Trails: an alternative to the field demonstration?

For many students, the traditional field demonstration has several disadvantages. The trail is suggested as an alternative technique, which may be appropriate for students who are not biology specialists, and for senior pupils. The advantages of this method include simpler presentation of information and questions, freedom for the tutor to assist weaker or more questioning students, flexibility in the timing of the exercise, and the need for careful preparation. The use of trails in assessment is suggested. Examples from trails used with Landscape Architecture students are given.     

Unemployment rates: an alternative to the Jarman index?

OBJECTIVE--To compare the Jarman index with alternative deprivation measures with regard to its usefulness to district health authorities as an indicator of need at small area level. DESIGN--The Jarman index (UPA (8)), Townsend''s index of material deprivation, the Scottish Development Department''s index, the Department of the Environment''s basic index, and unemployment rates were compared in respect of their correlation with measures of morbidity by electoral ward in a typical English district health authority. Measures of morbidity comprised standardised mortality ratios, admission rates (standardised and non-standardised), and permanent sickness rates. Spearman rank correlation coefficients were calculated for each combination of measures and were then ranked for each of the deprivation indices. SETTING--The 59 electoral wards of the Central Nottinghamshire Health Authority. RESULTS--The Jarman index consistently ranked lower in respect of its correlation with measures of morbidity than did the other deprivation measures. Current unemployment rates correlated well with morbidity measures, in particular with hospital admission rates, with correlations ranging from 0.669 to 0.830 for average and standardised all age admission rates. CONCLUSIONS--The Jarman index seems to be the least appropriate of these indices for health authority use. Unemployment rate merits further consideration as a simple, up to date marker for deprivation and consequent need for health service provision.     

How to evaluate the risk-benefit ratio of the low-dose hormone replacement therapy?

Since the results of the women health initiative study showing an overall negative risk-benefit ratio with 0.625 mg of conjugated estrogens plus 2.5 mg of medroxyprogesterone acetate, the use of the lowest effective dose of steroids in hormone replacement therapy (HRT) is recommended.

A low-dose regimen appears to induce less side effects such as breast tenderness or leg pain than do higher dose preparations.

The decrease in hot flashes with low-dose estrogens, range 60–70%, is less than the 80–90% reduction with standard dosing. But this mean that 60–70% of menopausal women do not need higher doses.

The same applies to bone preservation which is dose dependent: the number of non-respondant women will be higher than with standard doses. However, randomized double-blind, placebo controls trials have defined positive effects on bone of low doses of HRT with adequate calcium and Vitamin D in elderly women. The use of bone densitometry and of biochemical markers of bone turnover is mandatory in women using low or ultra-low-dose preparations.

In spite of the lack of trials conducted with low-dose HRT, this treatment seems to be safer:

• the plasma levels of estradiol are lower; as far as breast cancer risk is concerned, the decrease of this subrogate marker is considered as favourable;

• the increase in breast density is less pronounced;

• the nurses's health study found a dose relationship for stroke, with no increase in risk with low-dose of estrogens;

• the effects on subrogate markers of cardiovascular risk seem to be more favourable.

Beside the low-dose HRT, one must consider some other facts:

• the “critical window” theory: it is biologically plausible that HRT, if started early after the menopause can slow the progression of coronary atherosclerosis;

• the way of administration of HRT: some observational studies have shown no increase in the risk of venous thromboembolism risk among women treated with transdermal estrogens;

• the progestogen used: a French cohort study recently performed found no increase in breast cancer risk with the use of micronized progesterone meanwhile the increase in risk observed with other progestogens was similar to the findings of the WHI study.

In the future, it is conceivable that more comprehensive pharmacogenomic studies will lead to effective algorithms for individualizing the right dose of steroids to be used in HRT.     

Antifungal lock therapy: an eternal promise or an effective alternative therapeutic approach?

Each year, millions of central venous catheter insertions are performed in intensive care units worldwide. The usage of these indwelling devices is associated with a high risk of bacterial and fungal colonization, leading to the development of microbial consortia, namely biofilms. These sessile structures provide fungal cells with resistance to the majority of antifungals, environmental stress and host immune responses. Based on different guidelines, colonized/infected catheters should be removed and changed immediately in the case of Candida-related central line infections. However, catheter replacement is not feasible for all patient populations. An alternative therapeutic approach may be antifungal lock therapy, which has received high interest, especially in the last decade. This review summarizes the published Candida-related in vitro, in vivo data and case studies in terms of antifungal lock therapy. The number of clinical studies remains limited and further studies are needed for safe implementation of the antifungal lock therapy into clinical practice.     

High-frequency oscillations via the pleural surface: an alternative mode of ventilation?

We applied high-frequency oscillatory ventilation (HFOV) of low amplitude to the pleural surface of the isolated rat lung (IPL) perfused at 10 ml X min-1 with Krebs bicarbonate containing 4.5% albumin (hematocrit 34%). Lung volume was held constant by a continuous positive airways pressure (CPAP) of 5 cmH2O. Varying CPAP from 2 to 15 cmH2O did not affect O2 uptake. Tidal volume (VT) was estimated with an impedance pneumograph, and it bore a direct linear relationship to the amplitude of both the loudspeaker input signal and the pressure change in the chamber up to 30 Hz; VT was inversely proportional to the frequency (f). However, at a constant loudspeaker input of 10 V, minute expired ventilation (VE) remained constant (mean 104 ml X min-1) as f increased from 5 to 30 Hz. Hemoglobin saturation increased by more than 80% during HFOV of 5-40 Hz and amplitude of 10 V, the maximum O2 uptake being 14.6 ml O2 per 100 ml perfusate. Whereas dead space was approximately 335 microliters, a VT of less than 40 microliters could effect normal O2 uptake, suggesting that bulk flow is playing only a minor role in gas exchange. HFOV for 60 min (CPAP 5 cmH2O) did not affect the amount of alveolar surfactant compared with conventional ventilation at the same mean airway pressure. We conclude that normal O2 uptake can be maintained by applying HFOV to the pleural surface of the IPL held at constant volume.     

Cyclopentane-nucleobase coupling in the synthesis of carbocyclic L-nucleosides: is a SN2-reaction an alternative to the Mitsunobu-reaction?

Several carbocyclic L-nucleosides have been synthesized by coupling a cyclopentane-system with heterocycles according to a modified Mitsunobu-protocol. This reaction gave two regioisomers, the N1-alkylated product and an unwanted O(2)-product. A simple S(N)2-reaction has been investigated as an alternative for such couplings.     

Is there an alternative to increasing the sample size in microarray studies?

Our answer to the question posed in the title is negative. This intentionally provocative note discusses the issue of sample size in microarray studies from several angles. We suggest that the current view of microarrays as no more than a screening tool be changed and small sample studies no longer be considered appropriate.     

Genomic rearrangements in trypanosomatids: an alternative to the "one gene" evolutionary hypotheses?

Most molecular trees of trypanosomatids are based on point mutations within DNA sequences. In contrast, there are very few evolutionary studies considering DNA (re) arrangement as genetic characters. Waiting for the completion of the various parasite genome projects, first information may already be obtained from chromosome size-polymorphism, using the appropriate algorithms for data processing. Three illustrative models are presented here. First, the case of Leishmania (Viannia) braziliensis/L. (V.) peruviana is described. Thanks to a fast evolution rate (due essentially to amplification/deletion of tandemly repeated genes), molecular karyotyping seems particularly appropriate for studying recent evolutionary divergence, including eco-geographical diversification. Secondly, karyotype evolution is considered at the level of whole genus Leishmania. Despite the fast chromosome evolution rate, there is qualitative congruence with MLEE- and RAPD-based evolutionary hypotheses. Significant differences may be observed between major lineages, likely corresponding to major and less frequent rearrangements (fusion/fission, translocation). Thirdly, comparison is made with Trypanosoma cruzi. Again congruence is observed with other hypotheses and major lineages are delineated by significant chromosome rearrangements. The level of karyotype polymorphism within that "species" is similar to the one observed in "genus" Leishmania. The relativity of the species concept among these two groups of parasites is discussed.     

Do regulatory antibodies offer an alternative mechanism to explain the hygiene hypothesis?

The 'hygiene hypothesis', or lack of microbial and parasite exposure during early life, is postulated as an explanation for the recent increase in autoimmune and allergic diseases in developed countries. The favored mechanism is that microbial and parasite-derived products interact directly with pathogen recognition receptors to subvert proinflammatory signaling via T regulatory cells, thereby inducing anti-inflammatory effects and control of autoimmune disease. Parasites, such as helminths, are considered to have a major role in the induction of immune regulatory mechanisms among children living in developing countries. Invoking Occam's razor, we believe we can select an alternative mechanism to explain the hygiene hypothesis, based on antibody-mediated inhibition of immune responses that may more simply explain the available evidence.     

Lepidopteran cells,an alternative for the production of recombinant antibodies?

Monoclonal antibodies are used with great success in many different therapeutic domains. In order to satisfy the growing demand and to lower the production cost of these molecules, many alternative systems have been explored. Among them, the baculovirus/insect cells system is a good candidate. This system is very safe, given that the baculoviruses have a highly restricted host range and they are not pathogenic to vertebrates or plants. But the major asset is the speed with which it is possible to obtain very stable recombinant viruses capable of producing fully active proteins whose glycosylation pattern can be modulated to make it similar to the human one. These features could ultimately make the difference by enabling the production of antibodies with very low costs. However, efforts are still needed, in particular to increase production rates and thus make this system commercially viable for the production of these therapeutic agents.     

Manipulation of callus after linear distraction: a "lifeboat" or an alternative to multivectorial distraction osteogenesis of the mandible?

Despite impressive results, distraction osteogenesis of the mandible is still compromised by difficulties with vector control. Because of the action of the masticatory muscles, the gonion angle has the tendency to open, resulting in an open bite. We report two patients, aged 10 and 12 years, who developed a severe open bite during mandibular distraction. As a salvage procedure, manual shaping of the soft regenerate was done immediately after distraction. Uneventful bony consolidation was observed, which resulted in anatomically shaped gonion angles. The fact that a regenerate created by distraction osteogenesis can be molded to virtually any shape offers interesting perspectives for the correction of complex mandibular deformities.     

Probiotics and pharmabiotics: alternative medicine or an evidence-based alternative?

That commensal bacteria play an important role in human health is beyond doubt, and it is now widely accepted that humans function as super organisms, whose collective metabolic potential exceeds the sum of our individual eukaryotic and prokaryotic components. However, while it is has been established that the prokaryotic component of the human superorganism is amenable to manipulation by chemotherapeutic, dietary or microbial interventions, the significance of such alterations in terms of human health or well being is less well established. Prebiotics (non- digestible food ingredients that stimulate the growth and/or activity of bacteria in the digestive system) and probiotics (live microorganisms that when administered in adequate amounts, confer a health benefit on the host) are often bracketed among 'alternative' approaches to influencing human health, such as homeopathy, naturopathy, acupuncture and hypnotherapy. Others believe that prebiotics and probiotics have proven their effectiveness in properly conducted, clinically controlled human trials and therefore can be considered as evidence-based alternatives or adjuncts to conventional medicines. My journey from a position of total skepticism to 'reluctant convert' is the basis of this article, which should not be considered in any sense as a review of the literature but simply a personal account of this transition. While I am not bent on converting other doubters, I will recount some of the thought processes and evidence that has helped to form my current opinion.