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Objective: To objectively evaluate the nasal function in adults operated on for unilateral cleft lip and palate with one-stage or two-stage palate closure. Design: The population consists of all unilateral cleft lip and palate patients born from 1960 to 1987 and treated at the Cleft Lip and Palate Center, Uppsala University Hospital, Sweden. The patients were treated according to the same protocol except for palate closure, which was performed in one stage until 1977 and in two stages thereafter. Eighty-three patients participated. Mean follow-up time after primary surgery was 32 years. An age-matched control group underwent the same examinations. Main Outcome Measures: Nasal minimum cross-sectional area (cm²) and volume (cm(3)) were assessed (acoustic rhinometry). Airflow resistance (Pa s/ cm(3)) (rhinomanometry), peak inspiratory flow (L/min) (peak nasal inspiratory flow), and number of identified odors (Scandinavian Odor Identification Test) were determined. Results: The cleft side of unilateral cleft lip and palate patients had significantly lower values for all parameters compared with controls (p <.001). No difference was found between one-stage and two-stage procedures in values for the cleft side. However, the nasal area and volume of the noncleft side were significantly larger in patients who underwent one-stage as compared with two-stage procedures (p <.05). Conclusion: The nasal airway of unilateral cleft lip and palate patients demonstrates a wide range of impairments that can be quantified by objective measurements. However, the measurements used did not differentiate between patients operated on with the one-stage and two-stage procedures except for values of the noncleft side. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the association between cleft size in infancy and crossbite at 5 years of age in children with cleft palate (CP) and unilateral cleft lip and palate (UCLP). DESIGN: Retrospective study. SETTING: University Hospital, Uppsala, Sweden. PATIENTS: Dental study models of 80 consecutive children, 51 children with CP and 29 children with UCLP, born between 1990 and 1999 were analyzed. INTERVENTIONS: Lip repair at 3 to 4 months in UCLP children. Primary soft palate repair at 6 to 10 months and secondary hard palate closure at 25 to 26 months of age. MAIN OUTCOME MEASURES: Maxillary arch dimensions and cleft size were measured on infancy dental casts. At follow-up at 5 years, crossbite scores were registered on dental study models. RESULTS: The cleft dimensions in infancy showed large interindividual variation. Mean posterior cleft width was larger in UCLP children than in children with CP. The UCLP group also had significantly more crossbite at 5 years than the CP group. No significant association was noted between initial cleft size and crossbite scores at 5 years in the CP group. For the UCLP group, larger cleft widths at the level of the cuspid points were significantly associated with less anterior and posterior crossbite. CONCLUSIONS: The findings support the hypothesis that cleft size in infancy affects early outcome with respect to crossbite in children with UCLP, but not in children with CP. [ABSTRACT FROM AUTHOR]

To compare the receptor patterns for mitogenic and non-mitogenic substances, surface glycoproteins of human lymphocytes were labelled with the lactoperioxidase-catalysed iodination technique and with a galactose oxidase-tritiated sodium borohydride technique. Labelled cells were detergent-solubilized and the lysates were allowed lo react with insolubilized purified mitogenic lectins, phytohaemagglulinin, lcucoagglutinin and an insolubilized non-mitogenic lectin, oxidized leucoagglutinin. Lectin-reactive proteins were eluted with sodium dodecyl sulphate (SDS) buffer. Cell membrane components reactive with anti-lymphocyte globulin (ALG) were retrieved b) indirect immunoprecipitation with protein-A-bearing staphylococcus Cowan 1 strum (SuCI). Lectin- and ALG-reactive proteins were analysed by SDS polyacrylamide gel electrophoresis. Iodinated glycoproteins regularly showed lour major components with molecular weights of 120,000, 70,000, 60,000 and 43,000 daltons, respectively on 7%, gets. An additional broad peak in the molecular weight range 20,000-35,000 daltons was found on 10% gets. Tritiated glycoproteins also showed four major components with MW 120,000, 70,000, 60.000 and 42,000 respectively. which reacted with lectin und ALG. In addition, ALG reacted with some glycoproteins with MW between 150,00 and 230,000 daltons. On 10% gels additional lectin-and ALG-binding glycoproteins with MW around 30,000 daltons were found. The similarity in structures bound by mitogenic and non-mitogenic substances indicates that lymphocyte activation may depend on some properly conferred by the mitogen. [ABSTRACT FROM AUTHOR]

Background: The Uppsala Craniofacial Center has been treating patients with unilateral cleft lip deformity using the lip repair technique described by Tord Skoog. The aim of this study was to determine complications after lip surgery and the incidence and indications for lip revisions in all patients born with unilateral cleft lip from 1960 to 2004., Methods: All patients who were born from 1960 to 2004 with unilateral cleft lip, cleft lip and alveolus, or cleft lip and palate and underwent lip repair were studied retrospectively. The timing, indication, complications of the primary procedure, and type of secondary surgery were recorded. Kruskal-Wallis and Fisher's exact tests were used, with Bonferroni correction., Results: The study included 443 patients. The total rate of early surgical complications was 6 percent (n = 26). Secondary surgery for short upper lip was performed in 3.8 percent (n = 17), 8.4 percent (n = 37) underwent reduction of excess vermillion, 8.6 percent (n = 38) underwent scar revision, 11 percent (n = 51) underwent revision for incongruent vermillion-cutaneous border, and 10 percent (n = 45) underwent revision for other indications. Altogether, 45 percent had no secondary revisions., Conclusion: In conclusion, the Skoog lip repair is associated with a low total revision rate, and a short-lip deformity is rare., Clinical Question/level of Evidence: Therapeutic, IV.

Objective : To evaluate the importance of dental status for long-term outcome after alveolar bone grafting in patients with unilateral cleft lip and palate. Design : Retrospective longitudinal study. Setting : Cleft lip and palate-craniofacial center, Uppsala University Hospital, Sweden. Patients : A total of 67 consecutive patients with unilateral complete cleft lip and palate. Interventions : Secondary alveolar bone grafting, prior to the eruption of the permanent canine, was performed at the average age of 10.0 years (range, 8.5 to 12.0 years). Main Outcome Measures : Alveolar bone height was evaluated with the modified Bergland index at 1 and 10 years after surgery. Results : Of the patients, 97% had modified Bergland index grade I and the remaining 3% had modified Bergland index grade II at 1 year after surgery. At 10 years' follow-up, 43% showed modified Bergland index grade I; 55%, modified Bergland index grade II; and 2% (one patient), modified Bergland index grade III. The degree of dental anomalies in the cleft area, such as enamel hypoplasia, incisor rotation, incisor inclination, canine inclination, and oral hygiene registered preoperatively, all correlated negatively to the modified Bergland index at 10 years after surgery. Enamel hypoplasia (ρ = 0.70195, P < .0001), followed by canine inclination (ρ = 0.55429, P < .0001), showed the strongest correlation to reduced bone height in the cleft area. Conclusions : In patients with unilateral cleft lip and palate, excellent results from secondary alveolar bone grafting in terms of bone height in the alveolar cleft tend to decrease with time. This seems to be correlated with factors that might to some extent be treated preoperatively through adequate planning and execution of the orthodontic treatment.

Objective : To study early changes in cleft size and maxillary arch dimensions and to evaluate these changes in relation to performed surgical procedures. Design : Retrospective longitudinal study. Setting : The Cleft Lip and Palate Center, Uppsala University Hospital, Sweden. Patients : Dental study models of 79 consecutive children (28 with unilateral cleft lip and palate, 39 with cleft palate, and 12 with Pierre Robin sequence) were analyzed. Interventions : Lip repair at 3 to 4 months, soft palate repair at 6 to 10 months, and hard palate repair at 25 to 26 months of age. Main Outcome Measures : Cleft size was measured before each surgical intervention up to 2 years and arch dimensions were measured before each surgical intervention and at 5 years. Results : Cleft widths decreased from infancy up to 2 years, but the anteroposterior cleft length in cleft palate was unchanged. Arch widths between cuspid points (C-C1) and tuberosity points (T-T1) and also the change over time in C-C1 and T-T1 differed significantly between the groups from infancy up to 5 years. Conclusions : Cleft widths decreased after lip closure and/or soft palate closure. The children with unilateral cleft lip and palate had wider maxillary arch dimensions than the children with cleft palate or Pierre Robin sequence during the first years of life, but after hard palate closure the transverse growth was reduced in the children with unilateral cleft lip and palate. At 5 years the children with unilateral cleft lip and palate had similar maxillary widths as the children with cleft palate and/or Pierre Robin sequence.

Objective : To identify factors related to quality of life (QoL) and satisfaction with nasal appearance among patients treated for unilateral cleft lip and palate (UCLP). Design : Cross-sectional population study with long-term follow-up. Patients/Settings : All patients with UCLP born between 1960 and 1987, treated at Uppsala University Hospital, were invited (n  =  109); 86 (79%) participated. Mean follow-up time was 35 years. Main Outcome Measures : Quality of life was measured with Short Form-36 (SF-36) and analyzed using mental and physical cluster scores (MCS and PCS). Nasal appearance was self-assessed with the "Satisfaction With Appearance" questionnaire and by panel judgment. Multivariate regression analyses explored endogenous factors (age, gender, infancy cleft width, nasal function, nasolabial appearance) and exogenous factors (marital status, number of children, education level, operation method, number of rhinoplasties performed). Results : A larger cleft width in infancy was associated with less satisfaction with nasal appearance as adults. A lower mental health QoL was associated with less satisfaction with nasal appearance. Despite female gender being linked to less satisfaction with nasal appearance, it was associated with higher mental health QoL. Higher resistance during nasal breathing was associated with lower physical health QoL. Conclusions : Gender and infant cleft width may affect QoL and satisfaction with nasal appearance among adults. They are potential predictive factors for satisfaction with nasal appearance and QoL during adulthood. The correlation of nasal function impairment and decreased physical health QoL underlines the importance of treatment of nasal symptoms in these patients.

This retrospective, long-term study evaluated the influence of two different treatment protocols, one including infant periosteoplasty, on facial growth and occlusion in patients with complete bilateral cleft lip and palate (BCLP). Thirty-five patients with records of 5-, 8- and 16-19-year-olds were included. Sixteen of these received infant periosteoplasty (BCLP-pp) to the cleft alveolus in conjunction with lip repair and a one-stage closure of the palate. The remaining 19 patients with a two-stage closure of the palate did not have an infant periosteoplasty (BCLP-np). The bone formation induced by periosteoplasty in the BCLP-np group was insufficient and both groups had secondary bone grafting to the alveolar clefts before the eruption of the lateral incisor or the canine. Facial growth was evaluated with cephalometry at the recorded ages and dental arch relationships with the Huddart and Bodenham crossbite scores at the age of 16-19 years. Until 19 years a significant retrusion of the maxillary position (SNA) was observed in both groups. At 16-19 years of age there was no significant difference of maxillary protrusion (SNA), intermaxillary position (ANB), maxillary length (ss-pm) or vertical skeletal relationships (ML/NSL, Ml/NL) between the two groups. However, a significant difference of the crossbite scores was found. The BCLP-pp group did not show more facial growth problems but more malocclusion and the insufficient bone formation of the alveolar clefts after infant periosteoplasty required a secondary bone grafting.

Malmö and Uppsala have been regional centres for the treatment of cleft lip and palate since the beginning of the 1950s. We have about 80 new cases every year and most patients have conventional oronasal clefts, either cleft lip and palate or isolated cleft palate. During a 10-year period we have come across four patients who have had varying degrees of midface dysplasia combined with intracranial anomalies. One child died at an early age, but the other three children were given medical substitution of hypopituitarism and have had their clefts reconstructed.

This article presents a treatment strategy for early release of interalveolar synechiae, aiming to facilitate early oral feeding and prevent temporomandibular joint ankylosis.The treatment results of 2 patients with van der Woude syndrome were retrospectively studied. Both patients underwent early surgical release of interalveolar synechiae under general anesthesia through fiberscopic nasal intubation. The 2 patients were treated at the ages of 6 and 14 days, respectively. The interincisival distances increased from 5 and 6 mm preoperatively to 11 and 10 mm immediately after surgery. This was increased further to 25 and 20 mm at long-term follow-up (6 and 24 months).In conclusion, synechiae between the upper and lower jaws can be safely treated at a very early age under general anesthesia with fiberscopic nasotracheal intubation. The purpose of early intervention in these cases is to facilitate oral feeding and prevent temporomandibular joint ankylosis.

Objective: To objectively evaluate the nasal function in adults operated on for unilateral cleft lip and palate with one-stage or two-stage palate closure., Design: The population consists of all unilateral cleft lip and palate patients born from 1960 to 1987 and treated at the Cleft Lip and Palate Center, Uppsala University Hospital, Sweden. The patients were treated according to the same protocol except for palate closure, which was performed in one stage until 1977 and in two stages thereafter. Eighty-three patients participated. Mean follow-up time after primary surgery was 32 years. An age-matched control group underwent the same examinations., Main Outcome Measures: Nasal minimum cross-sectional area (cm(2)) and volume (cm(3)) were assessed (acoustic rhinometry). Airflow resistance (Pa s/cm(3)) (rhinomanometry), peak inspiratory flow (L/min) (peak nasal inspiratory flow), and number of identified odors (Scandinavian Odor Identification Test) were determined., Results: The cleft side of unilateral cleft lip and palate patients had significantly lower values for all parameters compared with controls (p < .001). No difference was found between one-stage and two-stage procedures in values for the cleft side. However, the nasal area and volume of the noncleft side were significantly larger in patients who underwent one-stage as compared with two-stage procedures (p < .05)., Conclusion: The nasal airway of unilateral cleft lip and palate patients demonstrates a wide range of impairments that can be quantified by objective measurements. However, the measurements used did not differentiate between patients operated on with the one-stage and two-stage procedures except for values of the noncleft side.

We describe a technique by which the intravelar veloplasty was reinforced by including the superior part of posterior pillars and their palatopharyngeal muscle sheet in patients with cleft lip and palate. Our aim was to increase the functional length and strength of the velum and to reduce nasal emission and the need for pharyngeal flaps. Since 1990 more than 200 patients have been operated on in this way at Uppsala University Hospital. This is a retrospective follow-up of 162 consecutive patients operated on by two senior surgeons between 1990 and 2000. We describe the technique, timing, and operative observations as well as the outcome and the need for revision of the palatoplasty in some cases because of complications. To facilitate speech, 21 patients born between 1990 and 1997 (16%) were provided with a pharyngeal flap.

A retrospective study was conducted on 98 consecutive patients who had reduction mammaplasty done by different techniques during 1995, to find out the effect of dextran 70 on operative blood loss and postoperative complications. The most common procedure was reduction with a laterally based flap (n = 67) followed by a Lejour vertical mammaplasty (n = 15) and a medially based flap (n = 12). Four had other operations. Dextran 70 was given peroperatively to 64 patients and their median (range) blood loss was 350 (30-1000) ml and drainage volume 80 (10-465) ml. In 33 patients not treated with dextran 70 the median (range) blood loss was 200 (25-650) ml and the drainage volume 40 (0-115) ml. Ten patients developed major complications and 16 minor complications and there was no difference in the complication rate between those given dextran 70 (18/64, 28%) and those who were not (8/33, 24%), p = 0.8. Complications were no more common in smokers, overweight patients or those whose breasts were reduced by more than 1500 g, but there was a tendency to find more complications after the Lejour vertical mammaplasty. In conclusion, the study shows that patients undergoing mammaplasty and given Dextran 70 have an acceptable blood loss and drainage. In patients with a high risk of developing thromboembolism there is a need for a prophylactic agent and this study shows that dextran 70 may safely be used during reduction mammaplasty.

Closure of the palate is an operation with a higher risk of postoperative hypoxaemia than other plastic surgical procedures. An increase in anaesthetic complications was noticed among our children with a cleft palate who were operated on with a palatoplasty, and this was further investigated. The records of 154 patients operated on between 1979 and 1996 were eligible for the study. A total of 128 had isolated cleft palate (ICP), 19 had Pierre Robin syndrome (PRS), and seven had other identified syndromes (IS). The results showed that the risk of anaesthetic complications was four times greater when the operation was done when the child was less than 1 year old, and there was a sixfold increase when a more elaborate velopharyngoplasty technique was used. Children with Pierre Robin syndrome were further classified according to the degree of neonatal difficulties. The 12 children with most severe problems were at increased risk. When the diagnostic criteria as well as the type of operation were taken into account the incidence of anaesthetic complications was 7/11, which was the highest risk encountered in the present study. When the first operation on the palate in children with Pierre Robin syndrome is planned, it should be based on a classification of neonatal problems and an investigation of their clinical condition. In children at risk the palatoplasty procedure should be postponed until the age of 12-18 months.

An experimental study was done in two rabbits to establish whether the early stages of cartilage generation involves stimulation via the platelet-derived growth factor beta receptor (PDGFR-beta). Rib perichondrium was dissected off and transplanted to the knee joint. The perichondrial grafts were removed for microscopic investigation at day 0 and day 6 and kept frozen until analysed by immunohistochemistry and in situ hybridisation for the presence of PDGF beta receptor protein and mRNA, respectively. Samples from day 0 showed sparse cells with a positive immunohistochemical reaction. In samples from day 6 there were signs of perichondrial proliferation and chondroid maturation and a more widespread immunohistochemical staining reaction could be seen mainly on proliferating perichondrial cells, but also on some chondrocytes. In situ hybridisation confirmed the expression of PDGF beta receptor mRNA in the same areas of serial sections. These findings may indicate that PDGF beta receptor activity is part of the early response after autotransplantation of perichondrium.

Peptides of 11 and 15 residue lengths were synthesised according to the sequence of the N-terminal region of the human MC1 melanocyte stimulating hormone receptor. The peptides were conjugated to thyroglobulin and used for preparation of antisera in the rabbit. Each of the conjugates raised antisera which showed high titre and specificity for its respective peptide antigen when evaluated in an ELISA test. Both types of antisera immunostained MC1 receptor expressing COS-7 cells. By contrast, the sera did not stain control COS-7 cells not expressing the MC1 receptor. Moreover, preimmune sera or antiserum preadsorbed with its respective peptide did not stain the MC1 receptor expressing cells. The antisera were used to immunostain sections of normal human skin, as well as samples of cutaneous malignant melanoma tumours obtained from a patient. The cells of the melanoma tumours were very strongly immunostained with the MC1 receptor antisera. By contrast, melanocytes which were present in the normal skin could not be visualised with our antisera.

Reconstruction of cartilage with perichondrium depends on the chondrogenic property of the perichondrial fibrocytes. The present investigation concerns the conditions for the differentiation of fibrocytes into chondrocytes both in vivo and in vitro. For the in vivo studies specimens of rib and auricular perichondrium from adult rabbits were wrapped round silicon rods which were enclosed in dialysis bags. One was placed in the suprapatellar pouch of the knee joint and one was placed intraperitoneally in each rabbit. After two months the bags were extracted, the perichondrium prepared for microscopic examination, and the chondrogenesis evaluated. In vitro the perichondrium was divided into small pieces and incubated with tissue culture medium. The medium was supplemented with fetal calf serum, together with epidermal growth factor, platelet derived growth factor, synovial fluid, or with human serum albumin (control group). After three weeks the explants were prepared for microscopy. Chondrogenesis was judged by the degree of cellular enlargement, capsule formation, deposition of matrix, and activation of the outer fibrocytic layer. In vivo, good cartilage development was found in all specimens placed in the knee joint but, in those placed intraperitoneally, little if any chondrogenesis was seen. In vitro profound differentiation occurred in all cultures supplemented with epidermal growth factor and platelet derived growth factor. An equivalent differentiation was found in perichondrium that had been incubated with synovial fluid. We conclude that the differentiation of perichondrial fibrocytes is initiated in vitro by growth factors. In addition, we have shown that synovial fluid contains factors that promote and enhance the development of cartilage from perichondrium.

A series of 127 patients treated for cancer of the biliary tract during the period 1965-1974 was studied with a follow-up period of at least five years. The mean age was 66 years and the female:male ratio was 3:1. An early diagnosis of biliary tract carcinoma is difficult and the prognosis unfavourable although not hopeless. The surgical treatment given in the present series included a radical approach whenever possible. In the total series 56 patients died within a month, 24 lived for more than one year, 9 longer than three years and 5 longer than five years and 3 are still alive. A mean survival time of 25.6 months was reached when a radical operation was attempted while a palliative procedure gave a mean survival time of 5.5 months. These figures indicated that a careful selection of patients for an attempt of radical surgery should be done since removal of the tumour gives a more effective palliation, often a longer survival time, an improvement of quality of live and in a few patients cure.

Nipple discharge, especially the blood-stained type, is regarded as an important symptom in breast disease. In many reports the high incidence of malignancy is stressed and an active surgical approach has often been recommended. In this series of 80 women with nipple discharge the type of secretion and the result of exfoliative cytology were evaluated. Three women had cancer but the nipple discharge was important for the diagnosis in only one case. Six women had papilloma and in all the nipple discharge was essential for the diagnosis. Fibroadenosis and duct ectasia were the most common diagnoses. The blood-stained secretion was due to fibroadenosis in about half of the cases. No cancer was found in 46 women with a serous secretion. When a tumour is present nipple discharge is of little importance for the diagnosis and treatment. In the absence of a tumour and when exfoliative cytology gives no suspicion of cancer and no atypical cells or papillomatous clusters are present, an expectant attitude towards surgery seems satisfactory. With such an approach many surgical biopsies prove unnecessary, but a prerequisite is an organized follow-up.

In an experimental study the cartilaginous protential of the rabbit ear perichondrium has been compared with that of the rib in vivo and in vitro. Perichondrium was transferred as free autologous grafts to the subcutaneous tissue on the scalp and as loose bodies into the knee joint. The presence of cartilage in the grafts was examined after six weeks. In vitro explants of rabbit perichondrium from the ear and the rib were maintained in an organ culture system. The presence of cartilage was analyzed after one to three weeks. Rabbit perichondrium from the rib appeared to have a greater cartilaginous potential than that from the ear both in vivo and in vitro. Chondrogenesis in perichondrium was demonstrated in vitro.

Patients with carcinoma of the hepatic duct junction often present the surgeon with a difficult problem. If at all possible radical surgery may be performed either as a resection of the tumour and an anastomosis according to Roux-en-Y or a resection of the left or right hepatic lobe together with the obliterated hepatic duct or ducts. The present series consists of 17 patients treated for cancer of the hepatic duct junction during the period 1965-1974 with a follow-up period of at least five years. The surgical treatment given included a radical procedure in 8 cases, a palliative procedure in 7 cases and in 2 cases surgery of the hepatic ducts was not possible. Radical procedures included 4 patients with a resection of the left hepatic lobe and 4 patients with resection of the left and right hepatic ducts and anastomosis according to Roux. A mean survival time of 22.8 months was reached when a radical operation was attempted with a longest survival time of 8 years. A palliative procedure gave a mean survival time of 2.0 months. These figures indicate that a careful selection of patients for an attempt of radical surgery could be made since removal of the tumour gives a more effective palliation, often a longer survival time and an improvement of quality of life.

The morphology and histochemistry of gastroduodenal endocrine tumors from 16 patients were studied. All patients underwent operation, in most cases with a preoperative diagnosis of nonendocrine tumor, ulcer, o polyp(s). The argentaffin reaction was positive in three tumors, and the Hellerström--Hellman argyrophil reaction was positive in four tumors. All tumors reacted positively to the Grimelius argyrophil stain, and 13 were positive with the Sevier--Munger argyrophil stain. Gastrin immunoreactivity was found in eight tumors, and substance-P immunoreactivity in seven tumors. No enteroglucagon, adrenal cortex hormone, or pancreatic polypeptide was observed in any of the tumors. Three patients with Sevier--Munger-positive gastric tumors had concurrent pernicious anemia, and 2 patients with gastrin-immunoreactive tumors had acute or chronic gastroduodenal ulceration. The results indicate that the gastroduodenal endocrine tumor as a rule gives no endocrine symptoms and that the tumor type is an unexpected finding at operation. The tumors may contain gastrin, substance P, somatostatin, and serotonin and tend to be multihormonal.

The presence of serotonin, substance P and enteroglucagon was investigated in 8 argentaffin and argyrophil midgut carcinoid tumours. All tumours were argentaffin and displayed formalin-induced fluorescence indicating a content of serotonin. In addition, all 8 tumours showed substance P immunoreactivity and 7 of them enteroglucagon immunoreactivity. The results indicate that the midgut carcinoid tumours are as a rule multihormonal.