Interferon in the treatment of hairy-cell leukemia

The introduction of alpha interferon in 1984 initiated a new and exciting turnaround in the treatment of hairy-cell leukemia. Until that time splenectomy was the only known effective therapy for this disease. Interferon proved to benefit hairy-cell leukemia patients with active disease, whether or not they had undergone prior splenectomy. However, most interferon-induced responses were partial and were of relatively short duration. Purine analogues such as cladribine and pentostatin have since been found to be more effective than alpha interferon and, therefore, have now replaced interferon as first-line therapy for hairy-cell leukemia. At the present time, interferon has a relatively limited role in the treatment of hairy-cell leukemia and it is reserved for a group of selected patients who have failed nucleoside analogue therapy. In this chapter, we discuss the efficacy of interferon and its response duration, toxicity and possible mechanism of action in patients with hairy-cell leukemia.     

Proteasomal degradation of human peptidyl prolyl isomerase pin1-pointing phospho Bcl2 toward dephosphorylation

Microtubule inhibitor-induced Bcl2 phosphorylation is detrimental to its antiapoptotic function. Phosphorylation of Bcl2 predominantly occurs on two serine residues (70 and 87) in cells arrested at G2-M phase by microtubule disarraying agents. Phospho Bcl2 can associate with a cis-trans peptidyl prolyl isomerase, Pin1. Pin1 and its homologues are known to target the proline residue carboxyl terminal to the phosphorylated threonine or serine residue of mitotic phosphoproteins, such as Bcl2. However, it was not clear how an extranuclear protein could associate with nuclear Pin1. The confocal images of the immunofluorescence studies employing phospho Bcl2-specific antibody developed in the laboratory demonstrated the translocation of phospho Bcl2 inside the nucleus. Interestingly, proteasomal degradation of Pin1 facilitates dephosphorylation of phospho Bcl2 due to longer exposure of Taxol. Here we show for the first time that proteasomal degradation of Pin1 is the key factor to determine the fate of phosphoforms of Bcl2. When Pin1 is degraded by proteasomes, phospho Bcl2 is converted to its native form. Thus, transient conformational change of Bcl2 due to association with peptidyl prolyl isomerase can contribute to irreversible apoptotic signaling.     

Epidemiology of epilepsy--Indian perspective

There are about 20 epidemiological studies on epilepsy from different parts of India. They include both rural and urban studies. The prevalence rate stands at around 5/1000 population (at this rate present estimate of total epileptics in this country is about 5 million) and incidence rate varies from 38 to 49.3 per 100,000 population per year from two community-based studies in India. Case-control studies indicate that febrile seizures, family history of epilepsy and head trauma are significant risk factors. Type of seizure pattern showed maximum number of cases belonged to generalised seizures which is different from Western countries where partial seizure is the commonest variety. Treatment gap, which is a measure of per cent of patient populations not receiving the treatment, estimated to be up to 73.7% to 78% in India. Aetiology is unknown in about two-thirds of cases. Hot water epilepsy is unique in South India and single solitary ring enhancing lesion in brain imaging is a common feature in Indian subcontinent. Evaluation of prevalence study indicates that more case-control studies to find out the aetiology, pharmaco-economic study to find out the affordable drug for general public and mass health education should be undertaken to dispel the social stigma and to bring about change in the attitude about the disease.     

Pineal Gland and Humidity Effects on Testicular Function of the Indian Palm Squirrel, Funambulus pennanti

The effect of two different conditions of humidity (80 +/- 5% and 40 +/- 5%) under stimulatory photoperiod (14L/10D) and high temperature (38 +/- 2 degrees C) was studied on the testes and accessory sex organs of the Indian palm squirrel, Funambulus pennanti, during the sexually active phase. High humidity (80 +/- 5%) reduced significantly the testes weight of the sham-operated animals as compared to the controls under natural environmental conditions but had no effect on that of pinealectomized animals. Moderate humidity (40 +/- 5%) did not affect the testes of sham-operated as well as pinealectomized animals, as compared to the respective controls. The seminal and prostatic weights showed no significant difference in high or moderate humidity conditions. However, the epididymal weight of the animals exposed to high humidity was significantly reduced in sham-operated animals only. Thus, these results indicate that the pineal gland may be implicated in mediating the humidity information to control the male gonadal function in the Indian palm squirrel, Funambulus pennanti.     

Alpha-thalassemia among tribal populations of Eastern India

Five hundred and thirteen unrelated subjects belonging to various tribes of West Bengal, Arunachal Pradesh and Assam in Eastern India, were screened for the presence of alpha-thalassemia (thal) gene deletion(s) as a possible cause of unexplained anemia (Hb < 11 g/dL and/or MCH <28 pg, MCV < 78 fL). As reported earlier, beta-globin gene mutant alleles were found with a frequency of up to 20% in some tribes. In the present study, alpha-globin gene deletion alleles were found in 18% of subjects from West Bengal, 3.9% from Arunachal Pradesh and 3.84% from Assam tribesmen. Coexistence of alpha- and beta-globin gene abnormalities was observed in up to 18% of some tribal groups. The high inbreeding rate and lack of appropriate medical care make these populations particularly vulnerable.     

Anesthetic considerations in steroid-induced mediastinal lipomatosis

Mediastinal lipomatosis (ML) is a benign condition characterized by circumscribed overgrowth of adipose tissue producing mediastinal widening that can cause errors in diagnosis on chest roentgenogram. We describe a case of steroid-induced ML leading to difficulty in central venous catheterization during surgery and its other implications for anesthesiologists. Because many patients receive long-term steroid administration and present for surgical intervention, it is essential that they undergo detailed preoperative evaluation to exclude Cushing's syndrome and various pressure effects. IMPLICATIONS: This case report highlights problems during right internal jugular vein cannulation resulting from high back pressure and flow from superior vena cava obstruction in steroid-induced mediastinal lipomatosis. Other anesthetic considerations in mediastinal lipomatosis are also discussed.