Fetal liver infusion: an adjuvant in the therapy of acute myeloid leukemia (AML).
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Biomedical subjects
Publications and source records attributed to N K Mehra.
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Twenty-five multiple case families of pulmonary tuberculosis were HLA typed and the data analysed by the lod score method. There was no evidence of linkage between the susceptibility gene and pulmonary TB, though there were consistently positive female scores. A number of other chromosome 6 genetic markers tested did not reveal any significant deviation in the patient group as compared to the controls, except GLO 2-1 which occurred with a significantly decreased frequency in the former.
Fifty-one North Indian patients with ankylosing spondylitis (AS) are described with mean age of onset 21.2 years and male to female ratio of 16:1. AS began with peripheral arthritis in 47%, low back pain in 41%, acute anterior uveitis in 10%, and heel pain in 2% of the patients. 76% of 51 patients had one of the extra-axial features of AS: peripheral arthritis (61%), heel pain (24%), anterior uveitis (22%), urethritis (12%), kidney disease (10%), mucosal ulcerations (6%), aortic incompetence (4%), and apical pulmonary fibrosis (4%). A majority (71%) of the patients with peripheral arthritis had mono- or oligoarthritis affecting mainly the lower limb joints. Two patients had coexistent rheumatoid arthritis also. HLA-B27 antigen was detected in 48 (94%) of 51 patients compared with 7 (6%) of 118 controls (relative risk 254; Fisher's exact p = 3.49(-29]. On comparing patients with juvenile onset AS and patients with adult onset disease we found peripheral arthritis to be more frequent at the beginning and during the course of disease in the former.
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Quantitative sacroiliac scintigraphy (QSS) was evaluated for the detection of sacroiliac (SI) joint disease before the appearance of radiographic/changes. QSS with fractional quantitation was done in 13 age- and sex-matched controls and 28 patients with different grades of radiographic sacroiliitis. The SI index of each joint was considered separately. The mean SI index values in patients with grade I radiographic sacroiliitis (1.54) and HLA-B27 positive patients with low back pain (1.50) were significantly (P less than 0.01) higher than the mean SI index of controls (1.22); but more than 50% of their SI index values were within the 97.5% confidence limits of the control range. The mean SI index values of patients with grade II (1.38) and grade III (1.34) radiographic sacroiliitis did not differ significantly from the mean SI index of controls (P greater than 0.05). Thus a large overlap between the normal and abnormal ranges of sacroiliac ratios limits the utility of quantitative sacroiliac scintigraphy for the early diagnosis of sacroiliac joint disease.
Thirty-six patients fulfilling the criteria for Reiter's disease were studied (29 men and 7 women; 4:1). The mean age of onset was 23.8 years; in 75% of patients the onset was in the second and third decades. Clinical manifestations included low back pain and stiffness (69%), non specific urethritis (53%), heel pain (44%), radiographic sacroiliitis (42%), conjunctivitis (39%), dysentery and diarrhoea (33%), mucosal ulcerations (17%) kidney disease (14%), anterior uveitis (19%), and keratoderma blennorrhagicum (8%). Peripheral arthritis was mono or oligoarthritis in 58% of patients, mainly affecting the large joints of lower extremities, and it was often asymmetric (mean degree of asymmetry = 0.37). HLA-B27 antigen was detected in 83% of 36 patients compared with 5.9% of 118 controls (relative risk 79, corrected Fisher's P = 7.719E-18).
A total of 258 patients with classic rheumatoid arthritis seen over a 7-year period were included in this study. The majority of the patients had relatively mild disease at the time of presentation. The incidence of extraarticular manifestations such as subcutaneous nodules, vasculitis, amyloidosis and pulmonary involvement was low although one or two pulmonary function test parameters were abnormal in some. Seventy patients were tested for all three subclasses of rheumatoid factors - IgM, IgG and IgA. Of these, 23 patients had all three whilst four had only IgG. The 62 patients who had most typical and severe manifestations were typed for four major HLA loci A, B, C and DR. Of these 42 (67.7%) had DR4 antigen while DR3 antigen was detected in 14 (22.6%).
To demonstrate human leukocyte antigen (HLA)-linked control of susceptibility to pulmonary tuberculosis, 25 multiple-case families were tissue typed for class I and class II HLA specificities. Eight non-HLA genetic markers were also examined for any indication of other genetic factors that might influence the Mycobacterium tuberculosis infection. Observations on estimated HLA haplotype segregation in the sibs suggest that 84% of the affected sibs shared significantly more often than expected a common haplotype with each other than the normal unaffected sibs (P less than 0.001). Also, there was a skewed transmission of DR2 to diseased offspring from diseased parents (21 of 27) and to diseased offspring from healthy parents (15 of 17) in contrast to the transmission of DR2 from either group of parents to healthy offspring (six of 15 and 10 of 16, respectively). The segregation of non-HLA polymorphisms did not deviate significantly from the expected figures. These data provide strong evidence in favor of DR2-associated susceptibility to pulmonary tuberculosis.
Investigations for the HLA-A, -B, -C and -DR antigens were conducted on 124 random North Indian patients with confirmed diagnosis of pulmonary tuberculosis by the demonstration of acid fast bacilli in the sputum. 109 appropriately matched controls from the same ethnic background were also tissue typed. No significant deviation was observed in the HLA-A, -B, and -C locus antigens. With the HLA-DR typing, there was a marginal increase in DR2 and a concurrent significant decrease in DRw6 in the patient group. These deviations were, however, insignificant when correction for the P value was made. ABO blood group typing results indicate that blood group 'O' may afford protection against TB. The involvement of both DR2 and DRw6 is interesting as it is also implicated in leprosy, another mycobacterial disease. The results suggest the possibility of a common gene in the MHC for both tuberculosis and leprosy.
Twenty-five patients (22 males and 3 females) are described who had 'unclassifiable' seronegative peripheral arthritis affecting mainly the large joints of the lower limbs with other typical features of spondyloarthropathies such as heel pain, low back pain, and mucosal ulcers. But their disorders could not be diagnosed as any specific spondyloarthropathy such as ankylosing spondylitis, Reiter's disease, etc. The mean age of onset of disease was 21.4 years and 60% of them had mono- or oligoarthritis; 60% had arthritis of only lower limb joints. Knee, ankle, and hip joints were most commonly involved, often asymmetrically (mean degree of asymmetry = 0.28). Minimal radiographic sacroiliitis was present in 4 patients, though 13 had low back pain. HLA B27 antigen was detected in 21 (84%) of these patients and only 5.9% of 118 controls (relative risk 83). In addition to these 25 patients there were 4 others whose only symptom was severe bilateral heel pain: 3 of them were positive for HLA B27.
The HLA antigen distribution was studied in 37 north Indian patients with myasthenia gravis. The control group consisted of 118 normal, healthy individuals of the same ethnic group. The antigens showing the highest frequency were Bw21 (18.9% vs 4.2% p less than 0.005), Bw35 (24.3% vs 6.8%, p less than 0.005) and A9 (51.3% vs 30.5%, p less than 0.025). HLA-B8 was increased nearly two fold in the myasthenia gravis patients (RR = 2.4) and was confined mainly to the young females without thymoma. The possibility that Bw21 and Bw35 might be the markers for susceptibility to autoimmune disorders in India is discussed. The observations also support those of others that HLA-B8 linked susceptibility gene is more frequently found in myasthenia gravis patients with thymic hyperplasia.
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HLA antigen frequencies in 53 unrelated Asian Indian patients with acute anterior uveitis, with or without associated spondyloarthropathies, were compared with our published data on American Whites and Blacks. The most frequent HLA phenotype among uveitis patients with associated ankylosing spondylitis was A9(W24), B27 in Asian Indians as compared to A2, B27 in the American Whites and Blacks.
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