Biomedical subjects

K Schulze

Publications and source records attributed to K Schulze.

At least 37 records · Page 2Linked to original sources

PubMed2001

The role of computed tomography in the T classification of laryngeal carcinoma.

BACKGROUND: The objectives of this study were 1) to describe patterns of use of computed tomography (CT) in laryngeal carcinoma, and 2) to characterize the contribution of CT to the T classification of laryngeal carcinoma. METHODS: The study population comprised 1195 patients with laryngeal carcinoma diagnosed from 1982 through 1995 chosen randomly from the Ontario provincial cancer registry. A chart review was conducted to obtain data on each case. Patient-related, tumor-related, and health-system-related factors were analyzed to identify factors associated with the use of CT. Descriptions of clinical exams and CT reports were reviewed to see how CT information modified T classification. Actuarial local control and cause specific survival curves were plotted by clinical T classification without and with CT to evaluate stage migration. The percentage of the variance in outcome explained by T classification in a Cox analysis was used to evaluate whether the prognostic accuracy of T classification was improved with the use of information from CT. RESULTS: Patients with glottic (20.1%) and supraglottic (41.7%) carcinoma underwent CT. The use of CT increased over time in glottic and supraglottic carcinoma combined from 17.2% in 1982-5 to 33.9% in 1991-5. Computed tomography was used less often in older patients with a 16% (95% confidence interval, 5-27%) decrease in the odds of having CT with each 10-year age increment. Computed tomography use varied considerably across the cancer center regions in Ontario. Computed tomography altered the T classification in 20.2% of those patients who had CT, with most being "upstages." Stage migration due to CT was demonstrated. Using information from CT in the assignment of T classification for 27.8% of this study population did not make a significant contribution to the ability of T classification to predict outcome over the entire group. CONCLUSIONS: There is large variation in the use of CT among different age groups and regions. The ability to compare outcomes by stage across geographic areas is compromised when the use of CT varies.

Analysis of Variance↗

PubMed2001

A comparison of published head and neck stage groupings in carcinomas of the oral cavity.

BACKGROUND: The combination of T, N, and M classifications into stage groupings is meant to facilitate a number of activities, including the estimation of prognosis and the comparison of therapeutic interventions among similar groups of cases. We tested the UICC/AJCC 5th edition stage grouping and seven other TNM-based groupings proposed for head and neck cancer for their ability to meet these expectations in a specific site: carcinomas of the oral cavity. METHODS: We defined four criteria to assess each grouping scheme: (1) the subgroups defined by T, N, and M that make up a given group within a grouping scheme have similar survival rates (hazard consistency); (2) the survival rates differ among the groups (hazard discrimination); (3) the prediction of cure is high (outcome prediction); and (4) the distribution of patients among the groups is balanced. We identified or derived a measure for each criterion, and the findings were summarized by use of a scoring system. The range of scores was from 0 (best) to 7 (worst). The data are population based from a prospectively gathered series in Southern Norway, with 556 patients diagnosed from 1983 through 1995. Clinical stage assignment was used, and the outcome of interest was cause-specific survival. RESULTS: Summary scores across the eight schemes ranged from 1.66 for TANIS-3 to 6.50 for UICC/AJCC-5. The TANIS-7 staging scheme performed best on the hazard consistency criterion. The Kiricuta scheme performed best on the hazard discrimination criterion. Synderman predicted outcome best overall and Berg produced the most balanced distribution of cases among its groups. CONCLUSIONS: UICC/AJCC stage groupings were defined without empirical investigation. When tested, this scheme did not perform as well as any of seven empirically derived schemes we evaluated. Our results suggest that the usefulness of the TNM system could be enhanced by optimizing the design of stage groupings through empirical investigation.

Carcinoma, Squamous Cell↗

PubMed2001

Matrix composition in opossum esophagus.

The esophagus of mammalian species is organized into mucosa, connective tissue, and muscle, but little is known about the matrix of these layers. We studied by immunohistochemistry the distribution of collagens, fibronectin, versican, and elastin in the smooth muscle segment of the American opossum. Cryosections were exposed to specific antibodies and fluorescent-stained using conjugates of rhodamine or isothiocyanate. Staining was scored by two observers. We found that collagen I was prominent in the submucosa and in the muscular septa; collagen III formed fibrillar meshes in the lamina propria and the submucosa but was virtually absent from the epithelial and muscular layers; collagen IV was restricted to the base of the epithelium; collagen V, in contrast to collagen III, was prominent in epithelium and muscularis mucosae and sparse in muscular septa and submucosa. Fibronectin distribution followed collagen III; it formed layers in lamina propria and submucosa and strands in muscle septa and between individual muscle cells. Versican distribution followed collagen V; it was prominent in large muscle septa and formed thick sheets at the boundaries of submucosa/circular muscle and of circular/longitudinal muscle. We also determined the tissue contents of protein, hexuronic acid, and fibronectin. The mucosal layers exceeded the muscular layers in their content of hexuronic acid and fibronectin but not protein. We conclude that individual layers of the smooth muscle esophagus each have their own characteristic matrix. Lamina propria and submucosa are similar with regard to fiber orientation but lamina propria contains relatively more collagen III (small fibril) and submucosa comparatively more collagen I (large fibril). Nonfibrillar collagen V and versican are particularly prominent specifically on the boundaries between contracting muscle tissue and connective tissue framework.

Animals↗

PubMed2001

Fluorescent tracer in pilocarpine-treated rats shows widespread aberrant hippocampal neuronal connectivity.

Neuronal fibres of the hippocampal formation of normal and chronic epileptic rats were investigated by fluorescent tracing methods using the pilocarpine model of limbic epilepsy. Two months after onset of spontaneous limbic seizures, hippocampal slices were prepared and maintained in vitro for 10 h. Small crystals of fluorescent dye [fluorescein (fluoro-emerald) and tetramethylrhodamine (fluoro-ruby)] were applied to different hippocampal regions. The main findings were: (i) in control rats there was no supragranular labelling when the mossy fibre tract was stained in stratum radiatum of area CA3. However, in epileptic rats a fibre network in the inner molecular layer of the dentate gyrus was retrogradely labelled; (ii) a retrograde innervation of area CA3 by CA1 pyramidal cells was disclosed by labelling remote CA1 neurons after dye injection into the stratum radiatum of area CA3 in chronic epileptic rats; (iii) labelling of CA1 neurons apart from the injection site within area CA1 was observed in epileptic rats but not in control animals; and (iv), a subicular-hippocampal projection was present in pilocarpine-treated rats when the tracer was injected just below the stratum pyramidale of area CA1. The findings show that fibre rearrangement in distinct regions of the epileptic hippocampal formation can occur as an aftermath of pilocarpine-induced status epilepticus.

Action Potentials↗

PubMed2001

[On-scene helicopter transport at night].

Air medical rescue services at night are associated with an increased risk for life and health of the helicopter crew. They are not allowed in all federal states of Germany and only a few bases provide this service. The advantage of short transportation times by air cannot be achieved at night due to a flight preparation phase of at least 30 minutes until lift-off. Two case reports demonstrate that requests for helicopters at night may even lead to a transportation associated delay of treatment because of the time until the helicopter arrives on-scene. Thus emergency physicians have to know the possibilities and limitations of helicopter emergency medical services at night.

Air Ambulances↗

PubMed2001

Activity-dependent changes of the presynaptic synaptophysin-synaptobrevin complex in adult rat brain.

The vesicular protein synaptobrevin contributes to two mutually exclusive complexes in mature synapses. Synaptobrevin tightly interacts with the plasma membrane proteins syntaxin and SNAP 25 forming the SNARE complex as a prerequisite for exocytotic membrane fusion. Alternatively, synaptobrevin binds to the vesicular protein synaptophysin. It is unclear whether SNARE complex formation is diminished or facilitated when synaptobrevin is bound to synaptophysin. Here we show that the synaptophysin-synaptobrevin complex is increased in adult rat brain after repeated synaptic hyperactivity in the kindling model of epilepsy. Two days after the last kindling-induced stage V seizure the relative amount of synaptophysin-synaptobrevin complex obtained by co-immunoprecipitation from cortical and hippocampal membranes was increased twofold compared to controls. By contrast the relative amounts of various synaptic proteins as well as that of the SNARE complex did not change in membrane preparations from kindled rats compared to controls. The increased amount of synaptophysin-synaptobrevin complex in kindled rats supports the idea that this complex represents a reserve pool for synaptobrevin enabling synaptic vesicles to adjust to an increased demand for synaptic efficiency. We conclude that the synaptophysin-synaptobrevin interaction is involved in activity-dependent plastic changes in adult rat brain.

Age Factors↗

PubMed2001

Characterization of the domain of fibronectin-binding protein I of Streptococcus pyogenes responsible for elicitation of a protective immune response.

Fibronectin-binding protein I (SfbI) represents a major adhesin of Streptococcus pyogenes. Mice were intranasally immunized with recombinant proteins spanning different portions of SfbI to identify the minimal fragment able to elicit a protective response against a lethal challenge with S. pyogenes. The strongest cellular responses and the highest levels of antigen-specific secretory immunoglobulin A (IgA) were detected in mice immunized with the fibronectin-binding region of SfbI. In contrast, animals vaccinated with a polypeptide spanning the aromatic and proline-rich regions showed the highest titers and fastest IgG response in serum. Vaccination with either SfbI without a membrane anchor and signal peptide or a polypeptide encompassing its fibronectin-binding regions resulted in efficient protection against heterologous challenge (60% and 80%, respectively), whereas the use of a polypeptide lacking this region conferred marginal protection (10%) with respect to the control group (0%). These results demonstrate that the fibronectin-binding region of SfbI is a promising candidate antigen for developing anti-S. pyogenes vaccines.

Adhesins, Bacterial↗

PubMed2001

Effects of quality of energy intake on growth and metabolic response of enterally fed low-birth-weight infants.

Carbohydrate and fat may vary in their ability to support protein accretion and growth. If so, variations in the source of nonprotein energy might be used to therapeutic advantage in enterally fed low-birth-weight infants. To test the hypothesis that high-carbohydrate diets are more effective than isocaloric high-fat diets in promoting growth and protein accretion, low-birth-weight infants weighing 750-1600 g at birth were randomized in a double blind study to receive one of five formulas differing only in the quantity and quality of nonprotein energy. Groups 1, 2, and control received 130 kcal x kg(-1) x d(-1) with 35, 65, and 50% of the nonprotein energy as carbohydrate. Groups 3 and 4 received energy intake of 155 kcal x kg(-1) x d(-1) with 35 and 65% of the nonprotein energy as carbohydrate. Protein intake of all groups was 4 g x kg(-1) x d(-1). Growth and metabolic responses were followed weekly, and macronutrient balances including 6-h indirect calorimetry were performed biweekly. Greater rates of weight gain and nitrogen retention were observed at high-carbohydrate intake compared with high-fat intake at both gross energy intakes. Greater rates of energy storage and an increase in skinfold thickness were observed in group 4 (high-energy high-carbohydrate diet) despite higher rates of energy expenditure. These data support the hypothesis that at isocaloric intakes, carbohydrate is more effective than fat in enhancing growth and protein accretion in enterally fed low-birth-weight infants. However, a diet with high-energy and high-carbohydrate content also results in increased fat deposition.

Body Weight↗

PubMed2000

The management and outcome of bladder carcinoma in Ontario, 1982-1994.

BACKGROUND: To the authors' knowledge no previous study has described the management and outcome of bladder carcinoma on a population-based level. The objective of the current study was to describe the characteristics, treatment, and outcome of newly diagnosed invasive bladder carcinoma (n = 20,822) reported in Ontario, Canada between 1982-1994. METHODS: Electronic records of invasive bladder carcinoma (International Classification of Diseases code 188) from the Ontario Cancer Registry were linked to surgical and radiotherapy (RT) records. Bivariate and multivariate techniques were used to assess variations in the use of initial cystectomy and pelvic RT. The authors modeled the likelihood of death after diagnosis and the probability of cystectomy free survival. All analyses were controlled for age, gender, histology, and year of diagnosis. RESULTS: The most common histologic type was papillary transitional cell carcinoma. Maximum initial treatment was comprised of total cystectomy (5.1%), partial cystectomy or open excision (3. 5%), pelvic RT (5.9%), transurethral resection of the bladder (66. 7%), or lesser or no procedures (18.7%). The use of total cystectomy and pelvic RT varied among the regions of Ontario. Overall 5-year survival was 58.8%, and was 86.5% for patients with papillary histology. In multivariate analysis, although survival was similar among the regions, the relative risk of cystectomy conditional on survival varied. CONCLUSIONS: Papillary tumors portend a better survival than nonpapillary tumors. Variations in the use of total cystectomy and in the use of pelvic RT among the regions of Ontario did not appear to be associated with variations in survival. However, cystectomy free survival appeared to vary among the regions. These results suggest that patients can be managed safely using a bladder-preserving approach.

Adult↗

PubMed2000

Association between age and the utilization of radiotherapy in Ontario.

PURPOSE: The purpose of this study was to assess whether: (i) radiotherapy (RT) utilization varies with age in Ontario cancer patients; (ii) age-associated differences in the use of RT (if they exist) vary with cancer site and treatment intent; (iii) the age-associated variation in RT utilization is comparable to the decline in functional status in the general population; and (iv) the variation with age is due to differences in referral to a cancer center or to subsequent decisions. METHODS AND MATERIALS: Details for several cancer sites diagnosed between 1984-1994 were obtained from the Ontario Cancer Registry (OCR). RT records from all treatment centers were linked to the OCR database. Information about the functional status of the Canadian population was obtained from the 1994 National Population Health Survey conducted by Statistics Canada. RESULTS: The rate of RT use declined with age, particularly for adjuvant and palliative indications. The relative decline in RT with age exceeded the relative decline in functional status with age in the general population. Most of the decline in RT use was related to a decline in referral to cancer centers. CONCLUSIONS: The referral for, and use of, palliative and adjuvant RT decreases more with age than can be explained by age-associated decline in functional status observed in the general population.

Age Distribution↗

PubMed2000

The function of plakophilin 1 in desmosome assembly and actin filament organization.

Plakophilin 1, a member of the armadillo multigene family, is a protein with dual localization in the nucleus and in desmosomes. To elucidate its role in desmosome assembly and regulation, we have analyzed its localization and binding partners in vivo. When overexpressed in HaCaT keratinocytes, plakophilin 1 localized to the nucleus and to desmosomes, and dramatically enhanced the recruitment of desmosomal proteins to the plasma membrane. This effect was mediated by plakophilin 1's head domain, which interacted with desmoglein 1, desmoplakin, and keratins in the yeast two-hybrid system. Overexpression of the armadillo repeat domain induced a striking dominant negative phenotype with the formation of filopodia and long cellular protrusions, where plakophilin 1 colocalized with actin filaments. This phenotype was strictly dependent on a conserved motif in the center of the armadillo repeat domain. Our results demonstrate that plakophilin 1 contains two functionally distinct domains: the head domain, which could play a role in organizing the desmosomal plaque in suprabasal cells, and the armadillo repeat domain, which might be involved in regulating the dynamics of the actin cytoskeleton.

Actins↗

PubMed2000

A population-based study of the effectiveness of breast conservation for newly diagnosed breast cancer.

PURPOSE: Our objective was to evaluate the effectiveness of breast conservation for newly diagnosed breast cancer. Effectiveness was operationalized as two outcomes within 5 years of the diagnosis of breast cancer: the probability of mastectomy-free survival (either death or mastectomy count as event, whichever comes first), and the probability of mastectomy conditional on survival (mastectomy counts as event, observations censored at death). METHODS AND MATERIALS: We linked records of 46,687 new cases of breast cancer from 1982 to 1991 in the Ontario Cancer Registry to records of surgery from 1982 to 1995, radiotherapy (RT) from 1982 to 1992, and median household income from the 1986 census. We labeled breast surgery within 4 months and postoperative RT within 12 months of diagnosis as treatment for newly diagnosed breast cancer. Surgery was categorized as mastectomy, lumpectomy plus RT, lumpectomy alone, or no surgical procedure. Among cases that did not undergo mastectomy within 4 months of diagnosis, we labeled mastectomy subsequent to 4 months after diagnosis as treatment failure. We performed life-table analysis and Cox proportional hazards regression, to describe the probability of mastectomy conditional on survival and the probability of mastectomy-free survival. RESULTS: A total of 16,279 cases underwent lumpectomy as the maximum procedure on the breast within 4 months of diagnosis, and 49.7% of these received postoperative RT. Compared to the provincial mean, regions with higher rates of lumpectomy plus RT have higher probability of mastectomy-free survival and lower probability of mastectomy conditional upon survival 5 years after diagnosis of breast cancer. CONCLUSIONS: These findings are consistent with a hypothesis that breast conservation is effective in the overall breast cancer population of Ontario within the first 5 years after diagnosis.

Adult↗

PubMed2000

Age-related decline of PCr/ATP-ratio in progressively hypertrophied hearts of spontaneously hypertensive rats.

Although the ultimate cause for the myocardial dysfunction of hypertensive heart disease is still unclear, a crucial role of the myocardial energy metabolism has been suggested. Therefore, the aim of the present study was to investigate whether age-related myocardial dysfunction in hearts of spontaneously hypertensive rats (SHR) is associated with an impaired myocardial energy metabolism. Isolated hearts of SHR and Wistar Kyoto rats (WKY) aged about 40, 60, and 80 weeks, respectively (each n = 4-5), were perfused according to the working heart technique. Cardiac work and coronary flow were monitored online. Myocardial energy metabolism was evaluated by calculating the ratio of phosphocreatine (PCr) and adenosine triphosphate (ATP) which were measured by nuclear magnetic resonance (31P-NMR) spectroscopy. All hearts were subjected to work for 30min at baseline conditions (low afterload), followed by another 30min under a moderate pressure load (high afterload). Each SHR group showed a higher heart weight/body weight ratio than the age-matched WKY controls. The SHR showed a progressive age-dependent reduction of cardiac work (40 weeks = 5.1+/-0.3, 60 weeks = 4.0+/-0.3, 80 weeks = 3.8+/-0.2 (mW/g) at baseline conditions) and PCr/ATP-ratio (40 weeks = 1.82+/-0.06, 60 weeks = 1.69+/-0.05, 80 weeks = 1.59+/-0.09 (PCr/ATP) at baseline conditions). Similar results were found for hearts of SHR at high afterload. In WKY no significant decline in cardiac work or PCr/ATP-ratio was found under either low or under high afterload. The cardiac work capacity of hearts of SHR progressively decreases with increasing age and left ventricular hypertrophy. This myocardial dysfunction is closely associated with an impaired PCr/ATP-ratio, suggesting a decreased energy reserve.

Adenosine Triphosphate↗

PubMed2000

Enteroviral and immune mediated myocarditis in SCID mice.

Severe combined immune deficiency (SCID) mice have been used as an animal model to study both the direct cytopathic effect of enteroviruses on the heart in the absence of an effective immune system and to investigate the role of immune mediated processes in the pathogenesis of human myocarditis. The infection of SCID mice with coxsackievirus B3 resulted in severe myocarditis with very high titers of the virus in the myocardium and severe necrosis of myocytes. This direct cytopathic effect caused an impairment of the myocardial function and resulted in a high mortality rate of the infected animals. For the study of the immune mechanisms in human myocarditis, peripheral blood leukocytes of patients with myocarditis, having an impaired left ventricular function without viral persistence in the myocardium, were transferred into SCID mice. As controls peripheral blood leukocytes of normal donors were used. At 60 days after transfer, human immunoglobulines could be demonstrated in the peripheral blood of the SCID mice, however, human autoantibodies against the adenine nucleotide translocator, a myocardial autoantigen, were only present in the animals receiving peripheral blood leukocytes from patients with myocarditis. Cellular infiltrates of human leukocytes in the myocardium and an impaired left ventricular function were also only observed in animals reconstituted with peripheral blood leukocytes from patients. These effects were T cell dependent as shown by differential transfer. These results are of interest for the treatment of human myocarditis, suggesting the avoidance of an immunosuppressive therapy in acute or chronic myocarditis with viral persistence to prevent a direct cytopathic effect in the absence of an effective immune system. However, in the setting of a chronic, (auto-)immunological myocarditis with the proven absence of entero- or adenoviral sequences an immunomodulatory therapy seems to be effective and safe.

Animals↗

PubMed2000

A prospective trial of short-course radiotherapy plus chemotherapy for palliation of dysphagia from advanced esophageal cancer.

PURPOSE: Between 1994 and 1997, 22 patients with dysphagia from advanced incurable esophageal cancer were enrolled in a phase I/II prospective study to assess the palliative benefit and toxicity of a short course of radiotherapy with chemotherapy. METHODS: The study population included 17 men and five women with a median age of 69 (range 43-84). Patients were treated with 30 Gy in ten fractions to the mediastinum with a concurrent single course of chemotherapy (5-FU, 1000 mg/m(2), days 1-4 and mitomycin-C 10 mg/m(2), day 1). Swallowing ability was recorded each day on a self-administered diary card using the five point dysphagia index of the MRC (UK). The median baseline MRC swallowing score was 4 (cannot swallow solids). RESULTS: Treatment was generally well tolerated, but seven (32%) patients had transient worsening of dysphagia scores immediately following treatment because of esophagitis; fifteen (68%) achieved a complete response (score 1: no difficulty on swallowing) with a median time to normalization of swallowing of 5 weeks. For these patients, the median dysphagia-free interval from time of onset of improvement was 11 weeks (range 1-131 weeks) and 11 (73%) remained dysphagia-free until death. The remaining patients had no or marginal improvement. Univariate analysis showed no difference between responders and non-responders with respect to age, gender, or histology. Median survival for the entire study population was 20 weeks (range 3-135 weeks). CONCLUSIONS: This prospective trial shows that a short course of radiotherapy plus chemotherapy may produce complete relief of swallowing difficulties in a substantial proportion of patients with acceptable toxicity.

Adult↗

PubMed2000

In vivo correction of genetic defects of monocyte/macrophages using attenuated Salmonella as oral vectors for targeted gene delivery.

Macrophages are normal targets for Salmonella during natural infections, and it has been demonstrated that attenuated bacteria can deliver nucleic acid vaccine constructs. Therefore, we assessed if attenuated Salmonella can be used for the in vivo delivery of transgenes to their natural cellular target, in an attempt to correct genetic defects associated with monocytes/macrophages. This system would offer the distinct advantage of achieving a specific targeting of defective cells in a non-invasive form. Using a reporter gene, we demonstrated that attenuated Salmonella could be used as an effective in vitro delivery system to transfer genetic material into nondividing cells like murine macrophages. In vivo, the oral administration of attenuated Salmonella allows targeted delivery of transgenes to macrophages and subsequently expression of transgenes at a systemic level. IFNgamma-deficient mice (GKO) were thus selected as a model for the in vivo validation of the Salmonella-based delivery approach. Attenuated Salmonella, used as the carrier for a eukaryotic expression vector encoding the murine IFNgamma gene, was able to restore the production of this cytokine in GKO macrophages. Their oral administration to IFNgamma-deficient mice also re-established, in these immunocompromised animals, the natural resistance to bacterial infections. These results demonstrate, for the first time, that attenuated Salmonella can be successfully used in vivo as a DNA delivery system for the correction of a genetic defect associated with monocyte/macrophages.

Animals↗

PubMed2000

Alterations of glial cell function in temporal lobe epilepsy.

PURPOSE: Comparison of extracellular K+ regulation in sclerotic and nonsclerotic epileptic hippocampus. METHODS: Measurements of K+ signals with double-barreled K+-selective reference microelectrodes in area CAI of slices from human and rat hippocampus, induction of increases in extracellular potassium concentration by repetitive alvear stimulation or iontophoresis. and block of inward-rectifying and background K+ channels in astrocytes by barium. RESULTS: In the CA1 pyramidal layer from normal rat hippocampus, barium augmented extracellular K+ accumulation induced by iontophoresis or antidromic stimulation in a dose-dependent manner. Similarly, barium augmented stimulus-induced K+ signals from nonsclerotic hippocampi (human mesial temporal lobe epilepsy). In contrast, barium failed to do so in sclerotic hippocampi (human mesial temporal lobe epilepsy, rat pilocarpine model). CONCLUSIONS: Our findings suggest that in areas of reduced neuronal density (hippocampal sclerosis), glial cells adapt to permit rather large increases in extracellular potassium accumulation. Such increases might be involved in the transmission of activity through the sclerotic area.

Animals↗

PubMed2000

Alterations of neuronal connectivity in area CA1 of hippocampal slices from temporal lobe epilepsy patients and from pilocarpine-treated epileptic rats.

PURPOSE: Neuronal network reorganization might be involved in epileptogenesis in human and rat limbic epilepsy. Apart from aberrant mossy fiber sprouting, a more widespread fiber rearrangement in the hippocampal formation might occur. Therefore, we studied sprouting in area CA1 because this region is most affected in human temporal lobe epilepsy. METHODS: In slices from hippocampi of patients operated on for temporal lobe epilepsy (n = 134), from pilocarpine-treated rats (n = 74), and from control rats (n = 15), viable neurons were labeled with fluorescent dextran amines. RESULTS: In human hippocampi as well as in pilocarpine-treated rats, the degree of nerve cell loss varied. In 67 of 134 slices from human specimens with distinct Ammon's horn sclerosis and in 23 of 74 slices from pilocarpine-treated rats, a severe shrunken area CA1 presented with a similar picture: few damaged neurons were labeled, and aberrant fiber connections were not visible. This was in contrast to human resected hippocampi and hippocampi from pilocarpine-treated rats with no or moderate loss of neurons. In these cases, pyramidal cells remote from the injection site were labeled (human tissue, n = 59 of 134; pilocarpine-treated rats, n = 39 of 74). In human resected hippocampi without obvious pathology and in control animals, no pyramidal neurons were labeled apart from the injection site. CONCLUSIONS: Axon collaterals of CA1 pyramidal cells are increased in human temporal lobe epilepsy and in pilocarpine-treated rats. Adjacent CA1 pyramidal cells project via aberrant collaterals to the stratum pyramidale and the stratum radiatum of area CA1. This network reorganization can contribute to hyperexcitability via increased backward excitation.

Animals↗