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Biomedical subjects

K M Lin

Publications and source records attributed to K M Lin.

At least 37 records · Page 2Linked to original sources
PubMed1999

Sulindac inhibits activation of the NF-kappaB pathway.

Sulindac is a non-steroidal anti-inflammatory agent that is related both structurally and pharmacologically to indomethacin. In addition to its anti-inflammatory properties, sulindac has been demonstrated to have a role in the prevention of colon cancer. Both its growth inhibitory and anti-inflammatory properties are due at least in part to its ability to decrease prostaglandin synthesis by inhibiting the activity of cyclooxygenases. Recently, we demonstrated that both aspirin and sodium salicylate, but not indomethacin, inhibited the activity of an IkappaB kinase beta (IKKbeta) that is required to activate the nuclear factor-kappaB (NF-kappaB) pathway. In this study, we show that sulindac and its metabolites sulindac sulfide and sulindac sulfone can also inhibit the NF-kappaB pathway in both colon cancer and other cell lines. Similar to our previous results with aspirin, this inhibition is due to sulindac-mediated decreases in IKKbeta kinase activity. Concentrations of sulindac that inhibit IKKbeta activity also reduce the proliferation of colon cancer cells. These results suggest that the growth inhibitory and anti-inflammatory properties of sulindac may be regulated in part by inhibition of kinases that regulate the NF-kappaB pathway.

Animals↗
PubMed1999

Influence of arginine dietary supplementation on healing colonic anastomosis in the rat.

INTRODUCTION: This study sought to determine whether dietary arginine influences colonic anastomotic healing in the rat model. METHODS: Three groups of 42 Sprague-Dawley rats were fed 0, 1, and 3 percent arginine diets for three preoperative and three postoperative days. Animals underwent transection of the transverse colon with hand-sewn anastomosis. Subgroups of 14 animals in each dietary group were killed on postoperative Days 6, 10, or 14, and bursting pressures, histologic inflammation, and collagen content were compared. RESULTS: Mean anastomotic bursting pressures on postoperative Day 6 were lower for the 0 percent arginine group than the 1 and 3 percent arginine groups (mean +/- standard error of the mean = 134+/-6 mm Hg, 164+/-7 mm Hg, and 166+/-7 mm Hg, respectively; P<0.0005). On Days 10 and 14, no significant differences in bursting pressures were noted between arginine diets. Mean bursting pressures on postoperative Day 6 (155+/-4 mm Hg) were significantly lower than on Days 10 (204+/-5 mm Hg) and 14 (217+/-6 mm Hg; P<0.001) for all arginine diets. Microscopic evaluation of the anastomoses did not show significant differences in inflammation or collagen content between arginine diets. Collagen content in all dietary groups peaked at Day 10. CONCLUSIONS: Perioperative arginine deficiency in the rat model is associated with impaired anastomotic healing during the first week, as reflected by lower bursting pressures. Arginine supplementation to 3 percent does not improve bursting pressures above those found in the usual 1 percent arginine diet at 6, 10, or 14 days. Bursting pressures plateau by Day 10 regardless of perioperative dietary arginine, whereas collagen content peaks at Day 10 after six-day perioperative arginine diet manipulation.

Anastomosis, Surgical↗
PubMed1999

Colorectal cancer in hereditary breast cancer kindreds.

PURPOSE: This study compared characteristics of colorectal cancer between families with dominant breast cancer inheritance and the general population. The cumulative incidence of colorectal cancer was also studied in genetically determined breast cancer syndrome subjects with BRCA1 and BRCA2 mutations and compared with the general population. METHODS: Subjects included 42 patients with colorectal cancer from 32 clinically determined hereditary breast cancer kindreds based on the autosomal dominant inheritance of breast cancers and early age of onset. The general population colorectal cancer cohort was composed of 755 patients from a tumor registry. Lifetime risk of colorectal cancer was determined in 164 BRCA1 and 88 BRCA2 gene mutation carriers and compared with the general population. Mean age of colorectal cancer onset, anatomic site distribution, histologic stage at presentation, and five year stage-stratified survival rates were compared between clinically determined hereditary breast cancer family members and the general population. RESULTS: The lifetime risk of colorectal cancer in male BRCA1 and BRCA2 mutation carriers was 5.6 percent, which was not different from 6 percent in males from the general population. Likewise, the lifetime colorectal cancer risk in female BRCA1 and BRCA2 mutation carriers was 3.2 percent, which was not different from 5.9 percent in females from the general population. Mean age of onset +/- standard error for patients with colorectal cancer was 60 +/- 2 years for hereditary breast cancer kindreds compared with 67 +/- 0.4 years for the general population (P = 0.0004). Colorectal cancer site distribution did not vary between hereditary breast cancer and the general population. Overall colorectal cancer stage distribution was significantly different, with more Stage I and fewer Stage IV cancers in subjects with hereditary breast cancer compared with the general population (P = 0.01). Overall five year stage-stratified colorectal cancer survival rate +/- standard error was 66 +/- 8 percent for hereditary breast cancer kindreds and 46 +/- 2 percent for the general population (P = 0.023). CONCLUSION: Lifetime cumulative colorectal cancer incidence in subjects with BRCA1 and BRCA2 gene mutations was not different from the general population. However, significant differences in colorectal cancer were noted between hereditary breast cancer family members and the general population. Hereditary breast cancer-associated colorectal cancer had an earlier age of onset, lower tumor stage, and better survival rate than the general population. Except for age of onset, colorectal cancer in hereditary breast cancer kindreds exhibited more favorable characteristics than colorectal cancer in the general population.

Adult↗
PubMed1999

Histologic comparison of hereditary nonpolyposis colorectal cancer associated with MSH2 and MLH1 and colorectal cancer from the general population.

PURPOSE: Hereditary nonpolyposis colorectal cancer is reported to have special histologic features. This study compares the histologic features of hereditary nonpolyposis colorectal cancer to colorectal cancers from the general population when hereditary nonpolyposis colorectal cancer cases are restricted to families with known MSH2 and MLH1 mutations. METHODS: Thirty-seven cancers from kindreds carrying MSH2 mutations, 27 cancers from kindreds carrying MLH1 mutations, and 37 colorectal cancers from the general population were reviewed by a pathologist blinded to hereditary nonpolyposis colorectal cancer gene status. Tumor grade, growth pattern, Crohn's-like lymphoid reaction, mucin production, extent of disease in the bowel wall, and lymph node status were evaluated. RESULTS: Poor differentiation and Crohn's-like reaction were a feature of 44 and 49 percent of hereditary nonpolyposis colorectal cancer compared with 14 percent (P = 0.002) and 27 percent (P = 0.049) of colorectal cancers from the general population, respectively. There was no difference in growth pattern, mucin production, lymph node involvement, or local extent of disease between hereditary nonpolyposis colorectal cancer and colorectal cancers from the general population. Poor differentiation and lymph node metastases were found in 57 and 49 percent of MSH2 compared with 26 percent (P = 0.002) and 10 percent (P = 0.03) of MLH1-associated cancers, respectively. There was no difference in growth pattern, mucin production, Crohn's-like lymphoid reaction, or local extent of disease between subgroups of hereditary nonpolyposis colorectal cancer. CONCLUSIONS: Poor differentiation and Crohn's-like reaction are more common in hereditary nonpolyposis colorectal cancer than colorectal cancers from general population. Poor differentiation and lymph node metastases are more commonly seen in MSH2-associated cancers than MLH1. Evaluation of the natural history, pathogenesis, and prognosis of colorectal cancer in hereditary nonpolyposis colorectal cancer should include consideration of which mismatch repair genes are mutated and what the specific mutations are.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Use of preoperative ultrasound staging for treatment of rectal cancer.

INTRODUCTION: Transrectal ultrasound is the standard method for preoperative staging of rectal cancer. This study reviews the accuracy of transrectal ultrasound staging for T3 disease and its use in the selection of patients for neoadjuvant chemoradiation. METHODS: One hundred seventeen patients underwent preoperative transrectal ultrasound evaluation for rectal cancer. Accuracy of transrectal ultrasound was evaluated among 70 patients not receiving preoperative chemoradiation. Forty-seven patients received neoadjuvant chemoradiation based on transrectal ultrasound results. Tumor downstaging and early recurrence were evaluated among 45 of 47 patients receiving neoadjuvant chemoradiation. RESULTS: Among 70 nonirradiated patients, 19 were pathologic Stage pT3. Transrectal ultrasound correctly identified 18 of 19 patients with Stage pT3 (sensitivity, 94.7 percent). Transrectal ultrasound correctly identified 44 of 51 patients with less than pT3 disease (specificity, 86.3 percent). After preoperative chemoradiation in 45 patients with ultrasound Stage uT3 or uT4 tumors, 56 percent of them experienced a reduction in T stage. Residual nodal disease was found in 31 percent of patients. A complete pathologic response with no residual disease at operation was observed in 22 percent of patients. During a median follow-up period of 21 months after diagnosis, seven patients experienced a recurrence of their disease at a median of 12 months after diagnosis. Five of seven patients with recurrence were among a subgroup of ten patients who both failed to downstage T and had residual nodal disease at operation. CONCLUSION: Transrectal ultrasound is an accurate modality for selecting patients for neoadjuvant treatment. Preoperative chemoradiation produced downstaging in 56 percent of patients. Factors related to early recurrence included residual nodal disease and failure to downstage T after neoadjuvant chemoradiation.

Adolescent↗
PubMed1999

The place of culture in DSM-IV.

This paper critically reviews the process and outcome of an effort to enhance the cultural validity of DSM-IV and outlines recommendations to improve future diagnostic systems. An ordered presentation of the antecedents and the main phases of this developmental effort is followed by a content analysis of what was proposed and what was actually incorporated, and a conceptual analysis of underlying biases and their implications. The cultural effort for DSM-IV, spearheaded by a scholarly independent NIMH workgroup, resulted in significant innovations including an introductory cultural statement, cultural considerations for the use of diagnostic categories and criteria, a glossary of culture-bound syndromes and idioms of distress, and an outline for a cultural formulation. However, proposals that challenged universalistic nosological assumptions and argued for the contextualization of illness, diagnosis, and care were minimally incorporated and marginally placed. Although a step forward has been taken to introduce cultural elements in DSM-IV much remains to be done. Further culturally informed research is needed to ensure that future diagnostic systems incorporate a genuinely comprehensive framework, responsive to the complexity of health problems in increasingly multicultural societies.

Culture↗
PubMed1999

Mental health issues for Asian Americans.

One of fastest-growing population groups in recent decades, Asian Americans represent a vastly diversified and rich mixture of cultures, languages, beliefs, and practices, many of which differ widely from those of European Americans. As immigrants, Asian Americans have experienced and continue to experience various emotional and behavioral problems. However, they tend to underuse existing services except those that are culturally appropriate and linguistically compatible. Misdiagnosis frequently occurs, and the existence of culture-bound syndromes points to a lack of precise correspondence between indigenous labels and established diagnostic categories. Due to Asian traditions of viewing the body and mind as unitary rather than dualistic, patients tend to focus more on physical discomforts than emotional symptoms, leading to an overrepresentation of somatic complaints. Traditional practices and healing methods are frequently used to alleviate distress both before and after patients and their family members approach the conventional mental health care system. Help seeking typically is a family venture. Asian patients respond well to highly structured therapeutic interventions such as those used in behavioral, cognitive, and interpersonal models. When applying pharmacotherapy, clinicians should pay attention to Asians' unique responses to psychotropics, especially in regard to dosage requirements and side effects. Research in this area as well as on other important issues is in the early stage of development.

Asian↗
PubMed1998

Colorectal carcinoma survival among hereditary nonpolyposis colorectal carcinoma family members.

BACKGROUND: Patients with hereditary nonpolyposis colorectal carcinoma (HNPCC) reportedly have better prognoses than sporadic colorectal carcinoma (CRC) patients, but it has been unclear whether this could be due to differences in stage at diagnosis. The current study compared stage and survival in a retrospective cohort of HNPCC family members who developed CRC with the same factors in an unselected hospital series of patients with sporadic CRC. METHODS: This retrospective cohort study compared HNPCC cases (274 cases from 98 HNPCC families) with an unselected hospital series comprising 820 consecutive CRC cases. All patients were staged according to the TNM system of the American Joint Committee on Cancer and the International Union Against Cancer. Median follow-up among living patients was > 10 years and 8.5 years, respectively, for the two cohorts. Cox regression was used to compare survival in stage-stratified analyses of time from diagnosis to death. RESULTS: Compared with the unselected series, the HNPCC cases had lower stage disease (P < 0.001), and fewer had distant metastases at diagnosis (P < 0.001 in an analysis stratified by T classification). In stage-stratified survival analysis, the HNPCC cases had a significant overall survival advantage regardless of adjustment for their younger age. A conservative estimate of the hazard ratio (of HNPCC cases to the unselected series) was 0.67 (P < 0.0012). CONCLUSIONS: HNPCC patients had lower stage disease at diagnosis than the unselected CRC cases, mainly due to rarer distant metastases at diagnosis. They survived longer than unselected CRC patients with tumors of the same stage. The estimated death rate for the HNPCC cases, adjusted for stage and age differences, was at most two-thirds of the rate for the hospital series.

Adult↗
PubMed1998

Synergistic activation of dynamin GTPase by Grb2 and phosphoinositides.

Hydrolysis of GTP by dynamin is essential for budding clathrin-coated vesicles from the plasma membrane. Two distinct domains of dynamin are implicated in the interactions with dynamin GTPase activators. Microtubules and Grb2 bind to the carboxyl-terminal proline/arginine-rich domain (PRD), whereas phosphoinositides bind to the pleckstrin homology (PH) domain. In this study we tested the effect of different phosphoinositides on dynamin GTPase activity and found that the best activator is phosphatidylinositol 4,5-bisphosphate followed by 1-O-(1, 2-di-O-palmitoyl-sn-glycerol-3-benzyloxyphosphoryl)-D-myo-inositol 3,4,5-triphosphate. Phosphatidylinositol 4-phosphate was a weak activator and phosphatidylinositol 3,4-bisphosphate did not activate GTPase at all. We then addressed the question of whether both domains of dynamin, PRD and PH, can be engaged simultaneously, and determined the effects of dual occupancy on dynamin GTPase activity. We found that Grb2 and phosphatidylinositol 4,5-bisphosphate together increased the dynamin GTPase activity up to 4-fold higher than that obtained by these activators tested separately, and also reduced the dynamin concentration required for half-maximal activities by 3-fold. These results indicate that both stimulators can bind to dynamin simultaneously resulting in superactivation of dynamin GTPase activity. We propose that SH3-containing proteins such as Grb2 bind to the dynamin PRD to target it to clathrin-coated pits and prime it for superactivation by phosphoinositides.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Colorectal and extracolonic cancer variations in MLH1/MSH2 hereditary nonpolyposis colorectal cancer kindreds and the general population.

PURPOSE: This clinical case review aimed to identify phenotypic variations in colorectal and extracolonic cancer expression between hereditary nonpolyposis colorectal cancer (HNPCC) families with MLH1 and MSH2 germline mutations and the general population. METHODS: Colorectal cancer onset and site distribution were compared among 67 members of MLH1 kindreds, 45 members of MSH2 kindreds, and 1,189 patients from the general population. Synchronous and metachronous cancer rates, tumor stage, extracolonic cancer incidence, and survival were also compared. RESULTS: Mean ages of colorectal cancer onset were 44, 46, and 69 years for MLH1, MSH2, and the general population, respectively (P < 0.001). More proximal and fewer distal colon cancers were noted in HNPCC than the general population (P < 0.001, P = 0.04). Site distribution showed disparity of rectal cancers (8 percent MLH1 vs. 28 percent MSH2; P = 0.01) based on genotypes. Overall, synchronous colorectal cancer rates were 7.4, 6.7, and 2.4 percent for MLH1, MSH2, and the general population, respectively (P = 0.016). Annual metachronous colorectal cancer rates were 2.1, 1.7, and 0.33 percent for MLH1, MSH2, and the general population, respectively (P = 0.041). Colorectal cancer stage presentation was lower in HNPCC than the general population (P = 0.0028). Extracolonic cancers were noted in 33 percent of MSH2 patients, compared with 12 percent of MLH1 patients and 7.3 percent of the general population with colorectal cancers (P < 0.001). Combined MLH1 and MSH2 ten-year survival was 68.7 percent compared with 47.8 percent for the general population (P = 0.009 stage stratified, hazard ratio 0.57). CONCLUSION: The presence of rectal cancer should not preclude the diagnosis of HNPCC, because the incidence of rectal cancer in MSH2 was comparable with that in the general population. Phenotypic variations, including the preponderance of extracolonic cancers in MSH2 patients, did not result in survival differences between genotypic subgroups. These phenotypic features of HNPCC genotypes may have clinical significance in the design of specific screening, surveillance, and follow-up for affected individuals.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Genetic polymorphism of CYP2E1, ADH2, and ALDH2 in Mexican-Americans.

The major enzymes involved in the metabolism of ethanol are alcohol dehydrogenases (ADH) and aldehyde dehydrogenase (ALDH). Some of the isozymes of ADH are expressed polymorphically. Studies investigating a causal link between ADH expression and alcoholic liver disease (ALD) have so far produced conflicting results. The cytochrome P450 2E1 (CYP2E1) represents a second enzyme that can metabolize ethanol. Although normally a minor route of metabolism, its role in chronic alcoholics may be proportionately greater than in nonalcoholics because CYP2E1 is inducible by ethanol. An Rsa I restriction fragment length polymorphism (RFLP) in the 5'-flanking region of the CYP2E1 gene has been identified. Studies have shown that the mutant allele demonstrates greater transcriptional rate, protein level, and enzyme activity when compared with the wild-type allele. The association between the Rsa I site polymorphism and ALD has been reported. In this report, we examined the genotypes of ADH2(2), ALDH2(2), and CYP2E1 in a group of healthy subjects of Mexican-American descent. The ADH2(2) and ALDH2(2) frequencies are 6% and 0%, respectively, which are similar to those which have been reported for Caucasians. In contrast, the Rsa I allele frequency of the CYP2E1 gene is 16%, which is significantly higher than in Caucasians. The high RsaI allele frequency found in Mexican-Americans suggests that it might play a role in the development of ALD in this rapidly growing minority population where ALD is common.

Alcohol Dehydrogenase↗
PubMed1998

Lifetime and twelve-month prevalence rates of major depressive episodes and dysthymia among Chinese Americans in Los Angeles.

OBJECTIVE: The authors' goal was to estimate the lifetime and 12-month rates of major depressive episodes and dysthymia for Chinese Americans who reside in Los Angeles. This effort, the Chinese American Psychiatric Epidemiological Study, is the first large-scale community psychiatric epidemiological study on an Asian American ethnic group that used DSM-III-R criteria for major depressive episodes and dysthymia. METHOD: A multi-stage sampling design was used to select respondents for participation in the survey. The sample included 1,747 adults, 18-65 years of age, who resided in Los Angeles County and who spoke English, Mandarin, or Cantonese. RESULTS: Approximately 6.9% of the respondents had experienced an episode of major depression and 5.2% had had dysthymia in their lifetime. The 12-month rates of depressive episode and dysthymia were 3.4% and 0.9%, respectively. The most consistent correlate of lifetime and 12-month depressive episode and dysthymia was social stress, measured by past traumatic events and recent negative life events. CONCLUSIONS: The Chinese American Psychiatric Epidemiological Study provides a rare opportunity to investigate the heterogeneity within a single Asian American ethnic group, Chinese Americans, and to identify the subgroups among Chinese Americans who may be most at risk for mental health problems.

Acculturation↗
PubMed1997

Gelsolin binding to phosphatidylinositol 4,5-bisphosphate is modulated by calcium and pH.

The actin cytoskeleton of nonmuscle cells undergoes extensive remodeling during agonist stimulation. Lamellipodial extension is initiated by uncapping of actin nuclei at the cortical cytoplasm to allow filament elongation. Many actin filament capping proteins are regulated by phosphatidylinositol 4,5-bisphosphate (PIP2), which is hydrolyzed by phospholipase C. It is hypothesized that PIP2 dissociates capping proteins from filament ends to promote actin assembly. However, since actin polymerization often occurs at a time when PIP2 concentration is decreased rather than increased, capping protein interactions with PIP2 may not be regulated solely by the bulk PIP2 concentration. We present evidence that PIP2 binding to the gelsolin family of capping proteins is enhanced by Ca2+. Binding was examined by equilibrium and nonequilibrium gel filtration and by monitoring intrinsic tryptophan fluorescence. Gelsolin and CapG affinity for PIP2 were increased 8- and 4-fold, respectively, by microM Ca2+, and the Ca2+ requirement was reduced by lowering the pH from 7.5 to 7.0. Studies with the NH2- and COOH-terminal halves of gelsolin showed that PIP2 binding occurred primarily at the NH2-terminal half, and Ca2+ exposed its PIP2 binding sites through a change in the COOH-terminal half. Mild acidification promotes PIP2 binding by directly affecting the NH2-terminal sites. Our findings can explain increased PIP2-induced uncapping even as the PIP2 concentration drops during cell activation. The change in gelsolin family PIP2 binding affinity during cell activation can impact divergent PIP2-dependent processes by altering PIP2 availability. Cross-talk between these proteins provides a multilayered mechanism for positive and negative modulation of signal transduction from the plasma membrane to the cytoskeleton.

Calcium↗
PubMed1997

Differential response of rapid eye movement sleep to cholinergic blockade by scopolamine in currently depressed, remitted, and normal control subjects.

The degree of cholinergic dysregulation of sleep in adult depression was evaluated using scopolamine. On separate sessions, placebo and scopolamine (4.5 micrograms/kg, IM) were administered to 14 patients with unipolar major depression, 16 recovered/remitted patients, and 18 normal controls. Scopolamine increased rapid eye movement (REM) latency (RL), reduced REM activity (RA), REM density (RD), and REM duration, and increased the percentage of stage 4 sleep in all groups. There was a differential effect of scopolamine on RL, RA, and REM duration for the first REM period, and on percentage of stage 4 sleep. Whereas a primary cholinergic hyperactivity could account for the RA and RD responses, the response profile for RL was more compatible with reduced aminergic tone as the proximal cause of the cholinergic hyperactivity. Whether the sleep abnormalities observed in remitted patients reflect an underlying vulnerability for development or recurrence of depression, and/or a scar, remains to be determined.

Adult↗
PubMed1997

Advantage of surgery and adjuvant chemotherapy in the treatment of primary gastrointestinal lymphoma.

BACKGROUND: Surgery has been the mainstay of treatment for gastrointestinal (GI) lymphoma. The role of adjuvant chemotherapy to surgery has not been clearly elucidated. METHODS: The review covered 100 patients who were diagnosed with primary GI lymphoma and treated from 1980 to 1993 at Providence Hospital (Southfield, MI), and Hartford and St. Francis Hospitals (Hartford, CT) with a median follow-up of 5 years. Forty-two patients were treated with surgery alone; 31 patients with surgery and adjuvant chemotherapy; 23 patients with primary chemotherapy, and 4 patients received no treatment. RESULTS: The 5-year actuarial survival based on the above treatments calculated by life-table analysis were 57%, 76%, 58%, and 0%, respectively. This series showed that surgery with adjuvant chemotherapy significantly improved the 5-year actuarial survival of patients with primary GI Lymphoma and that primary chemotherapy showed comparable survival to surgery alone. There was no difference in prognosis when comparing patients with different stage, grade, or location of disease in the GI tract. CONCLUSIONS: We recommend surgery when feasible with adjuvant chemotherapy as the mainstay of treatment for primary GI lymphoma. However, if a patient presents with comorbid factors, primary chemotherapy offers an effective alternative.

Adolescent↗
PubMed1997

The pharmacokinetics and pharmacodynamics of adinazolam: multi-ethnic comparisons.

The pharmacokinetics and pharmacodynamics of adinazolam and N-demethyladinazolam (NDMAD), its major active metabolite, were compared in 39 healthy male volunteers (13 Asian, 12 Caucasian and 14 African-American). In a four-way, double-blind crossover design, subjects were administered (1) 30 mg oral adinazolam mesylate SR tablets, (2) 10 mg parenteral (i.v.) adinazolam mesylate, (3) 30 mg i.v. NDMAD and (4) placebo. Venous blood samples were collected at specific time intervals after drug administration and assayed for adinazolam and NDMAD concentrations. Sedation was rated at the time of each blood draw according to the Nurse-Rated Sedation Scale, and the digit-symbol substitution test was administered to evaluate psychomotor performance. After i.v. administration of adinazolam, Asians manifested significantly higher Cmax, larger AUC and lower CL of both adinazolam and NDMAD than their Caucasian and African-American counterparts. Likewise, after i.v. NDMAD Asians had significantly higher NDMAD Cmax and AUC than Caucasians and African-Americans. Most of these differences remained statistically significant after controlling for body surface area. With PO adinazolam, Asians also manifested substantially higher Cmax, larger AUC and lower CL for both adinazolam and NDMAD; however, with the exception of Cmax, these differences did not reach statistical significance. These results are in accordance with previous observations for ethnic-related differences in drug pharmacokinetics. In contrast, pharmacodynamic differences were not noted among the three study groups.

Adult↗