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Biomedical subjects

H W Schroeder

Publications and source records attributed to H W Schroeder.

At least 19 recordsLinked to original sources

The management of posterior polar cataract: the role of patching and grading.

BACKGROUND: The milder form of posterior polar cataract is often discovered late in preschool children if secondary symptoms like strabismus are not present. The question addressed in this paper is: do such children still profit from orthoptic and surgical treatment? PATIENTS AND METHODS: This was a retrospective study of the data from 13 patients, median age 4 years (range: 1 month to 12 years), with a mean follow-up of 4 years. Four changes to the red reflex were introduced. RESULTS: Surgery followed from two weeks to three years after starting occlusion therapy. Before therapy, the best visual acuity was 0.3 and the worst 0.06 (median 0.16). A median of four years after starting therapy, the visual acuity ranged from 0.9 to 0.4 (median 0.6). CONCLUSION: All milder cases profited from the treatment despite its late start. An earlier discovery would improve the prognosis. In any case, however, ophthalmologists should be encouraged to try patching before resorting to surgery.

Cataract↗

Complement activation in factor D-deficient mice.

To assess the contribution of the alternative pathway in complement activation and host defense and its possible role in the regulation of systemic energy balance in vivo, factor D-deficient mice were generated by gene targeting. The mutant mice have no apparent abnormality in development and their body weights are similar to those of factor D-sufficient littermates. Complement activation could not be initiated in the serum of deficient mice by the alternative pathway activators rabbit erythrocytes and zymosan. Surprisingly, injection of cobra venom factor (CVF) caused a profound and reproducible reduction in serum C3 levels, whereas, as expected, there was no C3 reduction in factor B-deficient mice treated similarly. Studies of C3 and factor B activation in vitro by CVF demonstrated that in factor D-deficient serum the alpha chain of C3 was cleaved gradually over a period of 60 min without detectable cleavage of factor B. CVF-dependent C3 cleavage in the deficient serum required the presence of Mg(2+), whereas in normal mouse serum the presence of divalent cations was not required. These results suggest that in mouse proteolytic cleavage of factor B by factor D is not an absolute requirement for the zymogen to active enzyme conformational transition of CVF-bound factor B. Kinetics of opsonization of Streptococcus pneumoniae by C3 fragments was much slower in factor D-deficient serum, suggesting a significant contribution of the alternative pathway to antibacterial host defense early after infection.

Animals↗

Slow, programmed maturation of the immunoglobulin HCDR3 repertoire during the third trimester of fetal life.

The mean distribution of lengths in the third complementarity-determining region of the heavy chain (HCDR3) serves as a measure of the development of the antibody repertoire during ontogeny. To determine the timing and pattern of HCDR3 length maturation during the third trimester of pregnancy, the mean distribution of HCDR3 lengths among variable-diversity-joining-constant-mu (VDJC(mu)) transcripts from the cord blood was analyzed from 138 infants of 23 to 40 weeks' gestation, including 3 sets of twins, 2 of which were of dizygotic origin. HCDR3 maturation begins at the start of the third trimester; follows a slow, continuous expansion over a 5-month period; and is unaffected by race or sex. The range and mean distribution of lengths may vary in dizygotic twins, indicating individual rates of development. The mean HCDR3 length distribution in 10 premature infants with documented bacterial sepsis was then followed for 2 to 12 weeks after their first positive blood culture. HCDR3 spectrotype analysis demonstrated oligoclonal B-cell activation and expansion after sepsis, but maturation of the repertoire was not accelerated even by the systemic exposure to external antigen represented by bacteremia. Antibody repertoire development appears to be endogenously controlled and adheres to an individualized developmental progression that probably contributes to the relative immaturity of the neonatal immune response.

Antibody Diversity↗

An immune defect causing dominant chronic mucocutaneous candidiasis and thyroid disease maps to chromosome 2p in a single family.

We describe a large family in which a combination of chronic mucocutaneous candidiasis (fungal infections of the skin, nails, and mucous membranes) and thyroid disease segregate as an autosomal dominant trait with reduced penetrance. The family includes (a) four members with both candidiasis and thyroid disease, (b) five members, including one pair of phenotype-concordant MZ twins, with candidiasis only, and (c) three members with thyroid disease only. A whole-genome scan using DNA samples from 20 members of the family identified a candidate linkage region on chromosome 2p. By sampling additional individuals and genotyping supplementary markers, we established linkage to a region of approximately 15 cM bounded by D2S367 and D2S2240 and including seven adjacent markers consistent with linkage. With a penetrance estimate of.8, which was based on pedigree and affected status, the peak two-point LOD score was 3.70 with marker D2S2328, and the peak three-point LOD score was 3.82. This is the first linkage assignment of a dominant locus for mucocutaneous candidiasis.

Adult↗

A genomewide screen in multiplex rheumatoid arthritis families suggests genetic overlap with other autoimmune diseases.

Rheumatoid arthritis (RA) is an autoimmune/inflammatory disorder with a complex genetic component. We report the first major genomewide screen of multiplex families with RA gathered in the United States. The North American Rheumatoid Arthritis Consortium, using well-defined clinical criteria, has collected 257 families containing 301 affected sibling pairs with RA. A genome screen for allele sharing was performed, using 379 microsatellite markers. A nonparametric analysis using SIBPAL confirmed linkage of the HLA locus to RA (P < .00005), with lambdaHLA = 1.79. However, the analysis also revealed a number of non-HLA loci on chromosomes 1 (D1S235), 4 (D4S1647), 12 (D12S373), 16 (D16S403), and 17 (D17S1301), with evidence for linkage at a significance level of P<.005. Analysis of X-linked markers using the MLOD method from ASPEX also suggests linkage to the telomeric marker DXS6807. Stratifying the families into white or seropositive subgroups revealed some additional markers that showed improvement in significance over the full data set. Several of the regions that showed evidence for nominal significance (P < .05) in our data set had previously been implicated in RA (D16S516 and D17S1301) or in other diseases of an autoimmune nature, including systemic lupus erythematosus (D1S235), inflammatory bowel disease (D4S1647, D5S1462, and D16S516), multiple sclerosis (D12S1052), and ankylosing spondylitis (D16S516). Therefore, genes in the HLA complex play a major role in RA susceptibility, but several other regions also contribute significantly to overall genetic risk.

Alleles↗

Frameless neuronavigation in intracranial endoscopic neurosurgery.

OBJECT: Frameless computerized neuronavigation has been increasingly used in intracranial endoscopic neurosurgery. However, clear indications for the application of neuronavigation in neuroendoscopy have not yet been defined. The purpose of this study was to determine in which intracranial neuroendoscopic procedures frameless neuronavigation is necessary and really beneficial compared with a free-hand endoscopic approach. METHODS: A frameless infrared-based computerized neuronavigation system was used in 44 patients who underwent intracranial endoscopic procedures, including 13 third ventriculostomies, nine aqueductoplasties, eight intraventricular tumor biopsy procedures or resections, six cystocistemostomies in arachnoid cysts, five colloid cyst removals, four septostomies in multiloculated hydrocephalus, four cystoventriculostomies in intraparenchymal cysts, two aqueductal stent placements, and fenestration of one pineal cyst and one cavum veli interpositi. All interventions were successfully accomplished. In all procedures, the navigational system guided the surgeons precisely to the target. Navigational tracking was helpful in entering small ventricles, in approaching the posterior third ventricle when the foramen of Monro was narrow, and in selecting the best approach to colloid cysts. Neuronavigation was essential in some cystic lesions lacking clear landmarks, such as intraparenchymal cysts or multiloculated hydrocephalus. Neuronavigation was not necessary in standard third ventriculostomies, tumor biopsy procedures, and large sylvian arachnoid cysts, or for approaching the posterior third ventricle when the foramen of Monro was enlarged. CONCLUSIONS: Frameless neuronavigation has proven to be accurate, reliable, and extremely useful in selected intracranial neuroendoscopic procedures. Image-guided neuroendoscopy improved the accuracy of the endoscopic approach and minimized brain trauma.

Adolescent↗

Treatment with nimodipine or mannitol reduces programmed cell death and infarct size following focal cerebral ischemia.

The present study was conducted to evaluate the effects of nimodipine and mannitol on infarct size and on the amount of apoptosis after transient focal cerebral ischemia. Focal cerebral ischemia was induced in male Sprague-Dawley rats (weight 300-380 g) by transient occlusion of the right middle cerebral artery (MCAO) using an intraluminal thread model. All animals underwent ischemia for 2 h, followed by 24 h of reperfusion. Group I (n=16) was untreated. Group II (n=16) received 15% mannitol (1 g/kg as bolus) and group III (n=9) received 15 microg/kg/h nimodipine intravenously beginning 15 min prior to MCAO. Twenty-four hours after reperfusion, the brain was taken and sectioned in coronal slices. The slices were stained with H&E and with the transferase dUTP nick-end labeling (TUNEL) technique. Histopathological analysis revealed a significant (P<0.05) decrease in infarct size in the striatum with both drugs: mannitol (group II) 25.4+/-5.9% and nimodipine (group III) 21.5+/-11.0% versus control (group I) 34.9+/-7.0% and in the cortex 2.7+/-2.0% (group II) and 6.3+/-2.4% (group III) versus control 14.4+/-9.0% (group I). The number of apoptotic cells was statistically lower in the therapy groups (group III 9.6, group II 25.8) versus control (group I 57.9) (Mann-Whitney-Wilcoxon U-test Z>1.96, P<0.05). This study indicates that mannitol and nimodipine provide neuroprotection by preventing both the necrotic and apoptotic components of cell death after transient focal cerebral ischemia and may be effective as neuroprotective drugs for cerebrovascular surgery.

Animals↗

[Neuro-navigation in the central area: impact on different surgical steps related to the location and various pathological processes].

The neurosurgical treatment of space occupying processes in the central area bears a relatively high risk of either postoperative neurological deficits ("radical approach") or of residual tumor ("conservative approach"). Therefore, special techniques of intraoperative topographic orientation (image-guided surgery) play an important role here. The possible impact of neuronavigation on different neurosurgical steps (craniotomy, corticotomy, localization of the process, definition of borders of resection) was studied in relation to the site of pathology (extraaxial, intraaxial/superficial, intraaxial/deep) in 46 patients harbouring space occupying lesions of the central area. In intraaxial pathologies, additional electrophysiological monitoring was done. It could be shown, that in cases of deep seated processes, neuronavigation had the greatest impact on craniotomy, corticotomy and localization of the process, whereas the borders of resection were defined predominantly on the basis of differences in colour or consistency. In extraaxial pathologies, neuronavigation was of significance only for craniotomy; in intraaxial processes visible at the surface, it had an impact on craniotomy and--in a few cases--on definition of resection borders. In neurosurgery of intraaxial pathologies of the central area (particularly those not visible at the surface), the use of neuronavigation (or another method of intraoperative localization) in combination with neurophysiologic monitoring is strongly recommended.

Aged↗

Cranial neuronavigation in neurosurgery: assessment of usefulness in relation to type and site of pathology in 284 patients.

OBJECTIVE: Neuronavigation improves intraoperative topographical orientation in neurosurgery. We wanted to better define the practical value of this technique in relation to the pathology operated on and the types of cranial surgery that profit the most from it. METHODS: Usefulness, interactive use and probably preventive effect of neuronavigation in cranial neurosurgery were assessed in a consecutive series of 284 patients on the basis of questionnaires with two- or five-point scale ratings by different neurosurgeons. RESULTS: Neuronavigation was most helpful in tumors of the hemispheres (particularly the central area) not visible at the cortical surface or resembling normal white matter, and in endoscopic procedures within small ventricles or cysts with non-translucent walls or when vision was blurred by cloudy CSF. In the same pathologies and surgical procedures, the device was interactively used, taking advantage of the specific possibilities of interactive image-guided neurosurgery. A probably preventive effect of neuronavigation was noted in operations in eloquent areas; highest scores were given for intraaxial tumors of the central region. The subjective assessments of usefulness, interactive use or preventive effect were not dependent on the involvement of the neurosurgeons in this study. CONCLUSION: We recommend this technique in resecting tumors in eloquent areas of the cortex or white matter, in approaching deep-seated processes not visible at the cortical surface, in defining borders of tumors resembling normal brain tissue, and in guiding endoscopes where ventricles are small or vision is blurred. This recommendation applies to any neurosurgeon familiar with the technique and managing neurosurgical cases requiring precise topographical orientation where normal anatomic landmarks are missing.

Adolescent↗

Early expression of iepsilon, CD23 (FcepsilonRII), IL-4Ralpha, and IgE in the human fetus.

BACKGROUND: A major predictor of childhood atopy is the concentration of IgE in the cord blood, but whether the source of cord blood IgE is maternal or fetal remains unclear. OBJECTIVE: We sought to determine the pattern of in situ IgE production during ontogeny. METHODS: Ninety-seven fetal, 142 natal, and 96 childhood samples were analyzed by using reverse transcription PCR for transcription of VDJCepsilon, Iepsilon, and CD23. Thirty-eight fetal liver samples were analyzed for the IL4RA genotype. RESULTS: IL-4Ralpha, CD23a, CD23b, and sterile Iepsilon transcripts were present as early as 8 weeks' gestation. VDJCepsilon transcripts were found in second-trimester fetal liver and third-trimester cord blood, although they were rare. VDJCepsilon transcripts were more common in the blood of children 9 months and older. Sequence analysis suggested that fetal VDJCepsilon was the product of selection. All fetal livers actively transcribing Iepsilon, VDJCepsilon, and IL-4Ralpha contained at least one copy of the atopy-associated IL4RA*A1902G polymorphism. CONCLUSION: The human fetus contains B cells that are primed to undergo IgE class switching from the earliest stages of ontogeny and can produce endogenous IgE by 20 weeks' gestation. However, IgE-producing cells are rare until 9 months after birth.

Adult↗

Analysis of aqueductal cerebrospinal fluid flow after endoscopic aqueductoplasty by using cine phase-contrast magnetic resonance imaging.

OBJECT: The purpose of this prospective study was to evaluate aqueductal cerebrospinal fluid (CSF) flow after endoscopic aqueductoplasty. In all patients, preoperative magnetic resonance (MR) imaging revealed hydrocephalus caused by aqueductal stenosis and lack of aqueductal CSF flow. METHODS: In 14 healthy volunteers and in eight patients with aqueductal stenosis who had undergone endoscopic aqueductoplasty, aqueductal CSF flow was investigated using cine cardiac-gated phase-contrast MR imaging. For qualitative evaluation of CSF flow, the authors used an in-plane phase-contrast sequence in the midsagittal plane. The MR images were displayed in a closed-loop cine format. Quantitative through-plane measurements were performed in the axial plane perpendicular to the aqueduct. Evaluation revealed no significant difference in aqueductal CSF flow between healthy volunteers and patients with regard to temporal parameters, CSF peak and mean velocities, mean flow, and stroke volume. All restored aqueducts have remained patent 7 to 31 months after surgery. CONCLUSIONS: Aqueductal CSF flow after endoscopic aqueductoplasty is similar to aqueductal CSF flow in healthy volunteers. The data indicate that endoscopic aqueductoplasty seems to restore physiological aqueductal CSF flow.

Adolescent↗

IgM heavy chain complementarity-determining region 3 diversity is constrained by genetic and somatic mechanisms until two months after birth.

Due to the greater range of lengths available to the third complementarity determining region of the heavy chain (HCDR3), the Ab repertoire of normal adults includes larger Ag binding site structures than those seen in first and second trimester fetal tissues. Transition to a steady state range of HCDR3 lengths is not complete until the infant reaches 2 mo of age. Fetal constraints on length begin with a genetic predilection for use of short DH (D7-27 or DQ52) gene segments and against use of long DH (e.g., D3 or DXP) and JH (JH6) gene segments in both fetal liver and fetal bone marrow. Further control of length is achieved through DH-specific limitations in N addition, with D7-27 DJ joins including extensive N addition and D3-containing DJ joins showing a paucity of N addition. DH-specific constraints on N addition are no longer apparent in adult bone marrow. Superimposed upon these genetic mechanisms to control length is a process of somatic selection that appears to ensure expression of a restricted range of HCDR3 lengths in both fetus and adult. B cells that express Abs of an "inappropriate" length appear to be eliminated when they first display IgM on their cell surface. Control of N addition appears aberrant in X-linked agammaglobulinemia, which may exacerbate the block in B cell development seen in this disease. Restriction of the fetal repertoire appears to be an active process, forcing limits on the diversity, and hence range of Ab specificities, available to the young.

Adult↗

Fatal subarachnoid hemorrhage after endoscopic third ventriculostomy. Case report.

In recent years, endoscopic third ventriculostomy has become a well-established procedure for the treatment of various forms of noncommunicating hydrocephalus. Endoscopic third ventriculostomy is considered to be an easy and safe procedure. Complications have rarely been reported in the literature. The authors present a case in which the patient suffered a fatal subarachnoid hemorrhage (SAH) after endoscopic third ventriculostomy. This 63-year-old man presented with confusion and drowsiness and was admitted in to the hospital in poor general condition. Computerized tomography scanning revealed an obstructive hydrocephalus caused by a tumor located in the cerebellopontine angle. An endoscopic third ventriculostomy was performed with the aid of a Fogarty balloon catheter. Some hours postoperatively, the patient became comatose. Computerized tomography scanning revealed a severe perimesencephalic-peripontine SAH and progressive hydrocephalus. Despite emergency external ventricular drainage, the patient died a few hours later. Although endoscopic third ventriculostomy is considered to be a simple and safe procedure, one should be aware that severe and sometimes fatal complications may occur. To avoid vascular injury, perforation of the floor of the third ventricle should be performed in the midline, halfway between the infundibular recess and the mamillary bodies, just behind the dorsum sellae.

Journal Article↗

Neuroendoscopic approach to intraventricular lesions.

Object. The purpose of this study was to determine the efficacy of endoscopic treatment in patients with intraventricular tumors. Methods. A series of 30 patients with endoscopically treated intraventricular lesions is reported. The lesions included seven colloid cysts, six astrocytomas, three subependymomas, two ependymomas, and one each of the following: pineoblastoma, pineocytoma/pineoblastoma (intermediate type), epidermoid cyst, pineal cyst, medulloblastoma, arteriovenous hemangioma, cavernoma, choroid plexus papilloma, pituitary adenoma, craniopharyngioma, melanoma, and germinoma. Total tumor resections, partial resections, biopsies, stent implantations, septostomies, and third ventriculostomies were performed. In two cases (two subependymomas > 2 cm in diameter), piecemeal endoscopic resection was ineffective because of the very firm consistency of the tumors. Therefore the endoscopic procedure was discontinued and the tumors were removed microsurgically. In the remaining cases the procedures were completed as planned. Even in the presence of difficulties such as poor orientation or significant bleeding, there was no need to abandon the endoscopic procedure. A total of 28 strictly endoscopic interventions were performed, in which the average duration was 85 minutes (range 35-170 minutes). All colloid cysts and the epidermoid lesion were completely evacuated and the capsules were widely resected. Total extirpation of solid tumors was achieved in five cases, whereas most astrocytomas were partially resected. The hydrocephalus-related symptoms resolved in all of the 22 patients with cerebrospinal fluid pathway obstruction. There were no endoscopy-related deaths. In two cases, major bleeding occurred and was controlled endoscopically. The authors observed one case of meningitis, one of mutism, two of memory loss attributed to forniceal injury, one of transient trochlear palsy after a biopsy specimen of an aqueductal tumor was obtained, and one of transient confusion after a biopsy specimen of a germinoma was obtained. Conclusions. In the authors' preliminary experience, the endoscopic approach was found to be safe and effective. In this series, it was possible to achieve relief of noncommunicating hydrocephalus, tumor resections, and even complete tumor removals by using endoscopic techniques. Based on the results, the authors believe that endoscopic techniques should be considered in the treatment of selected intraventricular lesions.

Journal Article↗

VH gene usage by family members affected with chronic lymphocytic leukaemia.

The excess risk of chronic lymphocytic leukaemia (CLL) in the first-degree relatives of affected patients suggests that familial CLL might constitute a useful model to study the pathogenesis of this disease, as has been demonstrated in numerous other neoplastic disorders. Previous studies have shown non-random utilization of immunoglobulin genes in CLL, some germline in sequence and others containing numerous somatic mutations. To investigate whether familial cases of CLL exhibit similarities in the composition of the B-cell receptor repertoire to the pattern expressed by CLL patients as a whole, we have studied 25 CLL patients belonging to 12 different families (four French and eight Italian), each of which contained at least two affected members. Among familial cases, VH gene segment utilization proved non-random and diverged from the frequencies previously reported among unrelated patients with CLL. Specifically, although the 4-34 and 5-51 gene segments were found repeatedly, the 1-69 and 4-39 gene segments were used sparingly and the 3-23 gene segment presented with increased frequency. Following the pattern detected in studies of unrelated patients, the single 1-69 expressing CLL contained an unmutated H chain sequence and included a long HCDR3 interval. In contrast, 3-23 containing H chains all used JH4, retained at most 93% homology with germline sequence, and included only short HCDR3 intervals. The vast majority of the CLL variable domains contained a high degree of somatic mutation and exhibited an excess of replacement mutations in the CDR intervals. These findings suggest that familial CLL cases may preferentially derive from B-cell progenitors that have responded to antigen.

Adult↗