Multiple test procedures other than Bonferroni's deserve wider use.
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Data Interpretation, Statistical↗
Biomedical subjects
R Bender
Publications and source records attributed to R Bender.
Value of blood pressure self-monitoring as a predictor of progression of diabetic nephropathy.
OBJECTIVE: To determine the impact of self-monitoring of blood pressure values (BP(S)) as compared with office blood pressure measurements (BP(O)) on the progression of diabetic nephropathy. DESIGN: Long-term, follow-up cohort study. SUBJECTS AND METHODS: Hypertensive, type 1 diabetic patients with overt diabetic nephropathy were investigated. Patients initially participated in a hypertension treatment and teaching programme including extensive advice on blood pressure self-monitoring. Self-monitoring and office blood pressure values were continuously assessed during the entire follow-up period. Progression of diabetic nephropathy over the study period was individually assessed as the mean decline of glomerular filtration rate (GFR) per patient per year. Baseline and follow-up parameters were included in stepwise multiple regression analyses with the decline of GFR per year as the dependent variable. RESULTS: Seventy-seven type 1 diabetic patients (37 women, 40 men) were followed for a mean period of 6.2 +/- 2.8 years (mean +/- SD; range 2-12) resulting in a total of 481 patient-years. During the follow-up period, mean BP(O) decreased from 166/95 at baseline to 154/89 mmHg during follow-up, and mean BP(S) fell from 159/93 to 138/83 mmHg. The mean decline of GFR was 4.1 +/- 5.6 ml/min per year. Loss of kidney function was significantly correlated with proteinuria, blood pressure and glycosylated haemoglobin values. In the multiple regression analyses, BP(S) predicted the loss of renal function better than BP(O) (R2 = 0.52 versus 0.42). The simple correlation between BP(S) and GFR decline was higher compared to BP(O) and GFR (r = -0.42; P < 0.0001 versus -0.33; P < 0.004). CONCLUSION: Blood pressure self-monitoring values are a better predictor of progression of diabetic nephropathy when compared with office blood pressure measurements.
Adult↗
Effects of intensified antihypertensive treatment in diabetic nephropathy: mortality and morbidity results of a prospective controlled 10-year study.
OBJECTIVE: The aim of this study was to describe the effect of intensified antihypertensive therapy based on a structured teaching and treatment programme on the prognosis of hypertensive type 1 (insulin-dependent) diabetic patients with kidney disease. DESIGN: The study was a controlled, prospective, parallel, 10-year follow-up trial. PATIENTS AND INTERVENTIONS: A sequential sample of 91 hypertensive type 1 diabetic patients with overt diabetic nephropathy was prospectively followed for 10 years. Forty-five patients (intensified antihypertensive therapy; IT group) participated in an intensified antihypertensive therapy programme and 46 patients received routine antihypertensive treatment as provided by family physicians, consultants and local hospitals (routine antihypertensive therapy; RT group). OUTCOME MEASURES: The main endpoint was death; secondary endpoints were renal replacement therapy, blindness and amputation. RESULTS: Blood pressure was reduced in the IT group and increased in the RT group. During the follow-up period, 29 patients died, seven in the IT group and 22 in the RT group. The survival curves were significantly different (P = 0.0008). The main causes of death were cardiac. In a multiple Cox proportional hazards model, allocation to the IT group reduced the mortality risk [relative risk (RR) = 0.213; 95% confidence interval 0.089-0.509, P = 0.00051, while age (P = 0.0039) and mean blood pressure (P= 0.0113) increased this risk. In multiple Cox or multiple logistic regression models, the risks of dialysis (RR = 0.269, 95% confidence interval 0.110-0.656, P = 0.0039), blindness (odds ratio = 0.158, 95% confidence interval 0.037-0.684, P= 0.0136), and amputation (RR = 0.181, 95% confidence interval 0.047-0.703, P= 0.0135) were significantly lower in the IT group compared with the RT group (log rank P = 0.0008). CONCLUSION: We conclude that intensified antihypertensive treatment, based on a hypertension teaching and treatment programme, reduces long-term morbidity and mortality in patients with diabetic nephropathy.
Adult↗
Influence of continuous combined estradiol-norethisterone acetate preparations on insulin sensitivity in postmenopausal nondiabetic women.
OBJECTIVE: Estrogen-progestogen replacement therapy (HRT) may be associated with deterioration of insulin sensitivity in comparison to estrogens alone, which tend to improve insulin sensitivity in postmenopausal women. Insulin sensitivity with the use of continuous combined 17-beta estradiol/norethisterone acetate (E2/NETA) preparations has not been examined before in postmenopausal women. DESIGN: In a double-blind randomized parallel study, we evaluated the effect of 2 mg E2/1 mg NETA (high dose E2/NETA), 1 mg E2/0.5 mg NETA (low dose E2/NETA), or placebo (P) on the insulin sensitivity index (SI) in three groups (18 women/group) of postmenopausal nondiabetic women (follicle stimulating hormone [FSH] > 40 mIU/mL, mean +/- SD) aged 56 +/- 3 years, BMI 25 +/- 4 kg/m2, cholesterol 233 +/- 42 mg/dL, and triglycerides 87 +/- 36 mg/dL. Insulin sensitivity was measured by means of a two-step hyperinsulinemic euglycemic glucose clamp (insulin infusion rate, 0.25 and 1.0 mU/kg/min for 120 min each) at baseline and after 3 months of daily administration of high dose E2/NETA, low dose E2/NETA, or P. Analysis was performed assuming equivalence of start-end changes of insulin sensitivity among treatment groups (Anderson-Hauck test). RESULTS: SI was 7.7 +/- 2.9, 7.5 +/- 3.4, 6.8 +/- 2.2 at baseline and 6.3 +/- 3.0, 7.9 +/- 2.5, 7.1 +/- 3.1 mL/min/m2 per mu U/mL 3 months after the administration of high dose E2/NETA, low dose E2/NETA, and P, respectively. The low dose E2/NETA group had start-to-end changes of SI which were equivalent to the P group (0.4 [95% confidence interval [CI] -0.8; 1.7] vs. 0.4 [-0.3; 1.0]) (p = 0.02). For the high dose E2/NETA group, equivalence could not be shown with either the P (p = 0.89) or with the low dose E2/NETA group (p = 0.90). SI within the high dose E2/NETA group decreased by -1.5 (95% CI -2.7; -0.2) mL/min/m2 per mu U/mL. HbAlc decreased from 5.3 +/- 0.3 to 5.1 +/- 0.3% within the high dose E2/NETA group (p < 0.03) and remained unchanged within the low dose E2/NETA and P group. Fasting plasma glucose, fasting serum insulin, and C-peptide, as well as triglycerides and BMI were comparable among the groups at baseline and after 3 months. Total cholesterol decreased by 12% and 8% in women treated with high dose and low dose E2/NETA (p < 0.02), respectively, and remained unchanged within the P group. CONCLUSIONS: These results indicate that 3 months use of a low dose continuous E2/NETA preparation does not change insulin sensitivity in postmenopausal women. At high dose of E2/NETA, a modest decrease seems possible. The effects of E2/NETA on other parameters of carbohydrate and lipid metabolism are neutral or favorable.
Aged↗
Variation of sensitivity, specificity, likelihood ratios and predictive values with disease prevalence by H. Brenner and O. Gefeller, Statistics in Medicine, 16, 981-991 (1997)
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Bias↗
Assessment of excess mortality in obesity.
Quantification of the excess mortality from all causes associated with obesity remains controversial. In this paper, 6,193 obese patients, those with a body mass index (weight (kg)/height (m)2 (BMI)) range of 25-74 kg/m2, recruited from 1961 to 1994 in Düsseldorf, Germany, were followed for a mean time of 14 (standard deviation, 8.2) years, yielding 87,179 observed patient-years. During the study period, 1,028 patients (16.6%) died. The entire cohort was grouped into approximate quartiles according to BMI: group 1, BMI from 25 to < 32; group 2, BMI from 32 to < 36; group 3, BMI from 36 to < 40; group 4, BMI > or = 40 kg/m2. The following risk ratios were estimated by means of Cox proportional hazards models using the lowest BMI group as reference category: group 2 for men, 1.02 (95% confidence interval 0.76-1.37); for women, 1.23 (95% confidence interval 0.96-1.58); group 3 for men, 1.50 (95% confidence interval 1.09-2.06); for women, 1.33 (95% confidence interval 1.03-1.73); and group 4 for men, 2.10 (95% confidence interval 1.53-2.88); for women, 2.25 (95% confidence interval 1.78-2.84). The following standardized mortality ratios were calculated by using the respective geographic area (the Federal State of North Rhine Westphalia) as reference population: group 1 for men, 1.26 (95% confidence interval 0.98-1.61); for women, 1.00 (95% confidence interval 0.81-1.23); group 2 for men, 1.31 (95% confidence interval 1.09-1.57); for women, 1.20 (95% confidence interval 1.02-1.40); group 3 for men, 1.92 (95% confidence interval 1.53-2.38); for women, 1.27 (95% confidence interval 1.07-1.50); and group 4 for men, 3.05 (95% confidence interval 2.47-3.73); for women, 2.31 (95% confidence interval 2.04-2.60). In addition to age, sex, and BMI, Cox proportional hazards models revealed systolic blood pressure, glucose intolerance, diabetes, and smoking as significant independent mortality risk factors, whereas cholesterol was not significant. In this prospective study of a large cohort of obese persons, morbid obesity (BMI of > or = 40 kg/m2) was a strong predictor of premature death. Excess mortality risks associated with gross obesity (BMI from 32 to < 40 kg/m2) were considerably lower than hitherto assumed; moderate degrees of obesity (BMI from 25 to < 32 kg/m2) were not significantly associated with excess mortality.
Adult↗
Intramuscular versus subcutaneous injection of soluble and lispro insulin: comparison of metabolic effects in healthy subjects.
The aim of this study was to compare the glucodynamic effects of soluble insulin and the rapid acting insulin analogue insulin lispro after subcutaneous (s.c.) and intramuscular (i.m.) injection. Twelve healthy male volunteers (age 26.8 +/- 1.7 years, BMI 23.2 +/- 2.3 kg m(-2); mean +/- SD) participated in this single-centre, open-labelled, euglycaemic glucose clamp study on four different days. Soluble insulin or insulin lispro (0.2 U kg(-1)) were injected s.c. or i.m. into the thigh by syringe. The glucodynamic effects were assessed by registering the glucose infusion rates necessary to maintain blood glucose at 5.0 mmol l(-1) for the subsequent 420 min. Intramuscular injection of soluble insulin led to an earlier peak of metabolic action when compared to s.c. administered soluble insulin (tmax 138 +/- 29 vs 179 +/- 34 min; p < 0.05). The maximal metabolic effect and metabolic activity during the first 2 h after i.m. and s.c. injection of soluble insulin were comparable (GIRmax 9.7 +/- 2.3 vs 7.8 +/- 2.3 mg kg(-1) min(-1); n.s., AUC0-120min 0.60 +/- 0.18 vs 0.50 +/- 0.15 g kg(-1) 120 min; n.s.). Subcutaneous administration of insulin lispro led to a metabolic effect resembling that induced by i.m. application of soluble insulin (tmax 116 +/- 26 vs 138 +/- 29 min; n.s., GIRmax 11.1 +/- 2.3 mg vs 9.7 +/- mg kg(-1) min(-1); n.s.). However, the overall metabolic response during the first 2 h after injection was higher with s.c. insulin lispro (AUC0-120min 0.81 +/- 0.26 vs 0.60 +/- 0.18 g kg(-1) 120 min; p < 0.05). The glucodynamic activity of i.m. applied insulin lispro was comparable to that of lispro s.c.. Following i.m. injection of soluble insulin, the metabolic activity peaked more rapidly than with s.c. administration. In contrast, the metabolic effect of insulin lispro was similar with either route. The time-action profile of i.m. injected soluble insulin lies between that of s.c. applied soluble insulin and insulin lispro.
Adult↗
Social status and the quality of care for adult people with type I (insulin-dependent) diabetes mellitus--a population-based study.
UNLABELLED: The objective of this study was to assess the degree of diabetes care and education achieved for Type I (insulin-dependent) diabetes mellitus at the community level in relation to social status and to elucidate potential pathways that mediate any social class gradient. A population-based sample of 684 adults with Type I diabetes (41% women, mean +/- SD age 36 +/- 11, diabetes duration 18 +/- 11 years) in the district of North-Rhine (9.5 million inhabitants), Germany, were examined in their homes using a mobile ambulance. RESULTS: HbA1c (normal 4.3-6.1%) 8.0 +/- 1.5%, incidence of severe hypoglycaemia (injection of glucose or glucagon) 0.21 cases per patient-year; 62% of patients had participated in a structured group treatment and teaching programme for intensification of insulin therapy; 70% used 3 or more insulin injections per day, 9% were on continuous subcutaneous insulin infusion; 91% reported to have had measurements of HbA1c during the preceding year, and 80% to have had an examination of the retina by an ophthalmologist. Care was insufficient with respect to the quality of blood pressure control (70% of patients on antihypertensive drugs had blood pressure values > or = 160/95 mmHg), patient awareness of proteinuria/albuminuria (27% of patients had not heard about it) and prevention of foot complications (only 42% with a diabetes duration over 10 years had remembered to have a foot examination during the preceding 12 months). There was a pronounced social gradient with respect to micro- and macrovascular complications (prevalence of overt nephropathy 7 vs 20% for highest vs lowest quintiles of social class [OR 3.5, 95% CI 1.6-7.5, p = 0.002]) and diabetes-specific quality of life. HbA1c, blood pressure and smoking accounted for part of the association between social class and microvascular complications. The social class gradient was not due to inequality to access to health services, but to lower acceptance among low social class patients of preventive and health maintaining behaviour. In conclusion, achieved standards of care are high with respect to the implementation of intensified treatment regimens, the level of patient education achieved, treatment control and eye care, whereas areas for improvement are blood pressure control and preventive measures for foot care. A substantial social gradient in diabetes care persists despite equal access of patients to health services.
Adolescent↗
Risk factors of severe hypoglycaemia in adult patients with Type I diabetes--a prospective population based study.
The objective of this study was to identify possible risk factors of severe hypoglycaemia (SH) in a prospective population based study of adult Type I (insulin-dependent) diabetic patients. A representative sample of 684 patients (41% women, mean +/- SD age 36 +/- 11, diabetes duration 18 +/- 11 years), living in the district of Northrhine (9.5 million inhabitants), Germany, were examined in their homes using a mobile ambulance. A comprehensive baseline assessment of possible predictors of SH included sociodemographic and disease related variables, hypoglycaemia awareness, diabetes management, and attitudes and behavioural aspects as expressed by the patients. After a mean of 19 +/- 6 months 669 (98%) patients were interviewed about events of SH since the baseline examination. Using the multiple Cox proportional hazards model, five risk factors of SH were identified: SH during the preceding year [hazard ratio (HR) 2.7, 95% confidence intervals (CI) 1.8-4.2], any history of SH (HR 1.9, CI 1.1-3.4), C-peptide negativity (HR 4.0, CI 1.2-12.7), social status (HR 0.8 for a difference of 5 units for a value range of 0-24, CI 0.6-0.9), and patients' determination to reach normoglycaemia (HR 0.7 for a difference of 1 unit for a value range of 1-6, CI 0.5-0.9), indicating that the lower the social status and the higher the patients' determination to reach normoglycaemia, the higher the risk of SH. After eliminating the history of hypoglycaemia from the model, impaired hypoglycaemia awareness and patients' inappropriate denial of SH as their particular problem became additional significant risk factors of SH. In conclusion, in this population based study of adult Type I diabetic patients, C-peptide negativity, a previous event of SH, patients' determination to reach normoglycaemia and social class were risk factors of SH.
Adult↗
Hippocampal mossy fiber sprouting is not impaired in brain-derived neurotrophic factor-deficient mice.
In human temporal lobe epilepsy, a loss of hilar neurons followed by the sprouting of recurrent mossy fiber collaterals and the reinnervation of free synaptic sites on granule cell dendrites are discussed as possible mechanisms underlying hippocampal hyperexcitability. Dentate granule cells have been shown to upregulate brain-derived neurotrophic factor (BDNF) as well as TrkB, the high-affinity receptor for BDNF, in response to limbic seizures. This raised the possibility that BDNF is an important factor in hippocampal mossy fiber sprouting. Here we have used slice cultures of hippocampus, in which mossy fibers sprout and form a supragranular plexus in response to granule cell deafferentation, and have compared cultures from early postnatal BDNF-deficient mice and wild-type mice. We demonstrate that there is sprouting of supragranular mossy fibers in cultured slices from both BDNF knock-out and wild-type mice. We conclude that BDNF is not an essential factor for mossy fiber sprouting. However, our data do not exclude a role for BDNF in mossy fiber sprouting in wild-type mice, as compensatory mechanisms might have become effective in the mutant.
Animals↗
Using binary logistic regression models for ordinal data with non-proportional odds.
The proportional odds model (POM) is the most popular logistic regression model for analyzing ordinal response variables. However, violation of the main model assumption can lead to invalid results. This is demonstrated by application of this method to data of a study investigating the effect of smoking on diabetic retinopathy. Since the proportional odds assumption is not fulfilled, separate binary logistic regression models are used for dichotomized response variables based upon cumulative probabilities. This approach is compared with polytomous logistic regression and the partial proportional odds model. The separate binary logistic regression approach is slightly less efficient than a joint model for the ordinal response. However, model building, investigating goodness-of-fit, and interpretation of the results is much easier for binary responses. The careful application of separate binary logistic regressions represents a simple and adequate tool to analyze ordinal data with non-proportional odds.
Bias↗
The value of QT interval dispersion for identification of total mortality risk in non-insulin-dependent diabetes mellitus.
OBJECTIVES: To delineate different risk markers including the difference between the maximum and the minimum length of the QT interval in ECG corrected for heart rate (QTc dispersion) as predictors of total, cardiac and cerebrovascular mortality in NIDDM patients. DESIGN: Case-control, follow-up study until death or for a period of 15 to 16 years. SETTING: Tertiary care centre, University Hospital of Düsseldorf, Germany. SUBJECTS: 216 unselected consecutive NIDDM patients. MAIN OUTCOME MEASURES: Total, cardiac, and cerebrovascular mortality. RESULTS: During the follow-up 158 (73%) patients died. In the Cox proportional hazards model QTc dispersion was the most important independent predictor of total mortality (risk ratio (RR) 3.3; difference for RR: 0.05 s1/2; P = 0.001). Additional independent risk markers were age, male sex, systolic blood pressure, diabetic retinopathy, micro- or macroproteinuria, total serum cholesterol and HDL cholesterol. The QTc dispersion was also an independent predictor of cardiac and cerebrovascular mortality. CONCLUSIONS: The results of this long-term follow-up study indicate that QT dispersion in a routine ECG is a useful marker to identify NIDDM patients with a high mortality risk.
Aged↗
Disseminated Intravascular Coagulopathy: A Complication Following Cardiac Angiography.
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Journal Article↗
A novel type of GABAergic interneuron connecting the input and the output regions of the hippocampus.
The main excitatory pathway of the hippocampal formation is controlled by a network of morphologically distinct populations of GABAergic interneurons. Here we describe a novel type of GABAergic interneuron located in the outer molecular layer (OML) of the rat dentate gyrus with a long-range forward projection from the dentate gyrus to the subiculum across the hippocampal fissure. OML interneurons were recorded in hippocampal slices by using the whole-cell patch-clamp configuration. During recording, cells were filled with biocytin for subsequent light and electron microscopic analysis. Neurons projecting to the subiculum were distributed throughout the entire OML. They had round or ovoid somata and a multipolar dendritic morphology. Two axonal domains could be distinguished: an extensive, tangential distribution within the OML and a long-range vertical and tangential projection to layer 1 and stratum pyramidale of the subiculum. Symmetric synaptic contacts were established by these interneurons on dendritic shafts in the OML and subiculum. OML interneurons were characterized physiologically by short action potential duration and marked afterhyperpolarization that followed the spike. On sustained current injection, they generated high-frequency (up to 130 Hz, 34 degrees C) trains of action potentials with only little adaptation. In situ hybridization and single-cell RT-PCR analysis for GAD67 mRNA confirmed the GABAergic nature of OML interneurons. GABAergic interneurons in the OML projecting to the subiculum connect the input and output regions of the hippocampus. Hence, they could mediate long-range feed-forward inhibition and may participate in an oscillating cross-regional interneuron network that may synchronize the activity of spatially distributed principal neurons in the dentate gyrus and the subiculum.
Animals↗
Development of cholinergic and GABAergic neurons in the rat medial septum: effect of target removal in early postnatal development.
During normal development of the nervous system, the target fields influence the survival and differentiation of projection neurons, but the factors regulating this interaction remain obscure. In the present study, we have raised the question whether the target region is essential for the postnatal development and maintenance of two different types of central projection neurons, cholinergic and GABAergic septohippocampal cells. In early postnatal rats (P5, P10), the hippocampus was eliminated by unilateral intrahippocampal injections of the excitotoxin N-methyl-D-aspartate. After a long survival time (at P70), we have immunostained serial sections of the septal region with antibodies against choline acetyltransferase (ChAT), the acetylcholine-synthesizing enzyme, or the calcium-binding protein parvalbumin (PARV) which is known to be contained in GABAergic septohippocampal neurons. In the medial septum ipsilateral to the lesioned side, about 60% of ChAT-immunoreactive neurons and 62% of PARV-immunoreactive neurons were found in adulthood even after complete elimination of the hippocampus. Some immunoreactive cells appeared heavily shrunken, but electron microscopic analysis revealed ultrastructural characteristics typical for medial septal neurons obtained from controls. Our results indicate that target elimination during development affected both types of projection cells, although only the cholinergic cells are known to be responsive to target-derived factors.
Animals↗
Endometrial collection and interpretation using the Tao brush and the CytoRich fixative system: a feasibility study.
BACKGROUND: The cytological assessment of endometrium entails: (1) a collection device that is easy to use, collects material only from the endometrium, and obtains adequate samples; (2) a fixation process that ensures the preservation of individual cells, maintains cell polarity, and allows the recognition of three-dimensional tissue structures (microbiopsies); and, (3) interpretative algorithms that translate histopathologic to cytopathologic diagnoses. The purpose of this study is to show that it is feasible to achieve these ends when endometrial brush sampling is coupled with suspension fixation. METHODS: Obtain endometrium from 100 consecutive hysterectomy uteri using an Indiana University Medical Center sampler (Tao Brush), suspension-fix it in CytoRich fixative, prepare it with a cytocentrifuge using large diameter sample chambers, and compare the cytologic diagnosis to the histologic diagnosis of the hysterectomy specimen. RESULTS: There were no inadequate collections. Cytology regularly separated (1) benign endometrium, (2) low-grade (non-atypical) hyperplasia, (3) high-grade (atypical) hyperplasia/FIGO Grade I adenocarcinoma, and (4) higher-grade carcinomas from one another. Endometrial atrophy was diagnosed in three patients whose histology showed clinically asymptomatic, benign fibrous endometrial polyps. A low volume of abnormal cell aggregates interpreted as endometrial intraepithelial carcinoma was detected in one patient whose initial histology was reported as simple hyperplasia, but whose histology on review after p53 staining revealed intraepithelial surface cancer. In the remaining 96 cases, the cytologic diagnosis consistently represented the histologic diagnosis of the hysterectomy specimen. On a case-by-case basis, any one cytology slide accurately represented the diagnosis of the other cytology slides. CONCLUSION: Endometrial brushing with suspension-fixation is advocated for the detection of endometrial lesions because (1) fixation is uniform, (2) there is substantial preservation of three-dimensional structures among cell aggregates, which allows pattern-based histologic diagnostic criteria to be applied to cytologic samples, and (3) only a limited number of slides need to be examined.
Adult↗
192 IgG-saporin-induced loss of cholinergic neurons in the septum abolishes cholinergic sprouting after unilateral entorhinal lesion in the rat.
After unilateral lesion of the entorhinal cortex, cholinergic septohippocampal fibres are believed to sprout in the denervated outer molecular layer of the rat dentate gyrus. This cholinergic sprouting has been demonstrated by acetylcholinesterase (AChE) histochemistry, a method said selectively to label cholinergic septohippocampal fibres in the hippocampus. However, a recent report has questioned this concept, suggesting that AChE may not be an adequate marker to monitor cholinergic sprouting and that other, non-cholinergic axons sprouting after entorhinal cortex lesion cause the dense AChE-positive band in the denervated outer molecular layer. In order to determine the contribution of cholinergic septohippocampal fibres to the dense AChE band appearing after entorhinal cortex lesion, the neurotoxin 192 IgG-saporin, known to destroy cholinergic neurons in the basal forebrain selectively, was used. Rats received bilateral injections of 192 IgG-saporin into the lateral ventricles 3 weeks before entorhinal cortex lesion, simultaneously with entorhinal cortex lesion, or 8 weeks after entorhinal cortex lesion. Immunocytochemistry for choline acetyltransferase (ChAT) and in situ hybridization for ChAT mRNA demonstrated the loss of cholinergic neurons in the medial septum and diagonal band after 192 IgG-saporin treatment. The cholinergic sprouting response in the molecular layer, as visualized with AChE histochemistry, was abolished in all animals treated with immunotoxin. These data indicate that the dense AChE band forming after entorhinal cortex lesion represents the sprouting of cholinergic septohippocampal fibres.
Acetylcholinesterase↗
[Acquisition of human bipedal gait from the viewpoint of the aquatic ape theory].
We are convinced that human bipedalism is better accounted for by the Aquatic Ape Theory than by the hypotheses, now commonly accepted, that the vertical gait is part of an adaptation for life in the savannahs. The advantages of the upright gait are easily understood by the versatility of this locomotion in a semi-aquatic mode of life. Early hominid bipedalism cannot be described as an ideal adaptation for one isolated form of locomotion, since human bipedalism covers a wide range of locomoter behaviours such as diving, swimming, wading, climbing trees and rocks, and moving on land. This locomotor versatility, however, should not be confused with theories that consider humans and their ancestors as "primitive" or "unspecialized" creatures. The pronounced swimming and diving abilities of humans--and the features that make these abilities possible--represents the most striking element of our species locomotor spectrum in comparison with highly specialized "savannah primates". On the one hand baboons and geladas are clearly better-adapted to savannah conditions than humans are, if the acquisitions of modern technology are not taken into consideration. To these adaptations belongs quadrupedalism, which is the most common and successful form of locomotion among terrestrial tetrapods. On the other hand, humans are in most respects much better swimmers and divers than nonhuman primates even without technological help. The only satisfying explanation for these different adaptations of humans and nonhuman primates is provided by the Aquatic Ape Theory. It is the only model of humans evolution that accounts for the numerous examples of convergent features between people and other vertebrates and the only model that explains these convergences in connection with a well-defined ecological niche.
Animals↗