The Americleft Project: A Comparison of Short- and Longer-Term Secondary Alveolar Bone Graft Outcomes in Two Centers Using the Standardized Way to Assess Grafts Scale.

OBJECTIVE: To compare length of follow-up and cleft site dental management on bone graft ratings from two centers. DESIGN: Blind retrospective analysis of cleft site radiographs and chart reviews for determination of cleft-site lateral incisor management. PATIENTS: A total of 78 consecutively grafted patients with complete clefts from two major cleft/craniofacial centers (43 from Center 1 and 35 from Center 2). INTERVENTIONS: Secondary iliac crest alveolar bone grafting, at a mean age of 9 years 9 months (Center 1: 9 years 7 months; Center 2: 10 years 0 month). MAIN OUTCOME MEASURES: The Americleft Standardized Way to Assess Grafts scale from 0 (failed graft) to 6 (ideal) was used to rate graft outcome at two time points (T1, T2). Average T1 was 11 years 1 month of age, 1 year 3 months postgraft. Average T2 was 17 years 11 months of age, 8 years 0 months postgraft. Six trained and calibrated raters scored each radiograph twice. Reliability was calculated at T1 and T2 using weighted kappa. A paired Wilcoxon signed rank test (P < .05) tested T1 and T2 differences for each center. A Kruskal-Wallis test was used to determine the significance of differences between centers at T1 and T2. Correlation tested whether T1 ratings predicted T2. Linear regression determined possible factors that might contribute to graft rating changes over time. RESULTS: Reliability was good at T1 and T2 (interrater = .713 and .701, respectively; intrarater = .790 and .805, respectively). Center 1 scores were significantly better than those from Center 2 at both T1 (5.21 versus 3.29) and T2 (5.18 versus 3.44). There was no statistical difference between T1 and T2 scores for either center; although, there was a greater chance of bone graft score improving with completion of canine eruption and substitution for missing lateral incisors. CONCLUSIONS: Short-term ratings of graft outcomes identified significant differences between centers that persisted over time. Dental cleft-site management influenced final graft outcome.

The Americleft Project: A Proposed Expanded Nasolabial Appearance Yardstick for 5- to 7-Year-Old Patients With Complete Unilateral Cleft Lip and Palate (CUCLP).

OBJECTIVE: To develop a yardstick of reference photographs for nasolabial appearance assessments of 5- to 7-year-old patients with complete unilateral cleft lip and palate (CUCLP). DESIGN: Blind retrospective analysis of clinical records and comparison to historical controls. PATIENTS: Subjects were two groups of 6- to 12-year-olds (n = 124 and n = 135) and one group of 5- to 7-year-olds (n = 149) with nonsyndromic CUCLP from three previous Americleft studies, including cohorts from seven different cleft/craniofacial centers. INTERVENTIONS: All patients received the infant management protocols of their respective centers. Eleven trained and calibrated judges (five participated in all three studies) did blind ratings of nasolabial appearance using the Asher-McDade method. MAIN OUTCOME MEASURES: Patients receiving the most consistent ratings between judges, selected first from the groups of 6- to 12-year-olds, were used to create a pilot yardstick for eventual use in the third study of 5- to 7-year-olds. For each of the Asher-McDade categories, 8 of the 5- to 7-year-old patients receiving the most consistent scores between raters were ranked by 10 judges for a final elimination to leave three per category. RESULTS: Using this method of successive changes in rating methods, a new reference yardstick for nasolabial appearance rating was established and linked to the original Asher-McDade method as well as the single examples in a previously published yardstick for patients with CUCLP. Pilot testing using the yardstick improved reliabilities. CONCLUSIONS: Use of an expanded nasolabial yardstick of reference photographs representative of the range of possibilities of each of the five Asher-McDade categories is now available to see if reliability of these ratings can be improved.

Effect of the carbocyclic nucleoside analogue MDL 201,112 on inhibition of interferon-gamma-induced priming of Lewis (LEW/N) rat macrophages for enhanced respiratory burst and MHC class II Ia+ antigen expression.

The effects of the carbocyclic nucleoside MDL 201,112 and the purine nucleoside adenosine on the interferon-gamma (IFN-gamma)-induced priming of macrophages (m phi s) for the respiratory burst and major histocompatibility class II (MHC class II) Ia+ antigen expression were compared. Priming of purified, peritoneal m phi s from Lewis (LEW/N) rats for 18 h with recombinant rat IFN-gamma (rRaIFN-gamma) in the presence of either adenosine (100 microM) or MDL 201,112 (10 microM) resulted in a fourfold decrease in superoxide anion (O2-) production after stimulation with opsonized zymosan. Both agents were effective even when added 2 or 4 h after rRaIFN-gamma treatment. Peritoneal m phi s from LEW/N rats stimulated with LPS/rRaIFN-gamma were observed to secrete immunoreactive and bioactive TNF-alpha over 18 h in vitro and this cytokine could be dose-dependently inhibited by MDL 201,112. MDL 201,112 did not bind to classical A1 or A2 receptors on rat brain homogenates. Physiological levels of adenosine deaminase, or treatment with the nucleoside transport inhibitor dipyridamole, reversed the effects of adenosine; however, these agents at physiological concentrations had little or no effect on the inhibition of O2- release mediated by MDL 201,112. Furthermore, incubation of LEW/N m phi s for 18 h in vitro with rRaIFN-gamma resulted in significant enhancement of MHC class II Ia+ antigen expression, and these levels could be blocked by nearly 50% by either MDL 201,112 (10 microM) or adenosine (100 microM). MDL 201,112 and adenosine were also effective in decreasing m phi opsonized zymosan-stimulated O2- levels and MHC class II Ia+ antigen expression in vivo. The effects of MDL 201,112 on the down-regulation of heat-killed M. tuberculosis-activated LEW/N m phi MHC class II Ia+ antigen expression in vitro appear to be mediated by a novel pathway, because there was no rank order of potency of ADO A1 or A2 agonist/antagonists (CCPA, NECA, XAC, or CPT) in our in vitro system. In summary, our data provide compelling evidence that immunoregulatory carbocyclic nucleoside analogues such as MDL 201,112 or adenosine appear to regulate LEW/N rat m phi activation through novel molecular mechanisms and may have important therapeutic implications for acute and chronic inflammatory diseases.

Quantitative and qualitative immunohistochemical detection of myc and src oncogene proteins in normal, nodule, and neoplastic rat liver.

This study examined the possibility of using an immunohistochemical technique to detect the expression of myc and src oncogene proteins (ops) in livers of male Sprague-Dawley rats after treatment with the carcinogen diethylnitrosamine (with or without phenobarbital promotion) or untreated. We found that the majority of nodules and tumors from these livers stained for myc and src ops, indicating that myc and src expression did occur in these structures. These results were expected, since myc and src expression has been previously observed by others using different techniques. However, in our study, myc and src op staining was also noted in normal liver areas from rats in any of the four treatment groups (DENA, DENA + PB, PB alone, or untreated). The staining pattern of normal liver was different for each oncogene probe but was consistent within the four groups. In most cases, oncogene expression of normal liver occurred at sites of abnormal (but non-neoplastic) hepatocytes. The method reported here used both a qualitative technique of op expression analysis and a quantitative method using a Zeiss computer-driven image analysis system.

Dose-response relationship of phenobarbital promotion of diethylnitrosamine initiated tumors in rat liver.

The dose-response relationship was determined in rats for the enhancement by phenobarbital of diethylnitrosamine (DENA)-initiated neoplastic nodules and hepatocellular carcinomas. Male Sprague-Dawley rats received a single oral dose of either 80 mg/kg DENA or water. Seven days later, the animals were divided into groups that started to receive 0, 62.5, 125, 250, 500 or 1000 ppm sodium phenobarbital in the drinking water. Animals from each group were killed at 48 and 70 weeks after the DENA. No significant difference was observed in the low response of neoplastic nodules among the DENA-initiated groups. The incidence of DENA-initiated hepatocellular carcinoma was enhanced at 70 weeks by 250, 500 and 1000 ppm sodium phenobarbital but not by 62.5 or 125 ppm sodium phenobarbital. Equal enhancement of the incidence of hepatocellular carcinomas was obtained with 250, 500 and 1000 ppm sodium phenobarbital. In non-DENA-initiated rats, phenobarbital did not induce neoplastic nodules or hepatocellular carcinomas. Our results suggest that a daily dose of at least 250 ppm sodium phenobarbital is required in order for it to exert tumor promoting activity.

Myeloid hyperplasia in the SENCAR mouse: differentiation from granulocytic leukemia.

The term myeloid hyperplasia has been used interchangeably with many other terms to describe an increased production of granulocytes, megakaryocytes, and erythrocytes in the spleen and other organs in the mouse. This process is occasionally misdiagnosed as granulocytic leukemia. This paper reviews some of the terms used interchangeably with myeloid hyperplasia and describes criteria that can be used to differentiate myeloid hyperplasia from granulocytic leukemia. Additionally, the results of a study in which myeloid hyperplasia was induced following the formation of skin tumors in SENCAR mice is discussed. In this study, positive correlations were found between skin lesions, the spleen weight, and histologic appearance of the spleen. The liver rarely showed microscopic changes of myeloid hyperplasia unless the spleen weighed at least 1.0% of the body weight.

Epidermal hyperplasia in mouse skin following treatment with alternative drinking water disinfectants.

Female SENCAR mice were treated with aqueous solutions of hypochlorous acid (HOCl), sodium hypochlorite (NaOCl), chlorine dioxide (ClO2), and monochloramine (NH2Cl) by whole body exposure (except head) for a 10-min period for 4 days in the first experiment and for 1 day (except NH2Cl) in the second experiment. Animals were sacrificed the day following the last treatment (experiment 1) or on day 1, 2, 3, 4, 5, 8, 10, and 12 following treatment (experiment 2), and skin thickness was measured by light microscopy at X400 by use of an eyepiece micrometer. Concentrations of disinfectants were 1, 10, 100, 300, and 1000 mg/L, for experiment 1 and 1000 mg/L for experiment 2. Thickness of the interfollicular epidermis (IFE) for control animals was 15.4 +/- 1.5 micron. After 4 days of treatment at 1000 mg/L, HOCl and ClO2 increased thickness to 39 +/- 7.0 and 40.2 +/- 11.8, and NaOCl increased thickness to 25.2 +/- 6.1 micron. Only HOCl and ClO2 were tested at 300 mg/L, yielding an IFE thickness of 30.0 +/- 13.1 and 16.8 +/- 0.8 micron, respectively. The response to HOCl was found to be dose-related; the minimally effective dose was 100 mg/L. In earlier, preliminary tests to determine optimum treatment schedule, the response to HOCl appeared to be maximal after 4 days of treatment and tended to decrease with further treatment. The time-course study following a single treatment of 1000 mg/L HOCl, however, showed a progression of IFE thickening of from 18.3 +/- 1.4 at 1 day to 30.8 +/- 8.0 at 8 days, decreasing to 19.1 +/- 6.2 micron at 12 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Dominant lethal effects of subchronic acrylamide administration in the male Long-Evans rat.

Acrylamide, a widely used vinyl monomer, is well known as a neurotoxin but inactive as a mutagen in bacterial test systems. The experiments reported demonstrate that after subchronic oral dosing in the male rat, acrylamide induced significant elevations in both pre- and post-implantation loss following dominant lethal testing. These effects were seen at doses which failed to produce clinical or pathological evidence of neurotoxicity. In an accompanying cytogenetic study, no increase in chromosome aberrations was observed in spermatogonia or spermatocytes of treated animals. When spermatocytes from treated spermatogonial stem cells were analyzed, reciprocal translocations (4) were observed in the treated animals and not in the control, but the significance of this result still needs to be established.

Multidisciplinary management of Crouzon syndrome.

The comprehensive management of Crouzon syndrome in a 14-year-old girl has been presented. Because of the complexity of the facial and associated problems, a multidisciplinary approach is necessary to provide maximum functional and esthetic results; however, with such a cooperative interdisciplinary effort, the improvement and benefits derived for these patients are rewarding to all concerned.

Frequency and antimicrobial susceptibility of Staphylococcus species isolated from canine pyodermas.

Specimens obtained from pyogenic skin lesions of 210 dogs were culturally examined for staphylococci. A total of 215 isolates of staphylococci were biotyped, using the biochemical tests contained in a commercial staphylococcal identification system. Of 201 coagulase-positive isolates, 197 were identified as Staphylococcus intermedius, 3 as S aureus, and 1 as S hyicus. Of 14 coagulase-negative isolates, 5 were identified as S epidermidis, 5 as S xylosus, 3 as S simulans, and 1 as S hominis. Antimicrobial susceptibility tests were done on all staphylococcal isolates, using the standard disk-diffusion method. Staphylococcus intermedius isolates were susceptible to cephalothin, methicillin, and gentamicin. Resistance to ampicillin, penicillin G, and tetracycline was frequent. Antibiotic resistance was not associated with the depth of skin infection. Resistance to ampicillin, penicillin, tetracycline, and trimethoprim-sulfamethoxazole was not associated with previous antibiotic use. Increased resistance to chloramphenicol, clindamycin, and erythromycin was associated with previous antibiotic therapy. Antimicrobial susceptibilities of the other Staphylococcus species isolated are reported, but the small numbers of these species precluded making meaningful comparison with S intermedius.

Glucagon-producing pancreatic endocrine tumors in two dogs with superficial necrolytic dermatitis.

A newly recognized disease in dogs, ulcerative dermatosis associated with diabetes mellitus (diabetic dermatopathy), was diagnosed in 2 dogs with pancreatic endocrine tumors that had immunohistologic evidence of glucagon production. Dogs developed diabetes mellitus in the later stages of the illness, months after the skin disease was first observed. Liver disease was identified and characterized by high serum alkaline phosphatase and alanine transaminase activities. Clinically, erythema and crusting involved the footpads, the face, perioral and genital skin, and ventrum. Histologically, skin lesions were intercellular and intracellular edema and necrosis of the upper half of the epidermis and diffuse parakeratosis. Clinically and histologically, skin lesions closely resembled necrolytic migratory erythema of people, a skin disease that usually is associated with a glucagon-secreting pancreatic endocrine tumor and diabetes mellitus (glucagonoma syndrome): The morphologically descriptive term, superficial necrolytic dermatitis, was preferred over the previously proposed names hepatocutaneous syndrome and diabetic dermatopathy, which each connote only a single feature of the disease.

Growth in width following pharyngeal flap surgery.

The data reported in this investigation can be summarized in the following statements: Pharyngeal flap surgery in this sample of 17 cleft patients did not appear to produce or be related to any dramatic alterations in growth in width of the jaws or dental arches following the surgery. The only significant finding was related to an increase in basal maxillary width following flap surgery, a result opposite that described as typical of nasorespiratory obstruction. In general, the more interesting and significant relationships found between pharyngeal flap surgery and dentofacial growth in studies in the vertical and sagittal planes were not found in this evaluation of growth in width. Nasal cavity width changes with growth could not be related to the flap, but point out the possible usefulness of evaluating data such as these grouped according to cleft type.

Facial growth following pharyngeal flap surgery: skeletal assessment on serial lateral cephalometric radiographs.

The purpose of this study was to evaluate the effect of pharyngeal flap surgery on subsequent facial growth in patients with cleft lip and/or palate. Pharyngeal flap surgery is used in such patients to partially obliterate the velopharyngeal port, reducing hypernasal speech. Thirty-four patients (18 with cleft palate only, 16 with unilateral cleft lip and palate) were selected from the longitudinal growth study of the H.K. Cooper Clinic. Seventeen of these (9 with cleft palate only, 8 with unilateral cleft lip and palate) underwent pharyngeal flap surgery between the ages of 5 and 7 years. The other seventeen patients did not undergo pharyngeal flap surgery and served as a control group for this study. Serial lateral cephalometric radiographs were traced and digitized (ages 3 to 5, preflap; ages 7-10, postflap). Fourteen skeletodental measurements (six angular, six linear, two derived) were taken to determine whether pharyngeal flap surgery may be related to subsequent facial growth changes. The data from the 17 flap patients were compared with control data taken from the other seventeen patients. The groups were matched for sex, cleft type, and similarity of presurgical mandibular growth direction (facial axis angle). Results obtained demonstrate several significant areas of change following flap surgery, including a decrease in facial axis angle, an increase in Frankfort-mandibular plane angle, an increase in incremental gains in lower anterior face height, and increased retroclination of upper and lower incisors in the flap group as compared to their matched controls.

Effect of cuspid positioning in the cleft at the time of secondary alveolar bone grafting on eventual graft success.

This investigation was to determine the relationship between the success of secondary alveolar bone grafting and the position of the permanent cuspid relative to the cleft at the time of grafting. In this retrospective study utilizing periapical radiographs take on cleft patients to evaluate bone grafting results, the subjects were patients treated at the Lancaster Cleft Palate Clinic, a private institution specializing in the care of cleft patients. Sixty-seven patients (20 BCLP; 47 UCLP) were selected for this study based on availability of quality radiographs and a minimum of 6-month post-surgical follow-up. All patients underwent alveolar bone grafting (mean age, 10 years 7 months). Presurgical radiographs were taken within 3 months of the operation. Post-surgical radiographs were taken to evaluate the outcome of grafting (mean follow-up, 2 years 10 months). Radiographs were traced and digitized on a total of 86 cleft sites. Presurgically, a ratio was used to determine the amount of cuspid crown emerged through the alveolus into the cleft site relative to the anatomic cuspid-crown length. Post-surgically, ratios of bone support for the teeth mesial and distal to the cleft were established by dividing the amount of root covered by bone by the anatomic root length. Ratios expressing the height of alveolar crest relative to the cementoenamel junction (CEJ) of adjacent teeth and amount of alveolar notching relative to the mesial tooth root length were also evaluated. Linear regressions of each of the five ratios of graft outcome on the cuspid-eruption ratio were done. No significant correlations could be found between final graft success and the amount of cuspid crown exposed in the cleft at the time of grafting. Cuspid position could not be shown to be a significant factor in determining graft success.

Sex differences in craniofacial growth from one month to ten years of cleft lip and palate.

This study is based on serial lateral X-ray headfilms from one month to ten years for 64 children with unilateral cleft of lip and palate (UCLP), 32 children with bilateral cleft lip and palate (BCLP), and 78 children with cleft palate only (CPO). Measurements for eleven dimensions and three angles were obtained. These included measurements for the cranial base, facial heights, midfacial depths, and the mandible. The 10-year period was divided into infancy, i.e., birth to one year; early childhood, i.e., one to six years; and mid childhood, i.e., six to ten years. All measurements were evaluated on the basis of growth time and growth velocity. The shape of the cranial base as seen in the sellar angle was influenced by clefting whereas the size, i.e., the clival length and the anterior cranial base length were affected by sex. No sex differences were observed for the angle S-N-A. Face heights, midfacial depths, and mandibular body length were all found to be larger for males.

Comparison of velopharyngeal growth patterns between cleft lip and/or palate patients requiring or not requiring pharyngeal flap surgery.

This investigation compares the patterns of velopharyngeal growth in cleft lip and/or palate patients. Those who had velopharyngeal competence and acceptable speech are compared with those who presented with velopharyngeal incompetence requiring pharyngeal flap surgery or prosthesis later. Lateral cephalograms of 30 cleft palate only (CPO), 35 unilateral cleft lip and palate (UCLP), and 20 bilateral cleft lip and palate (BCLP) children of the Lancaster Cleft Palate Clinic were studied. These records were taken at 6 month intervals during the first 2 postnatal years and annually thereafter up to 6 years of age. Soft tissue landmark points in the velopharyngeal region were digitized. Length and thickness of the soft palate and height and depth of the nasopharynx were measured. Evaluation of the growth curves of these four cephalometric variables indicated only two significant differences between children who later required pharyngeal flap surgery and those who did not. These differences were found in the growth in length of the soft palate of the CPO group and in the growth in depth of the nasopharynx of the BCLP group. Based on the present cephalometric data, it is impossible to predict at an early age those cleft lip and/or palate patients who will later require pharyngeal flaps.