Biomedical subjects
Publications and source records attributed to P K Lee.
A retrospective analysis of 29 patients with a histologically confirmed diagnosis of unicystic ameloblastoma is reported with special emphasis on a treatment regime employing enucleation and application of Carnoy's solution. Despite the finding that 93% of lesions exhibited mural invasion, a recurrence rate of 10% after treatment is reported, suggesting a possible benefit of Carnoy's solution against recurrence.
In this Phase I trial, patients' peripheral blood dendritic cells were pulsed with peptides eluted from the surface of autologous glioma cells. Three biweekly intradermal vaccinations of peptide-pulsed dendritic cells were administered to seven patients with glioblastoma multiforme and two patients with anaplastic astrocytoma. Dendritic cell vaccination elicited systemic cytotoxicity in four of seven tested patients. Robust intratumoral cytotoxic and memory T-cell infiltration was detected in two of four patients who underwent reoperation after vaccination. This Phase I study demonstrated the feasibility, safety, and bioactivity of an autologous peptide-pulsed dendritic cell vaccine for patients with malignant glioma.
The secretion of immunosuppressive factors like interleukin-10 (IL-10), either by tumor cells or by tumor-infiltrating leukocytes, has been recognized as one of the mechanisms involved in tumor immunological escape and a serious obstacle for successful immunotherapy. Therefore, any therapeutic attempts aimed at inducing antitumor immunity in tumor-bearing hosts must overcome this immunosuppressive state. This study aimed to determine whether dendritic cell (DC) immunization, a promising approach to induce antitumor immunity, could break IL-10-induced anergic state in CD4+ T cells, essential cells in generating tumor-specific immunity. We found that the ability of DC to reverse IL-10-induced anergic state in human CD4+ T cells is dependent on the IL-10 concentration that T cells have been exposed to and the degree of DC maturation. The efficacy of mature DC in reversing T cell anergy can be mimicked by higher cell numbers of immature DC. In addition, activated T cells induced by DC stimulation are sensitive to IL-10 treatment. Collectively, our results suggest the use of mature DC and the necessity of antagonizing the action of tumor-derived IL-10 in immunotherapy of cancer with DC immunization.
Basal cell carcinoma (BCC) is the most common skin cancer in the Western world. Ultraviolet (UV) exposure, race, age, gender, and decreased DNA repair capacity are known risk factors for the development of BCC. Of these, UVB irradiation from sunlight is the most significant risk factor. The incidence of sporadic BCC increases in individuals older than age 55, with the greatest incidence reported in individuals who are older than 70, and is rare in individuals who are younger than 30. In this study, we analyzed 24 BCC samples from individuals who had BCC diagnosed by the age of 30. Fifteen single-stranded conformation polymorphism variants in the PTCH gene were identified in 13 BCC samples. Sequence analysis of these single-stranded conformation polymorphism variants revealed 13 single nucleotide changes, one AT insertion, and one 15-bp deletion. Most of these nucleotide changes (nine of 15) were predicted to result in truncated PTCH proteins. Fifteen p53 mutations were also found in 11 of the 24 BCC samples. Thirty-three percent (five of 15) and 60% (nine of 15) of the nucleotide changes in the PTCH and p53 genes, respectively, were UV-specific C-->T and CC-->TT nucleotide changes. Our data demonstrate that the p53 and PTCH genes are both implicated in the development of early-onset BCC. The identification of UV-specific nucleotide changes in both tumor suppressor genes suggests that UV exposure is an important risk factor in early onset of BCC.
BACKGROUND: A novel electrosurgical technology that uses a bipolar electrode-tipped stylet to deliver relatively low-radiofrequency energy through an electrically conductive medium has been developed. OBJECTIVE: To evaluate the efficacy and safety of the radiofrequency resurfacing system for the treatment of facial wrinkles. DESIGN: Multicenter, prospective, noncomparative study with longitudinal follow-up. SETTING: Four US academic dermatologic surgery clinics. PATIENTS: Ninety-five patients with mild to severe photodamage (Fitzpatrick classes I-III) involving periorbital (75 treatment sites) and perioral (50 sites) facial skin. INTERVENTION: Radiofrequency resurfacing with the use of 2 to 3 passes at 125 or 139 V. MAIN OUTCOME MEASURES: Wrinkle and cosmetic improvements evaluated by patients, investigators, and, by means of photographs, an independent panel of 5 evaluators. RESULTS: All evaluators determined a positive mean improvement in wrinkles for both periorbital and perioral anatomic sites, with greater improvement for patients with more severe wrinkles at baseline. An increased number of passes and higher voltage settings had a positive impact on wrinkle improvement. Transient postinflammatory hyperpigmentation occurred in 26% of periorbital and 4% of perioral sites. Hypertrophic scars occurred in 3.8% of treatment sites, with all but 1 scar resolving by 6 months. For the most part, healing was rapid, pain was minimal, and erythema largely resolved within 2 months. Other untoward effects were relatively few and short-lived. CONCLUSIONS: At the study settings used, radiofrequency resurfacing is an effective modality in the treatment of periorbital and perioral wrinkles in patients with Fitzpatrick class I, II, and III photodamage. There is less severe postoperative morbidity than seen with carbon dioxide or coagulating erbium:YAG lasers. The potential risks are similar to those seen with other resurfacing modalities.
A case of life-threatening complication resulting from a lumbar epidural block is presented. A 70-year-old woman with spinal stenosis developed cardiac and respiratory arrest 5 minutes after receiving a lumbar epidural block containing 80 mg of triamcinolone acetonide and 6mL of 1.5% lidocaine. The patient received cardiopulmonary resuscitation and recovered without any sequelae. It is suggested that this complication was caused by subdural or intravascular injection of local anesthetics. It might be preventable by injecting a test dose of local anesthetics before injecting a full dose of local anesthetics and by using fluoroscopy.
Mutations in the PTEN/MMAC1 gene have been identified in several types of human cancers and cancer cell lines, including brain, endometrial, prostate, breast, thyroid, and melanoma. In this study, we screened a total of 96 hepatocellular carcinoma (HCC) samples from Taiwan, where HCC is the leading cancer in males and third leading cancer in females, for mutations in the PTEN/MMAC1 gene. Complete sequence analysis of these samples demonstrated a missense mutation in exon 5 (K144I) and exon 7 (V255A) from HCC samples B6-21 and B6-2, respectively. A putative splice site mutation was also detected in intron 3 from sample B6-2. Both B6-21 and B6-2 were previously shown to contain missense mutations in the coding sequences of the p53 gene. Functional studies with the two missense mutations demonstrated that while mutation V255A in exon 7 resulted in a loss of phosphatase activity, mutation K144I in exon 5 retained its phosphatase activity. Additionally, we identified a silent mutation (P96P) in exon 5 of the PTEN/MMAC1 gene from HCC sample B6-22. These data provide the first evidence that the PTEN/MMAC1 gene is mutated in a subset of HCC samples.
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There are several treatment modalities for zone 1 or zone 2 fingertip amputations that cannot be replanted by using microsurgical techniques, such as delayed secondary healing, stump revision, skin graft, local flaps, distant flaps, and composite graft. Among these, composite graft of the amputated digit tip is the only possible means of achieving a full-length digit with a normal nail complex. The pocket principle can provide an extra blood supply for survival of the composite graft of the amputated finger by enlarging the area of vascular contact. The surgery was performed in two stages. The amputated digit was debrided, deepithelialized, and reattached to the proximal stump. The reattached finger was inserted into the abdominal pocket. About 3 weeks later, the finger was removed from the pocket and covered with a skin graft. We have consecutively replanted 29 fingers in 25 adult patients with fingertip amputations by using the pocket principle. All were complete amputations with crushing or avulsion injuries. Average age was 33.64 years, and men were predominant. The right hand, the dominant one, was more frequently injured, with the middle finger being the most commonly injured. Of the 29 fingers, 16 (55.2 percent) survived completely and 10 (34.5 percent) had partial necrosis less than one-quarter of the length of the amputated part. The results of the above 26 fingers were satisfactory from both functional and cosmetic aspects. Twenty of the 29 fingers, which had been followed up for more than 6 months (an average of 16 months), were included in a sensory evaluation. Fifteen of these 20 fingers (75 percent) were classified as "good" (static two-point discrimination of less than 8 mm and normal use). From the overall results and our experience, we suggest that the pocket principle is a safe and valuable method in replantation of zone 1 or zone 2 fingertip amputation, an alternative to microvascular replantation, even in adults.
The diagnosis and management of porphyria cutanea tarda (PCT) is complicated when it occurs in the context of renal failure, chronic hemodialysis, and anemia. We report a case of a woman who presented with painful acral blisters and hyperpigmentation. Her medical history included systemic lupus erythematosus, chronic hepatitis C infection, and renal failure necessitating chronic hemodialysis with a baseline anemia. A highly elevated serum porphyrin level led to the diagnosis of PCT. Treatment with small repeated phlebotomies and concomitant administration of erythropoietin was effective in managing her PCT.
Cutaneous lasers, including argon, Q-switched Nd:YAG, Q-switched ruby, Q-switched alexandrite, and short pulsed dye lasers, have been used to treat solar lentigines and other benign melanocytic lesions. However, the effects of these lasers at standard fluences on atypical melanocytic lesions have not been examined. We describe two patients in whom the Q-switched ruby laser failed to successfully treat clinically atypical-appearing solar lentigines. In both, clinically atypical-appearing melanocytic lesions were treated with excellent initial cosmetic results. In the first patient, the pigmentation returned several months after treatment and continued to increase in size and color. A biopsy specimen 30 months after Q-switched ruby laser therapy revealed a lentigo maligna melanoma. In the second patient, the lesion recurred 6 months after Q-switched ruby laser therapy, and a biopsy specimen 1 year after treatment showed an early lentigo maligna. Thus Q-switched ruby lasers and other cutaneous lasers capable of targeting melanin may be inadequate to eliminate lentigo maligna and other atypical melanocytic lesions completely. These cases emphasize the importance of careful clinical assessment before any laser surgery and the need to advise patients to return for evaluation should pigmentation return.
Leaf colour, size and toughness were investigated in five plant species important in the diet of Macaca fascicularis in Singapore. Leaf colour and size were examined as potential visual cues for food selection, whereas toughness mirrored fibre content, the inverse of food quality. As leaves matured, they changed colour and toughened. Leaf lightness and yellowness were strongly negatively correlated with toughness, but variation in both the red-green axis of the CIE Lab colour space and leaf size were not. Leaves selected as food by the macaques were distinguished by being very light, yellow to slightly green. Some leaves were dappled with red. The literature suggests that these leaves are relatively rich in protein without being tough and therefore would be sought after by primates. We argue that leaf colour is an important indicator of the nutritive value of leaves. Trichromatic vision is an important advantage in finding those palatable leaves that are dappled red. These would appear dark to dichromatic primates and be deceptive by making leaves look older (lower in quality) than they actually are. This would decrease the perceived window of feeding opportunity for such primates who would be at a disadvantage in trying to find these leaves. It is possible that trichromatic vision in catarrhine primates may have originally evolved for the detection of red coloration in the leaves of shade-tolerant tropical plants, enabling the better exploitation of a food resource.
A retention pond is a part of a drainage system designed to control water flow during rainstorms and to trap contaminated solid particles washed off by runoff water from a motorway. A series of studies have been carried out concerning the physico-chemical characteristics of the particles which settle down in such a pond in order to evaluate the effectiveness of the pond as a trap for heavy metals such as Pb, Zn and Cd. The highly contaminated roadside soil and the uncontaminated background soil were also studied for comparison. The settling particles had heavy metal concentrations 2-8 times higher than the background Sologne soil, depending on the metals. Heavy metal concentrations in the roadside soil were 7-26 times higher than those in the former. Sequential extractions, using the procedure of Tessier et al. (1979) illustrate that the highly contaminated roadside soil consisted mainly of the readily soluble fractions for all three heavy metals, with a limited proportion of residual metals. In the settling particles, the proportion of the latter is significantly increased, up to one-third of the total. The high concentration differences between the roadside soil and the settling particles indicates that most of the heavy metals are lost to the surroundings even before reaching the retention pond. Cadmium exhibited a specific behavior in that the most soluble fraction (exchangeable), which is negligible for Pb and Zn, occupied as much as one-fourth of the total in the roadside soil. Based on the 'enrichment factor' normalized to Fe introduced by Helz in 1976, the degree of contamination by heavy metals for the roadside soil and the settling particles was evaluated. The level of contamination was very severe in the roadside soil, while it was not so great in the settling particles. Suggestions are made to improve their removal efficiency.
AIMS: The objective of this study was to investigate drug utilization in the management of hypertension in Hong Kong. METHODS: We conducted a prescription survey to examine the use of antihypertensive drugs in a hypertension clinic in a regional hospital and the resulting expenditure incurred. The use of concurrent medications such as antidiabetic drugs and lipid-lowering agents was also examined. RESULTS: During a 7-week study period, 530 prescriptions were collected. All except 14 patients received antihypertensive drugs with 262 (50.8%) on monotherapy and 254 (49.2%) on combination therapy. Calcium channel blocking agents and beta-adrenoceptor blocking agents were the two most popular antihypertensive drugs used in both monotherapy (38% and 31%, respectively) and combination therapy (27% and 33%, respectively). Forty-nine patients (19%) received three antihypertensive drugs or more. The number of antihypertensive drugs showed a significant positive correlation with the duration of attendance at the clinic (r=0.88, P < 0.001). Of the total 530 prescriptions, 5.6% and 10% contained antidiabetic drugs and lipid-lowering agents, respectively. Calcium channel blocking agents, angiotensin converting enzyme (ACE) inhibitors and lipid lowering agents, accounted for 82% (HK$211,654; pounds sterling 1 approximately HK$12) of the total drug expenditure (HK$258,115). Seventy-nine percent of the lipid lowering agents prescribed were hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitors. Amlodipine accounted for 26% of usage but contributed to 41% of the overall costs of calcium channel blocking agents. Alpha1-adrenoceptor blocking agents were only used infrequently and were the most expensive class of drugs, due to the preferred use of doxazosin rather than prazosin which is far cheaper than the former. CONCLUSIONS: In view of the use of these often costly drugs for long-term therapy, monitoring of their use and its correlation with clinical outcomes and quality of life is essential to ensure the optimal use of health care resources.
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Toxic shock syndrome toxin (TSST) 1 was purified from ovine (TSST-ovine) and bovine (TSST-bovine) mastitis-associated Staphylococcus aureus. These toxins were previously reported to have molecular weights identical to that of human TSST-1. However, TSST-ovine was reported as having an isoelectric point (pI) of 8.5, whereas TSST-bovine has the same pI (7.2) as TSST-1. Nucleotide sequence analysis revealed that TSST-bovine was identical to TSST-1 and that TSST-ovine had 14 nucleotide differences that changed 9 amino acid residues. Only 1 nucleotide difference, at position 514, was predicted to cause an amino acid charge difference, as glutamic acid at position 132 of TSST-1 was changed to lysine in TSST-ovine. Like TSST-1, TSST-ovine was mitogenic, but unlike TSST-1, it was not pyrogenic, was unable to enhance endotoxic shock, and was unable to induce TSS in a rabbit model. Also, TSST-ovine was less reactive to certain monoclonal antibodies raised against TSST-1.
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In staphylococcal toxic shock syndrome, hypotension and shock due to capillary leak may rapidly lead to death of the host. To investigate its pathogenesis, the cytotoxic effects of toxic shock syndrome toxin 1 (TSST-1) on porcine aortic endothelial cells (PAEC) were examined in vitro. TSST-1 killed PAEC (as measured by 51Cr release) in a dose- and time-dependent fashion and was blocked by anti-TSST-1 antibodies. Receptor-mediated endocytosis may be critical for the cytotoxic effects of TSST-1, as killing was inhibited by cold (4 degrees C) and by addition of chloroquine and methylamine. Furthermore, calcium and oxygen appeared necessary for TSST-1 effects on PAEC. Membrane receptor binding studies indicated PAEC bind TSST-1 with high affinity (Kd = 5.7 x 10(-7) M) and had 2.2 x 10(4) receptors/cell. Last, as measured by 125I-labeled albumin flux in a transendothelial permeability model, TSST-1 enhanced the permeability of PAEC monolayers in a dose- and time-dependent manner.