The neuropsychiatry of megaloblastic anaemia.

The neuropsychiatric states of 50 patients with vitamin B12 deficiency and 34 patients with folate deficiency presenting with megaloblastosis in a general hospital were examined and compared. Abnormalities of the nervous system were found in two-thirds of both groups. Peripheral neuropathy was the most common condition associated with vitamin B12 deficiency and affective disorder with folate deficiency. The proportions of patients with organic mental change were similar in the two groups. Subacute combined degeneration of the cord was an uncommon complication and occurred only in the patients with vitamin B12 deficiency. There was no relation between haematological and neuropsychiatric abnormalities. The neuropsychiatry of megaloblastic anaemia seen in this study of patients presenting to haematologists or general physicians contrasts with that reported previously, before haematological techniques for separating the two deficiencies were introduced.     

Defective DNA synthesis in megaloblastic anaemia. Studies employing velocity sedimentation in alkaline sucrose gradients.

1. Autoradiographic experiments revealed that the average size of the replicating unit (replicon) in human phytohaemagglutunin-stimulated lymphocytes is 45 (+/- 1.3) micron. 2. A 5 min pulse of [3H]thymidine labelled DNA chains of approximately 40 S (15 micron) in control lymphocytes as revealed by velocity sedimentation in alkaline sucrose density gradients. Upon chasing in the absence of [3H]-thymidine the labelled DNA increased in size. By 6 h the bulk of the label co-sedimented with full-sized chromosomal DNA. 3. In untreated lymphocytes from patients with megaloblastic anaemia due to vitamin B-12 or folate deficiency or lymphocytes treated with methotrexate (10(-5) M) or hydroxyurea (5 . 10(-4) M) the increase in size of pulse-labelled DNA was slower than in control cells. 4. The block in maturation of pulse-labelled DNA to bulk DNA was not permanent. At 24 h of chase 75-80% of the pulse-label in both control and megaloblastic lymphocytes co-sedimented with bulk DNA. 5. We conclude that the lesions seen in DNA synthesis in megaloblastic anaemia due to folate or vitamin B-12 deficiencies occur through impaired biosynthesis of nucleotide precursors of DNA. Possible explanations of why the defects in DNA synthesis cause altered morphology of proliferating cells in megaloblastic anaemia are suggested.     

Interaction of phenytoin and primidone.

The ratio of derived phenobarbitone to unmetabolized primidone in the serum was significantly higher in 50 epileptic patients on a combination of primidone and phenytoin than in 12 patients on primidone alone, though the dose and serum levels of primidone were similar in the two groups. Out of 253 patients attending a seizure clinic 47% were taking a combination of these two anticonvulsants. The effect of phenytoin on the metabolism of primidone may have clinical implications in view of the frequency of their combined use.     

Neuropathy and fatal hepatitis in a patient receiving amiodarone.

Muscle weakness, neuropathy, and transient rises in hepatic enzyme activity have been reported with the use of the antiarrhythmic agent amiodarone. A 68 year old teetotaller with normal liver function was given amiodarone for resistant supraventricular arrhythmias. He presented 19 months later with vomiting, muscle weakness and wasting, sensory neuropathy, and hepatomegaly. Liver biopsy showed fibrosis and the presence of hyaline. The amiodarone was withdrawn. Three months later he developed ascites. Oesophageal varices were found and he later died. The liver showed micronodular cirrhosis. The large volume of distribution and long half life of amiodarone may explain the persistence of toxicity, which may have been aggravated by simultaneously administered doxepin in this case. Amiodarone should be withdrawn if abnormal liver function or neuropathy develops.     

Lymphadenopathy and selective IgA deficiency.

Four men presented with unexplained lymphadenopathy. Three had a history of recurrent respiratory infections for several years, and two had lymph node or hepatic granulomas. None was noted to have symptoms of immunodeficiency at the time of presentation. In one patient routine direct immunofluorescence study failed to detect IgA, and immunological investigations were therefore conducted in the rest. In all patients the findings were similar and characterised by a severe deficiency of IgA. In the absence of a more serious cause selective IgA deficiency may be enough to explain "idiopathic" lymphadenopathy.     

AIDS in a patient with hemophilia receiving mainly cryoprecipitate.

A 25-year-old man with hemophilia who had been treated primarily with cryoprecipitate presented with epigastric pain and loose, melenic stools. He had a long history of malaise and intermittent upper respiratory tract infection with fever. The patient was shown to have disseminated histoplasmosis and refractory herpes simplex. Immunologic studies demonstrated a markedly decreased ratio of helper to suppressor T cells, lymphopenia, cutaneous anergy and a slightly elevated serum IgA level. These findings met the criteria for the diagnosis of acquired immune deficiency syndrome. In addition, antibodies to human T-cell leukemia virus were detectable in the serum.     

Benign familial tremor treated with primidone.

Primidone given to a patient for epilepsy produced an unexpected reduction in benign familial tremor. Over the next eight years the drug was therefore tried in a prospective study of 20 other patients with benign familial tremor alone. Of these, six could not tolerate the drug because of vertigo and nausea but 12 obtained a good response, which in some cases was dramatic. Investigations in two patients suggested that the effect was mediated predominantly by derived phenylethylmalonamide, though primidone had some effect, since tremor recurred slightly on withdrawing the drug despite a constant or rising blood phenylethylmalonamide concentration. Primidone is highly effective in benign familial tremor. More patients with the condition are intolerant of the drug than are usually found with epilepsy.     

Eperythrozoon infection identified in an unknown aetiology anaemia patient

In this report,Eperythrozoon leading haemolysis was identified in human blood. A patient with long-term anaemia was selected for blood smear examination and electron microscopy. The microscopic results showed a lot of small organisms attaching on the surface of erythrocytes. The partial 16S rRNA gene was amplified and confirmed as haemoplasma by sequence alignment. Phylogenetic analysis showed it fell in the same cluster with otherEperythrozoon species in haemoplasma group. It was the first time to confirm the haemoplasma infection in human blood by molecular assay combined with microscope. Such infection may be a potential criminal of some cases of human unknown origin anaemia.     

Problems in the diagnosis and investigation of megaloblastic anemia.

The diagnosis of megaloblastic anemia and the differentiation of folate and vitamin B12 deficiency require, in addition to careful attention to the history and physical findings, the use of laboratory tests. In this paper the commonly ordered tests for such a diagnosis are discussed, with emphasis on the conditions that may cause false-positive or false-negative results in the complete blood count, examination of a peripheral blood smear and a bone marrow specimen, serum and erythrocyte folate assays, serum vitamin B12 assays, tests of vitamin B12 absorption and gastric analysis.