Evidence that banana bunchy top virus has a multiple component genome

Summary A 93 nucleotide sequence was found to be strongly conserved between two ssDNA genomic components of banana bunchy top virus (BBTV). Two outwardly extending degenerate primers were designed from this sequence and used in a polymerase chain reaction (PCR) with DNA extracted from purified BBTV virions. PCR amplified products consisting of at least seven distinct bands all approximately 1 kb and possibly representing full-length BBTV dsDNA were resolved. The PCR amplified products were cloned and the clones screened by restriction enzyme analysis. Four distinct restriction analysis groups were identified. These results confirm that the genome of BBTV contains at least five components and that it belongs to a previously undescribed group of plant viruses which may also contain subterranean clover stunt virus.     

Reducing the dose of depot neuroleptics in stable schizophrenia.

In order to determine the safety of reducing maintenance neuroleptic dose in long-term ambulatory schizophrenia, a step-wise depot reduction study was carried out on patients over a six month period. Doses were reduced by 1/8 of original approximately every two months for a total of three reductions. At the end of dose reduction and at six month follow-up, relapse rate was calculated. Relapse in this study was defined as the clinical decision to either increase neuroleptic dose or to hospitalize. Approximately 50% of the patients relapsed. There was no association with life events as measured by the Paykel scale. Where relapse occurred, it was usually seen subsequent to the second dose reduction. Patients who survived dose reduction had been maintained for a significantly longer period on depot neuroleptics and tended to suffer from a form of schizophrenia which required the co-administration of antidepressants. The findings show that, for a population on long-term depot medication, the risk of symptom exacerbation after gradual step-wise neuroleptic reduction is 50%. The results help to delineate which patients will fall into that 50%.     

Haemodynamic changes and oxygen uptake during crossclamping of the thoracic aorta in dexmedetomidine pretreated dogs

This study was designed to test the hypothesis that the alpha 2 adrenergic agonist, dexmedetomidine (DEX), decreases tissue oxygen demand thereby increasing tolerance to hypoxic insult. In 17 anaesthetized dogs, cardiac output was measured with thermodilution, blood flow through the inferior caval vein was determined using an electromagnetic flowmeter, and oxygen consumption was calculated by the Fick principle. The animals were divided into three groups: control group (n = 5), D3 and D30 groups (n = 6 for each group) treated with two doses of DEX (3 micrograms.kg-1 and 30 micrograms.kg-1, respectively) prior to aortic crossclamping. Upon crossclamping of the thoracic aorta, the cardiac index decreased in all three groups with the largest decrease in the D30 group, and the smallest decrease in the control group. Blood flow through the inferior vena cava decreased in all three groups of animals while blood flow through the superior caval vein increased in the control group, did not change in the D3 group, and decreased in the D30 group. Oxygen saturation in mixed venous blood increased in the control group, did not change in the D3 group and decreased in D30 group. Blood flow and oxygen uptake in the lower part of the body decreased in all groups. Oxygen consumption in the upper part of the body decreased equally in all three groups. Arterial lactate concentrations increased almost two-fold in the control group while it increased by only 30% in animals treated with DEX. A lesser increase in lactate concentrations and oxygen extraction in tissues below aortic crossclamping is consistent with the hypothesis that DEX decreases tissue oxygen requirement which might prove particularly useful in clinical situations where tissue hypoxia is expected.     

Subtype-specific transmission probabilities for human immunodeficiency virus type 1 among injecting drug users in Bangkok, Thailand.

The Bangkok (Thailand) Metropolitan Administration cohort of injecting drug users (IDUs) consisted of 1,209 IDUs initially seronegative for human immunodeficiency virus (HIV) who were followed from 1995 to 1998 at 15 Administration drug treatment clinics. At enrollment and approximately every 4 months thereafter, participants were assessed for HIV seropositivity. As of December 1998, there were 133 HIV type 1 seroconversions and approximately 2,300 person-years of follow-up. Of the 133 observed seroconversions, specimens from 126 persons were available for subtyping (27 subtype B, 99 subtype E). In this analysis, the authors assessed differences in subtype-specific transmission while controlling for important risk factors. The methodology used accounts for left truncation, interval censoring, and competing risks as well as for time-varying covariates such as each IDU's history of reported frequency of injection and of incarceration. Using plausible epidemiologic assumptions and controlling for behavioral risks, the authors found that a significantly higher transmission probability was associated with subtype E compared with subtype B in this population. Since many epidemiologic, virologic, and host factors can influence HIV transmission, it was difficult to conclude whether these differences in transmission probabilities were due to biologic properties associated with subtype.     

Hyperpolarized (3)He MRI of mouse lung.

Hyperpolarized (3)He images of mouse lung are presented. Ventilation images and measurements of (3)He apparent diffusion coefficient (ADC) are reported in healthy mice, and preliminary studies of emphysema and lung cancer in mice are described using these techniques. The design and operation of an electronically controlled small-animal ventilator to deliver the hyperpolarized gas and control animal respiration are described. Images are acquired using an asymmetric gradient echo imaging method to enhance the signal-to-noise ratio of the rapidly diffusing (3)He. In mice with elastase-induced emphysema, the whole-lung average ADC is greater by approximately 25%, a statistically significant difference, compared to healthy animals. By contrast, mice exposed to cigarette smoke for up to 12 months reveal no statistically relevant increases in ADC, although emphysema was not confirmed in these mice. A study of lung cancer (melanoma) in mice is also presented. While tumors are shown to cause substantial ventilation defects in the lung, these defects appear confined to the cancerous regions and do not extend to large-scale regions of the lung distal to the tumors.     

Radiobiologically based assessments of the net costs of fractionated focal radiotherapy

Purpose: To assess the potential changes in the net costs of focal radiotherapy techniques at differing doses per fraction and interfraction intervals.

Methods: Linear quadratic radiobiological modeling is used with appropriate variations in the radiosensitivity and tumor cell proliferation parameters. The notional cost of treatment is calculated from the number of fractions, cost per fraction and the cost of treatment failure, which is itself related to (1-TCP) where TCP is the tumor cure probability. Additional Monte Carlo calculations from ranges of radiobiological parameters have been used to simulate the cost of treatment of tumor populations.

Results: The optimum dose per fraction (and optimum overall cost) for conventional (nonfocal) radiotherapy is generally at low doses of around 2 Gy per fraction. The use of hyperfractionated and accelerated radiotherapy in addition to focal radiotherapy techniques appear to be indicated for more radioresistant tumors and if tumor proliferation is extremely rapid, but the need for treatment acceleration is much reduced where effective focal techniques are used.

Conclusions: Radiobiological and economic modeling can be used to guide clinical choices of dose fractionation techniques providing the key radiobiological parameters are known or if the ranges of likely parameters in a tumor population are known. Focal radiotherapy, by the introduction of changes in the physical dose distribution, produces an upward shift in the optimum dose per fraction and a reduced dependency on overall treatment time.