RESUMEN
Prior research on donor monoclonal gammopathy of undetermined significance (MGUS) has been inadequate regarding the risk for lymphoproliferative disease in solid organ transplantation recipients. Seven organ recipients from two different donors developed lymphoproliferative disease. The origin of the malignancy was determined by use of microsatellite analysis, and the plasma of the two donors was analyzed with the use of electrophoresis. The clinical courses of the seven recipients were followed for 36-60 months. One donor transmitted lymphoplasmacytic lymphoma to two kidney recipients and MGUS to a liver recipient, all IgMκ. A second donor caused IgGλ myeloma in two kidney and one liver recipient, and IgGλ gammopathy in a heart recipient. Transplant nephrectomy was performed in three kidney recipients and remission was achieved. The fourth kidney recipient has kept the graft and the disease has progressed. The liver recipient died from myeloma. There were no clinical signs of lymphoproliferative disease in the donors, but retrospective serum analyses showed M-components, IgMκ (37 g/L) and IgGλ (8 g/L). Donors with MGUS may cause donor-transmitted malignancies via passenger lymphocytes/plasma cells in solid organ recipients. The results call for a large register study of the incidence of donor MGUS and lymphoproliferative disease in their recipients.
Asunto(s)
Rechazo de Injerto/etiología , Trastornos Linfoproliferativos/etiología , Trasplante de Órganos/efectos adversos , Paraproteinemias/complicaciones , Donantes de Tejidos , Receptores de Trasplantes , Adulto , Anciano , Femenino , Estudios de Seguimiento , Rechazo de Injerto/diagnóstico , Supervivencia de Injerto , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Pronóstico , Factores de RiesgoRESUMEN
BACKGROUND: Improved glycaemic control during pregnancy in mothers with type 1 diabetes (T1DM) and gestational diabetes (GDM) has resulted in a marked reduction of perinatal mortality and morbidity, but the prevalence of macrosomia is usually high. OBJECTIVE: We used non-invasive anthropometric methods to estimate the body composition and the thickness of the interventricular heart septum in 18 infants of mothers with well-controlled T1DM, 10 infants of mothers with GDM and 28 infants of healthy control mothers matched for gestational age and mode of delivery. METHODS: Skinfold measurements were obtained with a Harpenden calliper within 48 h after delivery. Echocardiography was also performed to measure the thickness of the interventricular septum. Cord blood was sampled for assays of C-peptide, leptin and IGF-I. RESULTS: The rates of macrosomia (gestational age-adjusted birth weight >2 standard deviation score, SDS) were 56 and 30% in infants of mothers with T1DM and GDM, respectively, compared to 10% in control infants. The body fat content was 40% (0.2 kg) higher and the interventricular heart septum thickness was increased by 20% in both groups of infants of diabetic mothers. We found no associations between maternal levels of HbA1c during pregnancy and body composition or interventricular heart septum thickness. Cord levels of C-peptide and leptin were significantly higher in infants of T1DM mothers than in control infants. Cord leptin level was associated with birth weight SDS and percent body fat in infants of T1DM mothers. IGF-I was associated with percent body fat in infants of GDM mothers and control mothers. A multiple-regression analysis showed that 50% of the variation in body weight SDS could be determined, with IGF-I, leptin and C-peptide as independent variables. CONCLUSION: Both fat mass and cardiac septal thickness are increased in newborn infants of women with T1DM and GDM in spite of efforts to achieve good glycaemic control during pregnancy.
Asunto(s)
Tejido Adiposo , Diabetes Mellitus Tipo 1/fisiopatología , Diabetes Gestacional/fisiopatología , Macrosomía Fetal/epidemiología , Hemoglobina Glucada/fisiología , Tabiques Cardíacos/patología , Recién Nacido , Adulto , Glucemia/metabolismo , Composición Corporal/fisiología , Péptido C/sangre , Estudios de Casos y Controles , Diabetes Mellitus Tipo 1/sangre , Diabetes Gestacional/sangre , Femenino , Humanos , Hipertrofia/epidemiología , Factor I del Crecimiento Similar a la Insulina/metabolismo , Leptina/sangre , Embarazo , Prevalencia , Análisis de RegresiónRESUMEN
Thirty patients with gonarthrosis were operated on with the PCA primary total knee prosthesis and had the tibial component fixed to the bone by partial cementation. In the first two groups of patients, cementation was by a peripheral rim of high and low-viscosity cement, respectively. In the third group, the pegs were cemented with the low-viscosity cement. Follow-up was performed with use of clinical parameters and roentgen stereophotogrammetric analysis. Clinically, the series was successful apart from a problem with tibial component wear, necessitating revision in five patients. At 8 years, the mean Hospital for Special Surgery score was 81 points. Venn-diagram scores revealed four failures and three acceptable cases; the remaining cases were satisfactory. Apart from one loose patellar component, there was no mechanical loosening. Roentgen stereophotogrammetric analysis showed that the tibial components moved relative to the bone; this indicated fibrous tissue fixation, which was corroborated histologically in two patients. The objective, to achieve bone ingrowth, was thus not successfully met. Radiolucent lines were consistently seen, and their size correlated with the migration as measured by roentgen stereophotogrammetric analysis. Furthermore, five continuously migrating prostheses showed significantly larger radiolucent zones than the prostheses that migrated only initially, and they were less well bonded to the bone at 1 year. In conclusion, partial cementation does not appear to be a way to achieve bone ingrowth in porous-coated implants under load.
Asunto(s)
Cementos para Huesos/uso terapéutico , Prótesis de la Rodilla , Tibia/crecimiento & desarrollo , Anciano , Migración de Cuerpo Extraño/diagnóstico por imagen , Humanos , Estudios Longitudinales , Persona de Mediana Edad , Fotogrametría , Falla de Prótesis , Radiografía , Tibia/diagnóstico por imagen , Tibia/patología , Insuficiencia del TratamientoRESUMEN
Eight total knee arthroplasties involving major bone grafting to repair noncontained defects of the proximal tibia were studied. In all knees, autologous bone was used. Cement was used for implant fixation. At follow-up evaluation 5 years after surgery, 7 knees had excellent results, and 1 had fair results; the mean Hospital for Special Surgery score was 84. Radiostereometric analysis showed a mean migration of 0.5 mm (range, 0.2-1.5 mm). None of the knees in which major structural autologous bone grafting was used showed increased micromotion of the adjacent tibial implant.
Asunto(s)
Artroplastia de Reemplazo de Rodilla , Trasplante Óseo , Articulación de la Rodilla/diagnóstico por imagen , Tibia/cirugía , Anciano , Anciano de 80 o más Años , Artroplastia de Reemplazo de Rodilla/métodos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/cirugía , Radiografía , Reoperación , Tibia/diagnóstico por imagenRESUMEN
In this paper, the authors show that liquid-liquid partition chromatography in an aqueous two-phase system offers unique possibilities of comparing the overall surface properties of intact antibodies in solution before and after binding of antigen. The authors demonstrate that the surface properties of antigen-antibody complexes are dependent on the variable regions of the antibodies, the nature of the antigen and/or possible conformational changes induced by antigen binding. Thus, each antigen-IgG antibody pair formed one type of complex with respect to the exposed dominant surface. The antigen-binding sites of IgG antibodies were exposed and dominant even after binding of hapten or hapten-carrier. In contrast, the antibody-combining sites were concealed upon protein binding and the exposed surfaces of the protein-antibody complexes were related mainly to those of the antigen. IgA1, IgA2, IgE and IgM formed, in comparison to the IgG, hapten-antibody complexes which exhibited surface properties that could be related to both the antigen-binding sites and Fc parts of the antibodies. Moreover, the results indicated that antigen-induced conformational changes occurred in either IgA1, IgA2, IgE, or IgM, but not in IgG1, -2, -3 and -4, making the surfaces of their heavy chain constant regions more similar.
Asunto(s)
Anticuerpos Monoclonales/química , Complejo Antígeno-Anticuerpo/química , Antígenos/química , Sitios de Unión de Anticuerpos , Animales , Anticuerpos Biespecíficos/química , Anticuerpos Biespecíficos/metabolismo , Anticuerpos Monoclonales/metabolismo , Complejo Antígeno-Anticuerpo/metabolismo , Antígenos/metabolismo , Cromatografía Liquida , Haptenos/química , Haptenos/metabolismo , Humanos , Ratones , Conformación Proteica , Propiedades de SuperficieRESUMEN
The purpose of this study was to determine why apparently homogeneous IgG antibodies were, in some cases, fractionated into at least two components by liquid-liquid partition chromatography (LLPC) in an aqueous two-phase system. Four mouse monoclonal IgG antibodies, two against albumin, one against IgG and one against thyroxine, were shown to adopt different conformational isomeric forms. The four antibodies existed in an equilibrium between two or three conformational forms, the proportion of which could also be estimated by LLPC. Since LLPC detects mainly conformational differences within the antigen-binding sites of IgG antibodies, it could be concluded that the conformational forms differed with respect to their combining sites. Moreover, the isomeric forms of an antibody directed against a protein antigen, formed antigen-antibody complexes with almost identical surface properties. In contrast, complexes with different surface properties were formed when the hapten or hapten conjugated to BSA was bound. Thus, both the conformational isomers could bind antigen, at least when the antigen was a small hapten or a hapten conjugated to a carrier protein. Our results suggest that six out of 57 monoclonal IgG antibodies exist in equilibrium between at least two conformational forms and the biological significance of this isomerism is discussed.
Asunto(s)
Inmunoglobulina G/química , Conformación Proteica , Animales , Anticuerpos Monoclonales/química , Sitios de Unión de Anticuerpos , Cromatografía Líquida de Alta Presión , Cromatografía Liquida , Electroforesis en Gel de Poliacrilamida , Humanos , Inmunoglobulina G/inmunología , Focalización Isoeléctrica , Ratones , Albúmina Sérica/inmunología , Albúmina Sérica Bovina/inmunología , Tiroxina/inmunologíaRESUMEN
A number of triacylglycerols with branched acyl groups were prepared via 1,2-isopropylidene glycerol for the purpose of studying three different physical properties: gel point, refractive index, and density. The monoacid triacylglycerols were prepared either via the corresponding acids or the acyl chlorides.
Asunto(s)
Ácidos Grasos/química , Triglicéridos/síntesis químicaRESUMEN
Three different physical properties, the gel point ("solidification point"), the refractive index and the density, were determined and related to the structure of the branched triacylglycerols. A four-factor central composite face-centered design was constructed where the four variables were the length of the main chain, the branching position, the length of the side chain, and the number of branched fatty acyl groups attached to the glycerol backbone. Second-order models were calculated in which the three physical properties were related to the structure. Four additional branched triacylglycerols were analyzed in order to confirm the validity of each model. Contour plots are shown in order to visualize the prediction equations which were obtained.
Asunto(s)
Triglicéridos/química , Ácidos Grasos/química , Geles , Refractometría , Relación Estructura-Actividad , Triglicéridos/síntesis químicaRESUMEN
In this paper, the authors report the use of liquid-liquid partition chromatography (LLPC) in an aqueous polyethylene glycol (PEG)/dextran two-phase system to compare the surface properties (partition properties) of human antibodies and fragments thereof. The surface properties of all the monoclonal antibodies of different classes and subclasses investigated were within the same broad range as that observed for the polyclonal antibodies and no relationship was found between the exposed surfaces of the immunoglobulins (Ig) and their heavy chain isotype. Moreover, Fc fragments from various IgG1, 2 and 4 myeloma proteins were found to exhibit similar surface properties. Employing chimeric antibodies with identical variable regions the authors found that intact IgG1, 2 and 4 displayed identical surface properties, while the corresponding IgA1, IgA2, IgG3, IgE and IgM antibodies differed both from each other and from the IgGs. The surface properties of chimeric IgG3 could be made similar to those of the IgG1, 2 and 4 chimers by partially reducing the length of the hinge section, but new differences in surface properties appeared when their hinges were of similar length. Thus, LLPC can be used to detect differences or similarities in the surface properties of the antigen-binding regions as well as the Fc part in the various isotypes. This can shed light on biological activities such as antigen binding and effector function.
Asunto(s)
Especificidad de Anticuerpos , Inmunoglobulinas/química , Reacciones Antígeno-Anticuerpo , Antígenos/inmunología , Cromatografía Liquida , Dextranos , Humanos , Inmunoglobulina A/química , Inmunoglobulina A/inmunología , Inmunoglobulina E/química , Inmunoglobulina E/inmunología , Inmunoglobulina G/química , Inmunoglobulina G/inmunología , Cadenas Pesadas de Inmunoglobulina/química , Isotipos de Inmunoglobulinas/química , Inmunoglobulina M/química , Inmunoglobulina M/inmunología , Inmunoglobulinas/inmunología , Polietilenglicoles , Conformación Proteica , Propiedades de SuperficieRESUMEN
In this paper, we demonstrate the ability of liquid-liquid partition chromatography (LLPC) to detect conformational alterations occurring in well-characterized enzymes. The conformational changes induced in dehydrogenases such as alcohol dehydrogenase (ADH), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), lactate dehydrogenases (LDH) and malate dehydrogenase (MDH) upon binding of ligand(s) were detectable by LLPC. The ligand-dependent equilibrium between two forms of citrate synthase (CS), glutamate-oxaloacetate transaminase (GOT), hexokinase (HK) and 3-phosphoglycerate kinase (PGK) could also be demonstrated. Furthermore, different conformational forms of some of the apoenzymes could also be detected and separated by LLPC. The results obtained here are discussed in relation to those obtained by other methods.
Asunto(s)
Cromatografía Liquida/métodos , Enzimas/química , Citrato (si)-Sintasa/química , Citrato (si)-Sintasa/metabolismo , Dextranos/química , Enzimas/metabolismo , Ligandos , Oxidorreductasas/química , Oxidorreductasas/metabolismo , Polietilenglicoles/química , Conformación Proteica , Reproducibilidad de los Resultados , Solventes/química , Transferasas/química , Transferasas/metabolismoRESUMEN
In this investigation, the modulating effects of non-immune human IgG and rheumatoid factors (RFs) on antigen-antibody complexations were studied. Non-immune human IgG, as well as RF, were found to inhibit the binding of antigen to specific antibodies of both human and rabbit origin. In addition, human immunoglobulins were also able to modify the composition of preformed antigen-antibody complexes. The effects were detected by immunological methods in two different antigen-antibody systems (human serum albumin-rabbit anti-HSA and tetanus toxoid-human anti-TT). Changes in biological activities could be followed by employing enzymes (glucose-6-phosphate dehydrogenase and human placental alkaline phosphatase) as antigens. The outcome of the effects was found to be dependent on the ratio of antigen to antibody, the antigen-binding properties of the antibody and its origin, and on the properties of the immunoglobulins added. The observed changes could not be explained only by the presence of specific antibodies in the immunoglobulin preparations. The ability of immunoglobulins to modulate antigen-antibody complexations may provide a rationale for the large amounts of non-specific immunoglobulins in the circulation by preventing premature precipitation and promoting the elimination of antigenic molecules.
Asunto(s)
Albúminas/inmunología , Complejo Antígeno-Anticuerpo/efectos de los fármacos , Inmunoglobulinas/farmacología , Toxoide Tetánico/inmunología , Animales , Complejo Antígeno-Anticuerpo/inmunología , Humanos , Inmunoglobulinas/inmunología , ConejosRESUMEN
A new technique, liquid-liquid partition chromatography in an aqueous polyethylene glycol-dextran two-phase system, was used to detect differences in surface properties of antibodies with different antigen-binding sites. Employing well-characterized monoclonal IgG antibodies and Fab and Fc fragments thereof as well as chimeric IgG antibodies we found a remarkable relationship between structure of the antibody combining site and chromatographic behaviour. The surface properties of the IgG antibodies were dominated by those of its antigen-binding regions. In addition, our results indicated that the constant parts of the IgGs form similar scaffoldings, on to which CDRs of variable shapes and sizes are interspaced and constitute the major dominant differences in exposed surface properties.
Asunto(s)
Epítopos/química , Fragmentos Fab de Inmunoglobulinas/química , Inmunoglobulina G/química , Animales , Cromatografía Liquida/métodos , Mapeo Epitopo , Humanos , Fragmentos Fab de Inmunoglobulinas/inmunología , Inmunoglobulina G/inmunología , Ratones , Relación Estructura-ActividadRESUMEN
Liquid-liquid partition chromatography in an aqueous poly(ethylene glycol)/dextran two-phase system (LLPC) is shown to be a quick and sensitive method for detecting conformational changes occurring upon binding of ligands by biospecific molecules. Two groups of well-characterized proteins, enzymes and monoclonal antibodies, were employed. As an example, LLPC demonstrated that isoforms of lactate dehydrogenase as well as of hexokinase existed in a ligand-dependent equilibrium between two forms and that conformational changes occurred when monoclonal antibodies bound haptens. We also demonstrate that the method could be used to detect and separate subfractions in preparations of unliganded proteins that appeared to be homogeneous when analysed by other techniques.
Asunto(s)
Cromatografía Liquida/métodos , Conformación Proteica , Anticuerpos/química , Reacciones Antígeno-Anticuerpo , Dextranos , Haptenos , Hexoquinasa/química , Técnicas In Vitro , L-Lactato Deshidrogenasa/química , Ligandos , Malato Deshidrogenasa/química , Polietilenglicoles , Unión ProteicaRESUMEN
The aim of this study is to investigate the degree of job satisfaction, burnout and strain among nurses (n = 134) working in three care units for demented people in southern Sweden. Three questionnaires were used: the Maslach burnout inventory (MBI), the work-related strain inventory (WRSI), and a recently developed measure for assessing job satisfaction. Based on principal component analysis, an eight-factor job satisfaction scale was chosen. Nurses in general were found to be satisfied, with registered nurses (RNs) being most satisfied with their work and the nursing care provided. The nurses in one of the care units were more satisfied than the nurses on the other two. The MBI and WRSI results showed a low degree of burnout and work-related strain and there was little difference between the care units or the categories of nurses. Job satisfaction scores were relatively independent from the MBI and WRSI scores. However, scores from these two inventories of burnout and strain at work were positively correlated. The results of the questionnaires seem to indicate that positive work experience and negative experience are not opposites. This particular method of evaluating job satisfaction needs further development. However, it seems important to include one specific measure for job satisfaction when action is taken in connection with the working situation of nurses.
Asunto(s)
Demencia/enfermería , Satisfacción en el Trabajo , Personal de Enfermería en Hospital/psicología , Adulto , Agotamiento Profesional/psicología , Femenino , Unidades Hospitalarias , Humanos , Masculino , Calidad de la Atención de Salud , Encuestas y CuestionariosRESUMEN
Women with previous gestational diabetes (n = 113) and controls (n = 226) were studied retrospectively by means of questionnaires. Women with gestational diabetes reported less well-being (p < 0.05), psychic health (p < 0.001) and vigour (p < 0.001) during pregnancy and a less positive experience of pregnancy (p < 0.001) than controls. They also recalled more worry about health during pregnancy than controls (p < 0.001), reported more physical health problems (p < 0.05), more worry about health (p < 0.05) and kept to a diet more often after pregnancy (women with gestational diabetes 34%, controls 13%, p < 0.001). Although most of the women in the groups were not troubled, it was clear that the gestational diabetes influenced their experience of health negatively but motivated them to adopt a healthy lifestyle. Initial treatment with insulin seemed to be slightly more stressful than diet only.
Asunto(s)
Protección a la Infancia , Diabetes Gestacional , Estado de Salud , Embarazo , Salud de la Mujer , Adaptación Psicológica , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Recién Nacido , Persona de Mediana EdadRESUMEN
The aim of this study was to study creativity and innovative climate, tedium and burnout among the nurses on two wards during 1 year of systematic clinic supervision combined with the implementation of individualized care on an experimental ward (EW) for severely demented patients, as compared with a similar control ward (CW). EW nurses had systematic clinic supervision and each patient had his/her nursing care carefully planned, documented and evaluated. The intervention was evaluated by means of the Creative Climate Questionnaire, Burnout Measure and the Maslach Burnout Inventory. Creativity and innovative climate improved significantly among the EW nurses (n = 19) in eight out of 10 factors during the year of intervention while there was no change on the control ward (n = 20). Tedium and burnout decreased significantly among the EW nurses while no change was seen in this respect among the CW nurses. It seems reasonable to assume that systematic clinical supervision and individualized planned care decreases the negative outcome of stress caused by the psychological burden imposed by nursing care. It also increases nurses' creativity, which, in turn, may benefit patient care. The findings of this study point to the necessity for a support system that focuses on the work itself, i.e. the nursing care. Individualized planned care and systematic clinical supervision may offer this kind of support.
Asunto(s)
Tedio , Agotamiento Profesional/epidemiología , Creatividad , Demencia/enfermería , Personal de Enfermería en Hospital/psicología , Supervisión de Enfermería/organización & administración , Planificación de Atención al Paciente/organización & administración , Adulto , Agotamiento Profesional/diagnóstico , Agotamiento Profesional/psicología , Investigación en Enfermería Clínica , Difusión de Innovaciones , Femenino , Unidades Hospitalarias/organización & administración , Humanos , Masculino , Investigación en Administración de Enfermería , Personal de Enfermería en Hospital/organización & administración , Cultura Organizacional , Apoyo SocialRESUMEN
The Radiotherapy group of the European Organisation for Research and Treatment of Cancer (EORTC-RT) has been performing quality assurance with mailed TL dosimetry since 1986. The programme consists of therapy machine output checks, in vivo measurements, and dosimetry for brachytherapy. The therapy machine output checks have revealed a few large deviations (greater than 7%) between EORTC-measured and institute-stated dose, but also shown an improvement in the dosimetry of the participating institutes as a result of consecutive mailings. The use of in vivo dosimetry with mailed TLD has proven that it is feasible to detect deviations of +/- 5%. The results have shown deviations within +/- 5% for dosimeters located well within the radiation field for internal measurements in the pelvic region. Dosimetry of brachytherapy has been performed for low dose rate 192Ir sources. Differences of 14% can be seen between the participating centres.
Asunto(s)
Neoplasias/radioterapia , Dosimetría Termoluminiscente/normas , Braquiterapia/métodos , Europa (Continente) , Humanos , Cooperación Internacional , Garantía de la Calidad de Atención de SaludRESUMEN
In 1987 mechanical checks of megavoltage units and simulators were included in the on-site physics program of the EORTC. The results reported were obtained in 16 different centres and concern 23 accelerators, 14 cobalt units and 14 simulators. In general, the deviations observed for accelerators and simulators are smaller than for cobalt units. A single score, based on the deviations observed for the mechanical checks, is attributed to each centre.
Asunto(s)
Neoplasias/radioterapia , Radioterapia de Alta Energía/instrumentación , Radioisótopos de Cobalto/uso terapéutico , Europa (Continente) , Humanos , Cooperación Internacional , Modelos Estructurales , Aceleradores de Partículas/normas , Garantía de la Calidad de Atención de Salud , Planificación de la Radioterapia Asistida por Computador , Radioterapia de Alta Energía/normasRESUMEN
We demonstrate liquid-liquid partition chromatography in aqueous two-phase systems (LLPC) as a simple method for examining the surface properties of immunoglobulins and antigen-antibody complexes in solution. LLPC separates molecules with respect to the properties of the exposed surfaces. As an example, the method may be used to detect changes in the conformation of IgG following chemical modification like acylation or iodination. We have studied the partitioning of antibodies and antigen-antibody complexes, modelled by rabbit antibodies against three human serum proteins, in aqueous polyethylene glycol/dextran two-phase systems at pH 7. Analysis of both polyclonal and monoclonal antibodies against various antigens suggested that the partition properties of immunoglobulins are related mainly to their antigen specificity and not to subclass-specific structures. Furthermore, experiments indicated that changes in the surface properties of antigen and/or antibody following complexation may be detected. Thus, LLPC may prove to be a new way of studying the relation between antibody structure and function in solution.
Asunto(s)
Anticuerpos/química , Complejo Antígeno-Anticuerpo/química , Acilación , Animales , Cromatografía Liquida , Dextranos , Humanos , Radioisótopos de Yodo , Polietilenglicoles , Conejos , Albúmina Sérica/química , Propiedades de Superficie , Transferrina/químicaRESUMEN
Normally there is a very close relationship between maternal and fetal glucose concentrations during both early and late gestation. Maternal hypoglycaemia during pregnancy will therefore not only affect the mother herself but also the conceptus. As can be judged from the literature, acute hypoglycaemic episodes are only rarely seen in non-diabetic pregnancies. In recent years it has become increasingly evident that insulin-dependent diabetic patients, whether pregnant or not, run a much increased risk of having severe hypoglycaemia (SH) attacks (i.e. the patient needs the assistance of another person to relieve the attack) whenever attempts are made to introduce tight blood glucose control. Very high incidence rates of SH between 19% and 44% have been reported in diabetic pregnancy. Episodes of SH could have serious consequences; neuroglycopenia seems especially hazardous for the mother particularly during the performance of a critical task like driving a car. While hypoglycaemia has embryopathic effects in rodents, there are no data in the human to support a teratogenic effect. Insulin-induced hypoglycaemia in the last trimester of diabetic pregnancy may increase fetal body movement and decrease the fetal heart rate variability. A number of very rare conditions such as insulinoma, severe malaria, HELLP syndrome (haemolysis, elevated liver enzymes, low platelet count), severe fulminating liver disease, and ACTH and/or growth hormone deficiency have been reported to be associated with SH. Relative hypoglycaemia--i.e. low fasting blood glucose and 'flat' glucose tolerance test--is frequently seen in normotensive pregnant women with intrauterine fetal growth retardation. This pattern of maternal carbohydrate metabolism could lead to fetal hypoglycaemia and hypoinsulinaemia and contribute to poor fetal growth.