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Biomedical subjects

M Chan

Publications and source records attributed to M Chan.

At least 19 recordsLinked to original sources

A hepaticojejunostomy: technical errors with 'twists and turns'.

Excision of a choledochal cyst followed by biliary reconstruction with a Roux-en-Y hepaticojejunostomy is the treatment of choice for type I and IV choledochal cysts. We present a rare complication which was identified 8 years after the original reconstructive surgery. Conventional imaging modalities failed to identify the pathology. Only a contrast enhanced CT scan supported by image rendering software allowed for the visualization of the underlying chronic obstruction of part of the mesentery.

Anastomosis, Roux-en-Y↗

Improved survival with statins, angiotensin receptor blockers, and steroid weaning after heart transplantation.

Various immunosuppressive and adjunctive pharmacological regimens exist for cardiac transplantation, though the associations between these regimens and long-term survival are unclear. We reviewed demographic, clinical, and pharmacological data from 220 consecutive adult heart transplant recipients between 1986 and 2003 who survived beyond 3 months. Immunosuppression was cyclosporine-based (n=94) or tacrolimus-based (n=126), and 104 patients were weaned off steroids (all receiving tacrolimus). Covariates of mortality were assessed in a Cox proportional hazards analysis. The mean age was 5.2+/-13 years. Survival was 96%, 88%, and 81% at 1, 3, and 5 years, respectively. Significant covariates associated with mortality included pretransplant diabetes mellitus (hazard ratio [HR] 2.83, 95% confidence interval [CI] 1.45 to 5.04), black race (HR 1.41, 95% CI 1.01 to 1.94), higher pretransplant creatinine clearance (HR 0.99, 95% CI 0.98 to 1.00), steroid withdrawal (HR 0.60, 95% CI 0.39 to 0.85), and exposure to a statin (HR 0.53, 95% CI 0.40 to 0.70) or an angiotensin receptor blocker (HR 0.50, 95% CI 0.20 to 0.95) after transplantation. Treatment with a statin, an angiotensin receptor blocker, and steroid withdrawal were each associated with improved survival in heart transplant recipients. These findings warrant prospective study, with specific emphasis on identifying the clinical effects of these medications in transplant recipients.

Adrenal Cortex Hormones↗

[Efficacy and safety of two dosing regimens with Tadalafil in Spanish men with erectile dysfunction: results from the SURE study in 14 European countries].

OBJECTIVE: [corrected] To compare the efficacy and safety of tadalafil 20 mg administered 3 times/week (SCH) vs. on demand (OD) in a cohort of Spanish men with erectile dysfunction (ED), since Tadalafil period of responsiveness lasts up to 36 hours post-dosing. MATERIAL AND METHODS: The 418 Spanish patients participating in the European multicenter, crossover, open-label SURE clinical trial (comprising 4262 men) were randomly assigned to one of the treatment sequences: tadalafil 20 mg SCH for 5-6 weeks followed by tadalafil 20 mg OD for 5-6 weeks, or the inverse sequence. At completion, patients were asked to select the regimen they preferred to receive in an extension phase. RESULTS: In both regimens, tadalafil led to a similar improvement in erectile function compared to baseline. However, the SCH regimen showed statistically significant higher scores for several IIEF questions (i.e. sexual desire domain). Normal erectile function (IIEF EF domain score > or = 26) was achieved by 69.3% of patients on SCH and 64.3 % on OD, with a sexual intercourse success rate (SEP3) of 75.6% and 72.2% respectively (p<0.05). Nevertheless, more patients preferred to receive tadalafil OD for the extension phase (55.9% vs 44.1%, p<0.05). Tadalafil was well tolerated in both regimens. The most common TEAEs (> or = 5%) were headache, dyspepsia and back pain. There were no clinically significant differences in the incidence of TEAEs between regimens. CONCLUSIONS: Tadalafil 20 mg is efficacious and well tolerated for the treatment of ED, regardless the regimen of administration (OD or SCH). Patients can choose the pattern of administration that fits better with their expectations.

Adult↗

The sense of movement elicited by transcranial magnetic stimulation in humans is due to sensory feedback.

It has been claimed that transcranial magnetic stimulation (TMS) of the human motor cortex can produce a sense of movement of the contralateral hand, even when the hand is paralysed. The sense of movement was equated with a 'corollary discharge', a nulling mechanism originally posited for maintaining constancy of the visual field during eye movements. Our experiments were designed to test whether the sensation that accompanies TMS-evoked finger movements is generated centrally or whether it arises as a result of sensory feedback. Matched twitches of the left and right fingers were elicited either by bilateral electrical stimulation of forearm extensor muscles, or by a combination of TMS of left motor cortex (eliciting twitches of the right forefinger), and electrical stimulation of the left forearm muscles (eliciting twitches of the left forefinger). The time interval between stimuli activating left and right twitches was varied randomly (range +/- 90 ms) from trial to trial. Subjects reported whether they sensed that the left or the right movement occurred first, or if they could detect no difference. The left and right movements evoked by bilateral electrical stimulation of muscles were sensed as near simultaneous when there was zero delay between them. When TMS was applied in conjunction with unilateral muscle stimulation, the TMS-evoked movement was felt, on average, 20 ms after the movement evoked by muscle stimulation. Similar results were obtained when the skin under the cathodal electrodes was anaesthetized. Since the TMS-evoked movements were felt later rather than earlier than the electrically evoked movements, the results do not support the idea that the sensation of movement was elicited centrally by TMS. Rather, they favour sensory feedback as the source of the sense of movement. The earlier perception of electrically evoked versus TMS-evoked movements was probably due to earlier sensory responses in the periphery rather than a suppression of the excitability of somatosensory cortex.

Adult↗

Can initial tacrolimus trough levels be predicted from clinical variables?

In eligible patients, cardiac transplantation has become the definitive treatment for end-stage heart failure. The initial posttransplantation course is marked by many potential difficulties, including renal insufficiency, hemodynamic instability, and perioperative bleeding. It is important to prevent early rejection; calcineurin inhibitors, such as tacrolimus or cyclosporine, are integral parts of such management. However, these drugs are associated with renal toxicity in some patients. Previous work suggests that limiting the increase in tacrolimus levels is associated with less renal insufficiency. The hypothesis of the current study was that a combination of clinical or laboratory variables could identify patients at risk for rapid changes in tacrolimus target levels. No single variable was strongly associated with high resultant trough levels following a standard 1-mg oral "test dose" of tacrolimus. However, the combination of 2 indices of liver metabolism (alanine aminotransferase and total bilirubin) along with serum creatinine did identify patients who tended toward elevated levels of tacrolimus (> or =4.5 ng/dL). Other variables, such as demographics, and even functional variables, such as right ventricular function by echocardiography, did not enhance the predictive value of this simple scoring system.

Adult↗

Refractory humoral cardiac allograft rejection successfully treated with a single dose of rituximab.

Despite improvements in immunosuppression over the last two decades, the risk of allograft rejection is still high in the early postoperative period. Cellular rejection accounts for the majority of these episodes. However, humoral rejection is a distinct phenomenon that carries a high rate of graft loss and mortality. The currently available treatments for this serious clinical problem include anti-lymphocyte antibodies, immune globulin infusions, as well as plasmapheresis, all of which have limitations. We describe a case of refractory humoral cardiac rejection successfully treated with a single dose of rituximab (375 mg/m2). No further episodes occurred with 2 years of follow-up.

Adult↗

Functional characterization of an alternative [lactate dehydrogenase-like] malate dehydrogenase in Plasmodium falciparum.

The catalysis of malate dehydrogenase (MDH) in Plasmodium falciparum (pfMDH) which involves NAD/NADH coupling is crucial for the parasite's pathogenicity. Primers were designed based on the P. falciparum genome resource, and these facilitated the cloning of a gene coding for pfMDH from a local clinical isolate. The DNA sequence of the cloned gene revealed an open-reading frame that encodes a protein of 313 amino acids. After induction in Escherichia coli BL21, enzyme assays of the expressed pfMDH purified by affinity chromatography exhibited significant enzyme activity of about 50 U/mg, where one unit (U) of enzyme activity is defined as the amount of enzyme oxidising 1 microol NADH/min. Based on its phylogenetic status amongst MDHs and lactate dehydrogenases (LDHs), the cloned gene was clearly defined as belonging to the NADH-dependent [LDH-like] MDHs. It is noteworthy that pfMDH harbours unique structural characteristics potentially useful for screening drugs specific for disabling parasitic enzymes.

Amino Acid Sequence↗

Cardiac transplantation in the older recipient: excellent long-term survival based on pretransplant screening.

BACKGROUND: Cardiac transplantation has become the established treatment of choice for eligible patients with end-stage congestive heart failure. Older recipients (over the age of 60) are sometimes regarded as too high risk for transplant. Because chronological age is frequently disparate from physiologic age, we hypothesized that with careful selection after a comprehensive screening evaluation we would be able to achieve comparable survival and quality of life in an older population. METHODS: Between January 1989 and December 2002, 240 de novo adult cardiac transplants were performed for 74 female and 176 male patients. Prior to listing for cardiac transplantation, the patients were evaluated to exclude significant comorbidities that would limit survival or functional capacity postsurgery. In patients over the age of 60, particularly rigorous testing was conducted to eliminate significant extracardiac disease. RESULTS: The patients are divided in this analysis into three groups based on age at transplant (age 18 to 45, 46 to 59, and 60 years or older). Older recipients experienced similar rates of moderately severe cellular rejection (ISHLT grade 3A/ B). Survival as derived by Kaplan-Meier analysis was equivalent for all groups by Mantel-Cox logrank test (P = NS). The survival for patients older than age 60 was 83.1%, 73.7%, 67.7%, 57.4%, and 43.1% at 1,3, 5, 7, and 10 years posttransplant, respectively. CONCLUSION: We conclude that chronological age over 60 years old should not exclude a patient from the potential long-term benefit of cardiac transplant, ensuring added longevity and excellent quality of life.

Adolescent↗

Violations of service fairness and legal ramifications: the case of the managed care industry.

Adapted from Chan's (2000) model depicting success of litigation, this paper argues that with the application of various legislation, health maintenance organizations' (HMOs') violations of service fairness to each group: enrollees, physicians, and hospitals give rise to each group's lawsuits against the HMOs. Various authors (Bowen et al., 1999; Seiders and Berry, 1998) indicate that justice concepts such as distributive, procedural, and interactional justice can be applied to the area of service fairness. The violation of these underlying justice principles with HMOs' service unfairness to enrollees, physicians, and hospitals is examined. A general synopsis of the ethical issues in the managed care industry is provided. The various lawsuits launched by each group: enrollees, physicians, and hospitals together with the key statutes used are discussed. This paper also highlights the provisions and ramifications of the 11 April 2000 landmark agreement that Aetna made with Texas Attorney General John Cornyn to settle the 1998 lawsuit brought against the company. Lastly, the current ethical issues in the managed care industry are further discussed. The value of this paper can be adapted to the study of organizations' service fairness violations in other industries or in the educational, governmental, and not-for-profit sectors both nationally and internationally.

Conflict of Interest↗

Breast conservation treatment in Hong Kong-early results of 203 patients: retrospective study.

OBJECTIVE: To study the clinical outcomes of patients with invasive or non-invasive breast cancer after breast conservation treatment. DESIGN: Retrospective study. SETTING: Clinical oncology department of a public hospital, Hong Kong. PATIENTS: Two hundred and three patients who received postlumpectomy radiotherapy at the Pamela Youde Nethersole Eastern Hospital between January 1994 and June 1999. INTERVENTIONS: Adjuvant radiotherapy with or without systemic adjuvant treatment. MAIN OUTCOME MEASURES: Actuarial local control rate, progression-free survival rate, disease-specific survival rate, and cosmetic score. RESULTS: The median follow-up was 3.5 years. Two of the 25 patients with carcinoma in situ only developed local recurrence; the 5-year actuarial local control rate was 91.3%. Among the 178 patients with invasive cancer, seven had a local recurrence and 12 developed distant metastases without local failure. The 5-year actuarial local control, progression-free survival, and disease-specific survival rates for patients with invasive cancer were 95.5%, 85.8%, and 95.2%, respectively. The risk of local recurrence was significantly increased for younger patients (age <40 years) and those with positive final margins. Cosmetic scores were rated good to excellent by 95.6% of patients. CONCLUSIONS: The early clinical outcomes of these patients are comparable to those in large overseas trials, which have demonstrated the equivalence of mastectomy and breast conservation treatment in terms of survival. In addition to mastectomy, with or without breast reconstruction, breast conservation treatment should be offered as an alternative to suitable Chinese women. To maximise local control, further excision or mastectomy is recommended for patients with positive final margins.

Adult↗

Proteolytic processing of a human salivary proline-rich protein precursor by proprotein convertases.

Salivary proline-rich proteins (PRPs) are synthesized as precursors that are cleaved before secretion giving rise to glycosylated PRPs which have lubricating function and basic PRPs which are potent precipitators of dietary tannins. The putative cleavage sites in the precursors for basic and glycosylated PRPs all conform to the sequence RSXR downward arrowS (X can be A, S or P) in agreement with the recognition sequence (RXXR downward arrow) for various proprotein convertases. PRB4S, a proprotein giving rise to a basic PRP (IB-5) as well as a glycosylated PRP (II-1) was synthesized by in vitro transcription-translation. It was cleaved by furin at RSAR downward arrowS(173-178) giving rise to two proteins II-1 and IB-5. Similarly another precursor with the sequence RSAR downward arrowS(173-178) was also cleaved by furin. This together with previous results show that in vitro furin can cleave all RSXR downward arrowS sequences in the proproteins that give rise to glycosylated and basic PRPs. To demonstrate cellular cleavage, a human submandibular cell line (HSG) was transfected with a vector encoding PRB4S. This resulted in secretion of II-1 and IB-5. The degree of cleavage was enhanced by coexpressing furin and PRB4S. No cleavage occurred if the cells expressed a mutant PRB4S, R177Q, where the furin cleavage site had been destroyed. Cleavage was also inhibited if a furin inhibitor was coexpressed with PRB4S. Incubating the cells at 20 degrees C which blocks exit of proteins from the trans-Golgi network demonstrated that cleavage occurs before exit of the proteins from this network. These results show that furin may be responsible for in vivo cleavage of PRP precursors. Transfecting furin-deficient RPE.40 cells with a vector encoding PRB4S also led to secretion of II-1 and IB-5 showing that convertases other than furin can also cleave PRB4S in tissue culture.

Base Sequence↗

Penoplasty for buried penis in children: report of 50 cases.

PURPOSE: The authors report their experience with a large number of children with buried penis and describe their surgical technique. METHODS: Fifty consecutive cases of buried penis that occurred between 1993 and 1999 were analyzed by chart review. Age at the time of surgery was 11 months to 13 years. Each patient underwent elective surgical repair utilizing a surgical technique not described previously. The authors' technique avoids a circumferential incision at the base of the penis, decreasing postoperative edema. The authors also utilize a unique through and through vertical mattress suture at the base of the penis that firmly attaches the shaft skin to the underlying corpora. RESULTS: All patients had a good to excellent outcome with a low postoperative complication rate. One patient fell during the postoperative period and developed a wound dehiscence. Early in the series 3 patients underwent additional procedures for recurrent retraction (6%). All patients experienced some postoperative discomfort as expected. Edema, when present, was mild and resolved within an acceptable period of time. All patients had a good cosmetic result with increased visualization of the penile shaft. CONCLUSIONS: A surgical approach to the buried penis is warranted in most circumstances. There are psychological benefits to both the patients and the parents. Although the authors perform the procedure as early as 11 months, it can be performed safely at 3 months. The procedure reported here provides immediate excellent cosmetic results with a low complication rate. The authors do not recommend suprapubic lipectomy either alone or in combination with the buried penis procedure. Circumcision should be avoided in an infant with a definite diagnosis of buried penis.

Adolescent↗