Folates in human serum.

Constituent serum folates have been shown to be altered and in some cases raised in diseases in which total folate levels are known to be frequently decreased. Absorption experiments showed that orally administered folate analogues affect the folate pool in different ways. The stability of the 10-formyltetrahydrofolate level in normal subjects is demonstrated.

Serum folates in man.

In an aseptic microbiological assay of folate compounds and their breakdown compounds, using Lactobacillus casei, Streptococcus faecalis, and Pediococcus cerevisiae, 4a-hydroxy-5methyl-4,5,6,7-tetrahydrofolate and 5-methyl-5,8-dihydrofolate were inactive under all conditions to all three organisms and 5-methyl-5,6-dihydrofolate was inactive unless ascorbate was present in the incubation medium, and then only to L. casei. 5-Methyltetrahydrofolate was active only for L. casei, and activity in purified samples to S. faecalis was due to trace amounts of folic acid. Analysis of S. faecalis values in the serum in normal subjects and in patients with various disorders showed that levels of 10-formyltetrahydrofolate are raised in coeliac disease, leukaemia, rheumatoid arthritis, and schizophrenia. 5-Methyltetrahydrofolate is readily absorbed by normal human subjects and by patients with pernicious anaemia but poorly absorbed by patients with coeliac disease or leukaemia. 5-Methyl-5,6-dihydrofolate was quickly absorbed by normal human subjects, being reflected by a considerably raised level of 5-methyltetrahydrofolate in serum when sodium bicarbonate was given by mouth before the 5-methyl-5,6-dihydrofolate. These higher levels were comparable to those in patients with pernicious anaemia after oral administration of 5-methyl-5,6-dihydrofolate. Oral 5-methyl-5,8-dihydrofolate and 4a-hydroxy-5-methyl-tetrahydrofolate did not appear as microbiologically active folates in the serum. The findings of this study suggest that the availability for biological utilisation of the major dietary folate compounds will depend on the amount of gastric acidity and of ascorbate in the intestinal chyme. Many may be unavailable for metabolic utilization in the body.

Biopterin derivatives in human body fluids and tissues.

Levels of biopterin derivatives in urine, serum, milk, cerebrospinal fluid, brain, and liver have been measured with the Crithidia fasciculata assay. Normal levels in serum and urine have been given and compared with those in a number of benign and malignant proliferative disorders, phenylketonuria, kidney disease, Parkinson's disease, schizophrenia, controlled epilepsy, rheumatoid arthritis, and pernicious anaemia. The active component of Crithidia factor in serum was 7,8-dihydrobiopterin. Tissue, urine, and some serum samples contained two active materials, the principal one being 7,8-dihydrobiopterin; a minor constituent was probably tetrahydrobiopterin. Serum biopterin levels following methotrexate administration were raised and subsequent administration of folic acid and 5-formyltetrahydrofolic acid further increased serum levels of biopterin derivatives; this was in contrast to the total absence of response to oral folates without prior methotrexate and to 5-methyltetrahydrofolic acid either with or without methotrexate being given.

[The differentiated treatment of traumatic intracranial hematomas]. / Differentsirovannoe lechenie travmaticheskikh vnutrimozgovykh gematom.

The article deals with the analysis of the clinical and computed tomography data, treatment, and outcomes in 94 patients with traumatic intracerebral hematomas (TICH). The indications for nonoperative treatment of TICH are a level of consciousness of the patient of no lower than 10 marks of the Glasgow coma scale, hematoma diameter of less than 4 cm, and the absence of clinical and computed tomography signs of brain stem compression. Osteoplastic trephination and encephalotomy is the principal surgical method. Puncture evacuation of the TICH may be resorted to if more than three fourths of its volume can be aspirated. The stereotaxic method is recommended for removal of TICH situated in the region of the basal ganglia.

Oxygen-derived free radical inhibition in the healing of experimental zone-of-stasis burns.

When dehydration, infection, and mechanical trauma are prevented, procedures (such as cooling and/or oral antithromboxane) designed to diminish ischemia in experimental zone-of-stasis burns have been associated with no or only minor improvement in wound healing. To test the hypothesis that ongoing skin damage occurring postburn (PB) may in part be due to release of oxygen-derived free radicals during the 16-hour through 4-day PB period of reperfusion in such burns, beginning immediately and for a period of 5 days PB, equal numbers of guinea pigs received: allopurinol 150 mg/kg PO q 6 h vs. placebo, dimethylsulfoxide (DMSO) 75% applied topically q 12 h vs. placebo, or yeast-derived superoxide dismutase coupled with polyethylene glycol (PEG-SOD, Pharmacia) 10,000 U (Fridovich) given IV q 8 h producing a concentration of 16 U/cc of plasma 8 hr after injection vs. placebo. Gross and histologic examination of wounds by a 'blinded' investigator at 1 week and 3 weeks PB revealed no difference between treatment and control groups when rates of re-epithelialization and frequencies of hair-follicle retention were compared. Using the dosages, routes, and model described, treatment of a zone-of-stasis burn with PO allopurinol (a xanthine oxidase inhibitor), topical DMSO (a scavenger of the hydroxyl radical), or IV PEG-SOD (a scavenger of the superoxide radical) during the first 5 days PB was associated with no increase in the rate of re-epithelialization or frequency of hair follicle retention at 1 and 3 weeks PB when compared with controls.

The stimulant effect of drugs on indocyanine green clearance by the liver.

The rate of removal of a standard dose of 25 mg indocyanine green was studied in 67 patients at the bedside using dichromatic ear densitometry. The determination of the percentage disappearance rate per minute and the half life of the dye permitted separation of patients into three groups: those with normal liver function, those with liver damage, and a group taking opiates (9), anticonvulsants (8), phenylbutazone (2), haloperidol (1), and nitrofurantoin (1). The last group showed enhanced clearance of indocyanine green from the circulation.

Thromboembolism in inflammatory bowel disease: role of platelets.

Patients with inflammatory bowel disease are susceptible to thromboembolism and recently small vessel thrombosis has been implicated as an aetiological factor in Crohn's disease. This study therefore investigated platelet function in 104 patients with inflammatory bowel disease of whom eight had previous thromboembolism. Thirty five patients had reproducible spontaneous platelet aggregation of more than 30% (0 in controls) (p < 0.0001). A further 20 patients showed hypersensitivity of platelets to low concentrations of aggregating agents (p < 0.001). Plasma thromboxane B2 and beta thromboglobulin levels were significantly higher than controls (p < 0.001 and p < 0.001), but platelet lifespan studies were normal. There was no correlation with disease activity. Patients with inflammatory bowel disease have abnormal platelet activity, which may contribute to the inflammatory process.

Intravascular haemolysis after valve replacement: comparative study between Starr-Edwards (ball valve) and Björk-Shiley (disc valve) prosthesis.

Seventy-four patients with single prosthetic valves (Björk-Shiley or Starr-Edwards) in the mitral or aortic position and 18 controls with rheumatic valvar heart disease were investigated for evidence of intravascular haemolysis. Serum lactate dehydrogenase (LDH) was used as the most sensitive indicator of haemolysis. Raised concentrations were found in a third of 39 patients with Björk-Shiley prostheses (mean 281 IU/l) and in all 35 patients with Starr-Edwards prostheses (mean 859 IU/l. Values were considerably higher in patients with Starr-Edwards prostheses and particularly in those with aortic prostheses (mean 927 IU/l). Eight out of 12 patients with haemosiderinuria had Starr-Edwards valves. Intravascular haemolysis was of little clinical significance in patients with Björk-Shiley prostheses, but some patients with Starr-Edwards prostheses became iron deficient as a result.

Spontaneous rupture of the spleen in association with idiopathic thrombocytopaenic purpura.

Spontaneous rupture of the spleen is rare and has not been previously reported in association with idiopathic thrombocytopaenic purpura. Its rarity makes familiarity with its presentation difficult and may result in a potentially fatal delay in diagnosis and treatment.

Serum alkaline phosphatase and rickets in urban schoolchildren.

Among 569 schoolchildren (386 boys and 183 girls) aged 14-17 years, 233 had serum alkaline phosphatase values of 30 K.A. units or greater. There was no significant difference in the results in Asian, white, or West Indian children. The mean values were significantly greater in boys than girls and both showed a fall in mean values with increasing age. Radiological rickets occurred in at least 4% of the survey, and was more common in Asians. Low calcium and high hydroxyproline excretion in most of those investigated and the response to vitamin D therapy suggests that most children with alkaline phosphatase levels above 30 K.A. units have rickets.Since the decline of the widespread supplementation of the diet with vitamin D, the demands of the physiological growth spurt for extra vitamin D in adolescents already on a borderline intake may be responsible for the great increase in "biochemical" rickets. Once the growth spurt is over the condition subsides but the results of impaired growth or permanent pelvic deformity will not necessarily be eradicated.

Rickets, growth, and alkaline phosphatase in urban adolescents.

Calciferol therapy for 12 months in white, Asian, and West Indian schoolchildren resulted in a highly significant increase in height and weight when compared with schoolchildren not so treated. The rate of fall of serum alkaline phosphatase was similar in both the treated and untreated schoolchildren and in other children treated in hospital for rickets. Dietary studies on 9% of the total survey by weighed inventory methods showed a low average intake of vitamin D, while random estimates of 25-hydroxycalciferol levels on 6% of the children were less than 3.8 ng/ml in 40% of those studied (principally Asian). It was concluded that there was a significant problem of vitamin D deficiency among Asian and West Indian teenagers and that white children were also affected to a less degree.

Seroepidemiology of Helicobacter pylori infection in vegans and meat-eaters.

An enzyme-linked immunosorbent assay has been used to diagnose serologically the prevalence of Helicobacter pylori infection in Asian life-long vegans. There was no difference in the seropositivity between these individuals and a group of age- and sex-matched Asian meat-eaters, indicating the meat consumption is not a risk factor for H. pylori infection. However, both Asian groups had a higher prevalence of infection than age- and sex-matched Caucasian meat-eaters. Additionally, the Asian individuals had a wider range of specific IgG antibody concentrations than the Caucasians. This did not appear to be due to antigenic cross-reactivity between H. pylori and Campylobacter jejuni. The significance of these observations to the establishment of cut-off levels for the serodiagnosis of certain ethnic groups is discussed.

Erythrocyte membrane modification in malignant diseases of myeloid and lymphoreticular tissues. I. Tn-polyagglutination in acute myelocytic leukaemia.

Tn polyagglutination (persistent mixed-field polyagglutination) occurring in a patient with an acute myelocytic leukemia is described. The association of this RBC membrane change, thought to be due to somatic mutation at stem cell level, with a myeloproliferative disorder, has not been previously reported.

Rapid intravenous injection of tobramycin: suggested dosage schedule and concentrations in serum.

A single, rapid intravenous injection of tobramycin in doses of 1.5 mg/kg or 80 mg administered to subjects with normal renal function produced a wide range of concentrations in serum. Serum concentrations peaked at greater than 20mug/ml in one third of the subjects, but these peaks were transitory. At 6 hr the serum levels were less than 2 mug/ml in all but one subject and were less than 0.1 mug/ml in 50% of the subjects. A dosage interval of 6 hr with a total dosage of 6 mg/kg per day is recommended. The variation in individual dose responses emphasizes the need for monitoring of levels of tobramycin in serum during treatment. Serum concentrations of 4-6 mug/ml 1 hr after injection can be considered indicative of adequate therapy. Levels in serum 6 hr after administration should also be monitored, particularly in the elderly. No immediate or delayed toxic effects were observed after intravenous injection of tobramycin.

Ranitidine in reflux oesophagitis. A double-blind placebo-controlled study.

This study was designed to assess the effect of ranitidine on patients with symptomatic oesophageal reflux. In a double-blind comparative trial in 46 patients a twice daily dose of 150 mg ranitidine was compared with placebo. Relief of pain, endoscopic healing and histological improvement were significantly better in those treated with ranitidine. Thus, ranitidine is of value in the management of patients with reflux oesophagitis and may prevent the development of peptic stricture.

Neuroleptic malignant syndrome: a case for electroconvulsive therapy.

A case of prolonged and refractory neuroleptic malignant syndrome was treated successfully with electroconvulsive therapy. Neuroleptic malignant syndrome and its treatment are reviewed.

Campylobacter pyloridis and associated gastritis: investigator blind, placebo controlled trial of bismuth salicylate and erythromycin ethylsuccinate.

An investigator blind trial was performed comparing bismuth salicylate, erythromycin ethylsuccinate, and placebo in the treatment of Campylobacter pyloridis associated gastritis in patients without peptic ulceration. Fifty patients fulfilled the study criteria. There was a strong correlation between the presence of C pyloridis and histologically confirmed gastritis. Clearance of organisms led to improvement of the gastritis. C pyloridis was cleared from 15 patients; of these, 13 had gastritis initially, which resolved in 12. Conversely, gastritis resolved in only four of 32 patients not cleared of organisms (p less than 0.0001). There was significantly greater improvement in endoscopic appearances in the patients cleared of C pyloridis compared with those whose infection persisted (p less than 0.001). In the three treatment groups organisms were cleared from 14 of 18 patients receiving the locally active bismuth salicylate, only one of 15 patients receiving erythromycin ethylsuccinate, and none of 17 patients taking placebo. These findings suggest that the ideal antimicrobial for the successful eradication of C pyloridis associated gastritis should be locally active, stable at low pH, and should penetrate gastric mucus. The resolution of gastritis and improvement in endoscopic appearances associated with clearance of C pyloridis support the view that these organisms may play a part in this condition.