Congenital sucrase-isomaltase deficiency. Identification of a glutamine to proline substitution that leads to a transport block of sucrase-isomaltase in a pre-Golgi compartment.

Congenital sucrase-isomaltase deficiency is an example of a disease in which mutant phenotypes generate transport-incompetent molecules. Here, we analyze at the molecular level a phenotype of congenital sucrase-isomaltase deficiency in which sucrase-isomaltase (SI) is not transported to the brush border membrane but accumulates as a mannose-rich precursor in the endoplasmic reticulum (ER), ER-Golgi intermediate compartment, and the cis-Golgi, where it is finally degraded. A 6-kb clone containing the full-length cDNA encoding SI was isolated from the patient's intestinal tissue and from normal controls. Sequencing of the cDNA revealed a single mutation, A/C at nucleotide 3298 in the coding region of the sucrase subunit of the enzyme complex. The mutation leads to a substitution of the glutamine residue by a proline at amino acid 1098 (Q1098P). The Q1098P mutation lies in a region that is highly conserved between sucrase and isomaltase from different species and several other structurally and functionally related proteins. This is the first report that characterizes a point mutation in the SI gene that is responsible for the transport incompetence of SI and for its retention between the ER and the Golgi.

Laugier-Hunziker syndrome: a rare cause of mucocutaneous pigmentation.

An 80-year-old white woman presented with brown pigmentation on both sides of the buccal mucosa and lower lip and patchy freckling in her nails, which was diagnosed as Laugier-Hunziker syndrome.

Analysis of a naturally occurring mutation in sucrase-isomaltase: glutamine 1098 is not essential for transport to the surface of COS-1 cells.

A glutamine for proline substitution at position 1098 was previously shown to result in accumulation of brush-border sucrase-isomaltase in the Golgi apparatus. The substitution is present in a highly homologous region of the protein, and results in a comparable accumulation when introduced into the same region in lysosomal alpha-glucosidase. To study the importance of the glutamine-1098, we analyzed the transport compatibility of two mutants in which glutamine-1098 is substituted by lysine or alanine. Both mutants were transported to the cell surface and processed comparable to wild type. We concluded that glutamine-1098 is not essential for transport to the cell surface.

Another use of the Foley catheter: retraction for operations on the floor of mouth and ventral aspect of the tongue.

A Foley catheter that is passed through the nose and sutured to the tip of the tongue can be used to facilitate retraction for operations on lesions on the ventral aspect of the tongue and the floor of the mouth. It provides excellent access and is simple, inexpensive, atraumatic, minimises frustration, reduces the operating time, and eliminates some of the difficulties associated with the use of metal retractors.

Effects of methylprednisolone and azathioprine on bronchial healing following lung autotransplantation.

The effect of low-dose immunosuppressive therapy upon the healing of the bronchial anastomosis and skin wound following lung autotransplantation was evaluated. Autotransplantation was performed in two groups of dogs: Group 1 (15 dogs) received no immunosuppression and Group 2 (13 dogs) received postoperative immunosuppression with methylprednisolone (2 mg/kg) and azathioprine (1.5 mg/kg). Two to four skin incisions 7 cm in length were made in the dorsal region of each dog. Dogs were put to death at 4, 9, 16, and 23 days postoperatively and the bronchial anastomoses and skin wounds were evaluated by breaking strength measurements. Bronchus and skin breaking strength increased with time in both groups. Bronchus breaking strength was similar in the two groups at day 4 and day 9. However, by day 23 bronchus breaking strength was significantly higher in Group 1 (p less than 0.001). Skin breaking strength was significantly higher in Group 1 on days 9 and 16 (p less than 0.005) and on day 23 (p less than 0.001). Our results suggest that low-dose methylprednisolone and azathioprine significantly affect the breaking strength of both bronchial anastomoses and healing skin incisions following canine lung autotransplantation.

A comparison between cyclosporin A and methylprednisolone plus azathioprine on bronchial healing following canine lung autotransplantation.

The effects of two low-dose immunosuppressive therapies upon the healing of the bronchial anastomosis and skin wounds following lung autotransplantation were evaluated. Autotransplantation was performed in three groups of dogs: Group 1 (nine dogs) received no immunosuppression, Group 2 (seven dogs) received postoperative immunosuppression with methylprednisolone (2 mg/kg) and azathioprine (1.5 mg/kg), and Group 3 (four dogs) received postoperative immunosuppression with cyclosporin A (20 mg/kg/day). Skin incisions 7 cm in length were made in the dorsal region of each dog. Dogs were put to death 23 days postoperatively, and the breaking strength of the bronchial anastomoses and skin wounds was evaluated with the Instron Universal Testing Machine, with a cross-head speed of 0.5 cm/min. Bronchial breaking strengths were similar in Groups 1 and 3 and significantly higher than in Group 2 (p less than 0.001). Skin breaking strengths were similar in Groups 1 and 3 and significantly higher than in Group 2 (p less than 0.001). Scanning electron microscopic (SEM) studies of both skin and bronchial wounds showed normal formation of collagen bundles in Groups 1 and 3 but a disorganized pattern in Group 2. Our results suggest that low-dose immunosuppression with methylprednisolone and azathioprine significantly affects wound healing and breaking strength of both bronchial anastomoses and healed skin incisions following canine lung autotransplantation. Immunosuppression with cyclosporin A had no adverse effect on either bronchial or skin healing.

Validation of a new formula for calculating the energy requirements of burn patients.

In a previous study, we analyzed the roles of the estimated basal energy expenditure (EBEE) calculated by the Harris-Benedict equation, caloric intake (CI), total burn surface area (TBSA), body temperature (Temp) and number of post-burn days (PBD) in order to estimate the resting energy expenditure (EE) of burn patients. By multiple regression analysis we found that the measured EE (MEE) is best approximated by the following formula: -4343 + (10.5 x %TBSA) + (0.23 x CI) + (0.84 x EBEE) + (114 x Temp (degree C)) - (4.5 x PBD), r = 0.82, p less than 0.001, (Toronto formula (TF)). To validate this, 10 patients with a mean TBSA of 49.1 +/- 5.5% had their resting MEE done by indirect calorimetry when fed either by the TF or by 2 x EBEE. The caloric intake when on 2 x EBEE was 3260 +/- 45 kcal/day which significantly exceeded the MEE (2765 +/- 101 kcal/day, p less than 0.001). The caloric intake when on the TF was 2542 +/- 52 kcal/day and matches the MEE which was 2537 +/- 86 kcal/day (NS). These results show that the TF matches the MEE very closely. With the addition of a factor of activity for the 24-hr EE, it can be used to accurately feed individual burn patients.

Work-related burns: a 6-year retrospective study.

During the 6 years from July 1984 to May 1990, 193 patients (30.2 per cent of all patients) were admitted to our regional adult burn centre, for treatment of work-related burn injuries. The median age of patients was 32.5 years (range 18-64 per cent), and 94 per cent were males. Fifty-nine per cent of the patients came from metropolitan Toronto, and 40 per cent from rural Ontario. Most of the patients (97.3 per cent) were referred to the burn centre within 24 h of their injury. The most common aetiology was electrical injury (29.5 per cent), followed by flame (24.4 per cent), contact (10.4 per cent), flash (9.8 per cent), tar and asphalt (9.3 per cent), scald (7.8 per cent), chemical (5.1 per cent), steam (4.7 per cent) and grease (1 per cent). Within the electrical burn group, about one-half were flash burns, one-quarter were clothing fire injuries, and one-quarter were contact injuries. These occupational burns tended to be extensive injuries. The median body surface area (BSA) was 16.5 per cent, with a median full thickness (FT) component of 5.0 per cent. The average length of stay was 20.0 days. Inhalation injury requiring intubation occurred in 14.8 per cent of patients. Sepsis--confirmed by positive blood cultures--developed in 14 per cent of the patients, at an average time of 8.8 days postburn. Staphylococcus aureus was the commonest organism isolated from blood cultures. Pneumonia occurred in 6.3 per cent of patients. A total of 207 surgical procedures was performed on 113 of the 193 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of IgM production in thermally injured patients.

This report examines the capacity of autologous and exogenous interleukin-2 (IL2) to regulate and/or induce immunoglobulin M (IgM) production in these patients. Pokeweed mitogen (PWM)-induced lymphocyte proliferation and PWM- and IL2-induced IgM secretion were monitored in vitro during the postburn period (10 to over 60 days) in 40 patients aged 16-72 years, with burns 20-90 per cent TBSA. PWM-induced IgM secretion fluctuated considerably during this period. Twelve of 40 patients demonstrated no IgM production and a significant (P less than 0.001-0.05) proportion of them had profoundly suppressed levels. Of the survivors, restoration of IgM secretion to normal levels was achieved in only 60 per cent at time of discharge. Even more consistently suppressed was exogenous IL2-driven production of IgM. In contrast, PWM-induced lymphoproliferation was normal in over 70 per cent of the patients. Thus, the T-cell-dependent antibody response was suppressed for long periods of time, possibly from some deficiency in IL2-regulated secretion or reception of helper T-cell-derived factors necessary for B cell differentiation into Ig-secreting cells.

Plasma levels of cutaneous burn toxin and lipid peroxides in thermal injury.

Lipid peroxides, formed as a consequence of oxygen free radical formation, are responsible for tissue damage in a great variety of pathological conditions including thermal injury. 'Cutaneous burn toxin', formed by application of heat to skin, is thought to be specific to the burn injury. It causes dose-dependent damage to mitochondrial and red cell membranes, and dose-dependent inhibition of interleukin-2-dependent growth of lymphocytes. The possibility that the toxicity of 'cutaneous burn toxin', a lipid-protein, is exerted through lipid peroxides, was examined by measuring the levels of both agents in plasmas of eight burn patients during the first week after their injury. It was observed that plasma lipid peroxides did not appear in parallel with absorption into the circulation of 'cutaneous burn toxin'. Lipid peroxide levels equally common to very low and very high burn toxin levels, were recorded. The pair of agents correlated negatively (r = -0.26) at a significance of only 0.1. In addition, isolated purified 'cutaneous burn toxin' contained no measurable lipid peroxide. No relationship was therefore demonstrated between plasma levels of 'cutaneous burn toxin' and lipid peroxides.

Soluble interleukin 2-receptor alpha secretion is related to altered interleukin 2 production in thermally injured patients.

This study examines the relationship between the capacity for interleukin-2 (IL2) production and the magnitude of the in vitro and in vivo secretion of IL2R alpha in 43 patients with major burns (30-90 per cent total body surface area). Throughout the postburn period a significant (P less than 0.001-0.05) proportion of patients studied demonstrated increasingly high levels of serum IL2 ranging from 2 to over 500 U/mL. Serum IL2R alpha also increased, reaching its highest levels at 15-40 days postburn, while serum IL2 gradually declined. In this period in vitro IL2 production and IL2R alpha secretion in patient's cultures were significantly reduced compared to control. However, in parallel cultures supplemented with exogenous IL2, IL2R alpha levels could be significantly increased (2.5 fold). IL2R alpha levels also approached normal in peripheral blood mononuclear cell cultures from recovering patients whose in vitro IL2 production had improved. These observations suggest that in the burn patient altered synthesis and/or secretion of the soluble form of IL2R alpha may be related to IL2 content. Above physiological levels of IL2R alpha and its ligand in postburn serum also indicate that thermal injury induces strong in vivo activation of the lymphoid system.

Ivalon breast prostheses: evaluation 19 years after implantation.

Ivalon sponge prostheses, which had been removed from a patient after 19 years, were studied mechanically by light microscopy, by scanning electron microscopy, and by dot map x-ray microanalysis. This study revealed the following. The firmness of these implants was due entirely to their external fibrous capsule, which was 4 to 5 mm in thickness. Once this capsule was incised through, the mechanical compression properties of the implants were identical to fresh unused Ivalon sponge. Contrary to previous observations that Ivalon sponge becomes extensively infiltrated with fibrous tissue, the present implants demonstrated fibrous tissue ingrowth only 2 to 3 mm into the sponge. The open porous nature of the sponge had been preserved after the 19-year implantation period. Whereas extensive calcium and phosphate deposition had previously been demonstrated when Ivalon was implanted into animals, no significant deposition of these ions was observed in the present study.

Heterotopic ossification: can early surgery be performed, with a positive bone scan?

It has been previously suggested that the surgical removal of areas of heterotopic ossification in patients with burns should be delayed until bone scans return to normal. The present study describes a patient who underwent surgical removal of heterotopic ossification from both elbows, 1 year after burn injury, with strongly positive bone scans, because of progressive ulnar nerve compression. Subsequently, 7 years after burn injury and 6 years after this surgery, the patient maintained an excellent range of motion in both elbows. At this time, his bone scans continue to be strongly positive. Didronel (Norwich Eaton, Norwich, N.Y.), a diphosphonate, may have played a role in this patient's recovery by decreasing bony deposition following surgery.

Thermal injury-associated neopterin production: regulation by interleukin-2.

Pteridin neopterin production by monocytes/macrophages has been linked to the biologic activity of immune activation- and/or infection-related cytokines. In patients with thermal injuries who succumb to infections, serum levels of both interleukin-2 (IL-2) and neopterin are significantly increased. However, the relationship between these two markers of immune activation remains unclear. This study examines the role of IL-2 in the biosynthesis of neopterin after major burn. Up to 4 weeks after burn, the levels of plasma neopterin and endotoxin were elevated in all patients studied (N = 9, 30% to > 90% total body surface area). Intact (unsupplemented) peripheral blood mononuclear cell (PBMC) cultures from patients with sepsis secreted high levels of neopterin spontaneously. The spontaneous release of neopterin was significantly decreased (p < 0.05) after supplementation with exogenous IL-2. The reverse was observed in peripheral blood mononuclear cell cultures from infection-free or control groups where relatively low neopterin secretion was markedly augmented in the presence of IL-2. The effect of IL-2 in patient cultures was unrelated to the activity of endogenous interferon gamma, because the production of this cytokine was profoundly reduced. However, IL-2-induced alterations in neopterin secretion paralleled those in the production of tumor necrosis factor alpha. This suggests that after thermal injury, biologic responses of neopterin-secreting peripheral blood mononuclear cells are directly or indirectly regulated by IL-2.

Acute and chronic respiratory complications of toxic epidermal necrolysis.

Toxic epidermal necrolysis (TEN) is a rare disease resulting in bullous necrosis of the epidermis with partial-thickness loss of skin and mucous membranes. Previous reports of TEN have not focused on respiratory complications. During a 6-year period, 12 patients with biopsy-proven TEN were referred to a regional burn unit at the Wellesley Hospital, Toronto. Five patients required mechanical ventilatory support, and nine showed roentgenographic evidence of respiratory complications that had developed. Intensive therapy in a critical care burn unit resulted in a 75% survival rate. The four nonsurvivors had severe preexisting multisystem disease. Four survivors were observed prospectively, with 3 monthly pulmonary function testings performed. The four survivors tested, even if they did not require mechanical ventilatory support, showed evidence of respiratory involvement. Three patients demonstrated a persistent reduction in carbon monoxide diffusing capacity of up to 35% to 40% below normal. From our case series we suggest that TEN, although primarily a dermatologic condition, may result in life-threatening acute respiratory decompensation requiring ventilatory support and long-term pulmonary function abnormalities. Patients with TEN should be closely monitored for pulmonary complications.

Serum interleukin-2 receptor as a possible mediator of immunosuppression after burn injury.

Concentrations of the interleukin-2 receptor are significantly elevated in serum after burn injury. To examine the immunoregulatory potential of this molecule, suppressive activity of sera from patients with major burns (n = 16; 40% to 80% total body surface area) was assessed before and after immunoaffinity adsorption with interleukin-2. The preadsorption level of interleukin-2 receptor in the pooled serum after burn injury was 6250 U/ml. This serum demonstrated a strong suppressive activity, inhibiting expression of cellular interleukin-2 receptor and proliferative responses of normal human lymphocytes to alloantigen and exogenous interleukin-2 by 60% to 90%. Adsorption of pooled serum after burn injury with interleukin-2 lowered the level of interleukin-2 receptor to 1800 U/ml and reduced its immunosuppressive activity. The percentage of interleukin-2 receptor-bearing cells, and cell proliferative responses, increased by 50% to 70% compared with sham adsorbed pooled serum after burn injury. Thus serum interleukin-2 receptor after burn injury may represent a specific mediator for downregulation of interleukin-2-dependent responses.

Severe multiple mononeuropathy in patients with major thermal burns.

Multiple mononeuropathy after thermal burns covering greater than 40% total body surface area occurred in nine of 121 of our burn center admissions for an incidence of 7.4%. The number of nerves involved per patient ranged from three to seven, with the average being 4.9. Upper-extremity nerves were more commonly involved than were lower extremity nerves (33 versus 11). All patients had burns over the involved areas. The source was believed to be due to a multiple crush syndrome, in which multiple different neuropathic factors in each patient summate to cause a multiple mononeuropathy. The outcome with conservative treatment was variable, with lower-extremity nerve lesions having a very good outcome and upper-extremity lesions not having as good an outcome, particularly when the median nerve was affected.

Submandibular gland surgery: an audit of clinical findings, pathology and postoperative morbidity.

A series of 86 patients who underwent submandibular gland surgery were reviewed retrospectively. Of the 92 glands excised, non-neoplastic disease accounted for 96% of cases. Preoperative clinical findings were inconsistent such that early surgery should be considered for an enlarged non-tender submandibular gland. The incidence of temporary paresis of the lower branches of the facial nerve was 36% with full recovery, on average, 4 months after surgery. The low 'non-identification' approach to the submandibular gland appears to be the technique which offers the least likelihood of permanent damage to the lower branches of the facial nerve.

Surgical emphysema and Collet-Sicard syndrome after cryoblockade of the inferior alveolar nerve.

We present a case of Collet-Sicard syndrome (palsy of cranial nerves IX-XII) together with cervicofacial emphysema after cryoblockade to the mandibular division of the trigeminal nerve.

Subdural empyema and herpes zoster syndrome (Hunt syndrome) complicating removal of third molars.

We report a case of subdural empyema and herpes zoster syndrome (Hunt syndrome) complicating routine removal of third molars. Subdural empyema is an extremely rare but life-threatening complication of dental sepsis arising spontaneously or after dental surgery. The clinician should be familiar with its presentation and have a high index of suspicion, because late recognition and delay in its treatment can increase the associated morbidity and mortality. Surgical procedures and in particular maxillofacial surgery have also been known to trigger varicella zoster reactivation resulting in Hunt syndrome. Some patients develop the characteristic rash several days after the onset of facial weakness, so that Hunt syndrome may initially be misdiagnosed as Bell's palsy. We highlight the difficulties in diagnosing Hunt syndrome and argue the case for early treatment of all patients with Hunt syndrome and Bell's palsy with a combination of systemic steroids and antiviral drugs.