, although it did differ significantly between the trabecular and layering CSDH groups. Concentrations of IL-6 and IL-8 in the CSDHs did not differ significantly in relation to either the age of the hematoma (measured as the interval from trauma) or the age of the patient. CONCLUSIONS: Brain trauma causes the onset of an inflammatory process within the dural border cell layer; high levels of inflammatory cytokines were significantly correlated with recurrence and layering CSDH. A prolonged postoperative antiinflammatory medicine given as prophylaxis may help prevent the recurrence of a CSDH.