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Biomedical subjects

G Mohr

Publications and source records attributed to G Mohr.

At least 19 recordsLinked to original sources
PubMed2005

Management of intra-operative cerebrospinal fluid leak in transnasal transsphenoidal pituitary microsurgery: use of post-operative lumbar drain and sellar reconstruction without fat packing.

BACKGROUND: This study aims at describing primary reconstruction of sella turcica using lyophilized dura graft and fibrin glue without fat packing of the sphenoid sinus, together with postoperative lumbar drain in the management of intraoperative cerebrospinal fluid (CSF) leak. METHOD: Records of 127 consecutive patients undergoing 129 transnasal transsphenoidal procedures were reviewed retrospectively with respect to intra- and post-operative CSF leak and lumbar drain use. One hundred and ten patients had adenomas (60 secreting adenomas, 48 non-functioning), 10 Rathke's cleft cysts and 9 miscellaneous lesions. FINDINGS: Intra-operative leak was detected in 43 (33.3%) of 129 procedures: 38 (34.5%) of 110 adenoma related procedures and 5 (26.3%) of 19 non-adenomas. Among adenomas, leak occurred in 35 (41.2%) of 85 patients with suprasellar extension (SSE) and in 3 (12%) of 25 without SSE (p = 0.007). Lumbar drain was used in 61 cases (47.3%): in 34 it was inserted immediately before and in 27 at the end of procedure. In 24 of 34 patients (70.6%) with pre-operative drain (all adenomas), saline infusion was used to mobilize SSE. Only 2 patients (1.6%) developed post-operative leak, requiring an endoscopic procedure with fascia and muscle obliteration of the sphenoid sinus. CONCLUSIONS: Meticulous duroplasty and routine postoperative lumbar drain has shown satisfactory results in dealing with intra-operative CSF leaks. It compares favorably with other techniques and obviates the need for fat harvesting. In patients with SSE, where leak occurs more frequently, we recommend inserting the lumbar drain before the procedure. As an adjunctive benefit, this allows for the saline-infusion method to mobilize the SSE without producing the venous engorgement of the Valsalva maneuver.

Adolescent↗
PubMed2004

Critical appraisal of the International Subarachnoid Aneurysm Trial (ISAT).

The results of the International Subarachnoid Aneurysm Trial (ISAT) drew attention from both scientific and lay press, impacting the management of aneurysm patients significantly. In this review, the ISAT report was analyzed critically and the available literature was scrutinized stratifying the common criticisms as to the weak aspects of this study. The aim of ISAT was to compare the safety and efficacy of endovascular coiling with neurosurgical clipping for aneurysms, which were suitable for both treatments. The results showed a 22.5% relative and 6.9% absolute risk reduction at one year in the disability outcome of patients who were treated with coiling. However, long-term risk of re-bleeding from the treated aneurysms and the risk of repeat procedures was higher in this group also. Lack of angiographic data following the initial treatment and long-term follow-up represents one of the main flaws of this study. The outcome assessment scale, biases regarding patient selection and center participation criteria were further issues of criticism. The results of ISAT are not sufficient to provide a definitive answer as to the superiority of endovascular treatment over microsurgery, although coiling appears to produce less peri-procedural morbidity in a selected group of patients. An optimum outcome assessment should include a universally accepted scale and a detailed long-term angiographic outcome.

Cerebral Angiography↗
PubMed2001

In vitro evidence for homologous recombinational repair in resistance to melphalan.

BACKGROUND: The generation of DNA interstrand cross-links is thought to be important in the cytotoxicity of nitrogen mustard alkylating agents, such as melphalan, which have antitumor activity. Cell lines with mutations in recombinational repair pathways are hypersensitive to nitrogen mustards. Thus, resistance to melphalan may require accelerated DNA repair by either recombinational repair mechanisms involving Rad51-related proteins (including x-ray repair cross-complementing proteins Xrcc2, Xrcc3, and Rad52) or by nonhomologous endjoining involving DNA-dependent protein kinase (DNA-PK) and Ku proteins. We investigated the role of DNA repair in melphalan resistance in epithelial tumor cell lines. METHODS: Melphalan cytotoxicity was determined in 14 epithelial tumor cell lines by use of the sulforhodamine assay. Homologous recombinational repair involving Rad51-related proteins was investigated by determining the levels of Rad51, Rad52, and Xrcc3 proteins and the density of nuclear melphalan-induced Rad51 foci, which represent sites of homologous recombinational repair. Nonhomologous endjoining was investigated by determining the levels of Ku70 and Ku86 proteins and DNA-PK activity. Linear regression analysis was used to analyze correlations between the various protein levels, DNA-PK activity, or Rad51 foci formation and melphalan cytotoxicity. All statistical tests were two-sided. RESULTS: Melphalan resistance was correlated with Xrcc3 levels (r =.587; P =.027) and the density of melphalan-induced Rad51 foci (r =.848; P =.008). We found no correlation between melphalan resistance and Rad51, Rad52, or Ku protein levels or DNA-PK activity. CONCLUSION: Correlations of melphalan resistance in epithelial tumor cell lines with Xrcc3 protein levels and melphalan-induced Rad51 foci density suggest that homologous recombinational repair is involved in resistance to this nitrogen mustard.

Antigens, Nuclear↗
PubMed2001

Heritability of the timing of autumn migration in a natural bird population.

In recent decades, global temperature has increased at an unprecedented rate. This has been causing rapid environmental shifts that have altered the selective regimes determining the annual organization of birds. In order to assess the potential for adaptive evolution in the timing of autumn migration, we estimated heritabilities of the onset of migratory activity in a southern German blackcap (Sylvia atricapilla) population. Heritabilities (h2=0.34-0.45) and coefficients of additive genetic variation (CV(A)=4.7-5.7) were significant and consistent when estimated by different methods, irrespective of whether they were derived from birds hatched in the wild or bred in captivity. In an artificial selection experiment, we selected for later onset of migratory activity, simulating expected natural selection on this trait. We obtained a significant delay in the mean onset of migratory activity by more than one week after two generations of selection. Realized heritability (h2=0.55) was in agreement with expected heritability in the cohort that the selection line was derived from. Our results suggest that evolutionary changes in the timing of autumn migration may take place over a very short time period and will most probably be unconstrained by the lack of additive genetic variation.

Acclimatization↗
PubMed2001

Function of the Neurospora crassa mitochondrial tyrosyl-tRNA synthetase in RNA splicing. Role of the idiosyncratic N-terminal extension and different modes of interaction with different group I introns.

The Neurospora crassa mitochondrial tyrosyl-tRNA synthetase (CYT-18 protein) promotes the splicing of group I introns by helping the intron RNA fold into the catalytically active structure. The regions required for splicing include an idiosyncratic N-terminal extension, the nucleotide-binding fold domain, and the C-terminal RNA-binding domain. Here, we show that the idiosyncratic N-terminal region is in fact comprised of two functionally distinct parts: an upstream region consisting predominantly of a predicted amphipathic alpha-helix (H0), which is absent from bacterial tyrosyl-tRNA synthetases (TyrRSs), and a downstream region, which contains predicted alpha-helices H1 and H2, corresponding to features in the X-ray crystal structure of the Bacillus stearothermophilus TyrRS. Bacterial genetic assays with libraries of CYT-18 mutants having random mutations in the N-terminal region identified functionally important amino acid residues and supported the predicted structures of the H0 and H1 alpha-helices. The function of N and C-terminal domains of CYT-18 was investigated by detailed biochemical analysis of deletion mutants. The results confirmed that the N-terminal extension is required only for splicing activity, but surprisingly, at least in the case of the N. crassa mitochondrial (mt) large ribosomal subunit (LSU) intron, it appears to act primarily by stabilizing the structure of another region that interacts directly with the intron RNA. The H1/H2 region is required for splicing activity and TyrRS activity with the N. crassa mt tRNA(Tyr), but not for TyrRS activity with Escherichia coli tRNA(Tyr), implying a somewhat different mode of recognition of the two tyrosyl-tRNAs. Finally, a CYT-18 mutant lacking the N-terminal H0 region is totally defective in binding or splicing the N. crassa ND1 intron, but retains substantial residual activity with the mt LSU intron, and conversely, a CYT-18 mutant lacking the C-terminal RNA-binding domain is totally defective in binding or splicing the mt LSU intron, but retains substantial residual activity with the ND1 intron. These findings lead to the surprising conclusion that CYT-18 promotes splicing via different sets of interactions with different group I introns. We suggest that these different modes of promoting splicing evolved from an initial interaction based on the recognition of conserved tRNA-like structural features of the group I intron catalytic core.

Adenosine Monophosphate↗
PubMed2001

'Shed' furin: mapping of the cleavage determinants and identification of its C-terminus.

The human endoprotease furin is involved in the proteolytic maturation of the precursor molecules of a wide variety of bioactive proteins. Despite its localization in the membranes of the trans-Golgi system by means of a transmembrane domain, it has repeatedly been reported to form a C-terminally truncated, naturally secreted form referred to as 'shed' furin. In order to identify the cleavage site, internal deletion mutants of increasing size, N-terminal to Leu(708), and subsequently individual amino acid substitutions were introduced, and Arg(683) was identified as the prime determinant for shedding. MS analysis determined Ser(682) as the C-terminus of shed furin, suggesting that monobasic cleavage may occur N-terminal to Arg(683). Alteration of Arg(683) directs the shedding mechanism to alternative cleaving sites previously unused.

Amino Acid Sequence↗
PubMed2001

Rathke's cleft cyst presenting as sphenoid sinusitis.

Rathke's cleft cysts are developmental abnormalities of the craniopharyngeal duct composed of retained stratified ciliated cuboidal cells of the respiratory type. Incidentally found in the pars intermedia in 13% to 33% of routine autopsies, they are discovered in growing numbers on CT and MRI scans. From 1991 to 1999, 9 cases of Rathke's cleft cysts were encountered by the senior authors, 4 of which were treated surgically (3 by using a transsphenoidal approach and one by using a transcranial subfrontal approach). Of the 3 patients treated with a transsphenoidal approach, 2 presented with symptoms mimicking sphenoid sinusitis and were initially referred for otolaryngologic evaluation. The clinical, pathologic, and radiologic features, as well as management and follow-up of those 2 patients, are reviewed. There has been only one previous case report of Rathke's cleft cysts presenting as sinusitis. Nevertheless, the otolaryngologist should be aware of this condition because it may present with other significant symptomatic extracranial extensions.

Adult↗
PubMed2001

Mycotic aneurysm of the carotid bifurcation in the neck: case report and review of the literature.

OBJECTIVE AND IMPORTANCE: Mycotic aneurysms of the extracranial carotid artery are rare and difficult to diagnose. A search of the world literature published since 1966 reveals at least six cases of mycotic carotid aneurysms due to a Salmonella septicemia. We present an exceptional case of mycotic pseudoaneurysm of the bifurcation of the carotid artery due to Salmonella septicemia and discuss the pathogenesis as well as various aspects of the diagnosis and surgical management. CLINICAL PRESENTATION: A 68-year-old man presented in Poland with Salmonella sepsis; 1 month later, he was admitted to the emergency department of the Sir Mortimer B. Davis-Jewish General Hospital in Montreal with a bulky and pulsatile right cervical mass. An angiogram and a computed tomographic scan revealed a voluminous and partially thrombosed aneurysm the size of a tangerine originating from the posterior aspect of the carotid junction. INTERVENTION: Balloon trapping was attempted at the Montreal Neurological Hospital. Subsequently, the patient developed a significant neurological deficit, which was quickly reversed by the administration of hypertensive, hypervolemic, and hemodilution therapy. Thereafter, the pseudoaneurysm was resected surgically, and the internal and external carotid arteries were sacrificed. Pathological examination of the excised specimen of the carotid junction revealed a pseudoaneurysm. Bacterial culture of the lesion showed growth of Salmonella. CONCLUSION: The postoperative course was satisfactory except for laryngeal paralysis due to involvement of the vagus nerve. Four months later, a computed tomographic scan showed only small lacunae in both centra semiovale.

Aged↗
PubMed2001

Hearing preservation in acoustic neuroma surgery.

This article reviews the Montreal experience of hearing preservation in acoustic neuroma surgery. The medical records since 1995 of 36 patients who underwent acoustic neuroma extirpation with the intent to preserve hearing were examined. Intraoperative monitoring was conducted using auditory brainstem response measurement with electrocochleography via a transtympanic electrode. The role of intraoperative monitoring in guiding surgical technique and its correlation with postoperative hearing outcome are discussed. A review of the literature regarding hearing preservation in acoustic neuroma surgery is included.

Adult↗
PubMed2001

Both extraneuronal monoamine transporter and O(6)-methylguanine-DNA methyltransferase expression influence the antitumor efficacy of 2-chloroethyl-3-sarcosinamide- 1-nitrosourea in human tumor xenografts.

We previously have found that 2-chloroethyl-3-sarcosinamide-1-nitrosourea (SarCNU) is a selective cytotoxin that enters cells via the extraneuronal transporter for monoamine transmitters (EMT). Both in vitro and in vivo studies demonstrated that SarCNU was more effective than BCNU against human gliomas. To clarify whether EMT expression correlates with antitumor efficacy of SarCNU, we determined human EMT (EMTh) and O(6)-methylguanine-DNA methyltransferase (MGMT) expression in nine human xenograft models using semiquantitative reverse-transcription polymerase chain reaction. These results were compared with the antitumor effects of SarCNU and the standard chloroethylnitrosourea antitumor agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). There was no significant correlation between EMTh expression and antitumor efficacy of SarCNU or BCNU. Also, there was no significant correlation between MGMT expression and SarCNU efficacy. However, a significant correlation was found between MGMT expression and BCNU antitumor efficacy. Interestingly, multiple regression analysis demonstrated a significant correlation between SarCNU efficacy and EMTh plus MGMT expression, whereas there was no correlation between BCNU efficacy and MGMT plus EMTh expression. Thus, the absence of a linear correlation between SarCNU efficacy and EMTh expression appears to be due, at least in part, to the presence of DNA repair, specifically, MGMT, in these xenograft models. These studies suggest that MGMT expression alone correlates with BCNU activity, whereas both EMTh and MGMT expression are important determinants of SarCNU activity against human tumor xenograft models. SarCNU is in clinical trials and these results may have important clinical implications.

Animals↗
PubMed2000

Rules for DNA target-site recognition by a lactococcal group II intron enable retargeting of the intron to specific DNA sequences.

Group II intron homing occurs primarily by a mechanism in which the intron RNA reverse splices into a DNA target site and is then reverse transcribed by the intron-encoded protein. The DNA target site is recognized by an RNP complex containing the intron-encoded protein and the excised intron RNA. Here, we analyzed DNA target-site requirements for the Lactococcus lactis Ll.LtrB group II intron in vitro and in vivo. Our results suggest a model similar to yeast mtDNA introns, in which the intron-encoded protein first recognizes a small number of nucleotide residues in double-stranded DNA and causes DNA unwinding, enabling the intron RNA to base-pair with the DNA for reverse splicing. Antisense-strand cleavage requires additional interactions between the protein and 3' exon. Key nucleotide residues are recognized directly by the intron-encoded protein independent of sequence context, and there is a stringent requirement for fixed spacing between target site elements recognized by the protein and RNA components of the endonuclease. Experiments with DNA substrates containing GC-clamps or "bubbles" indicate a requirement for DNA unwinding in the 3' exon but not the distal 5' exon region. Finally, by applying the target-site recognition rules, we show that the L1.LtrB intron can be modified to insert at new sites in a plasmid-borne thyA gene in Escherichia coli. This strategy should be generally applicable to retargeting group II introns and to delivering foreign sequences to specific sites in heterologous genomes.

Base Pairing↗
PubMed2000

High dose tamoxifen and radiotherapy in patients with glioblastoma multiforme: a phase IB study.

PURPOSE: To assess the feasibility and the toxicity of adjuvant high dose tamoxifen (TAM) and postoperative brain irradiation for patients with newly-diagnosed glioblastoma multiforme (GBM). MATERIAL AND METHODS: Twelve patients with histopathologically confirmed GBM entered the study. There were nine males and three females, with median age of 48.8 years (range 30-75 years). Karnofsky performance status (KPS) was 60-70% for four patients and 80-100% for eight patients. Based on the Radiation Therapy Oncology Group recursive partition analysis, there were three class III patients, six class IV, one class V, and two class VI. Eleven patients underwent partial surgical tumor resection and one patient had a near complete resection. Two weeks post surgery, the patients were started on high dose TAM (120 mg/m2 P.O. BID for three months). Two weeks from date of starting TAM, external beam radiotherapy (RT) was given at a dose of 59.4 Gy/33 qd fractions/6.5 weeks. Patients were assessed weekly for toxicity during treatment. Imaging studies were done at the end of two weeks of TAM, then monthly. RESULTS: Median follow-up was 40 weeks (range 22-84 weeks). In one patient, TAM was associated with significant vomiting, necessitating the TAM dose to be decreased at three weeks and then stopped at two months. One other patient had bilateral deep venous thrombosis after 52 weeks on TAM, although the relationship to TAM was not firmly established. There were no radiological responses after two weeks of TAM or at the end of RT. The median time to progression was 17.7 weeks (range 5.1-43.8 weeks). Median survival time was 33.4 weeks (range 10-79.7). Actuarial survival at 48 and 74 weeks was 40% and 15%, respectively. CONCLUSION: Our study shows that adjuvant high dose TAM is feasible and relatively well-tolerated. Furthermore, the combined use of high dose TAM and RT postoperatively was not associated with any significant increase in radiation-induced neurological toxicity. However, high dose TAM does not appear to improve treatment results.

Adult↗
PubMed1999

The various MRI patterns of pituitary apoplexy.

The aim of this study was to describe the various MRI features, in correlation to surgical and pathological findings, in patients who presented with pituitary apoplexy (PA). Eleven patients presenting with PA, were evaluated with various MR protocols including spin-echo (SE) T1-weighted sequences in 9 of 11 patients, post gadolinium SE T1-weighted sequences in only 8 of 11 patients, and with T2-weighted SE sequences in 2 of 11 patients. All patients had transsphenoidal pituitary surgery after MR studies. The severity of presenting symptoms ranged from headaches to coma. Ten patients had pituitary macroadenoma; one had a non-hemorrhagic metastatic lesion into a non-adenomatous pituitary gland. Of the 11 patients, one was studied at the acute stage of PA (1 day after onset), 9 at the subacute period (3-15 days after onset), and one at the late stage (5 months after onset). Images compatible with intratumoral hemorrhage were found in all macroadenomas, whereas the metastatic pituitary lesion did not show evidence of bleeding. All gadolinium-enhanced studies showed partial tumoral enhancement. The SE T2-weighted studies demonstrated areas of low and high signal intensities in keeping with the presence of blood degradation contents. Pituitary apoplexy present with different MR features, including hemorrhagic and non-hemorrhagic characteristics on T1-weighted images. Gadolinium-enhanced images do not provide complementary diagnostic information when the presence of blood is assessed on plain images.

Adult↗
PubMed1999

Acceleration of ageing-related gliopathic changes and hippocampal dysfunction following intracerebroventricular infusion of cysteamine in adult rats.

The sulphydryl agent, cysteamine, accelerates the ageing-related accumulation of peroxidase-positive (iron-rich) cytoplasmic inclusions in rat subcortical astroglia and induces their appearance in primary neuroglial cultures. In the present study, infusion of cysteamine into the lateral ventricle of young, adult rats (1 mg/day for three weeks followed by a one-month drug "washout" period) significantly increased numbers of peroxidase-positive astrocytic granules in the stratum oriens of the CA1 hippocampus relative to saline-infused controls. In contrast to the gliopathic changes, no evidence of neuronal or myelin damage was observed in the cysteamine-exposed rats. The cysteamine-treated animals exhibited significant impairment in spatial learning as determined using a three-panel runway task. The working memory deficits were more robust at the end of the drug washout period than immediately following cessation of the cysteamine infusion. Thus, the cysteamine-related memory deficits are of long duration and are not due to any acute neuroactive properties of the drug itself. Using hippocampal slices prepared after the drug washout period, we observed attenuated paired-pulse depression, with no significant effects on basal excitatory synaptic transmission or induction of long-term potentiation, in the cysteamine-infused animals relative to controls. We propose that, in cysteamine-treated rats and in the course of normal ageing, hippocampal dysfunction and associated cognitive deficits may be secondary to fundamental pathological processes originating within the astroglial compartment.

Aging↗