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Biomedical subjects

K W To

Publications and source records attributed to K W To.

At least 19 recordsLinked to original sources
PubMed2006

Nasal CPAP reduces systemic blood pressure in patients with obstructive sleep apnoea and mild sleepiness.

BACKGROUND: A randomised controlled study was undertaken to examine the effect of nasal continuous positive airway pressure (CPAP) on 24 hour systemic blood pressure (BP) in patients with obstructive sleep apnoea (OSA). METHODS: Patients were fitted with an ambulatory BP measuring device as outpatients during normal activities and recorded for 24 hours before starting therapeutic or subtherapeutic (4 cm H(2)O) CPAP treatment. BP monitoring was repeated before completion of 12 weeks of treatment. The primary end point was the change in 24 hour mean BP. RESULTS: Twenty three of 28 participants in each treatment arm completed the study. There was no significant difference between the two groups in age, body mass index, Epworth Sleepiness Score, apnoea-hypopnoea index, arousal index, and minimum Sao(2). Twenty four patients were hypertensive. The pressure in the therapeutic CPAP group was 10.7 (0.4) cm H(2)O. CPAP usage was 5.1 (0.4) and 2.6 (0.4) hours/night for the therapeutic and subtherapeutic CPAP groups, respectively (p<0.001). After 12 weeks of treatment there were significant differences between the two CPAP groups in mean (SE) changes in 24 hour diastolic BP (-2.4 (1.2) v 1.1 (1.0) mm Hg (95% CI -6.6 to -0.5), p = 0.025); 24 hour mean BP (-2.5 (1.3) v 1.3 (1.1) mm Hg (95% CI -7.2 to -0.2), p = 0.037); sleep time systolic BP (-4.1 (2.1) v 2.2 (1.8) mm Hg (95% CI -11.8 to -0.7), p = 0.028); and sleep time mean BP (-3.6 (1.7) v 1.3 (1.4) mm Hg (95% CI -9.2 to -0.4), p = 0.033). CONCLUSIONS: Compared with subtherapeutic CPAP, 12 weeks of treatment with therapeutic CPAP leads to reductions in 24 hour mean and diastolic BP by 3.8 mm Hg and 3.5 mm Hg, respectively, in mildly sleepy patients with OSA.

Antihypertensive Agents↗
PubMed2005

Fatal interaction between clarithromycin and colchicine in patients with renal insufficiency: a retrospective study.

BACKGROUND: Clarithromycin is frequently used to treat community-acquired pneumonia in elderly persons. Like erythromycin, it may interact with other drugs by interfering with metabolism by cytochrome P450 enzymes and with the P-glycoprotein transporter system. Colchicine, used for treatment of acute gout and for prophylaxis, may cause bone marrow toxicity. It is metabolized by CYP3A4 and is transported by P-glycoprotein. Initial case reports suggested potentially fatal interactions between clarithromycin and colchicine. METHODS: A retrospective study was conducted with 116 patients who were prescribed clarithromycin and colchicine during the same clinical admission. Case-control comparisons were made between patients who received concomitant therapy with the 2 drugs and patients who received sequential therapy. We assessed the clinical presentations and outcomes of the 2 patient groups and analyzed the risk factors associated with fatal outcomes. RESULTS: Nine (10.2%) of the 88 patients who received the 2 drugs concomitantly died. Only 1 (3.6%) of the 28 patients who received the drugs sequentially died. Multivariate analysis of the 88 patients who received concomitant therapy showed that longer overlapped therapy (relative risk [RR], 2.16; 95% confidence interval [CI], 1.41-3.31; P< or =.01), the presence of baseline renal impairment (RR, 9.1; 95% CI, 1.75-47.06; P<.001), and the development of pancytopenia (RR, 23.4; 95% CI, 4.48-122.7; P<.001) were independently associated with death. CONCLUSIONS: Clarithromycin increases the risk of fatal colchicine toxicity, especially for patients with renal insufficiency. Since there are other drugs for treatment of pneumonia and gout, these 2 drugs should not be coprescribed, because of the risk of fatality.

Aged↗
PubMed2003

Alterations of RAS signalling in Chinese multiple myeloma patients: absent BRAF and rare RAS mutations, but frequent inactivation of RASSF1A by transcriptional silencing or expression of a non-functional variant transcript.

The methylation status, mutation and expression of RASSF1A, and mutations of RAS and BRAF were studied in 52 patients with multiple myeloma (MM), one plasma cell leukaemia (PCL) patient and four MM-derived cell lines. Aberrant methylation of RASSF1A was found in nine of 32 MM patients and in one of four MM cell lines (U266), where the associated loss of transcription was reversible by demethylation treatment. RASSF1A transcription was further investigated on anti-CD138-sorted plasma cell-enriched bone marrow samples from 10 MM, one PCL and three reactive plasmacytosis patients. While the wild-type RASSF1A transcript was detected in all three reactive plasmacytosis and the PCL samples, we found no detectable wild-type transcripts in six of 10 MM samples studied. In two MM samples, only the non-functional variant transcript was detected, whereas the other four showed loss of transcription. In great contrast to western data, RAS mutations were identified in only four of 31 (13%) MM patients. While no RASSF1A or BRAF mutation (V599E) was detected in any of the primary MM studied (n = 21), the latter was found in the U266 cell line. Taken together, these data indicate that alterations of RAS signalling are critical in MM pathogenesis. In our current studies of Chinese MM patients, these alterations involved frequent RASSF1A inactivation (60%) as a result of transcriptional silencing or expression of a non-functional variant transcript.

Adult↗
PubMed2001

Frequent death-associated protein kinase promoter hypermethylation in multiple myeloma.

UNLABELLED: Death-associated protein (DAP) kinase is a novel gene regulating apoptosis induced by IFN-gamma. In B-cell malignancies, loss of DAP kinase expression is commonly associated with promoter hypermethylation. These characteristics of DAP kinase may be of particular relevance in multiple myeloma (MM), a B-lineage malignancy in which prolonged survival capacity of the malignant plasma cells may be critical in the induction and maintenance of tumor cells. PURPOSE: The involvement and potential role of DAP kinase in MM pathogenesis was examined. EXPERIMENTAL DESIGN: In this investigation, methylation-specific PCR was conducted on primary MM and MM cell lines. Methylation status findings were correlated with clinical parameters. RESULTS: We first demonstrated frequent DAP kinase hypermethylation in 24 of 36 primary MMs (20 of 26 at diagnosis and 4 of 10 with relapse/residual MM after treatment), 1 of 2 patients with monoclonal gammopathy of undetermined significance, and 1 of 3 MM cell lines studied. The high frequency of DAP kinase hypermethylation was similarly observed in MM of different stages, immunoglobulin isotypes, and histological grades, with or without plasmacytomas. Although not statistically significant, the overall survival of patients with DAP kinase methylation was notably shortened among 23 MM patients followed prospectively (P = 0.38 by Kaplan-Meier method and log-rank test). This preliminary finding suggests prognostic implications of DAP kinase in MM that may deserve further investigation. CONCLUSIONS: Our data suggest an important role for DAP kinase in MM tumorigenesis.

Adult↗
PubMed1999

Comparison of the vascular relaxant effects of ATP-dependent K+ channel openers on aorta and pulmonary artery isolated from spontaneously hypertensive and Wistar-Kyoto rats.

The vasorelaxant actions of adenosine 5'-triphosphate (ATP)-dependent K+ channel openers and sodium nitroprusside in isolated thoracic aorta and pulmonary artery of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats (14-18 weeks old) were investigated. Cumulative addition of sodium nitroprusside and different ATP-dependent K+ channel openers (pinacidil, cromakalim, nicorandil, 2-(2"(1",3"-dioxolone)-2-methyl-4-(2'-oxo-1'-pyrrolidinyl)-6-nitro -2H-1-benzopyren (KR-30450) and aprikalim) to these preparations caused a concentration-dependent relaxation of noradrenaline-pre-contracted aorta and pulmonary artery from both strains. The relative order of relaxation potency, estimated by comparing the IC50, was sodium nitroprusside > KR-30450 > aprikalim > or = cromakalim > pinacidil > nicorandil in pulmonary artery and aorta from both strains. At high concentrations (> or =1 microM), cromakalim, aprikalim and KR-30450 produced a greater percentage relaxation in SHR aorta than in WKY aorta. However, there was no apparent difference between SHR and WKY in the relaxation response to all drugs tested on the pulmonary artery. The effects of cromakalim, aprikalim, pinacidil and KR-30450 observed in aorta and pulmonary artery were significantly attenuated by 3 microM glibenclamide. 6-Anilino-5,8-quinolinequinone (LY 83583, 1 microM), a soluble guanylate cyclase inhibitor, abolished the vasorelaxant effects of nicorandil and sodium nitroprusside. In conclusion, sodium nitroprusside and ATP-dependent K+ channel openers cause relaxation of noradrenaline-pre-contracted aorta and pulmonary artery from both strains. However, all the drugs tested failed to cause selective relaxation of the pulmonary artery relative to the thoracic aorta.

Adenosine Triphosphate↗
PubMed1998

Histopathologic and immunohistochemical study of an autopsy eye with X-linked cone degeneration.

We performed a histopathologic and immunohistochemical study of eyes obtained at autopsy of an 84-year-old man from a family with X-linked cone degeneration in which affected members have a 6.5-kilobase deletion in the red cone pigment gene. At his most recent ocular examination, at age 71 years, this patient had had a visual acuity of 20/200 OU, fundus changes suggestive of macular degeneration, borderline-normal full-field rod electroretinograms, and profoundly reduced full-field cone electroretinograms. Histopathologic examination demonstrated marked loss of cone and rod photoreceptors and the retinal pigment epithelium in the central macula. The peripheral cone population was reduced, while the peripheral rod population was relatively preserved. Immunohistochemical examination with an antibody to both red and green cone opsin and an antibody to blue cone opsin disclosed a prominent loss of the red and green cone population and preservation of the blue cone population. These findings show that a defect in the red cone pigment gene can result in extensive degeneration of the red and green cone population across the retina.

Aged↗
PubMed1998

Comparison of the effects of enucleation and orbital reconstruction using free-fat grafts, dermis grafts, and porous polyethylene implants in infant rabbits.

Twenty-nine infant rabbits from four litters were randomly assigned to three groups. No surgery was performed on left eyes. All right eyes were enucleated. Group 1, the control group, had no right-socket reconstruction. Group 2 had reconstruction using free-fat and dermis grafts. Group 3 had reconstruction using porous polyethylene implants. On attaining adult size, rabbits were killed, decapitated, and prepared for measurements. Orbital volume measurements were performed twice and orbital entrance areas were determined once. No significant differences were noted between first and second measurements of orbital volumes. Right orbital volumes were significantly smaller than left orbits in all groups except for the second measurement of the polyethylene implant group. Right orbital entrance areas were significantly smaller than left areas in the control and the free-fat and dermis graft groups. Right orbital entrance areas of the polyethylene group were not significantly smaller than the corresponding left orbital entrance areas. The use of free-fat and dermis grafts for orbital reconstruction in anophthalmic infant rabbits did not significantly stimulate orbital bone growth. In one trial, the polyethylene implant group displayed right orbital volumes and orbital entrance areas that were not significantly smaller than controls.

Adipose Tissue↗
PubMed1996

Clinical and histopathologic findings in clumped pigmentary retinal degeneration.

OBJECTIVE: To describe the clinical and histopathologic features of clumped pigmentary retinal degeneration (CPRD). DESIGN: Retrospective case series. SETTING: Tertiary referral center. PATIENTS: Twenty-four patients, aged 7 to 83 years, were identified from the medical record filed of the Berman-Gund Laboratory, Boston, Mass, as having the clinical features of CPRD. The autopsy eye from a 56-year-old man with CPRD was studied with light and electron microscopy. MAIN OUTCOME MEASURES: Visual acuities, visual fields, dark-adaptation thresholds, and results of electroretinograms; histopathologic study of an autopsy eye. RESULTS: The functional deficit of patients with CPRD seems to be similar to that of patients with typical retinitis pigmentosa. Different degrees of severity were observed among patients of similar age. The histopathologic data showed that the clinically distinct areas of clumped pigment are due to excessive accumulation of melanin granules in retinal pigment epithelial cells. CONCLUSION: Based on the distinct clinical and histopathologic appearance, CPRD should be considered as a separate form of retinal degeneration.

Adolescent↗
PubMed1994

Association and chance occurrence of aniridia and retinoblastoma.

PURPOSE/METHODS: A 9-month-old infant had inherited aniridia and unilateral retinoblastoma. Family history disclosed three generations of aniridia; yet there were no instances of retinoblastoma. The coincidental occurrence of retinoblastoma and aniridia is rare. RESULTS/CONCLUSIONS: With DNA probes from within the retinoblastoma gene, we were able to determine that a retinoblastoma-predisposing mutation was not inherited with aniridia in this family. The occurrence of these two diseases in the same individual therefore represents a chance event.

Aniridia↗
PubMed1994

Group B streptococcal metastatic endophthalmitis.

Reports of invasive Group B Streptococcus infection in adults with underlying medical conditions have been increasing. Ocular infection with this organism is unusual. Metastatic endophthalmitis in adults caused by this organism has been reported rarely and has only been associated with endocarditis. We encountered two cases of Group B streptococcal metastatic endophthalmitis in adults who did not have endocarditis. These cases reflect the increasing incidence of invasive Group B Streptococcus infection with its varying manifestations. Additionally, they emphasize the importance of considering this pathogen as a cause of metastatic endophthalmitis in adults with predisposing illnesses.

Bacteremia↗
PubMed1993

Olivopontocerebellar atrophy with retinal degeneration. An electroretinographic and histopathologic investigation.

BACKGROUND: Olivopontocerebellar atrophy is an uncommon disorder with variable clinical manifestations that affects the cerebellum, the spinocerebellar tracts, and other structures of the brainstem. A deficiency of glutamate dehydrogenase, which results in an excess of glutamate, has been suggested to play a role in the pathogenesis of olivopontocerebellar atrophy. In experimental animals, toxic levels of glutamate are known to cause a selective loss of the b-wave on electroretinographic (ERG) testing and a degeneration of the inner retinal layers. One of the subtypes of olivopontocerebellar atrophy, type II, according to Harding's classification, is associated with retinal degeneration. METHODS: The authors describe the ophthalmologic and ERG findings in a family with olivopontocerebellar atrophy type II. Histopathologic study of an eye from a 6-year-old family member who died of severe neurologic deterioration secondary to olivopontocerebellar atrophy type II was performed. RESULTS: Electroretinographic changes may be present in affected family members who are entirely asymptomatic and have a normal ophthalmologic evaluation. The changes on the ERG in one patient suggest that cone dysfunction is one of the subtle changes that may be seen in olivopontocerebellar atrophy type II. Our ERG results did not show a selective loss of the b-wave but instead showed a loss of both the a-wave and b-wave in affected family members. Results of light and electron microscopic examination showed diffuse and extensive degeneration of the photoreceptors involving both rods and cones, the most prominent changes being present in the macula. An amorphous debris, presumably degenerated photoreceptors, was noted between the outer nuclear layer and retinal pigment epithelium. CONCLUSION: Patients with olivopontocerebellar atrophy type II have photoreceptor abnormalities as revealed in abnormal ERGs seen in many patients and histopathologic study of an autopsy eye from an affected 6-year-old boy. Our results do not support the hypothesis that glutamate toxicity may be responsible for the development of retinal degeneration in this condition.

Adult↗
PubMed1991

Ophthalmologic complications in hemoglobinopathies.

The various forms of sickle cell disease share the common feature of an abnormal globin chain that, under certain conditions such as hypoxia, results in the sickling of red blood cells and obstruction of blood vessels. The ophthalmic manifestations of sickle cell disease are present in various segments of the eye, which include the conjunctiva, iris, retina, and optic nerve. Patients with SC disease and SB thalassemia tend to have more severe ophthalmic complications than their counterparts with the more severe systemic form of sickle cell disease--SS disease. It is important for patients with sickle cell disease to have periodic examinations by ophthalmologists, because the early identification of peripheral retinal disease can be adequately treated, with preservation of vision. Without treatment, peripheral retinal changes can lead to retinal detachments and vitreous hemorrhages, which account for the majority of visual impairment in patients with sickle cell disease.

Anemia, Sickle Cell↗
PubMed1991

Bilateral optic disc neovascularization in association with retinitis pigmentosa.

Bilateral neovascularization of the optic disc developed in a 16-year-old Hispanic girl with retinitis pigmentosa. The neovascularization regressed in both eyes over 1 year without treatment. Ocular and systemic evaluation failed to reveal a recognized cause for the neovascularization. To our knowledge this is only the third case reported of this unusual association.

Adolescent↗