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PubMed1991

Heterozygous pyruvate kinase deficiency and severe hemolytic anemia in a pregnant woman with concomitant, glucose-6-phosphate dehydrogenase deficiency.

The aim of this paper is to describe the clinical and hematological characteristics of a 32-year-old woman with concomitant heterozygous pyruvate kinase (PK) and glucose-6-phosphate dehydrogenase (G6PD) deficiencies and severe hemolytic anemia during pregnancy. In 1964, Oski et al. described a family in which a clinically healthy woman was heterozygous for both PK and G6PD deficiencies. To our knowledge, the present case is the first described in which the same condition is associated with hemolysis. A heterozygous condition for both enzymopathies was clearly demonstrated by family study criteria, and all other causes of hemolytic anemia were eliminated. No evidence of genetic relationship between the two disorders was demonstrated. Since late onset of hemolysis in heterozygous PK-deficient women has been observed in association with pregnancy and the molecular characteristics of the concomitant deficient G6PD enzyme were kinetically favorable, partial PK deficiency is suggested as the major cause of hemolysis in this patient.

Adult↗

PubMed1998

Chronic allograft vasculopathy: new strategies for drug development.

Chronic rejection reflects cumulative trauma to the allograft regardless of its origin. The main histologic feature in chronic rejection in all allografts is proliferative allograft vasculopathy. According to the current paradigm, chronic rejection can be prevented by more intensive and selective immunosuppression. Experimental retransplantation to donor strain suggests that elimination of histoincompatibility does not prevent progression of the disorder after the initial stimulus has been sufficiently strong or long-lasting. In order to design additional sites for intervention after this point of no return, attention has focused on the regulation of the synthesis and/or action of smooth muscle cell growth factors. In several preclinical models, the blocking of growth factor synthesis, blocking of the binding of the growth factors to their receptors, and/or growth factor signaling downstream of the receptor, have successfully been used in the inhibition of the intimal response and allograft vasculopathy. Inhibition of proteolytic enzymes, necessary for smooth muscle cell locomotion, may provide additional sites of intervention. However, on most occasions, the inhibitory effect is incomplete only 30% to 50% of maximal. The future will demonstrate whether several approaches must be applied concomitantly, or whether genes regulating several of these ligands and their receptors simultaneously can be identified and exploited.

Animals↗

PubMed1996

Aquaretic agents: a new potential treatment of dilutional hyponatremia in cirrhosis.

An impairment in the renal capacity to excrete water is a common finding in patients with cirrhosis and ascites. In some patients this abnormality is minor since it is only detectable by measuring urine volume or free water clearance after a water load and is not associated with changes in plasma osmolality and serum sodium concentration. In other patients the intensity of the disorder is such that they are not able to eliminate their regular water intake, and develop dilutional hyponatremia and hypoosmolality. The renal capacity to excrete water is one of the most useful prognostic indicators in patients with cirrhosis and ascites. The main pathogenic factors of the impaired water excretion in human cirrhosis are an increased plasma concentration of AVP, a reduced renal synthesis of prostaglandins and a reduced delivery of filtrate to the ascending limb of the loop of Henle. At present, no effective therapy exists for the management of this complication. Two types of drugs have recently been reported that selectively increase renal water excretion, antagonists of the AVP V2 receptors and kappa-opioid agonists. Experimental studies have shown that both substances improve water excretion in rats with cirrhosis and ascites. Therefore, these drugs may represent a novel therapeutic tool in the management of spontaneous hyponatremia in cirrhosis and in the treatment or prevention of diuretic-induced hyponatremia in these patients.

Animals↗

PubMed1989

[Design and effect of sports shoe insoles for the runner].

Running injuries of the lower extremities are more frequent with increasing intensity and extent of training. Biomechanical investigations demonstrate that exertion induced injuries of the foot, achillotendinitis, patellar tendinitis and shin splint syndrome are correlated with disorders in footstrike patterns. Therefore running shoe insoles can eliminate peak forces by exactly placing supporting elements. Furthermore peak forces may be distributed and complaints may be reduced. 50 runners with exertion induced injuries of the lower extremity were provided with appropriate running shoe insoles. There were excellent results in 34% and good results in 42%. 20% had moderate improvements while only 4% had unchanged complaints.

Achilles Tendon↗

PubMed1986

[Familial proximal tubular azotemia. Elevated urea plasma levels in normal kidney function].

A family showed a renal disturbance, characterized by an elevated urea plasma concentration while glomerular filtration was found to be normal. A detailed study of renal clearance was performed on two members of this family in order to define the nature and site of the disorder. Evidence points to an isolated impairment of urea elimination, giving rise to a reduced urea concentrating ability and thus to a decrease in maximum urine concentration and water conservation. The most probable site of this impairment seems to be the proximal tubule.

Adult↗

PubMed1999

Phenotypic analysis of seizure-prone mice lacking L-isoaspartate (D-aspartate) O-methyltransferase.

Within proteins and peptides, both L-asparaginyl and L-aspartyl residues spontaneously degrade, generating isomerized and racemized aspartyl residues. The enzyme protein L-isoaspartate (D-aspartate) O-methyltransferase (E.C. 2.1.1.77) initiates the conversion of L-isoaspartyl and D-aspartyl residues to normal L-aspartyl residues. This "repair" reaction helps to maintain proper protein conformation by preventing the accumulation of damaged proteins containing abnormal amino acid residues. Pcmt1-/- mice manifest two key phenotypes: a fatal seizure disorder and retarded growth. In this study, we characterized both phenotypes and demonstrated that they are linked. Continuous electroencephalogram monitoring of Pcmt1-/- mice revealed that abnormal cortical activity for approximately 50% of each 24-h period, even in mice that had no visible evidence of convulsions. The fatal seizure disorder in Pcmt1-/- mice can be mitigated but not eliminated by antiepileptic drugs. Interestingly, antiepileptic therapy normalized the growth of Pcmt1-/- mice, suggesting that the growth retardation is due to seizures rather than a global disturbance in growth at the cellular level. Consistent with this concept, the growth rate of Pcmt1-/- fibroblasts was indistinguishable from that of wild-type fibroblasts.

Animals↗

PubMedDate not supplied

Allergen-induced inflammation and the role of immunoglobulin E (IgE).

The prevalence of common allergic disorders such as asthma, allergic rhinitis, and atopic dermatitis has increased significantly in the past 30 years. The impact of these atopic diseases on the patient and the health care system is considerable: Allergic disorders are associated with a high degree of morbidity, which can profoundly impact patient quality of life and health care resource use. Existing strategies to treat allergic disorders beyond simple allergen avoidance focus on diminishing or eliminating the recurrent and/or persistent signs and symptoms that characterize the allergic response. A new strategy has been developed that uses antibodies directed against immunoglobulin E (IgE) to prevent it from binding to cells bearing its receptors and thus neutralizing the allergic response before it begins. These new agents reduce allergic responses in atopic individuals and improve their symptoms while reducing rescue medication and corticosteroid use in patients with allergic asthma or seasonal allergic rhinitis. Thus, anti-IgE antibodies represent proof that IgE plays a central role in allergic reactions and that anti-IgE therapy is a potentially effective treatment for allergic disease.

Anti-Allergic Agents↗

PubMed2005

The mechanism of high-pressure-induced ordering in a macromolecular crystal.

A previous study showed that the diffraction from cubic crystals of an icosahedral virus, cowpea mosaic virus (CPMV), was dramatically improved under elevated hydrostatic pressure. This use of pressure may have a significant impact on structural biology if it is found to be generally applicable. There were two types of cubic crystals assigned in either an I23 or P23 space group. They show the same rhombic dodecahedral morphology at atmospheric pressure. The crystals assigned to the I23 space group diffracted X-rays to higher resolution than those with P23 space group. The assignment of P23 space group was owing to the presence of reflections with indices of h + k + l = (2n + 1) (odd reflections), which are forbidden in space group I23. Analysis of the odd reflections from the P23 crystals at atmospheric pressure showed that they can originate from a rotational disorder in the I23 crystals. The odd reflections were eliminated with the application of 3.5 kbar of pressure, which transformed the crystals from the apparently primitive cell to the body-centered I23 space group with dramatic improvement in diffraction. A mechanistic model is proposed to describe the induction of order by rectifying the imperfection, which is consistent with the experimental data.

Comovirus↗

PubMed1995

Burning mouth syndrome.

BACKGROUND AND OBJECTIVES: Burning mouth syndrome (BMS) is a frequent process that produces marked oral dysesthetic symptoms. There is controversy over its etiopathogenesis and diagnosis. Therapeutic results are unsatisfactory. The objectives of this study were: (1) to analyze a possible agreement on the definition of BMS; (2) to analyze its cause; (3) to propose a therapeutic scheme that has been shown to be highly effective in our experience and has not been previously reported. METHODS: Five hundred patients with symptomatology of BMS were retrospectively evaluated with a study protocol, specially designed for this disease. Patients with local or general disease processes that could cause secondary asymptomatic stomatodynia were excluded from the study. RESULTS: Most of the patients evaluated were women over 60 years of age with oral symptoms, including a sensation of heat and burning, and pain, lasting for months or years, and a history of multiple unsuccessful treatments. The patients showed depression associated with anxiety, with evidence of psychiatric disorders in the family. Based on these findings and eliminating symptomatic painful conditions of the mouth that may stimulate this syndrome, we diagnosed a genuine or basic BMS of psychosomatic origin. Therapies used in the treatment of these neurotic conditions were not always useful. Tranylcypromine associated with anxiolytics and hypnotics in low doses plus the support of psychotherapy by the stomatologist were the most effective treatments. CONCLUSIONS: The BMS should be defined as a psychosomatic process causing oral dysesthesias for months or years.

Adult↗

PubMed2006

The clinical pharmacokinetics of darifenacin.

Darifenacin hydrobromide is a selective muscarinic M(3) receptor antagonist that is indicated for use in treatment of overactive bladder disorder. Darifenacin was found to have a short terminal elimination half-life after intravenous and immediate-release oral dosage forms (3-4 hours) but this increased with a prolonged-release (PR) formulation (14-16 hours). The absolute bioavailability of darifenacin from 7.5 and 15 mg PR tablets was estimated to be 15.4% and 18.6%, respectively. With repeated once-daily oral administration of the PR formulation, peak plasma concentrations of darifenacin are achieved approximately 7 hours post-dose. After oral administration, darifenacin is well absorbed from the gastrointestinal tract and very little unchanged drug (<2%) is recovered in the faeces. Steady state is achieved after 6 days of once-daily administration of the PR formulation. As expected, values of peak plasma concentration (C(max)) and area under the plasma concentration-time curve are dose dependent, although the increase in plasma concentrations is proportionally greater than the increase in dose owing to saturation of presystemic metabolism. From intravenous administration, it has been established that darifenacin possesses a moderate-to-high hepatic extraction ratio, with high plasma clearance (36-52 L/h) and a volume of distribution (165-276L) that exceeds total body water. It is highly protein bound (98%), primarily to alpha(1)-acid glycoprotein. Darifenacin is subject to extensive hepatic metabolism, with 3% of unchanged drug excreted in urine and faeces. Metabolism is mediated by hepatic cytochrome P450 2D6 and 3A4, the main metabolic routes being monohydroxylation in the dihydrobenzfuran ring, dihydrobenzfuran ring opening, and N-dealkylation of the pyrrolidine nitrogen. Several possibly important drug-drug interactions have been identified with darifenacin, including ketoconazole, erythromycin and fluconazole, each of which increases darifenacin mean C(max) by 9.52-, 2.28- and 1.88-fold, respectively. When given with imipramine, darifenacin causes 1.6-fold higher plasma concentrations of the antidepressant and its major metabolite. Moderate hepatic impairment, but not renal insufficiency, has been shown to increase plasma concentrations of the drug. The pharmacokinetic profile of darifenacin is not affected by food.

Benzofurans↗

PubMedDate not supplied

[Meningococcal sepsis and DIC in childhood: a report of a clinical case].

Disseminated intravascular coagulation (DIC) is a frequent complication of meningococcal sepsis in children. The clinical course variability, the severity of manifestations and the need of an early diagnosis for appropriate treatment, guides us to report a case of meningococcal sepsis and DIC. The patient, male, prematurely born, 11 months years old, presented himself with high fever of sudden onset, malaise, diarrhea, diffuse skin rash with abdominal petechiae, and no clinical evidence of meningitidis. Initial hematochemical findings, peripheral leukocytosis, quantitative and qualitative changes in plasma coagulation factors, liquoral hypocellularity together with the development of signs of meningeal irritation (stiff neck and back) were considered diagnostic clues for meningococcal sepsis associated with DIC. A gram-negative diplococcus was cultured from liquor. Primary goals of the treatment of this life-threatening clinical picture were the elimination of the bacterial component, the correction of clotting disorders and careful control of shock and metabolic acidosis often related with DIC. The patient then received a wide spectrum Cephalosporin, fresh frozen plasma, appropriate electrolyte solutions and eventually heparin, which led to a complete control and resolution of symptomatology.

Acidosis↗

PubMed1990

[Neuromuscular disorders].

In this study, the author focuses on three neuromuscular disorders that have historically been isolated to a specific region in Québec. The author is convinced that appropriate nursing interventions can help in the detection of these disorders and can, using data on social behavior, help eliminate harmful genetic mutations.

Health Education↗

PubMed1989

[Usefulness of the evaluation of blood supply and mass of the liver for predicting the rate of pharmacokinetics of lidocaine, propranolol and phenazone].

A group of patients with hepatocirrhosis were studied for the speed of liver elimination of lidocaine iv (n = 11), propranolol per os (n = 8) and phenazone per os (n = 19); they were also studied for blood supply in liver by means of sequential hepatoscintigraphy. Ultrasonography was used to evaluate the portal system and collaterals of the collateral circulation, endoscopy was used to evaluate the size of oesophageal varices, lateral projection of scintigraphic picture made it possible to calculate the liver mass. The half-life of propranolol and lidocaine in the initial phase of elimination correlated with the degree of portal-arterial disorders in liver blood supply. Propranolol bioavailability correlated with the diameter of the portal vein and was dependent on the size of oesophageal varices and the presence of cavernous transformation of the portal vein. No correlation was found between hepatic clearance of phenazone and vascular pathology of cirrhotic liver, but positive correlation was found between clearance and liver mass. Morphological and functional examinations of the vascular system of the cirrhotic liver were of greater predicative value for the evaluation of the pharmacokinetics of drugs than clinical progression of hepatocirrhosis in the Child-Turcott classification.

Adult↗

PubMed1989

[The "normal" pneumatization of the temporal bone].

Radiographs of the mastoids and the petrous pyramids of ear-healthy adults were investigated to ascertain the normal appearance of the temporal bone pneumatisation. The radiographs included those of patients with skull trauma, provided that these subjects had had no signs or symptoms of middle ear disease or hearing loss before the trauma. The extent of pneumatisation of the mastoid and petrous pyramid ranged from small cell groups around the mastoid antrum to extensive cell formations in the squamous temporal bone, in the apex of the petrous pyramid and in the retrosinus area. The planimetric measurements did not correspond to a normal distribution. It was also striking that ears could be found among these healthy individuals with irregular, asymmetric or indistinct pneumatisation, probably as a residual of sub-clinical middle ear disorders during the development of the cell system. After eliminating these irregular findings the ears with exclusively regular, symmetric and clear cell pictures also did not follow a normal distribution. Rather, they resulted in a typical curve with a steep ascent rising from a functionally-necessary minimum of about 4 cm2 to mean values of 8-12 cm2, and then a wide distribution reaching a value of 26 cm2. All these can be taken as genetically-determined "normal variants". The irregular cell-formations were seen mainly in the smaller pneumatised mastoids, so that it can be concluded that exogenous influences have at some time disturbed the pneumatisation process.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1988

Radiotherapy of metastatic renal cell carcinoma.

Modern oncological treatment of metastatic renal cell carcinoma may have different goals: first of all, improvement of survival rates; secondly, elimination of symptoms like pain from osseous lesions or disorders of central nervous system functions. Chemotherapy or radiotherapy or the combination of both should improve life quality and be tolerable to the patient. Close interdisciplinary contacts of medical and radiological oncologists are therefore necessary. Radiotherapy should be carried out under conditions of high-voltage energy and modern treatment planning to concentrate and limit the irradiation volume as much as possible. Split-course technique and radiation as interval treatment between chemotherapy courses seem to be optimal. Our clinical results indicate that the reported radioresistance of renal cell carcinoma might result from radiobiological and methodological misinterpretations.

Bone Neoplasms↗

PubMed1988

Liver transplantation for protoporphyria. Evidence for the predominant role of the erythropoietic tissue in protoporphyrin overproduction.

Protoporphyria is an inherited disorder of heme biosynthesis characterized by an overproduction of protoporphyrin in the erythropoietic and hepatic tissues, the relative contribution of which in the metabolic disorder has not been directly quantitated. Excess protoporphyrin is eliminated solely by the liver into the bile and feces. We describe the case of a patient with protoporphyria complicated by severe cirrhosis in whom liver transplantation was performed and resulted in almost complete disappearance of skin photosensitivity manifestations and reduction in the level of protoporphyrin in erythrocytes. However, the level of protoporphyrin in feces was not markedly different before and after liver transplantation, which suggests that overproduction of protoporphyrin was unchanged. These findings are consistent with the view that the diseased liver and ensuing low hepatic clearance of protoporphyrin contributed to accumulation of protoporphyrin in the body and that, at least in this patient, the role of the hepatic tissue in the overproduction of protoporphyrin was small in comparison with that of the erythropoietic tissue.

Adult↗

PubMed1982

[Value of physical methods in therapy].

Although the possibilities of physical methods and the active principles of physical medicine can only used to a very modest and small extent in the treatment of lymphatic edemas, they are nevertheless some of the few approaches to helping patients with such disorders effectively. As in so many chronic diseases, we must first of all restrict ourselves to assiduous and consistent control of functional disorders in order to improve them and perhaps occasionally eliminate them in mild cases. The active principle is the control of function!

Geriatrics↗

PubMed1981

Does metapsychology still exist?

Metapsychology has been under attack from two principal directions: from those who believe that metapsychology is no longer congruent with observations; and from those who see metapsychology as irrelevant, as they no longer share Freud's belief that psychoanalysis is a form of natural science. In addition there is no shared agreement as to the definition of metapsychology itself. The author observes three different functions of metapsychology: a selection of psychological phenomena that could be termed universal in the sense that they are characteristic of the human species; secondly a set of assumptions upon which a psychological system can be founded and made explicit; and thirdly metapsychology functions as a modelling device, an imaginary entity, an experiment in thinking. When we refer to metapsychology we are not describing a single entity but a broad heading that contains at least these three distinct functions. We believe that psychoanalysis is a unique discipline in that it shares with the hermeneutic disciplines the use of empathy as a mode of observation, viewing man from the inside, but subjects these observations to the organizing functions of metapsychology which views man from the outside. It is characteristic of psychoanalysis that there are rapid shifts from the I-Thou (empathic identification) to the I-It (naturalist observer) position. For this reason psychoanalysis cannot be fitted into any ready made epistemology. Any attempt to replace metapsychology by action theory or by the organizing principles of the structure of language are announcements of programmes yet to be realized and there is reason to doubt whether such programmes are realizable. There are, however, empiric discrepancies which require a modification but not the elimination of metapsychology. Our newer observations of narcissistic character disorders, especially the mirroring function, suggest that maturation is not necessarily equated with internalization - that a "fitting in" front the environment remains an adult requirement and is not necessarily the persistence of something infantile. So that the ego and its relation to the human environment is not a closed system. The task of contemporary metapsychology is to encompass this newer knowledge from the narcissistic disorders without "reifying' a system of "internalized' objects or returning to a simplistic theory of "interpersonal relationships'. Metapsychology needs to be modified but not abandoned.

Ego↗