Modulation of carcinogenicity in 1,2,3,4-tetrahydro-7,12- dimethylbenz[a]anthracene (THDMBA) by fluorine substitution: crystal structures of the 5- and 6-fluoro regioisomers.

1,2,3,4-Tetrahydro-7,12-dimethylbenz[a]anthracene (THDMBA) is an animal carcinogen which lacks an aromatic bay-region and shows promise as a model to investigate non-classical mechanisms of carcinogenesis. The fluorine-substituted derivatives at positions 5 and 6 on the B-ring exhibit a striking range of oncogenic potential wherein the 6F-THDMBA is twice as potent as the parent carcinogen, but the 5F-THDMBA is virtually inactive. To study structure-reactivity relationships for these fluorine regioisomers, we have determined the three-dimensional structures of the compounds by single-crystal X-ray diffraction. These crystal structures are the first such to be reported for any monofluoro anthracene (or pyrene) derivative. The partially-reduced A-ring exists in both enantiomeric half-chair conformers in the crystalline state, and the compounds have quasi-planar anthracene ring systems which exhibit a right-handed twist in the 'beta'-conformer, with the expected opposite twist in the other. A complete analysis of bond lengths, bond angles and torsion angles is presented. Preliminary electrostatic potentials have been derived from the X-ray data sets, and the results indicate significant differences in potential between 5F- and 6F-THDMBA at positions near the partially reduced bay region. Such results are likely to be of importance in the understanding of metabolic activation to reactive intermediates capable of bonding covalently to DNA.     

Primary hydatid cyst of the breast: A case report

We describe herein the rare case of a hydatid cyst found in the breast of a 26-year-old woman. Clinically, the mass was at first suspected of being a fibroadenoma, but fine needle aspiration cytology (FNAC) yielded clear fluid only. Histopathologic examination of the resected speciman confirmed that it was a hydatid cyst.     

Analysis of clozapine response and polymorphisms of the dopamine D4 receptor gene (DRD4) in schizophrenic patients

We have examined the hypothesis that a variable number of tandem repeats in the third cytoplasmic loop of the dopamine D4 receptor influences clinical response to clozapine using a sample of 189 schizophrenic patients. Alleles of the 48-bp repeat, which range from two to ten copies in the normal human population, were analysed by the polymerase chain reaction using genomic DNA as template. Association between these alleles and response to clozapine was tested using the difference in pre-and post-treatment GAS scores as a measure of response. We found no statistically significant variation between genotypic groups and response by analysis of variance. We conclude that the variation of the number of 48-bp repeats alone does not determine response to clozapine. Larger studies are underway to determine if there is a more subtle relationship with sequence variation within the repeats or at other polymorphic sites within the gene that may provide evidence for a component of clozapine's action being at D4 receptors. © 1995 Wiley-Liss, Inc.     

Is maintenance antiparkinsonian treatment necessary?

The authors designed a three-phase prospective trial in which only those patients who developed an acute, neuroleptic-induced extrapyramidal side effect (EPSE) received benztropine (BZ) at 2 mg i.m. and then 1 mg p.o. b.i.d. for 2 days after their symptoms were rated for severity and type (Preparatory Phase 1). They were then randomly assigned under double-blind conditions to continue BZ or be switched to placebo for 8 days (Experimental Phase 2). Finally in Phase 3 (Followup), all patients continued on placebo in a single-blind design until Day 30. If the patient re-experienced an acute EPSE that was of sufficient severity to require immediate BZ administration, he or she was rated, treated, and then dropped from the study. EPSE scores and dropout rates did not differ in Phase 2 between the placebo- and BZ-treated groups. Implications for the continuation, cessation, or intermittent use of antiparkinsonian (AP) drugs are discussed.     

Anopheles culicifacies: siblings species composition and its relationship to malaria incidence

Entomological and epidemiological surveys in May, August and November 1985 and March 1986 were conducted in villages in Bulandshahr, a western district in Uttar Pradesh and in three eastern districts, Jaunpur, Ballia and Saran. In Bulandshahr, Anopheles culicifacies sibling species A and B were found, with a predominance of species A. Both Plasmodium vivax and P. falciparum were present and the malaria incidence remained high (SPR, 6-50%) indicating an active transmission. In contrast, in three eastern districts predominance of species B with an occasional occurrence of species A was observed. Malaria cases were almost absent in Ballia and Saran and in Jaunpur 10.3% slide positivity rate was observed in May but in later surveys cases were considerably lower (SPR, 0.5-2.9%) indicating the absence of indigenous transmission. In the eastern districts, malaria parasites are regularly brought in from endemic areas by the migrant labor population. Although An. culicifacies s.l. occurs in both the areas, the difference in malaria incidence appears to be due to the difference in the composition of the sibling species which is, the predominant presence of species A in the western district and its absence in eastern districts. This indicates that species A is responsible for active malaria transmission while species B is not.     

Cross leg posterior tibial artery fasciocutaneous island flap for reconstruction of lower leg defects.

We have utilised a posterior tibial artery flap from the opposite healthy limb for reconstruction of defects of middle and lower third of leg in 6 patients. The flap can be based either distally or proximally as the need be. The results have been quite encouraging.     

Study of IgM aggregation in serum of patients with macroglobulinemia.

The effect of solvent conditions on the aggregation of IgM in serum specimens from patients with macroglobulinemia was studied by a turbidimetric procedure. Aggregation of IgM varied considerably among the samples and was affected by a number of experimental parameters. In general, IgM aggregation was more pronounced under acidic conditions and in solvents with low ionic strength. The presence of water-miscible organic solvents also promoted aggregation. Based on these studies, it was concluded that the major force involved in the formation of immunoglobulin aggregates in the serum of patients with macroglobulinemia was electrostatic, rather than hydrophobic, interactions. A number of additives known to prevent protein aggregation were evaluated for their effectiveness in inhibiting IgM aggregation. The only additives that were shown to inhibit or reduce IgM aggregation were charged molecules, such as arginine, sodium chloride, ethylenediamintetraacetic acid and quaternary ammonium beta-cyclodextrin. Some of these charged additives were also effective in dissociating the IgM aggregates once they were formed, even in the presence of detergent.     

Prospective Randomized Comparison of Sodium Tetradecyl Sulfate and Polidocanol as Variceal Sclerosing Agents

A prospective randomized controlled study was designed to evaluate differences in efficacy and complication rate between the two most commonly used sclerosing agents, sodium tetradecyl sulfate (STD) and polidocanol. Of 52 patients with esophageal variceal bleeding, 26 were randomized to receive sclerotherapy with 1.5% STD and 26 to receive 1% polidocanol at weekly intervals. Eradication of varices was achieved in 88% patients each of the STD and polidocanol group. There was no significant difference between patients injected with STD and polidocanol with regard to re-bleeding (27% vs. 15%) and mortality (11.5% in both). The use of STD, in contrast to polidocanol, was associated with a higher incidence of complications in terms of severe retrosternal pain (27% vs. 4%), deep ulceration (53% vs. 23%), dysphagia (88% vs. 46%), and stricture formation (27% vs. 8%). It was concluded that these two agents were similar in efficacy. However, polidocanol was superior due to a lower incidence of complications.     

Domiciliary mechanical ventilation in a patient with severe chronic obstructive lung disease and respiratory failure.

A patient of chronic obstructive pulmonary disease (COPD) with cor-pulmonale and chronic respiratory failure, who was given intermittent positive pressure ventilation at home, is reported. The patient did remarkably well on home mechanical ventilatory support. We believe this to be the first case report of domiciliary mechanical ventilation in a patient of COPD from India.     

A parallel group randomised comparative study of felodipine and nifedipine in hypertension.

We compared the antihypertensive effects and tolerability of a new calcium channel antagonist felodipine with nifedipine in an open randomised parallel group study in 49 patients with moderate hypertension (diastolic blood pressure 105-120 mm Hg). After two weeks run in period felodipine 5 mg and 10 mg once daily was compared with nifedipine 10 mg tid for an active treatment period of 4 weeks. Twenty three patients (mean age 42 +/- 10 years) received felodipine 5 mg once daily for first 2 weeks and 10 mg once daily for subsequent 2 weeks. Twenty six patients (mean age 45 +/- 9 years) received nifedipine 10 mg tid for 4 weeks. The mean reduction in supine diastolic blood pressure in two groups was 17 +/- 6 mm Hg (nifedipine) and 19 +/- 8 mm Hg (felodipine) (p = NS). The goal diastolic blood pressure of less than or equal to 90 mm Hg was achieved in 31 percent (nifedipine group) and 43.5 percent (felodipine group) of patients (p = NS). Side effects were common with both drugs; however, the tolerability was better with felodipine than with nifedipine. In conclusion felodipine was as effective as nifedipine and had the advantage of once a day dosage.