Biomedical subjects
Publications and source records attributed to A Keller.
Focusing on a variety of relevant psychological theories, this chapter addresses important elements in the recovery process for people with serious mental disabilities.
The first purpose of this study was to evaluate the saddle prosthesis in patients with periacetabular tumors in terms of the functional results obtained after several postoperative intervals. The second purpose was to evaluate the complications and how they might be prevented in the future. Functional results according to the MSTS functional rating system were evaluated at several postoperative intervals in 15 patients treated with internal hemipelvectomy and reconstruction with the saddle prosthesis because of periacetabular primary (n = 9) or secondary (n = 6) malignancies. All complications were evaluated. Three months postoperatively, 7/9 patients with a primary tumor and 2/4 patients with a secondary tumor were able to walk outside without pain. Median functional results 3 and 6 months postoperatively were 40% and 50%, respectively. Deep infection occurred in 4 patients and fracture of the iliac remnant in 2. Heterotopic ossifications along the interpositional component were seen in 5 patients, but they did not negatively influence the functional outcome. Three (relative) contraindications to reconstruction with the saddle prosthesis could be ascertained: osteoporosis, extended involvement of the iliac wing by tumor, and insufficient soft-tissue quality after previous procedures. (Short-term) functional results after reconstruction with the saddle prosthesis are satisfactory if the above-mentioned contraindications are taken into consideration.
Enolase is a dimeric glycolytic enzyme exhibiting tissue specific isoforms. During ontogenesis, a transition occurs from the embryonic alphaalpha towards the specific alphabeta, and betabeta isoforms in striated muscle. Immunocytochemical analyses on transverse sections of adult mouse gastrocnemius muscle, allowed us to compare the expression of alpha and beta subunits to that of myosin heavy chain (MHC) isoforms. Levels of beta immunoreactivity followed the order IIB > IIX > IIA > I. This gradient parallels the ATPase activity associated to MHC isoforms, indicating that the expression of beta enolase in myofibres is finely regulated as a function of energetic requirements. By contrast, variations in alpha immunolabelling intensity appeared independent of fibre types. Longitudinal muscle sections exhibited a striated pattern of alpha immunoreactivity. Confocal microscopy analyses demonstrated that alpha was localised at the M band. Most beta immunoreactivity was diffuse all over the sarcoplasm. However, some beta immunoreactivity was striated and localized at both Z and M bands. Thus, betabeta enolase could participate to multi-enzyme complexes present at the I band, and involved with local ATP production. Our results support the notion that isozymes differ in their ability to interact with other macromolecules, thus segregating to different subcellular sites where they would respond to specific functional demands.
Although microsurgery is generally regarded as the conventional treatment of choice for most vestibular schwannomas, there remains a group of patients in whom a conservative management approach may be a desirable alternative. The aim of this study was to determine the natural history and outcome following the conservative management of 72 patients with unilateral vestibular schwannomas. The reasons for conservative management included poor general health, age, patient preference, small tumour size, minimal or no symptoms, and tumour in the only/better hearing ear. The mean duration of follow-up was 39.8 months (range 12-194 months). All patients underwent serial magnetic resonance imaging (MRI) for assessment of tumour growth. Patients were deemed to have failed conservative management if there was evidence of continuous or rapid radiological tumour growth and/or increasing symptoms or signs. The mean tumour growth rate, according to the 1995 guidelines of the American Academy of Otolaryngology/Head and Neck Surgery, was 1.16 mm/year (range: 0.75 9.65 mm/year). Approximately 83% of tumours grew at < 2 mm/year. Significant tumour growth was seen in 36.4%, no or insignificant growth in 50%, and negative growth in 13.6% of tumours. The growth rate of CPA tumours (1.4 mm/year) was significantly greater than that of IAC tumours (0.2 mm/year) (P = 0.001). Failure of conservative management, in which active treatment was required, occurred in 15.3%. The outcome of these patients appeared to be as favourable to a comparable group who underwent primary treatment, without a period of conservative management. The mean growth rate of tumours in patients who failed conservative management (4.2 mm/year) was significantly greater than that in patients who did not fail (0.5 mm/year) (P < 0.01). No factors predictive of tumour growth or failure of conservative management were identified. Deterioration of mean pure tone average (0.5, 1, 2, 3 kHz) and speech discrimination scores occurred regardless of whether radiological tumour growth was demonstrated or not. This study suggests that in a select number of cases of vestibular schwannoma, a conservative management approach may be appropriate. Regular follow-up with serial MRI is mandatory. Deterioration of auditory function occurs even in the absence of tumour growth.
Nothing is known about the expression of the glycolytic enzyme enolase in skeletal muscle alterations such as myofiber degeneration and regeneration. Enolase is a dimeric enzyme which exhibits cell type specific isoforms. The embryonic form, alphaalpha, remains expressed in most adult tissues, whereas a transition towards specific isoforms occurs during ontogenesis in two cell types with high energy requirements: alphagamma and gammagamma in neurons, alphabeta and betabeta in striated muscle cells. During murine myogenesis, beta enolase transcripts are detected early in the forming muscles, and the beta gene is further upregulated at specific stages of muscle development. The alpha and beta subunits exhibit characteristic developmental microheterogeneity patterns. High levels of beta enolase subunits characterize the glycolytic fast-twitch fibers of adult muscles. We have investigated the expression of enolase subunits in a mouse experimental model of muscle regeneration. Following a single intramuscular injection of the necrotic agent cardiotoxin, we observed a rapid decrease in the level of the major muscle enolase subunit beta, accounting for the drop in total enolase activity that correlated with the degeneration of myofibers. Concomitant with the regeneration of new fibers, beta subunit levels began to increase, reaching normal values by 30 days after injury. Changes in the embryonic and ubiquitous subunit, alpha, mimicked those occurring during development by two aspects: modifications in electrophoretic variants and redistribution between soluble and insoluble compartments of muscle extracts. Imunocytochemical analyses of alpha and beta enolase subunits first revealed a homogeneous labeling within myofibers. Striations characteristic of normal adult muscle tissue were visible again by day 14 after injury. A perinuclear alpha and beta immunoreactivity was often observed in regenerating myofibers but its functional significance remains to be elucidated. Double labeling experiments with anti-gamma enolase and FITC-alpha bungarotoxin allowed us to follow the neuromuscular junction remodeling that occurs during muscle regeneration despite the absence of nerve injury.
Theoretical models suggest a higher vulnerability of chronic schizophrenic patients for critical life events and rapid change of objective living circumstances. On the basis of these models one may hypothesise that the political change in East Germany in 1989/90 was objectively or subjectively distressing to such patients and had a negative impact on their illness. In a retrospective longitudinal study, we investigated patients' assessment of political change, life events that were potentially related to the political changes, impact of the changes on subjective quality of life, and hospitalization rates during five year periods prior to and following the change. 120 patients with chronic schizophrenia in East Berlin and 70 in Chemnitz were examined using quantitative and qualitative methods. Patients reported more individual freedom and better care after 1989. They complained about stress due to loss of employment, financial disadvantages and rising crime rates. Despite the occurrence of potentially change-related life events after 1989, patients stated very little impact of the changes on their illness. Retrospectively, patients in East Berlin reported a significantly better subjective quality of life in 1994 than in 1984. Hospitalization rates did not increase after 1989. The findings are not consistent with the hypothesis and do not suggest that political changes in East Germany in 1989/90 had--subjectively or objectively--a substantial negative effect on the illness of patients with chronic schizophrenia.
The intrinsic circuitry of the motor cortex comprises a complex network of connections whose synaptic relationships are poorly understood. This study was designed to determine the characteristics of subsets of GABAergic neurons containing the calcium-binding proteins parvalbumin (PV) and calbindin (CB), and their relationships with intrinsic axons in motor cortex. Immunohistochemically identified PV-containing neuronal profiles were more evenly distributed across cortical laminae (38% in II-III, 32% inV, 30% in VI) and more numerous (2.1/1) than CB-containing neuronal profiles (71% in II-III, 17% in V, 12% in VI). Relationships between neurons and axons intrinsic to motor cortex were visualized with fluorescent markers using the laser scanning confocal microscope. Similar percentages of PV (43%) and CB-immunoreactive (IR) (40%) neurons formed sparsely distributed appositions (1-5/neuron) with anterogradely labeled axons. The mean distances of such appositions from the somata were significantly different for the two groups (PV, mean = 22 microm, range = 1.6-93 microm; CB, mean = 32 microm, range = 6.2-132 microm). PV-IR neurons had a lower ratio of axosomatic/axodendritic appositions (1/99) compared with CB-IR neurons (14/86). Ultrastructural studies confirmed these findings. Fifty-seven percent of CB-IR neurons and 38% of PV-IR neurons formed synapses with intrinsic axons. Both populations received sparse input (1-6 synapses/neuron). Nearly all appositions between labeled terminals and postsynaptic profiles formed one synapse. Postsynaptic dendrites of PV-IR neurons (mean = 1.4 microm diameter) were larger than those of CB-IR neurons (mean = 1.1 microm), indicating more proximal synapses. Distinct input patterns of intrinsic axons to the two populations of neurons suggest unique roles in cortical processing.
Lysosomal protein trafficking is a fundamental process conserved from yeast to humans. This conservation extends to lysosome-like organelles such as mammalian melanosomes and insect eye pigment granules. Recently, eye and coat color mutations in mouse (mocha and pearl) and Drosophila (garnet and carmine) were shown to affect subunits of the heterotetrameric adaptor protein complex AP-3 involved in vesicle trafficking. Here we demonstrate that the Drosophila eye color mutant ruby is defective in the AP-3beta subunit gene. ruby expression was found in retinal pigment and photoreceptor cells and in the developing central nervous system. ruby mutations lead to a decreased number and altered size of pigment granules in various cell types in and adjacent to the retina. Humans with lesions in the related AP-3betaA gene suffer from Hermansky-Pudlak syndrome, which is caused by defects in a number of lysosome-related organelles. Hermansky-Pudlak patients have a reduced skin pigmentation and suffer from internal bleeding, pulmonary fibrosis, and visual system malfunction. The Drosophila AP-3beta adaptin also appears to be involved in processes other than eye pigment granule biogenesis because all ruby allele combinations tested exhibited defective behavior in a visual fixation paradigm.
OBJECTIVE: To estimate the risk of loss of serviceable hearing during the conservative management of vestibular schwannomas. STUDY DESIGN: Retrospective case review. METHODS: Twenty-five patients with a radiological diagnosis of unilateral vestibular schwannoma were managed conservatively for a mean duration of 43.8 months (range, 12-194 mo). The pure-tone average (PTA) (0.5, 1, 2, and 3 kHz) and speech discrimination scores (SDS) were measured at regular intervals throughout the entire duration of follow-up. Serviceable hearing was defined using two criteria: 70% SDS/30 dB PTA (the 70/30 rule) and 50% SDS/50 dB PTA (the 50/50 rule). The size and growth rate of tumors were determined according to the American Academy of Otolaryngology-Head and Neck Surgery guidelines (1995). Intervention was recommended if there was evidence of continuous or rapid radiological tumor growth, and/or increasing symptoms or signs suggestive of tumor growth. RESULTS: The risk of loss of serviceable hearing for the total group was 43% using the 70/30 rule and 42% using the 50/50 rule. Tumor growth was considered significant (> 1 mm) in 8 tumors (32%) and nonsignificant in 17 (68%). The risk of loss of serviceable hearing for the tumor-growth group was 67% using the 70/30 rule and 80% using the 50/50 rule. In contrast, the risk of loss of serviceable hearing for the no tumor-growth group was 25% using the 70/30 rule and 14% using the 50/50 rule. No audiological factors predictive of tumor growth were identified. CONCLUSIONS: There is a significant risk of loss of serviceable hearing during the conservative management of vestibular schwannomas. This risk appears to be greater in tumors that demonstrate significant growth.
SHV extended-spectrum beta-lactamases (ESBLs) arise through single amino acid substitutions in the parental enzyme, SHV-1. In order to evaluate the effect of genetic dissimilarities around the structural gene on MICs, we had previously devised an isogenic system of strains. Here, we present an extended version of the system that now allows assessment of all major types of SHV beta-lactamases as well as of two types of promoters of various strengths. Moreover, we devised a novel vector, pCCR9, to eliminate interference of the selection marker. A substitution within the signal sequence, I8F found in SHV-7, slightly increased MICs, suggesting more efficient transfer of enzyme precursor into the periplasmic space. We also noted that combination of G238S and E240K yielded higher resistance than G238S alone. However, the influence of the additional E240K change was more pronounced with ceftazidime and aztreonam than with cefotaxime and ceftriaxone. The SHV enzymes characterized by the single change, D179N, such as SHV-8, turned out to be the weakest SHV ESBLs. Only resistance to ceftazidime was moderately increased compared to SHV-1.
During muscle development, an isozymic transition of the glycolytic enzyme enolase occurs from the embryonic and ubiquitous alphaalpha-isoform to the muscle-specific betabeta-isoform. Here, we demonstrate a stimulatory role of thyroid hormones on these two enolase genes during rat development in hindlimb muscles and an inhibitory effect on the muscle-specific enolase gene in cardiac muscle. In hindlimb muscles the ubiquitous alpha-transcript level is diminished by hypothyroidism, starting at birth. On the contrary, the more abundant muscle-specific beta-transcript is insensitive to hypothyroidism before establishment of the functional diversification of fibers and is greatly decreased thereafter. Our data support the hypothesis of a role of thyroid hormones in coordinating the expressions of contractile proteins and metabolic enzymes during muscle development. The subcellular localization of isoenolases, established here, is not modified by hypothyroidism. Our results underline the specificity of action of thyroid hormones, which modulate differentially two isozymes in the same muscle and regulate, in opposite directions, the expression of the same gene in two different muscles.
OBJECTIVE: Before a scheduled increase of salt iodide content up to 20 p.p.m. in Switzerland, urinary iodine concentration (UIC, microg/l) of a randomly selected, area-covering, age-stratified population subgroup was sampled in spring 1997. In contrast to former published studies on UIC, we minimized biases by age, gender, rural/urban, socio-economic and cultural influences. METHODS: We contacted 750 households in the Bernese region using random telephone numbers. Per household, one proband selected by play dice collected a spot urine sample. We defined seven age categories: infants, children, adolescents, adults I-III and seniors, aged 0-5, 6-12, 13-20, 21-35, 36-50, 51-65 and >65 years respectively. Randomized UIC data were compared with WHO criteria of iodine deficiency (ID) and previous non-randomized, age-dependent Swiss UIC data. To recruit a perfect random group of volunteers proved difficult, as study participation of adolescent and male populations was somewhat lower than that of elder and female (P<0.005) populations respectively. Study participation of inhabitants of rural and suburban regions was comparable (P=0.139). Out of 413 obtained urine spots, 412 (55%) were analyzed statistically (58% women, 42% men, P<0.005). RESULTS: Ninety per cent of all UIC values ranged between 25 and 200 microg/l. Median UIC showed mild ID (94 microg/l). UIC varied significantly between age categories (P=0. 0006). Women had lower UIC than men (P=0.014). Infants had no ID. Women in child-bearing age (13-35 years), adults II, adults III and seniors had mild ID. Compared with recommended supplies of 150 and 200 microg I/day in children and male adolescents respectively, we consider their UIC (110 and 144 microg/l) as at least borderline deficient. Absolute UIC was lowest in seniors. Probands from rural/suburban households had similar UICs. Our UIC data were comparable to published ones. CONCLUSIONS: Despite long-term national efforts with iodized salt (15 p.p.m. in 1997), mild ID still prevailed in Bern in spring 1997, with rare extreme UIC values. Mild ID with women in child-bearing age (and probably also with children and male adolescents) was a serious concern, as goiter growth with puberty or pregnancy might be the consequence. Mild ID in adults and seniors might be due to restricted NaCl intake. Results of our randomly selected subgroup from a 650 000 population show that age- and gender-dependency are important when comparing our collected data with published UIC data. This fact must be considered with non-randomly selected population subgroups.
OBJECTIVE: The aim of this study was to investigate the natural history and outcome following the conservative management of a group of patients with unilateral vestibular schwannomas. METHODS: 72 patients with a radiological diagnosis of unilateral vestibular schwannoma were managed conservatively because of poor general health, advanced age, patient preference, small tumour size, minimal symptoms, or tumour in the only/better hearing ear. All patients underwent serial magnetic resonance imaging for assessment of tumour growth, according to American Academy of Otolaryngology-Head & Neck Surgery guidelines (1995). The mean duration of follow-up was 37.8 months (range 12-194 months). Patients were deemed to have failed conservative management if there was evidence of continuous or rapid radiological tumour growth, and/or increasing symptoms or signs. RESULTS: The mean tumour growth rate was 1.16 mm/year (range -0.75 to 9.65 mm/year). Approximately 83% of tumours grew at less than 2 mm/year. Significant tumour growth (total growth > 1 mm) was seen in 36.4%, no or insignificant growth (0-1 mm) in 50%, and negative growth (< 0 mm) in 13.6% of tumours. The growth rate of cerebellopontine angle (CPA) tumours (1.4 mm/year) was significantly greater than that of tumours limited to the internal auditory canal (IAC) (0.2 mm/year) (p = 0.001). Failure of conservative management, in which active treatment was required, occurred in 15.3%. The outcome of these patients appeared to be as favourable as those who underwent primary treatment, without a period of conservative management. The growth rate of tumours in patients who failed conservative management (4.2 mm/year) was significantly greater than that in patients who did not fail (0.5 mm/year) (p < 0.01). No factors predictive of tumour growth were identified. Deterioration of mean pure tone average (0.5, 1, 2, 3 kHz) and speech discrimination scores occurred regardless of whether radiological tumour growth was demonstrated or not. CONCLUSIONS: The majority of vestibular schwannomas are slow growing, although, CPA tumours appear to grow faster than IAC tumours. Deterioration of auditory function occurs even in the absence of tumour growth. Although most Otolaryngologists and Neurosurgeons would agree that the treatment of choice for the majority of vestibular schwannomas is microsurgery, there remains a small group of patients in whom a conservative management approach may be a desirable alternative.
OBJECTIVE: To compare two methods for measuring the size and growth rate of extracanalicular vestibular schwannomas: the method recommended in 1995 by the American Academy of Otolaryngology--Head Neck Surgery (AAO-HNS) and the maximum cerebellopontine angle (CPA) tumor diameter, i.e., the method often used in radiologic reports. STUDY DESIGN: Retrospective clinical study. SETTING: Tertiary referral center. PATIENTS: Fifty-four patients with a radiologic diagnosis of unilateral extracanalicular vestibular schwannoma whose tumors were managed conservatively for a mean duration of 39.8 months (range 12-194 months). INTERVENTION: The extracanalicular component was measured by use of high-resolution magnetic resonance imaging (2- to 3-mm axial slices) at 6- to 12-month intervals. MAIN OUTCOME MEASURES: Tumor diameter was calculated by two methods. In the AAO-HNS method, the axial image with the largest extracanalicular tumor diameter was selected, and the maximum anteroposterior (A-P) and medial-lateral (M-L) tumor diameters were calculated. The A-P diameter was calculated parallel to the posterior surface of the petrous temporal bone, and the M-L diameter was calculated perpendicular to it. The size of the tumor was calculated as the square root of the product of these two diameters. In the maximum CPA method, the maximum CPA tumor diameter in any direction was also measured. RESULTS: There was no significant difference between the two methods for measuring the extracanalicular tumor size and growth rate, although the maximum CPA diameter method was consistently greater than the AAO-HNS method. There was a strong positive correlation between the two methods for assessing tumor size and growth. The A-P and M-L extracanalicular tumor diameters also showed a strong positive correlation, suggesting that the extracanalicular portion of vestibular schwannomas tends to enlarge equally in both these directions. CONCLUSION: There is a strong positive correlation between these two methods for assessing both the tumor size and the growth rate of extracanalicular vestibular schwannomas. However, because vestibular schwannomas tend to grow in both the A-P and the M-L directions, this suggests that the AAO-HNS method is preferable.
Lithium is used with great success in the treatment of manic patients and for prophylaxis of bipolar disorders. There are only few reports about neuropsychiatric side effects at therapeutic serum levels. We report on a 38 year old woman with bipolar disorder who was treated with lithium for 20 years without side-effects. Subsequent to a manic episode, she became disoriented at night and showed marked memory deficits. The patient did not show any neurological or gastrointestinal signs of intoxication. Lithium serum-levels were in therapeutic range. The psychiatric symptoms disappeared when lithium was stopped. We interpret these symptoms as delirant syndrome with pseudo-dementia at therapeutic lithium serum levels. This side-effect must be taken into account even in patients on successful longtime lithium therapy.
The growth and development of a child is a mirror of his living conditions and health. For decades pediatricians have been trying to achieve an earlier identification of children with growth disorders. The measures of prevention in Germany have not been successful so far. Diagnosis for example of GH-deficiency to ensure optimal substitution with growth hormone is usually not early enough. A screening system using an auxological data bank for growth disorders has been set up by us recently. Since 1998 we have collected height and weight measurements in relation to age and sex from patients cared for by a large number of pediatricians in the region of Leipzig, Germany. By september 1999, 30,182 children of different ages have been screened. The system identifies children with short stature below the 3. centile and tall stature above the 97. centile of the German Synthetic Normcurve (Hermanussen/Burmeister 1999). In 6.81% of the children a growth disorder was identified (3.03% above 97. and 3.78% below 3. centile). In 54 cases (0.18%) we found a pathological reason for short or tall stature. A sensitive screening system has been set up for the early detection of growth disorders and obesity in childhood. We generate a data pool for multiple questions in research of human growth. We will generate yearly reports for the development of new strategies in preventive medicine.
We have generated a large complex library of single chain antibodies based on four individual libraries from each of 50 donors. DNA coding for the heavy and light chain variable domains of the IgM and IgG repertoires was amplified by PCR using two different sets of primers. Each individual library was composed of approximately 1-5x10(7) independent clones giving a final combined library of 4x10(9) members. Screening this library by phage display of single chain antibodies with small haptens, peptides and proteins yielded specific antibodies for each class of antigen.
Retrograde axonal transport of cholera toxin B subunit (CTB) was used to compare the development of intracortical and thalamocortical connections in normal rats with those in rats in which all of the whiskers were trimmed continuously from birth. In normal animals, injections of CTB into a single barrel column resulted in an asymmetrical labeling of cells that were distributed preferentially within columns related to the same row in which the injection was placed. This anisotropy in the patterns of intracortical connections was not observed in whisker-clipped animals. In these animals, there was a significant reduction in the mean number of labeled cells in the infragranular layers, and labeled cells were distributed symmetrically around the injection site. The same injections of CTB also labeled thalamocortical neurons in the ventrobasal thalamus. Analysis of the distribution of these cells revealed that, in both control and experimental animals, the vast majority of labeled cells were restricted to a homologous (i.e., corresponding to the injected cortical barrel) thalamic barreloid. These findings indicate that manipulations of sensory experience alter patterns of intracortical, but not thalamocortical, connections.