The effect of mucaine on gastrin release in man. The effect of Mucaine and Aludrox on basal and food stimulated immunoreactive gastrin has been assessed in normal control subjects and patients with duodenal or gastric ulcer. No differences in gastrin responses were observed either in the basal period or after the protein meal with the two antacids. As previously described, release of gastrin was greatest in gastric ulcer patients but in contrast to previous results,normal subjects seemed to show a greater response than duodenal ulcer patients but this was not statistically significant. Thus the combination of a local anaesthetic oxethazaine with aluminium hydroxide gel does not lead to diminished gastrin release and is not the prime mechanism of action of this agent.


The relationship between the control of diabetes mellitus and circulating glycosylated haemoglobin A1. The mean glycosylated haemoglobin A1 level in 200 diabetics, 13.2%+/-2.6 (1SD), was nearly twice the level found in 100 non-diabetics, 7.42%+/-0.6 (1SD), and overlap between the two populations was minimal. Glycosylated haemoglobin A1 levels, fasting and two hour post-prandial blood glucose concentrations and 24 hour urinary glucose excretion were measured at intervals over a period of 12 weeks in six diabetics requiring stabilisation. A close correlation was found between glycosylated haemoglobin A1 levels and short term parameters of control.


Retroperitoneal fibrosis, methysergide and malignant lymphoma. A patient who developed retroperitoneal fibrosis on low dose continuous methysergide therapy is presented. Discontinuing the drug led to rapid clinical improvement but the patient was subsequently found to have disseminated malignant lymphoma. This may have had a synergistic effect with methysergide in producing retroperitoneal fibrosis. The patient had also previously had thyrotoxicosis but no evidence of a continuing autoimmune process was found.


Membranous glomerulonephritis associated with sarcoidosis. Two patients with sarcoidosis involving pulmonary hilar lymph nodes developed the nephrotic syndrome. Renal biopsy in both cases showed membranous glomerulonephritis. In one patient, there was an associated renal vein thrombosis.


Chronic thromboembolic pulmonary hypertension following ventriculo-atrial shunting. Multiple pulmonary emboli and pulmonary hypertension occurred in a 49-year-old man four years after insertion of a ventriculoatrial shunt. Although this complication is a common finding at post-mortem in children with ventriculo-atrial shunts the frequency with which it occurs in adults is unknown. Routine electrocardiography and lung scanning is necessary for early diagnosis and treatment as symptoms are often insidious and the prognosis in established thromboembolic pulmonary hypertension is poor.


Echocardiographic diagnosis of cor triatriatum. M-mode echocardiography displayed abnormal echoes in the left atrium and posterior to the mitral leaflets in a child with severe heart failure. Cor triatriatum was demonstrated by angiography and cured by surgical excision. Subsequent echo studies no longer showed the abnormal structure.


Normal infant after treatment of acute myeloid leukaemia in pregnancy with daunorubicin. Daunorubicin, thioguanine and cytosine arabinoside were administered from the 17th to 34th weeks of pregnancy in a 23-year-old patient with acute myeloid leukaemia. The patient went into remission of her leukaemia, and a normal male infant was born after labour was induced in the 40th week. This experience supports the view that modern regimens of anti-leukaemic drugs may be administered during the second and third trimesters of pregnancy without harmful effects on the foetus.


Some uses of the continuous flow blood separator in the myeloproliferative syndrome. A continuous flow blood separator was used for leucapheresis in two patients with chronic myeloid leukaemia, complicated by pregnancy and leukastasis respectively, and for thrombocytopheresis in a patient with megakaryocytic myelosis. The cases described, outline some of the clinical uses of this machine in the myeloproliferative syndrome.


The current practice of paediatric surgery in Malaysia. This 10-year review of surgical conditions in infants at the University Hospital, Kuala Lumpur, highlights some of the more common problems encountered and outlines their management. Anorectal agenesis and Hirschsprung's disease were seen relatively more frequently than other anomalies of the gastrointestinal tract. The management of these two conditions and the operation of colostomy and its complications are singled out and presented in some detail.


Burns in childhood: an epidemiological survey. The epidemiology of 382 burns admitted to the Royal Children's Hospital, Brisbane, is reviewed. Accidents due to burn trauma are disproportionately common among children when compared with adults, and during childhood years make up a sizable proportion of all injuries. In addition to the immediate physical trauma, there can be severe psychological consequences as well as severe disturbances to family life. Seventy per cent of the children in this series were normal active children less than four years of age, who were too young to learn that certain things are dangerous, and for this group preventative measures must be directed towards the parents. Possible methods of prevention of burns in children are discussed, and it is tragic that the very traits that make young children so engaging also lead them to accidental burn injuries. Their only hope of prevention lies in increased parental concern.


Bone scintigraphy in discitis and related disorders in children. Thirty-nine children with suspected pathology involving the vertebral column were investigated haematologically, radiographically, and by bone scintigraphy using technetium 99M pyrophosphate. Fifteen children were shown to have inflammatory disease of the vertebrae. A further six suffered from Scheuermann's disease, two from benign tumours, and the remainder from miscellaneous diseases not specifically involving bony pathology. The nuclide scan was abnormal in all cases of discitis and osteomyelitis, and in the two tumours. All of the other conditions were associated with a normal bone scan. This finding is of considerable diagnostic importance, and leads support to the theory that discitis is due to bacterial infection.


A guideline to the management of patent ductus arteriosus in infants and children. Experience with multiple ligation of the patent ductus arteriosus (PDA) at the Hospital for Sick Children, Great Ormond Street, London, is presented. One hundred and sixty-one consecutive cases between January 1971 and December 1974 have been reviewed. Fifty-four children (33%) were less than one year of age. In the majority of cases the diagnosis was made on clinical grounds. Cardiac catheterization and angiography were carried out when associated intracardiac lesions were suspected. The overall mortality was 2.5%. All the deaths occurred in infants less than six months of age who had associated cardiac lesions. There were no deaths in patients who had an uncomplicated PDA or who were more than one year of age. Multiple ligation of the PDA is a simple and safe operation. The risk of operative treatment is affected more by the presence of associated cardiac lesions and the age of the patient than by the surgical technique employed.


Buerger's disease--a review of 105 patients. One hundred and five cases (101 males and four females) of Buerger's disease occurring in Hong Kong have been reviewed. In the foot the digits affected were predominantly the big, second and little toes, whereas in the hand the index and middle fingers were most commonly involved. There was no selective involvement of the left or right side in the upper or lower extremities. The majority of patients were operated on and had amputation, sympathectomy, or both procedures performed. Major lower limb amputation was carried out in 22.6% of patients with lower limb involvement. Reconstructive arterial surgery was possible in only four patients, and early failure of grafts in three patients resulted in major amputation.


The measurement of abdominal aortic aneurysms. A study was made of the accuracy of different methods currently used in assessing the transverse diameter of abdominal aortic aneurysms. The maximum transverse diameter of the abdominal aorta was estimated by clinical palpation, plain radiology, ultrasonography and aortography, in a group of 47 patients who were subjected to either a surgical exploration or elective aneurysm resection. The results of these estimations were compared with the actual measurements obtained during the surgical procedure. Measurements of aortic wall calcification seen on the plain X-ray film correlated best with the operative findings. However, calcification was seen in only 30% of the patients. Ultrasonography was almost universally applicable as a technique of assessing aortic size and was found to be a reliable technique for measuring the aortic diameter.


Mastectomy in a large public hospital.

Mastectomy in a large public hospital. Thirty women undergoing mastectomy for carcinoma of the breast in a large teaching hospital were interviewed. All indicated a very real need to discuss their experiences, and felt that the interview had been beneficial to them. Most had found the "lump" themselves--but often described it as a "hardness", a "ridge", or a "thickening". More than half felt that the counselling afforded to them had been inadequate--especially in the realm of sexual adjustment--but, if their marriages had been stable before operation, subsequent deterioration was unlikely. The threat of malignancy, rather than that of breast loss, was uppermost in the minds of most patients. It should not be assumed that postmastectomy problems do not exist because patients do not mention them, especially in large busy follow-up clinics, where privacy may be inadequate. If doctors are unable or unwilling to afford this service to their mastectomy patients, it may be necessary to delegate it to other health professionals and mastectomy volunteers.


The results of colonic anastomoses at the Royal Melbourne Hospital. One hundred consecutive colocolic and colorectal anastomoses are reviewed. The operative mortality was 5%, wound infection rate 27%, and faecal fistula rate 15%. These complications are shown to double the hospital bed stay. Factors affecting their occurence are examined, and recommendations are made with a view to lower this morbidity.


Local excision of carcinomas of the rectum, anus, and anal canal. Local resection has a place in the treatment of selected patients with carcinoma of the rectum, anus and anal canal. Selection depends on the ability of the surgeon to assess accurately the stage of the tumour. Favourable lesions are those which are small, exophytic, and mobile on the surrounding tissues. A transphincteric approach has been advocated for these tumours, but this seems unnecessarily destructive. The present series consists of 18 highly selected patients who were treated by transanal local removal. There have been two recurrences, one of which has been treated by abdominoperineal resection and the other by further local excision. All of these patients were diagnosed clinically as suffering from carcinoma before operation. Patients who had a preoperative diagnosis of carcinoma and were later found to have benign adenomas, and patients who were diagnosed as benign and later found to have histological malignancy, have been excluded.


Postoperative hypoxaemia: preoperative considerations. In a group of 31 consecutive patients undergoing major abdominal surgery, severe postoperative arterial hypoxaemia was present in 10 cases (32%). The predictive value of the preoperative expiratory spirogram and the arterial PO2 have been examined. It is concluded that a history of chronic bronchitis may be of more value than either of these investigations in predicting the likely occurrence of postoperative hypoxaemia.


Colloid osmotic pressure in surgical patients and its relationship to serum protein and albumin estimations. A series of calculated colloid osmotic pressure (C.O.P.) results have been compared with concurrently performed total serum protein and serum albumin estimations. It is concluded that in most critically ill patients, serial estimations of total serum protein, which are very easy to perform using a hand refractometer or copper sulphate bottles, give a useful guide to the C.O.P. level. In a second series of patients, colloid osmotic pressure has been calculated before and after operation in a group of patients undergoing routine abdominal surgery, and significant falls in C.O.P. have been found to occur after operation. It is suggested that this may be a contributing factor in some of those patients who suffer postoperative respiratory complications.


Papillary adenocarcinoma arising in a thyroglossal cyst. Carcinoma arising in a thyroglossal cyst is a rare but well-recognized condition. In this paper we present a further case of papillary adenocarcinoma arising in a thyroglossal cyst, and review the published experience of this condition.


Myxoma of the tricuspid valve.

Myxoma of the tricuspid valve. Myxomas of the intraventricular cavity are extremely rare, and those of right ventricular origin are the least frequent. Only three cases of myxoma of the tricuspid valve have so far been reported. In this communication a myxoma of the tricuspid valve in a 23-year-old woman is reported because of its unusual and interesting clinical presentation and the extreme rarity of this lesion.


Calcification of the mitral annulus.

Calcification of the mitral annulus. Successful valve replacement has been achieved within the first three years in two patients who had extensive calcification of the mitral valve annulus. This condition, although commonly reported in pathology and autopsy studies, has been rare in our clinical experience. Surgical management does not appear to us to have been reported previously. It was regarded in our earlier experience as a deterrent to mitral valve surgery. Certain technical factors which contributed to success are emphasized in the two cases described in this report.


The "yo-yo" operation for inguinal hernia. This article presents a new principle in the repair of difficult inguinal herniae. The testis is mobilized from the scrotum, returned to the abdominal cavity, brought down again through a new canal constructed through the rectus abdominis muscle, and then restored to the scrotum. The original inguinal canal can then be completely obliterated.


Black pigment stone in a male child aged two years and seven months. A case of cholelithiasis is reported occurring in a boy aged two years and seven months. The patient presented with biliary colic, and cholecystectomy was performed. Detailed analysis of the stone, including electron-probe studies, showed it to be an example of a polybilirubinate stone, containing also calcium, carbonate, and phosphate, with some sulphur, sodium, and magnesium. There were also traces of chlorine, aluminium, copper, nickel, and manganese.


The early diagnosis of acute occlusive mesenteric ischaemia: experimental results and clinical applications. The diagnosis of acute superior mesenteric artery occlusion in the dog has been achieved in every case by isotope scanning of the abdomen using technetium-labelled red cells or technetium-labelled human serum albumin. The white cell count is also significantly elevated, but the changes in the levels of the enzymes CPK, LDH, AST and serum amylase are not specific for actue mesenteric ischaemia. In the human the presence of a normal gut circulation can be demonstrated by isotope scanning provided that the patient is not severely shocked. The presence of a normal gut circulation as shown on the scintigram conclusively eliminates the possibility of acute main trunk occlusion of the superior mesenteric artery. This should be of help in differentiating acute occulusive mesenteric ischaemia from other causes of the acute abdomen. Abdominal scintiscanning is complementary to angiography, which still remains the most precise means of diagnosing acute mesenteric ischaemia. Although the abdominal scintigram is more limited in its application and is not as accurate as angiography, it is quicker to perform, non-invasive, and entirely safe. Abdominal scintiscanning is an excellent screening test to be used in patients suspected of suffering from acute occlusive mesenteric ischaemia.


Experimental replacement of the cervical oesophagus with a free transverse colon autograft using microvascular anastomoses. Microsurgical revascularization in the neck has improved the survival rate of free small-bowel grafts used to replace the cervical oesophagus. Colon vessels are larger than those in the jejunum, and even with naked-eye technique good results have been reported following free colon grafting of the oesophagus. The authors thought it might be possible to achieve even better results using microvascular anastomoses in the neck, and in this way replaced the cervical oesophagus in each of 15 dogs with a free transverse colon autotransplant. Four dogs died during operation and four within three days, two of the latter with graft necrosis. The next seven dogs survived eight days or more, and all their colon grafts were viable. Where patent arteries were demonstrated (three cases) the mucosa and myenteric plexuses of the graft survived. In all four dogs where the arteries were thrombosed or not demonstrated, the mucosa was absent, myenteric plexuses were absent in three, and one graft was grossly stenosed. Among these seven dogs there were three fistulae, one where graft arteries were patent and two where they were not; immediate anastomotic healing was not guaranteed by graft survival or arterial patency.


Prognostic factors in chronic granulocytic leukemia. A study of 798 cases. Between 1959 and 1973 were analyzed the records of 798 patients with chronic myelocytic leukemia. Mean survival (MS) for the entire group is 42 months. 342 patients have been followed closely during and after development of blastic transformation. Presence of following symptoms at the time of diagnosis: asthenia, weight loss, bone pain, fever, sweats and digestive disorders is of poor prognosis significance (MS: 36 months, no sign: MS 75 months) (P less than 0.001). Spleen size is also a prognostic factor. MS are respectively 70, 52 and 35 months if initial splenomegaly is moderate (less than 3 cm), marked (less than 6 cm) or tumoral (greater than or equal to 6 cm). Thrombocytopenia (less than 15,000/mm3 or thrombocythemia (greater than 1 million/mm3) have a poor prognosis with median survival 22 months and 28 months. If peripheral blast cells (hemocytoblasts + myeloblasts) exceed 5%, the prognosis is worse; beyond 10% MS is 26 months. In contrast certain factors have better prognosis: hemoglobin greater than or equal to 14 g/100 ml, young age (less than 20 y.) MS: 62 months), female sex and an initial WBC count below 25 x 10(3)/mm3 (MS: 70 months).


Cytogenetic "staging" of chronic myeloid leukemia (CML). Establishment of the exact chromosome constitution in the leukemic cells of CML can serve as a mean of "staging" of the disease. Such "staging" is of more than theoretical value, for it may be utilized not only in the differentiation of the type of CML present, but may also serve as a useful guide in the therapy of the disease. The most important determination is to ascertain whether the CML is Ph1 positive or negative, for the latter form of the disease has a much poorer prognosis and requires a different therapeutic approach than the Ph1-positive disease. A system of "staging" of Ph1-positive CML is proposed, allowing a clear understanding of the type of therapy to be used and the results that can be expected from such therapy. The presence or absence of chromosomally normal cells plays a crucial role in this respect and points to the importance of diagnosing CML in its very early stages, when normal cells are usually present and leading to a much more favourable prognosis. The possible role of a missing Y in the leukemic cells and Ph1-translocations other than the standard one in the prognosis and clinical picture of CML is discussed.


The relevance of extramedullary hemopoiesis to the staging of chronic myeloid leukemia. In chronic myeloid leukemia (CML) the spleen and the liver can lodge, trap and release a high proportion of leukemic cells, and are active sites of (leukemic) hemopoiesis throughout the disease. Evidence is provided that spleen and liver volume have a prognostic value, and that marrow, spleen, and liver differ as to cell composition, cell kinetic patterns, functional cell characters, and cell karyotype. In the majority of the patients, extramedullary hemopoiesis seems to be more abnormal than marrow hemopoiesis, supporting the hypothesis that spleen and/or liver can play an important role in the evolution of CML towards the blastic metamorphosis. However, present information on extramedullary hemopoiesis does not allow to identify specific patterns and to establish its relevance to the course of the disease.


Usefulness of cell kinetics for staging of chronic myeloid leukemia? In the blood, the labelling index of the immature myeloid cells of one patient out of three decreased progressively from diagnosis to blastic crisis. This parameter deserves more investigation. In the marrow however, the 3H thymidine labelling indexes of the myeloid cells were not useful in predicting the blastic transformation of CML. The colony inhibiting activity of the PMN in CML neither was found to be useful in staging the disease.


The L-5 protocol: intensive treatment for patients with chronic myeloid leukemia. An aggressive treatment program combining splenic irradiation, splenectomy and intensive cytotoxic combination chemotherapy was used in 37 patients with Ph1 chromosome positive chronic myelogenous leukemia. Cytogenetic Ph1 chromosome determination on marrow cells revealed a significant but transient decrease in the Ph1 positive cell population in 12/37 (32%) cases. Survival duration appears longer in patients who show a reduction in the Ph1 positive population. Blastic transformation occurred in 18/37 (49%) cases, not different from our historical control.


Progress report on immunotherapy of chronic myeloid leukemia. A total of 88 better risk patients and 47 poor-risk patients with chronic myeloid leukemia have received repeated vaccinations with BCG or BCG-cultured cell mixtures at our institutions. The number of viable BCG organisms injected appeared to be the most important parameter of immunologic stimulation in this study. Excessive doses of BCG were associated with a significant incidence of disabling complications and with no survival benefit. Better risk patients receiving lower doses of BCG had suggestive prolongation of survival (p less than 0.1). Immunotherapy had little effect on the course of poor-risk patients but evaluation of this heterogeneous population is difficult; additional studies would be desirable among patients in whom reversal of poor prognostic signs can be achieved.


Chronic myeloid leukemia: predictive value of sequential chromosomal surveys and their effect on survival. A program has been initiated to evaluate the efficacy of intensive therapy based on sequential cytogenetic studies in patients diagnosed as having Ph1 positive chronic myelocytic leukemia (CML). Eighteen patients have been induced into hematological remission with busulfan, splenectomized and treated with cycle active drugs. Maintenance therapy is continued during the benign chronic phase of the disease. Intervention with cycles of aggressive therapy is predicated on the results of chromosomal surveys of bone marrow aspirates. The results of this limited study suggest that survival can be improved by such a program.


Ultrastructural, cytochemical and surface marker analysis of cells during blast crisis of chronic granulocytic leukaemia. The blast cells of 19 patients with Ph1-positive chronic granulocytic leukaemia (CGL) in blast crisis (BC) were studied by means of several techniques: morphology, cytochemistry, ultrastructure, surface markers and the enzyme terminal transferase. Cells of BC were, in most case, extremely undifferentiated by morphology and cytochemistry. Our data showed that in 80% of cases the cells in BC were myeloid and in 20% they were "lymphoblastic". The M1, M2 and M3 forms (FAB classification) were rare in CGL BC compared with acute myeloid leukaemia (AML). A megakaryoblastic type was seen in 15% of BC cases; the existence of this form could only be demonstrated by electron microscopy. The limphoblastic BC cells were, as in acute lymphoblastic leukaemia (ALL), positive with Greaves' anti-ALL serum and had elevated levels of terminal transferase. A case of a 17-year old boy presenting as ALL, reverting to chronic-phase CGL after complete remission and developing terminally a myeloid BC is described in detail. This case helps to illustrate a new form of natural history of CGL unveiled by the present study.


Lymphoid blast crisis in chronic myeloid leukaemia and Philadelphia positive acute lymphoid leukaemia. Membrane markers (anti-ALL and anti-Ia antisera) and an enzyme marker (terminal transferase) have been used to define an L-type or "lymphoid" type of acute transformation in chronic myeloid leukaemia and Ph1 positive acute leukaemia. Patients with L-type ("lymphoid") blasts responded to regimens including vincristine and prednisolone (VP). The markers showed better correlation with survival than did the morphology of blasts. The clinical course of patients was variable; elimination Ph1 positive clone (and hypoplasia), return to the chronic phase and relapses (including meningeal leukaemia) were observed. In contrast, patients with myeloid blasts ("M" type of blast crisis) failed to respond to vincristine and prednisolone.


Effect of early splenectomy and cyclic acute leukemia-like chemotherapy on the course of chronic myeloid leukemia. This report provides information on the progress of two trials by the Italian Cooperative Study on Chronic Myeloid Leukemia (CML). Both trials were designed in order to test the effect of early splenectomy and of cyclic administration of either arabinosyl cytosine and vincristine plus prednisone, or arabinosyl cytosine plus thioguanine plus daunomycin, on the course of CML and on the survival. A preliminary analysis, performed on September, 1977, suggests that neither splenectomy nor the chemotherapy scheduled have resulted in a significant decrease of the rate of blastic transformation of CML, during the first 2 to 3 years from diagnosis.


Chronic myelocytic leukemia (CML): failure to detect residual normal committed stem cells in vitro. Granulocytic colonies grown in culture from marrow and peripheral blood from five patients with Ph1-positive CML and heterozygous at the G-6-PD locus were analyzed for G-6-PD in order to identify CFU-C that do not arise from the CML clone. The patients had both B and A enzymes in normal tissues, but their CML clones typed as B. Whereas about 50% of colonies from normal subjects heterozygous as the G-6-PD locus show type-A G-6-PD and 50% type B, only two of the 1308 colonies from the CML patients had type-A G-6-PD. These data provide little evidence for persistence of normal committed stem cells in CML, a finding in contrast to that made previously in polycythemia vera, another clonal stem cell myeloproliferative disorder.


Results of treatment of Ph'+ chronic myelogenous leukemia with an intensive treatment regimen (L-5 protocol). Thirty-seven patients with Philadelphia-chromosone-positive (Ph'+) chronic myelogenous leukemia who were untreated or minimally pretreated were entered on the L-5 protocol. This protocol consisted of sequential treatment with splenic irradiation, splenectomy, arabinosylcytosine and 6-thioguanine, and L-asparaginase. Maintenance therapy was hydroxyurea or a multiple-drug regimen. The median survival of the 37 patients is 50 mo. Twelve patients showed a temporary reduction in the percentage of Ph'+ marrow metaphases to less than one-third of the initial values and in 7 of these patients none were found. The duration of the Ph'+ chromosome reduction ranged from 1 to 43 mo. The median survival of the responders has not yet been reached. It is concluded that whereas overall survival is not appreciably extended, patients who have a reduction in Ph'+ cells in the marrow may survive longer than the average; also, the reduction occurs most frequently in patients who have relatively small spleens at diagnosis. The reduction is difficult to maintain, and it may be reinduced in some patients with intensive chemotherapy.


Paraplegia following intrathecal cytosine arabinoside. Paraplegia following prophylactic intrathecal cytosine arabinoside (Ara-C) is described in a patient with acute myelogenous leukemia in remission who received doses of 100 mg/m2/d for 5 consecutive days. Cerebrospinal fluid examination prior to the last dosage of cytosine arabinoside revealed a mononuclear pleocytosis and increased protein. The neurological manifestations developed within one week after the last dose of Ara-C and persisted for over 8 weeks. Administration of intrathecal Ara-C in the same dose over longer intervals within 3-5 days between consecutive doses resulted in mild, transient neurological symptoms (paresthesias) in only one of 30 patients so treated.


Alkaline phosphatase measurements of paired normal and osteosarcoma tissue culture lines obtained from the same patient. Markedly different levels of alkaline phosphatase production have been found in paired osteosarcoma cells and normal skin fibroblasts grown in tissue culture from 12 patients with osteosarcoma. In all cases, the osteosarcoma line contains significantly more alkaline phosphatase than does the paired normal line from that same patient. These criteria may be useful in distinguishing osteosarcoma from normal fibroblast overgrowth in tissue culture.


Induction by synthetic polyribonucleotide poly(I) of differentiation of cultured mouse myeloid leukemic cells. The effects of some synthetic polyribonucleotides on induction of differentiation of mouse myeloid leukemic M1 cells were examined. Poly(I) was found to be a potent inducer; on treatment with 100--200 microgram/ml of poly(I) for 2--4 days, M1 cells differentiated into cells resembling macrophages and granulocytes and developed phagocytosis and locomotive activities, Fc receptors and lysozyme activity. Poly(C) was less effective than poly(I) for induction of phagocytic activity, while the other single-stranded RNAs, poly(U) and poly(A), had no effect. Double-stranded RNAs, such as poly(I) . poly(C) and poly(A) . poly(U), were cytotoxic to M1 cells, and differentiation of the cells could not be detected even at the highest tolerable concentrations of these double-stranded RNAs.


The retention of lung secretions during the night in normal subjects. 1. Mucociliary clearance has been measured over a 6 h period by using the radioaerosol technique in seven normal male subjects lying supine, both during the day when awake, and during the night when asleep. 2. The percentage of radioaerosol cleared during the night, when asleep, was significantly less than during the day when awake (P less than 0.02). 3. A comparison of radioaerosol clearance before and after the time of onset of sleep demonstrates that reduced clearance occurred during sleep, indicating that this is probably a sleep-related phenomenon and not merely a result of diurnal variation. 4. This finding has important implications for patients with chronic bronchitis or asthma, in whom early morning cough or wheeze may be a predominant feature.


Assessment of early and delayed responses in vitamin B12 absorption during antibiotic therapy in tropical malabsorption. 1. Vitamin B12 absorption was measured in 18 patients with tropical malabsorption. 2. Absorption was particularly impaired in patients with severe mucosal lesions. 3. Sequential measurements with 57Co- and 58Co-labelled vitamin B12 were made before and 48 h after the start of tetracycline therapy. A rapid improvement (on average 22% increase in absorption) occurred in four of six patients with marked mucosal lesions. Further improvement occurred in four of five patients measured after 4 weeks' tetracycline, including the two who failed to improve initially. 4. These rapid changes in vitamin B12 absorption after antibiotics occur too early to be due to mucosal recovery and suggest that bacterial metabolism is an important factor in the malabsorption in these patients.


Acute effects of diuretics on potassium exchange, mechanical function and the action potential in rabbit myocardium. 1. We have studied the acute effects of frusemide, triamterene and amiloride on potassium exchange, the action potential and mechanical function of isolated rabbit myocardium. 2. Potassium exchange in the myocardium was unaltered by these diuretics. 3. Frusemide and amiloride did not affect the action potential of rabbit papillary muscles. Triamterene caused a transient shortening of the action potential. 4. Frusemide and triamterene did not alter myocardial mechanical function in rabbit papillary muscles or the interventricular septum. Amiloride caused a reduction of about 5% in developed tension in two out of three papillary muscles.


A survey of salivary kallikrein and amylase in a population of schoolgirls, throughout the menstrual cycle. 1. The values for kallikrein, amylase and protein were determined in samples of saliva obtained from 220 girls aged 14--18 years. 2. The concentrations of protein and amylase and kallikrein activities (per ml of saliva) were considerably more variable in samples taken in the morning than those in the afternnon. 3. The median amylase activity was about two and a half times greater in the morning than that in the afternoon. No such differences were seen in the median values for protein or kallikrein. 4. Examination of the vlues for salivary kallikrein during the menstrual cycle showed that there was significantly greater activity during days 29--32 and 1--4 than during the rest of the cycle. This pattern was most marked in the morning values of kallikrein but not apparent either in the morning or in the afternoon values of protein or amylase.


The formation of tri-iodothyronine and reverse tri-iodothyronine from thyroxine in isolated rat renal tubules. 1. Conversion of thyroxine into tri-iodothyronine and reverse tri-iodothyronine in intact cells was studied with isolated renal tubules prepared by collagenase digestion. 2. Conversion of thyroxine into tri-iodothyronine and reverse tri-iodothyronine increased progressively for at least 90 min. 3. Studies of tri-iodothyronine production from increasing amounts of thyroxine revealed that the thyroxine to tri-iodothyronine conversion is saturable. 4. Iodine and carbimazole had no effect on the thyroxine to tri-iodothyronine conversion. 5. 6-Propyl-2-thiouracil had a direct non-competitive inhibitory effect on the conversion of thyroxine into tri-iodothyronine with a 75% inhibition of the conversion at a propylthiouracil concentration within the therapeutic range in vivo. Propylthiouracil also inhibited the net formation of reverse tri-iodothyronine from thyroxine at a similar propylthiouracil concentration, as well as inhibiting the subsequent degradation of reverse tri-iodothyronine.


Hypoxanthine--guanine phosphoribosyltransferase activity in blood and skeletal muscles of normal and dystrophic mice. 1. Hypoxanthine--guanine phosphoribosyltransferase (HGPRT) activity was measured in erythrocyte haemolysates and quadriceps muscle extracts of normal and dystrophic 129 ReJ and C57 BL/6J mice with [8(-14)C]hypoxanthine as substrate and 5-phosphorylribose 1-pyrophosphate as a ribose 5-phosphate donor. [8(-14)C]Inosine monophosphate formed was separated by high-voltage electrophoresis and radioactivity was measured by liquid-scintillation counting. 2. In erythrocyte haemolysates, HGPRT activity was similar in normal and dystrophic C57 BL/6J mice but was significantly higher in dystrophic than in normal 129 ReJ mice. Elevated enzyme activity was observed only in mice that were clinically severely affected. 3. In muscle homogenates, HGPRT activity was significantly higher in dystrophic than in normal animals of both 129 ReJ and C57 BL/6J mice. Enzyme activity was not related to the severity of the disease. 4. It is suggested that changes in erythrocytes are secondary to the dystrophic process and that elevated HGPRT activity in skeletal muscle may be related to abnormal energy metabolism, possibly via the pentose monophosphate shunt.


Validation of data on demand and need for dental treatment in an elderly population. The present paper intended (1) to validate some key variables employed in a survey of a representative sample of 241 persons aged 65-79 in Troms in Northern Norway, and (2) to discuss aspects of social policy related to dental programs for pensioners. The participants were asked questions focused on potential demand for dental services, and oral problems. Treatment need was assessed professionally. It was explained to the subjects that pensioners were entitled to dental care at half price, and referral to a dentist was arranged if wanted. Validity was studied in terms of sensitivity and specificity. Using referral as a criterion, the question related to potential demand displayed a sensitivity of only 53%, probably because of the imprecise wording, while the specificity appeared to be 82%. Ninety-five persons reported oral problems. The existing subsidy arrangements operating in a traditional service setting did not seem to cope adequately with this problem group. Treatment need was a sensitive (88%), but not a specific (43%), indicator of oral problems. Viewed socio-politically, these findings may be interpreted as a need for visiting services and for an upgrading of the value of self-assessment. It was concluded that this method of validation provided additional information on the practical usefulness of the test methods employed.


Field testing of an information system for planning and evaluating dental services. A survey of the dental health and need for treatment of 796 children, one in 10 of those in the 1st and 3rd years of high schools in a health administrative area, was carried out using a comprehensive, computerized, epidemiological information system. The system was designed to aid in planning and evaluating services and expressed treatment need on the Resource Related Index as well as utilizing conventional indices. A baseline profile of the dental condition of children in four districts was obtained. This was compared with findings from other surveys. The problem of interexaminer reliability was also discussed.


Effect of regular small group instruction per se on oral health status of Danish schoolchildren. A 1-year study of the isolated effect of an intensive motivation program aimed at improving the oral health status of 11-13-year-old schoolchildren was conducted in a Danish provincial town where all children have access to a free and comprehensive school oral health program. The effect was negligible as measured by epidemiologic indices.


The application of the International Classification of Diseases to dentistry and stomatology. The Application of the International Classification of Diseases to Dentistry and Stomatology (ICD-DA) takes from the parent volume (the International Classification of Diseases) all those items of specific interest in regard to oral pathology whether they be common or rare conditions, or whether the pathology originates in the oral cavity or is a manifestation of a systemic disease. The initial advantage is convenience in finding the numerical classification of disease without searching through the large parent volume. However, an even greater advantage is the fact that these conditions are not sufficiently subclassified in the parent manual whereas in the ICD-DA they are classified down to the five-digit level to make differential diagnosis meaningful within the practice of dentistry.


A Markovian model for evaluating dental care programs. A Markov model is suggested as a means of evaluating dental care programs. Four mutually exclusive states of dental care are defined as Markovian states. These are episodic, initial, maintenance and nonuse. Records for all patients entering a university teaching clinic (n = 578) over a 12-month period were examined and classified in one of the states of care at entry into the clinic and at 1-year intervals from the date of entry for 3 years. An analysis of the findings indicated that the Markov model did fit reasonably well and provided a good approximation of the empirical data.


Dental health situation in privileged children in Addis Ababa, Ethiopia. Two hundred children 6-7 and 13-14 years of age from private schools in Addis Ababa were examined for oral deposits, periodontal condition, dental fluorosis, and dental caries. The findings indicated a higher level of both periodontal disease and dental carries in the privileged children than in previously surveyed nonprivileged children in Ethiopia. This difference was attributed to a higher sucrose intake in the privileged group. The findings may illustrate a dental health situation that will inevitably develop in Ethiopia with a continuous increase in the sucrose consumption.


Brisbane dental survey, 1977. A comparative study of caries experience of children in Brisbane, Australia over a 20-year period. A dental survey of 1,002 children aged 6, 8, 10, 12 and 14 years was carried out in Brisbane using criteria and methods of the World Health Organization. Mean DMFT per child were substantially lower than expected for a non-fluoridated area, being 0.7, 2.0, 3.1, 4.7 and 7.2 for the respective age groups. These scores represent a 50% reduction on levels reported in 1954 and a 20-35% reduction on caries experience of Queensland country children in 1967. 21% of the sample consumed fluoride tablets regularly and these had caries levels virtually identical with life-time residents of fluoridated areas. Compared with children never taking tablets they had 58-79% fewer dmft and 28-54% fewer DMFT. From data of a study of Townsville in 1975 after 10 years' fluoridation it can be calculated that there would be approximately 180,000 fewer restorations required in Brisbane if that city had been fluoridated 10 years previously.


Dental findings in high-fluoride areas in Ethiopia. A survey comprising 478 children aged 6-7 years and 13-14 years was conducted in high-fluoride areas (Wonji, 12.4 parts/10(6) F- and Awassa, 3.5 parts/10 F-) in the Rift Valley in Ethiopia. Dental fluorosis was found in 99% of the 6-7-year-old groups. Very mild to moderate fluorosis dominated in the primary teeth and moderate to severe fluorosis in the permanent teeth. All 13-14-year-old children born in Awassa of Wonji had fluorosis, mainly in the moderate to severe form. Eighty-four percent of the 13-14-year-old children not born in the area had fluorosis, mainly in the very mild form. The most severe fluorosis was seen in the last erupting teeth, but moderate fluorosis was also seen in primary incisors, indicating placental transfer of fluorides. Teeth with moderate and severe fluorosis more frequently had dental caries than teeth with no or very mild and mild fluorosis. The average DMFT was 2.46 +/- 2.34 in Wonji and 1.69 +/- 1.88 in Awassa. The average dft was 0.32 +/- 0.80 in Wonji and 0.40 +/- 0.96 in Awassa. Gingivitis was seen in 97% of the children and the average OHI-S was 1.94 +/- 0.71.


An epidemiologic approach to toothbrushing and dental abrasion. Abrasion lesions were recorded in 818 individuals representing the adult population of 430,000 residents of the Stockholm region, Sweden. The subjects were asked about toothbrushing habits, toothbrush quality and dentifrice usage; these factors were related to abrasion criteria. Abrasion was prevalent in 30% and wedge-like or deep depressions were observed in 12%. The relationship between abrasion and toothbrushing was evident, the prevalence and severity of abrasion being correlated to toothbrushing consumption. The importance of the toothbrushing technique for the development of abrasion lesions was elucidated. Horizontal brushing technique was strongly correlated to abrasion. It was demonstrated by treating the data with the statistical AID analysis that toothbrushing factors related to the individual (brushing frequency and brushing technique) exert a greater influence than material-oriented toothbrushing factor such as dentifrice abrasivity and bristle stiffness.


Superior vena cava syndrome caused by invasive aspergillosis. A 37-year-old man with blastic crisis of chronic myelogenous leukemia was admitted for chemotherapy. After treatment with an infusion of vincristine, he became leukopenic and febrile. Two episodes of gram-negative septicemia were treated with prolonged courses of antibiotics; however, fever persisted, and the patient developed the superior vena cava syndrome. Despite therapy with amphotericin B, the patient died. At autopsy a thrombus of Aspergillus was found completely occluding the superior vena cava.


[Infections and their current prevention in dental surgery]. Both the dentist and the gynecologist deal with areas of the body which are populated by endogenous microbes. The normal bacteria found in the oral and genital regions serve as a protective shield against infection. Recently however this protective shield has been increasingly broken down by pathogens. As a result, the physician and his assistants must use disinfectants to supplement the natural asepsis of the patient.


[Odontogenic soft tissue abscesses in the maxillofacial region. An analysis of 1386 cases from 1957--1976 at the Northwest-German Dental Clinic in Hamburg]. Between 1957 and 1976, 1386 patients with odontogenous abscesses in the area of the mouth, jaw, and face were treated on an in-patient basis at the Hospital for Jaw Surgery (Nordwestdeutschen) in Hamburg. The catamneses of these patients were evaluated noting the localization and frequency of each abscess, the age and sex distribution of the patients, and the possible teeth responsible for the abscess. Any pathogens demonstrated were carefully recorded. The degree of sensitivity and/or resistance of the various groups of pathogens were also included in the study, particularly streptococcus and staphylococcus. Uncritical and undifferentiated administration of antibiotic therapy for pyogenic inflammations in the area of the mouth, jaw, and face is not to be recommended.


[Microbial and resistance spectrum of jaw infections]. According to this investigation, antibiotic treatment of odontogenous abcesses should be directed primarily against streptococcus and staphylococcus, even if gram-negative pathogens have apparently increased. The response on the part of streptococcus to antibiotics has not changed essentially during the last five years. Staphylococcus however has developed a resistance to penicillin and ampicillin.


[Spectrum of pathogens in odontogenous abscesses in the patients of the Tübingen Department of Maxillofacial Surgery]. Bacteriological examination and evaluation of 475 smears of pus taken from odontogenous abcesses showed that the spectrum of pathogens is extremely broad. Chemotherapy therefore should not be started before the pathogen has been identified and an antibiogram has been made due to possible resistance on the part of the microorganisms. Clindamycin may be used for "blind treatment" until the bacteriologic findings are available because it is effective against streptococcus and staphylococcus as well as gram-negative asporous anaerobes. The risk of the possible ineffectiveness of clindamycin against gramnegative anaerobes however must be taken. Clindamycin and gentamicin together may be helpful in life-threatening situations because the combination covers an extremely broad spectrum of possible pathogens.


[Aging in human gingival fibroblasts in cell culture. A contribution to the understanding of proliferating inflammations]. Proliferation of gingival fibroblasts was studied in cell cultures under controlled conditions. Biopsies taken from 12 patients of different ages were analyzed in regard to the length of the generation  cycle and the ability to produce subcultures. Cultures from elderly individuals showed progressive, longer generation cycles than cultures from younger patients. The ability of the gingival cultures from elderly patients to produce subcultures is considerably less than those from young individuals. Apparently gingival fibroblasts are subject to aging processes in the patient himself and in the cell population within the cell culture. The growth characteristics differed depending on the location on the gingiva; the interdental papilla grow better cultures than do free and attached gingiva.


[Problems in the differential diagnosis between eosinophilic granuloma and marginal periodontitis]. Difficulties in the differential diagnosis from the alveolar form of eosinophilic granulomas and deep marginal periodontitis were repeatedly observed. The clinical and radiologic characteristics of eosinophilic granuloma were described on the basis of three cases which were diagnosed as severe juvenile marginal periodontitis and treated accordingly for a long period of time. Clinical differentiation from marginal periodontopathy is usually possible with these characteristics. Only a pathohistologic examination can ultimately clarify the diagnosis; the tissue specimen must be removed from material in the central bony focus which has not been reinfected.


[Contamination of surgical wounds in the maxillofacial region with microoranisms]. The analysis of 226 wound smears were statistically evaluated. Smears were taken immediately after beginning surgery (105) and during the course of the operation, usually toward the end (121). No bacteria were identified at the beginning of the operation in 11.6% of the smears; 8.6% of the smears taken toward the end of the operative procedure showed no bacteria. Microorganisms usually found in the buccal  cavity were identified in approximately two thirds of the wounds. Every third or fourth wound contained facultative pathogenic bacteria at the beginning of the operation. The necessity of antimicrobial measures was discussed.


[Odontogenic soft tissue infections (localization, treatment and course in 1002 cases)]. Between 1965 and 1974, 1002 patients were treated on an in-patient basis for odontogenous soft-tissue infections. Abcesses were observed in 960 patients; inflammatory infiltrate, in 39 patients; a phlegmon, in 3 patients. The relation of male to female patients was 56:44. The 21- to 30-year-old age group was most frequently affected. Antibiotic therapy was administered over a period of weeks prior to admission in 87% of the patients. Operative procedures prior to admission had been performed on only a few patients.


[Effect of weather on odontogenic abscesses]. An increased frequency of odontogenous abcesses was observed on certain days in the course of routine clinical practice. We therefore investigated the possibility of a statistically significant weather-related odontogenous soft-tissue purulence originating from chronic apical periodontitis. Medical reports of patients treated between 1970 and 1977 were used. Our study indicated that the frequency of odontogenous abcesses was significantly higher with cyclonic weather conditions, i.e., weather with low barometric pressure.


[Diagnosis and therapy of a retropharyngeal abscess]. A 53-year-old female patient developed a phlegmon of the floor of the mouth after external extraction of 38 acutely inflammed teeth. The phlegmon tracked retropharyngeally and settled on the opposite side. It was difficult to estimate the amount of tissue area affected by the abscessed phlegmon because of severe trismus. The fact that the inflammation had basically tracked retropharyngeally and inferiorly was ascertained via a lateral radiograph of the neck which showed that the lower part of the prevertebral soft-part shadow was considerably wider than normal. The life-threatening infection healed after the abscess was incised and drained externally. The abscess was approached medial of the  vascular band.


[Infected median and lateral neck cysts and fistulas]. During the last 10 years, 50 patients with congenital anomalies of the neck were treated in the Hospital for Oral and Plastic Surgery in Düsseldorf. Acute or chronic infection was observed in one third of the median and lateral cervical cysts and all cervical fistulas. Most of the cysts and fistulas were not diagnosed or considered in the differential diagnosis at the time of referral. The most frequent false diagnoses were: odontogenous abcess, odontogenous fistula, phlegmon of the floor of the mouth, specific lymphoma, abcess of the lymph node.


[Infected dermoid and epidermoid cysts in the maxillofacial region. Differential diagnosis and therapy]. More than 30% of the patients with dermoid and epidermoid cysts treated on an in-patient basis during the last 10 years in the Düsseldorf Hospital for Jaw and Plastic Surgery showed symptoms of acute or chronic inflammation. The difficulties involved in the clinical diagnosis of infected dermoid or epidermoid cysts were illustrated by example cases. Infected dermoid and epidermoid cysts may be mistaken for ondontogenous abscesses, infected atheromas, furuncles, superinfected tumors, and specific inflammations.


[Diagnosis of mandibular osteomyelitis]. Eighty-four cases were compared clinically, radiologically, and scintigraphically with inflammatory changes in and around the mandible. A diagnostic schema was worked out for osteomyelitis of the mandible. According to our scintigraphic findings, the term osteomyelitis should include odontogenous purulence and periapical periodontitis.


[Compression plate osteosynthesis in infected mandibular fractures]. Self-compromising osteosynthesis plates proved satisfactory for 19 patients with infected fractures of the mandible. After immediate stabilization of the fracture with osteosynthesis plates, the abscess was incised and drained, and antibiotic therapy was instituted. All the fractures consolidated without significant complications. Radiologic assessment revealed delayed bony healing. Our findings agree with those in the field of general traumatology for treating infected fractures.


[Evaluation of the basal parts of the maxillary sinus by means of panoramic tomography]. Information acquired via the panorama tomograph was compared with that obtained via the occipitodental plain film of the paranasal sinuses. Almost all findings in the basal maxillary sinuses were better identified and localized on the panorama film. A plain film of the paranasal sinuses however cannot be dispensed with since assessment of the whole maxillary sinus is only possible on the plain film.


[Comparative phorogrammetric studies on a periodontal index]. Reproducibile results are difficult to obtain with subjectively recorded periodontal indexes. The information acquired via such indexes therefore may be called into question. Inflammation of the gingiva was induced in 15 subjects. The degree of gingival swelling was determined via monophotogrammetry; the degree of inflammation, with the PMA index which emphasizes the symptom "swelling". The results were compared and discussed. It is highly probable that the PMA index is subjectively overrated.


[The effect of sorbide on the amount of lactobacillus in the saliva]. Saliva specimens from school children in the children's village of Fót were cultured in dentocult medium and the lactobacilli were counted. In addition to their usual food, the children also consumed 20 g of chocolate with either 40% sucrose or sorbitol. The control group was composed of children living in Budapest. High lactobacillus counts were observed less frequently in the sorbitol group than in the other groups. There was a positive correlation between the number of lactobacilli in the saliva and the intensity of caries.


[The caries-preventive effect of aluminum fluoride complexes and aluminum lactate in animal experiments]. To expand and substantiate earlier experimental studies of fluoride compounds (SnF2, NaF, Na2PO3F and amine fluoride) with animals, the effect of the compound aluminum-fluoride hydroxide AlFx(OH)y . zH2O and aluminum lactate A1 [CH3 . CH(OH) COO]3 individually, combined, and in various tooth paste bases on caries inhibition was studied in Osborne Mendel rats. The aluminum-fluoride hydroxide compound and its combination with aluminum lactate contributed to a signficant reduction in fissure caries when compared with other groupings and the control (placebo) group.


[Evaluation of the effectiveness of the diagnosis and initial therapy by means of bite plates]. A modified Krogh-Poulsen questionaire was used to study 210 patients with temperomandibular joint complaints. The patients were fitted with a biteplate. Pain at the pterygoideus lateralis muscle was noted in 59.6% of the patients. Constant improvement was demonstrable in 76% of the patients after a period of six months. The cracking in the joint was found in 51% of the patients resistant to therapy. The study of patients resistant to therapy indicated positive psychiatric findings in more than 80% of these patients. The diagnoses ranged from the beginning stages of depression to discovery of a basophilic adenoma.


[Comparative clinical and photogrammetric studies on the marginal periodontium after the use of dentifrices]. A suggestion was made for testing the therapeutic effect of certain substances on gingival inflammation. Gingivitis was induced in 60 subjects by discontinuing of all forms of oral hygiene. Three tooth pastes, one of which was a placebo, were used for the study. Regression of the inflammation was determined with the periodontal indexes and photogrammetry. Photogrammetry appears to be well suited for objective evaluation of the therapeutic value of certain substances.


[The problem of standards for composites]. The bending strenght to the breakage point was determined for five different composites. The testing instrument was set up in accordance with standard specifications under application of pressure. It could be established that the bending strength to the breakage point depends on the intensity and duration of the force. Values were 10% to 20% higher than with polymerized samples without pressure. Long-term studies carried out approximately 24 hours after the sample had been produced showed the highest values for bending strength to the breakage point. These values dropped about 20% during the course of 8 to 10 days. The influence of storage conditions was also determined. In these tests, the bending strength to the breakage point dropped 20% to 30% after 24 hours.


[Surgical therapy of odontogenic maxillary sinusitis. Report on 397 cases]. Operative procedures were carried out on 410 maxillary sinuses in 397 patients. The most frequent indications for surgery were communication between the mouth and the atrium (55.4%) and cysts (24.2%). A Caldwell-Luc operation was carried out in 76.6% of the cases (radical operation). Vestibulum-cheek flaps were used to close the fistula in 97% of the cases. A follow-up examination of 220 patients showed that 10.2% complained of pain. The indications for surgery were limited to avoid this lasting damage.


[Effect of dissolved heterologous collagen on human platelet aggregation]. Our in vitro experiments showed the positive effect of a solution containing collagen fleece on aggregation in platelet-rich plasma of healthy subjects and of patients with thrombocytic coagulation disturbances. The added collagen directly affects the adhesion and aggregation of the platelets. The platelets then complete the process of primary hemostasis by forming a thrombus and the plasmatic "intrinsic system" is started. These results have already been implemented at the practical level.


[Immune reaction as a cause for necrotizing epitheloid cell inflammation]. Disturbed wound healing following dentoalveolar procedures may be due to various causes. Necrotizing inflammations with epitheloid cells may easily be mistaken for specific inflammations. Atypical granulomas represent a response to foreign body material (e.g., gelatin sponges). The possibility of sensitization with Gelastypt was tested using immunologic methods.


[Contribution to the etiology and pathogenesis of chronic recurring parotitis]. Chronic, recurrent parotitis was classified as a disease of the salivary glands of bacterial and inflammatory origin. Forty biopsy specimens of the parotoid gland taken from patients with chronic, recurrent parotitis were examined via light and electron microscopy; virus or bacteria could not be identified. The pathomorphologic findings with chronic, recurrent parotitis correspond basically with those of an experimental ligature of the ganglia. The pathogenesis was discussed. The results of the investigation indicated that, in terms of the pathogenesis, chronic, recurrent parotitis represents a special form of electrolytic and/or obstructive sialadenitis.


[The effect of periodontal resistance on experimental gingivitis]. The distribution and degree of severity of periodontal diseases depends on many different factors. One of the factors, periodontal resistance, was studied in 62 subjects. The test with experimental gingivitis showed that the dividing the subjects into periodontal-resistant and periodontal-insufficient groups led to more differentiated results.


Dental anxiety--etiologic considerations. Dental disease is frequently accompanied by anxiety and fear of the treatment and of dentists. The etiology of any anxiety is sought in early conditioning life experiences; here it may be related to infants' responses to first teething. The universality of dental anxiety makes it a paradigm of psychosomatic disorders. These are conceptualized as pathologic exaggerated reactions to early traumatizing events, a causality not unlike that of conversive-hysteric symptoms or "normal" bodily characteristics. Psychiatric-etiologic considerations of dental anxiety are not to be found in the literature. Recalling the cheerful manner in which children's loss of their first tooth is greeted, one gathers that repressed ambivalence is involved. A clarification of the etiology is here attempted and the dynamics compared with those of other psychosomatic diseases.


Interpersonal managerial skills in the training of dental students. Responsibilities of the dental practitioner impose stress situations similar to those of any manager. These deal with elements of interpersonal behavior and skills not customarily taught to the dental practitioner. In an effort to train dentists so that they may better cope with these managerial situations a method was devised using as the primary instrument the Dental Managerial Situation Study (DMSS). The DMSS employs a variety of problem situations that the dentist is likely to encounter as a means of eliciting his or her managerial tendency (Managerial Profile). A managerial profile is then applied for diagnostic and training purposes. In group discussions, most appropriate behavior (i.e. normative responses) is determined and new ways to behave are learned as each student witnesses advantages and disadvantages of certain responses. The method described in this paper imparts a lexicon (knowledge) of alternative coping or non-coping behaviors to managerial situations. The dental practitioner is able to apply this knowledge in future situations in a way that is more coping and thus he or she may alleviate some managerial stress.


Orthodontics as an aid in adult restorative dentistry. The important role of orthodontics and its contribution to the success of prosthetic dentistry in the adult patient is discussed. Cases undergoing restorative dental procedures, where preliminary minor tooth movement was necessary, are presented. Orthodontic treatment was limited in these cases to local malpositions and to the movement of individual teeth with simple appliances.


The need for teaching emotional behavior in dentistry. A close doctor-patient relationship should be considered a prerequisite for successful treatment. Better communication will help the dentist to preceive a patient's fears and expectations and will provide the information that must precede diagnosis. A student should not devote his time solely to acquiring mechanical skills but should learn something of the behavioral sciences and understand emotional states. He should be able to assess a patient's ability to cooperate, adjust or reject, as well as the effect of the surgery environment on him. The patient as an individual should not be ignored. A dentist who recognizes his role in society and sees his profession as a vocation will anticipate patients' responses and deal with them more effectively and atraumatically.


Talon cusp in deciduous dentition.

Talon cusp in deciduous dentition. Talon cusp is a rare dental anomaly hitherto considered to affect permanent dentition only. A case of talon cusp in a deciduous maxillary incisor is described, suggesting that both dentitions may be affected by this anomaly.


The role of orthodontics as an adjunct to periodontal therapy. In the formulation of a treatment plan for patients with advanced periodontal disease, the benefits that orhtodontics can supply must be considered. By improving the position of malposed teeth, a better environment is created for the health of the gingivae and attachment apparatus, as well as the possibility to improve osseous defects as the result of orthodontically stimulated osteogenic activity. The ultimate goal of treatment must be, in addition to control of inflammation, plaque and trauma, the creation of optimal morphologic and functional conditions which will allow these objectives to be attained. This will provide the prosthodontist and periodontist with a better chance to prolong the life of the dention.


The bitewing roentgenogram and its diagnostic importance. The role of the bitewing roentgenogram in dentistry is reviewed, including the roentgenographic techniques used, accessories for stabilisation of the film, and execution of the roentgenograph. Common errors in application of the technique are listed. The literature on the bitewing roentgenogram is surveyed and the conclusion stated that this roentgenographic technique is a diagnostic instrument that has no substitute for the purpose of detecting incipient interproximal carious lesions and periodontal diseases in the early stages of affecting the alveolar bone. No dental examination can provide complete diagnosis without bitewing roentgenograms.


Oral tissue and irradiation therapy.

Oral tissue and irradiation therapy. For patients with certain oral and nasopharyngeal tumors irradiation therapy, alone or combined with surgical procedures, can be a life-saving treatment. The professionals involved should be aware of the clinical and histological changes brought about by the therapy so that they may better assist the patient at this difficult time through education and relief of discomfort. Treatment of the irradiated patient is a challenge to the knowledge and skills of any dentist and office staff.


Caries, periodontal diseases and oral hygiene among six- to twelve-year-old children in the Druze village of Yarka. The purpose of the present study was to assemble data on the prevalence of caries and periodontal diseases and on the state of oral hygiene in members of the Druze community in Israel aged six to twelve years, and to compare the findings for the different age sub-groups and for males and females within each age sub-group. The population investigated was a sample of 396 children aged six to twelve, 182 males and 213 females, in the village of Yarka in the Western Galilee. The indices used for the purpose of evaluation were: DMF for caries, PI for periodontal diseases, and OHI-S for oral hygiene. No significant differences were found in the incidence of gingivitis as between the various age sub-groups. Oral hygiene was found to deteriorate as age increased. Oral hygiene in ages 9 to 12 was found to be of a lower level in the males than in the females, while in ages 6 to 9 no significant variation was recorded between the sexes. A comparison of the prevalence of caries as established in this study with the figures recorded in earlier years shows an increase. Dental treatment supplied to the children studied had been zero. Comparison of this fact with earlier studies revealed that with regard to treatment no improvement had taken place in the Druze population in recent years.


The immediate overdenture. A case history. A case is described of application of the immediate overdenture technique to restore function, speech and aesthetics in a patient with extreme resorption of the maxillary anterior residual ridge. In the opinion of the authors, retention of the roots of the remaining teeth most definitely contributed to the retention, stability and overall success of the denture (Figs. 9, 10).


Burkitt's lymphoma in Israel.

Burkitt's lymphoma in Israel. A case is described of Burkitt's lymphoma in a nine-year-old Arab boy. The presenting symptom was swelling of the right maxilla, originally diagnosed as a dento-alveolar abscess. The clinical features of African and American Burkitt's lymphoma are compared, and the occurrence of the tumor mainly in the Arab population of Israel is noted.


Temporary restorative materials: properties and uses. Various materials used for temporary restorations are reviewed, with reference to their chemical and physical properties. Research and standard specifications should be instituted in order to standardize and improve the many products now available to the profession. Knowledge of the materials and their properties will enable the dentist to arrive at correct selection of the material for each case, thus promoting more successful clinical procedures.


Successive evaluation of multiple parameters in individual cells: the SEMPIC photometric system. An automated microphotometric system has been designed for the successive assessment of a maximum number of parameters from individual cells. The hardware and software elements are described as well as the various photometric functions that can be performed. The aim is to obtain a multiparameter analysis of morphology, cytochemistry, cell surface characteristics, and metabolic activity including cell cycle characteristics for any set of cells selected from a sample. The combination of DNA synthesis rate determination in a really quantitative approach with the analysis of features of nuclear chromatin texture opens up a new field for associating morphology with functional properties. Examples of application are presented to demonstrate the applicability of the system in a heterogeneous cell population of a very limited sample size. For this purpose, human peripheral blood cells grown in diffusion chambers in preirradiated mice were investigated. It is shown that, depending on their functions, different cell types may have quite different nuclear-to-cell area ratios. Further, a crude morphological parameter, such as the degree of basophilia of Giemsa-stained cells, may be associated with the rate of DNA synthesis, thus bearing information on the replicative activity of a cell. Cell surface properties related to the leukemia-associated cALL antigen are investigated in a human-derived cell line and correlated with cell-cycle characteristics. It is concluded that different antigenic sites rather than cell-cycle dependent differences of antigen density account for the outcome of a bimodal distribution.


Basement membrane reconstitution and cytodifferentiation of odontoblasts in isochronal and heterochronal reassociations of enamel organs and pulps. The restoration of the basement membrane and the terminal differentiation of odontoblasts were studied in iso- and heterochronal reassociations between dental mesenchyme and enamel organs. It was suggested that the cytodifferentiation of odontoblasts was triggered by the basement membrane secreted by the enamel organ of a specific stage.


Action of 5-bromodeoxyuridine on tooth germs "in vitro." I. - Effects on cytodifferentiation. Sixteen or eighteen day old mouse embryonic first lower molars were treated with 5-bromodeoxyuridine (BrdU) in vitro. --In 16-day old tooth germs cytodifferentiation of both odontoblasts and ameloblasts was inhibited. This inhibition was reversible. --In 18-day old tooth germs, the odontoblasts localized at the top of the principal cusps (post-mitotic cells) differentiated normally and secreted predentin. In these conditions ameloblasts localized in front of functional odontoblasts differentiated, although they were able to incorporate BrdU. --In others experiments, control and BrdU-treated tooth germs were dissociated into enamel organs and pulps. Cultivated associations between either control or BrdU treated pulps with either control or BrdU treated enamel organs were analyzed. It appeared that the primary effect of BrdU might result in its incorporation in the preameloblasts which were no longer able to interact normally with the preodontoblasts.


Action of 5-bromodeoxyuridine on tooth germs "in vitro". II. - Effects on collagen synthesis. The first lower molar tooth germs removed from 16-day-old mouse embryos were cultured for 2 days on a standard medium and then for 24 hours on the same medium containing BrdU (treated tooth germs) or not (controls). We attempted to study the effects of 5-Bromodeoxyuridine on the type I and type III collagen synthesis 24 (stage 16 + 4) and 72 (stage 16 + 6) hours after the incorporation of this thymidine analogue. At stage 16 + 4, type I and type III collagen were synthesized both in control and BrdU-treated tooth germs. However BrdU induced quantitative modifications in the type I collagen synthesis which might be explained by modifications in the turnover of this type of collagen. At stage 16 + 6, the BrdU treatment resulted in the inhibition of the terminal differentiation of odontoblasts. Consequently, the normal amplification of collagen type I synthesis could not occur. However, both control and BrdU-treated tooth germs synthesized type I and type III collagen. Quantitatively, the synthesis of type III collagen was slightly affected by BrdU treatment.


Ameloblast differentiation: protein synthesis and secretion in fetal New Zealand white rabbit molar tooth organs and isolated epithelia "in vitro". We have attempted in this preliminary communication to determine the kinetic behaviour pf intracellular and extracellular forms of secretory ameloblast proteins. Our experimental strategy assumes several intracellular forms of enamel proteins: preproenamel leads to proenamel leads to enamel protein (1) leads to enamel protein (2) leads to enamel protein (3) leads to etc. Intracellular preproenamel has a molecular weight of greater than 70,00 and is selectively inhibited by 6 micronM - 12 micronM proflavine. Synthesis and secretion requires 30 minutes in vitro. Secretory ameloblasts in vitro synthesize and secrete a number of proteins ranging from 94,000 daltons to 10,000 daltons. Isotopically-labeled leucine, cystine, proline, methionine and an amino acid mixture were all found to be incorporated into enamel proteins. Preliminary data with protease inhibitors indicates that an enamel protease is directly involved in proenamel leads to enamel protein processing.


On the potential of the adult rat incisor odontogenic organ to differentiate into two intact teeth. The odontogenic organ of 10 male albino rats weighing 200 g has been exposed by a longitudinal incision through the masseter muscle. Its site could be identified as a bluish elevation of the mandible. Into this region through the bone, a 2 X 2 mm. tinfoil has been inserted, deep into the odontogenic organ. The tinfoil direction was generally parallel or slightly oblique to the tooth longitudinal axis. The animals were killed after 1 month. Their lower incisors in the bony sockets were fixed and decalcified, cut sagittally and processed histologically. In 3 sockets two separate teeth could be identified, a labial and a lingual tooth. Generally only the labial tooth was covered by enamel, in one case however both teeth exhibited a regular enamel layer. Both teeth were separated by a periodontal ligament and exhibited separate tooth cavities. This experiment demonstrates the capability of the odontogenic organ to reproduce a whole new complex organ, the tooth. A phenomenon hitherto observed only in Urodela in which a severed limb regenerates from primitive pluripotential stem cells known as blastema. Contrary to the newt however, the incisor blastema reproduces continuously throughout the life of the individual and responds to the tinfoil stimulus by a production of an extra tooth.


Requirements for RNA and protein synthesis in the induction of several differentiation-markers in a myeloid leukemia cell line. In a myeloid leukemia cell line, the inducibilities of the Fc receptor, phagocytosis and cell motility were compared. Thymidine analogues such as BUdR, BCdR and IUdR blocked the induction of phagocytosis and motility but not induction of the Fc receptor. This BUdR susceptibility in the induction of phagocytosis and motility was lost in a BUdR resistant line which was isolated for its growth capability in a high concentration of BUdR. Actinomycin D and puromycin brought about a marked decrease in the inducibility of phagocytosis but not in that of the Fc receptor. This led us to the following conclusion: There is a genetic control in the inducibility of phagocytosis and motility in this cell line, and the incorporation of BUdR into cellular DNA results in the DNA becoming unresponsive to a differentiation-stimulating factor. In contrast, gene activation does not seem to be necessary for induction of the Fc receptor. The order of induction of several differentiation markers was also discussed.


Crown size-arch space relationships during human prenatal dental development. As shown in composite reconstructions made from optically-projected measurements of 10mu frontal maxillofacial sections of 20 histologically normal fetuses and embryos in the 70-255 mm CRL range, individual differences in relative tooth size and interdental spacing are evident by 10.5-11 weeks of gestation, and age-corrected crown-size correlations (r=0.40) approximate those in postnatal life. Despite an eight-fold increase in crown dimensions, interdental spacing remains approximately constant after 150 mm CRL, suggesting that the tooth organs or the periodontal membranes are able to maintain spacing, into the third trimester.


The chloride corrosion of low-gold casting alloys. Potentiodynamic polarization measurements have indicated that the so-called 'low-gold' casting alloys are characterized by decreased chloride corrosion resistance, when compared with ADA Type III and Type IV gold alloys. This decrease in chloride corrosion resistance results apparently from the presence of Ag-rich microsegregations with a possible minor contribution from Cu-rich segregations or precipitates.


Potential sweep and intensiostatic pulse studies of Sn, Sn8Hg and dental amalgam in chloride solution. The anodic behavior of the Sn, the Sn8Hg (gamma2) phase and the dental amalgam in a chloride solution has been investigated by means of the linear potential sweep and of the intensiostatic pulse method. The results indicate that anodic current varies with chloride concentration and that dissolution occurs prior to passivation of the electrode. The anodic charge needed for the passivation is smallest for the dental amalgam.


Thermal expansion of composite resins and sealants. Linear thermal coefficients of expansion (alpha) of seven commercial composite resins and four pit and fissure sealants were determined between 0 and 60 degrees C on a thermomechanical analyzer. The thermal expansion curves obtained were nonlinear. Values of alpha ranged from 26.5 to 39.6 x 10(-6) degrees C for the composite and from 70.9 to 93.7 x 10(-6)/degrees C for the sealants.


A method for assessing the relative abrasion of prophylaxis materials. A method for assessing the relative abrasion of prophylaxis materials is described. The method utilizes irradiated human enamel and dentin specimens, and treatments are performed using a simulated prophylaxis procedure. Results obtained with this method indicate that variations in treatment time, load, and cup speed may influence the relative abrasion.


An evaluation of beta titanium alloys for use in orthodontic appliances. A beta titanium alloy was evaluated for use in orthodontic appliances. Standard mechanical tests and aspecially designed spring test were used. Two particular thermo-mechanical treatments resulted in titanium springs with 1.8 times the extension of comparable stainless steel springs, and a 2.2 fold reduction in force per unit displacement.


Titanium and fluoride concentrations in titanium tetrafluoride and APF treated enamel. Greater fluoride concentrations were obtained in enamel treated with phosphate/fluoride solutions than in that treated with TiF4 at similar pH's (1.0) and F concentrations (0.6M F and 1.6M F). However, fluoride solution without added phosphate at pH 1.0 and 1.6M F concentration produced lower fluoride concentrations in enamel than in TiF4 treated enamel. It is proposed that in TiF4 treated enamal the fluoride uptake may be dependent upon the amount of Ti introduced into the enamel.


Inter-examiner reliability in caries trials. A statistical model is given for representing the several components of variability present in measurements (e.g., DMFS scores) given by examiners to patients. Methods for making inferences about the intraclass correlation coefficient of reliability are presented and illustrated on a real set of data. The proper analysis of data from a reliability study is shown to depend on the planned design and analysis of the clinical or field trial to be conducted following the reliability trial.


Characterization of calculus matrix calcification nucleator. The nucleator of dental calculus matrix calcification, in vitro, was analyzed. Attention focused on proteolipid singularity, amino acid composition and related polarity, and phospholipid components. The data were compared to those of the nucleator of Bacterionema matruchotii calcification.


The effect of vitamin A on hamster cheek pouch mucosa in organ culture. Vitamin A was added to the medium of neonatal hamster cheek pouch mucosa maintained in organ culture. The epithelium of the treated explants showed a reduction in keratinization and down-growth into the underlying connective tissue. The cytological and morphological changes in the epithelium were consistent with glandular metaplasia.


Cellular regulation of the metabolism of androgens in rat oral mucosa. II. Product activation of 17 beta-hydroxysteroid oxidoreductase enzyme system. Product activation of 17beta-hydroxysteroid oxidoreductase for testosterone and androstenedione was established using the enzyme preparation from rat oral mucosa. It is suggested that this activation could be due to the conformational changes of the enzyme.


Cellular regulation of the metabolism of androgens in rat oral mucosa. III. Activation of delta 4-3-ketosteroid-5alpha-A ring reductase enzyme system by 5,5-diphenylhydantoin. Systemic pretreatment of rats with diphenylhydantoin (DPH) or its addition into an in vitro assay increases 5alpha-reduction of testosterone by the oral mucosa. Enzyme kinetic studies showed that DPH binds to the enzyme and probably activates it by an allosteric mechanism.


Qualitative and quantitative analysis of bovine, rabbit and human dental pulp glycosaminoglycans. Bovine, rabbit and human dental pulp glycosaminoglycans were analyzed qualitatively and quantitatively using two-dimensional electrophoresis. The major components of bovine and rabbit dental pulp were chondroitin 4-sulphate and hyaluronic acid, while in the human dental pulp dermatan sulphate and chondroitin 4-sulphate were the major components.


Changes of serological activity by alpha-L-fucosidase isolated from Streptococcus sanguis ATCC 10557. alpha-L-Fucosidase isolated from the growth culture of Streptococcus sanguis ATCC 10557 acted on H- and Leb-blood group substances in porcine gastric lining, human gastric lining, human ovarian cyst fluid and human whole saliva, with consequent loss of H- and Leb -activities and a concomitant increase of Lea activity.


A simple ultrasound method to characterize in vitro plaque inhibition activity. A method employing ultrasound vibration for evaluating in vitro plaque derived from Streptococcus mutans was developed. It successfully detected small changes in the cohesive/adhesive characteristics of deposits briefly exposed to several antibacterials and "antiadherents". Increased structural fragility and diminished plaque growth were generally associated with the antibacterials.


Partial amino acid sequences of two proteins in developing porcine enamel. The enamel proteins prepared from porcine enamel samples at an early stage of development are separated at least 4 fractions by Sephadex G-100 gel filtration at pH 10.8. The main components of secondary and fourthly-eluted fraction were further purified by ion exchange chromatography. The results of sequence analyses of these proteins by sequential Edman degradation and by hydrolysis with carboxypeptidase Y showed that the partial amino acid sequences of these proteins were identical.


Ultrastructural study of the protein-polysaccharides distribution in enamel from rat incisors. The distribution pattern of the protein-polysaccharides in the rat incisor enamel was similar whether stained for glycoproteins (phosphotungstic acid) or for proteoglycans (alcian blue, bismith nitrate). Except for the holes at the dentino-enamel junction, where these components seem to exist as amorphous gel, protein-polysaccharides are closely associated to the proteinic fibrous matrix in rods and interrods structures as in prism sheaths where they are particularly abundant.


Proteolytic activity in developing bovine enamel. Partially mineralized enamel matrix removed from bovine incisor tooth germs contains proteolytic activity capable of completely degrading enamel matrix proteins at neutral and slightly alkaline pH. The protease activity also degrades common protease substrates such as casein and azocoll with optimal activity at pH 8-9. Inhibitor studies revealed that the enzyme involved is a serine protease of the chymotrypsin family.


Frozen ultrathin-sections for x-ray microanalysis of rat tooth germs. In order to detect the precise location and pathways of calcium in the ameloblastic layer with EM and EDX, frozen ultrathin-sections, potassium pyroantimonate (PPA) method and 45Ca-autoradiography (A.R) were employed. A population of dense granules containing Ca and P was mainly observed within the nuclei and mitochondria of the frozen-sectioned ameloblasts, whereas PPA-reaction was seen not only within them but in ER, Golgi vesicles and intercellular spaces. No granules were found at the enamel matrix by both methods, but peaks for Ca and P were distinct. Silver grains of 45Ca-A.R were located in nuclei, mitochondria. Golgi complex and intercellular spaces. These results indicate that calcium can transport across the ameloblastic layer through two main pathways, extracellular and transcellular.


Uptake of radioactive calcium by hard tissue cells. 45Ca was injected into prenatal mice to study the calcium uptake by tooth germ cells. Both dental papillae, containing the odontoblasts, and the enamel organs were found to actively metabolized the labeled calcium. The maximum specific radioactivity occurred at 15 minutes after injection. The subcellular organelles (e.g. mitochondria) of the papillae were more active in metabolizing the labeled calcium whereas a large portion of the radioactivity of the enamel organ was found in a fraction containing the precalcified material. In fetal tooth germs, the rate of incorporation of labeled calcium into the precalcified material was slower than in the postnatal tooth germs since a large portion of the radioactivity remained in the soluble fraction.


Effects of sequential calcium phosphate--fluoride rinses on fluoride uptake in rats. This study measured the effects of a calcium phosphate rinse followed by various fluoride rinses on fluoride uptake by enamel in rats. Calcium phosphate rinses promoted fluoride uptake by the enamel.


A non-destructive optical method to study de- and remineralization of enamel. The absorption and scattering of light in dental enamel or in a carious lesion have been studied quantitatively by using thin slabs. The method thus required destructive preparation techniques. In this paper we describe how the scattering by a bulk sample can be used to obtain semi-quantitative information.


Ameloblasts: secretory and resorptive functions. The sequence of steps which an ameloblast passes through in forming enamel appears remarkably similar in amphibian and man. Despite considerable improvements in understanding the early events in the life cycle that lead to the intracellular synthesis and secretion of enamel matrix by the cell, little is known about the cell's functional role at later stages of the life cycle when the extracellular enamel matrix undergoes classical maturation in becoming fully mineralized.


Ameloblasts--ion transport function.

Ameloblasts--ion transport function. Recent autoradiographic and in vitro studies have produced evidence that the cells of the enamel organ limit the movement of calcium into enamel during the matrix secretion phase, but have no effect on movement of calcium during the maturation phase. The cells of the enamel organ do not seem to control the flux of phosphorus into enamel at either phase of development. This concept is consistent with current theories on the control of ion fluxes into developing bone.


Disturbances and defects in enamel development. Ameloblastic disturbances are correlated with defects in enamel. Experimental disturbances created by tetracyclines, fluorides, and antimitotic drugs are emphasized. Cellular alterations are shown to interfere with both matrix production and secretion. Defects in enamel formation are characterized by abnormal crystal size and distribution. Further research in normal and particularly abnormal enamel development is needed to establish: 1. exact mode of matrix secretion and its relation to crystal nucleation and orientation 2. function of maturative ameloblast and its relation to the stratum intermedium and papillary layer during that phase 3. cause for lack of mineralization of matrix, particularly in ectopic areas.


Amelogenesis in vitro.

Amelogenesis in vitro. The processess by which diversity is acquired and maintained during embryogenesis have been repeatedly described but are as yet not understood. One fascinating example of diversity following gastrulation is epidermal organogenesis and in particular embryonic tooth morphogenesis. Tooth morphogenesis in situ and in vitro encompasses such interesting developmental problems as epithelial-mesenchymal interactions, cytodifferentiation, dentine and enamel extracellular matrix production, mineralization, issues of form and enamel maturation. In vitro methods provide access to many of these problem areas. This presentation will review selected issues related to amelogenesis in vitro and will emphasize avenues for future research.


Enamel proteins: biosynthesis and chemistry. Bovine ameloblast cell layer was incubated in 3H-proline containing medium and the incorporation of radioactivity into protein fractions of the cell and the medium was investigated by SDS- polyacrylamide gel electrophoresis. The results suggest that the ameloblasts synthesize and secrete a protein having a molecular weight of 25,000 daltons which is supposed to be the prototype of enamel proteins. This protein was degraded into dialyzable sizes by the cell extract. After a longer period of incubation another low molecular weight protein fraction appeared in the medium. Purification procedure with SDS gel filtration of the enamel protein is reported.


Enamel matrix: structural proteins.

Enamel matrix: structural proteins. Cell-free, fetal bovine enamel tissue was examined intact by high resolution. 13C Fourier transform, nuclear magnetic resonance spectroscopy. Two types of protein chains were observed under these conditions, one exhibiting rapid mobility and accounting for approximately two-thirds of the enamel matrix, while the other exhibited restricted or anisotropic segmental motion and accounted for the remaining third of the matrix. Sequential extraction of this fetal enamel under non-degradative conditions with dissociative solvents yielded two biochemically distinct populations of matrix protein. As expected, the bulk of the matrix consisted of proline-rich amelogenins, although the SDS-gel electrophoresis molecular weights for these proteins were somewhat higher than those reported using other extraction methods. Approximately fifteen percent of the total matrix consisted of much higher molecular weight phosphoproteins (46,000-72,000 daltons) whose amino acid composition closely resembled that reported for mature enamel protein. These high molecular weight proteins were tightly bound to the fetal enamel apatite crystallites.


Proteolytic enzyme in porcine immature enamel. A proteolytic enzyme cleaving the main component of enamel proteins obtained from immature enamel has been purified from a soluble extract of porcine immature enamel. It is optimally active around pH 6 against enamel protein. It is completely inhibited by phenylmethylsulfonyl fluoride and diisopropyl phosphofluoridate, and partially by benzamidine. EDTA does not affect its activity. The enzyme seems to sever initially its activity. The enzyme seems to sever initially enamel protein into two segments, one containing lysine, arginine and tyrosine and the other being free from these amino acids.


Phosphopeptides of enamel matrix.

Phosphopeptides of enamel matrix. Although the tripeptides Glu-O-Phosphoserine-Tyr and Glu-O-Phosphoserine-Leu have been identified in embryonic bovine enamel proteins, 1, 2 the issue of whether both sequences occur in each of the phosphopeptides, or whether certain sequences occur in specific peptides only, has recently been resolved by isolating homogeneous samples of E33 and E44. All three of the Ser residues of both peptides are phosphorylated. All three in E3 are in the sequence Glu-O-Phosphoserine-Leu, and all three in E4 are in the sequence Glu-O-Phosphoserine-Tyr. It was not possible to sequence either of the polypeptide chains directly by automatic peptide sequencing. However, a partial sequence of E4 was constructed from data derived from peptides isolated after cyanogen bromide, trypsin and chymotrypsin digestions. The presence of Glu, Tyr and Leu adjacent to and near the O-Phosphoserine [Ser(L)] residues and the 2 degrees, 3 degrees and higher ordered structures of the enamel phosphopeptides may be important in calcium binding and mineralization.


Immunogenicity of enamel protein.

Immunogenicity of enamel protein. Antisera to enamel proteins have been used primarily as a probe for biochemical and developmental studies of enamel proteins and tooth formation. More recently, the inherent immunogenicity of enamel protein has become a subject for investigation. Papers are reviewed which show that soluble enamel proteins are immunogenic across species barriers, and that solid-phase enamel proteins are immunogenic within a species. New data are presented which demonstrate that enamel proteins are autoantigenic both in vivo and in vitro. Future areas of research are suggested.


Dentin proteins: chemistry, structure and biosynthesis. One of the most abundant noncollagenous proteins of dentin is a phosphoprotein rich in aspartic acid and phosphoserine. This protein occurs in soluble and inextractable forms, the latter being associated with the insoluble collagenous matrix. This protein is capable of tightly binding a relatively high level of calcium. Biosynthetic and radioautographic data suggest that shortly after its biosynthesis, the phosphoprotein is transported and bound to the collagen at the predentin-dentin junction. This event is probably central to the mineralization process, though other glycoproteins may be involved.


Enamel apatite: chemistry, structure and properties. The crystal chemistry of enamel apatite is probably the best understood of all the biological apatites. It is an imperfect apatite, low in calcium and hydroxide ions, but rich in substitutional impurities. A few impurities, like fluoride, are beneficial but most appear to disrupt the lattice structure. In this paper, the composition and basic structural features of enamel apatite are described, with particular emphasis on what we presently know, and do not know, about the role impurities play in establishing the fine details of this structure.


Ultrastructural studies of synthetic apatite crystals. In this paper a survey is given of some ultrastructural properties of synthetic hydroxyapatite. The preparation method by which single crystals with a length in the range of 0.1-3.0mm and a defined purity and stoïchiometry can be produced is given. Two groups of materials are considered in detail: carbonate-rich (greater than 0.1% CO3) and low-carbonate hydroxyapatites. The experiments on carbonate-rich material, being the most interesting from a biological point of view, show that acids attack at an active site in the hexagonal basal-plane of the crystals. Later on the crystals dissolve in the center of the crystal parallel to the c-axis forming tube-like structures. The active site can be protected from dissolution if the crystals are pretreated by EHDP or MFP. A comparison with lattice defect theory shows that most likely dislocations of the "hollow-core" type are responsible for the preferential dissolution.