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At least 199 records · Page 11Linked to original sources
PubMed1995

Fetal telemedicine: interactive transfer of realtime ultrasound and video via ISDN for remote consultation.

Current referral practice for ultrasonically detected fetal abnormalities contributes to parental anxiety, inconvenience to patients, diagnostic inaccuracy, and general service inefficiency. To determine whether telemedicine would reduce these disadvantages, we established a 30-channel ISDN link between a district general hospital on an island and a subspecialty referral centre approximately 120 km away on mainland Britain. Live ultrasound images of the fetus were transmitted in realtime from a commercial scanner in the hospital using a total data transfer rate of 2 Mbit/s. After decompression at the receiving end, there was almost no perceptible loss of picture quality or frame rate. This report describes the technical aspects of the link and our preliminary experience with it. In the first two months of its operation, the link worked well and the consultants who used it found themselves confidently making diagnoses and carrying out counselling over it. If confirmed, the success of this technology has implications for future referral practice in fetal medicine.

Artifacts↗
PubMed2001

Excitation of T-phases by seafloor scattering.

T-phases excited by suboceanic earthquakes are classified into two types: abyssal phases which are excited near the earthquake epicenter at seafloor depths far below the SOFAR velocity channel, and slope T-phases which are excited at continental, or ocean island slopes and ridges at distances up to several hundreds of kilometers from the epicenter. In this article, it is demonstrated that approximate time-frequency characteristics of both classes of T-phase can be synthesized under the assumption that T-phases are excited by scattering from a rough seafloor. Seafloor scattering at shallow depths preferentially excites low order acoustic modes that propagate efficiently within the ocean sound channel minimum. At greater depths, scattering excites higher order modes which interact weakly with the seafloor along much of the propagation path. Using known variations in near-source bathymetry, T-phase envelopes are synthesized at several frequencies for several events south of the Fox Islands that excited both types of T-phase. The synthesized T-phases reproduce the main time vs frequency features of each type of arrival; a higher frequency, nearly symmetric arrival excited near the epicenter and a longer duration, lower frequency arrival excited near the continental shelf, with a peak amplitude at about 5 Hz.

Journal Article↗
PubMed1997

Methylation of discrete regions of the O6-methylguanine DNA methyltransferase (MGMT) CpG island is associated with heterochromatinization of the MGMT transcription start site and silencing of the gene.

O6-Methylguanine DNA methyltransferase (MGMT) repairs the mutagenic and cytotoxic O6-alkylguanine lesions produced by environmental carcinogens and the chemotherapeutic nitrosoureas. As such, MGMT-mediated repair of O6-alkylguanine lesions constitutes a major form of resistance to nitrosourea chemotherapy and makes control of MGMT expression of clinical interest. The variability of expression in cell lines and tissues, along with the ease with which the MGMT phenotype reverts under various conditions, suggests that MGMT is under epigenetic control. One such epigenetic mechanism, 5-methylation of cytosines, has been linked to MGMT expression. We have used an isogenic human multiple myeloma tumor cell line model composed of an MGMT-positive parent cell line, RPMI 8226/S, and its MGMT-negative variant, termed 8226/V, to study the control of MGMT expression. The loss of MGMT activity in 8226/V was found to be due to the loss of detectable MGMT gene expression. Bisulfite sequencing of the MGMT CpG island promoter revealed large increases in the levels of CpG methylation within discrete regions of the 8226/V MGMT CpG island compared to those in 8226/S. These changes in CpG methylation are associated with local heterochromatinization of the 8226/V MGMT transcription start site and provide a likely mechanism for the loss of MGMT transcription in 8226/V.

Calcium Channel Blockers↗
PubMed1994

A gene from the Xp22.3 region shares homology with voltage-gated chloride channels.

In the framework of constructing a comprehensive transcript map of the human Xp22.3 region, we identified an evolutionary conserved CpG island and cloned the corresponding gene. The predicted 760 amino acid protein encoded by this gene contains 12 hydrophobic domains and shares significant sequence and structural similarities with all the previously isolated members of a recently identified family of voltage-gated chloride channels (the 'CIC family'). This gene, termed CICN4 (Chloride Channel 4), contains at least 10 exons spanning 60 to 80 kb on the X chromosome. In contrast to most genes isolated from the human Xp22.3 region, the CICN4 gene does not share homology with the Y chromosome and it is conserved in mouse and hamster. Expression studies revealed the presence of a 7.5 kb transcript which is particularly abundant in skeletal muscle and is also detectable in brain and heart. These data suggest that we have identified a new voltage-gated chloride channel which is encoded by a gene located in the distal short arm of the X chromosome.

Amino Acid Sequence↗
PubMed1999

Barrels and septa: separate circuits in rat barrels field cortex.

The neural circuitry within sensory cortex determines its functional properties, and different solutions have evolved for integrating the activity that arises from an array of sensory inputs to cortex. In rodent, circumscribed receptors, such as whiskers, are represented in somatic sensory (S-I) cortex in islands of cells in layer IV called "barrels" surrounded by narrow channels that separate barrels called "septa." These two cortical domains were previously shown to receive sensory inputs through parallel subcortical pathways. Here, by using small biocytin injections, we demonstrate that distinct intrinsic and corticocortical circuitries arise from barrel and septal columns. The intracortical S-I projections originating from barrel columns are rather short-ranged, terminating for the most part within the far boundaries of the most immediate neighboring barrel columns, whereas corticocortical projections reach the second somatosensory (S-II) cortex. In contrast, the intrinsic projections arising from septal columns extend two to three barrels' distance along the row of whisker representation, producing terminals preferentially in other septal columns. Septal corticocortical projections terminate in the dysgranular cortex anterior to E-row barrels and in the posteromedial parietal cortex in addition to S-II. Whereas layer IV barrels are largely isolated from lateral connections, septa are the main conduits of intracortical projections arising from neighboring barrel and septal columns. These results indicate that the two subcortical pathways from whiskers to cortex continue as two distinct partially segregated pathways in cortex.

Animals↗
PubMed1980

Populations of methane-producing bacteria and in vitro methanogenesis in salt marsh and estuarine sediments.

Most probable numbers (MPNs) of methanogens in various salt marsh and estuarine sediments were determined with an anaerobic, habitat-simulating culture medium with 80% H(2) plus 20% CO(2) as substrate. Average MPNs for the short Spartina (SS) marsh sediments of Sapelo Island, Ga., were maximal at the 5- to 7-cm depth (1.2 x 10/g of dry sediment). Populations decreased to approximately 880/g of dry sediment at the 34- to 36-cm depth. There was no significant difference between summer and winter populations. In tall Spartina (TS) marsh sediments, average populations were maximal (1.2 x 10/g of dry sediment) in the upper 0- to 2-cm zone; populations from the 5- to 36-cm zones were similar (average of 9 x 10/g of dry sediment). Methanogenic populations for TS sediments of James Island Creek marsh, Charleston, S.C., were similar (average of 3 x 10/g of dry sediment) for all depths tested (0 to 22 cm), which was comparable to the trend observed for TS sediments at Sapelo Island, Ga. Sediment grab samples collected along a transect of James Island Creek and its adjacent Spartina marsh had MPNs that were approximately 20 times greater for the region of Spartina growth (average of 10/g of dry sediment) compared with the channel (approximately 5 x 10 methanogens per g of dry sediment). A similar trend was found at Pawley's Island marsh, S.C., but populations were approximately one order of magnitude lower. In vitro rates of methanogenesis with SS sediments incubated under 80% H(2)-20% CO(2) showed that the 5- to 7-cm region exhibited maximal activity (51 nmol of CH(4) g h), which was greater than rates for sediments above and below this depth. SS sediment samples (5 to 7 cm) incubated under 100% N(2) and supplemented with formate exhibited rates of methanogenesis similar to those generated by samples under 80% H(2)-20% CO(2). Replacing the N(2) atmosphere with H(2) resulted in an eightfold decrease in the rate of methanogenesis. In vitro methanogenic activity by TS salt marsh sediments, incubated under 80% H(2)-20% CO(2), was similar for all depths tested (0 to 22 cm). TS sediment samples (0 to 7 cm) supplemented with formate and incubated under 100% N(2) had greater rates of methanogenesis compared with unsupplemented samples.

Journal Article↗
PubMed2002

DNA methylation and environmental exposures in human hepatocellular carcinoma.

BACKGROUND: Hypermethylation of a CpG-rich promoter (CpG island) blocks expression of the corresponding gene. The CpG island methylator phenotype (CIMP), defined as a variable pattern of hypermethylation of CpG islands in tumor suppressor genes, may be associated with carcinogenesis. To determine whether CIMP is associated with the development of hepatocellular carcinoma (HCC) and with exposure to environmental agents, we examined the methylation status of CpG islands in HCCs from countries with various HCC risks. METHODS: We examined the methylation status of 12 CpG islands (eight for known genes) in 85 HCC tumors from various geographic locations by use of bisulfite-polymerase chain reaction methylation assays and analyzed results with univariate and multivariable methods. All statistical tests were two-sided. RESULTS: Eight CpG islands were hypermethylated. The frequency of hypermethylation in the 85 tumors was 62% for the estrogen receptor (ER), 42% for p16, 18% for cyclooxygenase-2, 21% for the T-type calcium channel gene, 38% for MINT31, 28% for MINT1, 15% for MINT27, and 11% for MINT2 (the latter four CpG islands are not yet associated with genes). Methylation levels of the eight frequently methylated CpG islands were positively correlated (from R =.2 [P =.05] to R =.6 [P<.001]), supporting the presence of CIMP. p16 methylation had statistically significant geographic variation (34.4% in tumors from China and Egypt versus 12.2% in tumors from the United States and Europe, difference = 22.2%; 95% confidence interval [CI] = 11.2% to 33.2%; P<.001). Similar geographic variations were observed for ER methylation and CIMP. This observation was partly related to higher methylation in tumors from patients with cirrhosis (33.6% for patients with cirrhosis versus 11.7% for those without it; difference = 21.9%; 95% CI = 10.9% to 32.8%; P<.001) or hepatitis (34.2% for patients with hepatitis versus 6.2% for those without it; difference = 28%; 95% CI = 18.3% to 37.6%; P<.001). CONCLUSION: Geographic variations in the methylation status of various CpG islands indicate that environmental factors may influence the frequent and concordant degree of hypermethylation in multiple genes in HCC tumors.

Aflatoxins↗
PubMed1977

Response to polychlorinated biphenyls of marine phytoplankton isolates cultured under natural conditions.

Polychlorinated biphenyls (PCB) at a concentration of 10 mug/liter substantially but temporarily suppressed the growth rate and photosynthesis of two species of Thalassiosira recently isolated from Long Island Sound and grown in dialysis membrane bags suspended in the tidal channel of an estuarine marsh. Inhibition of carbon fixation was apparently due to reduced levels of chlorophyll a per PCB-treated cell, but no significant loss of function per unit of existing chlorophyll a was observed. Cell concentrations in all size classes (3.2- to 18.6-mum-equivalent spherical diameters) were markedly lower in PCB-treated cultures, with toal biomass equaling only 30% of that in control cultures throughout the experiment.

Aroclors↗
PubMed1998

[Sinusoidal hemangioma].

INTRODUCTION: Sinusoidal hemangioma (SH) was described by two pathologists, Calonje and Fletcher, in 1991. This uncommon cutaneous benign vascular lesions with distinctive histologic features was considered a subset of lesions known as "cavernous hemangiomas". It is made of dilated interconnecting ("sinusoidal"), thin-walled channels with a single-layered lining endothelium and a lobular architecture. PATIENTS AND METHODS: Clinical, radiological (CT, MRI and arteriography), evolutive, and histologic data of 4 patients, whose lesions appeared very similar clinically and histologically, were reviewed and compared to the patterns of the so-called SH. RESULTS: There were 2 males and 2 females. Lesions had an infantile onset in 3 (congenital in 2). They exhibited a protracted course over years in the 4, and they all invaded the right forehead, eyelids and orbit areas. Clinically, they appeared as multilobulated, building, firm tumors under a normal shiny skin. Radiologically, lesions were strikingly nodular, with criteria of slow-flow vascular lesions on MRI and arteriograms. Histologically, all lesions were comprised of well-circumscribed nodules with a lobulated architecture, made of greatly dilated, blood-filled, thin-walled vascular channels, with scanty fibrous stroma between them. Interconnecting channels had the distinctive sinusoidal pattern. There were some elongated pseudopapillary structures. Islands of spindle cells were noted in 2 lesions. DISCUSSION: On the one hand histologic features of the lesions in our 4 patients are identical to those described by Calonje and Fletcher as SH, a lesion not to be confused with classic, involuting-type, hemangioma of infancy and childhood, and with venous or lymphatic malformations of the same location. SH fits into the group of lesions defined by pathologists as "cavenous hemangiomas". On the other hand the lesions in our 4 patients differed from the clinical description of SH as a solitary acquired small (less than 3 cm) nodule in adults. Otherwise the four lesions described herein constitute a distinctive clinicopathologic entity with a striking aggressive local growth although there is a histologic malformative pattern. The presence in 2 cases of islands of spindle cells led us to discuss the differences with spindle cell hemangioendothelioma.

Adolescent↗
PubMed1995

Membrane properties of the granule cells of the islands of Calleja of the rat studied in vitro.

1. Using patch-clamp techniques, we have studied granule neurones from the islands of Calleja in vitro: as isolated cells or as groups of varying numbers following enzymic digestion, or within untreated slices of approximately 100 microns thickness. 2. Recordings were made with patch pipettes in conventional or nystatin-perforated whole-cell mode. Current-clamp recordings indicated that these granule cells are excitable and at resting potential produce irregular spontaneous activity. In voltage clamp the transient inward current underlying these action potentials could be evoked. This current had a threshold for activation of about -50 mV and was sensitive to TTX. In some cells a TTX-resistant transient inward current was observed with a threshold for activation of about -70 mV. 3. Island of Calleja granule cells also exhibited outward currents. A rapidly activating transient current was observed that was resistant to TEA and sensitive to 4-AP, and therefore resembled IA. The current was half-maximally activated at -6 mV and steady-state inactivation was half-complete at -65 mV. 4. More sustained outward currents were also observed. Although some cells appeared to express a Ca(2+)-activated K+ current, the most common finding was a rapidly activating, slowly inactivating, voltage-dependent K+ current that was sensitive to TEA and Ba2+. This current resembled M-current more than delayed rectifier but displayed a number of idiosyncratic kinetic properties. Chief amongst these was the accumulation of an inactivating process when the current was repeatedly evoked from potentials near the cells' resting value by voltage steps that by themselves produced no observable inactivation during the voltage command; this behaviour was similar to the 'C-terminal' inactivation exhibited by lymphocytes and certain expressed K+ channel clones (Kv1.3). 5. These results indicate that the granule cells of the islands of Calleja are excitable and contain a number of additional regulatory conductances. The implications of these findings in, and the usefulness of this preparation to, the elucidation of the function(s) of the islands of Calleja are discussed.

Animals↗
PubMed1998

Evidence for enhancement of gap junctional coupling between rat island of Calleja granule cells in vitro by the activation of dopamine D3 receptors.

1. Using patch-clamp techniques, we have studied actions of dopamine and related compounds on granule neurones within the islands of Calleja in vitro, in slices if approximately 200 microns thickness or as groups of varying cell number following enzymic digestion. 2. Prior to agonist application, island of Calleja granule cells displayed spontaneous stepwise shifts in whole-cell conductance ranging from 104 to 632 pS. The reversal potentials of these conductance changes ranged widely and matched the distribution of the cells' membrane potentials. Reversal potentials and membrane potentials shifted equally when cells were uniformly depolarized in 24 mM external K+. 3. Bath-applied dopamine elicited, after a delay of 4-9 min, an exaggerated form of the spontaneous behaviour that frequently gave way to a sudden large (up to thirtyfold) conductance change. At concentrations of 100-300 nM, a range of agonists with increasing affinity for the D3 receptor (apomorphine, quinpirole, 7-OH DPAT and PD 128907) triggered the response. The actions were neither mimicked by SKF-38393 nor antagonized by SCH-23390 (a selective D1 agonist and antagonist, respectively). Haloperidol reversibly blocked responses elicited by the D3/D2 agonist quinpirole. The action of effective agonists was maintained when transmitter release was abolished. Given the reported lack of D2 receptors in the islands of Calleja, these findings indicate a direct action of dopamine at the D3 receptor. 4. The dopaminergic effects were not affected by Gd3+ or substantial replacement of external Na+ with TEA, Tris or choline, eliminating stretch-activated channels but suggesting that if transmembrane channels were to be involved in this dopaminergic action they posseses a non-selective permeability to large cations. The reported presence of gap junctions in the islands of Calleja offers the explanation that these effects derive from enhanced activity of such channels or their hemi-constituents. 5. In testing the possible involvement of gap junctional coupling the following experimental observations were made: (i) alkalinization of slices mimicked the effect of D3 agonists; (ii) in cell groups, recording from pairs provided evidence of intercellular coupling, and mechanical separation of recorded neurones from neighbouring cells during the agonist-evoked response caused shutdown of the additional conductance; (iii) when applied to slices, the gap junctional blocker, 18 alpha-glycyrrhetinic acid, whilst not preventing the full-blown dopamine response, significantly reduced both the variance of recorded granule cell input conductance and the cells' apparent capacitance. 6. Taken together the results indicate a D3 action in granule cells, which is best explained by a dopaminergic promotion of intercellular coupling. The physiological relevance of such a mechanism is discussed.

Animals↗
PubMed1989

Vascular adrenal cysts. A clinicopathologic and immunohistochemical study of endothelial and hemorrhagic (pseudocystic) variants.

Three endothelial cysts and five hemorrhagic cysts (pseudocysts) arose in the adrenal glands of seven patients aged 23-73 years. Four patients were male and three were female. Five were symptomatic and gave abdominal pain as their chief complaint. Endothelial cysts were collapsed or filled with serous fluid, multiloculated, had an endothelial lining, and often contained adrenal cortex in their outer walls. The endothelial lining reacted only weakly for Factor VIII-related antigen (FVII-RAg), but it stained strongly for collagen type IV (C-IV). The lack of hemorrhage and the FVIII-RAg/C-IV staining pattern in endothelial cysts suggest lymphatic differentiation. Hemorrhagic cysts were spherical, firm masses containing clotted blood and hyalinized thrombus with attenuated adrenal cortex in the outer fibrous wall. Islands of intact cortical cells were present deep within the thrombi of four hemorrhagic cysts. Three of five hemorrhagic cysts stained strongly for FVIII-RAg and C-IV in irregular vascular channels of the attenuated cortex and within the cyst contents. These channels suggest that at least some hemorrhagic cysts arise when hemorrhage occurs in a preexisting blood vascular anomaly. Entrapment of cortical islands by extravasated blood in hemorrhagic cysts may be misdiagnosed as necrotic cortical neoplasm. To avoid confusion, one must recognize the normality of the entrapped cortical cells, identify an intrinsic vascular anomaly, and distinguish thrombus from necrotic tumor.

Adrenal Gland Diseases↗
PubMed2002

Aberrant CpG island methylation in cancer cell lines arises in the primary cancers from which they were derived.

A higher prevalence of epigenetic inactivation of tumor suppressor genes has been reported in cancer cell line populations compared to primary cancer populations. Cancer-related genes are commonly methylated in cancer cell lines but it is not known the extent to which tumor suppressor genes may be artificially methylated in vitro. We therefore examined 10 pancreatic cancer cell lines and corresponding primary tumors for aberrant DNA methylation of promoter CpG islands of eight genes and seven CpG islands. Using methylation-specific PCR (MSP), methylation was not detected at any of the 15 CpG islands in 15 normal pancreata or in an immortalized normal pancreatic duct epithelial (HPDE) cell line. Of 150 loci examined, 49 loci were methylated in both primary carcinomas and their corresponding cell lines, 95 loci were not methylated in either cell lines or their corresponding primary carcinomas. There were four loci methylated only in cell lines while another two loci were methylated only in primary carcinomas. Overall, the methylation status of primary carcinomas and their cell lines were concordant in 96% of cases (144 of 150) (J statistic; J=0.92, P<0.0001). We conclude that most of the DNA methylation of tumor suppressor genes observed in cancer cell lines is present in the primary carcinomas from which they were derived.

Adenocarcinoma↗
PubMed2004

The marketing of menthol cigarettes in the United States: populations, messages, and channels.

This commentary looks at the marketing menthol cigarettes to various targeted populations--women, middle school youth and Asian/Pacific Islander immigrants as well as African Americans. The authors take the position that "ethnic awareness" as evidenced in the advertising of menthol cigarette brands to African Americans is just one of four distinct messages that tobacco marketers have used for what they have termed the "coolness" category. The other messages are: healthy/medicinal; fresh/refreshing/cool/clean/crisp; and youthfulness/silliness and fun. The commentary poses three questions: (a) Are new population segments being steered toward menthol cigarettes using marketing approaches that are similar to what has occurred with African Americans and women? (b) What exactly is the relationship between the marketing of menthol cigarettes and subsequent use of menthol tobacco products by specific population subgroups? (c) Are there lessons to be learned from the marketing of menthol cigarettes that can be used to improve the public health and medical communities' smoking cessation and tobacco use prevention communications efforts?

Adolescent↗
PubMed2003

Genetic unmasking of epigenetically silenced tumor suppressor genes in colon cancer cells deficient in DNA methyltransferases.

Hypermethylation associated silencing of the CpG islands of tumor suppressor genes is a common hallmark of human cancer. Here we report a functional search for hypermethylated CpG islands using the colorectal cancer cell line HCT-116, in which two major DNA methyltransferases, DNMT1 and DNMT3b, have been genetically disrupted (DKO cells). Using two molecular screenings for differentially methylated loci [differential methylation hybridization (DMH) and amplification of inter-methylated sites (AIMS)], we found that DKO cells, but not the single DNMT1 or DNMT3b knockouts, have a massive loss of hypermethylated CpG islands that induces the re-activation of the contiguous genes. We have characterized a substantial number of these CpG island associated genes with potentially important roles in tumorigenesis, such as the cadherin member FAT, or the homeobox genes LMX-1 and DUX-4. For other genes whose role in transformation has not been characterized, such as the calcium channel alpha1I or the thromboxane A2 receptor, their re-introduction in DKO cells inhibited colony formation. Thus, our results demonstrate the role of DNMT1 and DNMT3b in CpG island methylation associated silencing and the usefulness of genetic disruption strategies in searching for new hypermethylated loci.

Cadherins↗
PubMed2002

Multigene family isoform profiling from blood cell lineages.

BACKGROUND: Analysis of cell-selective gene expression for families of proteins of therapeutic interest is crucial when deducing the influence of genes upon complex traits and disease susceptibility. Presently, there is no convenient tool for examining isoform-selective expression for large gene families. A multigene isoform profiling strategy was developed and used to investigate the inwardly rectifying K+ (Kir) channel family in human leukocytes. Comprised of seven subfamilies, Kir channels have important roles in setting the resting membrane potential in excitable and non-excitable cells. RESULTS: Gene sequence alignment allowed determination of "islands" of amino acid homology, and sub-family "centred" priming permitted simultaneous co-amplification of each family member. Validation and cross-priming analysis was performed against a panel of cognate Kir channel clones. Radiolabelling and diagnostic restriction digestion of pooled PCR products enabled determination of distinct Kir gene expression profiles in pure populations of human neutrophils, eosinophils and lung mast cells, with conservation of Kir2.0 isoforms amongst the leukocyte subsets. We also identified a Kir2.0 channel product, which may potentially represent a novel family member. CONCLUSIONS: We have developed a novel, rapid and flexible strategy for the determination of gene family isoform composition in any cell type with the additional capacity to detect hitherto unidentified family members and verified its application in a study of Kir channel isoform expression in human leukocytes.

Journal Article↗
PubMed1995

Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium.

The vascular endothelial growth factor (VEGF) and its high-affinity binding receptors, the tyrosine kinases Flt-1 and Flk-1, are thought to be important for the development of embryonic vasculature. Here we report that Flt-1 is essential for the organization of embryonic vasculature, but is not essential for endothelial cell differentiation. Mouse embryos homozygous for a targeted mutation in the flt-1 locus, flt-1lcz, formed endothelial cells in both embryonic and extra-embryonic regions, but assembled these cells into abnormal vascular channels and died in utero at mid-somite stages. At earlier stages, the blood islands of flt-1lcz homozygotes were abnormal, with angioblasts in the interior as well as on the periphery. We suggest that the Flt-1 signalling pathway may regulate normal endothelial cell-cell or cell-matrix interactions during vascular development.

Animals↗
PubMed1980

[Experiences with surgery of the trachea. An analysis of 135 cases (author's transl)].

The different surgical approaches for the correction of tracheal stenosis are analysed in 135 patients who were treated by us during the past 15 years. Poor results were associated with dilatation alone. Tracheomalacia was successfully managed in 51% of the patients by using Schobel's technique of acrylic plastic frames, while sleeve resections succeeded in nearly 90% of the cases (particularly when absorbable suture material was used and the patient was given cortisone for six weeks postoperatively). The staged open "channel" technique described by Rethi (1959, 1967) was also used, and was modified by an island flap method. We have used this one-stage method during the past three years, and have been able to reduce the time needed for treatment from nearly one year to 110 days. In so doing, the average number of operations for one patient could be decreased from 4.25 to 1.27, while the success rate for surgery increased from 73 to 92%.

Age Factors↗