Comparative phytochemical analysis and antibacterial efficacy of in vitro and in vivo extracts from East Indian sandalwood tree (Santalum album L.).

UNLABELLED: Sandalwood oil has been found in numerous therapeutic applications in traditional medicines such as Chinese traditional medicine and Ayurveda. However, there are no comparative accounts available in the literature that focused on in vitro and in vivo tree sample-derived extracts. Combined dichloromethane and methanol extracts were obtained from in vitro samples, that is, callus, somatic embryo and seedlings, and in vivo from leaves of non-oil-yielding young and oil-yielding matured trees. Phytochemical evaluation of the extracts reveals that the tree is rich in terpenoids, saponin, phenolics and tannins. The antibacterial properties of the five extracts were compared with sandalwood oil by screening against nine Gram-negative and five Gram-positive bacterial strains by disc diffusion, agar spot and TLC bioautography methods. Minimum inhibitory concentration (MIC) for sandalwood oil was determined to be in the range of 0·078-5 µg ml(-1) for most of the test micro-organisms screened. Bioautography results indicated the presence of potential antimicrobial constituents in somatic embryo extracts and sandalwood oil. Among the extracts screened, the somatic embryo extracts showed the strongest antibacterial activity comparable only with sandalwood oil and matured tree leaves' extract. The findings presented here also suggest that apart from sandalwood oil, other parts of this tree across developmental stages are also enriched with antibacterial principles. SIGNIFICANCE AND IMPACT OF STUDY: This study constitutes the first systematic investigation on phytochemical composition and antimicrobial efficacy of sandalwood tree across in vitro and in vivo developmental stages screened against thirteen bacterial strains by four methods. Using a battery of antimicrobial assay techniques, it is possible to follow the differential bioactive metabolic richness of plant parts, to decipher, for example comparable efficacy of somatic embryo extracts and sandalwood oil.

Multiple cardiac metastases from Ewing's sarcoma.

Ewing's sarcoma commonly arises from bone and sometimes from extraskeletal soft tissues. It commonly metastasizes to the lungs, bone, bone marrow and brain. Cardiac metastasis is extremely uncommon. The present report discusses a case of Ewing's sarcoma metastasizing to the heart at the time of initial presentation.

Variation in routine electrocardiogram use in academic primary care practice.

BACKGROUND: Lack of practical consensus regarding routine electrocardiogram (ECG) ordering in primary care led us to hypothesize that nonclinical variations in ordering would exist among primary care providers. METHODS: We used 2 computerized billing systems to measure ECG ordering at visits to providers in 10 internal medicine group practices affiliated with a large, urban teaching hospital from October 1, 1996, to September 30, 1997. To focus on screening or routine ECGs, patients with known cardiac disease or suggestive symptoms were excluded, as were providers with fewer than 200 annual patient visits. Included were 69 921 patients making 190 238 visits to 125 primary care providers. Adjusted rates of ECG ordering accounted for patient age, sex, and 5 key diagnoses. Logistic regression evaluated additional predictors of ECG ordering. RESULTS: Electrocardiograms were ordered in 4.4% of visits to patients without reported cardiac disease. Among the 10 group practices, ECG ordering varied from 0.5% to 9.6% of visits (adjusted rates, 0.8%-8.6%). Variations between individual providers were even more dramatic: adjusted rates ranged from 0.0% to 24% of visits, with an interquartile range of 1.4% to 4.7% and a coefficient of variation of 88%. Significant predictors of ECG use were older patient age, male sex, and the presence of clinical comorbidities. Additional nonclinical predictors included Medicare as a payment source, older male providers, and providers who billed for ECG interpretation. CONCLUSIONS: Variations in ECG ordering are not explained by patient characteristics. The tremendous nonclinical variations in ECG test ordering suggest a need for greater consensus about use of screening ECGs in primary care.

Rate control and sinus rhythm maintenance in atrial fibrillation: national trends in medication use, 1980-1996.

BACKGROUND: Little is known about national patterns of pharmacological treatment of atrial fibrillation, in particular, use of medications for ventricular rate control and for restoration and maintenance of sinus rhythm. METHODS: We analyzed 1555 visits by patients with atrial fibrillation to randomly selected office-based US physicians included in National Ambulatory Medical Care surveys conducted in 1980, 1981, 1985, and 1989 through 1996. To determine national trends, we evaluated the proportion of atrial fibrillation visits with reported use of rate control medications (digoxin and antiarrhythmics in classes II and IV) and sinus rhythm medications (classes IA, IC, and III). RESULTS: The use of rate control agents decreased from 79% of atrial fibrillation visits in 1980-1981 to 62% in 1994-1996. Declining use was noted for both digoxin (76% in 1980-1981 to 53% in 1994-1996) and beta-blockers (19%-13%). After their introduction, the use of verapamil hydrochloride and diltiazem hydrochloride increased to 15% of atrial fibrillation visits in 1994-1996. Sinus rhythm agent use decreased from 18% of visits in 1980-1981 to 4% in 1992-1993 and then rose to 13% in 1994-1996. The use of class IA agents declined from 18% in 1980-1981 to 3.5% in 1992-1993 and then increased to 8% in 1994-1996. Quinidine remained the most widely used sinus rhythm medication, despite its declining share of this category. Newly available sotalol hydrochloride and amiodarone hydrochloride were used in 3.6% of visits in 1994-1996. CONCLUSIONS: Despite changes in the treatment of atrial fibrillation, digoxin remains the dominant rate control medication. Medications for sinus rhythm maintenance are not widely used. Quinidine use declined prominently in the 1980s, possibly because of concerns about proarrhythmic effects. The use of sinus rhythm agents, however, is now rising.

Antigens specified by the Tla locus are expressed on the surface of murine Langerhans cells.

A monoclonal antibody against the murine thymus leukemia antigen TL, was employed to demonstrate the presence of the antigen on the surface of dendritic cells in murine epidermis of Tla-positive strains, B.10A and A.TH. Immunofluorescence and immunoperoxidase staining of EDTA-separated epidermal sheets demonstrated dendritic cells with a distribution pattern and density comparable to that noted for anti-IAk staining. Tla-negative mouse strains such as A.TL, C3H/HeJ, and C57BL/6 did not show any staining of dendritic epidermal cells. Epidermal cell suspensions similarly contained 2-4% cells with discrete surface staining with anti-TL antibody. Capping was noted in these cells. Once again positive results were noted only in appropriate Tla-positive strains. Control staining was carried out in all cases on frozen sections of thymii from mice. Thymocytes in the cortical zones and some dendritic cells at the corticomedullary junction were stained. TL antigen in mouse appears to be analogous to T-6 antigen previously detected on human Langerhans cells.

Evaluation of recombinant human factor IX: pharmacokinetic studies in the rat and the dog.

The pharmacokinetics of intravenously administered recombinant human factor IX (rhFIX) were studied in Sprague-Dawley rats and Beagle dogs. Rats received rhFIX (50 IU/kg once daily) for 28 days, and the plasma half-life was 5 h. Anti-Human Factor IX serum antibody levels were found in only 1 of 12 rats. The pharmacokinetic profiles of rhFIX or Mononine, a purified human plasma-derived factor IX, after single 100 IU/kg i.v. doses in dogs, were similar. Peak plasma concentrations of rhFIX and Mononine were 4-5 micrograms/ml. The mean plasma half-lives were 13.2 +/- 1.6 h for rhFIX and 13.3 +/- 1.6 h for Mononine. Dogs also received rhFIX (40 IU/kg i.v., daily) for 28 days or Mononine (40 IU/kg i.v. daily) for 14 days. Anti-human Factor IX serum antibody levels were determined for each compound. Pharmacokinetic half-lives decreased in these treated dogs which developed antihuman Factor IX antibodies. The antibody responses in 28 day rhFIX (40 IU/kg) dogs were similar to 14 day Mononine (40 IU/kg) dogs.

Comparative tumorigenicity in newborn mice of chrysene- and 5-alkylchrysene-1,2-diol-3,4-epoxides.

We determined the tumorigenicity in newborn mice of racemic anti-1,2-diol-3,4-epoxides of chrysene, 5-methylchrysene, 5-ethylchrysene and 5-propylchrysene. Among the four diol epoxides, only anti-5-methylchrysene-1,2-diol-3,4-epoxide was highly tumorigenic. It was 15-30 times more potent in induction of pulmonary tumors than the other compounds. The results demonstrate that molecular shape is critical in determining the tumorigenic activity of alkylchrysene diol epoxides. A methyl group in the same bay region as the epoxide ring leads to exceptional activity. This may be a consequence of DNA adduct conformation.

N-ethyl-N-nitrosourea induced brain tumors in rats monitored by nuclear magnetic resonance imaging, plasma proton nuclear magnetic resonance spectroscopy and microscopy.

Characteristic slow growing brain gliomas were induced in rats by a single subcutaneous injection of N-ethyl-N-nitrosourea (ENU) within 24 h of birth. A parallel control group of rats was injected with saline. Seven treated rats developed gliomas within 2 years. Periodic nuclear magnetic resonance imaging (MRI) of the brain in 3-mm slices at 1.5 Tesla and monthly plasma sampling for proton magnetic resonance spectroscopy (MRS) at 360 MHz were started 6 months after the injection of ENU. In the MRS experiments, the Fossel index, average of the line widths of the methylene and methyl peaks at 360 MHz, was determined from half-line widths of methyl and methylene peaks at 0.8 ppm and 1.3 ppm. In five of the ENU injected animals that developed histologically verified brain tumors, these were also observed by MRI without contrast agents. There was no consistent correlation between the imaged tumors and the Fossel index obtained through MRS during the course of the study where repeated observations were performed on individual animals, nor was there any consistent statistical difference in the Fossel index between ENU-treated and control animals. The results of this study demonstrate that slowly developing carcinogen-induced brain tumors in rats can be successfully and reliably monitored noninvasively by MRI but not by MRS of plasma.

Orofacial pain sensitivity in adult rats following neonatal infraorbital nerve transection.

A modification of the formalin test was used to assess orofacial pain sensitivity in adult rats that received infraorbital nerve transection at birth. Normal and neonatally lesioned adult animals received an injection of either 5% formalin or saline vehicle into the whiskerpad and the duration of whiskerpad rubbing was observed for 45 min. Normal rats given formalin exhibited the previously reported biphasic pattern of rubbing. Neonatally lesioned rats given formalin did not exhibit this pattern, and were indistinguishable from either of the saline control groups.

Time course of serotonergic afferent plasticity within rat spinal trigeminal nucleus following infraorbital nerve transection.

High-performance liquid chromatography with electrochemical detection (HPLC-ED) and immunocytochemistry were used to examine the time course of serotonergic afferent plasticity within trigeminal subnucleus interpolaris (SpVi) following infraorbital nerve (ION) transection in adult rats. Biochemical analysis was also performed in trigeminal subnucleus caudalis (SpVc) to examine the possibility of transient lesion-induced changes in this region. No significant changes in serotonin (5-HT) or 5-hydroxyindoleacetic acid (5-HIAA) concentration, or in density of 5-HT-immunoreactive (5-HTIR) axonal varicosities were observed in either subnucleus on the lesioned side, up to 51 days following ION cut. However, at 76-79 days post-lesion, a significant increase in 5-HT concentration was again demonstrated within SpVi.

Effect of trimethoprim-sulphamethoxazole on vibrio clearance in cholera (El Tor): a comparative study.

The efficacy of trimethoprim-sulphamethoxazole (TMP-SMX) has been compared with that of tetracycline and chloramphenicol in 175 bacteriologically confirmed cases of cholera admitted to the Infectious Diseases Hospital Delhi. Vibrio cholerae, biotype El Tor, serotype ogawa, were isolated from all the patients. TMP-SMX showed greater in vitro inhibition and earlier eradication from the intestinal tract and is recommended as a suitable vibriocidal agent against cholera.

Extracerebral hematoma in association with dural substitute.

The authors present a patient who developed an acute hemorrhage around a Silastic dural substitute 13 weeks after excision of a meningioma and implantation of the graft. The relevant literature is reviewed.

De novo saccular aneurysms.

The authors report two patients with aneurysmal subarachnoid hemorrhage in whom carotid arteriography revealed aneurysms that had developed at previously normal locations and from infundibula during the years since initial angiography. Neither of these patients had congenital anomalies of the cerebral circulation and, apart from smoking in excess of 30 cigarettes a day, there were no common clinical features. The role of congenital and environmental factors in the formation of aneurysms and the enlargement of infundibula are reviewed.

Phototoxicity involving the ocular lens: in vivo and in vitro studies.

Our laboratory has demonstrated the cataractogenic potential of UV radiation and several photosensitizing drugs in laboratory animals and in humans. We have utilized lens fluorescence measurements (which we have demonstrated to be a reliable marker for pre-cataractous and early cataractous changes), NMR pulse relaxation techniques, and our recently developed magnetic resonance imaging method to measure lens T2 values in the normal and UV exposed Degus lens (in vivo and in vitro) to detect pre-cataractous changes in the lens. These approaches will permit us to employ two parameters (increased non-tryptophan fluorescence and a decrease in T2 values) to monitor for such changes months before the lens opacities become manifest by conventional slit lamp examinations.

Generation of free radicals during photosensitization of hypocrellin A and their effects on cardiac membranes.

Hypocrellin A (HA), a peryloquinone derivative, has recently been isolated from a fungus Hypocrella bambusae. This lipid soluble pigment, in combination with phototherapy, has been used to treat many skin diseases including the keloids caused by scalding and burns. We have studied the effects of photosensitized HA on biomembranes using pig heart microsomes. Photosensitization of HA was found to peroxidize the membrane lipids in the cardiac microsomes. The photodamage imposed by HA depended not only on the concentration of HA but also on the time of irradiation and pH of the system. Superoxide dismutase (SOD), ascorbic acid, beta-carotene and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) inhibited the lipid peroxidation approximately 50, approximately 50, approximately 30 and approximately 97%, respectively. Spin trapping in combination with EPR spectroscopic techniques was used to identify the reactive free radicals during the photoreaction. Formation of superoxide anion radical, (O2-.), was identified by the SOD-inhibitable DMPO-O2- EPR spectrum. Both SOD and ascorbic acid inhibited the EPR signal intensity in a dose-dependent manner with rate constants of 6.78 x 10(8) M-1 s-1 and 1.82 x 10(4) M-1 s-1, respectively. The lifetime of O2-., under these conditions, was found to be 1.1 s. Photoirradiation of HA yielded a HA free radical with a g = 2.002 which was not suppressed by SOD but in the presence of reductants such as ascorbic acid and catechol the septum was completely suppressed. The increase of the EPR signal intensity and malondialdehyde formation with increasing pH may be due, in part, to the production of predominant *HA- species at high pH which would be more reactive with oxygen to yield O2-.. These results indicate that the lipid peroxidation of the cardiac membranes observed during photooxidation of HA may arise, in part, from the interaction of membrane lipids with reactive species of oxygen and HA free radical produced during the photo-irradiation.

Pleomorphic xanthoastrocytoma. Report of four cases.

Four cases of pleomorphic xanthoastrocytoma (PXA), a low-grade leptomeningeal glioma with a reported favorable prognosis affecting young patients, are reported together with a discussion and review of management and prognosis. A literature review has confirmed a favorable prognosis in at least 50% of patients with this disorder. Seventeen of 35 reported patients are still alive and often seizure-free for a mean period of 7.4 years (range 2 to 18 years) after diagnosis. Five patients have died within 2 years and four between 9 and 25 years after diagnosis of PXA. In some cases in which death followed shortly after diagnosis, there may have been histological confusion between PXA and a malignant glioma with heavily lipidized tumor cells. Nonetheless, transformation of PXA into a malignant astrocytoma or glioblastoma with eventual death may occur many years after initial diagnosis. From the currently reported cases it does not appear possible on clinicopathological grounds to predict which patients will have a favorable prognosis. Optimal management of PXA seems to be primary surgical resection with later surgery for residual or recurrent tumor. The role of radiotherapy in the management of PXA is at this time uncertain.

Toxicological effects of dichlorvos (DDVP) on brain and liver acetylcholinesterase (AChE) activity of Tilapia mossambica, Peters.

Acetylcholinesterase (AChE) activity of T. mossambica in relation to the interacting effects of aging and sub-lethal concentrations of Dichlorvos was studied. The enzyme activity of brain and liver decreased with increasing size (and age) and DDVP-exposed fish showed considerable inhibition of brain and liver AChE. The degree of enzyme inhibition followed a positive correlation with the insecticide concentration and the time of exposure. Brain exhibited a higher degree of enzyme inhibition in all age groups of fish as compared to liver. Small fish were more susceptible to the insecticide with respect to AChE activity. When transferred to clean water most of the exposed fish recovered their AChE activity and the recovery was greater in liver than in brain. Small fish exhibited comparatively a high level of recovery in the AChE activity. The degree of recovery followed an inverse relationship with the time of exposure.

Effect of a mercurial ayurvedic drug (kajyoli) on the ion concentration and respiratory activity in brain, liver and kidney of the albino rat.

The effect of a mercurial ayurvedic drug (kajyoli), on the concentration of Na+, K+ and Ca2+ in rat liver, kidney and brain, and on the respiratory activity of these tissues is reported. The doses used were 20 mg and 40 mg X day-1 X kg-1 body wt. daily for 30 days, the lower level being equivalent to the human dose. A marked dose-dependent decrease in respiratory activity occurred in the three tissues. The only significant changes seen in the ion concentration were a decrease in Na+ at the higher dose level in the kidney and a dose-dependent decrease in Ca2+ in the liver.

Genetic toxicological testing of some dyes by the micronucleus test.

Three widely used dyes, acridine orange, blue VRS and fast green FCF were administered to male mice in order to study the induction of gross chromosomal anomalies using the micronucleus test. All 3 compounds were shown to be clastogenic.

Injuries of hepatic veins and retrohepatic vena cava.

Three cases of hepatic vein and retrohepatic inferior vena caval injuries are reported, and the literature is reviewed. Our experience, coupled with a critical review of the literature reveals that successful vascular isolation of the relatively inaccessible retrohepatic vena cava and/or hepatic veins is the key to optimal surgical management of major injuries to these structures. The various shunt techniques have been outlined with special emphasis made to the midline sternotomy incision as the incision of choice. This incision not only gives optimal exposure to the injured site, but also allows easy atrial-caval cannulation. If cross-clamping of the abdominal aorta is necessary, it can be easily done via a median sternotomy.