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Biomedical subjects

A Thorne

Publications and source records attributed to A Thorne.

At least 19 recordsLinked to original sources
PubMed2006

Pygmoid Australomelanesian Homo sapiens skeletal remains from Liang Bua, Flores: population affinities and pathological abnormalities.

Liang Bua 1 (LB1) exhibits marked craniofacial and postcranial asymmetries and other indicators of abnormal growth and development. Anomalies aside, 140 cranial features place LB1 within modern human ranges of variation, resembling Australomelanesian populations. Mandibular and dental features of LB1 and LB6/1 either show no substantial deviation from modern Homo sapiens or share features (receding chins and rotated premolars) with Rampasasa pygmies now living near Liang Bua Cave. We propose that LB1 is drawn from an earlier pygmy H. sapiens population but individually shows signs of a developmental abnormality, including microcephaly. Additional mandibular and postcranial remains from the site share small body size but not microcephaly.

Bicuspid↗
PubMed2006

Timing and tempo of primate speciation.

Published molecular clocks for primates are used to estimate typical divergence times for phylogroups (1.6 Ma), species (3.3 Ma), sister species (2.7 Ma), genera (8.9 Ma) and sister genera (8.6 Ma). Significant median differences exist between major groups (infraorders and superfamilies) for various divergence times. These data are employed to estimate typical maximum duration of speciation. Typical primate values (1.1 Ma) suggest this process to be faster than is characteristic of many vertebrates. However, after considering divergence times for hybridizing congeneric and confamilial primates, this value is likely only to estimate the commencement of prezygotic isolating mechanisms, rather than the completion of reproductive isolation. Thus, speciation typically takes around 1.0 Ma to more than 4.0 Ma to occur, depending on whether prezygotic or post-zygotic isolating mechanisms are emphasized. Typical primate genus age is around 5.3 Ma, but we note differences among major groups. In light of these estimates, the classification of humans and chimpanzees is reconsidered using a molecular yardstick approach. Three taxonomic frameworks may flow from molecular analyses, all of them having major implications for understanding the evolution of humans and chimpanzees.

Animals↗
PubMed2003

Number of ancestral human species: a molecular perspective.

Despite the remarkable developments in molecular biology over the past three decades, anthropological genetics has had only limited impact on systematics in human evolution. Genetics offers the opportunity to objectively test taxonomies based on morphology and may be used to supplement conventional approaches to hominid systematics. Our analyses, examining chromosomes and 46 estimates of genetic distance, indicate there may have been only around 4 species on the direct line to modern humans and 5 species in total. This contrasts with current taxonomies recognising up to 23 species. The genetic proximity of humans and chimpanzees has been used to suggest these species are congeneric. Our analysis of genetic distances between them is consistent with this proposal. It is time that chimpanzees, living humans and all fossil humans be classified in Homo. The creation of new genera can no longer be a solution to the complexities of fossil morphologies. Published genetic distances between common chimpanzees and bonobos, along with evidence for interbreeding, suggest they should be assigned to a single species. The short distance between humans and chimpanzees also places a strict limit on the number of possible evolutionary 'side branches' that might be recognised on the human lineage. All fossil taxa were genetically very close to each other and likely to have been below congeneric genetic distances seen for many mammals. Our estimates of genetic divergence suggest that periods of around 2 million years are required to produce sufficient genetic distance to represent speciation. Therefore, Neanderthals and so-called H. erectus were genetically so close to contemporary H. sapiens they were unlikely to have been separate species. Thus, it is likely there was only one species of human (H. sapiens) for most of the last 2 million years. We estimate the divergence time of H. sapiens from 16 genetic distances to be around 1.7 Ma which is consistent with evidence for the earliest migration out of Africa. These findings call into question the mitochondrial "African Eve" hypothesis based on a far more recent origin for H. sapiens and show that humans did not go through a bottleneck in their recent evolutionary history. Given the large offset in evolutionary rates of molecules and morphology seen in human evolution, Homo species are likely to be characterised by high levels of morphological variation and low levels of genetic variability. Thus, molecular data suggest the limits for intraspecific morphological variation used by many palaeoanthropologists have been set too low. The role of phenotypic plasticity has been greatly underestimated in human evolution. We call into question the use of mtDNA for studies of human evolution. This DNA is under strong selection, which violates the assumption of selective neutrality. This issue should be addressed by geneticists, including a reassessment of its use for molecular clocks. There is a need for greater cooperation between palaeoanthropologists and anthropological geneticists to better understand human evolution and to bring palaeoanthropology into the mainstream of evolutionary biology.

Animals↗
PubMed2001

Antenatal diagnosis of spinal lipomas.

OBJECT: The purpose of this study was to highlight the key prenatal diagnostic features of fetal spinal lipomas. METHODS AND RESULTS: All fetuses in whom a spinal lipoma was suspected prenatally or diagnosed postnatally were included in the study. Lumbosacral lipoma was diagnosed in 16 fetuses (group 1), but at birth 3 of these were found to have other forms of occult dysraphism. In 2 other fetuses (group 2) a meningocele was suspected but at birth these lesions were found to be lumbosacral lipomas. The lipomas were covering large meningoceles in 13 fetuses and filling the cul-de-sac in 2 others. Three sets of parents decided on termination. Of the 13 children born with a spinal lipoma, 9 were operated on and 4 were managed conservatively. At the last follow-up, 7 were neurologically intact. CONCLUSION: The distinction between meningomyelocele and spinal lipoma is possible antenatally. The differential diagnosis between lipoma and the other forms of occult dysraphism is more difficult.

Diagnosis, Differential↗
PubMed2001

Mitochondrial DNA sequences in ancient Australians: Implications for modern human origins.

DNA from ancient human remains provides perspectives on the origin of our species and the relationship between molecular and morphological variation. We report analysis of mtDNA from the remains of 10 ancient Australians. These include the morphologically gracile Lake Mungo 3 [ approximately 60 thousand years (ka) before present] and three other gracile individuals from Holocene deposits at Willandra Lakes (<10 ka), all within the skeletal range of living Australians, and six Pleistocene/early Holocene individuals (15 to <8 ka) from Kow Swamp with robust morphologies outside the skeletal range of contemporary indigenous Australians. Lake Mungo 3 is the oldest (Pleistocene) "anatomically modern" human from whom DNA has been recovered. His mtDNA belonged to a lineage that only survives as a segment inserted into chromosome 11 of the nuclear genome, which is now widespread among human populations. This lineage probably diverged before the most recent common ancestor of contemporary human mitochondrial genomes. This timing of divergence implies that the deepest known mtDNA lineage from an anatomically modern human occurred in Australia; analysis restricted to living humans places the deepest branches in East Africa. The other ancient Australian individuals we examined have mtDNA sequences descended from the most recent common ancestor of living humans. Our results indicate that anatomically modern humans were present in Australia before the complete fixation of the mtDNA lineage now found in all living people. Sequences from additional ancient humans may further challenge current concepts of modern human origins.

Africa, Eastern↗
PubMed2000

Personal memory telling and personality development.

Although personal memories have been appreciated by psychologists for nearly a century, their significance for personality development has tended to be relegated to internalized representations of early childhood experiences. Recent research, however, suggests that adolescence and early adulthood are the most memorable parts of the life span and perhaps the broadest period of memory telling. This article integrates recent work in cognitive and developmental psychology into a framework for studying how and why tellers proffer and make sense of momentous emotional events, and how families and friends collude in self-making. Promising areas for future research include individual differences in readiness for memory telling, gendered ecologies of memory telling, the developmental significance of parents' stories, and reconciling personal memories and personality traits. Personal memory telling is not just for fun and entertainment, but, more important, drives social and emotional development in concrete moments of social life.

Journal Article↗
PubMed2000

Symptomatic and health status outcomes in the Canadian randomized MAC treatment trial (CTN010). Canadian HIV Trials Network Protocol 010 Study Group.

Our objective was to compare the effect of 2 regimens for treatment of Mycobacterium avium complex (MAC) bacteraemia in an HIV-positive population on symptoms and health status outcomes using a substudy of an open-label randomized controlled trial. The study was conducted in 24 hospital-based human immunodeficiency virus (HIV) clinics in 16 Canadian cities. Patients had HIV infection and MAC bacteraemia and were given either rifampin 600 mg, ethambutol 15 mg/kg daily, clofazimine 100 mg daily and ciprofloxacin 750 mg twice daily (4-drug arm) or rifabutin 600 mg daily (amended to 300 mg daily in mid-trial), ethambutol 15 mg/kg daily and clarithromycin 1000 mg twice daily (3-drug arm). The primary health status outcome was the change on the 8-item symptom subscale of the Medical Outcome Study (MOS)-HIV Health Survey adapted for MAC. Changes on other MOS-HIV subscales and on the Karnofsky score were also evaluated. Patients on the 3-drug arm had better outcomes on the MOS-HIV symptom subscale at 16 weeks (P=0.06), with statistically significant differences restricted to night sweats and fever and chills (P < 0.001). The proportion of patients improving on the symptom subscale relative to baseline was 55% on the 3-drug arm and 40% on the 4-drug arm. Patients on the 3-drug arm also had better Karnofsky score at 16 weeks (P < 0.001) and better outcomes on the social function, mental health, energy/fatigue, health distress and cognitive function subscales of the MOS-HIV. The 3-drug arm is superior to the 4-drug arm in terms of impact on MAC-associated symptoms, functional status and other aspects of health status.

AIDS-Related Opportunistic Infections↗
PubMed1999

Predictors of survival and eradication of Mycobacterium avium complex bacteremia (MAC) in AIDS patients in the Canadian randomized MAC treatment trial. Canadian HIV Trials Network Protocol 010 Study Group.

OBJECTIVE: To assess the importance of baseline characteristics including medical history, indicators of current disease status, therapeutic drug use, in vitro drug susceptibility, immune status and mycobacterial load on bacteriologic response and survival in HIV-positive patients with Mycobacterium avium complex (MAC) bacteremia. DESIGN: An observational substudy of an open-label randomized controlled trial of two alternative therapeutic regimens for MAC. SETTING: Twenty-four hospital-based HIV clinics in 16 Canadian cities. MAIN OUTCOME MEASURES: The main outcome measures were survival and bacteriologic response, defined by consecutive negative blood cultures for MAC at least 2 weeks apart within 16 weeks of study entry. RESULTS: Prior AIDS diagnosis, low Karnofsky score, active unstable AIDS-related conditions, absence of antiretroviral therapy and absence of Pneumocystis carinii pneumonia prophylaxis were associated with shorter survival by univariate regression using the proportional hazards model. On multivariate analysis, antiretroviral therapy was not an independent predictor of mortality, and previous rifabutin prophylaxis was independently associated with poor survival outcomes, a result consistent across study treatment. Using a logistic regression model, baseline quantitative mycobacterial load [relative odds of clearing, 1.97 for a decrease of 1 log10 colony forming count; 95% confidence interval (CI), 1.36-2.87; P < 0.001] and Karnofsky score were the only statistically significant univariate predictors of clearance, although previous prophylaxis with rifabutin was also a significant predictor in a multivariate model (relative odds of clearing, 0.39; 95% CI, 0.17-0.88; P < 0.05). CONCLUSIONS: This study indicates that although the level of MAC bacteremia is an important predictor of clearance, it is not associated with survival.

AIDS-Related Opportunistic Infections↗
PubMed1999

Australia's oldest human remains: age of the Lake Mungo 3 skeleton.

We have carried out a comprehensive ESR and U-series dating study on the Lake Mungo 3 (LM3) human skeleton. The isotopic Th/U and Pa/U ratios indicate that some minor uranium mobilization may have occurred in the past. Taking such effects into account, the best age estimate for the human skeleton is obtained through the combination of U-series and ESR analyses yielding 62,000+/-6000 years. This age is in close agreement with OSL age estimates on the sediment into which the skeleton was buried of 61,000+/-2000 years. Furthermore, we obtained a U-series age of 81,000+/-21,000 years for the calcitic matrix that was precipitated on the bones after burial. All age results are considerably older than the previously assumed age of LM3 and demonstrate the necessity for directly dating hominid remains. We conclude that the Lake Mungo 3 burial documents the earliest known human presence on the Australian continent. The age implies that people who were skeletally within the range of the present Australian indigenous population colonized the continent during or before oxygen isotope stage 4 (57,000-71,000 years).

Animals↗
PubMed1998

Serum immunoreactive erythropoietin levels and associated factors amongst HIV-infected children.

OBJECTIVES: To determine the spectrum of serum immunoreactive erythropoietin (SIE) levels amongst HIV-infected children aged < 13 years in relation to the levels among healthy children as well as those with renal failure; to examine the relationship between clinical and laboratory parameters and SIE levels. DESIGN: A cross-sectional study with a descriptive non-interventional format. HIV-infected Canadian subjects were recruited through four tertiary Canadian and one Bahamian centre. Children with renal failure and healthy children were recruited from one of the Canadian centres. METHODS: Study subjects had clinical and laboratory profiles determined at baseline and at each of five follow-up periods over 1 year. SIE levels were measured by radioimmunoassay with a normal range of 12-28 IU/I. Data handling and statistical functions were performed by the Canadian HIV Trials Network. RESULTS: The study enrolled 133 HIV-infected subjects and 38 controls. Of these, 117 HIV-infected subjects, 24 healthy controls, and 11 controls with renal failure were eligible for analysis. The median age of infected subjects was 44 months, whereas that of healthy controls was 56 months, and 95 months for controls with renal failure. The median SIE levels were 14 and 11 IU/I for subjects with renal failure and healthy subjects, respectively. The median SIE level was 61 IU/I among zidovudine (ZDV)-treated subjects and 22 IU/I among ZDV-naive HIV-infected subjects. HIV-infected children almost invariably had SIE levels < 200 IU/I. The median SIE levels amongst HIV-infected subjects whose hemoglobin levels were < 100 g/l were 98 and 31 IU/I for ZDV-treated and ZDV-naive subjects, respectively (P = 0.002). This difference in median SIE levels between ZDV-treated subjects and ZDV-naive subjects was also observed among subjects whose hemoglobin levels were > 100 g/l (median, 58 and 15 IU/l, respectively; P < 0.001). Hemoglobin level was the most important predictor of log10 SIE (P < 0.01 for ZDV-treated and ZDV-naive subjects). CONCLUSIONS: SIE levels amongst HIV-infected children were affected by HIV infection, use of ZDV, and presence or absence of anemia. SIE levels amongst HIV-infected children were generally lower than 200 IU/I. This characterization of SIE levels will facilitate clinical trials of exogenous recombinant human erythropoietin in HIV-infected children with anemia.

Anemia↗
PubMed1998

ESR and U-series analyses of teeth from the palaeoanthropological site of Hexian, Anhui Province, China.

ESR and U-series analyses of teeth from the palaeoanthropological site of Hexian which contained Homo erectus remains, illustrate the limited effectiveness of stand-alone ESR and U-series age estimates on faunal materials. The problem lies in the unknown U-uptake history causing very large uncertainties in the age results of both techniques. This study demonstrates the particular strength that lies in the integration of ESR and U-series dating analyses allowing the estimation of the U-uptake history. We obtained a combined ESR/U-series age estimate of 412 +/- 25 ka (average of six analyses on two teeth). This pinpoints the deposition of the faunal remains to the time of the transition between oxygen isotope stages 12 and 11. This is in agreement with the faunal composition which show a mixture of cold adapted northern mammals and more subtropical-tropical southern elements. The age also implies that the advanced Hexian Homo erectus occurred at a similar time as the less advanced Homo erectus specimens at Locality 1 at Zhoukoudian (LI-LIII).

Animals↗
PubMed1998

Estimating the effect of treatment on quality of life in the presence of missing data due to drop-out and death.

Quality of life was measured in a study of two multidrug regimens for mycobacterium avium complex MAC bactaeremia using the MOS-HIV questionnaire. The effect of treatment on quality of life was estimated at each follow-up time in three ways: (1) using only the observed data, (2) after assigning the worst possible quality of life scores for individuals who died, and (3) after imputing missing scores for patients who either died or dropped out of the study. The overall quality of life scores were also compared between treatment groups with categorical generalized estimating equation models and three-dimensional graphs. Of the 179 patients included in these analyses, 84 (47%) either died or dropped out during the 16 week study period. When the quality of life scores were compared between the treatment groups with the Wilcoxon rank sum test using only the observed data, there was no significant difference between the groups at 16 weeks of follow-up. When the worst possible quality of life scores were assumed for patients who had died, both the magnitude and the statistical significance of the difference in the quality of life scores between the groups increased. Imputing missing data for patients who either dropped out or died resulted in even larger differences in quality of life between the treatment groups. We conclude that ignoring missing data due to drop-outs and death can result in an underestimation of the treatment effect and overly optimistic statements about the outcome of the participants on both treatment arms due to the selective drop-out of participants with poorer quality of life. To obtain a valid assessment of the effect of treatment on quality of life, the experience of the patients who died or dropped out of the study must be considered.

AIDS-Related Opportunistic Infections↗
PubMed1998

Clindamycin with primaquine vs. Trimethoprim-sulfamethoxazole therapy for mild and moderately severe Pneumocystis carinii pneumonia in patients with AIDS: a multicenter, double-blind, randomized trial (CTN 004). CTN-PCP Study Group.

This double-blind, randomized, multicenter trial compared clindamycin/primaquine (Cm/Prq) with trimethoprim-sulfamethoxazole (TMP-SMZ) as therapy for AIDS-related Pneumocystis carinii pneumonia (PCP). Forty-five patients received clindamycin (450 mg four times daily [q.i.d.]) and primaquine (15 mg of base/d); 42 received TMP-SMZ (320 mg/1,600 mg q.i.d. if weight of > or = 60 kg or 240 mg/1,200 mg q.i.d. if weight of < 60 kg) plus placebo primaquine. Overall, the efficacy of Cm/Prq was similar to that of TMP-SMZ (success rate, 76% vs. 79%, respectively); Cm/Prq was associated with fewer adverse events (P = .04), less steroid use (P = .18), and more rashes (P = .07). These differences were even greater for patients with PaO2 of > 70 mm Hg (P = .02, P = .04, and P = .02, respectively). For patients with PaO2 of < or = 70 mm Hg (23 Cm/Prq recipients and 21 TMP-SMZ recipients), the efficacy of Cm/Prq was similar to that of TMP-SMZ (success rate, 74% vs. 76%, respectively); Cm/Prq was associated with similar adverse events (P = .57), steroid use (P = .74), and rashes (P = .78). This trial confirms that Cm/Prq is a reasonable alternative therapy for mild and moderately severe PCP.

AIDS-Related Opportunistic Infections↗
PubMed1997

Correlation of virus load in plasma and lymph node tissue in human immunodeficiency virus infection. INCAS Study Group. Italy, Netherlands, Canada, Australia, and (United) States.

The impact of long-term changes in plasma viremia, produced by effective combination antiretroviral therapy, on human immunodeficiency virus (HIV) burden within tissue reservoirs is unknown. Fifteen patients who had received at least 1 year of therapy with two or three drug combinations of zidovudine, didanosine, and nevirapine had suitable samples of lymph node tissue obtained by ultrasound-guided core needle biopsy. HIV RNA was extracted from homogenized tissue samples and quantitated using a modified branched DNA assay. Results were correlated with antiretroviral treatment effect on the basis of plasma virus load measurements over the preceding 12-18 months. A statistically significant negative correlation was observed between magnitude of treatment effect on plasma viremia and lymph node virus load. These data suggest that combinations of antiretroviral drugs that produce sustained suppression of plasma HIV RNA may also be able to reduce the virus burden in lymphoid tissues.

Biopsy↗