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Biomedical subjects

M F Chan

Publications and source records attributed to M F Chan.

54 records · Page 3Linked to original sources
PubMed1994

Studies on the ocular hypotensive effects of prostaglandin F2 alpha ester prodrugs and receptor selective prostaglandin analogs.

The use of natural prostaglandins (PG), such as PGD2, PGE2, PGF2 alpha, and PGI2, for treating glaucoma is limited by their ocular side effects. One approach to achieve the required separation of ocular hypotensive activity from side effects is to employ ester prodrugs. From a novel series of 11- and 15-mono and 11,15-diacyl esters of PGF2 alpha we identified prodrugs where PGF2 alpha formation rates in the iris-ciliary body exceeded those in the conjunctiva, sclera, and corneal endothelium. Compared to PGF2 alpha-1-isopropyl ester the ocular tissue hydrolysis rates of the 11-monopivaloyl, the 11,15-dipivaloyl ester and the 1,11-lactone were up to 1000 fold less. Despite this large disparity in hydrolysis rates, the pivaloyl esters and the 1,11-lactone were potent ocular hypotensives in our animal models. In studying prostaglandin analogs, we found that a diverse variety of prostanoid receptor selective agonists lowered intraocular pressure in dogs and/or monkeys. These included DP-, EP1-, EP2-, EP3-, and FP-receptor selective compounds. These findings were surprising and prompted us to re-examine the receptor selectivity of these agonists by radioligand binding studies. Using radiolabelled PGE2, 17-phenyl PGF2 alpha, and sulprostone we were able to confirm the selectivity of the agonists currently used for receptor characterization directly by radioligand binding competition studies. It appears that multiple prostanoid receptor subtypes may be involved in regulating intraocular pressure.

3T3 Cells↗
PubMed1994

Studies on a novel series of acyl ester prodrugs of prostaglandin F2 alpha.

A novel series of prostaglandin F2 alpha (PGF2 alpha) prodrugs, with acyl ester groups at the 9, 11, and 15 positions, was prepared in order to design clinically acceptable prostaglandins for treating glaucoma. Studies involving isolated esterases and ocular tissue homogenates indicated that 9-acyl esters cannot provide a prodrug since PGF2 alpha would not be formed as a product. In contrast, 11-mono, 15-mono, and 11, 15-diesters were converted to PGF2 alpha in ocular tissues and could, therefore, be considered as prodrugs of PGF2 alpha. Carboxylesterase (CE) appeared critically important for the hydrolytic conversion of those PGF2 alpha prodrugs where the 11 or 15-OH group was esterified and such prodrugs were not substrates for acetylcholinesterase (ACHE) or butyrylcholinesterase (BuCHE). The enzymatic hydrolysis of PGF2 alpha-1-isopropyl ester was also investigated for comparative purposes. This PGF2 alpha prodrug was a good substrate for CE, but was also hydrolysed by BuCHE, albeit at a much slower rate. The most striking feature of the enzymatic hydrolysis of PGF2 alpha-1-isopropyl ester in ocular tissue homogenates was that it was much faster than for prodrugs esterified at the 11 and/or 15 positions. In terms of ocular hypotensive activity, all prodrugs which showed detectable conversion to nascent PGF2 alpha were potent ocular hypotensives. Although no separation of ocular hypotensive and ocular surface hyperaemic effects was apparent for PGF2 alpha-1-isopropyl ester, a temporal separation of these effects was apparent for the novel PGF2 alpha ester series. This difference may reflect an unfavourably rapid conversion of PGF2 alpha-1-isopropyl ester in ocular surface tissues compared with anterior segment tissues.

3T3 Cells↗
PubMed1993

Octreotide therapy for variceal hemorrhage.

Somatostatin and its analogue, octreotide, produce dramatic decreases in splanchnic arterial blood flow and portal venous pressure while preserving cardiac output and systemic blood pressure. A limited number of prospective randomized clinical trials of somatostatin and octreotide have noted superiority to placebo and equivalence to vasopressin in control of variceal hemorrhage. Moreover, several studies (Saari et al., Kravetz et al., McKee et al.) have reported a significant decrease in morbid side effects when somatostatin or octreotide is used to control variceal bleed. In addition, McKee et al. noted a significant reduction in mortality when octreotide was compared to balloon tamponade therapy for variceal hemorrhage. Somatostatin and octreotide are particularly advantageous in controlling vigorous variceal hemorrhage in hemodynamically unstable patients. This control often enables other effective therapy, endoscopic sclerotherapy and surgical (or radiologic) shunting, to be safely performed.

Animals↗
PubMed1993

Marginal sealing ability of four restorative materials placed in root surfaces.

The sealing ability of four restorative materials, placed in root surface cavities, was assessed by a range of standard in vitro microleakage tests. The rank order of the severity of microleakage associated with the four materials varied with the different tests. Although differences between the performance of unlined amalgam, two different dentine-bonded composites and a glass-ionomer restorative material were detected, most were not statistically significant. None of the materials tested completely eliminated microleakage and so even those materials reported to be adhesive to dentine cannot be considered ideal in the restoration of root surface cavities.

Composite Resins↗
PubMed1992

A comparison of four in vitro marginal leakage tests applied to root surface restorations.

Marginal leakage associated with a variety of restorative materials, placed in root surface cavities of extracted teeth, was assessed by immersing the teeth in either acidified gelatin, eosin dye, silver nitrate or a solution of radiocalcium. The allocation of a score, dependent on the depth of tracer penetration at the interface, allowed comparisons to be made between the leakage tests employed. The rank order of the four leakage tests was generally consistent. Eosin resulted in the most severe leakage, followed by silver nitrate and radiocalcium, whilst acidified gelatin was the least sensitive method for demonstrating marginal leakage. Differences in leakage scores were not, however, always statistically significant. None of the four tests investigated was ideal, although eosin dye was considered to be the most appropriate method of demonstrating marginal leakage associated with root restorations.

Calcium Radioisotopes↗
PubMed1991

Detection and identification of endogenous small molecules in ocular tissues by proton nuclear magnetic resonance spectroscopy.

Proton nuclear magnetic resonance (nmr) spectra of rabbit ocular tissue homogenates (corneal epithelium, conjunctiva and iris ciliary body) and aqueous humor have been recorded for the first time by incorporation of a spin-spin relaxation reagent and use of the CPMG pulse sequence. A number of endogenous species such as lactate, glucose, alanine and valine have been observed in these ocular homogenates and significant differences have been noted in the distribution of these small molecules in the ocular tissues studied. This technique has been used to study the hydrolysis of acetylcholine by ocular esterases in the iris ciliary body.

Amino Acids↗
PubMed1990

Prejunctional adrenoceptor activity of N-0437: a relatively selective DA2 dopamine receptor agonist.

Prejunctional adrenoceptor activity of N-0437, 2[N-n-propyl-N-2-(thienylethyl-amino)-5-hydroxytetralin], was investigated by means of the cat nictitating membrane (CNM) preparation. Intra-arterial (i.a.) administration of N-0437 produced a dose-related inhibition (ED50 = 14 micrograms) of the CNM contractions elicited by electrical stimulation of pre- and postganglionic sympathetic nerves of the superior cervical ganglion. Pretreatment with domperidone i.a., a relatively selective DA2 receptor antagonist, markedly attenuated the CNM response to racemic N-0437 (ED50 = 6.7 x 10(2) micrograms). However, pretreatment with rauwolscine i.a., a relatively selective alpha 2-receptor antagonist, did not alter the CNM responses to racemic N-0437. Evaluation of the (R)-(+) and (S)-(-) enantiomers showed that only the (S)-(-) enantiomer was active in suppressing the contractions in the CNM preparation. These results demonstrate that N-0437 is a potent agonist for prejunctional DA2 dopamine receptors on peripheral sympathetic nerves in the CNM and that these peripheral DA2 receptors appear to be enantioselective.

Animals↗
PubMed1987

Ocular effects of a N,N-disubstituted 5-OH aminotetralin (N-0437): evidence for a dual mechanism of action.

The selective DA2 agonist, N-0437, produced an acute reduction in intraocular pressure (IOP) and pupil diameter (PD) when applied topically to the eyes of normal monkeys. Ocular hypotension and miosis were primarily unilateral in nature, dose-related and lasted 3 to 5 hours following drug instillation. In normal monkeys, 24 to 48 hours following drug administration, a secondary chronic (greater than 24 hrs) reduction in pressure was observed. Once-a-day topical administration of N-0437 (250 micrograms), to normal monkeys, for 4 days produced a chronic unilateral reduction in IOP that persisted for 18 days. Associated with this reduction in pressure on day 2 through 6 were miosis and ptosis of the treated eye. Although topical administration did not lower IOP in rabbits, intracameral injection of N-0437 significantly depressed IOP for 3 days when compared to control injected eyes. Evaluation of ocular sympathetic innervation in N-0437 treated rabbits indicated that these fibers were not functional. In rabbits, intracameral administration of the active (S,-) and inactive (R,+) enantiomer of N-0437 produced equivalent reductions in pressure. These data provide further support for the hypothesis that DA2 receptor agonists can produce acute reductions in IOP. In addition, N-0437 appears to have a second non-receptor mediated mechanism of action that produces a chronic reduction in IOP. This chronic reduction in pressure appears, in part, to result from an interruption of ocular sympathetic nerves function.

Administration, Topical↗
PubMedDate not supplied

Zinc levels and infections in hospitalized patients with AIDS.

Impaired cellular and humoral immunity and phagocytic function have been attributed to zinc deficiency. This study examined the association between low serum zinc concentration and opportunistic infections in hospitalized patients with the acquired immune deficiency syndrome (AIDS). We examined the records from all 505 inpatient consultations performed by our Nutrition Service from May 1992 through June 1994. The medical records from all 228 patients with AIDS with known serum zinc levels (determined by atomic absorption spectrophotometry) were reviewed. The length of HIV seropositivity, most recent CD4 count, presence of diarrhea, and degree of malnutrition were noted. The principal diagnosis accounting for the admission was grouped according to the type of infection: Pneumocystis carinii pneumonia (PCP), viral, fungal, bacterial, and other. Sixty-seven patients (29%) had abnormally low serum zinc levels (LSZ < 55 micrograms/dL), 49 patients (21%) had borderline low serum zinc (BSZ > or = 55 and < or = 65 microgram/dL), and 112 (49%) patients had normal serum zinc levels (NSZ > 65 micrograms/dL). There was no significant difference among the groups in CD4 count, length of HIV seropositivity, presence of diarrhea, or severity of malnutrition. Patients with zinc deficiency (LSZ) had a significantly higher incidence of bacterial infection than did patients with normal zinc. Patients with borderline zinc levels had an intermediate incidence of bacterial infection. There were no significant differences among the three groups in the incidence of PCP, viral, or fungal infections. Severe zinc deficiency was noted in 29% and borderline levels in an additional 21% of hospitalized AIDS patients. A low zinc level was not associated with the length of HIV seropositivity, CD4 count, or degree of malnutrition. Hypozincemia was associated with an increased incidence of concomitant systemic bacterial infections.

AIDS-Related Opportunistic Infections↗
PubMedDate not supplied

Steatorrhea: a common manifestation in patients with HIV/AIDS.

Multiple infectious causes of diarrhea are known in patients with HIV/AIDS. Maldigestion and malabsorption have been reported in patients with HIV/AIDS and may be independent of infectious etiologies. Among ambulatory patients with HIV/AIDS, we examined the prevalence of fat malabsorption (steatorrhea). Sixty-one patients with unexplained diarrhea (defined as > 2 stools/d) and/or weight loss despite adequate caloric intake (and without clinical evidence of chronic pancreatitis) were evaluated in our outpatient Gastroenterology-Nutrition Clinic between March 1, 1993, and July 1994. Patients were instructed by a dietitian to follow a > or = 100 g/d fat diet for 24 h before submitting a stool sample for qualitative (or quantitative) fecal fat determination. Forty-five patients, 32 with ongoing diarrhea and 13 without diarrhea, submitted stool samples. Twenty-two of 45 patients (49%) had qualitative or quantitative steatorrhea, 16/32 with diarrhea (50%) and 6/13 patients without diarrhea (46%). Thirty of 32 patients with diarrhea had had extensive microbiologic and/or endoscopic evaluations. Only 9 patients had a detectable intestinal pathogen, 5 patients had cytomegalovirus (4 treated), 4 patients had cryptosporidia (3 treated), and 1 patient had microsporidia. Steatorrhea, as determined by abnormal qualitative fecal fat, is detectable in nearly 50% of patients with HIV/AIDS. Fat malabsorption appears to be a primary defect in these patients independent of detectable pathogens. Assessment of fat malabsorption should be considered in patients with unexplained weight loss or diarrhea before extensive evaluation for opportunistic infections.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Serum zinc and protein levels: lack of a correlation in hospitalized patients with AIDS.

Abnormally low serum zinc levels are associated with advanced states of malnutrition. Zinc levels are thought to parallel serum albumin, and repletion of zinc has reportedly led to increased albumin. We examined the correlation between zinc deficiency and serum proteins in hospitalized patients with AIDS. Over 500 inpatient consultations were performed by our Gastroenterology-Nutrition Consult Service from May 1992 to June 1994. We reviewed the medical records from all 228 AIDS patients in whom a serum zinc level was measured (by atomic absorption spectrophotometry). The correlation between serum zinc, albumin, prealbumin, and transferrin drawn on the same hospital day was analyzed by linear regression. The patients were stratified by the level of albumin, group A albumin < 2.0 g/dL, group B albumin 2.0-2.9 g/dL, and group C albumin > 3.0 g/dL, to allow comparison of the incidence of diarrhea and mean zinc level by chi square. Thirty-four patients had more than one serum zinc and albumin determination; the change over time was compared by linear regression. Serum zinc and albumin, prealbumin, and transferrin levels did not correlate strongly (r2 < or = 0.01). Furthermore, changes in zinc over time did not correlate with parallel changes in serum albumin (r2 < or = 0.01). In patients grouped by albumin, the proportion of patients with diarrhea did not differ significantly. The mean zinc levels were also not statistically significantly different. Serum zinc levels do not strongly correlate with serum proteins in hospitalized patients with AIDS. Serial measures of zinc over time also do not correlate strongly with changes in albumin. The incidence of diarrhea was not significantly different in patients with hypoalbuminemia or hypozincemia when compared with patients with near normal albumin or zinc. The relationship between zinc and serum proteins in AIDS patients is not linear. Zinc deficiency should be assessed in patients independent of the serum albumin.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

A cluster analysis to investigating nurses' knowledge, attitudes, and skills regarding the clinical management system.

Nurses' knowledge, attitudes, and skills regarding the Clinical Management System are explored by identifying profiles of nurses working in Hong Kong. A total of 282 nurses from four hospitals completed a self-reported questionnaire during the period from December 2004 to May 2005. Two-step cluster analysis yielded two clusters. The first cluster (n = 159, 56.4%) was labeled "negative attitudes, less skillful, and average knowledge" group. The second cluster (n = 123, 43.6%) was labeled "positive attitudes, good knowledge, but less skillful." There was a positive correlation in cluster 1 for nurses' knowledge and attitudes (rs = 0.28) and in cluster 2 for nurses' skills and attitudes (rs = 0.25) toward computerization. The study showed that senior and more highly educated nurses generally held more positive attitudes to computerization, whereas the attitudes among younger and less well educated nurses generally were more negative. Such findings should be used to formulate strategies to encourage nurses to resolve actual problems following computer training and to increase the depth and breadth of nurses' computer knowledge and skills and improve their attitudes toward computerization.

Cluster Analysis↗
PubMedDate not supplied

Conformational studies on model peptides with 1-aminocyclobutane 1-carboxylic acid residues.

Conformationally constrained peptidomimetics are being increasingly used in the development of 3-D pharmacophores of peptide-based drug candidates and to alter their metabolic stability towards achievements of oral bioavailability. Here we present conformational energy calculations on model compounds containing 1-aminocyclobutane carboxylic acid (ACBC) and its derivatives using molecular mechanics methods. The low-energy models adopt conformations characteristic of a variety of regular structures such as the alpha-helix, 3(10)-helix, gamma-turn and polyproline-II-type three- and fourfold helices. The energetically most favored models adopt the gamma-turn (2.2(7) helix) conformation or alpha-/3(10)-helical conformation, both of either handedness, depending on the substituents on the cyclobutane. These results are qualitatively consistent with the crystal structures of peptide analogs containing ACBC and have implications for the design of peptidomimetics.

Amino Acids↗
PubMedDate not supplied

Conformational studies on model peptides with 1-aminocyclopropane 1-carboxylic acid residues.

The design of metabolically stable, conformationally constrained peptidomimetics is an increasingly used approach in developing orally active drug candidates in pharmaceutical research. In this paper we present conformational energy calculations on model compounds containing 1-aminocyclopropane carboxylic acid (ACC) and its derivatives using molecular mechanics methods. The low energy models adopt conformations characteristic of a variety of regular structures such as the alpha-helix, gamma-turn and three- and fourfold helices. The energetically most favored models adopt either the left- or right-handed 2.2(7) helical conformation or the gamma-turn. These results are qualitatively consistent with the crystal structures of peptide analogs containing ACC and have potential implications for the design of peptidomimetics where the conformational features characteristic of a specific type of gamma-turn are desired.

Amino Acids↗
PubMedDate not supplied

Oral rehabilitation with implant-retained prostheses following ablative surgery and reconstruction with free flaps.

Ablative surgery of the oral tissues may result in significant facial deformity, poor oral function, and psychologic detriment. Immediate surgical reconstruction with vascularized free flaps has become increasingly popular, but the oral rehabilitation of these patients with conventional dental prostheses is usually unsuccessful. The results and clinical experiences of treating a group of 17 patients with ablative surgery, immediate reconstruction with free flaps, and restoration with mandibular implant-retained prostheses are presented after follow-up periods of 6 months to 7 years. Most patients expressed a high degree of satisfaction with their prostheses. General principles and guidelines for the provision of this effective treatment modality are discussed.

Adolescent↗
PubMedDate not supplied

Treatment of the atrophic edentulous maxilla with implant-supported overdentures: a review of the literature.

PURPOSE: This article reviews the literature on maxillary implant-supported overdentures. MATERIALS AND METHODS: Retrospective studies and clinical reports comprise the majority of publications, with few prospective studies. RESULTS: Maxillary implant-supported overdentures are associated with implant and prosthesis survival rates similar to those of fixed implant prostheses when patients are matched for bone quantity and quality. High failure rates are associated with extreme atrophy, poor bone quality, and the use of short implants, which represent situations in which overdentures are most commonly used. CONCLUSION: Further research is required to elucidate the most appropriate implant number and distribution as well as the most favorable prosthetic constructions.

Alveolar Bone Loss↗