Interactive effects of pre-industrial, current and future [CO2] and temperature on an insect herbivore of Eucalyptus.

Both atmospheric [CO2] and average surface temperatures are predicted to increase with potentially different, additive or opposing, effects on leaf quality and insect herbivore activity. Few studies have directly measured the interactive effects of concurrent changes in [CO2] and temperature on insect herbivores. None have done so over the entire developmental period of a tree-feeding insect, and none have compared responses to low pre-industrial [CO2] and present day [CO2] to estimate responses to future increases. Eucalypt herbivores may be particularly sensitive to climate-driven shifts in plant chemistry, as eucalypt foliage is naturally low in [N]. In this study, we assessed the development of the eucalypt herbivore Doratifera quadriguttata exposed concurrently to variable [CO2] (290, 400, 650 µmol mol(-1)) and temperature (ambient, ambient +4 °C) on glasshouse-grown Eucalyptus tereticornis. Overall, insects performed best on foliage grown at pre-industrial [CO2], indicating that modern insect herbivores have already experienced nutritional shifts since industrialisation. Rising [CO2] increased specific leaf mass and leaf carbohydrate concentration, subsequently reducing leaf [N]. Lower leaf [N] induced compensatory feeding and impeded insect performance, particularly by prolonging larval development. Importantly, elevated temperature dampened the negative effects of rising [CO2] on larval performance. Therefore, rising [CO2] over the past 200 years may have reduced forage quality for eucalypt insects, but concurrent temperature increases may have partially compensated for this, and may continue to do so in the future. These results highlight the importance of assessing plant-insect interactions within the context of multiple climate-change factors because of the interactive and potentially opposing effects of different factors within and between trophic levels.

A full genome search in multiple sclerosis.

The aetiology of multiple sclerosis (MS) is uncertain. There is strong circumstantial evidence to indicate it is an autoimmune complex trait. Risks for first degree relatives are increased some 20 fold over the general population. Twin studies have shown monozygotic concordance rates of 25-30% compared to 4% for dizygotic twins and siblings. Studies of adoptees and half sibs show that familial risk is determined by genes, but environmental factors strongly influence observed geographic differences. Studies of candidate genes have been largely unrewarding. We report a genome search using 257 microsatellite markers with average spacing of 15.2 cM in 100 sibling pairs (Table 1, data set 1 - DS1). A locus of lambda>3 was excluded from 88% of the genome. Five loci with maximum lod scores (MLS) of >1 were identified on chromosomes 2, 3, 5, 11 and X. Two additional data sets containing 44 (Table 1, DS2) and 78 sib pairs (Table 1, DS3) respectively, were used to further evaluate the HLA region on 6p21 and a locus on chromosome 5 with an MLS of 4.24. Markers within 6p21 gave MLS of 0.65 (non-significant, NS). However, D6S461, just outside the HLA region, showed significant evidence for linkage disequilibrium by the transmission disequilibrium test (TDT), in all three data sets (for DS1 chi2 = 10.8, adjusted P < 0.01)(DS2 and DS3 chi2 = 10.9, P < 0.0005), suggesting a modest susceptibility locus in this region. On chromosome 5p results from all three data sets (222 sib pairs) yielded a multipoint MLS of 1.6. The results support genetic epidemiological evidence that several genes interact epistatically to determine heritable susceptibility.

Disease progression among multiple sclerosis patients before and during a disease-modifying drug program: a longitudinal population-based evaluation.

Randomized controlled trials have demonstrated the efficacy of disease-modifying drugs (DMDs) in persons with relapsing-remitting multiple sclerosis (MS) and secondary progressive MS with superimposed relapses. However, these brief studies of selected patients have focused mainly on reducing attacks and must be complemented by evaluations in 'realworld' clinical settings to establish the effectiveness of DMD programs in slowing disease progression and to inform health policy and program decision-making. We assessed the effectiveness of DMDs as administered in a comprehensive publicly funded drug insurance program that provides DMDs to a geographically defined population of MS patients who meet specific eligibility criteria. Data from 1752 MS patients (10,312 assessments) seen between 1980 and 2004 at a regional MS Clinic serving the entire population of Nova Scotia, Canada were analysed. Using survival methods we observed a statistically significant reduction in disease progression to specific Expanded Disability Status Scale endpoints following the introduction of this program. Subgroup analyses of patients eligible for treatment using hierarchical linear regression methods also suggested that disease progression was slowed in patients treated with the first DMD prescribed. These findings provide evidence supporting DMD program effectiveness that can be used to inform the broader implementation of such programs.

ALS incidence in Nova Scotia over a 20-year-period: a prospective study.

OBJECTIVE: Previous studies have suggested that the incidence of amyotrophic lateral sclerosis (ALS) in Nova Scotia is relatively high and increasing over time. This study was performed to determine the current incidence of ALS in Nova Scotia and to compare this to data collected in 1984 and 1995. METHODS: All physiatrists and neurologists were surveyed on a monthly basis over one year to record all new cases of ALS diagnosed in Nova Scotia. Data was compared to that collected using similar methods in 1984 and 1995. To validate our methods, we also performed a retrospective study using a provincial health care database. RESULTS: There were 21 new ALS cases in Nova Scotia during the 2003 study period, yielding a crude incidence of 2.24/100,000. The age-adjusted incident rate for 2003 was 2.13 (95% CI = 0.11-4.15). The age-adjusted rate for 1995 was 2.3 (95% CI = 0.08-4.53) while the age-adjusted rate for 1984 was 2.22 (95% CI = 0.13-4.32). Analysis of provincial health records identified 24 cases of ALS and an age-adjusted incidence of 2.44/100,000. CONCLUSIONS: The age-adjusted incidence of ALS in Nova Scotia has remained stable over the period 1984-2003. The incidence is similar to that reported in several other parts of the world.

Human fetal testis: second trimester proliferative and steroidogenic capacities.

The period of Leydig cell hyperplasia (14-18 weeks gestation) in human fetal testis is crucial for normal gonad development. We have studied the spatio-temporal distribution of key developmental and functional markers in human fetal testis between 13-19 weeks gestation. Proliferating cell nuclear antigen-positive cells were immunolocalized to both interstitium and tubules. Image analysis confirmed an increase in positive interstitial cells during Leydig cell hyperplasia (P: < 0.05). c-Myc was localized to the interstitium with no gestational changes. The steroidogenic enzymes 3beta-hydroxysteroid dehydrogenase (protein) and cytochrome P450 17alpha-hydroxylase/C(17-20)-lyase (P450c17; messenger ribonucleic acid and protein) were confined to the Leydig cells. The number of immunopositive cells increased between 13 and 19 weeks (P: < 0.001). P450c17 mRNA (in situ hybridization) and protein were localized to the same population of interstitial Leydig cells. Androgen receptor and Bcl-2 protein (anti-apoptotic) were gradually restricted to the peritubular myoid cells as gestation progressed. Conversely, Bax protein (pro-apoptotic) was predominantly localized to the tubule Sertoli cells, whereas the germ cells were Bax immunonegative. In conclusion, human fetal Leydig cell hyperplasia is characterized by increasing numbers of proliferating cells and increased expression of steroidogenic enzymes. The Bcl-2-positive, Bax-negative status of the peritubular myoid cells may be a strategy for cell survival.

Patients with multiple sclerosis experience hearing loss specifically for shifts of tone frequency.

After exposure to a prolonged tone of changing intensity but constant frequency, controls, patients with peripheral hearing loss, and patients with multiple sclerosis (MS) demonstrated a reduced sensitivity to shifts in intensity; sensitivity to frequency shifts was unaffected. After exposure to a prolonged tone of changing frequency but constant intensity, control and patients with peripheral hearing loss demonstrated reduced sensitivity to shifts in frequency; sensitivity to intensity shifts was unaffected. Some patients with MS showed no loss of sensitivity to shifts in frequency. Our findings suggest that some patients with MS have abnormal mechanisms for processing changes of frequency. If such processing of frequency change is important for understanding speech, then this observation of a specific central hearing defect may help to explain poor speech discrimination in some patients with MS who have normal audiograms.

Auditory brainstem responses in postconcussion syndrome.

Evidence that head injuries can shear nerve fibers and end bulbs in the tracts between the diencephalon and brainstem led us to hypothesize that auditory brainstem responses might be abnormal in patients with postconcussion syndrome. We recorded brainstem responses in 11 patients and 12 control subjects. Comparing the two populations, our chief finding was that the patients showed significant delays for wave 3. This finding indicates organic changes involving a region at least as central as the superior olivary complex, thus refuting many authors' claims that the syndrome is entirely psychogenic.

Does a shift in the T-cell receptor repertoire precede the onset of MS?

BACKGROUND: Utz et al., in a study of identical twins discordant for MS, showed that antigen-stimulated T cells from the MS twins have a major shift in their T-cell receptor (TCR) repertoires when compared with the healthy twins. We hypothesized that a shift in the TCR repertoire precedes the onset of MS and tested this hypothesis by studying unstimulated naive T cells because the TCR repertoires of these cells are largely unaffected by disease. OBJECTIVE: To investigate whether unstimulated naive T cells from MS patients have a detectable shift in their TCR repertoires. METHODS: We analyzed the TCR J beta (TCRBJ) repertoires of naive T cells from identical twin pairs discordant for MS, healthy identical twin pairs, healthy unrelated pairs, and unrelated MS patient pairs. The correlation coefficient (r value) was used as a measure of similarity of TCRBJ repertoires in each pair of individuals. Fisher's z transformation was then used to test for the significance of the difference between the r values from different pairs. RESULTS: The TCRBJ repertoires of the discordant MS twin pairs were significantly different from those of the healthy identical twin pairs, whereas MS patient pairs had TCRBJ repertoires similar to those of the healthy unrelated pairs formed from healthy twin pairs and discordant MS twin pairs. CONCLUSIONS: MS patients have a major shift in their naive T-cell TCRBJ repertoires compared with healthy individuals, implying that this shift precedes the disease onset. This shift could represent the nongenetic factor that explains MS discordance in genetically identical individuals.

A model clinical neuroscience curriculum.

We have attempted to identify those attitudes, skills, and competencies in the clinical neurosciences that every graduating medical student should possess. Curricular guidelines are provided that may act as a model educational outline, to be adapted and utilized as individual circumstances dictate and resources permit. A universal, although not lockstep, curriculum emerges from these considerations.

Pain prevalence, severity and impact in a clinic sample of multiple sclerosis patients.

Previous studies have reported variable prevalence of pain in multiple sclerosis (MS) and have not documented the impact of pain on daily living. In this consecutive series, we report on data collected from structured interviews with 85 patients seen within a 16-month period at a regional referral clinic. The prevalence of pain for the month preceding assessment was 53%. There were no significant differences between patients who did and those who did not report pain on the basis of patient demographics (age, gender) and disease characteristics (disease subtype, duration and neurologic symptom severity). Disease duration and neurologic symptom severity were significantly correlated with the number of hours of pain per week but were not correlated with pain severity, the number of pain sites or pain-related distress. There was wide variability in the number of pain hours/week reported with 17.6% of the sample reporting continuous pain for the month preceding assessment. Sixty-five percent of patients with pain reported taking medications for pain and 90% of these patients evaluated their medication(s) as 50% effective or better. Nevertheless, patients with pain reported poorer mental health and more social-role handicap. Discussion focuses on the need for routine assessment of pain and the comprehensive evaluation of the effectiveness of pain interventions in the therapeutic management of patients with MS.

Temporal arteritis.

Temporal arteritis (granulomatous inflammation) usually involves the temporal and ophthalmic arteries, but may be part of a more widespread inflammation of the medium and large vessels. The patient usually presents with an associated group of constitutional symptoms (fever, malaise, anorexia, weight loss, anemia) and rheumatic complaints (polymyalgia rheumatic complaints (polymyalgia rheumatica). The diagnosis should be considered in any patient over 55 years old in whom these symptoms develop or in whom there is evidence of recent onset of headache, visual loss of localized arterial involvement. The diagnosis is also to be considered when the erythrocyte sedimentation rate is over 50 mm/hr, and the presence of arteritis is confirmed by temporalartery biopsy findings. Visual loss may occur in 50 percent of affected patients; other serious complications are less common. A strong clinical suspicion of temporal arteritis will permit diagnosis of the more uncommon and atypical presentations of the syndrome. Although cases of temporal arteritis may be self-limited, treatment is imperative because of the threat of blindness. Patients respond well to steroid (prednisone) therapy, which should be maintained for a prolonged period.

Drug therapy in multiple sclerosis: a study of Nova Scotia senior citizens.

We conducted a study to determine the types and costs of drugs used by Nova Scotia senior citizens with multiple sclerosis (MS) compared with the types and costs of drugs used by all senior citizens in Nova Scotia. Administrative claims databases from the Nova Scotia Seniors Pharmacare program for persons aged 65 years or older were linked to the Dalhousie Multiple Sclerosis Research Unit (DMSRU) clinical database (1980-1994). Analyses compared persons with MS aged 65 years or older who attended the DMSRU at least once with the general population of senior citizens. Not all persons with MS attended the DMSRU. In aggregate, Pharmacare costs in 1993-1994 for patients with MS aged 65 years or older (N = 52) were $975.00 Canadian per capita compared with $590.00 Canadian for all senior citizens in Nova Scotia (N = 108,646). Thus average drug costs for the senior citizens with MS were 65% greater than those for all senior citizens covered by Nova Scotia's comprehensive, publicly funded Pharmacare program. Compared with other senior citizens, those with MS more frequently received alpha-blockers, anticholinergics, cholinergics, tricyclic antidepressants, anticonvulsants, antifatigue agents, antispasticity agents, and antibiotics for bladder infections.

The psychosocial aspects of multiple sclerosis.

As we become more adept at measuring the neurologic deficits in MS, we are developing more effective measures of the broad psychosocial effects of the disease. These include emotional stresses, depression, cognitive changes, and decreasing activities in the family and community. In about half, cognitive changes will develop and, in some, the changes will occur early. Employment rates decline and the economic costs to the family and the health care system mount as the years go on. How well patients cope with the stresses on their personal lives, their relationships, and their families depends on many factors beyond the physical changes, such as their coping skills and their network of supportive people and resources. As we learn more about the changes occurring in the nervous system, we also are learning more about the psychological and social aspects of the disorder. Approaching the management of patients and their families with the broad view that recognizes both the neurologic and the psychosocial aspects of the disease results in more effective care for those with MS.

Amantadine therapy for fatigue in multiple sclerosis.

We carried out a double blind control study of fatigue in 32 patients with multiple sclerosis, comparing amantadine hydrochloride 100 mg twice a day and placebo. On amantadine 31% had marked improvement; 15.6% moderate improvement; 15.6% mild improvement; and 36.5% unchanged. On placebo, none noted marked improvement; one claimed moderate improvement on either amantadine or placebo. 18.7% reported mild improvement on placebo; and most of them had similar or more response to amantadine. No patient selected placebo over amantadine at the end of the trial. Overall improvement was seen in 62.5% of patients on amantadine and 21.8% on placebo. Additional experience up to two years suggests continued benefit but common and important side-effects.

Relevance in undergraduate neurological teaching.

About 10% of patients consulting a family practitioner have neurological complaints, and about 2% ultimately receive a neurological diagnosis. As it is not possible to train enough neurologists for these patients, graduating medical students must be competent and confident in assessing neurological problems, particularly those that are common, treatable or require emergency management. An evaluation was made of the neurological problems commonly seen in family practice, the difficulties in managing neurological problems by the family practitioner and the criteria for referral to a neurologist. To evaluate the teaching of medical students and house staff, the types of problems seen in a teaching hospital neurology service were examined. As a result of this study an approach to the training of physicians is outlined to assist them to handle confidently and competently the neurological problems they will see in daily practice.

An unusual occurrence of multiple sclerosis in a small rural community.

Ten patients with multiple sclerosis were found to have lived in close proximity in a Nova Scotia farming community of 150 people. All had drunk unpasteurized milk as children, were teetotallers, ate a high animal fat diet, and were well educated. Of greater interest was the observation that six of the ten cases were related in two family groups. The only time all patients lived in the community at the same time was in 1951 and 1952 during a polio outbreak. The relationship of polio to multiple sclerosis bears further study. The average age of the patients when they had measles was 11.8 years. Evidence suggests a link between risk of multiple sclerosis and both late onset of measles and pubertal age. Late onset of measles may be important in this cluster. Further epidemiological studies are needed to examine the age of onset of measles in M.S. cases.

Abnormal adaptation of visual contrast sensitivity in multiple sclerosis patients.

Some multiple sclerosis patients with 20/20 acuity complain of poor vision. In a previous report we accounted for this in our patient group by showing that multiple sclerosis had caused a depression of contrast sensitivity while sparing visual acuity. In this study we investigated whether some of this measured depression might be due to abnormally rapid or severe adaptation during the test procedure rather than a true permanent loss. Our finding was opposite to this supposition: adaptation was normally slight and/or slow. Depressed contrast sensitivity was not well correlated with abnormal adaptation to contrast. In patients whose contrast sensitivity losses were restricted to a band of spatial frequencies, we found no evidence that abnormalities of contrast adaptation were restricted to this same spatial frequency band. Further evidence of dissociation between abnormal contrast sensitivity and abnormal contrast adaptation is that some patients with normal contrast sensitivity showed abnormally small adaptation.

Delayed auditory tone perception in multiple sclerosis.

Delays of auditory perception at three frequencies were measured in 30 multiple sclerosis patients using a psychophysical technique. Nineteen patients had abnormal delays at one or more tone frequencies, though 15 had normal audiograms at those frequencies. In addition, auditory acuity for left-right asynchrony was abnormally poor in 13 patients, 9 of whom had normal audiograms. Such delays of auditory perception within a restricted frequency band may provide a partial explanation for degraded speech comprehension in some multiple sclerosis patients.

Impact of migraine and tension-type headache on life-style, consulting behaviour, and medication use: a Canadian population survey.

A large sample of Canadian adults was surveyed by telephone to determine the prevalence and characterization of headache, and the effects of headache on life-style, consulting behaviours and medication use. We reported prevalence and characterization in a previous issue; here, we detail the effects of headaches on sufferers. Sixteen and one-half percent of adult Canadians experience migraine and 29% tension-type headaches. In over 70% of headache sufferers interpersonal relationships are impaired. Regular activities are limited in 78% of migraine attacks and 38% of tension-type headaches. Despite this, only 64% of migraine and 45% of tension-type headache sufferers had ever sought medical attention, and of these only 32% returned for ongoing care. Fourteen percent of migraine and 8% of tension-type headache sufferers had used emergency departments. Most headache sufferers take medication, primarily over-the-counter varieties. Measures to reach the headache population are needed, as are safe effective treatment options that will encourage them to participate in their medical care.

A Canadian population survey on the clinical, epidemiologic and societal impact of migraine and tension-type headache.

Trained telephone interviewers contacted 1,573 adults across Canada about the nature and frequency of headaches suffered by them or by others in their households. Using a table of pain symptoms and other characteristics abstracted from the International Headache Society (IHS) classification, the headaches were assigned to migraine headache, tension-type headache or other diagnostic groups. Of the households sampled, 59% had at least one headache sufferer in residence. The proportion of headache sufferers with migraine was 14%; with tension-type, 36%; and with both, 14%. Migraine headache caused more disability than tension-type headache, with nearly 20% of migraine sufferers taking time off work and disability lasting for a mean of 1 day. It is concluded that the current prevalences of migraine and tension-type headache in Canada fall around the mean of previous studies, that the IHS criteria can form a basis for diagnostic classification and that the functional impact of migraine has been seriously underestimated in the past.