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Biomedical subjects

J B Mulliken

Publications and source records attributed to J B Mulliken.

At least 73 records · Page 4Linked to original sources
PubMed1998

Spastic diplegia as a complication of interferon Alfa-2a treatment of hemangiomas of infancy.

We report the development of spastic diplegia in infants during the course of interferon Alfa-2a (IFN) therapy for potentially life-endangering hemangiomas. Five infants who displayed diplegia were selected from a group of 26 infants treated with IFN. Diplegia persisted in three infants, and in the remaining two significant recovery occurred after IFN was discontinued. Magnetic resonance imaging showed no significant brain or spinal abnormalities except minor to moderate delayed myelination in two patients. Myelination was normal on subsequent radiographic examination in all five patients. We conclude that IFN can adversely affect the immature central nervous system and produce spastic diplegia, which is potentially reversible. We recommend careful clinical assessment of neurodevelopmental status during IFN therapy.

Cerebral Palsy↗
PubMed1998

Vascular anomalies. A primer for pediatricians.

The future is bright for children with vascular anomalies. Children with vascular anomalies no longer have to languish in the interface between various medical specialties. Vascular anomalies centers are available for consultation. Not only are specialists focusing on the conditions, but basic science has brought us to the horizon of new insights into etiology and thus the possibility for new treatment. For children with vascular tumors, newer antiangiogenic agents are already in clinical trials. For children with vascular malformations, research in molecular genetics has begun to uncover the genes responsible for normal fetal vasculogenesis and angiogenesis. Molecular studies of familial vascular malformative syndromes are just beginning to pinpoint causative mutations. Next, animal models of vascular abnormalities will be engineered to elucidate pathogenesis, and these studies, in turn, should lead to development of novel therapies.

Blood Vessels↗
PubMed1998

Midfacial growth after costochondral graft construction of the mandibular ramus in hemifacial microsomia.

PURPOSE: The purpose of this study was to document vertical midfacial growth after costochondral graft mandibular ramus construction in children with type IIB and type III hemifacial microsomia (HFM). METHODS: This is a retrospective study of 33 children who underwent costochondral graft (CCG) construction for mandibular type IIB (abnormal, small, and medially displaced ramus, n = 19) and mandibular type III (absent ramus and glenoid fossa, n = 14) HFM, between 1980 and 1990. Types I and IIA patients were not included because their milder mandibular deformities were lengthened by osteotomy. Mean age at operation was 6.2 (2 to 10) years, and the mean follow-up period was 5.5 (1 to 13.5) years. Occlusal cant, piriform angle, and intergonial angle were measured on the most current posteroanterior (PA) cephalogram. The ratio of unaffected to affected ramus length was determined on the most current panoramic radiograph. Patient outcomes were classified based on the occlusal cant at the latest follow-up: group 1, successful result with a symmetrical maxilla (occlusal cant of <5 degrees); group 2, acceptable result (occlusal cant > or =5 degrees but <8 degrees), and Group 3, failure (occlusal cant > or = 8 degrees). OMENS scores were calculated for each patient: each of the five major anatomic deformities of HFM (orbital, mandibular, auricular, neural, and soft tissue) were graded 0 to 3 and summed. The mean differences in age at operation and OMENS scores between groups were calculated (ANOVA). RESULTS: At the end of follow-up, patients defined as having a successful result (group 1) had a mean occlusal cant of 2 degrees, a mandibular length ratio of 1.0, and an intergonial angle of 2 degrees. However, the final piriform angle was 7 degrees, indicating less vertical midfacial growth than maxillary alveolar growth. These patients were older at the time of operation (mean age, 6.7 years), and their mean OMENS score (6.3) was significantly lower (P = .004) than in patients in group 2 (mean age at operation, 6.3 years; mean OMENS score, 6.8) and group 3 (mean age at operation, 5.8 years; mean OMENS score, 7.8). In group 2, the occlusal cant, mandibular length ratio, and intergonial and piriform angles did not improve. In group 3, the occlusal cant and piriform angle became worse during the follow-up period. CONCLUSIONS: The results of this study indicate that after construction of the ramus and condyle in type IIB and III HFM patients, vertical midface growth is secondary to a combination of midfacial and alveolar growth. Patients operated on at an older age were more likely to have a successful long-term result. Finally, the severity of the overall deformity, as reflected in a higher OMENS score, appeared to be an important factor in the response to early correction.

Age Factors↗
PubMed1998

New instrument for orbital anthropometry.

A new instrument for orbital anthropometry is described. It consists of the base for a slit-lamp upon which the patient's head rests and rulers mounted on three independently movable axes. The z-axis probe is used to measure sagittal relationship between the corneal apices and points on the orbital perimeter. The instrument was tested against a sliding caliper and its accuracy was found to be within 0.2 mm or 2%. Intra- and inter-observer reliability were assessed by repeated measurements of two subjects by three observers. The intra-observer reliability was 0.99. Variations between observers was not significantly different for points orbitale inferius (oi), nasion (n), and orbitale superius (os), however, there was a statistically significant difference for measurement of orbitale laterale (ol). The correlation between anthropometric readings for lateral orbital wall to apex corneal (ol-ac) and CT scans for the same landmarks was assessed. Analysis of variance showed no difference between the measurement methods. This anthropometer is convenient and accurate for measurement of the sagittal orbital-globe relationships. A disadvantage is that it cannot be used intraoperatively.

Analysis of Variance↗
PubMed1998

Molecular basis of vascular anomalies.

Vascular anomalies comprise a heterogeneous group of disorders that are divided into tumors (hemangiomas) and malformations. Recent advances in biomedical research provide insights into the molecular basis of these disorders and a deeper understanding of vascular morphogenesis. In the future, this emerging knowledge will contribute to novel ways to treat vascular anomalies and to regulate pathologic angiogenesis.

Journal Article↗
PubMed1998

Arteriovenous malformations of the head and neck: natural history and management.

This is a retrospective review of 81 patients with extracranial arteriovenous malformation of the head and neck who presented to the Vascular Anomalies Program in Boston over the last 20 years. This study focused on the natural history and effectiveness of treatment. The male to female ratio was 1:1.5. Arteriovenous malformations occur in anatomic patterns. Sixty-nine percent occurred in the midface, 14 percent in the upper third of the face, and 17 percent in the lower third. The most common sites were cheek (31 percent), ear (16 percent), nose (11 percent), and forehead (10 percent). A vascular anomaly was apparent at birth in 59 percent of patients (82 percent in men, 44 percent in women). Ten percent of patients noted onset in childhood, 10 percent in adolescence, and 21 percent in adulthood. Eight patients first noted the malformation at puberty, and six others experienced exacerbation during puberty. Fifteen women noted appearance or expansion of the malformation during pregnancy. Bony involvement occurred in 22 patients, most commonly in the maxilla and mandible. In seven patients, the bone was the primary site; in 15 other patients, the bone was involved secondarily. Arteriovenous malformations were categorized according to Schobinger clinical staging: 27 percent in stage I (quiescence), 38 percent in stage II (expansion), and 38 percent in stage III (destruction). There was a single patient with stage IV malformation (decompensation). Stage I lesions remained stable for long periods. Expansion (stage II) was usually followed by pain, bleeding, and ulceration (stage III). Once present, these symptoms and signs inevitably progressed until the malformation was resected. Resection margins were best determined intraoperatively by the bleeding pattern of the incised tissue and by Doppler. Subtotal excision or proximal ligation frequently resulted in rapid progression of the arteriovenous malformation. The overall cure rate was 60 percent, defined as radiographic absence of arteriovenous malformation. Cure rate for small malformations was 69 percent with excision only and 62 percent for extensive malformations with combined embolization-resection. The cure rate was 75 percent for stage I, 67 percent for stage II, and 48 percent for stage III malformations. Outcome was not affected significantly by age at treatment, sex, Schobinger stage, or treatment method. Mean follow-up was 4.6 years.

Adolescent↗
PubMed1998

Möbius syndrome: classification and grading system.

Möbius syndrome is characterized by facial abnormalities, but the limbs, chest wall, spine, and soft tissues also can be involved. There is no system for categorizing the various anomalies, grading phenotypic severity, designing treatment protocols, or assessing therapeutic results. This is a retrospective analysis of 27 patients with Möbius syndrome seen in our craniofacial unit from 1980 to 1994. We categorized and graded the cranial nerve deficits and diverse musculoskeletal abnormalities of the face, upper and lower limbs, and trunk. The first letter for each of five potentially involved structures, i.e., cranial nerve, lower limb, upper limb, face, and thorax, formed the acronym CLUFT. The structural and/or functional deficits for each component were graded on a scale of 0 to 3. Complete facial nerve paralysis was documented in 11 patients and paresis in 16. Facial nerve paralysis was bilaterally symmetric in 17 of 26 patients. Sixth nerve paralysis was present in 23 of 27 patients; other cranial nerves were affected in 8 of 27 patients. Lower limbs were involved in 10 of 27 patients and upper limbs in 7 of 27 patients. Facial structures were affected in 17 of 27 patients (e.g., microtia, micrognathia, and microphthalmia), and chest wall deformities were found in 8 of 27 patients (e.g., scoliosis, hypoplasia of the breast, pectoral muscles, and scapula). We noted that microtia primarily involved second pharyngeal arch-derived structures. The CLUFT system permits categorization and comparison of Möbius patients for phenotypic and management outcome studies. Documentation of the widespread structural anomalies suggests that pathogenesis involves vascular disruption; a detailed prenatal history is indicated.

Abnormalities, Multiple↗
PubMed1998

Photogrammetric comparison of two methods for synchronous repair of bilateral cleft lip and nasal deformity.

The principle of synchronous repair of bilateral complete cleft lip and nasal deformity is established, and the techniques are evolving. We undertook photogrammetric comparison of the method described by Mulliken (group I, n = 15) and that described by Trott (group II, n = 10). Facial proportions and angles were measured on preoperative and postoperative photographs using defined anthropometric points. The following criteria were quantified for each test group: nasolabial angle, nasal tip angle and projection, nasal width, columellar length and width, and philtral width. All parameters in both groups were compared against each other and against normal age-matched values. Results were analyzed by t test. The nasolabial angle, nasal tip angle, and nasal width were abnormally wide for both techniques (p < 0.01 for both), and there was no difference between them. Nasal tip projection was greater than normal in both techniques (p < 0.01); group I had significantly greater projection than group II (p = 0.02). Columellar length as a proportion of nasal tip protrusion approached normal in group I but was significantly shorter than normal in group II (p < 0.001). Columellar width, as a proportion of nasal width, was normal for both groups. Philtral width, in proportion to nasal width, was normal in group I and abnormally high in group II (p < 0.001). This difference was significant between the two groups (p < 0.001). In a separate cohort of 10 group I patients, the nasolabial angle was measured on lateral photographs taken 1 year post-repair and at intervals to late childhood and adolescence. Nasolabial angle changed with age from obtuse to normal in 7 of 10 patients followed to 9 years of age and in 5 of 6 patients followed until age 15 years. Columellar and upper labial inclination to the vertical were measured in 7 of these patients at 3 to 4 years and again at 13 to 15 years. There was an increase in inclination of both columella and the upper lip, between the ages of 3 to 4 and 13 to 15 years, reflecting improved lip support and growth of septum and lateral cartilages.

Child↗
PubMed1998

Transnasal endoscopic excision of midline nasal dermoid from the anterior cranial base.

We recommend that every patient with a midline nasal dermoid be evaluated preoperatively by fine-cut CT scan, in the axial and coronal planes, using both bone and soft-tissue algorithms. Because of CT limitations for assessing soft tissue at the cranial base, a complementary thin-section, high-resolution, multiplanar MRI scan should be considered. Transnasal endoscopic excision of midline nasal dermoid should be used if the dermoid is located within the nasal cavity, and there is minimal or no cutaneous involvement. This approach can be combined with a short vertical midline lenticular excision of a cutaneous punctum. Vertical cutaneous excision should be limited; the best location is the nasal tip. Vertical nasal scars over the bony pyramid invariably widen no matter what intradermal suture is used. Endoscopic removal should be considered even if preoperative radiologic studies show extension to the anterior cranial fossa. Endoscopic excision could also be used to resect a dermoid extending between the dural leaves of anterior fossa. However, a combined intra-extracranial approach is necessary if the dermoid is in the falx cerebri. We agree with other authors that frozen sectioning the superior margin of the specimen should be done to ensure that there is no intracranial extension. Valsalva maneuver during endoscopic visualization of the cranial base is a valuable means of ruling out a cerebral spinal fluid leak.

Child, Preschool↗
PubMed1998

Cerebral vasculopathy and neurologic sequelae in infants with cervicofacial hemangioma: report of eight patients.

PURPOSE: To determine the association of cerebral arterial anomalies and progressive cerebral arterial occlusive disease in infants with facial hemangiomas. MATERIALS AND METHODS: The cases of eight infants (seven girls and one boy) with the diagnosis of cervicofacial hemangioma and intracranial arterial anomalies were reviewed retrospectively. Findings from clinical and imaging examinations--including cranial computed tomography, magnetic resonance imaging and angiography, and catheter angiography--were evaluated. Serial imaging findings were studied to document progressive intracranial vascular changes. RESULTS: Five patients had additional associated congenital anomalies. Seven were treated with corticosteroids, interferon alfa-2a, or both. Progressive cerebrovascular occlusive changes were documented in four of the seven patients with serial imaging findings. Four other patients (all treated pharmacologically) had MR imaging documentation of cerebral infarction, and all had consistent, acquired neurologic symptoms. CONCLUSION: Intracranial arterial anomalies can coexist with cervicofacial hemangioma. Aneurysmal and occlusive changes are potentially progressive and can result in cerebral infarction. A causative association between occlusive cerebrovascular disease and pharmacologic treatment has not been excluded.

Abnormalities, Multiple↗
PubMed1998

Cleft lip with or without cleft palate: effect of family history on reproductive planning, surgical timing, and parental stress.

OBJECTIVE: This study tested whether the presence of a family history of nonsyndromic cleft lip with or without cleft palate (NSCLP) lessens the negative impact on reproductive planning, decreases treatment anxiety, and relieves parental stress when there is a recurrent cleft. DESIGN: Sixty-one participating families, retrospectively ascertained through their children with NSCLP, were divided into two groups: those with a family history of clefting and those in which only the proband was affected. SETTING: Each family completed a questionnaire either at their home or during a clinic visit. PARTICIPANTS: Questionnaires were distributed to 117 families with an NSCLP child. Of these 117, 49 (42%) had another family member with NSCLP and 68 (58%) had no prior history of clefting. Sixty-one (52%) families returned the questionnaire and were categorized by family history. MAIN OUTCOME MEASURES: The Parenting Stress Index and the Hollingshead Index of Social Position were included with family and medical history questions in the 137-item questionnaire. RESULTS: The reproductive plans of the two groups were quite similar and were not dependent on the families' actual or perceived recurrence risks of NSCLP. The majority (85%) of the children with NSCLP underwent surgical closure at the recommended age. The two groups did not significantly differ on any score on the Parenting Stress Index, indicating a similar parental stress level between the groups. CONCLUSIONS: These findings suggest that family history does not significantly influence reproductive plans, timing of cleft repair, or stress of parents of a child with NSCLP. Further, these results indicate a need for additional psychosocial study of this population.

Adolescent↗
PubMed1998

Velopharyngeal function in nonsyndromic cleft palate: relevance of surgical technique, age at repair, and cleft type.

OBJECTIVE: The goal of this study was to determine the relative importance of surgical technique, age at repair, and cleft type for velopharyngeal function. DESIGN: This was a retrospective study of patients operated on by two surgeons using different techniques (von Langenbeck and Veau-Wardill-Kilner [VY]) at Children's Hospital, Boston, MA. PATIENTS: We included 228 patients who were at least 4 years of age at the time of review. Patients with identifiable syndromes, nonsyndromic Robin sequence, central nervous system disorders, communicatively significant hearing loss, and inadequate speech data were excluded. MAIN OUTCOME MEASURE: Need for a pharyngeal flap was the measure of outcome. RESULTS: Pharyngeal flap was necessary in 14% of von Langenbeck and 15% of VY repaired patients. There was a significant linear association (p = .025) between age at repair and velopharyngeal insufficiency (VPI). Patients with an attached vomer, soft cleft palate (SCP), and unilateral cleft lip/palate (UCLP) had a 10% flap rate, whereas those with an unattached vomer, hard/soft cleft palate (HSCP), and bilateral cleft lip/palate (BCLP) had a 23% flap rate (p = .03). Age at repair was critical for the unattached-vomer group (p = .03) but was not statistically significant for the attached-vomer group (p = .52). CONCLUSIONS: Surgical technique was not a significant variable either in aggregate or for the Veau types. Patients in the earliest repair group (8-10 months) were the least likely to require a pharyngeal flap. Early repair was more critical for HSCP and BCLP patients. There was no correlation between velopharyngeal insufficiency and Veau hierarchy. The attached vomer/levator muscle complex may be a more important predictor of surgical success than the anatomic extent of cleft.

Age Factors↗
PubMed1998

Increased apoptosis coincides with onset of involution in infantile hemangioma.

OBJECTIVE: Hemangioma is an endothelial cell tumor that grows rapidly during infancy and regresses slowly during childhood. However, little is known about the natural history of this common tumor. To gain insight into the cellular mechanisms that underlie the switch from uncontrolled growth to involution of endothelium, we investigated the extent of cellular apoptosis versus proliferation in hemangioma specimens that spanned the natural life cycle of the tumor. METHODS: We analyzed apoptosis and cellular proliferation in frozen sections from 16 hemangioma specimens using the TUNEL assay to detect apoptotic cells and the Ki67 antigen to detect dividing cells. RESULTS: Apoptosis was low in proliferative phase hemangiomas but increased fivefold in involutive phase specimens obtained from children one to four years of age. Immunofluorescence double-labeling experiments showed that at least one third of the apoptotic cells were endothelial. As expected, cellular proliferation was high in specimens up to 2 years of age but decreased significantly thereafter. Apoptosis was consistently low in nine normal skin tissues (newborn to 4 years of age) obtained from discarded pathology specimens. CONCLUSIONS: These results suggest that increased apoptosis during the second year of life can offset cellular proliferation and may be involved in initiating regression of hemangioma.

Age Factors↗
PubMed1997

Mutations involving the transcription factor CBFA1 cause cleidocranial dysplasia.

Cleidocranial dysplasia (CCD) is an autosomal-dominant condition characterized by hypoplasia/aplasia of clavicles, patent fontanelles, supernumerary teeth, short stature, and other changes in skeletal patterning and growth. In some families, the phenotype segregates with deletions resulting in heterozygous loss of CBFA1, a member of the runt family of transcription factors. In other families, insertion, deletion, and missense mutations lead to translational stop codons in the DNA binding domain or in the C-terminal transactivating region. In-frame expansion of a polyalanine stretch segregates in an affected family with brachydactyly and minor clinical findings of CCD. We conclude that CBFA1 mutations cause CCD and that heterozygous loss of function is sufficient to produce the disorder.

Alleles↗
PubMed1997

Molding therapy for infants with deformational auricular anomalies.

Congenital auricular anomalies can be categorized as either malformed or deformational. Auricular deformations most commonly affect the helix and antehelix. Surgical correction involves sutural modeling, wedge excision, reshaping and reversing cartilage segments, and morselization. Since neonatal auricular cartilage is extremely pliable, we used early splinting to correct deformational ear anomalies. Splints were constructed of leadfree, soft soldering wire threaded into polyethylene tubing and held in place with Steri-Strips. From August 1995 through February 1996 we treated 19 infants with 32 deformed auricles: 10 infants were male and 9 were female, ranging in age from 1 day to 10 weeks. Thirteen infants had both ears affected. There were 8 prominent ears, 23 lop ears, 2 Stahl's ears, and 1 infant with an inverted concha. For prominent ears, the helical-mastoid distance decreased from an average of 16.8 to 12.2 mm, after an average of 13 weeks of splinting. Fourteen corrected lop ears had a normal appearance, and 9 were improved with minor residual deformity. There was only one complication: skin irritation requiring adjustment of the prosthesis. Five children had molding started after 3 months of age and all had no significant improvement. In addition, the parents of 5 children refused therapy and 12 children had either poor compliance to therapy or were lost to follow-up. Our experience with auricular molding confirmed that it is easy, effective, and inexpensive. If molded sufficiently early, most auricular deformations should not need surgical correction in childhood.

Ear, External↗
PubMed1997

Hemangioma in twins.

A cohort of 118 twin pairs with infantile hemangioma was reviewed to determine clinical characteristics and to estimate the relative contribution of hereditary and/or environmental factors to pathogenesis. Questionnaires were sent to parents of twins in Massachusetts and Australia. Zygosity was determined by clinical questions. Accuracy of ascertainment was based on clinical and anatomic criteria. Race, gender ratio, topographic distribution, number of lesions, age of onset, and complications were all consistent with demographic data from other studies of infantile hemangioma. Of the 118 pairs, 40 were monozygotic twins (32 like-sex females and 8 like-sex males, and 78 were dizygotic (30 like-sex females, 17 like-sex males) and 31 unlike sex). The concordances in monozygotic and dizygotic female twins were 32% and 20%, respectively (p = 0.5). In like-sex male monozygotic and dizygotic pairs, the concordances were 25% and 12%, respectively (p = 0.4). These differences were not statistically significant. This study suggests that hereditary factors are not paramount in causing hemangioma. However, being female, fair-skinned, Caucasian, and having a positive family history presumably lowers the threshold for hemangiogenesis wherein extragenetic factors can trigger the appearance of this most common tumor of infancy.

Child↗