Randomized Comparison of Hypochlorous Acid With 5% Sulfamylon Solution as Topical Therapy Following Skin Grafting.

Objective: Infections are a serious complication of thermal injury. Excision and grafting have led to a decrease in incidence, but to ensure successful skin grafting, antimicrobial irrigants are frequently utilized to prevent infection. A safe, efficacious, and cost-effective irrigant capable of preventing infections would be a valuable adjunctive therapy. The objectives of this study were to determine whether the test article was noninferior to current therapy in controlling infection and reducing postoperative pain in patients with skin graft. Methods: Patients with burns requiring skin grafting were randomized to hypochlorous acid or 5% Sulfamylon solution as topical dressings postoperatively. Inclusion criteria included thermal injury 20% or more total body surface area requiring excision and autografting, and age 18 years or more. Exclusion criteria included pregnant females, chlorine sensitivity, and electrical/chemical/cold injuries. The following outcomes were assessed: patient demographics, graft viability, infection, pain score, narcotic usage, adverse events, and cost. Results: Treatment groups were demographically equivalent. There were no differences in adverse or serious adverse events between the 2 groups. Graft viability and infection rate were equivalent between the 2 groups. In addition, pain scores and narcotic usage were similar. Hypochlorous acid was significantly less expensive than 5% Sulfamylon solution. Conclusions: Hypochlorous acid demonstrated equivalent efficacy and safety compared with 5% Sulfamylon when used as the postoperative topical dressing for skin grafts. Hypochlorous acid was more cost-effective. This pilot study was limited by its small sample size. However, hypochlorous acid shows promise as a topical wound dressing and further study with larger groups is warranted.

Source and origin of nerve fibres immunoreactive for substance P and calcitonin gene-related peptide in the normal and chronically denervated superior cervical sympathetic ganglion of the rat.

Immunohistochemical studies of sympathetic ganglia have indicated that the normal rat superior cervical ganglion contains both SP-IR and CGRP-IR fibres, and CGRP- and SP-immunoreactivity coexist in some fibres. In rat sympathetic ganglia decentralization by preganglionic denervation leads to intraganglionic increase of peptidergic fibres immunoreactive (IR) for substance P (SP) and calcitonin gene-related peptide. We explored the sources of SP- and CGRP-IR fibres in normal and in chronically decentralized rat SCGs. The distribution of immunoreactivities for CGRP and SP was determined in SCGs of normal rats and of rats following preganglionic denervation followed by sensory denervation. Ganglia were studied after short-term (2-5 days) sensory denervation, and long-term (7-16 months) sympathetic denervation followed by short-term (2 days) sensory denervation. To explore for the production of SP and CGRP by intrinsic neurones within the ganglion, normal and chronically decentralized SCGs were examined following pretreatment by local in vivo application of colchicine. Normal and chronically decentralized ganglia were also injected with fluorescent tracer Fluorogold for retrograde tracing of extrinsic fibres back to their neurones of origin. The observations suggest that in normal SCG in the rat the SP-IR and CGRP-IR nerve fibres are derived via direct links from vagus and glossopharyngeal nerves and the cervical plexus, or from nerve fibres running along the cervical sympathetic trunk, and the external carotid and the internal carotid nerves. Sensory nerve inputs to the rat SCG following decentralization may contribute to the low levels of ganglionic activation observable in the autonomic failure of multiple system atrophy in man.

Amylopectinosis disease isolated to the heart with normal glycogen branching enzyme activity and gene sequence.

We report a 17-month-old female patient with a rare cause of cardiomyopathy secondary to accumulation of amylopectin-like material (fibrillar glycogen) isolated to the heart. Evidence of amylopectinosis isolated to cardiac myocytes in this patient was demonstrated by histology and electron microscopy. Glycogen content, glycogen branching enzyme (GBE) activity, as well as phosphofructokinase enzyme activities measured in liver, skeletal muscle, fibroblasts and ex-transplanted heart tissue were all in the normal to lower normal ranges. Normal skeletal muscle and liver tissue histology and GBE activity, normal GBE activity in skin fibroblasts, plus normal GBE gene sequence in this patient exclude the classical branching enzyme deficiency (type IV GSD). We believe that this is an as yet uncharacterized and novel phenotype of GSD associated with cardiomyopathy, in which there is an imbalance in the regulation of glycogen metabolism limited to the heart.

Pilomatrixoma of the head and neck in children.

OBJECTIVE: Pilomatrixomas are benign skin neoplasms of hair follicle origin. They are one of the most common superficial masses of the head and neck excised in children. Although the entity has been well studied in the literature, few studies have been undertaken to evaluate the clinical characteristics of head and neck pilomatrixomas specifically in children. The purpose of this study was to review the clinical characteristics and management of children presenting with pilomatrixomas of the head and neck at a large tertiary care pediatric hospital. STUDY DESIGN: A retrospective chart review was performed of all patients with histologically confirmed pilomatrixoma of the head and neck excised during a 6-year period (1992-1997) at the Children's Hospital of Philadelphia. RESULTS: Ninety-one cases of pilomatrixoma were confirmed in 86 patients. The age range was 5 months to 17 years. The median age at time of excision was 6.0 years. The most common sites of occurrence were the cheek (36%), neck (20%), periorbital region (14%), and scalp (9%). The male to female ratio was 1:1.5. Multiple lesions were found in 8.2% of patients. Surgical excision was curative in all cases. CONCLUSION: Pilomatrixoma is a cutaneous neoplasm that is one of most common causes of superficial head and neck masses in children. Although the presurgical diagnosis may be difficult in some cases, pilomatrixoma must be kept in the differential of superficial head and neck masses in children. Surgical excision is almost always curative.

Glioma-associated antigen expression in oligodendroglial neoplasms. Tenascin and epidermal growth factor receptor.

Epidermal growth factor receptor (EGFR), its variant, EGFRvIII, and tenascin are glioma-associated antigens that are hyperexpressed by neoplastic glial cells relative to normal brain, making them attractive antigenic targets for immunotherapy. Preliminary surveys indicate that oligodendroglial tumors also produce these proteins, although the exact patterns and degrees of reactivity are not known. In this study we examined the immunoreactivity of tenascin among 50 oligodendroglial tumors, including 25 well-differentiated oligodendrogliomas (WDOs) and 12 glioblastomas (GBMs) exhibiting high proportions of oligodendroglia-like cells. We used well-characterized immunoreagents with defined specificities against the target antigens on formalin-fixed, paraffin-embedded archival tissue. The tumors were graded according to WHO guidelines. Immunoreactivity was reported on a 1-3 scale according to staining intensity multiplied by a 1-3 distribution scale distribution within tumor as focal (1), multifocal (2), and diffuse (3) for both the parenchymal and the perivascular components. Although there is considerable overlap in antigen production among the grades of tumor, this study establishes the production of tenascin and wild-type EGFR (but not EGFR vIII) in oligodendroglial neoplasms and supports the concept that antigen production increases with tumor grade.

Stimulant-induced exocytosis from neuronal somata, dendrites, and newly formed synaptic nerve terminals in chronically decentralized sympathetic ganglia of the rat.

Loss of preganglionic neurones underlies the autonomic failure of human multiple system atrophy. In rat sympathetic ganglia decentralization leads to new synapse formation. We explored whether these synapses are functional, and whether chronically decentralized neurones respond normally to activation, in terms of exocytosis. Potassium depolarization and cholinergic agonists were applied to freshly excised rat superior cervical sympathetic ganglia, preganglionically denervated with prevented reinnervation 5 months earlier. Ganglia were incubated and stimulated in the presence of tannic acid, which stabilizes released vesicle cores for subsequent electron microscopy. In denervated ganglia exocytosis was observed from newly formed synaptic nerve terminals, and from nonsynaptic surfaces of neurone somata and dendrites. The results demonstrated that the new intraganglionic synapses, which are mostly catecholaminergic, can function and that chronically decentralized sympathetic neurones remain capable of stimulant-induced exocytosis from somata and dendrites. The maximal release upon potassium depolarization did not differ significantly between denervated and contralateral ganglia. Relative to this, the exocytotic responses of decentralized somata and dendrites to nicotine resembled those of contralateral ganglia. Responses to muscarine were significantly less in denervated than in contralateral ganglia, indicating inhibition in dendrites. Responses to carbachol suggested interactions between nicotinic and excitatory muscarinic effects. Nerve terminals in denervated ganglia showed high basal release. Their responses to muscarine and carbachol resembled those of the decentralized neurones, from which most may originate. Their response to nicotine evidenced inhibition. Their actions, coupled with nonsynaptic effects of soma-dendritic exocytosis, might modulate responses of the decentralized neurone population to other surviving inputs. This modulation could be influential in disease-induced decentralization in man.

Ventral hernia synthetic mesh repair infected by Mycobacterium fortuitum.

We report the occurrence of a refractory infection caused by the "rapidly growing" nontuberculous mycobacterium, Mycobacterium fortuitum, after incisional hernia repair using synthetic mesh. The patient had previously undergone three herniorrhaphies incorporating polypropylene mesh. Multiple surgical debridements were required, along with complete removal of all the mesh, to eradicate the infection. Prolonged antimicrobial therapy with sulfamethoxazole, an agent active against the patient's isolate, was also used. Although this atypical mycobacterium has been reported to cause a variety of infections, including many types of periprosthetic infections, this case represents successful treatment of M. fortuitum infecting abdominal wall mesh.

Molecular genetic aspects of oligodendrogliomas including analysis by comparative genomic hybridization.

Oligodendroglial neoplasms are a subgroup of gliomas with distinctive morphological characteristics. In the present study we have evaluated a series of these tumors to define their molecular profiles and to determine whether there is a relationship between molecular genetic parameters and histological pattern in this tumor type. Loss of heterozygosity (LOH) for 1p and 19q was seen in 17/23 (74%) well-differentiated oligodendrogliomas, in 18/23 (83%) anaplastic oligodendrogliomas, and in 3/8 (38%) oligoastrocytomas grades II and III. LOH for 17p and/or mutations of the TP53 gene occurred in 14 of these 55 tumors. Only one of the 14 cases with 17p LOH/TP53 gene mutation also had LOH for 1p and 19q, and significant astrocytic elements were seen histologically in the majority of these 14 tumors. LOH for 9p and/or deletion of the CDKN2A gene occurred in 15 of these 55 tumors, and 11 of these cases were among the 24 (42%) anaplastic oligodendrogliomas. Comparative genomic hybridization (CGH) identified the majority of cases with 1p and 19q loss and, in addition, showed frequent loss of chromosomes 4, 14, 15, and 18. These findings demonstrate that oligodendroglial neoplasms usually have loss of 1p and 19q whereas astrocytomas of the progressive type frequently contain mutations of the TP53 gene, and that 9p loss and CDKN2A deletions are associated with progression from well-differentiated to anaplastic oligodendrogliomas.

Fine-needle aspiration cytology of "ancient" schwannoma.

The term "ancient" schwannoma was proposed for a group of neural tumors showing degenerative changes and marked nuclear atypia. Prior to the realization that the observed atypia was a regressive phenomenon, many of these lesions were erroneously diagnosed as sarcomas. Fine-needle aspiration (FNA) cytologic material from five patients is included in this study. Tissue examined histologically included four resected tumors and 18 gauge core biopsies of one tumor. Aspirates of ancient schwannoma showed many of the same features as FNA of regular schwannoma: aggregates of spindled cells with indistinct cytoplasm and elongate nuclei with blunt point ends. The feature unique to these lesions was nuclear pleomorphism, which was identified in all aspirates. Nuclear inclusions were identified in all but one case. Cystic degeneration, xanthomatous changes, and perivascular sclerosis were identified in excised lesions. Ancient schwannomas show most of the FNA features of benign schwannomas but can demonstrate marked nuclear atypia. The FNA features of ancient schwannoma are important to note because of the potential to confuse this lesion with a more serious one such as sarcoma on FNA.

Development of a colocutaneous fistula in a patient with a large surface area burn.

A 61 year old female sustained a large surface area burn, complicated by inhalation injury. One month before the incident, she had undergone a left hemicolectomy with colorectal anastomosis for diverticular disease. Due to the severity of her burns, multiple surgical debridement and skin grafting procedures were required, including a large fascial debridement of her flank and back. Her hospital course was complicated by recurrent episodes of pulmonary and systemic infection, as well as pre-existing malnutrition. Prior to her discharge to a rehabilitation center, stool began to drain from her left posterior flank. This complication represented a colonic fistula arising from the recent colon anastomosis. The fistula was managed nonoperatively and gradually closed. To our knowledge, this is the first report of a colocutaneous fistula spontaneously draining from the abdomen via the retroperitoneum in a burn victim, not related to direct thermal injury to the peritoneal cavity.

Continuous hemodialysis for the management of acute renal failure in the presence of cerebellar hemorrhage. Case report.

In this report the authors describe the use of continuous venovenous hemodialysis (CVVHD) in a medically unstable patient who suffered from a spontaneous cerebellar hemorrhage. Conventional dialysis techniques carry the risk of developing the dialysis disequilibrium syndrome (DDS) when performed in the presence of a variety of intracranial diseases. The CVVHD technique was used successfully in a morbidly obese, short-statured woman with a spontaneous hypertensive intraparenchymal cerebellar hemorrhage. The woman experienced acute renal failure several days after her hemorrhage and her general medical condition prevented her from undergoing surgical evacuation. The CVVHD did not result in elevations in intracranial pressure (ICP) and the patient made a full recovery from both acute renal failure and life-threatening posterior fossa hemorrhage. This case is noteworthy because of the absence of abnormally high ICP elevations or development of DDS in a patient with a large acute posterior fossa intraparenchymal brain hemorrhage and acute renal failure whose case was managed with CVVHD in the acute period.

Rationale for 'early' percutaneous dilatational tracheostomy in patients with burn injuries.

Several investigators have cited the numerous complications that occur with conventional tracheostomies in patients with burn injuries. However, none of these studies included the technique of percutaneous dilatational tracheostomy, which has been shown to significantly decrease operative time, cost, perioperative, and long-term sequelae as compared to conventional tracheostomy. A retrospective analysis of 36 patients with burn injuries, from 1400 burn admissions, was conducted to compare conventional tracheostomy versus percutaneous dilatational tracheostomy. In this study, percutaneous dilatational tracheostomy resulted in significantly decreased operative times and cost compared to conventional tracheostomy. There were no major operative complications in either group, and alveolar-arterial oxygen gradients were improved in 71% of the patients with a tracheostomy. Percutaneous dilatational tracheostomy is an efficacious technique for airway management in patients with burn injuries. It can be safely performed at the bedside, at one fourth the cost of a conventional tracheostomy. Percutaneous dilatational tracheostomy may also benefit the patient with severe burns by decreasing alveolar-arterial oxygen gradients. Improved ventilatory mechanics might allow for a shorter duration of mechanical ventilation, thereby decreasing patient morbidity, hospital stay, and cost.

Exocytotic release from neuronal cell bodies, dendrites and nerve terminals in sympathetic ganglia of the rat, and its differential regulation.

Stimulant-induced exocytosis has been demonstrated in sympathetic ganglia of the rat by in vitro incubation of excised ganglia in the presence of tannic acid, which stabilizes vesicle cores after their exocytotic release. Sites of exocytosis were observed along non-synaptic regions of the surfaces of neuron somata and dendrites, including regions of dendrosomatic and dendrodendritic apposition, as well as along the surfaces of nerve terminals About half the exocytoses associated with nerve terminals were parasynaptic or synaptic, and these appeared mostly to arise from the presynaptic terminal, but occasionally from the postsynaptic element. The results demonstrated that the neurons of sympathetic ganglia release materials intraganglionically in response to stimulation, that release from different parts of the neuron is subject to independent regulation, at least via cholinergic receptors, and that release is partly diffuse, potentially mediating autocrine or paracrine effects, and partly targeted toward other neurons, but that the latter mode is not necessarily, and not evidently, synaptic. Specifically, exocytosis from all locations increased significantly during incubation in modified Krebs' solution containing 56 nm potassium. Observation of the effects of cholinergic agonists (nicotine, carbachol, oxotremorine) and antagonists (atropine, AF-DX 116) showed that nicotinic and muscarinic excitation each, independently, increased the incidence of exocytosis from somata and dendrites. Exocytosis from nerve endings was not altered by nicotine, but was enhanced or, at high initial rates of exocytosis, decreased, by muscarinic stimulation. Evidence was obtained for muscarinic auto-inhibition of exocytosis from nerve terminals, occurring under basal incubation conditions, and for a muscarinic excitatory component of somatic exocytosis, elicitable by endogenous acetylcholine. The M2-selective muscarinic antagonist AF-DX 116 was found to modify the exocytotic response of the dendrites to oxotremorine, widening the range of its variation; this effect is consistent with recent evidence for the presence of M2-like muscarinic binding sites, in addition to M1-like binding, upon these dendrites [Ramcharan E. J. and Matthews M. R. (1996) Neuroscience 71, 797-832]. Over all conditions, disproportionately more sites of somatic and dendritic exocytosis were found to be located in regions of dendrosomatic and dendrodendritic apposition than would be expected from the relative extent of the neuronal surface occupied by these relationships. Such mechanisms of intraganglionic release may be expected to contribute to the regulation and integration of the behaviour of the various functionally distinctive populations of neurons in these ganglia, by autocrine, paracrine, and focal, neuroneuronal, routes of action. Similar phenomena of exocytotic soma-dendritic release might prove to subserve integrative neuroneuronal interactions more widely throughout the nervous system.