Can the use of physical modalities for pain control be rationalized by the research evidence?

Physical modalities, including cold and heat, are widely used in the conservative management of pain associated with musculoskeletal disorders. This review has critically appraised the literature supporting the use of these modalities in the treatment of musculoskeletal pain. It was concluded that, apart from a few exceptions and in a few types of disorders, existing evidence does not support the use of these modalities in long-term pain control. There was, however, evidence that several modalities, specifically cold and a form of deep heat (shortwave diathermy), do have short-lived analgesic effects and so may contribute to more painfree function in the short term. Further research is clearly warranted to define the short- and long-term therapeutic efficacy of physical modalities in the treatment of musculoskeletal pain to justify their continued use in clinical practice.     

Does the brain use sliding variables for the control of movements?

Delays in the transmission of sensory and motor information prevent errors from being instantaneously available to the central nervous system (CNS) and can reduce the stability of a closed-loop control strategy. On the other hand, the use of a pure feedforward control (inverse dynamics) requires a perfect knowledge of the dynamic behavior of the body and of manipulated objects. Sensory feedback is essential both to accommodate unexpected errors and events and to compensate for uncertainties about the dynamics of the body. Experimental observations concerning the control of posture, gaze and limbs have shown that the CNS certainly uses a combination of closed-loop and open-loop control. Feedforward components of movement, such as eye saccades, occur intermittently and present a stereotyped kinematic profile. In visuo-manual tracking tasks, hand movements exhibit velocity peaks that occur intermittently. When a delay or a slow dynamics are inserted in the visuo-manual control loop, intermittent step-and-hold movements appear clearly in the hand trajectory. In this study, we investigated strategies used by human subjects involved in the control of a particular dynamic system. We found strong evidence for substantial nonlinearities in the commands produced. The presence of step-and-hold movements seemed to be the major source of nonlinearities in the control loop. Furthermore, the stereotyped ballistic-like kinematics of these rapid and corrective movements suggests that they were produced in an open-loop way by the CNS. We analyzed the generation of ballistic movements in the light of sliding control theory assuming that they occurred when a sliding variable exceeded a constant threshold. In this framework, a sliding variable is defined as a composite variable (a combination of the instantaneous tracking error and its temporal derivatives) that fulfills a specific stability criterion. Based on this hypothesis and on the assumption of a constant reaction time, the tracking error and its derivatives should be correlated at a particular time lag before movement onset. A peak of correlation was found for a physiologically plausible reaction time, corresponding to a stable composite variable. The direction and amplitude of the ongoing stereotyped movements seemed also be adjusted in order to minimize this variable. These findings suggest that, during visually guided movements, human subjects attempt to minimize such a composite variable and not the instantaneous error. This minimization seems to be obtained by the execution of stereotyped corrective movements. Received: 18 February 1997 / Accepted in revised form: 29 July 1997     

Can Wolbachia be used to control malaria?

Malaria is a mosquito-borne infectious disease caused by Plasmodium parasites transmitted by the infectious bite of Anopheles mosquitoes. Vector control of malaria has predominantly focused on targeting the adult mosquito through insecticides and bed nets. However, current vector control methods are often not sustainable for long periods so alternative methods are needed. A novel biocontrol approach for mosquito-borne diseases has recently been proposed, it uses maternally inherited endosymbiotic Wolbachia bacteria transinfected into mosquitoes in order to interfere with pathogen transmission. Transinfected Wolbachia strains in Aedes aegypti mosquitoes, the primary vector of dengue fever, directly inhibit pathogen replication, including Plasmodium gallinaceum, and also affect mosquito reproduction to allow Wolbachia to spread through mosquito populations. In addition, transient Wolbachia infections in Anopheles gambiae significantly reduce Plasmodium levels. Here we review the prospects of using a Wolbachia-based approach to reduce human malaria transmission through transinfection of Anopheles mosquitoes.     

Should DDT be banned by international treaty?

The insecticide DDT has been an effective and affordable means of malaria control in many countries, but pressure for its use to be banned is mounting. Here, Chris Curtis and Jo Lines take a critical look at evidence that links house spraying by DDT with harm to the environment and human health, and stress the need for resources for alternatives to DDT to be made available to countries that would be affected by a DDT ban.     

Should there be a separate code of nomenclature for the protists?

The present Botanical and Zoological Codes of Nomenclature are often inadequate for resolution of all the peculiar problems caused by the very nature of the numerous and diverse groups of the so-called 'lower' eukaryotic organisms known as protists. Whether or not a separate code should therefore be created for these species--many but not all of which are unicellular in structure and microscopic in size--is complicated by several factors. The principal one is related to the wide dispersal of protists throughout many taxonomic classes and phyla/divisions; sometimes even multiple kingdoms are involved. If recognition of a single kingdom Protista is no longer tenable, then even the concept of one code per kingdom is not applicable. Other difficulties arise primarily from long-standing differences in major provisions of present Botanical and Zoological Codes. Numerous 'ambiregnal' forms exist, species currently under dual code jurisdiction. The matter of names for suprafamilial taxa of protists, irrespective of their ultimate kingdom assignment, poses another set of concerns not yet resolved. A plea is made to recognize the legitimacy of having distinct high-level ranks for protist species that seem to be widely separated phylogenetically from fellow protists or from other eukaryotic assemblages.     

Should colonoscopy be the first investigation for colonic disease?

Many patients with suspected colonic disease undergo rigid sigmoidoscopy, barium enema examination, and ultimately total colonoscopy, but the need for preliminary radiology has not been formally assessed. A total of 168 patients requiring large bowel investigation were therefore randomised to undergo either rigid sigmoidoscopy plus double contrast barium enema examination or total colonoscopy. Disease was found in 56 patients, including 14 with a carcinoma, 11 with polyps, and 16 with inflammatory bowel disease, the remainder having diverticular disease alone. Of the 89 patients allocated to double contrast barium enema examination, nine required a subsequent colonoscopy for suspected tumour or polyps, three because of incomplete radiological examination, and 12 for rectal bleeding for which no cause was found at the radiological examination. In 16 patients this yielded further information or altered treatment. Of the 79 patients undergoing total colonoscopy, only six required subsequent radiology.As both procedures were well tolerated with no major complications total colonoscopy may be the preferred initial investigation where facilities allow.     

Should the indications for prenatal chromosome analysis be changed?

Amniocentesis for chromosome analysis was performed in 1086 pergnant women, 739 of whom had an increased risk of giving birth to a child with chromosome abnormalities. Such abnormalities were found in almost identical proportions among the fetuses with an increased risk (1.2%) and among those with no increased risk (1.4%). Findings in several other studies seem to confirm that there is no significant difference between the risk groups in the proportion of abnormalities found. This suggests that our current risk groups may not be the right ones, but a much larger study is needed to confirm this.     

Roll Back Malaria? The scarcity of international aid for malaria control

Background

Intraerythrocytic malaria parasites actively import obligate nutrients from serum and export proteins and lipids to erythrocyte cytoplasm and membrane. The import of macromolecules in the malaria parasite has been the subject of many debates. To understand the import of macromolecules by the parasite, we studied the uptake of proteins by Plasmodium falciparum infected human erythrocyte.

Methods

Proteins were biotin labelled individually, purified on a gel filtration column and added to uninfected and infected asynchronized culture. The uptake of these proteins by malaria parasites was determined by western blot analysis of parasite pellet and their different fractions using streptavidin-horseradish conjugate. To further confirm this import, we studied the uptake of¹²⁵I-labelled proteins by western blot analysis as well as used direct immunofluorescence method.

Results

Here we show that biotin labelled and radio-iodinated polypeptides of molecular sizes in the range of 45 to 206 kDa, when added in the culture medium, get direct access to the parasite membrane through a membrane network by by-passing the erythrocyte cytosol. The import of these polypeptides is ATP-dependent as sodium azide treatment blocks this uptake. We also show that malaria parasites have the ability to take up and degrade biotin labelled human serum albumin, which has been shown to be essential for the parasite growth.

Conclusions

These results can be used, as a basis to explore the role of human serum albumin in the intraerythrocytic development of parasites, and this in turn can be an important adjunct to the development of novel antimalarial drugs.     

Can primaquine therapy for vivax malaria be improved?

The incidence and range of endemic malaria caused by Plasmodium vivax has expanded during the past 30 years. This parasite forms hypnozoites in the liver, creating a persistent reservoir of infection. Primaquine (PQ), introduced 50 years ago, is the only drug available to eliminate hypnozoites. However, lengthy treatment courses and follow-up periods are not conducive to assessing the effectiveness of this drug in preventing relapses. Resistance to standard therapy could be widespread. Studies are urgently needed to gauge this problem and to determine the safety, tolerability and efficacy of shorter courses and higher doses of PQ.     

Should Deceased Donors be Tested for vCJD?

The 1997 Bovine Spongiform Encephalopathy enquiry and the 2001 Hepatitis C litigation judgement set the UK scene for evoking the precautionary principle and the legal precedent that liability for defective transfusion products should not be dependent on medical negligence, but on the mere fact of defectiveness. Animal models indicate that vCJD in humans, with infection via the oral route, is likely to be associated with infectivity within the lymphoreticular system (LRS). This is likely to appear prior to the involvement of the central nervous system and thus infectivity is likely to be present in the LRS before the onset of clinical disease. A number of relevant epidemiological studies using LRS tissue have shown a low, but measurable, existence of the carrier state in vCJD. Two possible cases of transmission of the abnormal prion of vCJD by blood transfusion suggested that tissues might also transmit and that testing of LRS tissue from deceased potential tissue donors should be considered as a first measure towards the prevention of vCJD transmission by tissues designated for use in transplantation. A variety of different tissues could be used as representative of the LRS, but each is associated with problems of feasibility and practicality. Assays for vCJD have not been validated in the context of donor screening rather than epidemiological studies nor on deceased donors. However, given the number of vCJD cases in the UK, significant attention should be paid to the logistical, ethical, social and other issues associated with undertaking vCJD testing of tissue donors, with a view to introducing testing of deceased tissue donors for vCJD disease or latency.