Pilot study of a community pharmacist led program to treat hepatitis C virus among people who inject drugs.

Background: People who inject drugs (PWID) are a key population for treatment with direct-acting antiviral medications (DAAs) to eliminate hepatitis C virus (HCV). We developed a Pharmacist, Physician, and Patient Navigator Collaborative Care Model (PPP-CCM) for delivery of HCV treatment; this study describes clinical outcomes related to HCV treatment (initial evaluation, treatment initiation, completion, and cure), as well as patient satisfaction. Methods: We conducted a single-arm prospective pilot study of adult PWID living with HCV. Participants completed baseline and six-month follow-up surveys, and treatment and outcomes were abstracted from electronic health records. Primary outcome was linkage to pharmacist for HCV evaluation; secondary outcomes included DAA initiation, completion, and cure, as well as patient-reported satisfaction. Results: Of the 40 PWID enrolled, mean age was 43.6 years, 12 (30 %) were female, 20 (50 %) were non-white, and 15 (38 %) were unhoused. Thirty-eight (95 %) were successfully linked to the pharmacist for initial evaluation. Of those, 21/38 (55 %) initiated DAAs, and 16/21 (76 %) completed treatment. Among those completing treatment who had viral load data to document whether they achieved "sustained virologic response", i.e. cure, 10/11 (91 %) were found to be cured. There was high satisfaction with 100 % responding "agree or strongly agree" that they had a positive experience with the pharmacist. Conclusion: Nearly all participants in this pilot were successfully linked to the pharmacist for evaluation, and more than half were started on DAAs; results provide preliminary evidence of feasibility of pharmacist-led models of HCV treatment for PWID. Clinicaltrialsgov registration number: NCT04698629.

Dismantling the ability of CT and MRI to identify the target mismatch profile in patients with anterior circulation large vessel occlusion beyond six hours from symptom onset.

PURPOSE: Patients with large vessel occlusion and target mismatch on imaging may be thrombectomy candidates in the extended time window. However, the ability of imaging modalities including non-contrast CT Alberta Stroke Program Early Computed Tomographic Scoring (CT ASPECTS), CT angiography collateral score (CTA-CS), diffusion-weighted MRI ASPECTS (DWI ASPECTS), DWI lesion volume, and DWI volume with clinical deficit (DWI + NIHSS), to identify mismatch is unknown. METHODS: We defined target mismatch as core infarct (DWI volume) of < 70 mL, mismatch volume (tissue with TMax > 6 s) of ≥ 15 mL, and mismatch ratio of ≥ 1.8. Using experimental dismantling design, ability to identify this profile was determined for each imaging modality independently (phase 1) and then with knowledge from preceding modalities (phase 2). We used a generalized mixed model assuming binary distribution with PROC GLIMMIX/SAS for analysis. RESULTS: We identified 32 patients with anterior circulation occlusions, presenting > 6 h from symptom onset, with National Institute of Health Stroke Scale of ≥ 6, who had CT and MR before thrombectomy. Sensitivities for identifying target mismatch increased modestly from 88% for NCCT to 91% with the addition of CTA-CS, and up to 100% for all MR-based modalities. Significant gains in specificity were observed from successive tests (29, 19, and 16% increase for DWI ASPECTS, DWI volume, and DWI + NIHSS, respectively). CONCLUSIONS: The combination of NCCT ASPECTS and CTA-CS has high sensitivity for identifying the target mismatch in the extended time window. However, there are gains in specificity with MRI-based imaging, potentially identifying treatment candidates who may have been excluded based on CT imaging alone.

Anti-angiogenic pathway associations of the 3p21.3 mapped BLU gene in nasopharyngeal carcinoma.

Zinc-finger, MYND-type containing 10 (ZMYND10), or more commonly called BLU, expression is frequently downregulated in nasopharyngeal carcinoma (NPC) and many other tumors due to promoter hypermethylation. Functional evidence shows that the BLU gene inhibits tumor growth in animal assays, but the detailed molecular mechanism responsible for this is still not well understood. In current studies, we find that 93.5% of early-stage primary NPC tumors show downregulated BLU expression. Using a PCR array, overexpression of the BLU gene was correlated to the angiogenesis network in NPC cells. Moreover, expression changes of the MMP family, VEGF and TSP1, were often detected in different stages of NPC, suggesting the possibility that BLU may be directly involved in the microenvironment and anti-angiogenic activity in NPC development. Compared with vector-alone control cells, BLU stable transfectants, derived from poorly-differentiated NPC HONE1 cells, suppress VEGF165, VEGF189 and TSP1 expression at both the RNA and protein levels, and significantly reduce the secreted VEGF protein in these cells, reflecting an unknown regulatory mechanism mediated by the BLU gene in NPC. Cells expressing BLU inhibited cellular invasion, migration and tube formation. These in vitro results were further confirmed by in vivo tumor suppression and a matrigel plug angiogenesis assay in nude mice. Tube-forming ability was clearly inhibited, when the BLU gene is expressed in these cells. Up to 70-90% of injected tumor cells expressing increased exogenous BLU underwent cell death in animal assays. Overexpressed BLU only inhibited VEGF165 expression in differentiated squamous NPC HK1 cells, but also showed an anti-angiogenic effect in the animal assay, revealing a complicated mechanism regulating angiogenesis and the microenvironment in different NPC cell lines. Results of these studies indicate that alteration of BLU gene expression influences anti-angiogenesis pathways and is important for the development of NPC.

SAA1 polymorphisms are associated with variation in antiangiogenic and tumor-suppressive activities in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a cancer that occurs in high frequency in Southern China. A previous functional complementation approach and the subsequent cDNA microarray analysis have identified that serum amyloid A1 (SAA1) is an NPC candidate tumor suppressor gene. SAA1 belongs to a family of acute-phase proteins that are encoded by five polymorphic coding alleles. The SAA1 genotyping results showed that only three SAA1 isoforms (SAA1.1, 1.3 and 1.5) were observed in both Hong Kong NPC patients and healthy individuals. This study aims to determine the functional role of SAA1 polymorphisms in tumor progression and to investigate the relationship between SAA1 polymorphisms and NPC risk. Indeed, we have shown that restoration of SAA1.1 and 1.3 in the SAA1-deficient NPC cell lines could suppress tumor formation and angiogenesis in vitro and in vivo. The secreted SAA1.1 and SAA1.3 proteins can block cell adhesion and induce apoptosis in the vascular endothelial cells. In contrast, the SAA1.5 cannot induce apoptosis or inhibit angiogenesis because of its weaker binding affinity to αVß3 integrin. This can explain why SAA1.5 has no tumor-suppressive effects. Furthermore, the NPC tumors with this particular SAA1.5/1.5 genotype showed higher levels of SAA1 gene expression, and SAA1.1 and 1.3 alleles were preferentially inactivated in tumor tissues that were examined. These findings further strengthen the conclusion for the defective function of SAA1.5 in suppression of tumor formation and angiogenesis. Interestingly, the frequency of the SAA1.5/1.5 genotype in NPC patients was ~2-fold higher than in the healthy individuals (P=0.00128, odds ratio=2.28), which indicates that this SAA1 genotype is significantly associated with a higher NPC risk. Collectively, this homozygous SAA1.5/1.5 genotype appears to be a recessive susceptibility gene, which has lost the antiangiogenic function, whereas SAA1.1 and SAA1.3 are the dominant alleles of the tumor suppressor phenotype.

Development of monoclonal antibody-based galactomannoprotein antigen-capture ELISAs to detect Aspergillus fumigatus infection in the invasive aspergillosis rabbit models.

Aspergillus fumigatus is one of the most prominent opportunistic fungal pathogens in immunocompromised hosts. Early recognition of this infection along with prompt antifungal therapy may increase the survival rate. We expressed two potential bio-markers of A. fumigatus infection-galactomannoprotein Afmp1p and Afmp4p in Pichia pastoris. We generated 33 monoclonal antibodies (MAbs), 20 against recombinant Afmp1p (rAfmp1p) and the other 13 against recombinant Afmp4p (rAfmp4p). Subsequently, we developed two antigen-capture enzyme-linked immunosorbent assays (ELISAs) which employed MAbs as both the capture and the detection antibodies for rAfmp1p and rAfmp4p. The two antigen-capture ELISAs specifically detected Afmp1p/Afmp4p in cultures of A. fumigatus and had no cross-reaction with other tested pathogenic fungi, including Penicillium marneffei and other pathogenic Aspergillus species. The Afmp1p-captured ELISA would be positive even when the culture supernatant of A. fumigatus had been diluted to 128-fold of its original concentration. The two antigen ELISAs could capture circulating or excreted antigens during the acute phase of invasive aspergillosis (IA) in the animal model, and had no cross-reactivity to other Aspergillus-challenged animal models. We developed two antigen-capture ELISAs for the laboratory diagnosis of A. fumigatus infection. These two antigen-capture ELISAs may be useful in the clinical diagnosis of aspergillosis.

The effect of blocking radial abduction on palmar abduction strength of the thumb.

The measurement of palmar abduction strength of the thumb (PAST) is often used as a research tool to provide an objective assessment of thenar muscle function in patients with carpal tunnel syndrome (CTS). The purpose of this study is to determine the effect of blocking radial abduction on PAST in a normal population. PAST was measured for both hands of 100 healthy volunteers in two positions. In the first position a vertical board was placed perpendicular to the radial border of the hand to block radial abduction, and in the second position PAST was measured without the board. Men had greater PAST. There was no difference in PAST between the dominant and non-dominant hand for both men and women, when a vertical board was used. Without the board, the values were significantly greater in the dominant hand. Radial abduction should be blocked during measurement of PAST.

Familial and socio-environmental predictors of overweight and obesity among primary school children in Selangor and Kuala Lumpur.

INTRODUCTION: A cross-sectional study was conducted to determine the familial and socio-environmental predictors of overweight and obesity among 1430, 9-12 year-old primary school children and their parents in Selangor and Kuala Lumpur. METHODOLOGY: Body weight and height were measured and body mass index was calculated. Modified Child Feeding (CFQ) and Determinants of Adolescent Social Well-being and Health (DASH) questionnaires were used to measure familial and socio-environmental factors. RESULTS: A total of 17.9% of the children were overweight while 16.0% were obese. Positive relationships were found between child's BMI and parent's BMI (r = 0.129, p < or = 0.01), concern about child's weight (r = 0.125, p < or = 0.01) and restriction (r = 0.057, p < or = 0.05) to unhealthy foods. However, negative relationships were found between child's BMI with pressure to eat (r = -0.135, p < or = 0.01) and neighbourhood safety perception (r = -0.053, p < or = 0.05). The logistic regression analysis showed that being male (Exp (beta) = 0.538; 95% CI = 0.421-0.687), higher parent's BMI (Exp (beta) = 1.055; 95% CI = 1.028-1.082), higher concern about child's weight (Exp (beta) = 1.082; 95% CI = 1.030-1.127), low pressure to eat (Exp (beta) = 0.857; 95% CI = 0.801-0.916) and low perception of neighbourhood safety (Exp (beta) = 0.951; 95% CI = 0.913-0.990) were significantly associated with increased risk of overweight. CONCLUSION: Parents should be the main target for education to modify children's weight status. Further research should be carried out to understand the mechanism of influence of parents and the socio-environment on child's health.

Effect of the anticoagulant ethylenediamine tetra-acetic acid (EDTA) on the estimation of pharmacokinetic parameters: A case study with tigecycline and ciprofloxacin.

Tigecycline and ciprofloxacin were employed as the model compounds to study the effect of the anticoagulant ethylenediamine tetra-acetic acid (EDTA), which is used during plasma sample preparations, on the determination of pharmacokinetic parameters. The pharmacokinetic parameters were determined in rats following intravenous infusion with blood samples collected in serum separators, with either EDTA- or heparin-coated tubes. The blood-to-plasma (B:P) partition ratio and plasma protein binding were determined in vitro in rat or human blood collected in either EDTA- or heparin-coated tubes. Drug concentrations were quantified by liquid chromatography coupled with tandem mass spectrometry detection (LC-MS/MS) analysis. In tigecycline-treated rats drug concentrations were twofold lower in EDTA plasma, leading to a twofold lower area under plasma concentration-time curve (AUC) and twofold higher plasma clearance values as compared with those obtained from heparin plasma. No differences were noted in the pharmacokinetic parameters obtained from heparin-treated plasma versus serum. The B:P partition ratio and unbound fraction for tigecycline were significantly higher in EDTA-treated blood. When normalized to the B:P partition ratios, the tigecycline blood clearance values were identical between samples collected in EDTA- or heparin-coated tubes. Similar but smaller differences were observed for ciprofloxacin. It was concluded that EDTA might compete with tigecycline and ciprofloxacin for chelating metal ions and thus affect drug partition between blood and plasma compartments, leading to inaccurate measurement of pharmacokinetic parameters in plasma.

Site-specific effects of tau phosphorylation on its microtubule assembly activity and self-aggregation.

Microtubule-associated protein tau is abnormally hyperphosphorylated and aggregated into neurofibrillary tangles in brains with Alzheimer's disease. The phosphorylation sites of tau are mainly localized in the proline-rich (residues 172-251) and C-terminal tail (residues 368-441) regions, which flank the microtubule-binding repeats. Here, we investigated the effects of tau phosphorylation at these distinct sites/regions on its activity of stimulating microtubule assembly and its self-aggregation. We found that tau phosphorylation at the proline-rich region by dual-specificity tyrosine-phosphorylated and -regulated kinase 1A inhibited its microtubule assembly activity moderately and promoted its self-aggregation slightly. Tau phosphorylation at the C-terminal tail region by glycogen synthase kinase-3beta increased its activity and promoted its self-aggregation markedly. Tau phosphorylation at both regions plus the microtubule-binding region by cAMP-dependent protein kinase diminished its activity (approximately 70% inhibition) and disrupted microtubules. These studies reveal the differential regulation of tau's biological activity and self-aggregation by phosphorylation at various sites/regions.

Discovery of epigenetically silenced genes in acute myeloid leukemias.

The demethylating 5-aza-2'deoxycytidine (DAC) and the histone deacetylase inhibitor (HDACi) suberoyl anilide bishydroxamide (SAHA) possess potent antitumorigenic properties in myeloid disorders. However, the transcriptome alterations mediated by these drugs are poorly understood. We analyzed the transcriptional effects of DAC and SAHA in the AML cell line KG-1. Microarray analyses revealed 76 genes expressed in normal CD34+ cells, absent in KG-1 cells but whose expression was induced after drug treatment. A total of 39 of these genes harbored CpG islands in their promoters. We examined the expression level of these genes in 120 AML patient samples representing diverse karyotpyes. Gas2l1, tfIIs, ehd3, enolase 2, mx1, dral, astml and pxdn were diminished across all AML karyotypes examined. Ehd3 was methylated in 63% of AML patients examined. This methylation was lost upon complete remission, and not observed in normal CD34+ cells. CD34+ cells expressed ehd3 at approximately 10-fold higher levels than AML samples. Another highlighted gene, alpha-catenin, is located at q31 of chromosome 5. Analyses of 29 5q- AML/myelodysplastic syndrome (MDS) samples revealed marked decreases in expression of alpha-catenin, compared to non-5q- MDS samples (6.6+/-9-fold). However, no methylation was detected, suggesting indirect effects of these drugs on the expression of alpha-catenin.

Adjustment to perceived ovarian cancer risk.

Eighty-three women who perceived themselves to be at risk for ovarian cancer completed a battery of surveys. In addition to demographics, subjects were asked to complete the Brief Symptom Inventory, Multidimensional Health Locus of Control, Death Anxiety Scale, Taylor Anxiety Scale, Index of Sexual Satisfaction, Impact of Event Scale, and the Marlowe-Crowne Social Desirability Scale. Overall, the respondents were more similar to normal controls than to psychiatric outpatients. A correlation was drawn between higher levels of education and lower scores on the Brief Symptom Inventory, which measures characteristics such as somatization, obsessive compulsive behaviors, interpersonal sensitivity, and anxiety. However, those who had the highest scores on the Death Anxiety Scale were less likely to comply with the recommendation for a physical/gynecological examination. Patients who were most influenced by an external locus of control or 'powerful other' were more compliant with their physicians' recommendations for testing and examination. It is the authors' belief that individualized educational efforts and the presence of a solid support system may increase women's adherence to the recommended health care practices.

Alterations in theophylline metabolism during the first year of life.

Maturational changes in theophylline disposition were evaluated in 52 infants (gestational age, 24 to 40 weeks; postnatal age, 2 to 69 weeks) receiving maintenance theophylline therapy. Theophylline and metabolites were measured in serum and urine at steady state, and the influence of clinical parameters on the maturational changes was analyzed by multiple stepwise linear regression. Theophylline clearance and urine metabolite pattern reached adult values at 55 weeks' postconceptional age. Serum caffeine concentrations greater than 1 microgram/ml occurred in infants up to 50 weeks' postconceptional age. Disappearance of serum caffeine concentrations and maturation of theophylline clearance were primarily related (p < 0.001) to development of the demethylation pathway to 3-methylxanthine. Postconceptional age was the major factor (p < 0.001) explaining the interpatient variability in theophylline clearance (r2 = 0.57), serum caffeine to theophylline ratio (r2 = 0.46), and urinary excretion of theophylline (r2 = 0.51), caffeine (r2 = 0.49), 1,3-methyluric acid (r2 = 0.32), 1-methyluric acid (r2 = 0.53), and 3-methylxanthine (r2 = 0.58). Our findings indicate that postconceptional age rather than postnatal age should be used as a maturational marker during theophylline therapy in infancy.

Localization and therapy of human cervical tumor xenografts with radiolabeled monoclonal antibody 1H10.

Murine IgG3 monoclonal antibody (Mab) 1H10, which recognizes a tumor-associated antigen expressed on the surface of more than 40% of human cervical carcinoma tissues, was used for in vivo localization and therapy of cervical tumor xenografts. A human cervical carcinoma cell line, CaSki, was used as our experimental tumor system. Mab 1H10 antigen expression on the surface of CaSki cells was found to be cell-cycle independent. The ability of Mab 1H10 F(ab')2 to bind to CaSki tumor xenografts was verified by direct immunohistochemical staining of thin tumor sections with a Mab 1H10-peroxidase conjugate. Radioimmunoscintigraphy of nude mice bearing CaSki tumors after iv administration of [131I]1H10 F(ab')2 showed clear tumor images 48 hr after Mab injection. Radiolabeled Mab 1H10 F(ab')2 was found to specifically localize in solid CaSki tumors 96 hr after antibody injection. Radioactivity in tumor tissue was 4 times higher than that in kidney tissue and over 6 times higher than that in liver tissue. Mab 1H10 F(ab')2 binding to xenografted CaSki tumors was 17 times greater than a control IgG3 F(ab')2 after 96 hr. Therapy of athymic mice bearing established CaSki tumors with three iv injections of 100 microCi [131I]1H10 F(ab')2 resulted in extensive tumor necrosis and significant suppression (p < 0.05) of tumor growth compared to that in control mice. These results indicate that Mab 1H10 F(ab')2 may be clinically useful for detection or treatment of cervical cancer.

Specific activation of glucuronide prodrugs by antibody-targeted enzyme conjugates for cancer therapy.

Cancer chemotherapy may be improved by increasing antineoplastic drug specificity for tumor cells. We have synthesized a glucuronide prodrug that can be enzymatically converted to an antineoplastic agent at tumor cells that are able to bind beta-glucuronidase-monoclonal antibody conjugates. The glucuronide prodrug BHAMG, the tetra-n-butyl ammonium salt of (p-di-2-chloroethylaminophenyl-beta-D-glucopyranoside) uronic acid, was 150 times less toxic than the parent drug, N,N-di-(2-chloroethyl)-4-hydroxyaniline, to HepG2 human hepatoma cells and over 1000-fold less toxic than the parent drug to AS-30D rat hepatoma cells in vitro. In the presence of beta-glucuronidase, BHAMG was activated and became as toxic as the parent drug N,N-di-(2-chloroethyl)4-hydroxyaniline. A conjugate (RH1-beta G) was formed by linking beta-glucuronidase to a monoclonal antibody which binds to an antigen expressed on the surface of AS-30D cells. The concentration of BHAMG causing 50% inhibition of AS-30D cellular protein synthesis was reduced over 1000-fold, from greater than 770 microM to less than 0.74 microM after these cells were preincubated with RH1-beta G. Specificity of BHAMG activation at antigen-positive cells was shown by monoclonal antibody RH1 blocking of RH1-beta G conversion of BHAMG to toxic drug and by the inability of BHAMG to be converted to active drug when antigen-negative control cells were preincubated with RH1-beta G. Our results show that the targeted-beta-glucuronidase activation of BHAMG can increase the specificity of chemotherapy for rat hepatoma in vitro and suggest that the targeted activation of glucuronide prodrugs may be useful for cancer therapy.

Therapy of human cervical carcinoma with monoclonal antibody-Pseudomonas exotoxin conjugates.

Pseudomonas exotoxin A (PE) linked to the F(ab')2 fragment of 1H10, a murine monoclonal antibody recognizing a carbohydrate epitope of a glycoconjugate expressed on the surface of human cervical carcinoma tumor cells, was evaluated for in vitro and in vivo activity. PE can kill cells by ADP-ribosylating elongation factor 2 thus inhibiting protein synthesis. Disulfide- as well as thioether-linked immunotoxins (1H10-PE) killed cervical carcinoma cells in vitro and were 20-160 times more inhibitory to target than to control cells. Cell killing was antibody mediated as demonstrated by the reduction of 1H10-PE growth inhibition to target CaSki cells by free 1H10 F(ab')2. In addition, a control antibody immunotoxin was nontoxic to CaSki cells. Thioether-linked 1H10-PE administered either i.v. or i.p. suppressed the growth of established solid s.c. cervical carcinoma tumors xenografted in nude mice for over 30 days. Treatment with antibody alone or a control immunotoxin had no significant effect on tumor growth. Administration of immunotoxin i.p. was associated with less toxicity than administration i.v., but i.v. injections were more effective at suppressing the growth of established solid tumors.

Detection of a Thy-1 precursor in human T lymphoma cell lines.

In an attempt to gain insight into the biosynthesis and processing of human Thy-1, rabbit antisera (R alpha TP) were raised against a synthetic peptide (TP) of 13 amino acid residues of identical amino acid sequence to that of residues 110-122 of the putative Thy-1 precursor deduced from the cDNA sequencing. Immunoblotting assay showed that the IgG fraction of R alpha TP (R alpha TP-IgG) recognized the synthetic peptide without demonstrable cross-reactivity with isolated human brain Thy-1 and detergent-solubilized membrane proteins of human brain cells. Immunohistochemical studies showed that both R alpha TP-IgG and HB-2S-1 (a monoclonal antibody which reacts with both membrane-bound Thy-1 on viable cells and detergent-solubilized Thy-1) stained cells of two human T lymphoma cell lines (HUT-78 and HUT-102) but they did not stain cells of a human B lymphoma cell line (Raji). In contrast, in cell surface indirect immunofluorescence assay, HB-2S-1 reacted with HUT-78 and HUT-102 cells while R alpha TP-IgG did not. Taken together, these data indicate the existence of a precursor form of human Thy-1 which is processed prior to anchoring to the cell surface.

Pulmonary dirofilariasis: the great imitator of primary or metastatic lung tumor. A clinicopathologic analysis of seven cases and a review of the literature.

The clinical, radiologic, and pathologic features of seven patients with pulmonary dirofilariasis were studied. The findings were analyzed in conjunction with those of 76 cases previously reported from the United States. We found that, in most instances, the disease was acquired in states along the Atlantic and Gulf coasts and occurred predominantly in whites (94.7%) in their fifth or sixth decades of life, with a male to female ratio of 2:1. Symptoms, commonly chest pain, cough, or hemoptysis, were present in 37.6% of patients. Most patients (62.4%) were asymptomatic, and the disease was discovered incidentally on routine radiography or during the investigation of another problem. Peripheral eosinophilia was present in 20% of patients. The radiologic findings consisted of single (89.8%) or multiple (10.2%) pulmonary nodules that simulated primary or metastatic lung tumor. Dirofilariasis was not included in the clinical differential diagnosis in any of the patients. In one case, the diagnosis was accurately obtained by fine needle aspiration biopsy. All other patients required thoracotomy with excisional lung biopsy for diagnosis. Pathologically, the dirofilaria nodule consisted of a spherical subpleural infarct with a central thrombosed artery containing Dirofilaria immitis in various stages of disintegration.

Renal handling of beta-2-microglobulin in neonates treated with gentamicin.

Increased levels of urinary beta 2-microglobulin (beta 2M) have been used as a marker of proximal tubular dysfunction in human neonates. To assess the value of beta 2M in the detection of early stages of tubular damage caused by gentamicin, renal handling of beta 2M was studied sequentially in 18 gentamicin-treated neonates with idiopathic respiratory distress syndrome (mean birth weight 1,781 g, mean gestational age 33.7 weeks) during the first 7 days of life. These data were compared with those obtained from 10 control infants matched for gestational and postnatal ages. In addition, follow-up studies of renal function were conducted in 14 of 18 study infants 1 week after termination of therapy, on day 14 postpartum. The (+/- SD) fractional tubular excretion of beta 2M (FE beta 2M) tended to decrease significantly in the control infants from 10.3 +/- 1% on day 1 to 6.5 +/- 0.8% on day 7 postpartum (p less than 0.05). In infants treated with gentamicin, the mean FE beta 2M rose from 10.5 +/- 2% on day 1 to 17.1 +/- 1% on day 7 (p less than 0.01), followed by a decrease to 8.2 +/- 0.5% over the next 7 days (p less than 0.001). Compared with the control infants, values for the infants receiving gentamicin were significantly higher on postpartum days 3,5, and 7 (p less than 0.001). No significant differences in serum creatinine, creatinine clearance, or fractional tubular excretion of sodium were observed between the two groups during the study period.(ABSTRACT TRUNCATED AT 250 WORDS)