Efficacy of DSP30-IL2/TPA for detection of cytogenetic abnormalities in chronic lymphocytic leukaemia/small lymphocytic lymphoma.

INTRODUCTION: Chronic lymphocytic leukaemia (CLL) is the most prevalent leukaemia in the Western Hemisphere. Cytogenetic abnormalities in CLL are used for diagnosis, prognosis and treatment. However, detecting these is difficult because mature B cells do not readily divide in culture. Here, we present data on two mitogen cocktails: CpG-oligonucleotide DSP30/Interleukin-2 (IL-2) and DSP30/IL-2 in combination with 12-O-tetradecanoylphorbol-13-acetate (TPA). METHODS: We analysed 165 cases of CLL with FISH and cytogenetics from January 2011 to June 2013. In 2011, three cultures were set-up: unstimulated, DSP30/IL-2-stimulated and TPA-stimulated. In 2012-2013, two cultures were set-up: unstimulated and stimulated with TPA/DSP30/IL-2. RESULTS: In 2011, FISH had a detection rate of 91% and cytogenetics using DSP30/IL2 had a detection rate of 91% (n = 22). In 2012-2013, FISH had a detection rate of 79% and cytogenetics using TPA/DSP30/IL-2 had a detection rate of 98% (n = 40). The percentage of cases with normal FISH but abnormal cytogenetics increased from 9% in 2011 to 21% in 2012-2013. The TPA/DSP30/IL-2 cultures in 2012-2013 detected more novel abnormalities (n = 5) as compared to DSP30/IL-2 alone (n = 3). CONCLUSIONS: TPA/DSP30/IL2 was as good as or better than DSP30/IL2 alone. TPA/DSP30/IL-2 offers a high detection rate for CLL abnormalities with a single stimulated culture and may increase detection of clinically significant abnormalities.

Long term use of thalidomide: safe and effective.

PURPOSE: To assess the efficacy and safety of high dose thalidomide therapy for longer duration of time in relapsed or refractory Multiple Myeloma (MM) patients. MATERIALS AND METHODS: Twelve relapsed/refractory MM patients (7 Males, 5 Females), who received thalidomide for more than 2 years were selected from the Out Patient Department of Institute Rotary Cancer Hospital (IRCH), AIIMS, India. Patients received thalidomide beginning at a dose of 200 mg/day with fortnightly increment to a maximum dose of 800 mg/day. Patients were assessed for response on the basis of M proteins (MP), bone marrow biopsy with touch preparation and skeletal X-rays. RESULTS: Nine patients tolerated a maximum dose of 800 mg/day whereas three patients were given 600 mg/day. All patients showed > or = 25-50% decline in serum /urine M proteins. Complete response/ near complete response was seen in 50%, partial response in 17% and minimal response (SD) in 34% patients. Median duration of thalidomide therapy was 47 months (range 29-60 months). Currently 11 patients are alive. TOXICITY: Varying degree of constipation and sedation were seen universally. One patient had DVT, which responded to anti-coagulant therapy. Other toxic effects included infections, skin reactions. There was no toxic death. CONCLUSION: Long-term use of thalidomide is safe, effective and feasible. We feel that this is one of few reports describing safety and efficacy of long-term thalidomide in relapsed and refractory MM.

Use of simple hematological, biochemical and clinical parameters to monitor response of multiple myeloma patients on high dose thalidomide therapy.

BACKGROUND: Evidence of increased bone marrow vascularity in multiple myeloma (MM) has led to the use of anti-angiogenic drugs especially thalidomide in relapsed or refractory patients. Currently, parameters such as serum/ urine electrophoresis for M (monoclonal) proteins, bone marrow biopsy with touch preparation and b2 microglobulin are routinely used to assess response to therapy. These investigations are expensive, invasive and require high technical setup. AIM: To correlate simple and routine hematological and biochemical parameters with the key marker of disease i.e. M proteins. SETTINGS AND DESIGN: This is an open label, uncontrolled, single-arm study. MATERIALS AND METHODS: Twenty nine refractory or relapsed multiple myeloma patients of both sexes (M=20, F=9) with age ranging between 35-72 years were initiated on 200 mg/day of thalidomide with fortnightly increments of 200 mg to a maximum tolerated dose not exceeding 800 mg/day. All hematological and biochemical parameters were monitored at monthly intervals for one year. STATISTICAL ANALYSIS: Correlation analysis was performed between hemoglobin (Hb), total leukocyte count (TLC), absolute neutrophil count (ANC), platelet count (PC), total proteins (TP), serum albumin and serum globulin on one hand and M protein levels on the other using Pearsons Correlation test by SPSS version 7.5. RESULT: Hb, TLC, ANC, PC and serum albumin levels showed a significant negative correlation with M proteins. A highly significant positive correlation existed between M proteins on one hand and TP and globulin levels on the other. Dryness of skin indicated positive response to therapy. These correlations were found to be significant at the end of one month of therapy in all the above-mentioned parameters except in TLC where it was significant after 2 months of thalidomide therapy. CONCLUSION: Results suggest that sustained efficacy of thalidomide therapy may be amenable to monitoring by these simple, inexpensive and easily available investigations after ascertaining an initial response by M protein and marrow plasmacytosis as these parameters closely follow M protein levels. However more studies are required to further substantiate these findings.

The adverse effects of thalidomide in relapsed and refractory patients of multiple myeloma.

Thalidomide has shown efficacy in relapsed or refractory patients of multiple myeloma (MM). We present the adverse effect profile of thalidomide in 23 relapsed or refractory MM patients treated with this drug over a period of 15 months. Constipation (100% incidence) and sedation (87%) were the most common adverse effects. Neuropathy had low incidence and was late in onset (>12 months). Tolerance developed to sedation, constipation and skin lesions. All the adverse drug reactions were tolerable and did not warrant decrease or termination of therapy, except for peripheral neuropathy. Contrary to Western reports, peripheral neuropathy in Indian patients developed at a cumulative dose of 200 g or more after 10 months or more of therapy. Therapy was discontinued in one patient due to marked elevation of liver enzyme that was later attributed to acute hepatitis C infection. Only one patient dropped out of the trial for unknown reasons. Overall, thalidomide was found to be a relatively safe drug that can be used over a prolonged period of time.

Anthelmintics: a review.

Helminths infect 25% of the world's population. In the last 50 years specific, safe and effective anthelminitic drug therapy for various parasitic infestations have been developed. The population of the developing countries across the globe suffers not only as a direct result of these infections but due also to co-morbidity such as anemia, malnutrition and reduced immunity status. Earlier anthelmintic drugs suffered from serious drawbacks such as hepatotoxicity and required specific preparation of the patient before treatment such as 12-hour fasting and pre-post purging caused considerable inconvenience to the patient. However, successive discoveries were born out of rationale approach that contributed to the effective, more specific and more easily tolerated drugs i.e. benzimidazoles, piperazine derivatives, avermectins, pyrazinoquinoline, etc. The present approach is to identify the causative parasite on the basis of stool examination and as a result of this approach, different drugs are prescribed for different parasitic infections. Examples include thiabendazole for cutaneous larva migrans, mebendazole for ascariasis, trichiuriasis and hookworm, albendazole for inoperable cases of cystic hydatid disease, DEC for Toxocara induced visceral larva migrans and loiasis, ivermectin for onchocerciasis, praziquantel for schistosomiasis and niridazole for Dracunculus medinensis. The cure rates with these drugs is also high e.g. thiabendazole produces a cure-rate of 98% in cutaneous larva migrans while mebendazole gives cure rate of 76-95% in ascariasis, trichiuriasis and hookworm infestations. A cure rate of 96% is produced by praziquantel in schistosomiasis. Most of these drugs have broad-spectrum anthelmentic effect. The present review aims at evaluating the currently available anthelmintics with respect to their efficacy and adverse effects. Steps to prevent impending helminthic drug resistance are also discussed.

Dynamic electromyographic analysis of trunk musculature in professional golfers.

Using dynamic surface electrode electromyography, we evaluated muscle activity in 13 male professional golfers during the golf swing. Surface electrodes were used to record the level of muscle activity in the right abdominal oblique, left abdominal oblique, right gluteus maximus, left gluteus maximus, right erector spinae, left erector spinae, upper rectus abdominis, and lower rectus abdominis muscles during the golfer's swing. These signals were synchronized electronically with photographic images of the various phases of the golf swing; the images were recorded in slow motion through motion picture photography. The golf swing was divided into five phases: take away, forward swing, acceleration, early follow-through, and late follow-through. Despite individual differences among the subjects' swings, we observed reproducible patterns of trunk muscle activity throughout all phases of the golf swing. Our findings demonstrate the importance of the trunk muscles in stabilizing and controlling the loading response for maximal power and accuracy in the golfer's swing. This study provides a basis for developing a rehabilitation program for golfers that stresses strengthening of the trunk muscles and coordination exercises.

Glenoid cysts mimicking cervical radiculopathy.

STUDY DESIGN: Patients are often referred for the evaluation of neck or radiating shoulder or arm pain who are suspected of having a possible cervical spine origin of their symptoms. Careful evaluation may show ganglion cysts of the glenohumeral joint mimicking symptoms of cervical radiculopathy. OBJECTIVES: To present a series of patients in whom cysts originating from the glenohumeral joint caused symptoms mimicking cervical radiculopathy. SUMMARY OF BACKGROUND DATA: Suprascapular nerve entrapment in the suprascapular notch by ganglion cysts from the glenohumeral joint has been described as the source of vague radicular symptoms. This paper presents a series of patients referred to a spine practice for the evaluation of cervical radiculopathy who actually had glenoid cysts mimicking cervical radiculopathy. METHODS: Three hundred forty-two patients were evaluated for cervical radiculopathy; of these, eight had glenoid cysts that were the source of the patients' symptoms. RESULTS: All eight patients had a positive shoulder impingement sign, or, in all, symptoms were temporarily relieved with intra-articular lidocaine injection. Four of the eight patients had abnormal electromyelography and nerve conduction velocity for suprascapular nerve compression. Magnetic resonance imaging of the shoulder was diagnostic in all eight patients. CONCLUSION: Proper evaluation of the shoulder must be done because it may mimic symptoms of cervical radiculopathy.

Reversible urinary retention secondary to excessive morphine delivered by an intrathecal morphine pump.

Reversible complication of intrathecal morphine delivered by an implanted pump is described in one patient. The patient was evaluated initially using a contrast CT of the thoracic spine as well as urodynamics studies. After decreasing the intrathecally administered morphine from 2 mg/24 hr to .5 mg/24 hr, the patient's neurogenic bladder reversed within 4 days. Implanted pumps to deliver intrathecal narcotic medications are being used currently to treat intractable pain. This is a case report of reversible urinary retention secondary to the intrathecal narcotic.

Analysis of medications used in the treatment of cervical disk degeneration.

This review focuses on the scientific design and concepts of drug management of cervical disk disorders. Steroids, nonsteroidal anti-inflammatory medicines, narcotics, antidepressants and muscle relaxants are discussed.

Accurate compartment pressure measurement using the Intervenous Alarm Control (IVAC) Pump. Report of a technique.

This study demonstrates the accuracy of a common, readily available pressure transducer system (IVAC pump) for the measurement of compartment syndromes. An in vitro assay was used to compare the accuracy of the IVAC pump manometer with the Hewlett-Packard monometer (HP78532B) and a miniaturized digital fluid pressure manometer (Stryker). The IVAC pump was accurate within 2.4 mm Hg difference of the HP78532B and Stryker manometers. Twenty-five patients suspected of having compartment syndrome posttibial fracture had compartment pressures measured using the IVAC pump. In all the patients, compartment syndrome was accurately assessed (positive in one case and negative in the remainder). The IVAC pump is readily available in most hospitals. It is easy to use and provides accurate measurements of compartment pressures.

Treatment versus non-treatment of hip dislocations in ambulatory patients with myelomeningocele.

Thirty myelomeningocele patients with untreated hip dislocations who had functional quadriceps and good ambulatory capability were evaluated for hip pain, hip motion and sitting ability: they had no pain, good to excellent hip motion and no difficulty in sitting. Three were wheelchair-bound. Nine had a limb-length inequality requiring a shoe lift. They were compared with a similar series of 11 patients who underwent open reduction of a dislocated hip with a two-year follow-up. Two patients in this group had improved and three had worse sitting balance. Serious perioperative complications occurred in six patients. The authors conclude that surgical reduction of paralytic hip dislocations in ambulatory myelomeningocele patients is costly and offers little obvious benefit.

Accurate prediction of experimental cancer chemosensitivity using the subrenal capsule xenograft assay.

The chemosensitivity of a murine lung carcinoma grown as a xenograft under the kidney capsule of a rat was compared to the chemosensitivity of this tumor grown as a spontaneous metastasis in its syngeneic host. The chemosensitivity of the tumor to intravenously or subcutaneously administered drugs determined in the short-term xenograft assay accurately predicted the chemosensitivity of this tumor when it was growing as a spontaneous micrometastasis in its syngeneic host, indicating that in both situations the pharmacological determinants of tumor response to anticancer drugs were similar. These results suggest that tumors growing as xenografts under the kidney capsule accurately reflect the responsiveness of these tumors to chemotherapy and support further investigation of the xenograft subrenal capsule assay as a model that may be useful in predicting effective chemotherapy for human tumors.

Heroin activity in New York City, 1970-1978.

Heroin activity in New York City is traced from 1970 using a variety of indicators. A steady decline in the number of new "intensive" users (those who required treatment) is noted, beginning around 1970. Various possible explanations of this decline are examined. Reductions in the supply of heroin or in the demand for heroin do not appear to be causes of the decline in new users, as these reductions occurred after the decline in new users had already begun. Demographic changes--the passing of the baby boom cohort through the period of highest risk of beginning heroin use--also does not appear to be a viable explanation, as trends in use of other drugs do not show a decline. Changes in attitudes toward heroin as a specific drug are left as the most plausible explanation of the decline in the number of new intensive heroin users.

Assessing age-of-onset data on substance use among New York State public secondary school students.

This study was designed to assess the quality of age-of-onset data obtained in a state-wide secondary school survey on substance use. A representative sample (8,553), consisting of New York State students in public secondary schools (Grades 7-12) responded to a questionnaire during winter 1974/75. For each of eight substances, a parallel comparison was performed. The ages of onset for students of different current ages (12-17) were compared. All substances except alcohol and tobacco displayed similar patterns of age-of-onset response. The apparent discrepancies for alcohol and tobacco may be due to either a real instability in the age-of-onset pattern or to a recall error. The results of the study suggest that retrospective questions may provide useful information, particularly when they relate to memorable events.