Cardiovascular effects of carbon dioxide in ventilated preterm infants.

Sick preterm infants may, under certain conditions, demonstrate blood pressure passive cerebral blood flow in response to changes in arterial carbon dioxide tension. Blood pressure in turn depends on cardiac output and peripheral resistance. A Doppler technique for assessing cardiac output compared favourably in terms of reproducibility to a thermodilution technique in a group of infants undergoing cardiac catheterization for congenital heart disease. Doppler was subsequently used to monitor changes in cardiac output following an increase in arterial carbon dioxide tension of 1 kPa in 25 ventilated preterm infants. Blood pressure increased significantly (p = 0.006). However, heart rate did not change significantly (p = 0.16) and, in addition, both stroke and minute volume decreased (p = 0.023, p = 0.02, respectively). This suggests that accompanying changes in components of peripheral resistance exert important effects on blood pressure in the preterm neonate in response to changes in arterial carbon dioxide tension.


Human gastric lipase: ontogeny and variations in children.

The aim of this study was to investigate the precise origin of the acid pre-duodenal lipase during human development and to evaluate its possible changes, at the tissue level, in children with gastritis or pancreatic insufficiency. Human gastric lipase appears around the 11th week of gestation and increases slowly during pre- and postnatal development. It is localized in the fundus of the stomach without any lingual localization. Human gastric lipase reaches its adult level in the third month of life, and does not vary in relation to pancreatic insufficiency. It is only rarely impaired during gastritis.


The effect of dietary pectin on rapid catch-up weight gain and urea kinetics in children recovering from severe undernutrition.

The rates of weight gain and urea kinetics were measured in 12 children receiving one of two energy dense, isonitrogenous formulae (711 kJ/kg/day, 170 kcal/kg/day) during recovery from severe undernutrition. Both formulations contained added arachis oil but in one a source of complex carbohydrate was added in the form of pectin (3.4% of total energy). The children taking the pectin diet had a rate of weight gain which was highly significantly less (7 g/kg/day) than the children not receiving pectin (14 g/kg/day). Urea production was significantly less on the pectin diet (0.37 +/- 0.07 vs 0.55 +/- 0.18 gN/kg/day). On the pectin diet there was a reduction in the rate of excretion of urea in urine and in the rate at which urea nitrogen was salvaged by the lower bowel, but these differences failed to reach statistical significance.


Genetic analysis of cystic fibrosis in Denmark. Implications for genetic counselling, carrier diagnosis and prenatal diagnosis.

Cystic fibrosis is the most common, severe, inherited disease in the Caucasian population. As a consequence, the demand for genetic counselling of patients with cystic fibrosis and their families is large. In Denmark the incidence of cystic fibrosis is 1:4700, which is quite low compared to other European countries. We have investigated 268 Danish cystic fibrosis patients with respect to DNA markers (haplotypes) and the most common mutation delta F508. The delta F508 mutation is found on 88% of all cystic fibrosis chromosomes, the highest frequency reported so far. This had had an important impact on genetic counselling, prenatal diagnosis and eventually population screening. In the Danish population 78% of all couples at risk will be informative for delta F508 and will be identifiable by simple screening methods.


Cerebral and aortic blood flow velocity patterns in preterm infants receiving prophylactic surfactant treatment.

Blood velocity in the internal carotid artery (ICA) and in the descending thoracic aorta (DAo) was investigated used Duplex-Doppler ultrasound in 14 infants of less than 30 weeks gestation, treated prophylactically with surfactant, and in 11 comparable infants with relatively mature lungs who served as controls. After surfactant administration, blood gases, pH or FiO2 were not different between the groups. Temporal mean blood velocity in the ICA was used as a relative measure of cerebral flow (TMFV-cer), and its coefficient of variation (CV-cer) was used to assess fluctuations in cerebral blood velocity. The pulsatility index (PI) in the ICA (PI-cer) and DAo (PI-DAo) was used to estimate if a left-to-right shunt was present. During surfactant instillation TMFV-cer was abnormally low and CV-cer indicated a fluctuating cerebral blood velocity. At 10 min after surfactant administration, TMFV-cer of the treated infants was higher compared to the controls, while CV-cer was stable in both groups. PI-cer and PI-DAo were abnormally high during the first hour of life after surfactant treatment, suggesting a left-to-right shunt without, however, clinical signs of a hemodynamically important ductus arteriosus. We suggest that cerebral perfusion is affected during and at 10 min after surfactant instillation. Left-to-right shunting appears to be a common event following surfactant treatment.


Eight-year follow-up of pulmonary function and oxygen uptake during exercise in 16-year-old males with cystic fibrosis.

Eight of nine Norwegian 16-year-old males with cystic fibrosis, and six age-matched, physically active controls were included in an eight-year follow-up study, involving pulmonary and bicycle exercise testing. The individual's level of regular physical exercise was registered, and we investigated whether or not this could be correlated to changes in clinical status, lung function and maximal oxygen uptake. Four males with cystic fibrosis trained regularly for 4-7 h weekly, while the other four patients did no regular exercise. Three of the latter died during the study, and the fourth male in the non-training group deteriorated significantly during the study period of eight years. The four males in the training group showed improvement in lung function parameters and maximal oxygen uptake, but two of them had more marked obstructive lung disease after the age of 24 years. Even though the sample was small, and several other factors may influence the results, the study indicates that regular physical exercise has beneficial long-term effects on clinical status, lung function and physical fitness in adolescent cystic fibrosis males.


Assessment of thyroidal "C" cell secretion in osteoporotic girls with Turner's syndrome. Basal and calcium-stimulated levels of total calcitonin, extractable calcitonin and katakalcin.

Osteoporosis is a common finding in Turner's syndrome. To test the hypothesis that calcitonin deficiency may contribute to bone mineral loss in Turner's syndrome, we studied basal and calcium-stimulated (2 mg/kg body weight in 5 min) levels of total calcitonin, extractable calcitonin and katacalcin in 15 girls with Turner's syndrome and osteoporosis. Fifteen age-matched healthy girls were studied as controls. Both basal calcitonin (total and extractable) and katacalcin values were not significantly different in patients with Turner's syndrome in comparison with those of the controls. The calcium stimulation test showed a similar "C" cell secretory reserve in both groups. The calculation of delta CT/delta iCa of total and extractable calcitonin and delta KC/delta iCa, which accounts for individual variations in serum ionized calcium increases, did not show any significant difference between girls with Turner's syndrome and controls. We conclude that calcitonin deficiency is not a causative factor of osteoporosis in girls with Turner's syndrome and that in this syndrome long-life estrogen deficiency does not impair "C" cell secretory activity.


Hypoxaemia in infants with respiratory tract infections.

Nineteen infants who were graduates from special care baby units underwent two overnight tape recordings of oxygen saturation (SaO2) and breathing movements; one during an upper (n = 12) or lower (n = 7) respiratory tract infection and the other when free of infection. Baseline SaO2 was lower during infection (median 99.6 vs 100%, p less than 0.01), with four patients having values (84.3-95.5%) below the normal lower limit for full-term infants (97%). The median number of apnoeic pauses was also lower during respiratory tract infection (4.7 vs 15.7/h, p less than 0.02). The median number of episodic desaturations (SaO2 less than or equal to 80%) did not change significantly (1.3 vs 1.9/h, p greater than 0.05), with the exception of one patient who had extremely increased values during infection for both apnoeic pauses (63/h) and desaturations (112/h). No infant, however, was considered clinically hypoxaemic. Clinically unsuspected hypoxaemia may thus occur during respiratory tract infection in a proportion of infants graduating from special care baby units. Such hypoxaemia may have potentially deleterious effects.


Follow-up of nutritional status and dietary survey in children with cow's milk allergy.

The nutritional status of children with cow's milk allergy was followed during an elimination diet in 19 children (9 boys and 10 girls) beginning at the mean age of two years (range 0.6-4.1 years). The cow's milk allergy had been verified in hospital by a challenge test at a mean age of 0.9 years (range 0.2-1.9 years). Weight, height and laboratory indices to test protein, mineral and vitamin status were measured at three follow-up visits at three-month intervals. In addition to cow's milk allergy all these children had some other food allergies, and six of the 19 children were allergic to soy protein. Only two of the 19 children were given a soy-based formula. In the diets of the other children, cow's milk was replaced by increasing amounts of other foodstuffs and supplementary calcium. At the beginning of the study the relative heights of the children were slightly retarded (-0.6 SD) and remained unchanged during follow-up (-0.8 SD at the end of the study). The relative weights were found to be decreased during follow-up (p less than 0.05). There was a significant reduction in serum prealbumin values; eight of the 19 children showed abnormally low values. Low serum zinc values were seen in 12 children. Serum iron concentration was low in two children and two had high serum alkaline phosphatase values. Seven-day food recording indicated that dietary intake of energy was below the recommendation in some children, but protein intake was high. Some children had low intakes of riboflavin.(ABSTRACT TRUNCATED AT 250 WORDS)


Enhanced basal and stimulated PMN chemiluminescence activity in children with atopic dermatitis: stimulatory role of colonizing staphylococci?

In adults, intense staphylococcal skin colonization and hyperactivity of polymorphonuclear leukocyte (PMN) oxidative metabolism are characteristic features of atopic dermatitis. Precise data on childhood atopic dermatitis are lacking. In a prospective study we analysed the PMN chemiluminescence activity with special reference to staphylococcal stimuli in 19 children (mean age 6.2 years) with mild to moderate atopic dermatitis. Staphylococcus aureus was isolated from 17/19 (90%) of children with atopic dermatitis and 13/45 (29%) of healthy age-matched controls (p less than 0.001). The mean (SEM) chemiluminescence activity of unstimulated atopic dermatitis-PMN was 0.34 (0.009) (controls: 0.092 (0.003) x 10(6) cpm/10(6) PMN/min (p less than 0.02). Staphylococcal antigens (S. aureus, S. epidermidis, S. haemolyticus) induced a 1.9-3.1-fold higher peak chemiluminescence response in children with atopic dermatitis than in controls (p less than 0.05). The time interval until peak chemiluminescence activity was considerably shorter for all stimuli in atopic dermatitis. We conclude that PMN of children with atopic dermatitis are "primed", showing enhanced release of reactive oxygen metabolites even in the "resting" state, and are easily stimulated by staphylococcal antigens present on the skin of patients with atopic dermatitis from early childhood on. We speculate that PMN hyperreactivity may contribute to chronic skin damage in atopic dermatitis.


Recurrent parotid swelling in children: clinical features useful for differential diagnosis of Sjögren's syndrome.

Immunological evaluations were performed in 59 children with at least five episodes of parotid swelling. Autoantibody(ies) was transiently or persistently detected in 12 (20%) of 59 patients with recurrent parotitis. Three of the 12 children with autoantibodies were diagnosed as having Sjögren's syndrome. The mean age at onset of parotid swelling in Sjögren's syndrome was significantly higher than that of recurrent parotitis of unknown etiology. The present study and the review of the literature suggest that patients with the onset of parotid swelling at age five years or over deserve screening for underlying systemic immune disorders.


Feeding problems in an affluent society. Follow-up at four years of age in children with early refusal to eat.

Twenty-four children, previously investigated at 3-12 months of age for refusal to eat during at least four weeks with no apparent medical cause, were followed up prospectively and reinvestigated at four years of age. Comparisons were made with 38 controls, selected from the same child health care districts. Information was obtained from parental interviews, medical records and assessments by a speech therapist. At four years of age, 17 of the 24 children with early refusal to eat (71%) were reported by the parents to still have feeding problems and 10 (42%) were reported as hyperactive. Compared to the controls, the children with early refusal to eat seemed to have an equally good prognosis with respect to health, growth and development, but were at risk of later problems with their eating patterns and behaviour.


Cigarette smoke exposure and development of infants throughout the first year of life: influence of passive smoking and nursing on cotinine levels in breast milk and infant's urine.

The effects of smoke exposure via mothers' milk and/or via passive smoking during the first year of life were investigated in a prospective longitudinal matched-pair study. The somatic and mental development of 69 infants whose mothers smoked more than five cigarettes per day throughout pregnancy and continued smoking after childbirth were compared with 69 children of non-smoking mothers. At birth, mean body weight of neonates from smoking mothers was significantly lower than the weight of neonates from non-smoking mothers. This weight difference between the two groups was no longer significant in infants at 12 months of age. With the methods employed by the authors, neither psychomotor nor mental development was affected by smoke exposure during pregnancy and early infancy. Infections of the lower respiratory tract were more frequent in the children of smoking mothers. These mothers weaned their babies earlier than non-smokers, but the different feeding behaviour did not influence any of the clinical parameters that were investigated in this study. In order to evaluate the extent of smoke exposure, cotinine was measured in children's urine and in breast milk once a month throughout the first year of life. Cotinine in the urine was significantly dependent on feeding behaviour: infants breast fed showed concentrations 10-fold higher than those who were bottle fed. Cotinine excretion in urine of infants from smoking mothers, who were not breast fed (nicotine exposure via passive smoking only) was even higher than that of adult passive smokers. If infants from smoking mothers were breast fed, their urinary cotinine excretion was in the range of adult smokers.(ABSTRACT TRUNCATED AT 250 WORDS)


Increasing incidence of childhood coeliac disease in Sweden. Results of a national study.

A survey of the incidence of coeliac disease was carried out by asking all 43 paediatric departments in Sweden to report the number of children born between 1978 and 1987 in whom coeliac disease had been diagnosed. Thirty-four departments representing a population of 7.18 million reported 1944 cases of coeliac disease among 804,935 children born between 1978 and 1987. The cumulative incidence of coeliac disease was 1.7 per 1000 live births in children born between 1978 and 1982 and doubled to 3.5 per 1000 live births in children born after 1982. The highest incidence was found in the southern and south-eastern regions of the country. The observed increase may have been influenced by changes in infant feeding practices such as the postponed age of introduction of gluten from four to six months of age and an increase in gluten content of proprietary baby foods.


Diabetes-related autoantibodies do appear in children with coeliac disease.

Humoral immune factors related to type 1 diabetes have been investigated in children with coeliac disease. Anti-insulin (IAAb), immunoglobulin (alpha IgAb), islet cell (ICA) and glucagon autoantibodies were examined in 15 children with coeliac disease at diagnosis (group 1), in 15 children with coeliac disease following a gluten-free diet (group 2) and in 30 control patients (groups 3 and 4). IAAb were present in 27% of group 1 and in 20% of group 2 patients and alpha IgAb were significantly increased in group 1 and 2 patients; two patients in group 2 were positive for ICA; none of the coeliac disease patients were positive for anti-glucagon antibodies. The levels of anti-gliadin antibodies in group 1 were positively correlated with those of alpha IgAb. Coeliac disease-related HLA antigens were not correlated with antibody presence. The presence of diabetes-related humoral immune factors in coeliac disease raises the question as to whether or not they are predictive of subclinical pancreatic damage or whether they are simply indicators of a more general autoimmune diathesis.


The status of lactose absorption in Hong Kong Chinese children.

Lactose malabsorption was investigated in 169 Chinese children aged between two and 16 years using the breath hydrogen test. The challenge was either lactose solution (1 g/kg) or cow's milk (10 ml/kg). Overall, 68% of the children showed a significant increase in breath hydrogen following the lactose challenge while only 17% showed an increase after the cow's milk challenge and 13% after both challenges. The number of malabsorbers increased significantly (p less than 0.001) with age and no associated gastrointestinal symptoms or signs were found in any of the children following the challenges, suggesting a gradual and partial loss of intestinal lactase activity. We conclude that the prevalence of lactose malabsorption in Hong Kong children is very high using the standard lactose tolerance test but when a more realistic amount of lactose and a natural medium such as a glass of milk is used as the challenge, the number of malabsorbers becomes small and clinically insignificant.


Schistosoma haematobium: a neglected common parasitic disease of childhood in Nigeria. Incidence and intensity of infection.

A prospective and cross-sectional study was carried out in various communities in Kwara State, Nigeria, to access the status and implications of urinary schistosomiasis among schoolchildren. Of 425 pupils examined in nine communities, 193 (45.4%) were infected. Infection rates for boys (44.7%) and girls (47.9%) were not significantly different (p greater than 0.5). Children between 11 and 13 years of age had the highest incidence rates (33.6%). However, the percentage of children (25.9%) excreting at least 1000 eggs per 10 ml of urine sample during their first decade of life was significantly higher (p less than 0.01) than for older pupils. The health implications of schistosomiasis acquired early in life, as in this study, are highlighted in the discussion.


Obstructive sleep apnea in Arnold-Chiari malformation treated with acetazolamide.

We studied respiratory patterns and transcutaneous gas pressures in two infants with Arnold-Chiari type II malformation referred to us due to repeated episodes of stridor and cyanosis. During both active and quiet sleep, respiration was irregular and absent or inverse thoracic breathing movements and frequent decreases in oxygen saturation to below 80% were observed. When breathing air with 2% CO2 or when given acetazolamide 10 mg/kg, chest wall movements normalized and oxygenation increased to near normal levels. After three months of treatment with acetazolamide 20 mg/kg/24 h no further episodes of hypoventilation or hypoxemia were observed and further treatment could be discontinued. We conclude that stimulation of respiration by CO2 or by acetazolamide appears to recruit chest wall muscles and promote upper airway patency in Arnold-Chiari malformation. A treatment trial with acetazolamide seems justifiable in these infants when respiratory problems are present.


Recombinant factor VIIa in an infant with haemophilia A and inhibitors.

Post-traumatic bleeding from the gingiva in a 16-month-old boy with severe haemophilia A did not stop after treatment with factor VIII concentrate and tranexamic acid, and it was demonstrated that he had developed antibodies to factor VIII. Treatment with recombinant factor VIIa 60-90 micrograms/kg body weight four to eight times daily, together with local measures, stopped the bleeding and no complications were seen.


Neuroradiological findings in children with congenital myotonic dystrophy.

We studied seven children with congenital myotonic dystrophy, aged 2.1-8.3 years, and the results of computed tomography and magnetic resonance imaging of the brain were analyzed and neurological development was assessed from the neonatal period. We found that ventricular dilatation that had been seen on the first day of life in two of three infants had not progressed in sequential follow-up computed tomography scans taken at intervals of one to six years. Also, in T2-weighted magnetic resonance imagings, areas of periventricular hyperintensity were identified in all children, as well as areas of subcortical hyperintensity in one child. Further, an asphyxial episode had occurred at birth in five patients and the extent of the periventricular hyperintensity was found to correlate significantly with Apgar scores, indicating that the degree of perinatal asphyxia that had occurred was responsible for the abnormalities uncovered by the magnetic resonance imagings. However, there was no correlation between the neurodevelopment outcome and the extent of the periventricular hyperintensity or ventriculomegaly. Therefore, in patients with congenital myotonic dystrophy, a neonatal episode of asphyxia can be responsible for a finding of periventricular hyperintensity, but it is unlikely that an integral part of the mental retardation is attributable to brain damage due to perinatal asphyxia.


Sleep and wakefulness in preadolescent children with deficits in attention, motor control and perception.

In 10 children with deficits in attention, motor control and perception (DAMP), the relation between daytime vigilance and night-time sleep quality was examined with polygraphic sleep recordings, multiple sleep latency tests and measurements of reaction times. Two girls and eight boys, 6-12 years of age were studied. Eighteen normal children served as controls. Normal sleep regulation and sleep quality was found, but the children with DAMP tolerated the recording procedure less well than the controls. Most patients did not suffer from increased daytime sleepiness, but at MSLT 3, patients had short sleep latencies as in daytime hypersomnolence. Reaction times were significantly longer among the patients than among the controls. It is proposed that the findings may be related to functional changes in the forebrain.


Well-being of children with chronic illness. A population-based study in a Swedish primary care district.

According to a previous study, 8% of all children in Dalby primary care district were chronically ill. The impact of the illness on the children's well-being was investigated using parental questionnaires. No difference in socio-demographic variables was found between responders (70%) and non-responders. The study comprised 98 index and 168 control children. Comfort and well-being in school and pre-school were lower among the index than among the control children and lower among the index children in normal compared with special schools. According to the parents many teachers had insufficient knowledge of disorders/handicaps. Children with a physical disability more often had special remedial education compared with healthy children. The chronically ill children were bullied more often, had fewer contacts with peers and more emotional problems than the control group. Improved knowledge of chronic childhood disorders/disabilities and recognition of the psychosocial consequences at school/pre-school and in the child health services is advocated.


Normal Y sequences in Smith-Lemli-Opitz syndrome with total failure of masculinization.

We report an infant with characteristics of Smith-Lemli-Opitz syndrome who had anteverted nostrils, apparently low-set ears, micrognathia, high-arched palate, cleft palate, growth and psychomotor retardation, hypotonia, poor suck, cerebral hypotrophy and double renal pelvis and ureter. An EEG showed spike waves in the right temporal area. The patient appeared to have normal internal and external genitalia of the female type. Both ovaries were dysplastic. The karyotype was 46,XY. All of 26 loci on the Y chromosome were positive including SRY, a candidate gene for TDF.


Hoarseness in a child with gastroesophageal reflux.

Hoarseness is not generally appreciated to be a manifestation of pediatric gastroesophageal reflux. We describe a case in which treatment of well-documented gastroesophageal reflux and esophagitis in a young girl with hoarseness and nocturnal cough led to resolution of these symptoms. Possible pathogenetic mechanisms and the difficulty in associating hoarseness with reflux by standard reflux testing are discussed.


Progressive idiopathic cholestasis presenting with profuse watery diarrhoea and recurrent infections (Byler's disease).

The second child of healthy unrelated parents presented with chronic diarrhoea since the age of two months, initially associated with non-characteristic liver involvement. Recurrent infections, severe failure to thrive and various metabolic deficiencies complicated the further course, as well as profuse watery diarrhoea with elevated regulatory gut peptides, responding only to somatostatin analog treatment. At 22 months of age, intermittent cholestasis with permanently normal serum gamma-glutamyltransferase was evident. The child died of fulminant purulent meningitis at the age of three years six months. Liver histology showed intrahepatic cholestasis, bile duct paucity with focal proliferation as well as slight portal and intralobular fibrosis. The clinical, biochemical and histopathological findings were indicative of Byler's disease.


Septo-optic dysplasia and growth hormone deficiency: accelerated pubertal maturation during GH therapy.

We report four patients (three male, one female) with septo-optic dysplasia and growth hormone deficiency. All had GH therapy for a period of four to eight years until reaching final height. In all four cases bone maturation during puberty was accelerated (1.4 to 1.9 "years"/year), resulting in a final height which was clearly below the predicted height. The progress of pubertal stages was very short in all patients. In three patients TSH and prolactin release after TRH stimulation were increased. These data support a hypothalamic original of the endocrine disorder. Insufficient GH release, even after repeated GHRH stimulation, is in contrast to this assumption. In one case there was a late manifestation of neurohormonal diabetes insipidus, which indicates the possibility of later disease progression. MR imaging of the brain demonstrated variable malformation of the septum pellucidum, chiasma and nervus opticus or the pituitary gland, respectively.


Phenytoin-induced IgG2 and IgG4 deficiencies in a patient with epilepsy.

A five-year-old girl with epilepsy and recurrent respiratory infections was investigated for serum IgG subclass concentrations. She was diagnosed as having a combined deficiency of IgG2 and IgG4 with a decreased serum concentration of IgA and IgG3 and was given replacement therapy with i.v. immunoglobulins. Since then, she has been free from respiratory infections. After phenytoin therapy was stopped, IgG subclass deficiency improved. This case describes the further action of phenytoin on the immune system, adding IgG subclass deficiency to the list.


Self-inflicted ocular mutilation in the pediatric age group.

Three mentally retarded children with severe self-inflicted ocular injuries are presented. All three suffered from severe ocular injuries including retinal detachment resulting in progressive visual loss and even blindness. Self-inflicted injuries to the eyes, including self enucleation, is an extremely uncommon form of behavior, rarely encountered by pediatricians. The risk of ocular morbidity is high if the diagnosis is overlooked. Technical advances in ophthalmology permit much improvement in some formerly hopeless cases of ocular self-mutilation, but there is still no accurate method to repair destroyed retinal or nervous tissue. Early identification of patients at risk of ocular self-mutilation is essential in order to prevent or minimize such severe ocular injuries.


Congenital sideroblastic anaemia with intrauterine symptoms and early lethal outcome.

Sideroblastic anaemia is a rare disease, which most often presents in early childhood. A case of ringed sideroblastic anaemia with onset in early foetal life in a female infant, resulting in severe intrauterine symptoms, is reported. Six weeks after birth a bone marrow examination revealed a large amount of typical ringed sideroblasts, thus establishing the diagnosis. In spite of repeated blood transfusions, the haemoglobin content gradually decreased. The condition was refractory to pyridoxal phosphate treatment and continued to deteriorate with lethal outcome four months after birth.


Susceptibility of human leukemia to allogeneic and autologous lymphokine-activated killer cell activity: analysis of 252 samples.

The present study investigated the susceptibility of human leukemia cells to allogeneic lymphocytes with lymphokine-activated killer (LAK) activity from normal donors and autologous LAK activity from patients in complete remission. LAK activity was generated from peripheral-blood mononuclear cells cultured for 6 days with 1,000 U/ml recombinant interleukin-2 (IL-2). Cytotoxicity was evaluated using a standard 4-hour chromium release assay. Susceptibility of leukemic cells to LAK was defined on the basis of the mean Cr release in 52 samples of normal bone marrow cells. Using allogeneic LAK, we examined leukemic cells from bone marrow or peripheral blood of 252 patients [102 with acute myeloid leukemia (AML), 99 with acute lymphoblastic leukemia (ALL), 13 with chronic myelogenous leukemia in blast crisis (CML-BC) and 38 with chronic leukemias of various types]. A significant lysis could be detected in 62% of all leukemias tested (in 68% of AML, 60% ALL, 92% CML-BC, 39% chronic leukemias). The mean chromium release (effector-to-target cell ratio 50:1) was 28.8 +/- 13.5% for LAK-sensitive leukemias versus 5.2 +/- 3.2% for resistant leukemias. We observed a distinct susceptibility of various leukemia subtypes. LAK cytotoxicity against autologous leukemia cells was examined in 40 leukemia patients in complete remission (24 AML, 16 ALL). 63% of the patients developed a significant cytotoxicity against their autologous leukemia cells. Regarding mean Cr releases, the efficiency of allogeneic LAK activity of normal donors did not differ significantly from that of autologous LAK activity of patients in complete remission against the same leukemic target cells. Analysis of our data revealed that examinations with allogeneic LAK activity make it possible to predict whether patients will develop significant in vitro killing of their autologous leukemia cells during complete remission. These results may be of particular importance in determining which patients could benefit from immunologic therapy modalities and in scheduling immunotherapy. Further clinical studies are necessary to ascertain the clinical significance of therapeutic approaches with IL-2 or adoptive cellular immunotherapy combined with IL-2 for treatment of human leukemia.


Maintenance therapy for peptic ulcer disease: an overview of medical treatment.

Peptic ulcer disease is a chronic disorder that manifests as recurrent episodes of pain or complications such as bleeding or perforation. Current medical therapy with H2-receptor blockers or sucralfate effectively prevents most recurrences and, according to clinical trials, may prevent complications. Since this treatment does not alter the natural history of peptic ulcer disease, continued therapy is needed. Surgical treatment does permanently alter the history of recurrence. Medical therapy aimed at eradicating Helicobacter pylori infection is an exciting new development and shows promise of a medical "cure" for peptic ulcer disease. However, many questions remain unanswered about this treatment. This review examines the natural history and long-term treatment of peptic ulcer disease.


Gastroesophageal reflux disease and its consequences.

Gastroesophageal reflux is a common event characterized by orad movement into the esophagus of gastric and/or duodenal contents. Reflux may produce either no damage to the esophageal mucosa or erosions, exudates, ulcerations, strictures, and/or Barrett's (columnar-lined) esophagus. In addition to the esophagus, all the anatomic structures from the pharynx to the lung may be affected by reflux. Numerous factors promote abnormal esophageal mucosal contact time with acid and pepsin. These include incompetent lower esophageal sphincter, impaired esophageal clearance, increased frequency of reflux episodes, delayed gastric emptying, and the presence of a hiatal hernia. The relative contribution of each of these factors in the pathogenesis of esophageal mucosal disease has not been clearly defined. Epidemiologic and clinical data support an association between gastroesophageal reflux and pulmonary disease. Most asthmatic patients, independent of bronchodilator use, have evidence of gastroesophageal reflux, as demonstrated by ambulatory pH testing, endoscopy, and the presence of reflux symptoms. Studies with antireflux agents indicate that partial or complete symptom relief and healing of esophagitis are obtained in about half the patients using H2-receptor antagonists and almost all patients using omeprazole. Preliminary evidence suggests that surgical correction of reflux may lead to improved pulmonary status. Controlled clinical trials are needed, however, to further determine whether effective gastric acid suppression will improve reflux-associated pulmonary disease.


In vivo and ex vivo antitumor activity in patients receiving low-dose subcutaneous recombinant interleukin-2.

Alterations in cell-mediated cytotoxicity levels were studied in patients receiving recombinant interleukin-2 (rIL-2) via subcutaneous injection. Fourteen outpatients, aged 36-68 years, with progressive metastatic malignancies, were treated with weekly escalated doses of rIL-2, starting at 1.8 IU/m2/day for 6 days a week, up to 14.4 IU/m2/day during the 4th week of therapy. Patients presenting with stable disease thereafter were started on maintenance therapy and received 10.8 IU/m2 once weekly for up to 12 weeks. Patient mononuclear cells were isolated from fresh peripheral blood at various times throughout the treatment. Cells were assayed prior to and after further in vitro stimulation by rIL-2 (600 IU/ml for 7 days). Natural killing (NK) activity was measured by cytolysis of K 562 target cells, and lymphokine-activated killing (LAK) was determined by cytotoxicity against Daudi targets, respectively, in four effector:target ratios (E:T), using a standard 2-hour europium3+ release assay. Spontaneous NK cell function (E:T = 25:1) of freshly isolated peripheral blood mononuclear cells (PBMC) was enhanced significantly after 28 days of therapy (27.8 vs. 9.1% on day 0). LAK activity also markedly increased during therapy (26.2 vs. 5.4% on day 0). Further in vitro culture of these PBMC in the presence of rIL-2 resulted in day 28 non-MHC-restricted cytolytic activity of 63.2% (40.3% on day 0) against K 562 targets, and 64.9% (39.6% on day 0) against Daudi targets. Activation of cytolytic function by rIL-2 appeared to be dose-dependent, as measurable lytic capability decreased throughout maintenance therapy, while neither sex nor tumor entity prior to therapy or clinical response were correlated with cytotoxicity levels. Taken together, our observations demonstrate that stimulation of the non-MHC-restricted pathway of cytolytic activation, as measured by lysis of target cells, arises in patients treated with rIL-2 doses 5- to 30-fold lower than used previously in intravenous protocols, connecting effective clinical response rates with acceptable tolerability.


Activation of human peripheral-blood-derived monocytes by cis-diamminedichloroplatinum: enhanced tumoricidal activity and secretion of tumor necrosis factor-alpha.

The anticancer agent cis-diamminedichloroplatinum (CDDP) has been shown to have immunopotentiating and immuno-suppressive properties depending on the CDDP concentration used. Treatment of human peripheral-blood-derived monocytes (PBM) in vitro with low concentrations of CDDP resulted in a significant potentiation of antitumor cytotoxicity as assessed in an 18-hour 51Cr release assay. The potentiation of cytotoxicity by CDDP was also observed with PBM treated with recombinant interferon-gamma (rIFN-gamma). The monocyte-mediated cytotoxicity was significantly inhibited when antitumor necrosis factor (TNF) antibody was added to the assay culture. The role of TNF in the cytotoxic mechanism was further corroborated by demonstrating that significant levels of immunoreactive TNF-alpha in the supernatants were detected by ELISA. Further, supernatants derived from CDDP-treated monocytes were cytotoxic to the TNF-sensitive tumor cells and the cytotoxicity was neutralized by the addition of anti-TNF antibody. The secretion of TNF-alpha by CDDP-treated monocytes was readily detected as early as 4 h after culture and was dependent on de novo protein synthesis as inhibitors of RNA and protein synthesis abolished TNF-alpha secretion. Altogether, these results demonstrate that CDDP can potentiate monocyte-mediated antitumor cytotoxicity and stimulates TNF-alpha synthesis and secretion.


Surgical management of peptic ulcer disease.

Since the advent of H2-receptor antagonists, elective ulcer surgery is rare. The need for operation for complications of peptic ulcer disease, however, remains unchanged. Highly selective vagotomy is the elective operation of choice for duodenal ulcer worldwide. It has few side effects and a mortality that approaches 0%. Unfortunately, ulcers recur in 10% to 15% of patients, a much higher recurrence rate than that seen with vagotomy and antrectomy (less than 1%). The latter operation, however, is associated with significant side effects, such as dumping syndrome and diarrhea, and a higher operative mortality. The elective operation of choice for gastric ulcer is antrectomy. Recent prospective trials show that highly selective vagotomy should be performed routinely at the time of closure of perforated duodenal ulcer. Neither morbidity nor mortality is increased with the procedure, and the 40% to 60% ulcer recurrence rate with closure alone is reduced to 2% to 8%.


Prevention and treatment of ulcers induced by nonsteroidal anti-inflammatory drugs.

Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) can cause varying degrees of gastroduodenal mucosal damage. These agents are most frequently used for the treatment of rheumatic diseases because they are highly effective in reducing joint pain and swelling. Histamine H2-receptor antagonists, omeprazole, sucralfate, and misoprostol are drugs available for the treatment of gastric mucosal damage caused by NSAIDs. In controlled clinical studies, all these drugs effectively heal gastric and duodenal injury if NSAIDs are discontinued. However, current data suggest that if NSAIDs are continued while gastrointestinal damage is present, only misoprostol and omeprazole have demonstrated efficacy in healing gastric mucosal injury. Misoprostol also effectively heals NSAID-induced duodenal injury. At this time, no data exist on the efficacy of other antiulcer drugs in healing duodenal erosions or ulceration if NSAID administration is continued. Regarding prevention of NSAID-induced gastric ulcer, controlled clinical studies with H2 antagonists and sucralfate have failed to show any therapeutic benefit. Ranitidine, however, has shown efficacy in preventing NSAID-induced duodenal ulcers. The coadministration of misoprostol with NSAIDs to patients who have either osteoarthritis or rheumatoid arthritis prevents the development of gastric and duodenal ulcers. Based on current published information, this property distinguishes misoprostol from other antiulcer drugs.


Effects of macrophage colony-stimulating factor on the activities of murine monocytes and peritoneal macrophages in vivo.

The ability of peripheral blood monocytes, granulocytes and resident peritoneal macrophages to generate hydrogen peroxide in response to concanavalin A was enhanced by a single intravenous injection of macrophage colony-stimulating factor (M-CSF) of recombinant human type in AKR mice. In response to phorbol myristate acetate, only granulocytes and resident peritoneal macrophages showed the enhanced ability. Phagocytosis by those cells was not stimulated by M-CSF. Surface marker analysis showed an increased expression of F4/80 and Mac1 on monocytes, Mac1 expression on granulocytes and LFA-1 expression on resident peritoneal macrophages. Ia antigen on resident peritoneal macrophages was suppressed by M-CSF. M-CSF can induce monocytes, granulocytes and resident peritoneal macrophages to generate hydrogen peroxide and enhances their maturation in vivo.


Regulation of natural killer cell production in bone marrow of mice: no evidence for negative feedback control.

The possible presence of a negative feedback control mechanism regulating natural killer (NK) cell production in the bone marrow of B6 mice was investigated by depleting NK cells with a single intravenous injection of anti-ASGM1 antibody. At times ranging from 1 to 21 days following injection, the response of the bone marrow cells to this depletion was assessed by measuring both NK activity against YAC-1 target cells in a 51Cr assay and the frequency of NK precursors by limiting dilution analysis. For comparison, measurements of lytic activity were also done in the peripheral blood and spleen. Anti-ASGM1 injection resulted in a depletion of mature NK cell activity in all compartments tested as expected, as well as the depletion of NK precursors from the bone marrow. Clearance of the anti-ASGM1 from the circulation of recipient mice was biphasic. More than 99% of the antibody was eliminated in the first 4 min, while the remaining 0.24% had a half-life in the serum of 6 days. Bone marrow was able to produce new lytic NK cells which were detectable between days 6 and 10 after depletion. The bone marrow of the NK cell-depleted mice did not show an 'overshoot' (compensatory increase) in NK cell production through day 21 after depletion. It therefore appears that the NK cell production in the bone marrow is independent of the activity of the peripheral NK cell pool.


Protein-calorie malnutrition in liver cirrhosis.

The purpose of this article is to present detailed data on the nutritional assessment in cirrhotic patients. The exact frequency and types of malnutrition, its associations with the aetiology of liver disease, liver dysfunction and clinical staging in liver cirrhosis are unknown. A new classification system is presented which may help to suggest some interventional guidelines. Physical (anthropometry, 24-h urinary creatinine excretion, bioelectrical impedance analysis (BIA), total body potassium counting, ultrasound examination) and metabolic (indirect calorimetry) assessment of nutritional status was therefore performed in 123 patients with liver cirrhosis, who were considered as potential candidates for liver transplantation. Data were related to the clinical, biochemical, histological and prognostic data of liver disease. Of our patients 65% showed some signs of protein-calorie malnutrition as indicated by low body cell mass, reduced serum albumin concentrations or abnormal skinfold thickness. Of these 34% were considered as "kwashiorkor-like" (normal body composition, serum albumin less than 35 g/l), and 18% were "marastic" (reduced body weight, body cell mass, and fat mass). However, 49% of the malnourished group had reduced body cell mass in association with increased fat mass and frequently presented with a normal body weight ("mixed" or "obese" type). Protein-calorie malnutrition did not correlate with the aetiology of the disease and biochemical parameters of liver function. Malnutrition was observed at all clinical stages but was more frequently seen at advanced stages. We conclude that malnutrition associated with liver cirrhosis is not a clear phenomenon. Its clinical presentation is heterogenous and not reflected by the histological or biochemical parameters of liver disease.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of ethanol and commonly ingested alcoholic beverages on gastric emptying and gastrointestinal transit.

Acute ingestion of pure ethanol has been reported to delay gastric emptying and to enhance the propulsive movements of the intestine. The aim of the present study was to investigate the comparative effect of beer (7.0% v/v), white wine (7.5% v/v), ethanol (7.5% v/v), and water on the gastric emptying of a liquid test meal and on the gastrocaecal transit time of lactulose added to the test meal. Gastric liquid emptying was assessed by means of a nasogastric intubation technique using polyethylene glycol 4000 as the non-absorbable marker. The gastrocaecal transit time was evaluated by a hydrogen breath test. Beer (P less than 0.001) and white wine (P less than 0.05) significantly accelerated gastric emptying in comparison with ethanol of the same concentration. The gastrocaecal transit time was significantly shorter when the liquid meal was administered with beer compared with ethanol (P less than 0.005) and water (P less than 0.01). The constituents in beer and white wine responsible for our observations remain to be found.


Investigations into Ro-specific antibody-associated congenital cardiac conduction defects.

Forty-two babies with different congenital cardiac conduction defects, and in 12 cases the mothers, were tested for autoantibodies to Ro, La, U1RNP and Sm. Ro-specific antibodies were detected most frequently. They were to be found in 16 sera from infants and in 8 maternal serum samples. The occurrence of anti-Ro was associated preferentially with several atrioventricular conduction blocks. The sex relation of anti-Ro associated congenital heart block did not show a typical preference (6 male/10 female). At the time of giving birth, 5 anti-Ro-positive mothers did not have any clinical symptoms of rheumatic autoimmune diseases. Three of them had a first degree atrioventricular block. Our findings indicate that all pregnant women at risk for anti-Ro like connective tissue disease or cardiac conduction defects should be tested for these autoantibodies because of the suspicion of cardiac conduction abnormalities in the offspring. Anti-Ro-positive infants should be examined for structural heart disease by echocardiography.


Hypofibrinogenemia due to fibrin formation in subserosal type eosinophilic gastroenteropathy.

A 33-year-old woman presented with abdominal pain and distention, diarrhoea and marked eosinophilia in blood and ascites. As other causes could be excluded, the subserosal type of eosinophilic gastroenteropathy was diagnosed. The low plasma fibrinogen level (less than 100 mg/100 ml) found in this patient is an as yet undescribed feature. During prednisolone therapy it increased concurrently with the fall of blood eosinophils and the relief of clinical symptoms. Interest was further directed to the ascitic fluid where not only the presence of eosinophils (74%) enveloped in fibrin yarn and of basophils (2%) but also of 24% T lymphocytes (among them 75% CD4+, 24% CD8+, 4% CD25+, less than 1% CD19+, less than 1% natural killer cells) could be demonstrated. These lymphocytes are likely to be the source for lymphokine production chemoattracting eosinophils into the intestine. In addition they seem to be involved in IgE hyperproduction, which after adequate therapy and complete resolution of the clinical symptoms, tended to decrease slowly.


Filiform polyposis: a case report describing clinical, morphological, and immunohistochemical findings.

Filiform polyposis (FP) is a rare condition of uncertain pathogenesis, 28 cases of which have been published since it was first described in 1965. It is usually found in association with chronic inflammatory bowel disease, especially Crohn's disease and ulcerative colitis. The condition is characterized by the presence of numerous, densely packed, filiform polyps in the colon, which may resemble villous adenomas on endoscopy. We describe a case of FP occurring in a 33-year-old man with a 5-year history of Crohn's disease, in whom subtotal colectomy was performed because of perforation of the sigmoid colon. Microscopy revealed inflammatory pseudopolyps covered by largely normal and non-dysplastic colonic epithelium. The neuroendocrine system of the intestine in FP was investigated for the first time in this case: marked hyperplasia of endocrine cells immunoreactive for serotonin, somatostatin and enteroglucagon and of neural structures immunoreactive for substance P and vasoactive intestinal peptide was noted in the polyps and the adjacent intestinal mucosa. The patient has experienced no further complications in the 12 months since the operation. Medication administered in FP depends mainly on the nature of the underlying disease, and the amount of information published about this condition is as yet insufficient to allow any one specific type of treatment to be recommended. FP alone is not an indication for bowel resection but complications, such as massive haemorrhage or intestinal obstruction, may necessitate surgical intervention.


Acquired protein S deficiency.

Hereditary deficiencies of coagulation inhibitors like antithrombin III, protein C and protein S lead to an enhanced incidence of thromboembolic complications. Recently, acquired deficiencies of protein S were described in several disease states in which thromboembolic complications frequently occur. These acquired protein S deficiencies reach--in part--the extent realised by hereditary protein S deficiency. Thus, acquired protein S deficiencies seem to be one source of thromboembolic complications occurring in nephrotic syndrome, acute phase reactions, malignancy and pregnancy. In this presentation disease states accompanied by acquired protein S deficiency and the mechanisms leading to these alterations are discussed.


Distribution of lymphocyte subsets and natural killer cells in the human body.

The frequency and distribution of B and T lymphocyte subsets have been determined in many body tissues and fluids by preparing cell suspensions and tissue sections from lymphoid and nonlymphoid organs. In humans these studies often concentrate on the blood or on one particular cell source for obvious reasons. However, such data can only be interpreted correctly if the whole immune system is taken into consideration [64]. To facilitate this, reports on the frequencies and the absolute numbers of B and T lymphocyte subsets within various human tissues and fluids have been collected from a wide variety of journals and are briefly summarized here. Since the size of lymphoid organs varies with age (e.g. thymus, tonsils), only the data of adult individuals were included, unless otherwise stated. Natural killer (NK) cells are morphologically quite similar to lymphocytes [59], but very different functionally. For example, they are not able to recirculate from the blood via the lymph nodes and the thoracic duct back to the blood as lymphocytes do [19]. Thus, human NK cells have been compared with lymphocytes with respect to number and distribution.


Effects of atrial natriuretic factor on anterior pituitary hormone secretion in normal man.

The effects of intravenous human atrial natriuretic factor ANF(99-126) administration on anterior pituitary hormone secretion have not been extensively investigated in humans. We repeatedly studied 10 healthy volunteers (5 female, 5 male, aged 28 +/- 2 years) on 2 occasions, 3 days apart. In randomized, single blind order, subjects received pretreatment with either placebo or intravenous ANF(99-126) (bolus 100 micrograms/kg, 30-min infusion of 0.1 micrograms/kg.min). Subsequently on both occasions subjects received a combined intravenous bolus injection of pituitary releasing hormones (200 micrograms thyrotropin releasing hormone, 100 micrograms gonadotropin releasing hormone and 100 micrograms human adrenocorticotropin releasing hormone; Bissendorf, Hannover, FRG). Plasma concentrations of adrenocorticotropic hormone (ACTH), cortisol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), growth hormone (GH), thyrotropin (TSH), prolactin, ANF and cyclic guanosine monophosphate (GMP) were determined by radioimmunoassay. ANF(99-126) treatment induced a significant reduction in basal ACTH plasma concentrations and tended to decrease basal plasma cortisol. The TSH response to combined releasing hormone administration was significantly diminished after ANF(99-126) pretreatment. In women, the releasing hormone induced prolactin increase was reduced after ANF(99-126) pretreatment. With the present study design, ANF(99-126) did not alter the basal or releasing hormone stimulated plasma concentrations of cortisol, LH, FSH and GH. Releasing hormone administration did not affect ANF and cyclic GMP plasma levels. In humans, effects of natriuretic peptides on anterior pituitary hormone secretion may have to be considered with investigational or therapeutic administration of ANF analogues or agents interfering with the ANF metabolism.


Reduced bone mineral density and low parathyroid hormone levels in patients with the adult form of hypophosphatasia.

Hypophosphatasia is a heritable metabolic bone disease with characteristically reduced levels of alkaline phosphatase (ALP) in the blood, liver, kidney and bone. ALP levels are normal in the intestine and placenta. About 300 patients have been reported so far in the literature. Three kindreds with 52 known subjects are described here, whereby 12 subjects could be examined osteologically. Four subjects were patients and had clinical signs of the disease: spontaneous fractures of the metatarsals or femora and low ALP serum levels ranging between 8 and 23 U/l (normal range 40-170 U/l). Four other members without fractures had reduced ALP levels; they might be carriers of the disease and develop symptoms later in life. The four remaining subjects had normal ALP levels and no signs of the disease. Serum levels of intact parathyroid hormone (iPTH) were found to be in the lower normal range and serum calcium levels in the upper normal range. There was a significant (P less than 0.05) negative correlation between iPTH and serum calcium levels (r = -0.78). Urinary calcium excretion was increased in 3 subjects with fractures. 25-OH-D3 levels were increased in 6 of 8 subjects without any treatment. The bone mineral density (BMD) was measured using dual X-ray absorptiometry of the lumbar spine, representing mainly trabecular bone, and single-photon absorptiometry of the forearm, measuring mainly cortical bone. Z-scores of the spinal bone mass ranged between 0.38 and -1.95 SD; Z-scores of the forearm bone mass ranged between 0.53 and -2.47 SD with the lowest values in patients with fractures.(ABSTRACT TRUNCATED AT 250 WORDS)


Testosterone treatment of men with idiopathic hemochromatosis.

Patients with chronic liver disease usually exhibit low plasma levels of testosterone with loss of libido and potency; this is also valid in male patients suffering from idiopathic hemochromatosis (IHC), in whom nowadays the diagnosis is made at an earlier age. Therefore, the effect of testosterone treatment was studied in 10 patients with IHC. After the application of 250 mg testosterone enanthate i.m., the plasma testosterone (from 2.4 +/- 1.9 to 20.1 +/- 7.4 ng/ml) and estradiol (from 17.4 +/- 6.3 to 38.5 +/- 14.2 pg/ml) levels increased significantly. The rise of estradiol was in the range of controls and smaller than reported in other chronic liver diseases. In a long-term study, 250 mg testosterone enanthate was given 4-weekly for 33-96 months to 5 patients with IHC. General well-being, libido, and potency recovered almost immediately. Over a treatment period of 27.3 patient years, symptoms of hyperestrogenism (gynecomastia) or (portal vein) thrombosis were not seen, both of which had been described in patients with alcoholic liver cirrhosis. There was no deterioration of liver function. The effect of testosterone treatment on the patients' well-being and plasma hormone concentrations remained unchanged over the whole period of testosterone treatment. Thus, in male patients with IHC and lowered plasma testosterone, treatment with testosterone enanthate may be instituted. Because of the positive effects on general well-being, liver regeneration capacity, and potency, testosterone should especially be administered to younger subjects suffering from IHC.


Cause and frequency of posttransfusion hepatitis after open-heart surgery.

A total of 1476 patients who underwent open-heart surgery between 1986 and 1988 participated in a prospective study examining posttransfusion hepatitis. They received a total of 8327 units of whole blood, packed erythrocytes, or fresh frozen plasma. The aminotransferase activities were measured preoperatively and 1, 2, 3, 4, 6, 9, 12, and 24 weeks after the operation. Thirty-four patients in all (2.3% of the transfused patients) developed posttransfusion hepatitis, which could be identified as hepatitis B in 1 patient and hepatitis C in 14 patients. No cause for posttransfusion hepatitis could be found in 19 cases (hepatitis of unknown origin). Hepatitis C became chronic in 5 patients. In contrast to hepatitis C, the 19 patients with hepatitis of unknown origin all showed a milder clinical course with lower maximal aminotransferase activities and a shorter duration of the hepatitis. A chronic course was not observed among them. The cause of hepatitis of unknown origin is discussed.


Failure of vaccination against hepatitis B with Gen H-B-Vax-D in immunosuppressed heart transplant recipients.

Some 86 heart transplant recipients under immunosuppressive therapy were vaccinated against hepatitis B using the vaccine Gen H-B-Vax-D, but 95.3% failed to develop protective levels of HBs-specific antibody (more than 10 U/l) after the third vaccination.


Treatment of diarrhoea in human immunodeficiency virus-infected patients with immunoglobulins from bovine colostrum.

Diarrhoea and weight loss are found in more than 50% of patients with the acquired immunodeficiency syndrome (AIDS). In some patients the symptoms can be very severe, leading to death even in the absence of opportunistic infections. In 30% of these patients, enteric pathogens cannot be identified, and approximately only half of the identifiable aetiologic agents of diarrhoea in patients infected with the human immunodeficiency virus (HIV) were treatable with antibiotics. Immunoglobulins from bovine colostrum (Lactobin, Biotest, Dreieich, FRG) contain high titers of antibodies against a wide range of bacterial, viral and protozoal pathogens as well as against various bacterial toxins. Lactobin (LIG) is quite resistant to 24-h incubation with gastric juice. In a multi-center pilot study 37 immunodeficiency patients with chronic diarrhoea [29 HIV-infected patients, 2 patients with common variable immunodeficiency (CVID), one unidentified immunodeficiency, five patients with graft versus host disease (GvHD) following bone marrow transplantation] were treated with oral LIG (10 g/day for 10 days). Good therapeutic effects were observed. Out of 31 treatment periods in 29 HIV-infected patients 21 gave good results leading to transient (10 days) or long-lasting (more than 4 weeks) normalisation of the stool frequency. The mean daily stool frequency decreased from 7.4 to 2.2 at the end of the treatment. Eight HIV-infected patients showed no response. The diarrhoea recurred in 12 patients within 4 weeks (32.4%), while 19 patients were free of diarrhoea for at least 4 weeks (51.3%). In 5 patients intestinal cryptosporidiosis disappeared following oral LIG treatment. LIG treatment was also beneficial in 4 out of 5 GvHD patients.(ABSTRACT TRUNCATED AT 250 WORDS)


Long-term therapy with cyclosporin A does not influence serum concentrations of vitamin D metabolites in patients with multiple sclerosis.

Animal studies have shown that cyclosporin A (CyA) stimulates renal 25-hydroxyvitamin D3 [25(OH)D3]-1 alpha-hydroxylase activity; in contrast, studies in renal transplant recipients indirectly suggest that CyA reduces 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] production. To clarify the effect of CyA on vitamin D metabolite concentrations, we measured parameters of calcium metabolism in 37 CyA-treated patients (median trough whole blood levels 171-222 ng/ml) with multiple sclerosis and initially normal kidney function. The patients participated in a randomized double-blind study to assess the efficacy of CyA in multiple sclerosis. An age- and sex-matched control group (n = 39) received azathioprine (Aza). Measurements were made at the end of a 2-year treatment period. The 1,25(OH)2D3 serum concentrations were not significantly different between the two groups, although they were numerically lower in CyA-treated patients [median (range), 28.4 pg/ml (7.8-85.9) vs 41.0 pg/ml (9.2-105.1) in Aza-treated patients]. The 25(OH)D3 levels were comparable in both groups. There was no correlation between the 25(OH)D3 and 1,25(OH)2D3 concentrations. The renal function in both groups was stable in the last 6 months of the study. At the end of the study period, the endogenous creatinine clearance was significantly lower in the CyA-treated group (85 +/- 17 ml/min versus 99 +/- 22 in the Aza-treated group, P less than 0.05). The carboxyterminal parathyroid hormone (C-PTH) was within the normal range in both groups, although CyA-treated patients had significantly higher concentrations (P less than 0.01). The urinary excretion of mineral ions, cations and protein was similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)


Estimation of extracellular space and blood volume using bioelectrical impedance measurements.

The bromide-82 dilution space (extracellular space, ECS) and blood volume (BV) were measured in 21 patients with esophageal and gastric cancer and in 27 patients 18-96 months after total gastrectomy. Resistance (R) and reactance (Xc) from bioelectrical impedance measurements were used to obtain multiple regression equations for ECS and BV. The variables weight, gender, and height 2/Xc were independent predictors of ECS (r = 0.767; P less than 0.0001). Height 2/R and gender were predictors of blood volume (r = 0.856; P less than 0.0001). The mean difference between the Br space and the ECS predicted from impedance measurements was 0 +/- 1.54 (mean +/- SD). The limits of agreement (+/- 2 SD) were therefore +/- 3.08 l or 19.6% of the mean Br space of 15.7 l. The limits of agreement for BV were +/- 789 ml or +/- 19.7% of the average BV of 4008 ml. It is concluded that bioelectrical impedance plethysmography using a single frequency can be used for the estimation of ECS and BV. The wide limits of agreement, however, may limit its used in clinical practice.


Acute aortic thrombosis associated with spinal cord infarction in nephrotic syndrome.

Acute aortic thrombosis associated with spinal cord infarction in a 47-year-old man with nephrotic syndrome is described. He was admitted to our hospital presenting with the nephrotic syndrome. Renal biopsy revealed mild mesangial proliferative glomerulonephritis. The urinary protein excretion rate transiently decreased after the start of treatment with prednisolone, but it increased again and was followed by the development of the signs and symptoms of spinal cord infarction, which was diagnosed by magnetic resonance signal abnormalities, and then symptoms of ischemia in the lower limbs. Digital subtraction angiography revealed an obstruction at the bifurcation of the abdominal aorta. Emergency thrombectomy was performed, and the arterial blood flow was reestablished. Laboratory data on the fibrinocoagulation system showed a hypercoagulable state. In this case, fibrinocoagulation abnormalities due to the nephrotic syndrome led to the hypercoagulable state, and dehydration might have triggered the thrombotic complication.


Response to therapy of a type III hyperlipoproteinemic subject with the rare apolipoprotein E1 (Gly127----Asp, Arg158----Cys) variant.

In a preceding paper, we described the molecular biological defects in a patient with a severe form of the familial lipoprotein disorder type III hyperlipoproteinemia (HLP) and an unusual apolipoprotein (apo) E1 phenotype and epsilon 1/"null" genotype. The index case was a 60-year-old white male of German ancestry who suffered from a myocardial infarction at age 50 years. He had distinctly elevated levels of plasma lipids (triglycerides 551 mg/dl and cholesterol 747 mg/dl, respectively) and typical clinical signs of this inborn error of lipoprotein metabolism. His mutant apo E1 was shown to be identical to a rare (already described) apo E1 (Gly127----Asp, Arg158----Cys) variant. A second independent defect at the molecular level was a nucleotide deletion of a guanosine (G) in the codon for amino acid 31 of the proband's apo epsilon 3 allele. This single base deletion (not described before) changed his apo epsilon 3 allele to a nonfunctional "null" allele devoid of a stable gene product. Here we describe the response to combined dietary and medical treatment of the patient with this unusual form of type III HLP. His response to therapy was excellent, similar to patients with "classical" type III HLP and homozygosity for apo E2. However, the correct diagnosis of this familial lipoprotein disorder seems to be necessary, even in patients without the expected apo E2/2 phenotype, in terms of the prompt and beneficial response to therapeutic interventions.


The pharmacokinetics of two different concentrations of short-acting insulin, intermediate-acting insulin, and an insulin mixture following subcutaneous injection.

To compare the pharmacokinetics of two different concentrations, containing either 40 or 100 IU/ml of short-acting human insulin (Velasulin HM), intermediate-acting human insulin (Insulatard HM), or an insulin mixture (25% short-acting insulin, 75% intermediate-acting insulin; Mixtard HM), three randomized, single-blind, crossover trials were performed using the euglycemic clamp technique. Eighteen healthy volunteers received insulin of either formulation subcutaneously in each of the studies (15 IU Velasulin, 20 IU Insulatard, or Mixtard). The blood glucose levels were maintained constant by glucose infusions. In the trial using Velasulin, the two different insulin concentrations were equivalent regarding the total absorption [area under the curve (AUC) of serum insulin: 126 +/- 28 and 123 +/- 35 mU/l x 12 h for U40 and U100 (mean +/- SD)], but not in regard to the rate of absorption (t max 1.3 +/- 0.4 and 2.4 +/- 1.0 h for U40 and U100). In the case of Insulatard, total absorption was not equivalent (AUC 153 +/- 35 and 128 +/- 37 ml/l x 24 h for U40 and U100), but the rate of absorption was equivalent (t max 4.8 +/- 2.9 and 5.3 +/- 4.6 h). In the Mixtard series, total absorption was equivalent (AUC 142 +/- 32 and 128 +/- 22 mU/l x 24 h), but the rate of absorption was not (t max 2.2 +/- 0.9 and 3.2 +/- 4.2 h for U40 and U100). The glucose requirement was not equivalent in each of the three series.(ABSTRACT TRUNCATED AT 250 WORDS)


Fibrinolytic mechanisms in tumor growth and spreading.

The high prevalence of hypercoagulative states in cancer patients has been known for more than a century. Venous thrombosis in gastric cancer was described by Trousseau in 1865 [55]. In 1878, Billroth observed intravascular thrombus formation in association with metastasis [4]. Thrombohemorrhagic complications regularly occur in patients with disseminated malignancy and are related to an increase in fibrinogen and fibrin turnover. During the past decade, clinicians have witnessed considerable advances in the understanding of fibrinolysis. Initially centered on the role as part of a dynamic, hemostatic balance, research began to unravel the pathophysiological contribution of fibrinolysis to tumor progression. The mechanisms of tumor invasion and metastasis formation in cancer are of critical importance, since metastasis is the major cause of treatment failure and death. It has been suggested that cell-associated proteolytic enzymes contribute to tumor aggressiveness [11, 22, 23]. Fibrinolytic mechanisms are involved in a number of physiological processes in which tissue degradation and remodeling occurs. These include disruption of the ovarian follicle during ovulation and blastocyst implantation. These events in part resemble the invasive growth of cancer [37, 47]. Inspired by this hypothesis, the role of fibrinolytic processes in tumor invasion is under intensive study.


Behavior of lymphocyte subsets and expression of activation markers in response to immunotherapy with galactoside-specific lectin from mistletoe in breast cancer patients.

Cellular aspects of the immunomodulating activity of the galactoside-specific lectin from mistletoe (ML-1) were investigated in 10 cancer patients. Regular subcutaneous injections (4 weeks) of the optimal dosis of ML-1 (1 ng per kg body weight, twice a week) yielded notable increases in the apparent numbers of certain lymphocyte subsets [pan T cells; helper T cells; natural killer (NK) cells] which are generally believed to be involved in antitumor immunity. Moreover, ML-1 administration resulted in an increased level of expression of interleukin (IL)2 receptors on lymphatic cells, an indicator of cellular activation. In vitro, the exposure of human lymphocytes to ML-1 resulted in an enhanced expression of receptors for IL-2 (T cells) and HLA-DQ (B cells), which similarly substantiated the capacity of ML-1 to affect immunological parameters within the host defense system. Thorough clinical trials are now required to assess any impact of the application of the lectin on the course of the disease.


Association between serum-soluble CD8 levels and parameters of immune activation in patients with human immunodeficiency virus infection.

We compared the serum concentrations of soluble CD8 with the immune activation markers neopterin, interferon-gamma, tumour necrosis factor-alpha, soluble CD4, and with CD4+ and CD8+ T-cell counts in patients with human immunodeficiency virus (HIV) infection. The majority of patients had increased concentrations of soluble CD8, interferon-gamma and neopterin, and various significant correlations existed between them. Our results support the view that enhanced soluble CD8 levels indicate activated CD8+ T cells in patients with HIV infection.


The surfactant system of the adult lung: physiology and clinical perspectives.

Pulmonary surfactant is synthesized and secreted by alveolar type II cells and constitutes an important component of the alveolar lining fluid. It comprises a unique mixture of phospholipids and surfactant-specific proteins. More than 30 years after its first biochemical characterization, knowledge of the composition and functions of the surfactant complex has grown considerably. Its classically known role is to decrease surface tension in alveolar air spaces to a degree that facilitates adequate ventilation of the peripheral lung. More recently, other important surfactant functions have come into view. Probably most notable among these, surfactant has been demonstrated to enhance local pulmonary defense mechanisms and to modulate immune responses in the alveolar milieu. These findings have prompted interest in the role and the possible alterations of the surfactant system in a variety of lung diseases and in environmental impacts on the lung. However, only a limited number of studies investigating surfactant changes in human lung disease have hitherto been published. Preliminary results suggest that surfactant analyses, e.g., from bronchoalveolar lavage fluids, may reveal quantitative and qualitative abnormalities of the surfactant system in human lung disorders. It is hypothesized that in the future, surfactant studies may become one of our clinical tools to evaluate the activity and severity of peripheral lung diseases. In certain disorders they may also gain diagnostic significance. Further clinical studies will be necessary to investigate the potential therapeutic benefits of surfactant substitution and the usefulness of pharmacologic manipulation of the secretory activity of alveolar type II cells in pulmonary medicine.


Expansion of neopterin and beta 2-microglobulin in cerebrospinal fluid reaches maximum levels early and late in the course of human immunodeficiency virus infection.

Elevated cerebrospinal fluid (CSF) levels of neopterin and beta 2-microglobulin (beta 2MG) reflect activation of the cellular immune response in the central nervous system (CNS). In 118 consecutive subjects [15 controls and 103 patients with human immunodeficiency virus (HIV) infection classified according to the Walter Reed staging system (WR)], neopterin and beta 2MG were determined in paired samples of CSF and serum. The permeability of the blood-CSF barrier and local release of neopterin and beta 2MG were taken into account: The molecular weight and diameter were used to determine filtration at the blood-CSF barrier. CSF neopterin levels were increased in all stages of HIV infection. beta 2MG levels were elevated in WR2 and later stages. Neopterin, beta 2MG, and cell counts similarly showed peaks in WR2, as did neopterin and beta 2MG also in the later stages WR5 and WR6. Neurologically asymptomatic patients exhibited higher neopterin CSF levels than did controls (12.67 +/- 11.6 vs. 2.34 +/- 1.05 nmol/l, P less than 0.001) and higher CSF beta 2MG (2.12 +/- 1.25 vs. 1.3 +/- 0.37 mg/l, P = 0.001). Patients with HIV encephalopathy had higher levels of beta 2MG (3.75 +/- 1.83 mg/l) than asymptomatic patients (P less than 0.01). CSF levels of neopterin were markedly different in patients with HIV encephalopathy and toxoplasmosis (P less than 0.01). A high quantity of local release of the markers neopterin and beta 2MG may reflect HIV infection of the CNS in early and late stages and additional release upon opportunistic infections.


Cardiac involvement during and after malaria.

In 22 patients without a previous history of cardiac disease, we prospectively evaluated cardiac involvement during acute malaria and 9 +/- 5 months after recovery using non-invasive methods including resting electrocardiogram (ECG) and two-dimensional (2D) echocardiography. During the acute phase ECG abnormalities were common (5/22); pericardial effusion was found in 2 patients and global left ventricular hypokinesia in 1 patient infected with Plasmodium falciparum. At a follow-up of 19 patients, the resting ECG and echocardiography were normal or had normalized in all patients. The results of our study suggest that persistent cardiac damage following malarial infection seems to be rare; however, further trials in a larger patient population are needed to confirm our findings.


Urodilatin: a new peptide with beneficial effects in the postoperative therapy of cardiac transplant recipients.

Renal failure after heart transplantation (HTx) still remains a serious problem, especially when cyclosporin A is used for immunosuppression in the early postoperative therapy. To preserve good renal function without reducing immunosuppressive cyclosporin A treatment, we administered urodilatin (CDD/ANP-95-126) in a long-term, low-dose infusion in addition to the usual medication after heart transplantation. From November 1990 to June 1991, 51 patients (46 male and 5 female; mean age 48 years) were treated with a 6-20 ng/kg bw.min infusion for 96 h after HTx. The renal function and hemodynamic parameters of these urodilatin-treated patients were compared in this sequential study with 40 patients (33 male and 7 female; mean age 49 years) who had undergone HTx previously from May to November, 1990, as controls. In this phase IIa study, both groups did not differ significantly with respect to age, sex, indication for HTx, and preoperative renal function. In comparison with controls patients treated with urodilatin had a significantly better renal function: a reduction in the peak plasma creatinine (PC values day 4: 1.5 +/- 0.11 vs. 2.19 +/- 0.19 mg/dl; P = 0.002), a lower peak serum urea (SU values day 4: 109 +/- 8 vs. 154.7 +/- 8.94 mg/dl; P = 0.0036), and a lower incidence of hemodialysis (6% vs. 10%) were observed. Adequate diuresis was maintained in spite of the reduction of furosemide by more than 60% (P = 0.005) on each day of urodilatin infusion in comparison with controls.(ABSTRACT TRUNCATED AT 250 WORDS)


Elevated lipoprotein(a) levels in patients with acute myeloblastic leukaemia decrease after successful chemotherapeutic treatment.

Twenty-two patients with acute myeloblastic leukaemia (AML) were studied to investigate disease-associated changes in lipid metabolism. Lipoprotein (a) [Lp(a)] levels were found to be elevated at the time of diagnosis (median 23 mg/dl; 41% of patient group had levels greater than 25 mg/dl) and diminished after successful chemotherapeutic treatment in 9 of 10 cases, with a maximum decrease from 56 to 10 mg/dl. In contrast, reduced levels of total cholesterol, low density lipoprotein (LDL) and high density lipoprotein (HDL) (medians 137, 87 and 20 mg/dl, respectively) were observed at the time of diagnosis. Cholesterol and HDL levels increased in all 10 and LDL in 9 cases in which complete remission was achieved. These data suggest that the catabolism of LDL-cholesterol might be even more enhanced than assumed to date. Furthermore, it indicates that the Lp(a) level in acute myeloblastic leukaemia is influenced either directly or indirectly by the leukaemic blasts.


Subacute effects of thiazide administration on renal hemodynamics and calcium metabolism.

To elucidate the renal effects of thiazides as a function of sodium intake, 8 healthy volunteers without renal disease were studied at baseline and 1 day as well as 4 days after the administration of 100 mg hydrochlorothiazide/day. The subjects were compared on two different dietary sodium intakes (120 mmol/day and 220 mmol/day). Measurements comprised inulin clearance (Cin) and paraaminohippurate clearance (Cpah) by infusion clearance technique, total and ionised calcium, immunoreactive parathyroid hormone (1.84 iPTH), 1.25 (OH)2 vitamin D3, and indices of hemoconcentration. Acute administration of hydrochlorothiazide (HCTZ) caused no change in Cin (before 111 +/- 3 ml/min 1.73 m2; 24 h after, 107 +/- 2 ml/min 1.73 m2) or Cpah (before, 579 +/- 9 ml/min 1.73 m2; after, 584 +/- 12 ml/min 1.73 m2), while a significant (P less than 0.01) decrease was noted on the 4th day after 100 mg HCTZ/day and normal sodium intake. No significant change of creatinine clearance (Ccr) was seen with either manouever. Renal hemodynamic changes after HCTZ administration were marginal when hemoconcentration was prevented by a high salt intake. Acute administration (1 h) of HCTZ caused suppression of 1.84 iPTH (before, 2.3 +/- 0.5 pmol/l; after, 1.9 +/- 0.2 pmol/l; P less than 0.01), but after 4 days a lower ionised calcium (baseline, 1.25 +/- 0.01 mmol/l; day 5, 1.20 +/- 0.02 mmol/l; P less than 0.01) was noticed in parallel with hemoconcentration, metabolic alkalosis, and reduced 1.25 (OH)2 vitamin D3 concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)


Renal potassium bicarbonate release in humans exposed to an acute volume load.

Cells of the renal medulla regulate their volume by transmembrane ion movements when exposed to large changes in osmolality. Since renal cells in culture release KHCO3 in response to hypotonic stress [11], we investigated the effect of an acute water load on urinary KHCO3 excretion in 5 healthy individuals. Water diuresis was induced by the ingestion of 1.5 l hypoosmolal fluid (22 mosm/kg H2O) over 15 min. The rate of urinary volume excretion increased from an initial value of 1.4 ml/min to 9.3 ml/min after 75 min. Urinary osmolality dropped from an initial value of 940 +/- 32 mosm/kg H2O to 74 +/- 4 mosm/kg H2O (n = 5). The decrease of osmolality was accompanied by the transient release of potassium and bicarbonate. Peak values of KHCO3 excretion were observed between 30 and 45 min after the onset of the experiment corresponding to the drop of urinary osmolality. The magnitude of renal potassium release correlated significantly (r = 0.93; P less than 0.05) with endogenous plasma aldosterone concentrations measured prior to the experiment in the 5 volunteers. We conclude that medullary epithelial cells release KHCO3 when exposed to hypotonic stress. The volume regulatory response is upregulated by aldosterone.


Mesna side effects which imitate vasculitis.

Mesna (sodium-2-mercaptoethansulfonate) is used in the prophylaxis of cyclophosphamide (CYC)-induced hemorrhagic cystitis. Four patients being treated with "low dose" CYC and prednisone for vasculitis developed severe side effects to Mesna. Fever, arthralgia, myalgia, tachycardia, electrocardiogram changes consistent with perimyocarditis, erythroderma, bullous skin and mucous membrane lesions, and abdominal complaints with profuse diarrhea were noted approximately 3 weeks after the initiation of therapy for CYC-induced leukopenia and a conservatively reduced prednisone dosage. Positive reexposure tests confirmed the association to Mesna use, and hypersensitivity skin tests demonstrated a delayed hypersensitivity reaction.


The metabolism of tramadol by human liver microsomes.

The metabolism of tramadol was investigated in vitro using microsomal fractions of human liver. The parent compound and its main metabolites were determined by a newly developed high performance liquid chromatography assay. O-demethylation of tramadol was found to be stereoselective. The Vmax of the O-demethylation of (-)-tramadol was 210 pmol.mg-1.min-1, whereas (+)-tramadol was O-demethylated with a Vmax of 125 pmol.mg-1.min-1. The Km for both enantiomers was determined to be 210 microM. O-demethylation was inhibited competitively by quinidine (ki = 15 nM) and propafenone (ki = 34 nM). N-demethylation was also stereoselective, preferentially metabolizing the (+)-enantiomer. Whereas O-demethylation displayed monophasic Michaelis-Menten kinetics, N-demethylation was best described by a two-site model. Competitive inhibition of the O-demethylation both by quinidine and propafenone suggests that O-demethylation is carried out by P-450IID6.


Long-term effect of lovastatin alone and in combination with cholestyramine on lipoprotein (a) level in familial hypercholesterolemic subjects.

We have determined the effect of lovastatin alone or in combination with cholestyramine on lipoprotein (a) [Lp(a)] levels in 59 heterozygotes for familial hypercholesterolemia (FH) treated for 33.8 (+/- 6.1) months. The median pretrial Lp(a) value was 10.2 mg/100 ml, which is twice the median value in healthy people examined at the Institute of Medical Genetics, University of Oslo. The median Lp(a) level was insignificantly reduced by 10.3% during the first 20 weeks when the subjects were on a standardized medication of increasing doses of lovastatin and cholestyramine. The first 20 weeks were followed by usual care treatment period, and a further decrease in Lp(a) level to 16.2% (P = 0.0012) was observed at the end of the study. Comparison between the 20 subjects on lovastatin monotherapy and the 31 subjects on the combined therapy of lovastatin and cholestyramine, revealed that the subjects on monotherapy had a median reduction of 20.1%, and the subjects on the combined therapy had a reduction of 15.4%. Thus, it appears that the reduction in Lp(a) level could be ascribed to lovastatin alone.


Measuring patient anxiety in coronary care. Part 1.

Patient anxiety is a common problem identified by nurses. However, the difficulty of assessing the level and significance of the anxiety is problematic. This paper discusses the issue of measuring patient anxiety, specifically in Coronary Care. As well as discussing physiological measures, three appropriate psychometric instruments are identified (the State-Trait Anxiety Inventory--STAI; the Hospital Anxiety and Depression Scale--HAD; a Linear Analogue Anxiety Scale--LAAS), along with a review of the relevant literature. Systematic anxiety measurement, and management of maladaptive anxiety would appear to be appropriate and meaningful nursing functions within the provision of holistic patient care in Coronary Care.


A recent reminder of botulism.

Botulism is a rare yet potentially common form of food poisoning that can be fatal. (1) Few documented cases of botulism exist in Australia (2,3,4) and New Zealand (5), emphasising how infrequently it is encountered. The recent admission to our Intensive Care Unit (ICU) of a man suspected of having botulism was a timely reminder of just how dangerous this condition can be. This paper will review the contemporary knowledge and interventions necessary in the management of botulism. It will also utilise anecdotes from our recent experience to illustrate some of the clinical scenarios and potentially fatal complications seen in this condition.


Development of the nurse practitioner.

In the first of two articles on the development of the emergency nurse practitioner, Peter Howie reports on a new scheme in Lincoln where all first-level nurses have been trained as nurse practitioners. The initiative was introduced following a study in the theoretical management of patients by experienced accident and emergency sisters. The author outlines the training course provided and the protocols within which nurse practitioners work.


'Inappropriate attender' in A&E.

With the current emphasis on reducing patient waiting times, accident and emergency nurses may be tempted to close the doors on what they consider to be 'inappropriate attenders'. The author warns that public perceptions of A&E are often at odds with the nurses view, and that all patients should have access to accident and emergency services. This article takes a critical look at triage since its inception as a means of assessing wounded soldiers during the first world war. He explores patient assessment in accident and emergency departments and nurses' attitudes towards the 'inappropriate attender', highlighting the need for caution when dealing with enquiries from the general public.


Influence of chromium on some physiological variables of Anabaena doliolum: interaction with metabolic inhibitors.

The impact of 2,4-dinitrophenol and chlorophenyl dimethylurea on ATP content, carbon fixation, O2 evolution, nitrogenase activity and Cr uptake of Anabaena doliolum has been studied. 2,4-Dinitrophenol has been found to be more toxic than chlorophenyldimethylurea for all these processes. However, when Cr toxicity to above variables was assessed in their presence the interaction was less than additive. An initial (10-15 min) concentration-dependent rapid Cr uptake, followed by a slow one, indicates a biphasic uptake. A significant inhibition of Cr uptake in the presence of both these metabolic inhibitors suggests the involvement of metabolic processes in Cr uptake.


Increased urinary excretion of zinc and copper by mercuric chloride injection in rats.

The effects of HgCl2 on urinary excretion of Zn, Cu and metallothionein at different time intervals were observed in male Wistar rats. The rats were given a daily intraperitoneal injection of 203HgCl2 (0.5 or 1.0 mg Hg kg-1) for 2 days. 203Hg, Zn, Cu and metallothionein in urine, kidney and liver were analyzed. Significant increases in urinary Zn and Cu concentrations were found in HgCl2-dosed groups. Elevated urinary Zn and Cu concentrations were accompanied by an increased metallothionein excretion in urine at different time periods. Zn concentration in urine remained elevated during the entire observation period of 7 days. There were also increased concentrations of Cu and Zn in the renal cortex in one of the two exposed groups. The results indicate that urinary Cu and Zn are related to the manifestation of renal toxicity and/or the synthesis of metallothionein in kidney induced by mercury.


Antifeeding and insect-growth-regulating activity of certain metal complexes towards Spodoptera litura; F.

Metal complexes of divalent cobalt, nickel and copper and trivalent iron were synthesized using N-salicylidene-3-aminocoumarin as chelating agent. The ligand behaves as a monobasic ONO donor towards Co(II), Ni(II) and Cu(II) and as an ON as well as an ONO donor towards Fe(III). All the complexes have been proposed to have octahedral geometry on the basis of analytical, thermal conductivity, spectral and magnetic data. The complexes have been screened against Spodoptera litura; F (Lepidoptera: noctuiidae) for antifeeding and insect-growth-regulating activity. The results show appreciable insect-growth-regulating activity associated with metal complexation.


Iron(III) complexes of chrysobactin, the siderophore of Erwinia chrysanthemi.

The phytopathogenic bacterium Erwinia chrysanthemi produces the monocatecholate siderophore chrysobactin under conditions of iron deprivation. Only the catecholate hydroxyl groups participate in metal coordination, and chrysobactin is therefore unable to provide full 1:1 coordination of Fe(III). The stoichiometry in aqueous solution is a variable dependent on pH and metal/ligand ratio, in addition to being concentration dependent. At neutral pH and concentrations of about 0.1 mM, ferric chrysobactin exists as a mixture of bis and tris complexes. Chrysobactin and its isomers form optically active tris complexes. The dominant configuration depends on the chirality of the amino acid to which the catecholate moiety is attached.


Structure and function of vanadium compounds in living organisms.

Vanadium has been recognized as a metal of biological importance only recently. In this mini-review, its main functions uncovered during the past few years are addressed. These encompass (i) the regulation of phosphate metabolizing enzymes (which is exemplified for the inhibition of ribonucleases by vanadate), (ii) the halogenation of organic compounds by vanadate-dependent non-heme peroxidases from seaweeds, (iii) the reductive protonation of nitrogen (nitrogen fixation) by alternative, i.e. vanadium-containing, nitrogenases from N2-fixing bacteria, (iv) vanadium sequestering by sea squirts (ascidians), and (v) amavadine, a low molecular weight complex of V(IV) accumulated in the fly agaric and related toadstools. The function of vanadium, while still illusive in ascidians and toadstools, begins to be understood in vanadium-enzyme interaction. Investigations into the structure and function of model compounds play an increasingly important role in elucidating the biological significance of vanadium.


Identification of the ferrioxamine B receptor, FoxB, in Escherichia coli K12.

The photoreactive p-azidobenzoyl analog of ferrioxamine B was used to show that ferrioxamine-B-mediated iron transport is separate and distinct from coprogen-mediated iron transport in Escherichia coli. Photolysis of this analog inhibited uptake of [59Fe]ferrioxamine B but not [59Fe]ferrichrome. Conversely, photolysis of the p-azidobenzoyl analog of coprogen B inhibited uptake of [59Fe]coprogen but not [59Fe]ferrioxamine B or [59Fe]ferrichrome. Photolabeling of outer membranes with p-azidobenzoyl-[59Fe]ferrioxamine B resulted in the labeling of two iron-regulated peptides with molecular masses of about 66 and 26 kDa. Expression of these peptides was increased when ferrioxamine B was the sole iron source. Both peptides were present in outer membrane preparations of the fhuF mutant H1717, but the 66 kDa peptide was not inducible. These results are evidence for an outer membrane receptor in E. coli unique for linear ferrioxamines.


Comparison of the clastogenic effects of antimony trioxide on mice in vivo following acute and chronic exposure.

Antimony trioxide (Sb2O3), in aqueous suspension, was administered by gavaging to mice and monitored for chromosomal aberrations in bone marrow and sperm head abnormalities in germ cells. Acute exposure to the doses followed by observations after 6, 12, 18 and 24 h did not show any clastogenic effects. Chronic exposure daily to different doses for periods up to 21 days induced chromosomal aberrations in bone marrow. The frequencies were dose-dependent to a significant extent but no relationship could be seen with the sex of the animal. The findings indicate the harmful effects of cumulative exposure for prolonged periods to Sb2O3, which is being increasingly used in various industries.


Novel heme-binding component in the serum of the channel catfish (Ictalurus punctatus).

The serum of the channel catfish (Ictalurus punctatus) was examined for heme- and hemoglobin-binding proteins. Electrophoretic mobility retardation assays failed to detect a hemoglobin-binding material similar to mammalian haptoglobin; however, a heme-binding component (not previously described) was identified in catfish serum. The heme-binding component was purified by gel filtration chromatography; electrophoretic analyses suggested it to be composed of two polypeptide subunits of molecular masses about 115 and 98 kDa. This composition is inconsistent with hemopexin, the known heme-binding serum protein of mammals. Although it was not fully saturated with heme, the catfish component contained detectable heme in normal sera. When complexed by the binding material, heme was used as an iron source by isolates of the bacterial Gram-negative genus Aeromonas; the capacity of other bacteria to use the complex was not tested. The physiological function of the catfish heme-binding serum protein is presently not clear.


[Analysis of the correlations between immunological changes and syndrome groups in patients with immunological thrombocytopenic purpura (ITP)].

To study the relationship between the immunological changes and syndrome (Zheng,) groups by TCM of ITP, the T-lymphocyte subsets, B-lymphocyte, NK cell, platelet-associated IgG (PAIgG, PAIgA, PAIgM) and antiplatelet-autoantibodies (GPIIb, GPIIIa, GP I b) of 66 patients with ITP were assisted using APAAP and ELISA method separately. It was found that the T-lymphocyte subsets, PAIg and syndrome groups of ITP were closely related. From the group of blood-heat (Xuerewangxing) to the group of deficiency of both Qi and blood, the group of asthenia of both Spleen and Kidney, the group of deficiency of Liver-yin and Kidney-yin, and the group of deficiency Yin and Yang Ts lymphocyte successfully increased (from 29. 0 +/- 8.0% to 47.2 +/- 10.0%), Th/Ts ratio declined (from 1.35 +/- 0.60% to 0.69 +/- 10%), PAIg increased gradually except for PAIgM,PAIgG of the group of deficiency Yin and Yang. Only the Th of the group of asthenia of both Spleen and Kidney among 5 syndrome groups was decreased significantly and contrary to the group of deficiency of Liver-Yin and Kidney-Yin. These results indicated that every syndrome group has specific characteristics, and immunological changes of ITP could have prognostic value.


[Effects of Cordyceps sinensis (CS) on in vitro natural killer cells].

The effect of Cordyceps sinensis (CS) on peripheral NK cells from healthy persons and leukemia patients were studied. The results showed that CS could argument the NK cell activity, meanwhile, the dose-dependent effect was found within the range of dosage adopted (r = 0.984, P less than 0.01; r = 0.988, P less than 0.01). Furthermore, CS could also improve the CD16 marker expression on lymphocytes and the binding capacity to K562 cells. Cytotoxicity could not present when the PBNCs were co-incubated with CS. These results suggested that CS could be exploited and utilized as an approach of biological responsive modifier therapy (BRMT) in the treatment of leukemia.


[Preliminary study on the treatment of diabetic retinopathy utilizing with nourishing yin, tonifying kidney and blood-activating herbs].

23 cases including 45 eyes of diabetic retinopathy treated with nourishing Yin, tonifying Kidney and blood-activating herbs were presented. The results showed that the serum viscosity and cholesterol were markedly decreased (P less than 0.01), and the implicit times of a-wave and b-wave in flash electroretinogram(F-ERG) were significantly advanced than those of themselves before treatment (P less than 0.01 and P less than 0.05 respectively). The visual acuity in most cases was improved and the effective rate was 64.44%. The therapeutical mechanism for diabetic retinopathy used by nourishing Yin, tonifying Kidney and blood-activating herbs were discussed. The authors suggested that the Chinese herbs probably could change the chemical and physical properties of blood, promote the ocular circulation and the absorption of sludged blood and decrease the retinal ischemia.