Fragile X syndrome in two siblings with major congenital malformations.

We report on 2 brothers with both fragile X and VACTERL-H syndrome. The first sibling, age 5, had bilateral cleft lip and palate, ventricular septal defect, and a hypoplastic thumb. The second sibling, age 2 1/2, had a trachesophageal fistula, esophageal atresia, and vertebral abnormality. High-resolution chromosome analysis showed a 46, XY chromosome constitution in both siblings. By PCR and Southern blot analysis, the siblings were found to have large triplet repeat expansions in the fragile X gene (FMR 1) and both had methylation mosaicism. Enzyme kinetic studies of iduronate sulfatase demonstrated a two-fold increase in activity in the first sib as compared to the second. Possible mechanisms through which the fragile X mutation can cause down-regulation of adjacent loci are discussed.

Autoimmune disease and silicone breast implants.

An association between crystalline silica and immune disease has long been recognized. However, despite ongoing case reports of systemic autoimmune disease in silicone implant recipients, the available data has not been sufficient to prove or disprove a causal relationship. Silicone has been shown to "bleed" from the implants and can migrate to distant sites. There is evidence of cellular and humoral immune responses to silicone in vivo, but the role of these responses in the development of connective tissue disorders has not been determined. Further studies are necessary to elucidate the role of silicone, if any, in the pathogenesis of autoimmune connective tissue disease. Meanwhile, the implant population needs to be closely monitored; their clinical management should be based on a case by case evaluation.

The role of the Schirmer's test and orbital morphology in predicting dry-eye syndrome after blepharoplasty.

The Schirmer's test for tear production has been recommended to identify patients with diminished tear production prior to blepharoplasty. The decision to operate may rest with this simple clinical test. This paper reports a prospective clinical evaluation of 100 consecutive blepharoplasty patients to determine the role of preoperative assessment of the orbital and periorbital morphology and the Schirmer's test in predicting the likelihood of the development of the dry-eye syndrome (DES) postoperatively. Our findings indicate that the morphology of the orbital region is a more important and reliable method of evaluating a predisposition to developing dry eyes postoperatively than is the Schirmer's test. The value of the Schirmer's test is to flag patients prior to blepharoplasty, but it should not be relied on as the sole method of screening patients and it is definitely of less importance than the history and physical examination.

The role of rigid skeletal fixation in bone-graft augmentation of the craniofacial skeleton.

The type of fixation (rigid skeletal vs. wire) was assessed against embryologic origin (membranous vs. endochondral) and recipient site (depository vs. resorptive) as variables affecting inlay and onlay bone-graft survival in 20 mature dogs. Wet weight and volume measurements were made at operation and at sacrifice (16 weeks). The results were as follows: (1) Rigid skeletal fixation increased bone-graft volume survival over wire fixation (p less than 0.05). (2) Fixation (i.e., rigid skeletal) and embryologic origin (i.e., membranous) were equal determinants of bone-graft volume survival (p less than 0.001); the recipient site was not significant for onlay bone graft survival. (3) Embryologic origin was the only significant determinant of weight survival (p less than 0.001). (4) Inlay bone grafts demonstrated greater weight and volume survival than onlay bone grafts (p less than 0.05). (5) Histologic and microradiographic studies demonstrated bony union of bone grafts fixed with rigid skeletal fixation, while fibrous union predominated in bone grafts fixed with wire technique.

Bone graft survival in expanded skin.

The effect of tissue expansion on iliac bone graft (onlay) survival was studied on the skulls of 35 New Zealand white rabbits. Wet bone weights at the time of grafting and at sacrifice in control animals (group I) were compared to three experimental groups. Histologic sections of the developing and resolving pseudosheath and skin envelope were performed. A self-inflating 5-mil-thick silicone expander was used for soft-tissue expansion over the rabbit snout. Bone grafts were subsequently placed in this site. Elliptical snout excision without expansion (group II) demonstrated no statistically significant difference in bone graft survival when compared to controls (group I) (p = 0.350). Full tissue expansion followed by immediate bone grafting (group III) within the pseudosheath cavity likewise demonstrated no statistically significant difference in bone graft survival when compared to controls (group I) (p = 0.500); however, when full tissue expansion was followed by delayed (2 weeks) bone grafting to allow for resolution of the giant cell inflammatory reaction of the pseudosheath (group IV), a statistically significant increased bone graft survival was achieved (p less than 0.001). The study demonstrates that the increased vascularity in the pseudosheath and in the expanded soft-tissue envelope significantly increased bone graft survival only when bone grafting was delayed.

The effect of early fronto-orbital advancement on frontal sinus development and forehead aesthetics.

The frontal sinuses make an important contribution to normal forehead and glabellar contour. This study was designed to test our clinical impression that early fronto-orbital ("frontal bone") advancement could have an adverse effect on frontal sinus development and consequently on forehead aesthetics. A retrospective study was conducted on 11 patients who had undergone fronto-orbital advancement and also had a long period of follow-up at the Institute of Reconstructive Plastic Surgery at New York University. The longitudinal cephalometric data were compared with unoperated controls. With one exception, no patient who underwent bilateral fronto-orbital advancement developed a frontal sinus, and all such patients had a flattened brow contour when compared with unoperated patients, of whom 82 percent developed at least one frontal sinus. Of the three patients who underwent unilateral fronto-orbital advancement for plagiocephaly (flattened forehead), two developed a frontal sinus but only on the unoperated side and one developed bilateral frontal sinuses. The two patients with unilateral frontal sinus development had a particularly obvious deformity resulting from normal glabellar projection on the unoperated side and a flattened contour on the operated side. Fronto-orbital advancement affects forehead aesthetics and should be performed only in infant patients with moderate to severe deformities. patients with plagiocephaly whose deformity is sufficiently severe to warrant surgery should preferably undergo bilateral fronto-orbital advancement (by the technique described) rather than unilateral advancement in order to avoid the brow asymmetry that results from unilateral frontal sinus development.

Complete nasal agenesis with bilateral microphthalmia and unilateral duplication of the thumb.

Complete nasal aplasia is an extremely rare clinical entity and most infants are stillborn when this is associated with holoprosencephaly. A viable 3-year-old infant born with frontonasal arrest without holoprosencephaly is presented. The child's main complaint was lack of a nasal airway, which made eating extremely difficult. A method for craniofacial reconstruction of the nasopharynx is presented.

Donor leukocyte migration following extremity transplantation in an experimental model.

In an effort to further define the immunologic mechanisms leading to acute composite-tissue allograft rejection, the migratory patterns of donor leukocytes were evaluated. Using a rat model, 52 orthotopic vascularized hindlimb transplants were performed in strains representing major histocompatibility mismatches. In order to evaluate the effect of allogeneic skin on limb rejection, all donor skin was removed in a second group of allografts. Recipient lymphoid organs were examined during the week following transplantation for antigen-presenting cells using a donor-specific class II monoclonal antibody. Donor leukocytes, with dendritic cell morphology, were identified in recipient spleen and lymph nodes draining the allograft. Significantly higher numbers of donor leukocytes were present during postoperative days 1 through 4 for both groups. Association of these important passenger leukocytes with host T-lymphocytes may represent the site of initiation of the immune response.

Endermologie after external ultrasound-assisted lipoplasty (EUAL) versus EUAL alone.

BACKGROUND: Endermologie, despite its moderate success in the temporary reduction of the appearance of cellulite, has proven unsuccessful compared with lipoplasty for body contouring. OBJECTIVE: The purpose of this study was to determine whether a body contouring program combining Endermologie with lipoplasty would produce better long-term body contouring results than lipoplasty alone. METHODS: A prospective study comparing 2 closely matched, nonrandomized groups of 25 women each was conducted. Those in group 1 underwent external ultrasound-assisted lipoplasty (EUAL) to the superficial and deep subcutaneous areas of the flanks, hips, and thighs, followed in 10 days by a 20-week Endermologie course. Those in group 2 underwent only EUAL to the superficial and deep subcutaneous areas of the flanks, hips, and thighs. Patient evaluation preoperatively and 9 months postoperatively included standardized 35-mm photography; standardized circumferential body measurements of the waist, hips, thighs, knees, and calves; and body composition analysis. Patient satisfaction was assessed through the use of a questionnaire. RESULTS: No significant complications were noted in either group. The average volume of aspirate in the 2 groups was not significantly different (group 1, 2000 mL; group 2, 2100 mL), nor were the results of standard circumferential body measurements and body composition analysis. There was, however, a reduction in the rates of subsequent revisional surgery in the 2 groups (revision rates: group 1, 4%; group 2, 12%). The results of objective blind grading demonstrated no statistically significant difference (P [equals] .30) in body contouring between the 2 groups (group 1, 92% improvement; group 2, 87% improvement). However, a statistically significant (P [lt ] .005) difference was noted for reduction in the appearance of cellulite between the 2 groups (group 1, 50% improvement; group 2, 0% improvement). Patient satisfaction was 96% in group 1 and 92% in group 2. CONCLUSIONS: Endermologie after EUAL improves postoperative results with respect to reduction in the appearance of cellulite and reduces the rate of subsequent revision but demonstrates no significant improvement over EUAL alone with respect to body contour improvement.

Tumescent cervicofacial rhytidectomy.

A modification of the tumescent technique for body contouring has been adapted for patients undergoing face lift. Thirty women, average age 56 years, were prospectively studied, with a 1-year follow-up. All surgery was performed in a private ambulatory operating room facility. The patients were under intravenous sedation with a board-certified anesthesiologist in attendance at all times. The preferred solution was 0.3% lidocaine 1/250,000 epinephrine (average volume injected 500 mL). The solution was a mixture of Ringer's lactate 400 mL plus 2% lidocaine 50 mL and 1% lidocaine 50 mL plus 1:1000 epinephrine 2 mL. The average lidocaine dose per patient was 29.4 mg/kg. Serum lidocaine levels demonstrated a 1-hour peak at 2.7 microg/mL (no value exceeded 3.3 microg/mL). The technique began with superficial liposculpture followed by independent skin-lateral superficial musculoaponeurotic system-ectomy/platysmaplasty with wide skin undermining. Average operating time was 1 hour and 48 minutes. No operative complications were encountered. Excellent anesthetization was achieved in all patients without postoperative hematomas or nerve injuries. Tumescent cervicofacial rhytidectomy has been found to be a safe and effective rhytidectomy procedure that offers several advantages when compared with nontumescent techniques: avoidance of general inhalational agents, reduced operative bleeding and operative time, improved technical ease of superficial liposculpture and surgical dissection, and minimal postoperative bruising and swelling.

The growth of vascularized onlay bone transfers.

The growth of vascularized onlay bone (autogenous) transfers on the skulls of 27 newborn New Zealand white rabbits was studied. Freeze-dried bone weight in control newborns and control adults (group 1) was compared with that in experimental adult animals (group 2). In the experimental group, the bone was transferred on the auricularis anterior muscle and neurovascular pedicle. The flap was deliberately maintained without osseous contact or functional-myogenic stress. The myoosseous bone transfers (group 2) exhibited statistically significant osseous enlargement when compared with the control newborns (p = 0.006); however, the weights were significantly less than those of the adult matched controls (group 1, p less than 0.001). Representative histological sections were also studied. Skeletal unit growth of a portion of the New Zealand white rabbit's skull was achieved despite marked alteration in the "functional matrix." The study demonstrated that vascular supply is the other independent factor affecting bone growth. Generally neglected as a variable in the literature of the subject, vascular supply should be considered within the functional matrix concept of craniofacial growth.

Midline defects of the orofaciodigital syndrome type VI (Váradi syndrome).

The orofaciodigital syndromes (OFDS) represent a spectrum of anomalies of the palate, cranium, hands, and feet. Váradi syndrome, designated OFDS type VI, is a rare disorder that is additionally characterized by cerebellar anomalies. The following report is of a patient with OFDS VI and characteristic multiple midline defects: median cleft lip and palate, lingual cleft with nodules, and midline brain malformation. In addition, this case is uniquely associated with the presence of midline (metopic and sagittal) craniosynostoses as well. It is unusual that deformities which result from premature fusion of cranial vault sutures would appear synchronously in a syndrome based on the concept of failure of fusion or coalescence of facial growth centers. The midline represents an independent developmental field, whereby CNS defects and midline anomalies can present concurrently.

Migration of donor leukocytes from limb allografts into host lymphoid tissues.

This study was undertaken in an initial effort to characterize the immunology of extremity transplantation by examining the pattern and kinetics of leukocyte migration from rat limb transplants. Migration of donor leukocytes was evaluated by examining recipient lymphoid tissues with a donor-specific, anti-major histocompatibility complex, class I monoclonal antibody. Double-antibody, two-color labeling was used to localize donor cells to specific regions within these tissues. Donor leukocytes, with dendritic cell morphology, were found in the T-cell-rich areas of lymph nodes draining the allograft and spleen. The donor cells were present on postoperative days 1 through 3 but were not present on days 5 to 7. Donor leukocytes were not present in distant lymph nodes or liver. These findings indicate a migration of leukocytes, most likely the highly immunogenic dendritic cell, from rat limb transplants to the draining lymphoid tissues. Migration occurs shortly after transplantation and may lead to the sensitization of alloreactive T-cells.