Evaluation of the antiplatelet effect of generic ticagrelor 90 mg (ticaspan®) alone and in combination with aspirin 75 mg as compared to ticagrelor (innovator): An in vitro study.

Objective: To evaluate an in vitro antiplatelet effect of generic ticagrelor 90 mg (ticaspan) alone and in combination with aspirin 75 mg as compared to the innovator formulation of ticagrelor alone and in combination with aspirin among healthy Indian volunteers. Methods: 18 volunteers were enrolled and platelet viability was tested using lactate dehydrogenase (LDH) assay in six of 18 volunteers. In 12 volunteers, maximum platelet aggregation (MPA) and percentage inhibition of platelet aggregation (PI) were assessed using a platelet aggregometer in six study groups. Results: There was no significant increase in LDH levels when platelets were incubated with an innovator or generic drug alone and in combination with aspirin as compared to the dimethyl sulfoxide [DMSO] group. All five study groups showed a significant reduction in the MPA values compared to the DMSO group (P < 0.01). The extent of decrease in MPA observed with the generic drug was not significantly different from the innovator drug (P = 0.325). Similarly, the MPA observed with the two combination groups did not differ from each other (P = 1.000), but it was significantly different from the MPA observed with aspirin (P = 0.039, each). The PI of platelet aggregation was significantly more in four study groups [generic drug alone; innovator alone; generic drug + aspirin; and innovator drug + aspirin] (P < 0.01) as compared to the aspirin group. Conclusion: The generic ticagrelor and its combination with aspirin demonstrated an antiplatelet effect equivalent to the innovator drug and its combination with aspirin.

The relationship of sinus opacification, olfaction and dupilumab efficacy in patients with CRSwNP.

BACKGROUND: Loss of sense of smell is one of the most burdensome symptoms of chronic rhinosinusitis with nasal polyps (CRSwNP) but its relationship to sinus disease on imaging is unclear. Dupilumab improves sense of smell and radiographic severity of sinus disease in patients with CRSwNP. We investigated the relationship of sinus opacification severity and loci to olfactory impairment and dupilumab efficacy in patients with CRSwNP from the SINUS-24/SINUS-52 (NCT02912468/NCT02898454) studies. METHODS: Sinus opacification was evaluated using the Lund-Mackay computed tomography (LMK-CT) score and sense of smell using patient-reported loss of smell (LoS) score, University of Pennsylvania Smell Identification Test (UPSIT) score and the 22-item Sino-Nasal Outcome Test (SNOT-22) smell/taste item. RESULTS: At baseline, 95% of patients (688/724) had impaired sense of smell and opacification was extensive across all sinuses. Greater olfactory impairment was associated with greater opacification, especially in the ethmoid, sphenoid and frontal sinuses. At Week 24, reductions in LMK-CT total score and ethmoid and sphenoid sinus scores with dupilumab were weakly correlated with improvements in sense of smell assessed by LoS, UPSIT and SNOT-22 smell/taste item. More dupilumab than placebo patients achieved clinically meaningful improvement in LMK-CT total score at Week 24 and Week 52. CONCLUSION: Radiographic disease severity on imaging was associated with smell outcomes in this cohort. Opacification of the ethmoid, sphenoid and frontal sinuses was associated with severe smell loss. These data suggest that dupilumab effects on smell may be partly mediated through reduced sinus inflammation.

Assessment of prescribing pattern of drugs and completeness of prescriptions as per the World Health Organization prescribing indicators in various Indian tertiary care centers: A multicentric study by Rational Use of Medicines Centers-Indian Council of Medical Research network under National Virtual Centre Clinical Pharmacology activity.

OBJECTIVE: The rational use of medicines as per the World Health Organization (WHO) should be practiced globally. However, data regarding the completeness of the prescriptions and their rational use is lacking from developing countries like India. Thus, the aim of this study was to assess the prescribing patterns of drugs and completeness of prescriptions as per WHO core drug use and complementary indicators to provide real-life examples for the Indian Council of Medical Research (ICMR) online prescribing skill course for medical graduates. METHODS: Prescriptions of the patients, fulfilling inclusion criteria, attending Outpatient Departments of various specialties of tertiary care hospitals, were collected by thirteen ICMR Rational use of medicines centers located in tertiary care hospitals, throughout India. Prescriptions were evaluated for rational use of medicines according to the WHO guidelines and for appropriateness as per standard treatment guidelines using a common protocol approved by local Ethics committees. RESULTS: Among 4838 prescriptions, an average of about three drugs (3.34) was prescribed to the patients per prescription. Polypharmacy was noted in 83.05% of prescriptions. Generic drugs were prescribed in 47.58% of the prescriptions. Further, antimicrobials were prescribed in 17.63% of the prescriptions and only 4.98% of prescriptions were with injectables. During the prescription evaluation, 38.65% of the prescriptions were incomplete due to multiple omissions such as dose, duration, and formulation. CONCLUSION: Most of the parameters in the present study were out of the range of WHO-recommended prescribing indicators. Therefore, effective intervention program, like training, for the promotion of rational drug use practice was recommended to improve the prescribing pattern of drugs and the quality of prescriptions all over the country.

Dupilumab reduces systemic corticosteroid use and sinonasal surgery rate in CRSwNP.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease with a high symptom burden and poor quality of life. Treatment options include recurrent surgeries and/or frequent systemic corticosteroids (SCS). Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key drivers of type 2-mediated inflammation. We report results of pooled analyses from 2 randomised, double-blind, placebo-controlled phase 3 studies (SINUS 24 [NCT02912468]; SINUS-52 [NCT02898454]) to evaluate dupilumab effect versus placebo in adults with CRSwNP with/without SCS use and sinonasal surgery. METHODOLOGY: SINUS-24 patients were randomised 1:1 to subcutaneous dupilumab 300 mg (n=143) or placebo (n=133) every 2 weeks (q2w) for 24 weeks. SINUS-52 patients were randomised 1:1:1 to 52 weeks of subcutaneous dupilumab 300 mg q2w (n=150), 24 weeks q2w followed by 28 weeks of dupilumab 300 mg every 4 weeks (n=145) or 52 weeks of placebo q2w (n=153). RESULTS: Dupilumab reduced the number of patients undergoing sinonasal surgery (82.6%), the need for in-study SCS use (73.9%), and SCS courses (75.3%). Significant improvements were observed with dupilumab vs placebo regardless of prior sinonasal surgery or SCS use in nasal polyp, nasal congestion, Lund-MacKay, and Sinonasal Outcome Test (22-items) scores, and the University of Pennsylvania Smell Identification Test. CONCLUSIONS: Dupilumab demonstrated significant improvements in disease signs and symptoms and reduced the need for sino-nasal surgery and SCS use versus placebo in patients with severe CRSwNP, regardless of SCS use in the previous 2 years, or prior sinonasal surgery.

Over-the-counter medicines: Global perspective and Indian scenario.

Patients often approach a pharmacist instead of visiting a doctor for minor ailments such as cough, cold, allergies, pain, fever, acidity, diarrhea, and skin-related conditions. Purchase of specific medicines over the counter is legally recognized in most countries. 'Over-the-Counter (OTC) Medicines' means drugs which are legally allowed to be sold by pharmacists without need for a prescription. The term does not have a legal definition in India. Technically, drugs are OTC unless they are specifically stated as prescription only drugs. OTC drugs allow faster and cheaper access to healthcare; however, their misuse and adverse health effects cause concerns. This article describes concept of OTC medicines and practices in India against the background of globally prevalent regulations and practices. A recognized category of OTC medicines by law, patient awareness programs, and support of pharmacists and pharmaceutical companies are required to optimize the use of OTC medicines in India.

Chronic hyponatremia and association with osteoporosis among a large racially/ethnically diverse population.

Chronic hyponatremia may contribute to decreased bone density. We studied 341,003 men and women who underwent DXA testing and observed that individuals with chronic hyponatremia (sodium < 135 mEq/L) had an 11% greater likelihood of having osteoporosis. There was a dose-dependent effect with lower sodium and stronger association with osteoporosis. INTRODUCTION: Chronic hyponatremia has been associated with both neurologic deficits and increased risk of gait abnormalities leading to falls and resultant bone fractures. Whether chronic hyponatremia contributes to decreased bone density is uncertain. We evaluated whether chronic, mild hyponatremia based on serial sodium measurements was associated with increased risk of osteoporosis within a large, ethnically diverse population. METHODS: This is a retrospective cohort study between January 1, 1998 and December 31, 2014 within Kaiser Permanente Southern California, an integrated healthcare delivery system. Men and women were aged ≥ 55 years with ≥ 2 serum sodium measurements prior to dual-energy X-ray absorptiometry (DXA) testing. Time-weighted (TW) mean sodium values were calculated by using the proportion of time (weight) elapsed between sodium measurements and defined as < 135 mEq/L. Osteoporosis defined as any T-score value ≤ - 2.5 of lumbar spine, femoral neck, or hip. RESULTS: Among 341,003 individuals with 3,330,903 sodium measurements, 11,539 (3.4%) had chronic hyponatremia and 151,505 (44.4%) had osteoporosis. Chronic hyponatremic individuals had an osteoporosis RR (95% CI) of 1.11 (1.09, 1.13) compared to those with normonatremia. A TW mean sodium increase of 3 mEq/L was associated with a lower risk of osteoporosis [adjusted RR (95% CI) 0.95 (0.93, 0.96)]. A similar association was observed when the arithmetic mean sodium value was used for comparison. CONCLUSIONS: We observed a modest increase in risk for osteoporosis in people with chronic hyponatremia. There was also a graded association between higher TW mean sodium values and lower risk of osteoporosis. Our findings underscore the premise that chronic hyponatremia may lead to adverse physiological effects and responses which deserves better understanding.

Dialysis-requiring acute kidney injury among hospitalized adults with documented hepatitis C Virus infection: a nationwide inpatient sample analysis.

Chronic hepatitis C virus (HCV) infection may cause kidney injury, particularly in the setting of cryoglobulinemia or cirrhosis; however, few studies have evaluated the epidemiology of acute kidney injury in patients with HCV. We aimed to describe national temporal trends of incidence and impact of severe acute kidney injury (AKI) requiring renal replacement 'dialysis-requiring AKI' in hospitalized adults with HCV. We extracted our study cohort from the Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project using data from 2004 to 2012. We defined HCV and dialysis-requiring acute kidney injury based on previously validated ICD-9-CM codes. We analysed temporal changes in the proportion of hospitalizations complicated by dialysis-requiring AKI and utilized survey multivariable logistic regression models to estimate its impact on in-hospital mortality. We identified a total of 4,603,718 adult hospitalizations with an associated diagnosis of HCV from 2004 to 2012, of which 51,434 (1.12%) were complicated by dialysis-requiring acute kidney injury. The proportion of hospitalizations complicated by dialysis-requiring acute kidney injury increased significantly from 0.86% in 2004 to 1.28% in 2012. In-hospital mortality was significantly higher in hospitalizations complicated by dialysis-requiring acute kidney injury vs those without (27.38% vs 2.95%; adjusted odds ratio: 2.09; 95% confidence interval: 1.74-2.51). The proportion of HCV hospitalizations complicated by dialysis-requiring acute kidney injury increased significantly between 2004 and 2012. Similar to observations in the general population, dialysis-requiring acute kidney injury was associated with a twofold increase in odds of in-hospital mortality in adults with HCV. These results highlight the burden of acute kidney injury in hospitalized adults with HCV infection.

An ovary as unusual contents of an incarcerated umbilical hernia.

We present the unusual case of a woman presenting with an incarcerated umbilical hernia. Intraoperatively, the contents of the hernia were found to be an ovary. We outline the clinical presentation of our patient, investigations and management as well as a discussion on unusual contents of umbilical hernias. To our knowledge, this is the first case of a non-malignant ovary incarcerated in an umbilical hernia.

Projects not initiated by investigators: a retrospective analysis of the queries raised by the institutional ethics committees of a teaching hospital.

BACKGROUND: Some investigators on receiving queries from Institutional Ethics Committee (IEC), either leave the queries unanswered or withdraw their studies. The present study was conducted to assess the queries raised by two IECs after reviewing studies that were not initiated and to identify reasons for the same. Clinical Trials Registry-India (CTRI) website was checked to review approval status of these studies at other sites. MATERIALS AND METHODS: A retrospective analysis of studies (submitted between January 2006 and December 2011) not initiated by investigators on receiving queries from IECs were identified. The nature of of these studies: whether sponsored (pharmaceutical industry (pharma)/government/investigator initiated), single-centre/multi-centric, and queries raised were analyzed. Status of multi-centric trials; not initiated at our site was checked at CTRI. Data was analyzed using descriptive statistics. RESULTS: A total of 219/2075 (11%) studies were not initiated. The proportions in pharma sponsored, investigator initiated, and government sponsored were 33%. 7.4%, and 8%, respectively. Out of a total of 1676 queries, the maximum queries were related to ethics (42%) and the least were administrative (7%). The largest proportion of queries in the pharma studies was ethical (47%), whereas majority were scientific queries (45.5%) for the investigator initiated studies. Twenty-one of the 94 multi-centric studies not initiated at our site were found registered at the CTRI and were ongoing or completed at 2-55 sites. CONCLUSION: Inability of investigators to defend studies due to lack of good clinical research practice (GCP) and research methodology training or unwillingness of sponsors to comply with local IEC requirements could be potential reasons for studies remaining uninitiated. Continued GCP training of investigators and IEC members and development of uniform ethical review standards across IECs are strongly recommended.

Comparison of nifedipine and progesterone for maintenance tocolysis after arrested preterm labour.

The aim of our study was to compare the efficacy and safety of nifedipine and progesterone for maintenance tocolysis after arrested preterm labour, in prolonging pregnancy and preventing recurrence of preterm labour. This study was a randomised comparative study conducted on 110 pregnant women with arrested preterm labour, randomised to receive either nifedipine 20 mg Q 8-hourly or progesterone 400 mg daily for maintenance tocolysis. Other than demographic parameters, obstetric parameters like previous history of abortions or preterm deliveries, gestational age, cervical dilatation and effacement, ultrasound measured cervical length at admission, were noted. Outcome measures studied were mean prolongation of pregnancy, mode of delivery, neonatal outcome and side-effects of both the drugs. We found that there was no significant difference in the demographic profile, parity, number of abortions, previous preterm deliveries, gestational age, cervical dilatation and effacement at admission between the two groups. A total of 10% of the patients in the nifedipine group and 61% of the patients in the progesterone group delivered at term (p value 0.000). The mean prolongation of pregnancy in the nifedipine group was 16.63 days and 40.14 days in the progesterone group which was significant (p = 0.000). Neonates in the progesterone group had better birth weight, better Apgar scores at 1 and 5 min, lesser need for ventilation and significantly lesser composite morbidity. Nifedipine was associated significantly with side-effects. We conclude that when compared with nifedipine, progesterone significantly prolongs pregnancy in women with arrested preterm labour with better neonatal outcomes and fewer side-effects.

Xylitol production by Cyberlindnera (Williopsis) saturnus, a tropical mangrove yeast from xylose and corn cob hydrolysate.

AIM: Potential for xylitol production from xylose and corn cob hydrolysate by a tropical mangrove yeast. METHODS AND RESULTS: In the present study, 21 fungi were isolated from detritus-based mangrove wetlands along the Indian west coast. Of these, one yeast isolate had the ability to grow and assimilate xylose producing significant amounts of xylitol (38·63 g l(-1) ). A maximum yield of 0·54 g g(-1) was obtained after 144 h of growth on xylose (150 g l(-1) ) and corn cob hydrolysate (CCH, containing 65 g l(-1) xylose). Using biochemical and molecular methods, the yeast was identified as Cyberlindnera (Williopsis) saturnus. Preliminary characterization of enzymes in the cell-free extract revealed that while xylose reductase (XR) preferred NADPH to NADH as cofactor, xylitol dehydrogenase (XDH) was NAD specific. CONCLUSIONS: Significant amounts of xylitol could be produced on CCH using C. saturnus isolated from tropical mangrove wetlands. The yeast has the potential to assimilate rather than ferment xylose as its XR has a preference for NADPH. SIGNIFICANCE AND IMPACT OF THE STUDY: Microbes offer an economically viable and green approach for production of xylitol, an industrially important compound. A mangrove ecosystem with its battery of lignocellulolytic enzymes is an ideal location for isolating fungi capable of producing xylitol from agroindustrial waste such as CCH.

Antiinflammatory activity of Phyllanthus emblica, Plumbago zeylanica and Cyperus rotundus in acute models of inflammation.

Experimental studies conducted earlier have proved that Phyllanthus emblica (Pe), Plumbago zeylanica (Pz) and Cyperus rotundus (Cr), plants from the medohara group of Ayurveda possess antiatherosclerotic activity. As inflammation is also one of the pathophysiological factors, it was of interest to evaluate whether these drugs exhibit any antiinflammatory activity. Two models of acute inflammation, namely carrageenan induced rat paw edema and acetic acid induced peritonitis in mice were used. In the model of carrageenan induced paw edema Pe, Pz and Cr showed a trend to reduce the edema while the combination of Pe + Pz (PI: 20.64%) showed results comparable to aspirin (23.74%). Whereas in a model of acetic acid induced peritonitis, all the plant drugs i.e. Pe, Pz, Cr and a combination of Pe + Pz showed a significant decrease in the protein content of the peritoneal exudates compared with the disease control group (p < 0.05), however, only Pe + Pz exhibited activity comparable to aspirin.

Citrobacter freundii causing pharyngitis and secondary retropharyngeal abscess with intrathoracic extension to the diaphragm: minimally invasive management of a rare case.

INTRODUCTION: Citrobacter freundii is a rare but potentially aggressive cause of pharyngitis which may progress to retropharyngeal abscess with diaphragmatic extension. OBJECTIVE: To raise awareness of: (1) citrobacter as a potential cause of head and neck infection, including retropharyngeal abscess; (2) a novel surgical approach to draining such an abscess; and (3) citrobacter's particular biological properties which may affect the clinical course. METHOD: Case report. RESULTS: The abscess was drained via a minimally invasive posterior pharyngeal wall incision and placement of a suction catheter into the mediastinum through this incision. Residual intrathoracic collections were drained by the cardiothoracic team via percutaneous aspiration. The patient made a full recovery. CONCLUSION: Early recognition of citrobacter head and neck infections, an awareness of the peculiarities of the clinical course of such infections, and timely surgical intervention can prevent catastrophic outcomes. A minimally invasive approach to mediastinal collections can be considered as a viable alternative to open thoracotomy, which carries a high morbidity rate.

The effect of high energy mechanochemical processing on the microstructure, piezoelectric, ferroelectric and mechanical properties of PLZT ceramics.

Lead lanthanum zirconate titanate (PLZT) ceramics were synthesized using a high energy mechanochemical processing technique, using tungsten carbide grinding vials and balls. The ceramic powders were prepared using the constituent oxide powders, which were subjected to high energy milling, without the use of any excess PbO in the starting composition. TEM studies revealed the formation of very fine particles of the order of 30 nm, due to the milling effect. Highly dense ceramics could be prepared via sintering which resulted in ultra-high strains in these piezoelectric samples of up to 0.25%, a value which has not been reported hitherto by any other known process. The effect of the reduction in particle size on the microstructure, mechanical and electrical properties of PLZT ceramics were studied and are discussed herein.

Comparative effectiveness of rosuvastatin versus other statin therapies in patients at increased risk of failure to achieve low-density lipoprotein goals.

OBJECTIVES: Statins are increasingly used in the treatment of hypercholesterolemia. Research has shown difficulty in attaining LDL-C goals in routine clinical practice, especially in patients at high risk for coronary events. This study identified risk factors associated with failure to attain LDL-C goals in routine clinical practice and examined the effectiveness of rosuvastatin compared to other statins in patients presenting with these risk factors. METHODS: This retrospective observational study used administrative claims data on patients receiving statins. After stratifying patients into baseline National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) risk categories, logistic regression allowed identification of factors predicting failure to attain LDL-C goal. Separate analyses compared failure rates between rosuvastatin and other statins in patients at an increased risk of goal attainment failure. RESULTS: Of the 4661 patients identified, 50% and 14% had baseline NCEP ATP III high and moderate risk status, respectively. Risk factors associated with goal attainment failure were percentage change required to achieve goal > or = 30%, NCEP high risk status, percentage change required 15-29%, and NCEP moderate risk status. Patients at an increased risk of failure exhibited significantly higher failure rates in all other statin groups compared to rosuvastatin. CONCLUSIONS: This study demonstrates that patients requiring > or = 15% change in LDL-C or NCEP high or moderate risk patients are at a higher risk of goal attainment failure. Rosuvastatin is more effective compared to other statins in patients with these risk factors and given variations in clinical profiles of branded and generic statins, these results may aid in identifying patients most likely to benefit from rosuvastatin compared to other statin therapies. Validating the results of this study in other patient populations would help increase the generalizability of study findings.

Circulating mononuclear cells from euthyroid patients with thyroid-associated ophthalmopathy exhibit characteristic phenotypes.

Thyroid-associated ophthalmopathy (TAO) is a common yet poorly understood component of Graves' disease involving inflammation, congestion and soft tissue remodelling of the orbit. Unlike most autoimmune disorders, TAO has variable severity but follows a predictable course and is usually self-limited. The objective of this study was to investigate the phenotypic profile of peripheral blood mononuclear cells in euthyroid patients with TAO. The study was a prospective, consecutive analysis of the peripheral blood mononuclear cell phenotype in patients with TAO and normal controls. We demonstrate that the fraction of T cells expressing CD69, CD25 or CXCR4 is significantly greater in patients with TAO compared to control donors. In addition, the fraction of CD19(+) CD25(+) B cells is significantly greater. We did not find differences between the two groups of subjects in monocytes expressing these markers. There is a phenotypic shift in peripheral blood lymphocytes associated with TAO that appears durable and persists beyond the hyperthyroid phase of Graves' disease. These changes may support the immune reaction provoking orbital disease development.

Severe hypospadias with micropenis, case of confused sex, psychosocial changes and treatment.

Disorders such as severe hypospadias presenting as ambiguous genitalia have serious and potentially life-long consequences for affected individuals and, depending on the underlying cause, are likely to entail surgery in childhood and in later life, psychosocial and psychosexual support, and possible fertility treatment including assisted conception. Genetic males with severe hypospadias who were wrongly brought up as females formed the study group. They were reassigned as males and underwent surgery for correction of hypospadias. Three children with severe hypospadias were reassigned to male gender. Psychosocial changes were made and psychosexual counseling was done. All three have adjusted to their new environment and gender. It is preferable to reassign these children who are genetic males but wrongly assigned as females at birth. Repair of hypospadias, psychosocial changes, and psychosexual counseling will help these children to reorient themselves.

Mutations in dynamin-related protein result in gross changes in mitochondrial morphology and affect synaptic vesicle recycling at the Drosophila neuromuscular junction.

Mitochondria are the primary source of ATP needed for the steps of the synaptic vesicle cycle. Dynamin-related protein (DRP) is involved in the fission of mitochondria and peroxisomes. To assess the role of mitochondria in synaptic function, we characterized a Drosophila DRP mutant combination that shows an acute temperature-sensitive paralysis. Sequencing of the mutant reveals a single amino acid change in the guanosine triphosphate hydrolysing domain (GTPase domain) of DRP. The synaptic mitochondria in these mutants are remarkably elongated, suggesting a role for DRP in mitochondrial fission in Drosophila. There is a loss of neuronal transmission at restrictive temperatures in electroretinogram (ERG) recordings. Like stress-sensitive B (sesB), a mitochondrial adenosine triphosphate (ATP) translocase mutant we studied earlier for its effects on synaptic vesicle recycling, an allele-specific reduction in the temperature of paralysis of Drosophila synaptic vesicle recycling mutant shibire was seen in the DRP mutant background. These data, in addition to depletion of vesicles observed in electron microscopic sections of photoreceptor synapses at restrictive temperatures, suggest a block in synaptic vesicle recycling due to reduced mitochondrial function.

Limits on spin-independent interactions of weakly interacting massive particles with nucleons from the two-tower run of the cryogenic dark matter search.

We report new results from the Cryogenic Dark Matter Search (CDMS II) at the Soudan Underground Laboratory. Two towers, each consisting of six detectors, were operated for 74.5 live days, giving spectrum-weighted exposures of 34 (12) kg d for the Ge (Si) targets after cuts, averaged over recoil energies 10-100 keV for a weakly interacting massive particle (WIMP) mass of 60 GeV/c2. A blind analysis was conducted, incorporating improved techniques for rejecting surface events. No WIMP signal exceeding expected backgrounds was observed. When combined with our previous results from Soudan, the 90% C.L. upper limit on the spin-independent WIMP-nucleon cross section is 1.6 x 10(-43) cm2 from Ge and 3 x 10(-42) cm2 from Si, for a WIMP mass of 60 GeV/c2. The combined limit from Ge (Si) is a factor of 2.5 (10) lower than our previous results and constrains predictions of supersymmetric models.