Biomedical subjects

J Qian

Publications and source records attributed to J Qian.

At least 109 records · Page 6Linked to original sources

PubMed1999

Modulation of transmitter release by action potential duration at the hippocampal CA3-CA1 synapse.

Presynaptic Ca2+ influx through voltage-dependent Ca2+ channels triggers neurotransmitter release. Action potential duration plays a determinant role in the dynamics of presynaptic Ca2+ influx. In this study, the presynaptic Ca2+ influx was optically measured with a low-affinity Ca2+ indicator (Furaptra). The effect of action potential duration on Ca2+ influx and transmitter release was investigated. The K+ channel blocker 4-aminopyridine (4-AP) was applied to broaden the action potential and thereby increase presynaptic Ca2+ influx. This increase of Ca2+ influx appeared to be much less effective in enhancing transmitter release than raising the extracellular Ca2+ concentration. 4-AP did not change the Ca2+ dependence of transmitter release but instead shifted the synaptic transmission curve toward larger total Ca2+ influx. These results suggest that changing the duration of Ca2+ influx is not equivalent to changing its amplitude in locally building up an effective Ca2+ concentration near the Ca2+ sensor of the release machinery. Furthermore, in the presence of 4-AP, the N-type Ca2+ channel blocker omegaCgTx GVIA was much less effective in blocking transmitter release. This phenomenon was not simply due to a saturation of the release machinery by the increased overall Ca2+ influx because a similar reduction of Ca2+ influx by application of the nonspecific Ca2+ channel blocker Cd2+ resulted in much more inhibition of transmitter release. Rather, the different potencies of omega-CgTx GVIA and Cd2+ in inhibiting transmitter release suggest that the Ca2+ sensor is possibly located at a distance from a cluster of Ca2+ channels such that it is sensitive to the location of Ca2+ channels within the cluster.

4-Aminopyridine↗

PubMed1999

Genetic and chromosomal alterations in prostatic intraepithelial neoplasia and carcinoma detected by fluorescence in situ hybridization.

OBJECTIVE: In this review, we discuss the utility of fluorescence in situ hybridization (FISH) in the determination of genetic and chromosomal alterations in prostate cancer specimens. We also discuss the genetic association between prostatic intraepithelial neoplasia (PIN) and adenocarcinoma as detected by FISH and other techniques. METHODS AND RESULTS: FISH is a commonly used technique for the determination of gene and chromosome dosage. In tissue sections, FISH allows precise histopathologic correlation of multiple foci of normal epithelium, premalignant lesions, and carcinoma within a single specimen, including study of intratumoral heterogeneity. PIN and prostatic carcinoma foci have a similar proportion of genetic changes, but foci of carcinoma usually have more alterations. This supports the hypothesis that PIN is the most likely precursor of prostatic carcinoma. The most common genetic alterations in PIN and carcinoma are: (1) gain of chromosome 7, particularly 7q31; (2) loss of 8p and gain of 8q, and (3) loss of 10q, 16q and 18q. Inactivation of tumor suppressor genes and/or overexpression of oncogenes in these regions may be important for the initiation and progression of prostate cancer. CONCLUSIONS: FISH is a useful technique to determine genetic relationships between cancer and its precursors. PIN and prostatic carcinoma foci have a similar proportion of genetic alterations, suggesting that PIN is often a precursor of prostatic carcinoma. Genes on chromosomes 7, 8, 10, 16 and 18 may play an important role in both initiation and progression of prostatic carcinoma.

Adenocarcinoma↗

PubMed1999

Reversibility of prostatic intraepithelial neoplasia: implications for chemoprevention.

High-grade prostatic intraepithelial neoplasia is the most likely precursor of prostatic adenocarcinoma, according to virtually all available evidence. It has a high predictive value as a marker for adenocarcinoma, and its identification in biopsy specimens of the prostate warrants further search for concurrent invasive carcinoma. Androgen deprivation therapy and radiation therapy decrease its prevalence and extent, suggesting a role in chemoprevention.

Adenocarcinoma↗

PubMed1999

Reduced blood pressure and increased sensitivity of the vasculature to parathyroid hormone-related protein (PTHrP) in transgenic mice overexpressing the PTH/PTHrP receptor in vascular smooth muscle.

PTH-related protein (PTHrP) is produced in vascular smooth muscle, where it is postulated to exert vasorelaxant properties by activation of the PTH/PTHrP type 1 receptor. As a model for studying the actions of locally produced PTHrP in vascular smooth muscle in vivo, we developed transgenic mice that overexpress the PTH/PTHrP receptor (PTHrP-R) in smooth muscle. Oocyte injection with a SMP8-PTHrP-R fusion construct yielded six founder mice. F1 offspring were viable and demonstrated selective overexpression of the SMP8-PTHP-R messenger RNA in smooth muscle-rich tissues. Baseline blood pressure measured in conscious mice by tail sphygmomanometry was significantly lower in the receptor-overexpressing mice than that in controls (117 +/- 4 vs. 133 +/- 3 mm Hg; P < 0.05). In anesthetized animals, iv infusion of PTHrP-(1-34)NH2 caused a significantly greater reduction in blood pressure and total peripheral resistance in transgenic mice than in control animals. Vascular contractility was studied in paired, isometrically mounted aortas from 9-week-old transgenic and wild-type mice. The force of contraction in response to phenlyephrine was not significantly different between transgenic and wild-type mice. However, PTHrP-(1-34) NH2 relaxed aortic vessel preparations from transgenic mice to a greater extent than in controls (77.1 +/- 3% vs. 38.4 +/- 4%; P < 0.001). To determine the impact of overexpression of PTH/PTHrP type 1 receptor and its ligand on the development of the cardiovascular system, double transgenic mice were created by crossing SMP8-PTHrP-R transgenic mice with mice overexpressing PTHrP (SMP8-PTHrP). Double transgenic mice died around day E9 with abnormalities in the developing heart. In conclusion, overexpression of PTH/PTHrP type 1 receptor in vascular smooth muscle of transgenic mice reduces blood pressure, probably through sustained activation of the receptor by endogenous ligand. The cardiovascular defects observed in mice overexpressing both PTHrP and its receptor suggest that PTHrP may play a role in the normal development of the cardiovascular system.

Actins↗

PubMed1999

Targeted overexpression of parathyroid hormone-related protein (PTHrP) to vascular smooth muscle in transgenic mice lowers blood pressure and alters vascular contractility.

PTH-related protein (PTHrP) and its receptor are expressed in vascular smooth muscle cells and are believed to participate in the local regulation of vascular tone. To explore the function of locally produced PTHrP in vascular smooth muscle in vivo, we developed transgenic mice that overexpress PTHrP in smooth muscle using a smooth muscle alpha-actin promoter to direct expression of the transgene. In the PTHrP-overexpressing mice, messenger RNA expression was mainly restricted to smooth muscle-containing tissues. Several founders also expressed the transgene in bone and heart and exhibited striking abnormalities in the development of these tissues. In PTHrP-overexpressing mice, blood pressure was significantly lower than that in wild-type controls (121 +/- 3 vs. 135 +/- 2 mm Hg; P < 0.01). Moreover, the magnitude of the vasorelaxant response to iv infusions of PTHrP-(1-34)NH2 was significantly attenuated in the transgenic animals. A similar desensitization to PTHrP was observed in aortic ring and portal vein preparations. Surprisingly, PTHrP-overexpressing mice were also significantly less responsive to the hypotensive action of infused acetylcholine in vivo and to the relaxant actions of acetylcholine on aortic vessel preparations in vitro. In summary, we have successfully targeted overexpression of PTHrP to the smooth muscle of transgenic mice. When expressed in its normal autocrine/paracrine setting, PTHrP lowers systemic blood pressure and decreases vascular responsiveness to further relaxation by PTHrP and other endothelium-dependent vasorelaxants such as acetylcholine. We postulate that the heterologous desensitization to acetylcholine-induced relaxation in PTHrP-overexpressing blood vessels involves desensitization of second messenger/effector signaling pathways common to PTHrP and acetylcholine.

Actins↗

PubMed1999

Vasorelaxant properties of parathyroid hormone-related protein in the mouse: evidence for endothelium involvement independent of nitric oxide formation.

PTH-related peptide is produced in vascular smooth muscle and is believed to participate in the local control of vascular tone. The recent identification of mid-region PTHrP peptides, as well as the discovery of multiple receptors in blood vessels, raises new questions concerning the mechanisms by which PTHrP relaxes the vasculature. In this study, we examined these mechanisms in two vascular beds of the mouse. PTHrP-(1-34) and PTH-(1-34), but not PTHrP-(38-64) or PTHrP-(38-94), caused concentration-dependent relaxation of pre-contracted aortas and reduced the spontaneous phasic activity of the portal vein. PTHrP and PTH-induced aortic relaxations were largely endothelium dependent, whereas an intact endothelium was not necessary for maximal portal vein relaxation. The endothelium-dependent component of PTHrP and PTH-induced aortic relaxations were unaffected by pretreatment with either L-NNA or indomethacin but were abolished by pretreatment with tetrabutyl ammonium. These results demonstrate that the N-terminal portions of PTHrP and PTH are required for their vasorelaxant activity in the mouse. In addition, maximal relaxant activity of PTHrP and PTH in murine aorta is dependent on the endothelium, which appears to involve the generation of an endothelium-derived hyperpolarizing factor.

Animals↗

PubMed1999

Inhibitor antibody development and T cell response to human factor VIII in murine hemophilia A.

In order to understand better the mechanism of inhibitor formation in hemophilia A patients, we have characterized the immune response to human factor VIII in a murine model of hemophilia A. Mice with severe factor VIII deficiency caused by targeted gene disruptions in exons 16 and 17 were injected intravenously with human factor VIII. Anti-factor VIII was absent or was detected at only very low levels in hemophilic mice of both strains after a single injection of 0.2 microg factor VIII, but it was present in most mice after a second exposure. Subsequent exposures led to high titer anti-factor VIII antibodies in both ELISA and inhibitor assays. A human factor VIII-specific T cell proliferative response was detected with spleen cells obtained three days after a single injection with human factor VIII, before mice had detectable anti-factor VIII antibodies. Subsequent exposures to factor VIII were followed by an increased T cell proliferative response. These studies indicate that murine hemophilia A is a good model for the study of the immune response to human factor VIII, especially the role of the T cell in the early steps in inhibitor antibody formation.

Animals↗

PubMed1999

Beta- and gamma-catenin mutations, but not E-cadherin inactivation, underlie T-cell factor/lymphoid enhancer factor transcriptional deregulation in gastric and pancreatic cancer.

Adenomatous polyposis coli (APC) mutations are present in >70% of colon cancers. The APC protein binds to beta-catenin (beta-cat), a protein first identified because of its role in E-cadherin (E-cad) cell adhesion. In some colon cancers lacking APC defects, mutations in presumptive glycogen synthase kinase 3beta phosphorylation sites near the beta-cat NH2 terminus appear to render beta-cat resistant to regulation by APC and glycogen synthase kinase 3beta. In cells with APC or beta-cat defects, beta-cat is stabilized and, in turn, binds to and activates T-cell factor (Tcf)/lymphoid enhancer factor (Lef) transcription factors. To further explore the role of APC, beta-cat, Tcf, and E-cad defects in gastrointestinal cancers, we assessed gastric and pancreatic cancers for constitutive Tcf transcriptional activity (CTTA). Two of four gastric and two of eight pancreatic cancer lines showed CTTA. One gastric and one pancreatic cancer had mutations in the NH2-terminal phosphorylation sites of beta-cat. The other gastric cancer with CTTA had a missense mutation at serine 28 of gamma-cat, a potential phosphorylation site in this beta-cat-related protein. Although E-cad is an important binding partner for beta-cat and gamma-cat, E-cad inactivation did not result in CTTA. The beta-cat and gamma-cat mutant proteins identified in our studies strongly activated Tcf transcription in vitro, whereas beta-cat mutant proteins with large NH2-terminal deletions had only modest effects on Tcf. Our results suggest a role for Tcf deregulation in gastric and pancreatic cancer, resulting from beta-cat and gamma-cat mutations in some cases and, in others, from yet to be defined defects. Furthermore, these data imply that the consequences of APC and beta-cat mutations are distinct from the effects of E-cad inactivation.

Adenomatous Polyposis Coli Protein↗

PubMed1999

[Soft extravascular model (SEM) with beta-radioactive ray inhibits smooth muscle cell proliferation and intimal hyperplasia in autogenous vein graft].

OBJECTIVE: To investigate the effects of the soft extravascular model (SEM) with 32P on intimal hyperplasia and smooth muscle cell preliferation in autogenous vein grafts. METHODS: We transplanted the femoral veins to the co-lateral femoral arteries in rabbits. The animals were divided into three groups of Aspirin group, 32P group and control group. We observed the expression density of endothelin type A receptor cDNA (ETAcDNA) and intimal relative thickness by using in situ molecular hybridization of ETAcDNA by computerized image analysis technology. RESULTS: SEM with beta-ray obviously inhibited SMC preliferation from 1 W to 12 W postoperation, and notably restrained intimal hyperplasia at early to middle stage of graft. Aspirin could not inhibit SMC proliferation and intimal hyperplasia under the condition of this experiment.

Animals↗

PubMed1999

Effect of Astragalin on matrix secretion and beta 1 integrin mRNA expression in human mesangial cells.

OBJECTIVE: To investigate the effect of Astragalin on human renal mesangial cells. METHODS: Cultured human mesangial cells were treated with Astragalin and Astragalin serum in different concentrations in the presence or absence of PDGF-BB, the proliferation and type IV collagen secretion of mesangial cells were measured by MTT assay and ELISA, and expression of beta 1 integrin gene was estimated by reverse transcription-polymerase chain reaction (RT-PCR) method, suspectively. RESULTS: After 72 hours Astragalin or Astragalin serum treatment, the proliferation of mesangial cells induced by PDGF-BB was inhibited significantly in a dose-dependent manner compared with untreated controls (P < 0.05 and P < 0.01). After 24 hours of Astragalin or Astragalin serum treatment, the secretion of type IV collagen protein in presence of PDGF-BB was significantly decreased and beta 1 integrin mRNA level decreased significantly compared with untreated control (P < 0.05, P < 0.01). CONCLUSIONS: Astragalin inhibits cell proliferation and matrix over-synthesis which might be mediated, at least, partly by decrease of beta 1 integrin gene over-expression. The study suggested that Astragalin might play a role in preventing the progression of chronic renal diseases.

Antineoplastic Agents, Phytogenic↗

PubMed1999

Expression of leukocyte adhesion molecules CD11b, L-selectin and CD45 during hemodialysis.

OBJECTIVE: To examine the gene and protein expression of CD11b, L-selectin and CD45, and the relationship between their expression and leukocytopenia during a hemodialysis session. METHODS: Ten maintenance hemodialysis patients, 20 uremic non-dialysis patients and 10 healthy volunteers were included in this study. The mRNA expression of CD11b, L-selectin and CD45 in peripheral blood mononuclear cells was detected by RT-PCR, while cell surface expression of these molecules on monocytes was detected by flow cytometry and leukocyte number was counted manually. RESULTS: After the start of dialysis, both mRNA expression and cell surface expression of CD11b increased rapidly, while those of L-selectin and leukocyte number fell. The mRNA expression of CD45 first decreased and the cell surface expression increased, followed by a return to pre-dialysis levels, by the end of dialysis. CONCLUSIONS: Hemodialysis using a cuprophane membrane can induce rapid upregulation of CD11b and down-regulation of L-selectin, which might influence the normal adhesion and anti-inflammatory response of leukocytes. In this process CD45 may play a role in regulating and/or transducing activation signal.

Adult↗

PubMed1999

[Low level of residual renal function in the initial month and high transport characteristic as important causes of peritoneal dialysis failure].

OBJECTIVE: To evaluate what kind of patients was at high risk on peritoneal dialysis (PD) treatment. METHODS: 96 patients on PD for (23.1 +/- 10.0) months were studied. The patients were divided into two groups. Group A: patients (25) who died or switched to hemodialysis because of cardiovascular disease, malnutrition, ultrafiltration inefficiency, hydrothora, relapsing peritonitis, etc. Group B: stable PD patients (71) up to now. Age, body surface area (BSA) and dialysate fill volume (DV) were not different between the two groups. The nutritional status, dialysis adequacy, peritoneal membrane transport characteristics, and residual renal function (RRF) in the initial month of dialysis were compared. Patient survival rate was studied by Kaplan-Meier method. RESULTS: It was demonstrated that Kt/V and Ccr in group A were lower than those in group B (P < 0.05). Meanwhile, RRF was significantly different between the two groups; patients with better RRF (> or = 2 ml/min) had higher survival. The percentage of high transporters in group A was greater than in group B. CONCLUSION: Higher clearance in the initial month of dialysis seems to keep PD successful. PD failure maybe related to high transport characteristic and its treatment modality is DAPD. Hemodialysis will be a better choice when RRF is very low as water balance is poorly controlled by DAPD.

Adolescent↗

PubMed1999

[Plasma thyroid hormones during cardiopulmonary bypass].

OBJECTIVE: To study the changes and clinical significance of plasma thyroid hormones were during cardiopulmonary bypass (CPB). METHODS: Plasma thyroid hormones was studied in 36 patients during open heart surgery under CPB. Blood samples were taken preoperatively, and 1, 2, 3, 4, 5 days postoperatively. Doppler echocardiography was performed in 16 patients before and after surgery for evaluating heart function. RESULTS: Before CPB, the levels of thyroid hormones were within normal range. At early stage after CPB, the levels of FT(3), FT(4), TT(3) and TT(4) were significantly decreased and increased. Both TSH and rT(3) were increased significantly after CPB (P < 0.05) and reached their highest levels at the first postoperative day. TSH and rT(3) were gradually dropped subsequently, but TSH returned to the basic level and the level of rT(3) was still high. A positive relation was seen between plasma thyroid hormones and cardiac function. CONCLUSIONS: The changes of plasma thyroid hormones are closely related to cardiopulmonary bypass and could result in postoperative cardiac disfunction.

Adult↗

PubMed1999

[Improvements on radical neck dissection].

OBJECTIVE: To improve the surgery of radical neck dissection for a better curative effect. METHOD: Some improvements on incision, path to exploration and manipulation of operation were made in 65 patients with head and neck tumors while radical neck dissection were done. RESULT: The average surgical time was 110 minutes and the average amount of bleeding was 120 ml in the patients when radical neck dissection had been completed. The complications decreased to 1.54%. The surviual rates of 2 and 3 years are 86.2% (56/65) and 81.6 (31/38) respectively. CONCLUSION: With these improvements on radical neck dissection, the curative effect in the near future is improved.

Adolescent↗

PubMed1999

[Application of IL-1 beta and 8 mRNA and some other indices in monitoring the activity of ulcerative colitis].

OBJECTIVE: To evaluate the monitoring action of the expression of IL-1 beta, IL-8 mRNA, myeloperoxidase (MPO) and superoxide dismutase (SOD) activity in the active ulcerative celitis (UC). METHODS: Twenty active UC patients, 23 inactive UC patients; and 14 non-UC inflammation patients were selected. Twelve patients who complained of flatulence, abdominal pain and constipation receiving endoscopic examination were used as control. MPO and SOD activity, IL-1 beta and IL-8 mRNA expression (hybridization in situ) were determined on the endoscopic biopsy specimens of all patients. In 20 active UC patients, 14 patients received endoscopic examination and 4 indices detection were done once again after 2 months' treatment with prednisone and SASP. RESULTS: Mucosal MPO activities of active UC patients, inactive UC patients, and non-UC inflammation patients are higher than those of control patients, (19.37 +/- 0.54, 11.59 +/- 1.41, and 12.97 +/- 0.49) U/g tissue vs (9.49 +/- 0.51) U/g tissue (P < 0.01). SOD activities are lower than that of control patients, (5.03 +/- 07,7. 7.66 +/- 0.79, and 6.98 +/- 0.61) U/mg protein vs (8.82 +/- 0.58) U/mg protein (P < 0.05). Mucosal MPO activity of active UC patients is also higher than that of inactive and non-UC inflammation patients (P < 0.01); while SOD activity is lower than them (P < 0.01). After 2 months' medical treatment, MPO activity of 14 active UC patients decreased, (12.61 +/- 0.74) U/g tissue vs (19.31 +/- 0.44) U/g tissue (P < 0.01), while SOD activity elevated (7.44 +/- 0.55) U/mg protein vs (5.10 +/- 1.05) U/mg protein (P < 0.05), compared with that of before treatment. Positive expression of IL-1 beta mRNA appeared in the epithelial and inflammatory cells of all active UC patients, 9 inactive UC patients, and 7 non-UC inflammation patients. While expression of IL-8 mRNA only appeared positively in all active UC patients. In 14 active UC patients, there were no detection of interleukin mRNA expression after 2 months' treatment. CONCLUSIONS: Mucosal MPO, SOD, IL-1 beta, and IL-8 mRNA could be used as 4 indices monitoring the activity of UC. And IL-1 beta mRNA is also helpful to supervise early or late UC activity.

Biomarkers↗

PubMed1999

[Clinical features and changing trends of bacterial liver abscess: analysis of 48 cases].

OBJECTIVE: To analyse and compare the changing of clinical feature, pathogenic bacteria, and so is diagnosis and treatment of bacterial liver abscess up date. METHODS: Retrospective study of forty-eight patients over 10 years in PUMC hospital. RESULTS: Compared with the patients in 1960s, the complication and mortality of this disease decreased remarkably. The main clinical manifestations and signs became less typical. Cholelithes and tumor of biliary tract instead of biliary ascariasis became chief pathogenic factor (29.2%). Patients with diabetes mellitus complicating bacterial liver abscess tended to increase (8.3%). The case with negative bacterial culture has increased (52.1%). Ultrasonography should be the first choice for diagnosis, the confirmed diagnosis rate is 79.2%. Percutaneous drainage of the abscess and combined using antibiotics are the effective treatment method. Septic shock was the chief complication causing death. CONCLUSIONS: This disease becomes less typical and difficult to early diagnosis attention should be paid to clinical medicine.

Adolescent↗

PubMed1998

Independent origin of multiple foci of prostatic intraepithelial neoplasia: comparison with matched foci of prostate carcinoma.

BACKGROUND: Prostate carcinoma usually is heterogeneous and multifocal, with diverse clinical and morphologic manifestations. Understanding of the molecular basis for this heterogeneity is limited, particularly for the putative precursor, high grade prostatic intraepithelial neoplasia (PIN). In this study, the authors attempted to determine the genetic relation between multiple foci of PIN and matched foci of carcinoma, and whether they are independent in origin. METHODS: The distribution and prevalence of allelic imbalance at 6 microsatellite polymorphic markers on chromosomes 7q, 8p, 8q, and 18q were examined in 84 microscopically excised PIN foci (mean, 1.6 foci/case) and 95 foci of prostate carcinoma (mean, 1.8 foci/case) from 52 completely embedded, mapped whole mount prostates. RESULTS: PIN contained a lower overall proportion of allelic imbalance than matched prostate carcinoma foci for the 6 polymorphic microsatellite markers (65% vs. 82%), but this difference was not significant. The rate of allelic imbalance in PIN was similar to that in prostate carcinoma at 5 of 6 loci studied; the exception, D18S34 (18q12.2-12.3), had a significantly lower rate of allelic imbalance in PIN than in prostate carcinoma (19% vs. 52%), suggesting that genetic alterations in this chromosomal region may be important in carcinogenesis. Of 22 cases with allelic imbalance in at least 1 focus of PIN and 1 focus of prostate carcinoma, 21 informative cases (95%) showed a similar pattern of allelic imbalance at > or = 1 markers in the matched PIN and prostate carcinoma foci. Significant genetic heterogeneity was observed in both PIN and prostate carcinoma. Allelic imbalance was observed in at least 1 focus in 11 of 25 cases with multiple foci of PIN (44%) and 20 of 25 cases with multiple foci of prostate carcinoma (80%). There was no significant correlation between allelic imbalance and pathologic stage or tumor grade. CONCLUSIONS: Our findings indicate that multiple foci of PIN arise independently within the same prostate. This observation suggests that a field effect underlies prostatic neoplasia. Multiple foci of prostate carcinoma also often arise independently, lending additional support for this hypothesis. The strong genetic similarities between PIN and prostate carcinoma strongly suggest that evolution and clonal expansion of PIN may account for the multifocal etiology of carcinomas.

Aged↗

PubMed1998

Pharmacokinetic interaction between ritonavir and didanosine when administered concurrently to HIV-infected patients.

The effect of coadministration of ritonavir and didanosine (ddI) on the pharmacokinetics of these drugs was investigated in a single-center, three-period, crossover study. Eighteen asymptomatic, HIV-positive men were assigned randomly to 6 different sequences of 3 regimens: ddI (200 mg every 12 hours) alone for 4 days, ritonavir (600 mg every 12 hours) alone for 4 days, and 4 days of ddI with ritonavir under dose-staggering conditions. Although not statistically significant, ritonavir concentrations were slightly higher on average (<10%) with concurrent administration of ddI compared with those of ritonavir alone. In contrast, ddI concentrations were lower with concurrent administration compared with those of ddI alone; maximum concentration and area under the concentration-time curve were reduced by about 15% (p < .05). The ddI elimination rate constant was unaffected by ritonavir, suggesting no change in ddI's systemic metabolism. Adverse events were similar between regimens. The relatively minor changes in ritonavir and ddI pharmacokinetics are probably not clinically relevant; therefore, dosage adjustment of either compound appears unnecessary when administered concurrently. However, the combination regimen of ddI and ritonavir continue to be evaluated clinically.

Adult↗