New Zealand Maori family with the pro250arg fibroblast growth factor receptor 3 mutation associated with craniosynostosis.

BACKGROUND: A large New Zealand Maori family has non-syndromic coronal craniosynostosis, which is inherited as an autosomal dominant mutation with variable expression. The aim of the study is to determine whether the family has the pro250arg mutation in the gene for fibroblast growth factor receptor 3 (FGFR3), a mutation found in patients with various types of craniosynostosis. PATIENTS: Fourteen members of a New Zealand Maori family were evaluated, of whom five have coronal synostosis. A family pedigree tracing six generations was recorded. METHODS: Blood samples were drawn for genomic DNA analysis from 14 family members. Polymerase chain reaction, restriction-enzyme digestion and DNA sequencing was performed to identify the pro250arg mutation in FGFR3. RESULTS: Seven family members were heterozygous for the pro250arg mutation in FGFR3. The mutation showed autosomal dominance with reduced penetrance and variable expressivity. CONCLUSION: Our data and those of other investigators suggest that we should begin integrating molecular diagnosis with phenotypic diagnosis of craniosynostoses.

Burn area color changes after superficial burns in childhood: can they be predicted?

Pigmentation changes after superficial burn injuries are often difficult to predict. We analyzed a sample of patients with burn injuries, looking for clinical indicators of predictable color changes in burn wounds. A sample of 50 children, predominantly those with pigmented skins, who had sustained superficial partial-thickness, (second degree) thermal, scald, or friction burns, were retrospectively grouped. Chemical and electric burns, and those needing skin grafts were excluded. Forty-one patients returned for interview and examination, an average of 63 months after injury (range, 3 to 276 months). All patients had their skin color graded in terms of the Fitzpatrick scale--a numeric scale that combines innate skin color plus reported history of skin response to sun exposure, to assign a value from 1 to 6, where white skin that reddens but does not tan on sun exposure is 1 and heavily pigmented black skin is 6. The burn site, as well as unburned areas of control skin, were tested for reflectance and luminance with use of a well-validated spectrophotometric technique. As an addendum, clinical photographs of a further 50 patients were similarly analyzed. During the first 3 years after injury, burn site color changes were variable. Subsequently, there was cumulative hyperpigmentation at the burn site, provided that the melanocyte-bearing deep dermis had not been destroyed. Hyperpigmentation correlated significantly with skin color, as quantified by the Fitzpatrick scale (p < 0.01), and with time after injury (p < 0.05).

Case report: unilateral combined facial nerve and brachial plexus palsies in a neonate following a midlevel forceps delivery.

A case is described in which the 2.7-kg fetus of a nonobese primigravid patient, delivered by midlevel forceps manipulation sustained neurapraxias of both the marginal mandibular branch of the seventh cranial nerve and the upper trunks of the ipsilateral brachial plexus. The pregnancy was uneventful, but labor was complicated by an occipitoposterior presentation and a prolonged second stage. Examination of the neonate revealed bruising and skin markings consistent with injury by obstetric forceps and the anatomic location of these marks suggested that cervical and mandibular compression from the forceps, rather than traction by the accoucheur, would account for the observed findings. A review of the English language literature over the past 30 years revealed only four cases in which a combination of facial nerve and brachial plexus injuries could both be linked to obstetric instrumentation.

Exploring the use of the medicinal leech: a clinical risk-benefit analysis.

The medicinal leech, Hirudo medicinalis, has been used with increasing frequency for salvage of compromised pedicled flaps and microvascular free-tissue transfers. The data pertaining to 18 cases in which flap salvage with leeches was attempted were reviewed and contrasted with the data from 108 published cases from other centers. A further analysis isolated and examined 19 cases in which infection, secondary to leech utilization, supervened. Results suggested that successful salvage of tissue with leeches occurs in 70 to 80 percent of cases. In contrast, the infection rate of most series is between 7 and 20 percent and, when a clinically significant infection occurs, the flap salvage rate drops to 30 percent or less. In addition to infection, the risks of leech therapy include blood loss, which may require replacement transfusion, loss of leeches into body orifices and spaces, allergic reactions, and adverse psychological responses. Clinical indications and contraindications, and strategies to reduce the risks of leech usage, are discussed. Conclusions are that leeches are best used early, and in accordance with an accepted institutional protocol. For each case, the potential risks and benefits must be rigorously assessed and honestly applied.

Turribrachycephaly: a technical note.

We describe a technique for early correction of the so-called towering skull deformity, or turribrachycephaly. The technique makes use of the natural elasticity and plasticity of cranial bone, and it is best applied during the first year of life. Surgery consist of routine exposure of the cranial bone via a coronal incision. The frontal bone flap is elevated and removed. On either side, a bony osteotomy is then made, commencing low down in the temporal region and running posteriorly and superiorly toward the occiput. This approach leaves a superior bone flap, which may be left attached to the occipital bone via a flexible posterior hinge region, or completely detached by continuing the osteotomy across the midline. After the osteotomy, the bone flap is elevated up to the sagittal sinus on either side of the midline. The bone flap is not removed, but pushed down, compressing the brain along the craniocaudal axis. The lateral edge of the flap overlaps the temporal bone, and it can be fixed in the desired position by means of simple positional screws or Vicryl sutures. A standard fronto-orbital advancement is performed prior to lowering the skull vault, which permits the brain to be moved down and forward, filling the dead space in the anterior cranial fossa. The frontal bone flap is then shaped appropriately and fixed by means of plates and screws to the advanced fronto-orbital bar. Posteriorly, the frontal lobe is left "floating." To date, we have performed this technique on 5 patients, and we find it both faster and simpler than other techniques. Short-term results in terms of cranial shape are good. In older infants (> 2 years of age), this technique may not prove useful because of the loss of the loss of plasticity of the bone.

Decision making in primary surgical repair of myelomeningoceles.

A 5-year review of 43 consecutive patients presenting to Scottish Rite Children's Medical Center with an open myelomeningocele defect was undertaken. The aim of the present study was to analyze the myelomeningocele defects, dimensions, and area to better define those factors that dictate the need for plastic surgical consultation for wound closure. Of the 43 patients identified, two were excluded because they first presented as older children; the remaining 41 all had their myelomeningoceles repaired within the first 36 hours of life. Of these, 31 underwent repair by the Neurosurgical Service, whereas for 10 patients (24.4%), the Plastic Surgery Service was asked to assist with closure. Comparison showed the mean (+/- standard deviation) area in the referred patients was 27.4 (7.6) cm2 versus 17.6 (7.9) cm2 in the patients not referred for closure (p = 0.002). A trend analysis predicting referral as a function of myelomeningocele area showed that 0 of 10 (0%) with an area of less than 15 cm2, 2 of 13 (15.4%) with an area equal to 15 to 20 cm2, 3 of 7 (42.9%) with an area of 21 to 25 cm2, and 4 of 9 (44%) with an area greater than 25 cm2 were referred (p = 0.001). Data from the interpretation of maximum myelomeningocele dimension also showed statistically significant trends in referral. Using multiple logistic regression, it was found that the odds of referral increased by a factor of 3.3 for every 1 cm increase in maximum dimension.

Cytoskeletal actin: the influence of major burns on neutrophil structure and function.

It has been noted that major trauma and burns patients who survive beyond 48 h most frequently succumb to sepsis and multiple organ failure. Furthermore, such patients are usually markedly hypermetabolic and in negative nitrogen balance at the time of their demise. Along with many other systemic and immune dysfunctions, the polymorphonuclear white blood cells in this setting become functionally impaired. Given that the motile white blood cells contain significant proportions of the contractile protein, actin, we speculated that the leucocyte dysfunction might in part be related to the overall systemic catabolism of actin stores. Accordingly, this hypothesis was explored by comparing the functions and cytoskeletal structure of neutrophilic leucocytes from normal control adults and victims of fresh, major thermal injuries. On days 1 and 7 after a burn of > 25 per cent of total body surface area, peripheral blood was drawn from 10 patients (mean age 33 years, mean burn area 44.2 per cent), and seven unburned controls (mean age 35.2 years). Neutrophils isolated from these specimens were tested for stimulated chemotactic rate, efficacy of intracellular killing as determined by superoxide production rate, and the levels of soluble and insoluble intracellular actin. In addition, both light microscopy and scanning electron microscopy were used to visualize the actin cytoskeleton. The results indicated that both chemotactic rate (12 mu/min vs. 38 mu/min--P < 0.05) and superoxide production rate (9 vs 43 mumol/ml10E6 cells--P < 0.05), were significantly reduced in the burn patients by day 7.(ABSTRACT TRUNCATED AT 250 WORDS)

Hand infections secondary to fish bone injuries.

Hand injuries associated with fish bones and fin spines are not common but can cause morbidity out of proportion to the original injury. This is because such injuries often leave residual fragments of foreign organic matter in the tissues, leading to troublesome secondary infections. This report details 1 year's experience with nine hand infections after fish bone injury in a busy regional hand surgery referral centre. There were five males and four females with an average age of 45 years. Radiographs taken on presentation in five patients revealed a radiolucent foreign body in only two patients. Two patients presented with a flexor tendon sheath infection, three with a pulp space infection, one with infection of the hypothenar space, one with a subungual infection, one with cellulitis of the dorsum of the hand and one with an abscess on the dorsum of the hand. Antibiotics were prescribed for six patients and all patients except the one with cellulitis of his hand underwent surgical débridement. A single surgical procedure was adequate in five patients. One patient with a hypothenar space infection only had the foreign body removed during the third surgical débridement. The two patients with flexor tendon sheath infections required ray amputation. Fish bones cause a number of different infections in the hand. A foreign body should always be sought even if not present on the radiograph. Antibiotic selection should be tailored to eradicate the causative organism.

Idiopathic muscular torticollis in children: the Cape Town experience.

54 cases of Idiopathic Muscular Torticollis (IMT) referred for surgery over a 23-year period and 134 cases referred for physiotherapy over a 5-year period have been reviewed. Long-term cosmetic and functional results for 30% of the surgical cases are presented, with a mean follow-up time of 10.5 years. Demographic features, the role of physiotherapy, the timing of surgery and serial assessment are discussed and results are compared with similar studies from other centres. Locally, of the 134 cases referred primarily for physiotherapy, 36% defaulted from treatment, 60% enjoyed lasting benefit and 4% required subsequent surgical intervention. In the surgical cases, while early surgery appears preferable, delayed operation, even up to the ages of 4 or 5 years did not seem to prejudice long-term results, providing that the advent of facial hemihypoplasia did not precede surgery. Delay beyond this point, or roughly 6 or 7 years of age, would seem to prejudice function and/or cosmesis.

The effect of fuel source on amino acid metabolism in critically ill patients.

The ideal energy substrate for critically ill patients receiving total parenteral nutrition (TPN) remains controversial. While glucose has been proved to have nitrogen sparing properties in postoperative patients, critically ill patients tolerate glucose loads poorly and fat appears to be an obligatory fuel in sepsis. Furthermore, it is not yet certain whether the changes in whole body protein metabolism induced by critical illness are influenced by the nature of the TPN provided. This study was conducted on patients admitted to a surgical intensive care unit (SICU) who fulfilled the criteria of requiring TPN and mechanical ventilation for at least four days. Patients were randomized to receive either glucose (G) or equicaloric proportions of glucose and lipid (GF) as an intravenous energy source. TPN was commenced early, within 24-48 hr of trauma or surgery and admission to the ICU. Nonprotein calorie intake was 125% of calculated basal energy expenditure. Nitrogen balance was calculated from 24-hr urinary urea excretion. Protein synthesis, turnover, and catabolism were measured on Day 4 of the study using an established radiolabeled C14-leucine technique. Degree of sepsis and illness were calculated using published scores. Fifty patients entered the trial but 32 were excluded by Day 4. Of the 18 patients completing an initial four day study, eight went on to complete a second study on the alternative regimen--a total of 26 studies (14 G, 12 GF). Net protein synthesis was achieved in 18 studies (12 G, 6 FG) and positive nitrogen balance by Day 4 in 22 studies. Four patients on the G regimen were withdrawn due to glucose intolerance while none of the patients on GF developed glucose intolerance or hyperlipidaemia. Both whole body protein synthesis and catabolism correlated significantly with degree of sepsis. The type of TPN fuel used, G and GF, did not appear to influence whole body protein dynamics, both regimens achieving greatly improved whole body protein kinetics.

A simple device for the objective measurement of activity.

The activity of small experimental animals is difficult to quantify without prolonged observation and note-taking. We describe a relatively cheap and easily constructed device for monitoring and recording activity. Appropriate modifications make the basic device suitable for limited field applications.

Reticuloendothelial function and plasma fibronectin in a murine model of intra-abdominal sepsis.

The lung is the target organ most frequently involved in the early phase of multiple organ failure. Microembolisation of the pulmonary vasculature by bacterial and non-bacterial particles and debris with failure of the clearance mechanism of the reticuloendothelial system (RES) and depletion of plasma fibronectin have been implicated in the pathogenesis. The present study examined the concurrent changes in plasma fibronectin, RES phagocytic function, organ localisation of bacterial and non-bacterial particles and the levels of circulating endotoxin and fibrin degradation products in a clinically relevant murine model of severe intra-abdominal infection. Progressive sepsis was associated with deteriorating RES phagocytic function to 45% of control values within 48 h of sepsis induction. There was decreased hepatosplenic uptake and increased pulmonary localisation of bacterial and lipid emulsion particles. Plasma fibronectin increased in septic animals within 48 h suggesting increased fibronectin production. These changes would support the hypothesis that altered RES function may facilitate pulmonary microembolisation in the pathogenesis of septic multiple organ failure.

Hyperlipidemia, pregnancy and pancreatitis.

Hypertriglyceridemia is a recognized complication of pregnancy. In patients with familial hypertriglyceridemia, the biochemical changes are greatly enhanced during pregnancy and may be associated with acute pancreatitis, a potentially fatal triad. Three patients were studied, in one of whom previously undiagnosed hyperlipidemia resulted in a fatal attack of fulminant acute pancreatitis. In the other two patients, this complication was avoided by close monitoring and restriction of dietary facts. A history of episodic abdominal cramps, often beginning in early childhood, or the presence of lipemic fasting plasma should alert the clinician to the presence of severe familial hypertriglyceridemia. Early diagnosis allows for the institution of relatively simple management strategies, which diminish the risk of pancreatitis.