Immunoglobulin Levels and CD4 / CD8 Counts in β – Thalassemia Major.

Objective: This cross-sectional study determined the CD4, CD8 counts and serum immunoglobulins in transfusion dependent β - thalassemic patients, and correlated them with anti-HIV, anti-HCV and HBsAg status, number of transfusions, iron overload and splenectomy. Methods: Patients with acute or chronic diseases (except HIV, Hepatitis B and C), on immunosuppressive drugs or vaccinated within one month prior to study were excluded. CD4, CD8 counts and serum Immunoglobulins were documented. Results: Increasing transfusions led to higher IgA and IgM as well as a decline in CD4 and CD8 levels. Higher ferritin correlated with high IgM. CD4, CD8 and IgA were significantly higher in splenectomized subjects. HCV correlated significantly with lower IgA values. Conclusion: Higher transfusion requirement, iron overload, splenectomy and HCV infection correlated with alterations in different immunological parameters.

Is there a role for metronomic induction (and maintenance) therapy in elderly patients with acute myeloid leukemia: A literature review.

Acute myeloid leukemia (AML) in older adults differs biologically and clinically from that in younger patients and is characterized by adverse chromosomal abnormalities, stronger intrinsic resistance, and lower tolerance to chemotherapy. In patients over age 60 with AML, cure rates are under 10% despite intensive chemotherapy, and most of them die within a year of diagnosis. Over the last decade, metronomic chemotherapy has emerged as a potential strategy to control advanced/ refractory cancer. Here, we report a case of a 68‑year‑old gentleman having AML with high‑risk cytogenetic features, who achieved complete remission on our oral metronomic PrET (PrET: Prednisolone, etoposide, thioguanine) protocol on an outpatient basis. He was later treated with standard high‑dose (HD) cytosine arabinoside (Ara‑C) consolidation followed by maintenance with etoposide, thioguanine, and sodium valproate. Presently, the patient is nearly 35 months since diagnosis and 21 months off treatment. This case report and review highlights that the combination of oral low‑intensity metronomic therapy, followed by standard HD consolidation therapy and metronomic maintenance therapy may be well tolerated by elderly patients especially with less proliferative, high (cytogenetic)‑risk AML who are otherwise deemed to be unfit for intensive intravenous induction chemotherapy regimens. References for this review were identified through searches of Pubmed for recent publications on the subject as well as searches of the files of the authors themselves. The final list was generated on the basis of originality and relevance to this review.

Comparative study of knowledge about different Child Survival and Safe Motherhood intervention in two groups of mothers.

A cross-sectional study was conducted in an urban field practice slum area served by Urban Health Centre (UHC) attached to the Dept. of Preventive and Social Medicine, T. N. Medical College and Nair Hospital, Mumbai, to compare the knowledge about different Child Survival and Safe Motherhood interventions in two groups of mothers. 152 mother who regularly attended antenatal check-up in UHC constituted study group and 153 mothers selected by individual matching constituted the control group. Significant differences in the knowledge of study and control groups of mothers were observed about some interventions like time of initiation of breast feeding, duration of exclusive breast feeding, age of starting weaning and number of OPV and DPT doses to be given till 1 year of age.

Imatinib mesylate in chronic myeloid leukemia: a prospective, single arm, non-randomized study.

Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder characterized by the balanced reciprocal translocation t (9:22). The resulting fusion gene, the BCR-ABL, is responsible for oncogenesis. Imatinib mesylate is a novel molecule, which inhibits the protein product of this fusion gene and hence has been used in the treatment of CML. The present study evaluates 174 patients with CML treated with imatinib mesylate. Of these 174 patients, 97 were in chronic phase, 47 in accelerated phase and 30 patients had blast crisis. Patients in chronic phase received imatinib mesylate in the dose of 400-mg daily, while those in accelerated phase and blast crisis received 600 to 800 mg daily. Of the 97 patients with chronic phase, 49 patients (50.5%) achieved a major (major + complete) cytogenetic response. Of the 47 patients in accelerated phase, 10 patients (21.3%) achieved a major cytogenetic response and in 30 patients with blast crisis, 7 (23.3%) achieved a major cytogenetic response. Dermatitis, mucositis, neutropenia and thrombocytopenia were some of the major toxicities. Of interest, 121 of the 174 patients (69.5%) developed generalized hypopigmentation. We conclude that imatinib mesylate is a safe and effective first-line therapy for chronic myeloid leukemia.

Allogeneic blood stem cell transplantation in chronic myeloid leukaemia-chronic phase following conditioning with busulphan and cyclophosphamide: a follow up report.

BACKGROUND: Allogeneic bone marrow transplantation (BMT) or peripheral blood stem cell transplantation remains the only modality of treatment that can eradicate a leukaemia clone in the majority of patients with chronic myeloid leukaemia (CML). However, the advent of the targeted molecule imatinib mesylate (formerly STI-571) against the bcr-abl chimeric protein in the disease has brought the issue of managing newly diagnosed CML patients, especially those with available donors, to the crossroads. Although the curative potential of this agent remains unknown, it can produce complete cytogenetic response in > 60% of newly diagnosed patients. METHODS: From May 1991 to October 2002, a total of 55 Ph+ CML-chronic phase patients received oral busulphan 16 mg/kg and cyclophosphamide 120 mg/kg i.v. as a conditioning regimen. All patients received human leucocyte antigen (HLA)-identical sibling donor haematopoletic stem cells--bone marrow in 41 patients (74.5%) and peripheral blood stem cells in 14 (25.4%). Post-transplant prophylaxis for graft-versus-host disease included a short course of methotrexate (on days +1, +3, +6 and +11) and cyclosporin till day +180 in 38 patients (69.1%), while a combination of cyclosporin and methylprednisolone was used in the remaining 17 (29%). RESULTS: At a median follow up of 48 months (10-144 months), 26 patients (47.3%) are alive. Early mortality (100-day) occurred in 17 patients (30.9%). Acute graft-versus-host disease developed in 37 patients (67.3%), and was grade IV in 6 of them. Chronic graft-versus-host disease developed in 17 patients (30.9%). Relapse occurred in only 2 patients (3.6%) till date. The leukaemia-free survival is 64.3% in the peripheral stem cell group, whereas it is 41.5% in the bone marrow recipient group. CONCLUSION: Allogeneic BMT appears to result in eradication of CML and ensure disease-free survival in about half the patients. However, efforts should be made to prevent graft-versus-host disease and minimize early mortality.

A study of mast cells in granulomatous lesions of skin, with special emphasis on leprosy.

76 skin biopsies that included material from 7 controls, 65 granulomatous skin lesions and 2 each of granulation tissue and chronic non-specific inflammation, were subjected to histopathological evaluation on haematoxylin and eosin and pertinent special stains. Mast cell study was done on slides stained by toluidine blue method, with special reference to their location, and morphology and cell count were done with the help of occculomicrometre. In normal skin, mast cell density was 11.43/mm2 with a range of 6-22/mm2 and an S.D. of 5.94. Highest value in the whole series was seen in TVC (66/mm2), followed by lupus vulgaris (50/mm2). Mast cell counts were normal in indeterminate and TT leprosy and showed a rise over the immunological spectrum BT to LL, with values in LL being 32.86/mm2 (28-40/mm2).

Secondary ANLL with t(11;19)(q23;p13) following etoposide and cisplatin for ovarian germ cell tumor.

This is a case report of a ten year old girl with ovarian germ cell tumor who was successfully treated with BEP chemotherapy. She developed acute myloid leukemia, AML-M5 with t(11;19)(q23;p13), 29 months after being off therapy. She received a cumulative dose of 2000 mg/m2 of etoposide and 400 mg/m2 of cisplatin. The association of etoposide and therapy related leukemia is reviewed.

Effect of closed mitral valvotomy on spirometric pulmonary function tests in mitral stenosis.

The effect of closed mitral valvotomy on the spirometric pulmonary functions was studied in 25 patients with mitral stenosis. The tests were performed before and after operation, the latter at varying intervals (4 to 6 weeks and 8 to 12 months). The preoperative values were considerably low. After 4 to 6 weeks following surgery, further significant reduction in Forced Vital Capacity (FVC) and Forced Expiratory Volume in one second (FEV1) was observed. This was ascribed to the residual healing process and thoracotomy pain. However, Forced expiratory flow rate during mid segment of FVC (FEF25-75%), which reflects obstruction in small airways, did not show any variation. There was improvement in all the above parameters, 8-12 months after surgery. This suggests definite reversibility in the pulmonary functions following valvotomy.

Chromosome investigations & clinical outcome in patients with myelodysplastic syndromes.

A total of 25 patients with primary myelodysplastic syndrome (p-MDS) were cytogenetically investigated. The incidence of abnormal karyotypes was higher, detected in 88 per cent of the patients and the most frequent abnormality was a terminal deletion of chromosome 7 (45% of the patients with abnormal karyotypes) followed by an i (17q) (18%), +21(14%), -5/5q (9%), del (11) (q22) (9%). Cytogenetic analysis after therapy/after leukaemic transformation indicated either stable clones (2 patients) or emergence of new clones such as inv(5) (q32q36), del (17) (p13), +20, +22 (1 patient each). It is to be noted that of the 8 patients with leukaemic transformation, 5 had del (7q). The leukaemic transformation (32% of the patients) was not related to the percentage of abnormal karyotypes not to the percentage of blasts at the time of the MDS presentation. Chromosome instability was shown by 10 (45%) patients. Our data indicate that higher frequency of chromosomal aberrations with involvement of chromosome 7 may be the result of underlying disease.

Cytogenetic studies on patients of acute lymphoblastic leukemia Burkitt's type with (8;14) & (14;18) translocations.

Eight patients with acute lymphoblastic leukemia of Burkitt's type (ALL-L3) and two patients with Burkitt's lymphoma (BL) were subjected for cytogenetic studies. Translocation (8;14)(q24;q32) was present in nine (90%) patients; seven patients of ALL-L3 and two of BL. One ALL-L3 patient revealed t(14;18)(q32;q21) in 100 per cent metaphases. Additional clonal chromosomal anomalies present in these patients were deletion (6q) (40%) and trisomy 21(20%). The occurrence of t(8;14)(q24;q32) in ALL-L3 and BL patients in our series supports the association of t(8;14) with ALL-L3 and Burkitt's lymphoma.

Hypotensive anaesthesia for spine surgery--nitroglycerin vs halothane.

Thirty patients (ASA I or II) requiring spine surgery under general anesthesia were studied. To induce hypotension, halothane 0.5 to 2.5% (n = 15) or nitroglycerin infusion (1-2 micrograms/kg/min) (n = 15) was used. The parameters studied were blood pressure, blood loss, operating time and recovery score. The systolic blood pressure was maintained between 80-100 mmHg during surgery in both the groups. The blood loss with nitroglycerin was significantly less (202 +/- 114 ml) than halothane group (602 +/- 312 ml). All the patients were alert at the end of surgery in the nitroglycerin group (recovery score 9.8 +/- 0.76) as against the halothane group (7.98 +/- 0.9 p < 0.01). Tachycardia or tachyphylaxis was not observed with nitroglycerin. This study suggests that continuous intravenous infusion of nitroglycerin is effective and safe in reducing blood loss and operating time during spine surgery.

Aniridia--Wilms' tumour association--a case with 11p 13-14.1 deletion and ventricular septal defect.

A two year old female child with bilateral wilms tumor (WT) along with multiple congenital anomalies like bilateral aniridia with congenital cataracts and nystagmus, microcephaly, mental retardation and ventricular septal defect has been described. The karyotype analysis revealed 46 xx, del 11p 13-14.1. Association of ventricular septal defect with the classical features of 'Aniridia-Wilms' tumor association' is an unusual feature in this case.

Childhood myelodysplastic syndromes: clinical features, cytogenetics and prognosis.

Sixteen children with myelodysplastic syndrome as defined by the French-American-British co-operative group are presented. The mean age was 10.5 (2.5 to 16) years, with a male predominance. All patients belonged to the more aggressive subtypes of myelodysplastic syndromes. Seven patients presented with refractory anaemia with excess blasts, six had refractory anemia with excess blasts in transformation, and three had chronic myelomonocytic leukemia. Cytogenetic analysis done in 7 of the 16 patients, revealed karyotype abnormalities involving chromosomes 7, 8 and 17. One patient with Down's syndrome had karyotype of 47, XY, +21 (major clone) and 46, XY (minor clone). Five of these patients evolved to acute leukemia. The mean duration of survival was 5.5 months. Aggressive chemotherapy as a primary line of treatment induced remission in five out of six patients. Predominance of aggressive types of myelodysplastic syndromes in children and their good but short-lived response to aggressive chemotherapy suggests the need for early bone marrow transplantation following chemotherapy.

Fanconi's anemia: a clinico-hematological and cytogenetic study.

Eleven patients with typical features of Fanconi's anemia with cytogenetic studies were evaluated. Cytogenetic abnormalities was seen in all but one patient. Two patients had acute non-lymphoblastic leukemia (ANLL) and nine had Fanconi's anemia (FA). All patients with FA responded to oxymetholone and are well with a median follow up of 38.6 months. Both patients with ANLL died. This study stresses the need of an accurate cytogenetic analysis in FA patients along with a clinicohematological correlation.

Chronic myelomonocytic leukaemia (an analysis of fourteen consecutive cases).

Fourteen consecutive cases of chronic myelomonocytic leukaemia aged 6 to 73 (mean 40.5) years were reviewed to define the natural history of the disease and the risk of acute transformation. The common presenting features included anaemia, fever, purpura, and bleeding tendencies. Abnormal karyotypes were seen in 4 of 6 patients subjected to cytogenetic analysis. Low dose cytosine arabinoside achieved complete remission in two and partial remission in one, of the four patients treated with this modality. The mean survival was 5.6 (range 2-12) months and two patients) evolved to acute myeloid leukaemia. The long term survival with the present form of therapy in chronic myelomonocytic leukaemia is poor.

Cytogenetic studies in Hodgkin's disease.

Chromosome studies were carried out by G-banding technique on the bone marrow cells of 24 newly diagnosed, untreated Hodgkin's disease patients and 25 treated patients. Seven of these treated patients had also been studied at diagnosis. In the untreated group of patients, cytogenetic studies were carried out on stimulated peripheral blood lymphocytes in 11 patients and on skin fibroblasts in five. Of the 24 untreated patients, 14 showed normal diploid pattern, while 10 were seen with 8-30 per cent chromosomally aberrant cells in the bone marrow. The frequent anomalies were trisomy C/8 and trisomy 22 seen in 5 and 4 patients respectively. The cytogenetic picture of peripheral blood lymphocytes revealed normal diploid pattern in 7 patients; while 4 other patients showed abnormal clones with trisomy 21. The cultured skin fibroblasts represented normal diploid karyotypes. An altered karyotypic pattern was seen in the bone marrow of treated patients. In patients with abnormal karyotypes, the common anomalies were monosomy C, monosomy D/15 and trisomy 21. In patients which showed no involvement of the bone marrow by haematological parameters, chromosomally abnormal karyotypes were seen in the marrow. Thus, marrow involvement can be detected earlier cytogenetically.