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Biomedical subjects

H McFarlane

Publications and source records attributed to H McFarlane.

At least 37 records · Page 2Linked to original sources

Iron therapy and refeeding in experimentally malnourished rats.

1. Rats suffering from protein-energy malnutrition were found to have low serum iron, low PCV, and low hemoglobin concentrations. 2. Oral iron supplement during the refeeding of these animals caused various types of infection, the severity of which was related to the dose given. 3. A close association between high serum iron, low serum transferrin, and high incidence of bacterial infection was found. 4. A high protein diet without any oral iron supplement was found to raise the PCV and hemoglobin concentration to the same levels as a high protein diet containing 65 mg iron/kg body wt/day, although this dose of iron was sufficient to produce infection in the malnourished rats during refeeding. Speculation Iron supplementation during the treatment of children with protein-energy malnutrition may predispose to bacterial infection, the severity of which depends on the dose of iron given.

Animals↗

Detection, significance and treatment of paraprotein in patients presenting with 'idiopathic' proteinuria without myeloma.

This paper describes the detection of a paraprotein in blood or urine in 12 of 260 patients with 'idiopathic' proteinuria, most of whom presented with the nephrotic syndrome. None had myeloma at presentation and only two have developed it. Initial clinical and biochemical findings did not suggest paraprotein-associated disease, total serum globulins and individual immunoglobulin levels usually being in the normal range. In seven of the 12 cases the paraprotein was detected only after repeated analysis of serum and urine specimens over months or years. Renal histopathology varied from case to case and is described in detail; amyloid deposition did not occur in patients who excreted kappa chain Bence Jones protein and was extensive in only three. One of these eventually developed myeloma. Patients were aged 27--69 years at onset and were observed without specific therapy for up to 56 months. Glomerular filtration rate tended to decline and proteinuria persisted. All patients have now been treated by a chemotherapeutic regimen consisting of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), cyclophosphamide, melphalan, and prednisolone, in repeated short courses. In some patients, particularly those who had kappa Bence Jones protein, there was striking improvement. Overall survival is good, eight patients being alive 17--90 months after the onset of symptoms. The importance of repeated search for paraprotein in apparently idiopathic renal disease in adults is emphasized.

Adult↗

A study of enocrine function in protein-energy malnutrition.

Serum concentration of cortisol, growth hormone, thyroxine, thyroid stimulating hormone, follicle stimulating hormone and luteinising hormone, together with triiodothyronine uptake have been measured in Nigerian children with kwashiorkor and marasmus and compared with controls. In both types of malnutrition the cortisol and growth hormone concentrations are raised, whereas those of thyroxine and thyroid stimulating hormone are lowered compared with the controls. Triiodothyronine uptake is lowered in malnutrition but there is no apparent effect on follicle stimulating hormone or luteinising hormone in this age group.

Child, Preschool↗

Cell-mediated immunity in patients with cystic fibrosis.

Leucocytes from 26 patients with cystic fibrosis (CF) and 18 healthy controls were investigated by migration inhibition induced by a variety of antigens. In patients with CF cell-mediated immunity was found to human lung and pancreatic tissue extracts as well as to Aspergillus fumigatus, Pseudomonas aeruginosa, and food antigens but not to brain, heart, or kidney. Those patients with the severest form of the disease had the greatest impairment of cell-mediated immunity, but this impairment could be reversed by steroid treatment. Cell-mediated cytotoxicity may also be concerned in the pathogenesis of CF.

Adolescent↗

Malnutrition and impaired immune response to infection.

The cycle of events which leads to an impairment of the immune response in the malnourished child includes poverty, food deprivation and frequent infections. It is of great significance, however, that the marked suppression of the immune response can be repaired reasonably promptly, if the disease commences after the child has attained 1 year of age. Prenatal infection not only generates growth retardation but also a higher maternal to foetal IgG ratio, higher IgM in the neonate and a sustained immune depression. Passive cutaneous anaphylaxis measurements in the baboon skin and specific IgE determinations reveal that the elevated IgE in PEM is due to parasitic infestation and common allergens and has little or no relationship with decreased T-cell function.

Animals↗

The SIgA system and hypersensitivity in patients with cystic fibrosis.

A number of investigations have been used for the first time to examine the secretory IgA (SIgA) system in different body fluids from patients with cystic fibrosis (CF). Free J-chain was detected in all the sputum specimens examined. The isolated free secretory component (SC) from CF sputum differed in electrophoretic mobility from the SC isolated from normal human colostrum. In addition the free SC from some CF saliva formed precipitin lines of partial identity with normal human saliva or colostrum. A higher proportion of CF sera (33%) than of normal sera (10%) contained free SC. These investigations suggest that there may be some defect in the synthesis and/or the assembly of the SIgA immunoglobulins, which if confirmed, may help to explain the impaired Type I and Type III allergic manifestations in patients with CF.

Adolescent↗

Effects of early protein-calorie malnutrition on the immune response.

Intrauterine and early postnatal malnutrition caused a marked and protracted weight reduction of the body, spleen, and thymus. The mean body weight of the offspring of the malnourished mothers at weaning was 25 +/- 10 g whereas that of the controls was 75 +/- 20 g. At weaning the mean spleen weight of the malnourished offspring was 0.19 +/- 0.05 g and that of their controls was 0.4 +/- 0.13 g. During refeeding the spleen weight but not the thymus weight of the malnourished offspring caught up with that of the controls after about 70 days. After refeeding for as long as 4 months the thymus weight of the malnourished was still significantly (P less than 0.01) less than that of the corresponding weight-matched controls. Primary and secondary plaque-forming cells (PFC) in both the spleen and thymus of the weanling malnourished offspring were barely detectable whereas spleen of their controls had mean approximate values of 50 x 10(3) primary PFC and 70 x 10(3) secondary PFC. The corresponding values in the control thymus were 20 x 10(2) primary PFC and 8 x 10(2) secondary PFC. After refeeding for 4 months of the weanling malnourished offspring their primary and secondary PFC in the spleen increased to about one-half the level of that in their controls whereas the PFC in the thymus were still barely detectable. On the other hand, mean primary and secondary rosette-forming cells (RFC) in the spleen of the weanling malnourished offspring were less than 1 x 10(3) in comparison to the 80-90 x 10(3) in the controls (P less than 0.001). In the thymus too, mean primary and secondary RFC were also less than 1 x 10(3), whereas the corresponding figure in the controls was 30-50 x 10(3) RFC. After refeeding for 4 months the mean values of both the primary and secondary RFC in the spleen and thymus continued to remain less than 1 x 10(3). Although cell morphology in the spleen of the malnourished offspring had returned to normal appearance after 4 months of refeeding, that of the corresponding thymus had not done so completely. For instance, thymic corticomedullary function had reappeared by this time but thymocytes were still less in number than in the controls. By the 8th postnatal day serum IgG2b allotype became detectable in the control offspring, but it was not until day 20 that this IgG allotype could be detected in the malnourished offspring. IgG2a allotype could be detected in the sera of both the malnourished and control offspring.

Animal Feed↗

Complement components in children with protein-calorie malnutrition.

Complement components of C1-C9 were estimated in children with protein-calorie malnutrition. The diagnosis of kwashiorkor and marasmus were based on clinical examination, anthropometric measurements and on biochemical estimations. The children were examined clinically and bacteriologically for any evidence of infection. All the complement components except C4 and C5 were significantly lower in children with protein-calorie malnutrition: of all the complement components C3 and C9 were the most severely depressed. C5 was the only complement component that was significantly higher in malnourished children than in normal children. Malnourished children with C-reactive protein in their serum had significantly lower values of C3 and C9 and higher values of C5 than malnourished children without C-reactive protein in their serum. During refeeding C3 was the first complement to show a significant rise. This was followed by C9. There was a fall in C5 concentration while there was no change in C4 concentration. The roles of infection, malnutrition and C-reactive protein on complement depletion are discussed.

Child, Preschool↗

Specific protein assays in protein-calorie malnutrition.

Assessment of serum protein concentrations in protein-calorie malnutrition was carried out by two specific immunochemical methods, the Single Radial Immunodiffusion technique and the Automated Immunonephelometric procedure. The correlation coefficient (r) between the two methods was above 0.85 for all the serum proteins assayed. The automated nephelometric assay procedure has the advantages that it is rapid and that a large number of samples can be readily processed. The system in its present form could not be readily used to quantitate proteins such as prealbumin whose serum concentration was less than 50 mg/100 ml. The single radial immunodiffusiton technique gave more consitent results for IgA estimation than the automated technique. With the exception of C4 and the immunoglobulins, all the serum proteins assayed were lower in children with protein-calorie malnutrition than in control children. During refeeding in children with protein-calorie malnutrition the first serum protein to show a significant rise was C3. This was followed by transferin, then prealbumin and lastly albumin. C4 did not show any significant change. In experimental protein-calorie malnutrition in rats, the first serum protein to show a significant reduction was C3. This was followed by transferrin and then albumin. On refeeding the rats these serum proteins returned to normal values in the same order.

Animals↗

Immune complexes in cystic fibrosis.

Circulating immune complexes were detected in serum and sputum of patients with cystic fibrosis (C.F.). There were extensive deposits of immunoglobulins and complement immune complexes in several of the C.F. organs, especially the respiratory and gastrointestinal tracts, but not in the kidneys. Significant concentrations of IgG and of complement complexes could be eluted from the lungs of the C.F. patients but not from those of controls. Studies involving immunoabsorption, autoradiography, and molecular sieving through Sephadex G-200 columns identified both bovine serum albumin and staphylococcal alpha-haemolysin as two of the antigens present in the immune complexes. The sedimentation constant of the immune complexes was about 8S to 11S. The clinical significance of these immune complexes and the wide variety of antibodies detected in C.F. patients are discussed.

Adsorption↗

T and B cells in myelomatosis.

The majority of treated patients with myelomatosis had a significantly decreased number of T cells as measured by both lymphocyte stimulation to phytohaemagglutinin (PHA) and by their ability to form spontaneous rosettes with sheep red blood cells (SRBC). Seven untreated patients also had markedly depressed T cells. On the other hand, B-cell numbers' were significantly increased in the majority of the patients as judged by increased lymphocyte stimulation to pokeweed mitogen (PWM) and the markedly increased numbers of rosettes that were formed with antibody-coated complement activated SRBC, as well as by immunofluorescence cell markers to monospecific immunoglobulin antiserum.

B-Lymphocytes↗

Lymphocyte transformation in patients with paraproteinaemia.

The transformation of lymphocytes in cultures with phytohaemagglutinin (PHA) or with pokeweed mitogen (PWM) was carried out during treatment on 28 patients with paraproteinaemia and on 20 control subjects. 78.5% of the peripheral blood lymphocyte short-term cultures from the treated patients showed a subnormal PHA-induced but high PWM-induced lymphocyte transformation. The other 21.5% of the treated patients had a normal pattern of lymphocyte transformation. Eight of 12 untreated patients with multiple myelomatosis and four of five untreated patients with benign paraproteinaemia also had a subnormal lymphocyte transformation to PHA but a high response to PWM. Serial lymphocyte transformation studies in eight of 18 myeloma patients during chemotherapy revealed that the initial subnormal lymphocyte transformation to PHA subsequently became higher than that to PWM. 82% of the bone marrow cultures from the patients showed a higher PWM-induced than PHA-induced lymphocyte response, also suggesting a B cell type of disease. In both dose response and time dependent investigations peak transformation of peripheral blood lymphocytes did not always coincide.

Chlorambucil↗

Immediate hypersensitivity in patients with cystic fibrosis.

Twenty-three out of thirty patients with cystic fibrosis gave strong immediate skin hypersensitivity reaction to a wide variety of allergens. Seventy-five per cent of these had a markedly elevated serum IgE concentration whereas those patients who had negative Type 1 immediate skin reactions also had normal levels of serum IgE. The sputum of those patients with immediate skin reactivity also had positive precipitins to a variety of antigens.

Allergens↗

Complement components of C3 and C4 in Nigerians.

Serum complement component of C3 was lower in both Nigerian children and adults in corresponding British subjects whereas the concentrations of C4 were similar in all groups. It would appear that in the ontogeny of the complement system the concentration of C4 reaches adult level before that of C3.

Adult↗