Invasion Rate Versus Diversity in Population Dynamics with Catastrophes.

A key question in the current diversity crisis is how diversity has been maintained throughout evolution and how to preserve it. Modern coexistence theories suggest that a high invasion rate of rare new types is directly related to diversity. We show that adding almost any mechanism of catastrophes to a stochastic birth, death, and mutation process with limited carrying capacity induces a novel phase transition characterized by a positive invasion rate but a low diversity. In this phase, new types emerge and grow rapidly, but the resulting growth of very large types decreases diversity. This model also resolves two major drawbacks of neutral evolution models: their failure to explain balancing selection without resorting to fitness differences and the unrealistic time required for the creation of the observed large types. We test this model on a classical case of genetic polymorphism: the HLA locus.

Survival induced by short-scale autocorrelations in birth-death-diffusion models with negative growth.

In a birth, death, and diffusion process, the extinction-survival transition occurs when the average net growth rate is zero. For instance, in the presence of normally distributed time-varying stochastic growth rates with no autocorrelation, the transition indeed occurs at zero net growth rates. In contrast, if the growth rates are constant in time, a large enough variance in the growth rate will systematically ensure the survival of the global population even in a small system and, more importantly, even with a negative net growth rate. We here show that, surprisingly, for any intermediate temporal autocorrelation, any length of correlation, and any negative average growth rate, the same result holds. We test this argument on exponential and power law autocorrelation models and propose a simple condition for the growth rate variance at the transition.

High fraction of silent recombination in a finite-population two-locus neutral birth-death-mutation model.

A precise estimate of allele and haplotype polymorphism is of great interest in theoretical population genetics, but also has practical applications, such as bone marrow registries management. Allele polymorphism is driven mainly by point mutations, while haplotype polymorphism is also affected by recombination. Current estimates treat recombination as mutations in an infinite site model. We here show that even in the simple case of two loci in a haploid individual, for a finite population, most recombination events produce existing haplotypes, and as such are silent. Silent recombination considerably reduces the total number of haplotypes expected from the infinite site model for populations that are not much larger than one over the mutation rate. Moreover, in contrast with mutations, the number of haplotypes does not grow linearly with the population size. We hence propose a more accurate estimate of the total number of haplotypes that takes into account silent recombination. We study large-scale human leukocyte antigen (HLA) haplotype frequencies from human populations to show that the current estimated recombination rate in the HLA region is underestimated.

The effect of antibody against TNF alpha on cytokine response in Jarisch-Herxheimer reactions of louse-borne relapsing fever.

Severe Jarisch Herxheimer reaction (J-HR) precipitated by antibiotic treatment of louse-borne relapsing fever (LBRF) is associated with a transient, marked rise in circulating tumour necrosis factor alpha (TNF alpha), interleukin 6 (IL-6) and interleukin 8 (IL-8). Ovine polyclonal anti-TNF alpha antibody fragments (Fab) were used in a randomized double blind placebo controlled trial in an attempt to prevent this reaction. Within 4 h after penicillin, in controls (n = 29), a several-fold rise in cytokines occurred, concomitant with a fall in spirochaetes and maximal clinical manifestations of the J-HR. An intravenous infusion of anti-TNF alpha Fab, 30 min before penicillin in 20 patients reduced peak plasma levels of IL-6 and IL-8 (but not IL-1 beta) compared with controls (p = 0.01 and < 0.001, respectively) and the incidence of the J-HR, indicating some neutralization of TNF alpha. An apparent fall in TNF alpha reflected interference of anti-TNF alpha in the immunoassay.

Aetiology and outcome of non-traumatic altered states of consciousness in north western Ethiopia.

Awareness of the relative prevalence of diseases causing altered states of consciousness (ASC) in a particular geographic locality could greatly facilitate the approach to patient management. This prospective study has, therefore, evaluated 202 patients with ASC admitted to the medical wards of GCMS teaching hospital in a two year period, between January 1994 and December 1995. ASC was defined as a clinical state manifested by conditions ranging from confusion and disorientation in person, place and time to stupor and deep coma. History, physical examination, limited laboratory tests and course of the patient in the hospital were used to identify the aetiology. There were 122 (60.4%) males and 80 (39.6%) females with male to female ratio of 3:2. Most of the patients, 122 (60.4%), belong to the age group below 40 years and the median age was 33 years (range = 15.84). The median duration of hospital stay was six days (range = 1-90). The commonest cause was infections, 111 (55%) followed by metabolic disorders, 45 (22.3%), structural lesions, 30 (14.9%) and poisoning, seven (3.5%). The aetiology was not identified in nine (4.5%) of the patients. Cerebral malaria was the commonest infectious cause followed by chronic meningitis and/or encephalitis. In hospital mortality rate was 60.4%. Unknown diagnosis, structural neurologic and metabolic causes were associated with increased mortality rate, with p values of 0.002, 0.009 and 0.015, respectively. The same was true for presence of HIV infection, P = 0.02. Since infectious causes are the commonest causes in our series, of which most are treatable with a relatively favourable outcome, critical evaluation for infections and early intervention is recommended. In addition, diagnostic facilities, especially for structural central nervous system lesions has to be improved because successful treatment and prognosis depends on the identification of a specific aetiology.

Rheumatic heart disease in Gondar College of Medial Sciences Teaching Hospital: socio-demographic and clinical profile.

One hundred fourteen patients with rheumatic heart disease were seen between January 1994 and January 1995 at Gondar College of Medical Sciences Teaching Hospital. These patients were prospectively described using a prepared study protocol consisting of socio-demographic variables, clinical findings and laboratory tests. The mean and median age of the patients were 23 +/- 8 years and 22 years, respectively, (range = 5-50 years). About 66% of the patients were females with female to male ratio of 1.9:1. Eighty five cases (74.6%) were on follow up with mean and median duration of 4.32 +/- 4.5 years and 3 years, respectively (range = 1-20 years). The rest (25.4%) of the patients were new. History findings suggestive of rheumatic fever were obtained in 26% of the patients. Six patients (5.3%) had siblings with similar illness. Frequently encountered valve lesions were combined mitral regurgitation and stenosis seen in 29 (25.4%), followed by pure mitral stenosis in 25 (21.9%) and mitral regurgitation in 21 (18.4%). The commonest arrhythmia was atrial fibrillation, observed in 22.8% of the cases. Recurrence of rheumatic fever occurred in 11 patients (9.6%) over the study period. Of these, five were regularly taking a four weekly Banzanthine penicillin injections. The functional classes of patients according to the New York Heart Association's classification were 17%, 25%, 26% and 32% for classes I, II, III and IV, respectively. There were 85 episodes of decompensations. The commonest precipitating factor was drug discontinuation followed by infection and arrhythmia. Most episodes have multiple causes for deterioration. Critical evaluation and education of patients during follow up is recommended.

Symptomatic treatment of neurolathyrism with tolperisone HCL (Mydocalm): a randomized double blind and placebo controlled drug trial.

The efficacy and safety of oral Tolperisone HCL was evaluated in double blind, placebo-controlled, randomized trial in 72 patients with neurolathyrism in stages I, II, and III of the disease at Kolla Duba Health Centre of Dembia District of North Gondar between January and April 1995. Taken orally daily for 12 weeks, tolperisone HCL (Mydocalm) in a dose of 150 milligrams (mgs) twice daily significantly improved subjective complaints such as muscle cramps, heaviness of the legs, startle attacks, flexor spasms and repeated falls. An overall subjective improvement was observed in 75% of the patients on tolperisone HCL and 39% of the placebo group (P = 0.002). When objectively assessed spastic muscle tone in the abductors, stiffness of Achilles and spontaneous ankle clonus were significantly reduced in tolperisone HCL group (P values = 0.001, 0.04, and 0.0001, respectively). Walking ability and speed of walking was also significantly improved. The drug is most effective in relieving symptoms of stage I and stage II disease. Some adverse effects like muscle pain, generalized body weakness and dizziness were recorded in patients taking the drug but all were minor and self limited, none requiring discontinuation of treatment. It is concluded that tolperisone is a well tolerated and efficacious drug for symptomatic treatment of neurolathyrism.

Prevention of Jarisch-Herxheimer reactions by treatment with antibodies against tumor necrosis factor alpha.

BACKGROUND: In patients with louse-borne relapsing fever (Borrelia recurrentis infection), antimicrobial treatment is often followed by sudden fever, rigors, and persistent hypotension (Jarisch-Herxheimer reactions) that are associated with increases in plasma concentrations of tumor necrosis factor alpha (TNF-alpha), interleukin-6, and interleukin-8. We attempted to determine whether sheep polyclonal Fab antibody fragments against TNF-alpha (anti-TNF-alpha Fab) could suppress the Jarisch-Herxheimer reaction. METHODS: We conducted a randomized, double-blind, placebo-controlled trial in 49 patients with proven louse-borne relapsing fever. Immediately before the intramuscular injection of penicillin, the patients received an intravenous infusion of either anti-TNF-alpha Fab or a control solution. RESULTS: Ten of the 20 patients given anti-TNF-alpha Fab had Jarisch-Herxheimer reactions with rigors, as compared with 26 of the 29 control patients (P = 0.006). The controls had significantly greater mean maximal increases in temperature (1.5 vs. 0.8 degrees C, P < 0.001), pulse rate (31 vs. 13 per minute, P < 0.001), and systolic blood pressure (25 vs. 15 mm Hg, P < 0.003), as well as higher mean peak plasma concentrations of interleukin-6 (50 vs. 17 micrograms per liter) and interleukin-8 (2000 vs 205 ng per liter) (P < 0.001 for both comparisons). Levels of TNF-alpha were undetectable after treatment with anti-TNF-alpha Fab. CONCLUSIONS: Pretreatment with sheep anti-TNF-alpha Fab suppresses Jarisch-Herxheimer reactions that occur after penicillin treatment for louse-borne relapsing fever, reduces the associated increases in plasma concentrations of interleukin-6 and interleukin-8, and may be useful in other forms of sepsis.