Subclinical Neuropathy in Lead Workers

Evidence is presented for a minimal defect of peripheral nerve function in a group of lead accumulator workers without clinical evidence of a neurological lesion. Of the 19 men examined, 13 had blood levels above 80 μg./100 ml. and seven had haemoglobin levels below 12 g./100 ml., showing that considerable exposure to lead was occurring.     

Follow up Study of Coeliac Disease

In 9 out of 10 adults in whom a diagnosis of coeliac disease had been made in childhood, the diagnosis was confirmed by the finding of a flat intestinal mucosa. None showed abnormal physical signs, but three had a haemoglobin concentration below 10 g./100 ml. and all those not receiving folic acid supplements showed low serum folate levels. Five had moderate to severe symptoms at the time of investigation, but none was receiving treatment with a gluten-free diet.Periodic investigation of these patients may be necessary throughout life, and if they are found to have malnutrition they should be treated with a gluten-free diet.     

Clinical Trial of Iron Therapy on Psychomotor Function in Anaemic Women

A variety of aspects of psychomotor function were assessed in 47 women before and after iron therapy. These women, all of whom had initial haemoglobin levels below 10·5 g./100 ml., had been drawn from a population sample of 2,283 women seen at a haematological screening survey. There was no evidence of any beneficial effect of a rise in haemoglobin level on psychomotor function or on symptoms. Possibly this is because if an effect does occur it is unlikely to be apparent unless the haemoglobin level is very low. If this is true then anaemia is probably a rare cause of symptoms or impairment in psychomotor function in the community.     

Induction of mutations inSerratia marcescens by a proteosynthesis block

The formation of colour mutations ofSerratia marcescens by the action of chloramphenicol was studied. Pink variants were the commonest; the proportion of white variants was much smaller. Almost 100% mutations were formed in a two-day culture containing 100 μg. chloramphenicol/ml. Comparative experiments showed that the change in pigment formation was hereditary, i.e. that actual mutation, and not selection of chloramphenicol-resistant mutants, occurred. Mutation occurred both in strain 151 and strain HY. The resultant mutations remained constant throughout ten passages on normal nutrient medium. The minimum chloramphenicol concentration which produced an increase in the mutation frequency was 5 μg./ml. The combined effect of X-ray irradiation and chloramphenicol treatment somewhat stimulated the increase in the frequency of mutation as compared with cells which were only irradiated. The increase in the frequency of mutation was much slower on solid medium containing chloramphenicol.     

Retinal in the blood and liver of the fowl in relation to sex and maturity

1. Concentrations of retinal (vitamin A(1) aldehyde) in the plasma and liver of laying hens, mature cockerels, immature pullets and pullets undergoing sexual maturation have been measured. 2. The plasma of laying hens contained about 8mug. of retinal/100ml., about ten times that found in the plasma of mature cockerels and immature pullets. In laying hens that had received large doses of retinyl palmitate 8-4 weeks previously, the mean concentration of retinal was 18.3mug./100ml. of plasma. 3. The appearance of significant amounts of retinal in the plasma of maturing pullets coincided with hypertrophy of the oviduct, increase in concentration of plasma lipid and onset of egg-laying. 4. Retinal was present in the livers of all types of fowl examined and the concentrations, which ranged from 0.2 to 5.8mug./g. wet wt., were highly correlated (r=0.79) with the concentrations of liver retinyl esters, which ranged from 92 to 1530mug./g. wet wt.     

Benefits and risks of protracted treatment with human recombinant erythropoietin in patients having haemodialysis.

Fourteen patients with uraemic anaemia and having regular haemodialysis were given human recombinant erythropoietin in increasing doses, beginning with 24 U/kg thrice weekly. One patient was dropped from the study because of recurrent thrombosis of vascular access sites. In the other 13 patients, followed up for a mean of 9.1 months (range 8-11), haemoglobin concentrations increased from 62 (SD 8) to 105 (9) g/l. No antierythropoietin antibodies were detected during the study. The correction of anaemia was associated with a tendency to hyperkalaemia and a mild increase of unconjugated bilirubinaemia. In eight previously hypertensive patients antihypertensive treatment had to be reinforced, but in normotensive patients blood pressure did not change. Thrombosis of arteriovenous fistulas occurred in two patients and a cerebral ischaemic lesion in one. Protracted treatment with human recombinant erythropoietin evidently can maintain normal haemoglobin concentrations in uraemic patients over time. Full correction of anaemia, however, may trigger some vascular problems, particularly in hypertensive patients and those with a tendency to thromboembolism.     

Unclassified Mycobacteria Isolated from Human Suspect Tuberculosis Cases in Newfoundland: Preliminary Studies on Fifteen Strains

Unclassified mycobacteria were isolated from 36 of 35,555 clinical specimens cultured for M. tuberculosis. The majority of isolations were from patients suspected of having tuberculosis and from whom repeat attempts at culture failed to yield typical tubercle bacilli. Fifteen strains thus far studied were not capable of causing generalized tuberculosis in guinea pigs, and all were highly resistant to the commonly employed antituberculous therapeutic agents. Eleven of the 15 strains were resistant to 100 or more μg./ml. of streptomycin; 12 strains were resistant to 25 or more μg./ml. of para - aminosalicylic acid; and all 15 showed growth in the presence of 50 or more μg./ml. of isoniazid. All strains were niacin-negative and catalase-positive. In the absence of other cultural findings, isolation of anonymous mycobacteria poses a major problem, especially in those cases in which the clinical and radiographic findings are typically those of tuberculosis.     

Long-term antihypertensive treatment inhibiting progression of diabetic nephropathy

Six men aged 26-35 years with proteinuria due to insulindependent juvenile-onset diabetes were treated for moderate hypertension (mean blood pressure 162/103 mm Hg) and studied for a mean of 73 months for the effect on the progression of nephropathy. All patients were of normal weight. During a mean control period of 28 months before treatment the mean glomerular filtration rate (three or four measurements) was 86·1 ml/min and mean 24-hour urinary albumin excretion (also three or four measurements) 3·9 g (range 0·5-8·8 g).During antihypertensive treatment the mean systolic blood pressure fell to 144 mm Hg and mean diastolic pressure to 95 mm Hg. In the control period five patients had shown a mean monthly decline in glomerular filtration rate of 1·23 ml/min; with antihypertensive treatment, however, this decline fell to 0·49 ml/min (2p=0·042). In the remaining patient the glomerular filtration rate was 137 ml/min before treatment and 135 ml/min at the end of the treatment period. In all patients the mean yearly increase in albumin clearance (expressed as a percentage of the glomerular filtration rate) fell from 107% before treatment to 5% during treatment (2p=0·0099).This small study indicates that antihypertensive treatment slows the decline in renal function in diabetic nephropathy. Clinical trials beginning treatment in the incipient phase of diabetic nephropathy will define the optimal modality of treatment in this large patient population.     

The adenylate kinase of human plasma, erythrocytes and platelets in relation to the degradation of adenosine diphosphate in plasma

1. Adenylate kinase (EC 2.7.4.3) has been shown to be present in human plasma obtained by conventional means and the adenylate-kinase activities of plasma and of lysed and intact human platelets and erythrocytes have been measured at 37 degrees by sensitive spectrophotometric methods. 2. The activities found in plasma ranged from 2.7 to 22.9mumoles of ADP formed/min./l. and in lysed platelets and lysed erythrocytes mean values of 0.79 and 12.0mumoles of ADP formed/min./10(9) cells respectively were found. Intact platelets and erythrocytes showed little or no activity. 3. The apparent K(m) of plasma adenylate kinase for ADP was found to be 1.4-1.6mm. 4. The adenylate-kinase activity of plasma was correlated with the free haemoglobin present and the larger part of the activity could be accounted for by haemolysis occurring either during the withdrawal of the blood or in vivo. 5. Aggregation of platelets by ADP, collagen fibres or thrombin released up to 16% of the platelet adenylate kinase into the suspending medium. 6. Measurement of the rate of breakdown of 1.6mum-ADP in plasma gave values of about 0.1mmu-mole/min./ml. This was not increased by addition of sufficient erythrocyte lysate to increase the activity of plasma adenylate kinase five to ten times. 7. It was concluded that the activity of adenylate kinase found in plasma, even after aggregation of the platelets, is insufficient to account for the rate of breakdown of low concentrations of ADP usually observed, and that another enzyme is responsible for this process.     

Physiological Studies in the Mucorales: PART II SOME OBSERVATIONS ON GROWTH REGULATION IN THE SPORANGIOPHORE OF PHYCOMYCES

Lanolin emulsion paste incorporating indolylacetic acid in concentrationsof 10,000, 1,000, 100, and 10 µg./ml when applied witha micromanipulator to one side of Phycomyces sporangiophoreshad no clearly marked action on subsequent growth Griseofulvin, a metabolic product of Penicillium janczewskiiand certain other moulds, at a concentration of 1OO µg./ml.,produced a local increase in the rate of extension of the wallat or near the region to which it was similarly applied, withconsequent curvature from the normal erect growth habit. Previously proposed explanations of the regulation of sporangiophoregrowth, and of phototropism, in terms of the action of heteroauxinand auxin- are criticized, and attention directed to the dangerof assuming that substances active in regulating the growthof cellulose-walled times will have a similar action on chitin-walledfungal hyphae.     

Home blood glucose concentrations in maturity-onset diabetes.

Blood glucose concentrations during normal daily activities were measured in 106 patients with maturity-onset diabetes from capillary blood samples collected on to filter paper. Samples were taken before and two hours after main meals, before going to bed, and, in 51 cases, during the night. Fasting and mid-morning values were closely correlated with the mean values over 24 hours irrespective of the type of anti-diabetic treatment being given. Postprandial blood glucose concentrations remained below 11.5 mmol/l (207 mg/100 ml) when the fasting blood glucose value was 7.0 mmol/l (126 mg/100 ml) or less, and repeated fasting blood glucose values exceeding 7.0 mmol/l were associated with raised blood glycosylated haemoglobin concentrations. Diabetic control in maturity-onset diabetes may be satisfactorily monitored by regular measurement of fasting or mid-morning blood glucose values.     

Variation of Fungicide Resistance in Czech Populations of Pseudoperonospora cubensis

During the growing seasons between the years 2001 and 2004, 98 isolates of Pseudoperonospora cubensis from nine regions of Czech Republic were collected and screened for tolerance/resistance to the three frequently used fungicides (propamocarb, fosetyl‐Al, metalaxyl). Fungicides were tested in five different concentrations, using a floating disc bioassay. Fungicide effectiveness varied considerably. Propamocarb appeared most effective and all the isolates collected in the years 2001–2003 were found sensitive to all tested concentrations [607–9712 μg active ingredient (a.i.)/ml]. In 2004, some strains with increased resistance to propamocarb were detected. These strains were characterized by tolerance at the lowest concentrations (607 μg a.i./ml, eventually on 1214 μg a.i./ml); however, they were controlled by 2428 μg a.i./ml. Fosetyl‐Al was effective at the recommended concentration of 1600 μg a.i./ml against all isolates. However, the occurrence of isolates (collected in 2001) which sporulated at low concentrations (400 and 800 μg a.i./ml) indicated that the selection for tolerance occurs in the pathogen population. Nevertheless, this phenomenon was not confirmed with the P. cubensis isolates collected between the years 2002 and 2004. Metalaxyl was found ineffective, because 97% of the isolates showed the resistance to the recommended concentration (200 μg a.i./ml), and the other 3% of isolates expressed tolerant response. The majority of the isolates showed profuse and/or limited sporulation at higher concentrations (400 and 800 μg a.i./ml). A substantial shift to highly metalaxyl resistant strains was evident in the Czech P. cubensis populations during 2001–2004.     

Pancreatic spasmolytic polypeptide (PSP): II. Radioimmunological determination of PSP in porcine tissues, plasma and pancreatic juice

A radioimmunoassay (RIA) for the determination of porcine Pancreatic Spasmolytic Polypeptide (PSP) has been developed. The antisera raised in rabbits were sensitive to 5 pgequiv. of PSP in a volume of 100 microliter. Immunoreactive PSP (IR-PSP) has been determined in extracts from 22 porcine organs. Pancreas was found to be the only organ containing substantial amounts of IR-PSP (0.1 mgequiv. IR-PSP/g wet weight). The fasting porcine plasma level of IR-PSP was about 10 ngequiv./ml, corresponding to 850 pM. The concentration of IR-PSP in porcine pancreatic juice varied from 0.2 mugequiv./ml in the fasting state to 46-116 mugequiv./ml after stimulation with pancreozymin or secretin. A linear correlation was found between the exocrine secretion of IR-PSP and total protein.     

Resistance of Pseudomonas aeruginosa to gentamicin

The resistance to gentamicin 4 μg./ml. of 250 Pseudomonas aeruginosa isolates was measured by a proportion method. Twenty-eight (11.2%) of the cultures fell into the most resistant group, in whose populations between 10 and 100% of the organisms were resistant. A relatively high percentage of urinary isolates and a comparatively low percentage of isolates from respiratory sources occurred in this group. Three of the 28 were resistant to carbenicillin 150 μg./ml. and 6 of 18 tested were as resistant to gentamicin 8 μg./ml. as they were to 4 μg./ml. The distribution of Ps. aeruginosa isolates between the different grades of resistance did not change significantly during the 10 months in which the survey was performed.     

The effect of labour on uterine blood flow in the pregnant ewe.

The effect of labour on cardiac output and uterine blood flow was measured in pregnant ewes at a mean gestation of 124 days using radioactive microspheres labelled with 169Yb and 85Sr. Labour was induced by a continuous infusion of ACTH into the foetal circulation. Cardiac ouput measured before ACTH infusion in seven ewes was 5234 +/- 175-9 ml./min (mean +/- S.E.) and total uterine blood flow was 732 +/- 57-9 ml./min (mean +/- S.E.). Measurements during labour in six ewes showed a significant increase in cardiac output to 6175 +/- 149-6 ml./min (P less than 0-005) but no significant change in uterine blood flow. However, the partition of blood flow was altered; thus myometrial flow increased by 67% from 114 +/- 15-4 ml./min to 190 +/- 13-2 ml./min (P less than 0-005) while placental blood flow decreased, although not significantly, from 618 +/- 55-9 ml./min to 575 +/- 40-7 ml./min. Similar changes were observed in one ewe in spontaneous labour at term and in another ewe receiving an infusion of 4 mg oestradiol 17beta over a 24 hr period. It is concluded that labour is not associated with any major alternation in total uterine blood flow although myometrial blood flow is increased. It is not known whether this is due to the rise in circulating oestrogens which occurs prior to parturition in the ewe, or to other factors such as the work of uterine muscle during labour.     

Susceptibility of Neisseria gonorrhoeae to seven antibiotics in vitro

One hundred consecutive isolates of N. gonorrhoeae were tested for susceptibility to penicillin, ampicillin, tetracycline, erythromycin, kanamycin, cephaloridine and cephalexin by an agar dilution method. Relative resistance to penicillin was frequent. For 39% of isolates the minimum inhibitory concentration (MIC) of penicillin was 0.05 U./ml. or less; in 55% the MIC was 0.5 to 2.0 U./ml. Ampicillin was slightly more active than penicillin G: all isolates were inhibited by 0.5μg./ml. or less. Resistance to tetracycline and erythromycin was frequent with MIC of 1 μg./ml. or greater observed in 32 and 24% of isolates respectively. The MIC of kanamycin for all gonococci was 8 μg./ml. or greater. Cephalexin was slightly more active than cephaloridine, though each drug exhibited a wide range of MIC values. Gonococcus isolates resistant to penicillin (MIC of 1.0 U./ml. or greater) tended to be resistant to the other antibiotics tested.     

Inhibition of protein synthesis in Krebs 2 ascites cells and cell-free systems by phenylalanine and its effect on leucine and lysine in the amino acid pool

1. The inhibition of incorporation of ¹⁴C-labelled amino acids into protein of whole cells by phenylalanine has been reproduced in a cell-free system. In both cases only the l-isomer was inhibitory. 2. The effect of phenylalanine on incorporation of [¹⁴C]leucine and [¹⁴C]lysine into protein was different in both whole cells and cell-free systems. 3. In whole cells inhibition of incorporation of leucine at 2·5μg./ml. was very rapid, but when the concentration was increased to 100μg./ml. the inhibition was not apparent for about 1hr. The kinetics of inhibition of lysine was the same at both these concentrations and was similar to that found with leucine at 100μg./ml. 4. Neither a lower specific radioactivity of the two amino acids in the pool nor a decrease in their pool size could be consistently related with inhibition of protein synthesis. 5. In the cell-free system l-phenylalanine inhibited the incorporation of leucine but not of lysine. 6. Charging of transfer RNA by leucine was markedly decreased in the presence of phenylalanine, whereas charging of transfer RNA by lysine was not.     

Faecal blood loss in response to exercise.

Recently qualitative tests have indicated that gastrointestinal bleeding during exercise may be an important contributory factor in sports anaemia. In six healthy men who walked 37 km on four consecutive days faecal haemoglobin content remained normal (reference range 0.10-2.53 mg/g faeces) with no significant differences between values. In 28 marathon runners who refrained from taking drugs or food containing blood the median faecal haemoglobin content increased by 0.42 mg/g faeces (95% confidence interval 0.12 to 0.83 mg/g) from 1.06 (0.86 to 1.31) mg/g before the race. In 13 runners who had taken drugs before the race the corresponding increase in the median faecal haemoglobin content was 0.87 (-0.03 to 2.20) mg/g from the value before the race of 0.93 (0.46 to 1.55) mg/g. Prolonged walking had no effect on gastrointestinal blood loss. Intense endurance exercise in the form of marathon running induced a significant but clinically unimportant increase. This may be exaggerated by the ingestion of drugs and assume importance in causing iron deficiency and sports anaemia. The use of drugs, particularly analgesics, by marathon runners should be actively discouraged.     

Relatively Benign Sickle-cell Anaemia in 60 Patients Aged Over 30 in the West Indies

A study in Jamaica of 60 patients with sickle-cell anaemia over the age of 30 years showed that most of them were in full-time employment. Pains in the bones or joints, leg ulceration, and jaundice were the most frequent types of presentation, but only two patients had a haemoglobin level consistently below 6 g./ 100 ml. Most of the patients were well developed and of average height, and, though the development of secondary sexual characteristics was delayed, there was an average of 2.6 pregnancies per patient. These findings suggest that the course is more benign than has been realized.