Beta-interferons in multiple sclerosis: a single center experience in India.

BACKGROUND: Indian-Asian multiple sclerosis behaves somewhat differently from Western disease. It is not known if the response to beta-interferon is also different. AIM: To demonstrate the decrease in relapses with beta-interferon in Indian patients with multiple sclerosis. PATIENTS AND METHODS: Patients with relapsing-remitting or secondary progressive multiple sclerosis with at least two relapses were started on beta-interferon. RESULTS: Sixteen patients were followed up for a period of 1-3 years. Fifteen had relapsing-remitting multiple sclerosis (MS). The mean number of relapses in these patients before interferons were started was 3.4. The mean yearly relapse rate was 1.3. The mean Kurtzke Expanded Disability Status Scale (EDSS) at the start of beta-interferon therapy in relapsing-remitting MS was 1.7. Ten of these patients were on Avonex((R)) (interferon beta1a) and six (including the patient with secondary progressive MS) were on Betaferon((R)) (interferon beta1b). On follow-up, three patients (two on Avonex((R)) and one on Betaferon((R)) ) had relapses. The respective beta-interferon being received by these patients was continued, with no further relapses. The remaining patients had no relapse or clinical or MRI progression after starting the drug. The side effect profile of the drug in these patients was favorable; although nearly all developed fever on the first day of the injection, only 50% of the patients continued to have fever after 3 months. Two patients developed psychiatric symptoms, requiring discontinuation of the drug. CONCLUSION: Our prospective follow-up study shows that beta-interferons are safe and effective in Indian patients with relapsing-remitting or secondary progressive MS.

Impact of obesity on the left ventricular functions and morphology of healthy Asian Indians.

BACKGROUND: The aim of this study was to determine the impact of obesity on alteration of left ventricular (LV) functions and morphology in nondiabetic, nonhypertensive, and normo-lipidemic obese Asian Indians. A total of 239 consecutive Asian Indians (175 males and 64 females, ages 17-64 years) were divided into obese and nonobese groups based on body mass index (BMI), waist-to-hip circumference ratio (W-HR), and percentage of body fat (%BF). METHODS: Anthropometry (BMI, W-HR), %BF, and two-dimensional echocardiography including tissue Doppler imaging (TDI) were performed for all the subjects. The unpaired t-test was applied after matching age and gender in all the comparison groups. Nonobese subjects acted as controls for the obese subjects (cases). RESULTS: Obese subjects had a larger LV end-diastolic diameter (P < 0.001), LV end-systolic diameter (P < 0.001), and LV mass (P < 0.001) as compared to the nonobese subjects. Subclinical systolic dysfunction was apparent in obese subjects only on TDI in the form of reduced systolic mitral annular velocity (P = 0.009). Diastolic dysfunction, as suggested by a lower ratio of early to late transmitral ventricular filling velocity (E/A), lower early to late (Em/Am) diastolic mitral annular velocity, and a higher E/Em ratio (P < 0.001, p = 0.001 and P < 0.001, respectively), was noted in the obese cohort. In addition, the left atrial diameter (P < 0.001) was also increased in obese subjects. Alteration of LV morphology and function correlated with the anthropometric variables BMI, W-HR, and %BF. CONCLUSIONS: Asian Indians with uncomplicated obesity (without associated co-morbidities) had significant morphological and functional cardiac dysfunction (systolic and diastolic), which correlated with anthropometric variables.

Spectrum of Acute Viral Hepatitis in Southern India.

BACKGROUND: The incidence of hepatitis-A among adults in India is on the decline as majority develops protective immunity to it by late adolescence. Most of these studies are from northern India. Clinical spectrum of sporadic acute viral hepatitis from southern India has not been well documented. METHODS: A prospective hospital based study was conducted in a large military hospital in southern India. 224 consecutive patients with acute viral hepatitis were studied for their presentation, etiology and clinical features. RESULT: Hepatitis-E was detected in 102 (45.4%), hepatitis A in 74 (33%) and hepatitis B in 28 (12.5%) patients. Acute hepatitis C was detected in two patients. 15 patients had a mixed infection. Hepatitis A constituted 41.2% and 31.3% of all cases in the age groups 11-20 and 21-30 years respectively. Cholestasis was present in 68 (30.4%) patients with hepatitis E accounting for most (61.8%) cases. There were four (1.8%) cases of acute liver failure. Two cases were due to hepatitis E and one case each was due to hepatitis A and hepatitis B. A relapsing course was seen in four cases due to hepatitis-A. CONCLUSION: Hepatitis A remains a significant cause of sporadic acute viral hepatitis in young adults in southern India.

Impact of Body Mass Index on Left Ventricular Function.

BACKGROUND: Obesity is associated with increased cardiovascular morbidity and mortality. A direct effect of isolated obesity on cardiac function is not well established. The study was designed to determine the direct effect of various grades of isolated obesity on echocardiographic indices of systolic and diastolic left ventricular function. METHODS: Fifty one obese and 25 normal weight, serving personnel without any other pathological condition were studied. Group I (n=25) consisted of subjects with normal weight and body mass index (BMI <25kg/m(2)), Group II (n=34) of overweight subjects (BMI 25-29.9 kg/m(2)) and Group III (n=17) of obese subjects (BMI >30 kg/m(2)). Echocardiographic indices of systolic and diastolic function were obtained and dysfunction was assumed when at least two values differed by ≥ 2 SD from the normal weight group. RESULT: Ejection fraction, fractional shortening were increased (p<0.05) in Group II and III. Left ventricular dimensions were increased (p< 0.001) but relative wall thickness was unchanged. Systolic dysfunction was not observed in any of the obese patients. The mitral valve pressure half time (p< 0.01), left atrial diameter (p < 0.01) and the deceleration time were increased (p< 0.01) in obese subjects, while other diastolic variables were unchanged. No difference were found between obesity subgroups. Subclinical diastolic dysfunction was more prevalent among obese subjects. BMI correlated significantly with indices of left ventricular systolic and diastolic function. CONCLUSION: Subclinical left ventricular diastolic dysfunction was noted in all grades of obesity which correlates with BMI.

Profile of Culture Positive Enteric Fever from Bangalore.

BACKGROUND: Enteric fever is endemic in India. The aim of this study was to analyse the clinical, laboratory, antibiotic sensitivity profile and response to antibiotics of culture positive enteric fever patients from Bangalore. METHODS: In this retrospective study only culture positive enteric fever patients were taken and their clinical, laboratory, antibiotic sensitivity profile and the clinical response to antibiotics studied. RESULT: Eighty one culture positive enteric fever patients were taken into the study. Presenting symptoms included fever, pain abdomen (18.5%), loose stools (25%), vomiting (33%) and headache (30%). Absolute bradycardia at admission was not found in any of our patients. Normal or low total leucocyte count was seen in 97.5%. Typhoid hepatitis was seen in 8.5%. Salmonella enterica subspecies enterica serovar typhi (S typhi) were isolated in 80% of cases; 83% of all cases showed nalidixic acid resistance. All isolates were sensitive to chloramphenicol and third generation cephalosporins. Ciprofloxacin resistance was found in 19% cases. The time to defervescence in patients treated with ceftriaxone was 4.3 days. There was no statistical difference in time to defervescence in nalidixic acid resistant and sensitive strains. Complications included gastro intestinal bleed and encephalopathy. CONCLUSION: Prevalence of nalidixic acid resistance is high, while clinical resistance to quinolones may be higher than that found in the laboratory which requires detailed study. Chloramphenicol sensitivity has returned and nalidixic acid resistant and sensitive isolates are uniformly sensitive to third generation cephalosporins with no difference in time to defervescence.

Multiple myeloma: an immunoclinical study of disease and response to treatment.

Plasma cytokines and immune markers were assessed during the clinical management of 42 patients with multiple myeloma, MM. Of the patients 22/42 (all with progressive disease) were studied from the time of diagnosis, through various treatment regimes, to remission, progression or death. 5/42 patients had monoclonal gammopathy of undetermined significance (MGUS), 8/42 others had either indolent MM or stable MM, and a further 7/42 with progressive disease were also studied. IL-6, TNF-alpha, IL-1 alpha, IL-1 beta, beta 2 microglobulin (beta 2M), and neopterin were estimated in bloods taken under optimal conditions for cytokine detection. The levels were compared with a panel of samples from healthy volunteers. Both immunoreactive and biologically active plasma IL-6 levels were measured. Pretreatment IL-6 levels (both immunoreactive and biologically active) were found to correlate with severity of disease. In 13/22 patients with progressive disease who had been followed from the time of diagnosis over a 12-month period or until death, pretreatment IL-6 levels were predictive of response to therapy. Elevated plasma levels of TNF-alpha, beta 2M and neopterin were found in patients with progressive multiple myeloma, and this correlated with renal impairment. The analytes measured during the course of chemotherapy did not show correlation with disease progression or response to therapy.

Vincristine and oral etoposide in refractory multiple myeloma.

A total of 15 patients with refractory multiple myeloma (MM; 4 primary unresponsive and 11 relapsed and resistant to re-induction/salvage therapy) received i.v. vincristine on day 1 and oral etoposide daily for 4 days, the treatment being repeated at 3-weekly intervals. The patients were re-assessed after three cycles of chemotherapy, and non-responders received no further therapy. There was no complete or partial response. A minimal response was seen in two patients, and two others showed stable disease. None of the responses was sustained, and all patients eventually had progressive disease. It is concluded that combination chemotherapy with vincristine and oral etoposide given by this schedule is unlikely to be of any value in refractory myeloma.

Myeloma during a decade: clinical experience in a single centre.

One hundred and fifty-six patients with multiple myeloma were treated over a period of 12 years at St. Bartholomew's Hospital. The progress of the disease was affected in 96/156 patients (61%). Response was defined as achieving a plateau of M component. A partial or complete response was seen in 68/120 patients treated conventionally (56.5%), and in 28/36 patients treated with high-dose therapy (77.7%). The median survival of the group as a whole was 20 months, with a 2-year survival of just over 40%. In the 36 patients treated with high-dose therapy, median survival was 6 years, and in a small group who have had maintenance Interferon therapy, the median has not yet been reached. In a univariate analysis, age, intensity of therapy, haemoglobin and creatinine levels were significant, but multivariate analysis showed that only age and intensity of therapy were independent predictors for survival. The outlook for relapsed patients who showed progression of disease remains poor, but palliation was best achieved by steroid and Interferon in combination. Patients who achieve complete responses and are maintained on Interferon appear to be doing better both in terms of freedom from symptoms and in survival, and methods to enable an elderly population to tolerate this form of therapy need to be explored.

Mediastinal large-cell lymphoma with sclerosis (MLCLS).

In a retrospective analysis encompassing a 14 year period (1978-92), 22 patients (age range 19-71, median 30 years) were identified as having mediastinal large-cell lymphoma with sclerosis on the basis of clinical and pathological features. At presentation, 15/22 had 'bulky' disease and 11/22 had evidence of superior vena caval obstruction. Thirteen patients had stage II disease (6,II; 7,IIE), nine presented with stage IV disease. Complete remission (CR) was achieved in only 4/22 patients with the initial adriamycin-containing regimen. 'Good partial remission' (no clinical evidence of disease, minimal abnormalities of uncertain significance on radiological investigation) was achieved in a further seven patients and 'poor partial remission' (a reduction in measurable disease > 50%) in four, giving an overall response rate of 15/22 (68%). One patient died within 48 h of arrival at the hospital; 16 of the 17 remaining patients in whom anything less than CR was achieved subsequently received additional, alternative treatment (one chemotherapy, six mediastinal radiotherapy, nine both treatment modalities) but in only 2/16 did this result in any further degree of response. With a median follow-up of 5 1/2 years, 10/22 patients remain well without progression between 6 months and 14 years (5/6 in whom CR was eventually achieved and 5/11 in whom only partial remission was ever documented). The seven patients in whom the initial treatment demonstrably failed have all died. These results suggest that a proportion of patients with this rare subtype of high-grade B-cell lymphoma may be cured by chemotherapy alone and that the presence of a residual mediastinal mass after treatment does not necessarily imply treatment failure. However, patients in whom the initial chemotherapy fails have a very grave prognosis.

The management of chronic lymphocytic leukemia at a single centre over a 24-year period: prognostic factors for survival.

Over a 24-year period, 137 patients were referred for management of newly diagnosed chronic lymphocytic leukemia. One hundred and nineteen patients have been reviewed in terms of response to therapy and prognostic factors for survival; 18 patients were excluded either because lymph node biopsy was not compatible with the diagnosis of CLL (11 patients), or because the lymphocyte count at presentation was < 5 x 10(9)/l (seven patients). Patients were staged retrospectively according to both the Rai and Binet Classifications. Forty-eight per cent (57/119) were deemed not to be in need of any treatment at presentation, 36 per cent (43/119) have never received any specific therapy. The majority of patients received chlorambucil alone, at a dose of 10 mg daily given for 6 weeks, followed by a 2-week interval, followed by three, 2-week cycles. The overall response rate (complete+partial remission) was 38 per cent. In terms of survival, there was a trend in favour of patients who responded to treatment in comparison with those who did not but this did not reach statistical significance (P = 0.07). Correlations with stage were highly significant, the median survivals for patients with stage A, B and C disease (Binet) were 12.5, 8 and 3.5 years respectively. On univariate analysis, the absolute lymphocyte count at presentation was the most significant prognostic factor for survival, patients presenting with an absolute lymphocyte count above 50 x 10(9)/l having a less favourable prognosis (P = 0.002). However, on multivariate analysis, older age, a low hemoglobin, low platelet count, and the presence of lymphadenopathy and fever at presentation correlated adversely with survival. Overall, 40 patients died as a consequence of CLL or from disease-related causes, 34/40 dying of infection. Twenty-one patients developed second cancers. With a median follow-up of 13 years, these results confirm that the two staging systems can separate patients into prognostic groups, however in practice, there is heterogeneity of outcome within stage. New approaches are urgently needed.

Fludarabine in low-grade lymphoma.

During the last 4 years, 88 patients with low-grade non-Hodgkin's lymphoma have received fludarabine, 25 mg/m2 daily for 5 days, repeated every 3 to 4 weeks. Fifty-one patients received fludarabine at recurrence or when the disease was deemed resistant to conventional treatment, 21 patients received the drug in the context of "minimal residual disease" in the hope of complete remission being achieved with a view to proceeding to myeloablative therapy (cyclophosphamide and total body irradiation) with autologous bone marrow transplantation, and 16 newly diagnosed patients received fludarabine as first-line therapy. Myelosuppression was the predominant toxicity, with 55% and 31% of previously treated and newly diagnosed patents, respectively, becoming neutropenic (neutrophils < or = 1.0 X 10(9)/L). The response rate (complete and partial response) was 44% for both patients with recurrent/resistant disease (20 of 45 evaluable patients) and for those with "minimal residual disease" (nine of 20 evaluable patients). In newly diagnosed patients, the response rate was 69% (11 of 16 patients). Five patients died of infection while neutropenic. These results confirm the activity of fludarabine in low-grade non-Hodgkin's lymphoma. Its precise role remains to be determined.

Recombinant interferon-alpha 2b and high dose methyl prednisolone in relapsed and resistant multiple myeloma.

Twenty-one patients with refractory myeloma (10 primary resistant and 11 relapsed resistant) were treated with a combination of high dose methyl prednisolone and recombinant interferon alpha 2b (IFN-alpha 2b). This treatment included three megaunits/m2 of IFN-alpha 2b three times a week for 12 weeks, plus 5-day pulsed high dose methyl prednisolone every 3 weeks for two courses. A partial response (more than 50 per cent reduction in paraprotein) was observed in six patients; two of these had a greater than 75 per cent reduction in paraprotein, and evaluation of bone marrow showed <5 per cent plasma cells. A minimal response (more than 25 per cent reduction in paraprotein) was seen in four patients, giving an overall objective response rate of 10/21 (48 per cent). Subjective response, in terms of subsidence of pain and improvement of performance status, was seen in all patients who had adequate therapy. The protocol was generally well tolerated with minimal side-effects. There were 4/21 (19 per cent) treatment-related deaths which, though considerable, was anticipated in such a study population. The excellent subjective response seen supplements the objective response observed, and suggests a potential role for the combination of methyl prednisolone and IFN-alpha 2b in refractory myeloma.

Solitary plasmacytoma of bone--a rare disorder with an unusual evolution.

A 40 year old woman presented with a spinal epidural tumour, which on histology was shown to be a plasmacytoma. At that time she had no evidence of multiple myeloma. Ten months later, she developed a second isolated plasmacytoma in the spleen, for which she underwent splenectomy. Two years after her initial presentation she had another recurrence in the liver, followed by a full-blown picture of multiple myeloma. The myeloma was progressive and resistant to all forms of chemotherapy. She finally died of a massive gastrointestinal haemorrhage. The clinical features, natural evolution and management of solitary plasmacytomas are discussed.