Effects of intravenously administered hypertonic urea solution

Summary and Conclusions In 12 patients with increased intracranial pressure, caused by an expanding process, a hypertonic urea solution was intravenously administered during a craniotomy. At different times before, during and after the operation, the electrolytes, urea, glucose and total protein values were determined in various body fluids and tissues.This study disclosed that the urea administered was distributed through both the intracellular and the extracellular space after 20 minutes. The values of the electrolytes, except the calcium, in the extracellular fluid remained constant after administration of the urea solution; the total protein value, however, showed a considerable decrease.It was established that the blood-brain barrier plays no appreciable role in the mechanism of action of hypertonic urea solutions in dehydrating the brain tissue; the blood-C. S. P. and brain-C. S. F. barriers may do.

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Zusammenfassung Bei 12 Patienten mit intrakranieller Drucksteigerung infolge eines raumbeengenden Prozesses wurde Harnstofflösung intravenös während der Schädeleröffnung gegeben. Zu verschiedenen Zeitpunkten vor, während und nach der Operation wurden Elektrolyt, Harnstoff, Glukose und Gesamteiweiß quantitativ bestimmt und zwar sowohl in verschiedenen Körperflüssigkeiten wie auch in Geweben.Die Untersuchungen ergaben, daß der verabfolgte Harnstoff in 20 Minuten sich sowohl auf den intrazellulären, wie den extrazellulären Raum verteilt hat. Die Elektrolytwerte, mit Ausnahme von Kalzium, blieben nach der Harnstoffinfusion in den extrazellulären Flüssigkeiten unverändert, der Gesamteiweißwert nahm dagegen beträchtlich ab.Es wurde festgestellt, daß die Bluthirnschranke keine wesentliche Rolle für die entwässernde Wirkung des Harnstoffes auf das Hirngewebe spielt, während die Blut-Liquor-Schranke und die Hirn-Liquor-Schranke vielleicht von Bedeutung sind.

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Resumen Después de una craniectomía se administró una solución de urea hipertónica por via intravenosa a 12 pacientes que presentaban una presión intracraneal creciente a causa de una exposición de la hipófisis. Periódicamente, antes, durante y después de la operación se determinaron los valores de los electrolitos, de la urea, de la glucosa y de las proteinas totales en los diferentes líquidos y tejidos del organismo.Este estudio demostróque la urea administrada se distribuia a través del espacio intra y extracelular al cabo de 20 minutos. Los valores de los electrolitos, excepto el calcio, permanecieron constantes en el líquido extracelular después de la administración de la solución de urea; el valor de las proteinas totales, sin embargo, mostró un descenso considerable.Se concluyó que la barrera hemato-encefálica no juega ningún papel apreciable en los mecanismos de acción de las soluciones de urea hipertónica en la deshidratación del tejido cerebral; tal vez lo juegue en las barreras sangre-liquido cofalo-raquídeo y cerebro-líquido cefalo-raquídeo.

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Résumé Lors d'une craniotomie, une solution d'urée hypertonique fut administrée par voie intraveineuse chez 12 patients présentant une pression intracrânienne grandissante causée par une expansion de l'apophyse. De temps en temps, avant, pendant et après l'opération, les valeurs des électrolytes, de l'urée, du glucose et de la protéine totale étaient déterminées dans les différents liquides et tissus du corps.Cette étude démontra que l'urée administrée était distribuée à travers l'espace intra et extraecllulaire au bout de 20 minutes. Les valeurs des électrolytes, excepté le calcium, demeurèrent constantes dans le liquide extracellulaire après l'administration de la solution d'urée; la valeur de la protéïne totale, pourtant, montrait une baisse considérable.Il fut établi que la barrière hémato-encéphalique ne joue aucun rôle appréciable dans le mécanisme d'action des solutions d'urée hypertonique dans la déshydratation du tissu cérébral; les barrières sang-liquide céphalorachidien et cerveau-liquide céphalo-rachidien, peut-être.

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Riassunto In 12 pazienti con ipertensione endocranica, causata da un processo espansivo, è stata somministrata durante la craniotomia dell'urea in soluzione ipertonica per via venosa. A diversi tempi prima, durante e dopo l'intervento, sono stati dosati gli elettroliti, l'urea, il glueosio e le proteine totali in vari fluidi e tessuti corporei. Queste ricerche hanno evidenziato che l'urea viene distribuita tra spazio intracellulare ed extracellulare in 20 minuti. I livelli degli elettroliti, eccetto il calcio, rimangono costanti nel liquido extracellulare dopo la somministrazione di urea, i valori della proteinemia totali invece mostrano una notevole diminuizione.E' stato stabilito che la barriera emato-cerebrale non gioca alcun ruolo apprezzabile nel meccanismo d'azione dell'urea ipertonica nel disidratare il tessuto cerebrale; un ruolo importante potrebbe essere inveoe giocato dalla barriera emato-liquorale e tra liquor e sistema nervoso.

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This study was supported by a grant from the Netherlands Organization for the Advancement of Pure Research (Nederlandse Organisatie voor Zuiver-Wetenschappelijk Onderzoek, Z. W. O.).     

Evolution of renal replacement therapy in East Germany from 1989 to 1992

Diminished availability of facilities for renal replacementtherapy is known to cause spuriously low acceptance and treatmentrates. In this context the evolution of renal replacement therapyin the former German Democratic Republic is a useful model tostudy and to quantify some of the relevant factors. We performed a survey in all dialysis units for adults in EastGermany (excluding East Berlin) by questionnaire, achievinga response rate of 97%. From December 1989 to December 1992the number of dialysis centres increased from 53 to 96 (+81%),reaching 6.7 centres p.m.p. Of these facilities, 45% were hospitalunits, 29% private units, and 26% dialysis units run by non-profithealth care organizations. The number of dialysis stations forregular dialysis treatment increased from 602 to 1276 (+112%),i.e. 89 stations p.m.p. In parallel, the number of chronic dialysispatients increased from 2127 to 3848 (+81%), i.e. 267 patientsp.m.p. A more detailed survey was carried out in Thüringen andpart of Sachsen, in a region covering 5 million inhabitants.The acceptance rate for chronic dialysis treatment has increasedfrom 49 to 107 patients p.m.p. (+115%). The average age of newpatients increased from 49 to 59 years, the proportion of patientsaged 65 years increased from 16 to 42% and the proportion ofdiabetics from 13 to 35%. Introduction of alternative treatmentmodalities became possible, with 2.3% of the patients receivinghaemofiltrations and 3% CAPD. The proportion of HBs-antigen-positivepatients decreased from 14.2% to 5%. At the end of 1989 in the former GDR (excluding East Berlin),773 patients and, at the end of 1992, 1153 patients were alivewith functioning renal transplants (+49%). The annual rate oftransplantations was 254 in 1989, and 283 in 1992 (+11%), i.e.18 transplantations p.m.p. (including East Berlin). At the end of 1989 2900 patients (193 p.m.p.), and at the endof 1992 5001 patients (347 p.m.p.), werealive on renal replacementtherapy (dialysis or functioning renal transplant) in East Germany,excluding East Berlin; this represents a 72% increase. The figures in East Germany are now almost equivalent to thosein West Germany regarding the number of admissions (incidence),whereas the number of patients on renal replacement therapyis still lower (prevalence).     

Blood cholesterol and apolipoprotein B levels in relation to intakes of animal and plant proteins in US adults

Few studies have examined the association between specific sources of protein and blood lipids in a national sample of adults. We examined this relationship in a sample of adults 20 years and older who participated in phase 1 (1988-91) of the Third National Health and Nutrition Examination Survey, a representative sample of the United States non-institutionalized population. After excluding those participants who reported having been told they had high blood cholesterol concentrations, the final sample size was 6228. Mean intakes of different sources of proteins, as a percentage of total protein, were compared in quartiles of blood lipids. Intakes were adjusted for age, sex and race. Additional adjustments were made for other dietary variables, recall day, BMI, smoking, and income. We observed a lower percentage meat, fish and poultry (MFP) protein intake, including a lower percentage of beef and pork protein, among persons in the lowest quartile of serum total cholesterol and apolipoprotein B (ApoB) concentrations than among persons in the higher quartiles. The percentage of plant protein intake was higher in the lowest quartile than in the highest quartile of serum cholesterol. We also observed a higher percentage of fruit protein intake with lower serum cholesterol and ApoB concentrations. We conclude that in this cross-sectional sample, consumption of MFP proteins was consistently higher among persons with higher cholesterol concentrations while consumption of plant proteins was consistently higher among persons with lower cholesterol concentrations. Our findings support the importance of assessing intake of specific protein sources, especially in studies that address dietary intake in relation to blood lipids.     

Whipple's disease in a man with weight loss and diarrhea

In a 45-year-old man with diarrhoea, upper abdominal pain and malabsorption Whipple's disease was diagnosed by gastroduodenoscopy with small bowel biopsies. The disease is rare and can present with gastrointestinal problems but also with cardiac or neurological complaints. Tropheryma whippelii, the aetiological organism, can be demonstrated by pathological investigation of biopsies and with the polymerase chain reaction (PCR). Treatment with trimethoprim-sulfamethoxazole 160-800 mg twice daily is the therapy of choice: it must be continued for a year, otherwise there is a high possibility of relapse. Correct diagnosis, based mostly on gastroduodenoscopy, can lead to the right therapy and recovery of the patient.     

Transient lowering of plasma vitamin B12 concentrations in Ouessant sheep fed on a potassium-rich ration.

The hypothesis tested was that a high intake of potassium (K) interferes with cobalt (Co)-vitamin B12 metabolism in ruminants. Ouessant sheep were fed either a low- (8 g K/kg dry matter) or high-K diet (43 g K/kg dry matter) with an adequate amount of Co (124 micrograms Co/kg dry matter). Plasma vitamin B12 concentrations were measured. Sheep fed a low-K diet, but containing only 70 micrograms Co/kg dry matter, served as positive controls. Feeding the low-Co ration produced a significant decrease in plasma vitamin B12 concentrations. The high- versus low-K ration induced a significant decrease in plasma vitamin B12 during the first 6 weeks, but thereafter the values in the high-K group rose to those seen in the low-K group. The mechanism by which dietary K may interact with Co-vitamin B12 metabolism in sheep is unknown.     

Active enhancement in the primate by bone marrow I. Ia-like determinants on nucleated bone marrow cells.

This study investigates the possibility that the active enhancing properties of bone marrow (BM) cells may be related to Ia-like determinants on their surface membranes. Less chromium was released on a cell per cell basis from nucleated baboon BM cells used as targets in complement-dependent cytotoxicity than from labelled lymph node lymphocytes. On the other hand, BM cells stimulated allogeneic lymphocytes in culture more vigorously than lymph node lymphocytes. BM cells with lymphocyte-activating properties could be enriched by fractionation on a discontinous bovine serum albumin gradietnt. BM cells responded poorly to allogeneic cell stimulation in mixed culture. Platelet absorption studies of an alloantiserum supported the conclusion that nucleated BM cells, and particularly BM fractions collected from the less dense interfaces of a bovine serum albumin gradient, express relatively more lymphocyte-activating or Ia-like determinants than "serologically defined" determinants.     

Detection of migrated allogeneic oligodendrocytes throughout the central nervous system of the galactocerebrosidase-deficient twitcher mouse

Summary Galactocerebrosidase-deficient oligodendrocytes of twitcher (twi/twi) mice degenerate prematurely. Transplantation of normal bone marrow cells has been shown to alleviate symptoms and to prolong survival time. However, characteristic ataxia (twitching) is not cured. In an attempt to improve further the condition of twitcher mice, allogeneic foetal liver cells were transplanted as a source of normal haemopoietic stem cells and supplemented with intracerebral transplantation of foetal brain cells. A reliable method was developed to detect donor-type cells in brain tissue. Bacteriophage . transgenic foetal mice were used as donors of both foetal liver and brain cells. Integrated copies of . DNA in donor cells were detected byin situ hybridization with biotinylated probes, which were then stained using streptavidin alkaline phosphatase. This technique was combined with immunohistochemistry to distinguish donor-type oligodendrocytes from macrophages. Immunoperoxidase staining with an antiserum to carbonic anhydrase-II produced dark perikarya of oligodendrocytes. The results demonstrated that local foetal brain cell grafts resulted in a wide dissemination of donor-type oligodendrocytes throughout the twitcher brain. The addition of a foetal brain cell graft to haemopoietic cell transplantation resulted in significantly prolonged survival of twitcher mice.     

Psychological Problems among Head and Neck Cancer Patients in Relation to Utilization of Healthcare and Informal Care and Costs in the First Two Years after Diagnosis

Background: To investigate associations between psychological problems and the use of healthcare and informal care and total costs among head and neck cancer (HNC) patients. Method: Data were used of the NETherlands QUality of Life and Biomedical Cohort study. Anxiety and depression disorder (diagnostic interview), distress, symptoms of anxiety and depression (HADS), and fear of cancer recurrence (FCR) and cancer worry scale (CWS) were measured at baseline and at 12-month follow-up. Care use and costs (questionnaire) were measured at baseline, 3-, 6-, 12-, and 24-month follow-up. Associations between psychological problems and care use/costs were investigated using logistic and multiple regression analyses. Results: Data of 558 patients were used. Distress, symptoms of anxiety or depression, FCR, and/or anxiety disorder at baseline were significantly associated with higher use of primary care, supportive care, and/or informal care (odds ratios (ORs) between 1.55 and 4.76). Symptoms of anxiety, FCR, and/or depression disorder at 12-month follow-up were significantly associated with use of primary care, supportive care, and/or informal care (ORs between 1.74 and 6.42). Distress, symptoms of anxiety, and FCR at baseline were associated with higher total costs. Discussion: HNC patients with psychological problems make more use of healthcare and informal care and have higher costs. This is not the result of worse clinical outcomes.     

Modulation of IL-8 and RANTES release in human conjunctival epithelial cells: primary cells and cell line compared and contrasted

PURPOSE: Recent research indicates that epithelial cells of the ocular surface can contribute to the allergic reaction by the release of inflammatory and/or chemotactic mediators. In this study, the role of two inflammatory mediators, previously identified in the tear film of ocular allergy subjects, TNF-alpha and IFN-gamma, were evaluated for their effect on the release of two chemotactic mediators, IL-8 and RANTES, from cultured human conjunctival epithelial cells. METHODS: Human conjunctival epithelial cells (primary cells or HC0597 cell line) were grown to confluence and stimulated with various concentrations of TNF-alpha, IFN-gamma, or a combination of both. Supernatants were collected at 6, 24, and 48 hours and stored frozen for subsequent ELISA analyses of RANTES and IL-8. RESULTS: RANTES and IL-8 release from HC0597 cells was stimulated in a dose- and time-dependent manner following treatment with TNF-alpha. However, only RANTES release was modulated by IFN-gamma treatment. Treatment of HC0597 cells with both TNF-alpha and IFN-gamma resulted in a synergistic increase in the release of RANTES. This synergistic effect was confirmed using primary cultures of human conjunctival epithelial cells. CONCLUSIONS: Stimulation of conjunctival epithelium with proinflammatory mediators, TNF-alpha and/or IFN-gamma, generated the release of the chemotactic factors IL-8 and RANTES, which could act to prolong inflammation. These two chemokines may prolong inflammation by recruiting eosinophils to the ocular surface. This is the first study to compare chemokine release in a cell line and primary cells; similar chemokine release after mediator stimulation was demonstrated, indicating that the two cell types are phenotypically similar.     

Pharmacological aspects of neonatal antidepressant withdrawal

Depression is common in reproductive age women, and continued pharmacologic treatment of depression during pregnancy may be necessary to prevent relapse, which could be harmful for both the fetus and the mother. Although data on drug safety are imperfect and incomplete, the benefits of antidepressant therapy during pregnancy generally outweigh the risks. Neonates who are exposed to antidepressant medications during gestation are at increased risk to have neonatal withdrawal syndrome, although the exact incidence of this complication is unknown because the definition of the syndrome is not clear and withdrawal reactions are probably underreported. Tricyclic antidepressant withdrawal syndrome is most likely related to muscarinergic activity and individual drug half-lives, and selective serotonin reuptake inhibitor withdrawal may be due to a decrease in available synaptic serotonin in the face of down-regulated serotonin receptors, the secondary effects of other neurotransmitters, and biological or cognitive sensitivity. Other factors that influence neonatal toxicity or withdrawal include the normal physiologic changes of pregnancy, the altered activity of CYP450 enzymes during pregnancy, drug-drug transporter (PgP and OCT3) interaction, and the presence of genetic polymorphisms in genes influencing drug metabolism. Further research is necessary. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader should be able to explain the importance of antidepressant therapy during pregnancy and postpartum, summarize the important neonatal effects of antidepressants, and describe the potential teratogenic effects of antidepressants.