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.

Amelioration of experimental diabetic neuropathy and gastropathy in rats following oral administration of plant (Eugenia jambolana, Mucuna pruriens and Tinospora cordifolia) extracts.

Extract of M. charantia (200 mg/kg), E. jambolana (200 mg/kg), M. pruriens (200 mg/kg) and T. cordifolia (400 mg/kg) was administered for 50 days in STZ induced diabetic mice, the plasma glucose concentration was reduced by 24.4, 20.84, 7.45 and 9.07% respectively. Tail flick latency (TFL) and gastric transit percentage were significantly higher in diabetic controls versus normal controls. M. charantia and E. jambolana modified it favorably while M. pruriens and T. cordifolia did not exert any favorable change.

Effect of metronidazole on spermatogenesis and FSH, LH and testosterone levels of pre-pubertal rats.

Metronidazole, a 5-nitroimidazole drug has been reported to decrease testicular weight, testicular and epididymal spermatid counts and causes abnormal sperm morphology with degeneration of seminiferous tubules with 6 weeks treatment of metronidazole (400 mg/kg, day). In contrast to DNA flow cytometry (FCM), the histological and gravimetric parameters do not allow a rapid, sensitive, objective and multiparameteric evaluation of reproductive toxicants on spermatogenesis. Moreover, the exact mechanisms for such an effect are not entirely clear. The present study was therefore undertaken to assess the effects of intraperitoneal (i.p.) administration of metronidazole 400 mg/kg daily for 30 days on testicular germ cell changes assessed by DNA (FCM) and hormone levels of testosterone, FSH and LH in pre-pubertal rats. A significant reduction in the haploid cell population in metronidazole treated groups as compared to saline treated controls was observed. The mean serum FSH, LH and testosterone value were also lowered in treated animals. Thus, the spermatotoxic effects of metronidazole were probably mediated by decrease in the circulating hormones responsible for spermatogenesis.

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.

Association between lower hair zinc levels and neural tube defects.

Though folic acid supplementation has reduced the incidence of Neural Tube Defects (NTD), NTD still constitutes one of the important congenital malformations having wide medical, social and ethical implications. Zinc deficiency has been reported to produce NTD in animals. This study was designed to evaluate zinc status of the newborn babies with NTD and their mothers. Eighty newborn babies with NTD and their mothers served as cases. Eighty apparently normal newborn babies and their mothers served as controls. Serum and scalp hair zinc levels were analyzed by atomic absorption spectrophotometry. The mean (+/- SD) serum and hair levels in normal mothers were 74.1 +/- 4.1 micrograms/dl and 142.3 +/- 8.0 micrograms/g respectively. The mean (+/- SD) serum and hair levels of the mothers who delivered NTD babies were 75.7 +/- 5.6 micrograms/dl and 129.9 +/- 5.3 micrograms/g respectively. The mean (+/- SD) serum and hair levels in normal newborn babies were 77.8 +/- 5.3 micrograms/dl and 188.8 +/- 6.2 micrograms/g respectively. The mean (+/- SD) serum and hair levels in NTD babies were 80.1 +/- 12.9 micrograms/dl and 174.2 +/- 10.7 micrograms/g respectively. The hair zinc levels of the affected babies and their mothers were significantly lower (P < 0.001) than the controls. This study has found association between NTD and decreased hair zinc levels and large population based studies are recommended to confirm the association between zinc and NTD and to investigate whether zinc supplementation would reduce the overall incidence of NTD.

Thalidomide: from teratogen to anti-angiogenic.

Thalidomide, infamous for its teratogenic potential is now emerging as a therapeutic option for many disorders owing to its immunomodulant and anti-angiogenic effect. The demonstration of its ability to inhibit experimental angiogenesis in corneal micro-pocket assay in experimental animals led to the speculation that it might prove to be effective in certain angiogenesis dependent tumors. However, contrary to expectations, it failed to prevent tumor growth in certain animal models. The clinical study evaluating the effects of thalidomide in large number of patients suffering from refractory myeloma have shown encouraging results. Further trials are in progress to evaluate its effects in various other malignancies. In this review, various experimental and clinical studies demonstrating anti-angiogenic and anti-tumor effect of thalidomide are discussed with emphasis on its mechanism of action.

Thalidomide: a re-look.

Thalidomide was synthesized in 1954 in erstwhile West Germany and marketed as a sedative in over 46 countries until the early 1960s. Owing to serious teratogenic effects, the drug was withdrawn from the market in 1961. A chance observation suggested the utility of thalidomide in erythema nodosum leprosum (ENL). After many controlled and uncontrolled trials were published, the World Health Organization recommended its use in ENL. The Food and Drug Administration, USA approved it for use in ENL in July 1998. Only established and well-defined studies conducted to substantiate the efficacy of thalidomide have been included in this review. Thalidomide is considered the drug of choice for the treatment of ENL, but for other conditions, it is recommended only when resistance to the currently available form of therapy is encountered. Once the anti-inflammatory, immuno-modulatory, anti-TNF-alpha and anti-angiogenic properties of thalidomide were discovered, it was also tried in AIDS and related wasting, apthous ulcers, microsporidiosis and Kaposi's sarcoma. Thalidomide has no clinical place as an immunosuppressant in solid organ transplantation. However, it has a therapeutic role in graft-verus-host-disease. Among the dermatological conditions, thalidomide has been found to be effective in systemic lupus erythematosus, discoid lupus erythematosus, actinic prurigo and prurigo nodularis. Used correctly, it is a safe and effective medicine (except for its teratogenic potential and delayed neuropathy) in a variety of disease conditions.

Zinc levels in women and newborns.

Zinc is an important trace element having a definitive role in the metabolism, growth and development and reproduction. During pregnancy the requirements for zinc increase. This study was designed to evaluate the zinc status of normal women, normal pregnant women and their newborn babies. Forty normal adult females, 40 normal pregnant women and their newborn babies were randomly selected and their serum and hair zinc levels were analysed using atomic absorption spectrophotometer. The mean serum and hair zinc levels in normal women were 69.47 +/- 1.4 micrograms/dl and 147.45 +/- 6.12 micrograms/g respectively. The mean serum and hair zinc levels in normal pregnant women were 69.0 +/- 3.22 micrograms/dl and 142.83 +/- 4.39 micrograms/g respectively while the mean serum (cord blood) and hair levels in normal new born babies were 72.77 +/- 5.14 micrograms/dl and 188.36 +/- 4.12 micrograms/g respectively. There was a significant (p < 0.001) decrease in hair zinc levels during pregnancy. There was a significant (p < 0.05) decrease in zinc levels in new born babies when the time interval between the previous delivery and the present delivery was less than 3.4 years. The results of the present study reinforce the need for zinc supplementation during pregnancy especially if the interval between pregnancies is short.

Adverse reactions associated with aminopenicillins in Indian population.

The overall incidence of adverse drug reactions following ampicillin and amoxicillin administration to 439 and 169 indoor patients of All India Institute of Medical Sciences, New Delhi were 19.13% and 15.5% respectively. Ampicillin produced diarrhoea (7.74%), nausea and vomiting (7.74%) anorexia (5.46%) headache (4.10%) and allergic reactions (2.9%). With amoxicillin, anorexia was observed in 4.79%, epigastric distress in 5.9% headache in 6.58%, coating of tongue in 8.98% and dizziness in 1.79% of patients. Intramuscular route of administration of ampicillin produced least ADRs. Females were more susceptible to adverse reactions of ampicillin and males to amoxicillin. Incidence of ADRs by these two aminopenicillins is less than that reported from abroad.

Unwanted effects of ciprofloxacin in Indian population.

The present study was an attempt to evaluate epidemiological profile of adverse reactions of ciprofloxacin and factors influencing them in Indian population. The study was conducted in indoor patients of All-India Institute of Medical Sciences, New Delhi. The patients were in the age group of 21-65 years. Gastrointestinal upsets (nausea, vomiting, abdominal discomfort), headache, dizziness and skin rash were observed. Route of administration influenced the onset of ADRs. Severity of ADRs was proportional to dose. All reactions were reversible and the incidence of ADRs is lower in Indian population as compared to USA(1) but higher than seen in Japanese (2).

Antipyretic activity of diacetyl para-amino phenol.

Diacetyl para-amino phenol (DAPAP) was generated by interaction between aspirin and paracetamol in a mechanical shaker. It revealed antipyretic activity in albino rats. The antipyretic action was found to be having the same onset of action and duration as that of aspirin. This compound lacked ulcerogenic and analgesic activity. DAPAP therefore may have safety as an antipyretic drug in patients with history of peptic ulcer.