Prevalence and distribution of permanent canine agenesis in dental paediatric and orthodontic patients in Hungary.

Non-syndromic permanent canine agenesis, or combined with agenesis, or developmental absence of other tooth types, has occasionally been described in the literature, but isolated forms are rarely observed. The purpose of the present retrospective radiographic study was to provide data on the prevalence and distribution of permanent canine agenesis in the Hungarian population. Dental panoramic tomograms and the medical history data of 4417, 6- to 18-year-old children (average age 12 years, male-to-female ratio 1:1), who presented for treatment at the Department of Paediatric Dentistry and Orthodontics of the Semmelweis University Budapest, Hungary, were examined. Patients with systemic diseases were excluded. Chi-square and Fisher's tests were performed to determine statistical significance at a level of P < 0.05. Thirteen subjects had permanent canine agenesis. The overall prevalence was 0.29 per cent. The prevalence of permanent canine agenesis was 0.27 per cent in the maxilla and 0.09 per cent in the mandible (P < 0.01). The male-to-female ratio was 1:2.2. Dental anomalies associated with permanent canine agenesis were found: 11 patients had retention of the primary canines, 10 other types of agenesis of the permanent teeth, one a primary supernumerary tooth, one a supernumerary cusp, and nine occlusal disturbances.

Recombinant DNA technology in the treatment of diabetes: insulin analogs.

After more than half a century of treating diabetics with animal insulins, recombinant DNA technologies and advanced protein chemistry made human insulin preparations available in the early 1980s. As the next step, over the last decade, insulin analogs were constructed by changing the structure of the native protein with the goal of improving the therapeutic properties of it, because the pharmacokinetic characteristics of rapid-, intermediate-, and long-acting preparations of human insulin make it almost impossible to achieve sustained normoglycemia. The first clinically available insulin analog, lispro, confirmed the hopes by showing that improved glycemic control can be achieved without an increase in hypoglycemic events. Two new insulin analogs, insulin glargine and insulin aspart, have recently been approved for clinical use in the United States, and several other analogs are being intensively tested. Thus, it appears that a rapid acceleration of basic and clinical research in this arena will be seen, which will have direct significance to both patients and their physicians. The introduction of new short-acting analogs and the development of the first truly long-acting analogs and the development of analogs with increased stability, less variability, and perhaps selective action, will help to develop more individualized treatment strategies targeted to specific patient characteristics and to achieve further improvements in glycemic control. Data on the currently available and tested analogs, as well as data on those currently being developed, are reviewed.

The molecular and genetic basis of fibroblast growth factor receptor 3 disorders: the achondroplasia family of skeletal dysplasias, Muenke craniosynostosis, and Crouzon syndrome with acanthosis nigricans.

Achondroplasia, the most common form of short-limbed dwarfism in humans, occurs between 1 in 15,000 and 40,000 live births. More than 90% of cases are sporadic and there is, on average, an increased paternal age at the time of conception of affected individuals. More then 97% of persons with achondroplasia have a Gly380Arg mutation in the transmembrane domain of the fibroblast growth factor receptor (FGFR) 3 gene. Mutations in the FGFR3 gene also result in hypochondroplasia, the lethal thanatophoric dysplasias, the recently described SADDAN (severe achondroplasia with developmental delay and acanthosis nigricans) dysplasia, and two craniosynostosis disorders: Muenke coronal craniosynostosis and Crouzon syndrome with acanthosis nigricans. Recent evidence suggests that the phenotypic differences may be due to specific alleles with varying degrees of ligand-independent activation, allowing the receptor to be constitutively active. Since the Gly380Arg achondroplasia mutation was recognized, similar observations regarding the conserved nature of FGFR mutations and resulting phenotype have been made regarding other skeletal phenotypes, including hypochondroplasia, thanatophoric dysplasia, and Muenke coronal craniosynostosis. These specific genotype-phenotype correlations in the FGFR disorders seem to be unprecedented in the study of human disease. The explanation for this high degree of mutability at specific bases remains an intriguing question.

Complex care by multiple medical and dental specialists of a patient with aggressive Gorlin-Goltz syndrome.

Gorlin-Goltz syndrome is a genetically predisposed disease characterised by multiple basal cell carcinomas, odontogenic keratocysts and ectopic calcifications. The aim of this study was to show successful treatment of a 37-year-old male patient by cooperation between different dental and medical specialists. Because of the recurrence of a large basal cell carcinoma after multiple operations and a total dose telecobalt irradiation of 66 Gy, the patient's nose was ablated, with resection of the upper lip and part of the maxilla. The intraoral prosthetic treatment helped to restore the subtotal edentulousness. In order to enhance the application of the dental prosthesis, an Abbe plasty was performed at the second stage of surgery. As previous irradiation of the area precluded the use of facial implants immediately after the intraoral treatment, a temporary artificial nose prosthesis was created. The patient tolerated the procedures well and is completely disease-free 12 months after the surgery. Besides presenting a rare and complicated case of Gorlin-Goltz syndrome, the main purpose of this report is to show that, if different specialists in a dental-clinical team (maxillofacial surgeon, oncologist, radiation oncologist, prosthodontist and psychiatrist) combine their skills and expertise, successful management is possible even in a challenging complex case.

Impaired beta 2-adrenergic agonist-induced venodilation in Indians of Asian origin.

OBJECTIVES: Vascular responsiveness to infusions of vasoactive substances varies between ethnic groups. Indians of Asian origin are a rapidly growing ethnic group in the United States but have not been extensively studied. We sought to determine whether there was any difference in venous responsiveness to a local infusion of vasoactive substances between Indians of Asian origin and white subjects. METHODS: We used the dorsal hand vein compliance technique to construct full dose-response curves to the beta 2-agonist isoproterenol (2 to 270 ng/min) in hand veins preconstricted with phenylephrine in 11 young white subjects and in 11 young Asian Indian subjects. In addition, six subjects in each group were randomly selected to have full dose-response curves to nitroglycerin (0.006 to 1485 ng/min) generated. RESULTS: The maximal response (E(max)) to isoproterenol was smaller in Asian Indians (33.9% +/- 41.1% in Asian Indians versus 107.0% +/- 60.1% in white subjects; p < 0.01). There was no difference in the log of the dose that produced half-maximal venodilation [log(ED50)] between the two groups (1.10 +/- 0.57 in Asian Indians versus 1.15 +/- 0.50 in white subjects). However, nitroglycerin infusion produced similar responses for both the E(max) and the log(ED50) between the two groups. CONCLUSION: These results indicate that differences may exist in beta-adrenergic responsiveness among white subjects and Indians of Asian origin. Therapy for diseases that use beta-adrenergic responses, such as hypertension, must take into account these differential vascular responses because they may affect their efficacy in Asian Indians.

For debate: defective mitochondria, free radicals, cell death, aging-reality or myth-ochondria?

As both experimental evidence and theoretical considerations may suggest that free radicals and mitochondria might be associated as key factors in aging, these organelles have been implicated in various versions of the free radical theory of aging. However, except for a few cases, no evidence for a death process specifically activated in respiratory defective cells could be found in patients with a mitochondrial disorder, including those harboring high levels of mutant mtDNA associated with profound respiratory chain deficiencies. This and more recent evidence suggest that damages produced by free-radicals endogenously generated in the mitochondria result in a distinctive biochemical profile, only occur under exceptional conditions and that a dysfunction of the respiratory chain does not cause opening of the permeability transition pore and is not sufficient per se to trigger massive entrance of cells into death processes, neither apoptosis nor necrosis. Therefore, defective mitochondria and their particular genome, should not be considered as a major and primary source of free radicals either leading cells into a death cascade or resulting in an accelerated aging process.

Effect of ovariectomy and hormone replacement therapy on small artery biomechanics in angiotensin-induced hypertension in rats.

OBJECTIVES: To test the effects of chronic angiotensin II administration on blood pressure and small artery biomechanics in the female sex hormone-depleted state (proposed to increase cardiovascular vulnerability) and with hormone replacement. DESIGN: Biomechanical properties of saphenous artery segments from ovariectomized (n = 10), ovariectomized + chronically angiotensin II infused-(n = 10), and ovariectomized + chronically angiotensin II-infused + sex hormone-replaced (n = 10) rats were studied. METHODS: Surgical ovariectomy was performed. Osmotic minipumps were used for chronic angiotensin II infusion (100 ng/min per kg). For hormone replacement therapy, oestradiol-propionate, 450 microg/kg for 7 days + medroxyprogesterone-acetate, 15 mg/kg for 14 days were given, intramuscularly. After 4 weeks, cylindrical segments of the saphenous artery were prepared and subjected to in-vitro microarteriographic measurements. Pressure-diameter curves (0-200 mmHg) were recorded in Krebs-Ringer solution, with smooth muscle contracted (norepinephrine, 16 micromol/l) and with relaxed (papaverine, 28 micromol/l). RESULTS: Chronic angiotensin II infusion significantly reduced the inner radius (at 100 mmHg: 298 +/- 17 microm versus 347 +/- 7 microm, P< 0.001), while wall-thickness did not change. Hormone replacement restored the morphological radius (333 +/- 7 microm). Angiotensin II infusion slightly increased the full contraction range of the segments (defined as the percentage difference between fully contracted and fully relaxed diameters), which was further significantly increased by hormone replacement (39 +/- 4%, 46 +/- 8%, 62 +/- 7% at 100 mmHg, in the three groups, respectively; P < 0.05). Despite unaltered stiffness in relaxed state, elastic moduli computed for the contracted segments decreased after hormone replacement. CONCLUSIONS: These observations give further experimental support to the hypothesis that sex hormone replacement might be useful in preventing the development and/or stabilization of postmenopausal hypertension, as well as in treating existing disease.

Endobronchial thrombolysis with streptokinase for airway obstruction due to blood clots.

To our knowledge, only four reports have previously described endobronchial thrombolysis with streptokinase for airway obstruction due to blood clots; the highest dose used was 80,000 U. Herein we describe a 21-year-old woman with pulmonary embolism who experienced life-threatening airway obstruction due to a large blood clot in the distal trachea. Streptokinase (120,000 U), injected through a fiberoptic bronchoscope, partially dissolved the clot. The rest of the clot was removed easily with forceps and suctioning. No complications occurred.

Sex hormone replacement therapy reverses decreased venous distensibility in pharmacologically ovariectomized rats.

OBJECTIVE: To test the effect of female sex hormone depletion and replacement on the distensibility and geometry of the saphenous vein in female rats. DESIGN: Twenty Sprague-Dawley rats were pharmacologically ovariectomized by triptorelin. Ten of these animals received combined hormone replacement with estradiol and medroxyprogesterone acetate. The rest were given vehicle. Ten animals kept parallel without pharmacological ovariectomy served as controls. After 3 months of treatment, a segment of the saphenous vein was dissected. Pressure-diameter curves were recorded in relaxed, contracted, and control states using a microangiograph. RESULTS: Pharmacological ovariectomy lowered venous wall distensibility measured in contraction (at P=8 mm Hg: 4.41+/-1.21*10(-3) m2/N vs. control: 0.79+/-0.14*10(-3) m2/N; p < 0.05). Hormone replacement partially restored this value (1.8+/-0.49*10(-3) m2/N). No alterations in distensibility were found in the relaxed state. After adjusting for body weight, we found that pharmacological ovariectomy lowered venous inner radius significantly compared with control (p < 0.05), whereas hormone replacement increased it compared with pharmacological ovariectomy (p < 0.05) and more significantly compared with control (p < 0.01). CONCLUSION: Sex hormone depletion induces significant alterations in venous distensibility, presumably by inducing initial remodeling of the venous wall. Hormone dependency of distensibility differed in relaxed and contracted states of the vein, so some alterations of contractile elements of the wall may be hypothesized. Lower distensibility of the venous wall found after pharmacological ovariectomy could be part of the mechanism of predisposition for postmenopausal hypertension. This can be reversed by female sex hormone replacement.

Hormone replacement therapy reduces mean 24-hour blood pressure and its variability in postmenopausal women with treated hypertension.

BACKGROUND: The rate and severity of hypertension increase dramatically after menopause. Complications seem to be more frequent and marked in hypertensive patients with greater blood pressure (BP) variability, and antihypertensive treatment does not easily reduce this variability. The effect of hormone replacement therapy (HRT) on BP and its variability is not well understood in moderate to severe hypertension, but estrogen may have calcium channel-blocking properties. Cardiovascular events occur more frequently in the morning, likely in part because of a rise in BP. DESIGN: We prospectively studied 34 postmenopausal women with treated hypertension (mean age = 53 years) and receiving a cyclic combination of estradiol and norgestrel for 19 weeks with 24-h ambulatory BP monitoring. RESULTS: Mean daily BP and its variability decreased significantly with HRT (149.3 +/- 6.1 mm Hg vs. 140.3 +/- 8.5 mm Hg [p < 0.001]; diastolic: 95.4 +/- 4.7 mm Hg vs. 92.4 +/- 7.2 mm Hg [p < 0.05]). There was also a significant decrease in the early morning BP values after HRT (154.0 +/- 6.9 mm Hg vs. 145.6 +/- 11.0 mm Hg [p < 0.001]; diastolic: 98.0 +/- 4.8 mm Hg vs. 95.1 +/- 10.0 mm Hg [p < 0.05]). Subjects who were taking calcium channel blockers (n = 11) had only half the reduction in 24-h systolic BP compared with those who were not taking calcium channel blockers (5.3 mm Hg vs. 10.5 mm Hg), and the reduction in those who were taking calcium channel blockers failed to reach statistical significance. CONCLUSIONS: Our results demonstrate that HRT may have a role in decreasing the severity of hypertension, and the mechanism of its action might be through calcium channels.

Elevated endothelin-1 levels and persistent stage IV hypertension in a nonvolume overloaded anephric patient.

Persistent hypertension after nephrectomy is in most cases due to increased fluid volume. Endothelin-1 is a potent endogenous vasoconstrictor peptide. Its role in the development and maintenance of hypertension is not completely understood, but it might be significant in some cases. We report a case of stage IV hypertension after nephrectomy with elevated endothelin-1 levels and no volume overload.

Postmenopausal hormone replacement therapy and cardiovascular mortality in Central-Eastern Europe.

BACKGROUND: The leading cause of death among elderly women is cardiovascular (CV) disease in the United States and in Western Europe as well. The protective effect of postmenopausal hormone replacement therapy (HRT) on coronary heart disease has been verified in epidemiologic studies. There are no data available on the rate of HRT use in Eastern Europe. Our goals were to study the rates of HRT in Eastern Europe, to compare them to those of the United States and Western Europe, as well as to compare their CV mortality rates. METHODS: The use of HRT in Eastern Europe was calculated from sales records obtained from all pharmaceutical companies that ship HRT preparations to the given area. Data on HRT in Western countries were taken from the literature. Mortality rates were obtained from the World Health Organization. RESULTS: The rate (mean +/- SD) of HRT in Eastern Europe was 2.88 +/- 2.67%, whereas 12.67 +/- 9.97% in Western Europe and the United States, p < .05. The cardiovascular mortality rate per 100,000 women older than 45 years in Eastern Europe was higher (1766 +/- 158.3) than in the Western countries (1155 +/- 164.1, p < .001). CONCLUSIONS: The rate of HRT is markedly lower. whereas CV mortality rates are notably higher in Eastern Europe than in the United States or Western Europe. Because HRT seems to be underutilized in Eastern Europe, to increase its use might be an important tool to improve CV mortality rates. However, due to the risks associated with HRT, other measures to prevent coronary heart disease, such as smoking cessation programs, and other efforts should also be considered in Eastern Europe.

Hormone replacement reduces elevated in vivo venous tone in hypertensive ovariectomized rats.

OBJECTIVE: The venous system may play a role in the development and progression of postmenopausal hypertension. In the present study, we investigated the effect of chronic angiotensin II-induced hypertension on the geometric, elastic, and contractile properties of the saphenous vein in sex hormone deficient and replaced female rats. METHODS: Thirty Sprague-Dawley rats were ovariectomized (n = 10), ovariectomized and angiotensin-infused (n = 10), or ovariectomized plus angiotensin-infused and hormone replaced with estradiol and medroxyprogesterone (n= 10). After 4 weeks, the saphenous veins were removed and cylindrical segments of the vessels were placed into a microangiograph and cannulated at both ends. Intraluminal pressure versus outer diameter curves were registered in Krebs-Ringer solution, in maximal norepinephrine contraction, and in full papaverine relaxation. RESULTS: In vivo venous tone of the saphenous vein in ovariectomized plus angiotensin-infused animals was significantly higher than in ovariectomized animals without angiotensin treatment (27.2 +/- 3.7% versus 5.3 +/- 2.1%, respectively; P <.05). Hormone replacement restored venous tone (9.6 +/- 3.4%; P <.01). In vitro pressure-induced myogenic tone was markedly reduced by chronic angiotensin infusion, which was partially reversed by hormone replacement. Passive incremental distensibility was lowered after angiotensin infusion independently of the sex hormone state. CONCLUSION: Hormone replacement improved venous contractility (rapid adaptation response), which was seen as decreased in vivo venous tone, but venous distensibility (chronic adaptation) was not improved by hormone replacement in our short-term study. We demonstrate beneficial short-term effects of hormone replacement on the venous system in our model of postmenopausal hypertension. Further studies might be warranted to see whether long-term benefits can be achieved.

Advances in the treatment of diabetes-insulin analogues.

Insulin analogues are molecules derived by modifying the structure of the human insulin molecule, resulting in altered physico-chemical, biological and pharmacodynamic properties. The pharmacokinetic characteristics of the previously available rapid-, intermediate-, and long-acting preparations of human insulin make it almost impossible to achieve sustained normoglycemia. All currently available analogues have been shown to have a more physiological time-action profile with either a shorter onset and shorter duration of action (insulin lispro and insulin aspart) or a more constant effect lasting at least 24 hours (insulin glargine). These advantages in the time-action profiles have been shown to improve various surrogate parameters (e.g., postprandial blood glucose concentrations) in a number of randomized controlled trials. Insulin analogues also represent a unique tool to unravel structure-function relationships in insulin biochemistry and insulin action. Data on the currently available, currently tested and currently being developed analogs are reviewed.

Decreased beta2 adrenergic mediated venodilatation in Native Americans.

BACKGROUND: A considerable body of research has been accumulated regarding the pathogenesis and treatment of hypertension in Whites (Caucasians) and in Blacks. This research has led to more effective therapies geared specifically towards these ethnic groups. Unfortunately, very little information is available regarding the pathogenesis of hypertension and the effect of antihypertensive treatment in Native Americans (North-American Indians). Ethnic variability in the response to adrenergic mediated stimulation has been previously described, and reduced compliance of the venous system has been suggested among the possible mechanisms responsible for essential hypertension. The aim of this study was to compare venous responsiveness between Native Americans and Whites to vasoactive substances. METHODS: The alpha1-adrenergic agonist, phenylephrine and the beta2-adrenergic agonist isoproterenol were studied in 10 Native American and White volunteers. The dorsal hand vein technique was used, which is a simple, relatively non-invasive method to study the response to vasoactive substances, in vivo. RESULTS: The maximal venodilatory response to isoproterenol in the Native American group was 53.2+/-27.5%; while in the White group it was 103.4+/-66.0% (p<0.05). The maximal venoconstriction for phenylephrine in the Native American subject group was similar to that of the White group (85.4+/-24.0% vs. 89.4+/-10.9%) (p = n.s.). CONCLUSIONS: Based on our findings, we can anticipate that Native Americans may respond differently to antihypertensive therapy. However, further investigation needs to be done with an eye towards the development of drug therapy and treatment strategies tailored to this specific population.

Alterations of venous drug reactivity in humans: acquired and genetic factors.

Until recently, studies dealing with veins have almost always been the neglected part of vascular research. Recent data show an increasing rate of venous disease, and increasing evidence supports a role for veins in systemic diseases. The authors discuss and comment on findings of recent studies on venous drug reactivity. Alterations in venous reactivity to alpha- and beta-adrenergic, NO-dependent, and other drugs have been shown in many genetically determined and acquired conditions, such as hypertension, smoking, and aging. In some of them, the changes of venous responsiveness are most likely secondary to another process, while in others the they seem to play a primary role in the development of systemic disease states. Studying the drug reactivity of the venous system more extensively provides useful information for clinicians and researchers and will no doubt help to further knowledge of the normal and pathologic processes of the vasculature.

Supraclavicular abscess caused by Salmonella enteritidis in patient without gastrointestinal symptoms.

Soft tissue infections are among the rare manifestations of extra intestinal salmonellosis and occur more frequently in immunocompromised patients. Herein we report a case of a 51-year-old white male with type II. diabetes mellitus, diagnosed with supraclavicular abscess caused by Salmonella enteritidis. The patient denied any gastrointestinal symptoms, and stool cultures were negative. After incision, drainage, and administration of intravenous ampicillin (4 x 1.5 g/day for two weeks) the patient recovered completely. To our knowledge, this is the first reported case of cervical soft tissue abscess caused by Salmonella enteritidis without preceding gastrointestinal symptoms. We feel that the presence of diabetes was a risk factor for developing the infection.

[Quality of life and antihypertensive therapy]. / Eletminöség és antihypertensiv kezelés.

The patients' well-being during antihypertensive treatment markedly influences their compliance. Therefore, in the last several years the effect of antihypertensive medications on the quality of life has been examined all over the world. The terminological and methodical problems at the field of quality of life resulted in difficulties regarding the comparison of the results of different working groups. This review is focused on the results of randomised, double-blind studies. We found that ACE inhibitors, calcium channel blockers and selective beta blockers have the most beneficial effect on the quality of life.

[Basic principles of current trends in the management of hypertension and kidney disease in pregnancy]. / Hypertoniás és vesebeteg terhesek korszerü ellátásának alapelvei.

The approach to renal disease and hypertension in pregnancy has dramatically changed over the past two decades. As opposed to the past, now almost all the female patients with underlying renal disease can have successful pregnancy, and we are able to manage most of the renal complications occurring during the pregnancy. In this article the authors give an extensive review of the results of recent studies, concerning this subject. The options to prevent the predictable complications, the most recent therapeutic guidelines and the outcome of these patient's pregnancies are discussed, focused on the changes, compared to the recent past.