Sensitivity of 2DEG-based Hall-effect sensors at high temperatures.

The magnetic sensitivity of Hall-effect sensors made of InAlN/GaN and AlGaN/GaN heterostructures was measured between room temperature and 576 °C. Both devices showed decreasing voltage-scaled magnetic sensitivity at high temperatures, declining from 53 mV/V/T to 8.3 mV/V/T for the InAlN/GaN sample and from 89 mV/V/T to 8.5 mV/V/T for the AlGaN/GaN sample, corresponding to the decreasing electron mobility due to scattering effects at elevated temperatures. Alternatively, current-scaled sensitivities remained stable over the temperature range, only varying by 13.1% from the mean of 26.3 V/A/T and 10.5% from the mean of 60.2 V/A/T for the InAlN/GaN and AlGaN/GaN samples, respectively. This is due to the minimal temperature dependence of the electron sheet density on the 2-dimensional electron gas (2DEG). Both devices showed consistency in their voltage- and current-scaled sensitivity over multiple temperature cycles as well as nearly full recovery when returned to room temperature after thermal cycling. Additionally, an AlGaN/GaN sample held at 576 °C for 12 h also showed nearly full recovery at room temperature, further suggesting that GaN-based Hall-effect sensors are a good candidate for use in high temperature applications.

Decreased surfactant proteins in lambs with pulmonary hypertension secondary to increased blood flow.

Infants with increased pulmonary blood flow secondary to congenital heart disease suffer from tachypnea, dyspnea, and recurrent pulmonary infections. We have recently established a model of pulmonary hypertension secondary to increased pulmonary blood flow in lambs after in utero placement of an aortopulmonary vascular graft. The purpose of the present study was to utilize our animal model to determine the effects on the expression of surfactant proteins A (SP-A), B (SP-B), and C (SP-C). At age 4 wk, SP-A mRNA content in lambs decreased to 61.4 +/- 8% of age-matched control value (n = 5; P < 0.05). In addition, SP-A protein content was decreased to 50 +/- 12% of control value (n = 6; P < 0.0001). Although we did not observe statistically significant changes in SP-B mRNA content, SP-B protein was decreased to 74 +/- 25% of control value (n = 4; P < 0.02). There was no difference in SP-C mRNA. These data show that in a model of congenital heart disease with pulmonary hypertension secondary to increased pulmonary blood flow, there is a decrease in SP-A gene expression as well as a decrease in SP-A and SP-B protein contents.

Occurrence of arbuscular mycorrhizal fungi in a phosphorus-poor wetland and mycorrhizal response to phosphorus fertilization.

The presence of arbuscular mycorrhizas in fens has received little attention, but because fen plants are often phosphorus limited, the plant-fungus interaction could be an important factor in plant competition for phosphorus. In this field study, we determined mycorrhizal colonization rates for 18 fen plant species. Also in the field, we examined the effect of four different forms of phosphorus on the percentage colonization for one fen plant species, Solidago patula. We found that in a species-rich, phosphorus-poor wetland both mycorrhizal and nonmycorrhizal species were common. Nine of ten dicotyledonous species examined formed arbuscular mycorrhizas, while all monocotyledonous species were at most very weakly mycorrhizal. A morphological explanation for this pattern is that the monocots in our study have more extensive aerenchyma, especially in coarse roots. Therefore, monocots are able to transport oxygen to their roots more effectively than dicots. In the organic wetland soil, additional oxygen in the rhizosphere promotes phosphorus mineralization and availability. Two of the monocot species (Typha latifolia and Carex lasiocarpa), which have been described previously as mycorrhizal in other wetland types, are surprisingly nonmycorrhizal in our phosphorus-poor study site, suggesting that a mycorrhizal association would not offer improved phosphorus nutrition to these species. In contrast, our field phosphorus addition decreased mycorrhizal colonization in S. patula, suggesting that one benefit to S. patula of the mycorrhizas is phosphorus uptake.

Improving outpatient diabetes management through a collaboration of six competing, capitated Medicare managed care plans.

This report addresses diabetes care in the managed care setting and improvement in care brought about by collaboration between 6 Medicare managed care plans (MCPs) and a Peer Review Organization (PRO). The objective was to improve the quality of care of outpatient diabetes patients provided by primary care physicians through the mutual collaboration of 6 Medicare managed care plans and a Medicare Peer Review Organization. The design involved pre-post intervention trial based on 2 random samples, a baseline sample drawn in 1995 and a remeasurement sample drawn in 1996. Medical records of patients in both samples were reviewed by the PRO to determine provision of 14 quality indicator services over a 1-year period. The setting was 6 Arizona Medicare managed care plans comprising approximately 40% of the Arizona Medicare population. Two random samples were drawn from type 2 diabetes patients continuously enrolled in the same managed care plan for at least 1 year. The intervention was comparative feedback of baseline data by the PRO, enabling each plan to compare itself to any other plan on any or all indicators. Each plan developed and implemented its own intervention in response to the 1995 baseline results. The main outcome measures were mean HbA1c, the proportion of HbA1c values below 8%, and positive change in provision of 14 quality indicator services. At postintervention remeasurement, mean HbA1c values fell from 8.9 +/- 2.2 to 7.9% +/- 2.1, and the proportion of patients with HbA1c values below 8.0% rose from 40% to 61.6%. The proportion of the 14 indicator services provided to patients rose from 35% to 55%. The mean number of physician office visits fell 13% and the number of services provided per visit doubled. We conclude that improving the process of care improves glycemic control. Better outpatient diabetes management in competing, capitated managed care plans is an attainable goal when mediated through a neutral third party such as a PRO.

Apoptosis in the development of rat and human fetal lungs.

The establishment of an effective pulmonary alveolar-capillary interface occurs during mid to late gestation. This requires an expansion of endothelial, epithelial, and air space compartments with relative thinning of the interstitial compartment. Traditionally, these changes have been attributed to differences in the rate of cell growth in the respective compartments. We hypothesized that apoptosis also participates in this lung remodeling. Using light and electron microscopy, the nucleosomal ladder pattern of DNA digestion, and the detection of apoptotic cells in situ by the TUNEL method (Gavrieli, et al. J. Cell Biol. 1992;119:493-501), we demonstrated the occurrence of apoptosis in fetal lungs in vivo and in explant culture. In the rat fetal lung (RFL) in vivo we detected apoptosis from 16 through 22 d gestation. There was variation in the amount of DNA digestion between fetal lungs, but no correlation with gestational age. The findings in human fetal lungs (HFL) from 15 through 24 wk gestation were similar to those of the RFL; the apoptotic indices for both were about 2 apoptotic cells per thousand, suggesting that a significant percentage of cells are eliminated by this mechanism. In the HFL explant culture system, a rapid and massive wave of apoptosis occurred. In all samples of RFL and HFL examined, apoptosis was restricted to interstitial cells. This work has demonstrated for the first time that apoptosis is a feature of normal fetal lung development and that the process is accelerated in lung explant culture.

Effects of mechanical factors on growth and maturation of the lung in fetal sheep.

Previous fetal studies indicated that endocrine factors control surfactant maturation, whereas mechanical forces affect lung growth, but not surfactant. We altered mechanical forces in fetal sheep lungs at 100-108 days gestation by tracheal ligation (TL, n = 15, 7 successful studies) to accelerate lung growth, transection of cervical spinal cord (TCSC, n = 17, 6 successful studies) to produce lung hypoplasia, or sham operation (n = 11, 6 successful studies). The reasons for the high mortality rates are not known. At delivery (130-142 days), groups were similar in gestational age, weight, and cortisol. Effects on lung growth were similar to, but effects on surfactant differed from, previous reports. TL increased lung growth but decreased saturated phosphatidylcholine (SatPC) and surfactant protein (SP)A and apparently decreased SP-B and relative numbers of alveolar type II cells (based on immunohistochemical studies of 1 animal in each group); TCSC had opposite effects. In contrast to a previous study (J. A. Kitterman, G. C. Liggins, G. A. Campos, J. A. Clements, C. S. Forster, C. H. Lee, and R. K. Creasy, J. Appl. Physiol, 51: 384-390, 1981), SatPC did not correlate with cortisol. We conclude that altering mechanical forces in fetal lung affects not only lung growth but also surfactant maturation and possibly alveolar epithelial differentiation and disturbs the normal correlation between cortisol and surfactant. Associated changes in insulin-like growth factor I (IGF-I; increased by TL, P = 0.003) suggest a possible role for IGF-I in these effects.

Outpatient management of diabetes mellitus in five Arizona Medicare managed care plans.

We report findings on the outpatient management of diabetes mellitus in Medicare beneficiaries enrolled in five Arizona Medicare-managed care plans. These findings are the baseline of an ongoing collaboration between the Health Services Advisory Group, Inc., Arizona's Peer Review Organization (PRO), and the five plans whose object is improved care of diabetes patients. The purpose of the study was to determine congruity between quality indicators identified by the five plans and the care actually received by diabetes patients enrolled in the five plans. The five plans agreed on a common set of quality indicators, including 10 services and 10 measures of patient status. Each plan has identified its diabetic population, 75 of whom are randomly selected each quarter by the PRO for chart review and inclusion in the study. The findings in this report cover two quarters of data. Data from chart review were examined to determine the extent to which actual practice reflected the indicators. The mean patient age was 71.8, and for most patients onset occurred between 55 and 69 years of age. About 25% had a positive family history, and we estimate the annual incidence of diabetes in this population to be about 1.1%. Mean hemoglobin A1c (HbA1c) was 8.9 +/- 2.1%; 46% were hypertensive; 42% continued to smoke cigarettes; 36% had retinopathy; 20% had proteinuria; and only 22% were on some kind of exercise program. Thirty-two percent were hospitalized during the 1-year baseline period, and the average number of outpatient visits per patient was 11.1 +/- 7.4. When care provided to diabetes patients enrolled in the plans was compared with the 10 quality standards identified by the plans themselves, only two of these standards was attained in more than 60% of patients: blood pressure, 98.7%; and foot examination, 62.7%. Two standards were achieved less than one-third of the time: urine dipstick, 10.4%, and appropriate use of angiotensin-converting enzyme (ACE) inhibitors, 31.25%. The others were all between 40 and 55%. Of the 10 service standards, about one-third received 1-4, one-third received 5-6, and one-third received 7-10. Only 5% of patients received 9 or 10 services. Outpatient management of diabetes patients in managed-care plans is similar to that in fee-for-service. When compared with fee-for-service or another HMO, a higher proportion of Arizona-managed care patients had HbA1c, and a much lower proportion had a dipstick test for urine protein. Values for other variables were usually within 10 percentage points of each other. Regardless of payment scheme, diabetes care is characterized by inconsistencies, omissions, and a lower than desirable level of services. Although few patients received most of the indicator services, diabetes patients are nevertheless high utilizers of medical care, both in and out of the hospital. The hospitalization rate is twice that of Arizona Medicare beneficiaries as a whole, and the number of office visits is three or four times that reported in other studies. Further, it seems that many visits are required to achieve even these modest service levels. Had the average number of visits been six or less, HbA1c rates, for example, would have fallen to less than one-third in three of the five plans. We believe that these data are conservative because it is likely that some and perhaps most of these indicators are underreported. It should be emphasized that these are baseline data whose purpose is to provide a basis against which subsequent improvements many be measured.

Induction of stable microtubules in 3T3 fibroblasts by TGF-beta and serum.

Previous studies have shown that fibroblasts induced to migrate into an in vitro wound rapidly generate an array of stable, post-translationally detyrosinated microtubules (Glu MTs) oriented toward the direction of migration. To understand how cells generate a stable array of MTs at a specific location, we have analyzed the contribution of media components to the formation of oriented Glu MTs in wounded monolayers of 3T3 fibroblasts. When confluent monolayers were placed in serum-free medium (SFM) for 2 days before wounding, the cells contained virtually no Glu MTs or nocodazole-resistant MTs and were incapable of generating Glu MTs in response to wounding. Such SFM-treated monolayers were capable of generating oriented Glu MTs within 1 hour of wounding, if calf serum (CS) was added back to the medium. The Glu MTs in the CS refed cells were oriented toward the wound in cells at the wound edge, and were juxtanuclear in cells within the monolayer, demonstrating that CS restored the Glu MT array characteristic of each cell type. To determine the nature of the 'Glu MT-inducing' factor in CS, we subjected CS to different treatments and found that the CS factor was nondialyzable, resistant to heat, mild acid and trypsin, but inactivated by treatment with dithiothreitol. The factor was not absorbed by charcoal and was present in lipoprotein-deficient serum. These properties are consistent with the properties of a number of polypeptide growth factors, so we screened purified growth factors for their ability to induce Glu MTs in wounded SFM-treated monolayers. Of all the growth factors tested, only TGF-beta 1 and TGF-beta 2 induced a significant level (> or = 70% of the CS response) of oriented Glu MTs. The SFM-treated cells were exquisitely sensitive to TGF-beta 1, with significant induction of Glu MTs observed at 0.01 ng/ml TGF-beta 1. Induction of Glu MTs observed by immunofluorescence after CS or TGF-beta treatments were paralleled by increases in Glu tubulin detected on western blots. The Glu MTs formed after either CS or TGF-beta 1 treatment showed enhanced resistance to nocodazole, confirming that both treatments increased the level of stable MTs in cells. The TGF-beta 1 induction of stable MTs was slower than that of CS (2-4 hours onset versus 1 hour onset), but by 24 hours the level of MT stabilization in TGF-beta 1 was even greater than that in CS.(ABSTRACT TRUNCATED AT 400 WORDS)

Stability of time-tradeoff utilities in survivors of myocardial infarction.

To investigate whether time-tradeoff utilities of survivors of myocardial infarction change over time and whether changes in utilities correlate with changes in functional status, the authors conducted serial interviews using a time tradeoff and three measures of functional status in a cohort of 67 patients who had recently had myocardial infarction. The patients were also asked to rate their overall health on a rating scale and were asked about chest pain, exercise status, and employment status. Each patient was interviewed two to five times over one and a half years. The mean (95% CI) time-tradeoff score for all patients was 0.88 (0.84, 0.93). Over a mean interval of 8.4 months, 28 (42%) patients changed Karnofsky scores, 28 (42%) changed Specific Activity Scale classes, and 11 (16%) changed New York Heart Association classes, with most changes representing improvements in functional status. Scores on the rating scale improved by a mean (95% CI) of 0.06 [(0.03, 0.10); p < 0.002], but scores on the time tradeoff remained stable, with a mean (95% CI) change of 0.03 [(-0.02, 0.08); p = NS]. Changes in time-tradeoff scores did not correlate with changes in Specific Activity Scale classes (Kendall's tau = 0.21), New York Heart Association classes (tau = -0.02), or Karnofsky scores (tau = 0.14); with changes on the verbal rating scale (R = 0.20); with changes in chest pain status (tau = -0.05), exercise status (tau = 0.11), or employment status (tau = 0.11); or with interim hospitalizations (tau = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of the spatial occurrence of childhood leukaemia mortality using standardized rate ratios with a simple linear Poisson model.

Reports of a suspected cluster of childhood leukaemia cases in West Central Phoenix have led to a number of epidemiological studies in the geographical area. We report here on a death certificate-based mortality study, which indicated an elevated rate ratio of 1.95 during 1966-1986, using the remainder of the Phoenix standard metropolitan statistical area (SMSA) as a comparison region. In the process of analysing the data from this study, a methodology for dealing with denominator variability in a standardized mortality ratio was developed using a simple linear Poisson model. This new approach is seen as being of general use in the analysis of standardized rate ratios (SRR), as well as being particularly appropriate for cluster investigations.

Distribution of detyrosinated microtubules in motile NRK fibroblasts is rapidly altered upon cell-cell contact: implications for contact inhibition of locomotion.

Fibroblasts migrating into an experimental wound contain an extensive array of detyrosinated microtubules (Glu MTs) oriented in the direction of migration, whereas nonmotile cells in the interior of a monolayer contain Glu MTs that are primarily coiled around the nucleus. To determine the role of cell-cell contact in the formation of these distinct arrays of Glu MTs, we studied the distribution of Glu MTs by immunofluorescence in NRK fibroblasts that had been fixed at different intervals after they had established contact with other cells. Time-lapse video recordings were made of the contacting cells to provide a record of cellular behavior. In motile cells that became completely surrounded by virtue of contact with other cells, Glu MTs were found mostly coiled around the nucleus. The proportion of cells whose Glu MTs extended to the original leading edge decreased dramatically after the cells had been surrounded for 10 min or more. At earlier times, when the contact was confined to a portion of the cell margin, Glu MTs were absent from the area behind the contact site, yet were still oriented toward the noncontacting and ruffling margins. The contact-induced alteration of Glu MTs was not due to the cessation of forward locomotion of cells per se, since immobilization of cells with cytochalasin D did not cause a dramatic change in Glu MTs. That cell-cell contact also specifies the type of Glu MTs formed in cells was shown by experiments in which MTs were regrown following complete depolymerization with nocodazole. The remodeling of Glu MTs during cell-cell contact may be involved in cellular repolarization during contact inhibition of locomotion and will be a useful marker for further dissecting the molecular events of contact inhibition of motility.

Effect of antitumor diarylsulfonylureas on in vivo and in vitro mitochondrial structure and functions.

Diarylsulfonylureas are novel oncolytic agents shown to have therapeutic activity against both rodent solid tumors and xenografts of human tumors in mice. Previous studies have shown that diarylsulfonylureas localize in mitochondria and cause morphological changes in these organelles. We have investigated the mechanism of action of diarylsulfonylureas, namely, N-(5-indanylsulfonyl)-N'-(4-chlorophenyl)urea (ISCU) and the N-4-methyl analogue (MPCU), by studying their effect on mitochondrial morphology and uptake of rhodamine 123 in GC3/c1 cells in culture and the oxidative phosphorylation in isolated mitochondria from mouse liver, using pyruvate-malate and succinate as substrates. Morphometric analysis of mitochondria in GC3/c1 cells exposed to ISCU showed that ISCU (165 microM) doubled the mitochondrial size after 24-h exposure in culture. Also, ISCU (100 microM), like 40 microM carbonylcyanide p-trifluoromethoxyphenylhydrazone, significantly reduced the rhodamine 123 uptake by GC3/c1 cells studied by flow cytometry. In isolated mitochondria both ISCU and MPCU uncoupled oxidative phosphorylation at 50 microM, with pyruvate-malate as substrate, as was indicated by a significant increase in the State 4 oxygen consumption. This resulted in the loss of ADP phosphorylation and, therefore, the ADP/oxygen ratio was reduced to zero and the respiratory control ratio to one. The succinate oxidation was also significantly impaired by ISCU, causing some decrease in ADP phosphorylation. On the other hand, MPCU did not exhibit any significant effect on the oxidation of succinate. At concentrations of lower than 50 microM, both of these compounds exhibited a deleterious effect, causing damage to mitochondrial functions in the presence of pyruvate-malate as substrates. These data confirm, through morphometric analysis, our previous qualitative observations of abnormal mitochondrial morphology observed in GC3/c1 cells grown in the presence of high concentrations of ISCU and MPCU and further suggest that diarylsulfonylureas, by uncoupling mitochondrial oxidative phosphorylation, may lower cellular ATP. It is probable that this mechanism contributes, at least partially, to cytotoxicity in GC3/c1 cells exposed to high concentrations of ISCU for relatively brief periods (2 to 4 h) and possibly contributes to cytotoxicity at drug concentrations that can be achieved in rodents.

Influence of extracellular pH on the accumulation and cytotoxicity of N-(4-methylphenylsulfonyl)-N'-(4-chlorophenyl)urea in human cell lines.

The effect of extracellular pH (pH(e)) on the accumulation and cytotoxicity of the diarylsulfonylurea antitumor agent N-(4-methylphenylsulfonyl)-N'-(4-chlorophenyl)urea (MPCU) has been examined. In a human colon adenocarcinoma cell line, GC3/C1, the initial rate of uptake of [3H]MPCU (2.4 microM) was increased by 4.5-fold as pH(e) was reduced from 7.4 to 6.5. Steady state levels of MPCU were inversely proportional to pH(e) and were 5-fold greater at pH 6.0 compared to 7.4. Similar results were obtained using Rh30 cells derived from an alveolar rhabdomyosarcoma. MPCU rapidly re-equilibrated after achieving steady state when pH(e) was altered, indicating that MPCU was not tightly bound within cells. In both cell lines, the uncoupling agent, carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP), significantly reduced (GC3/C1) or completely inhibited (Rh30) accumulation of MPCU at each pH(e) examined. Sodium azide had the same effect on the accumulation of MPCU as FCCP. The effects of FCCP and azide appeared to be due to collapse of the pH differential across the mitochondrial inner membrane rather than the gradient across the plasma membrane. As extracellular pH (pH(e)) decreased, intracellular pH(pH(i)) also decreased in GC3/C1 cells, such that the greatest pH differential (pH(i) - pH(e)) was 0.2 units at pH(e) 6.0. Neither FCCP nor azide significantly altered this pH gradient, indicating a minor role, if any, for the plasma membrane pH gradient in accumulation of MPCU in GC3/C1 cells. The effect of pH(e) (7.4 to 6.0) on cytotoxicity of MPCU was determined after exposure of cells for 4 hr to various concentrations of MPCU in the presence of 10% fetal bovine serum. Decreasing the pH(e) from 7.4 to 6.0 increased the potency of MPCU by 4.7- and 4.5-fold in Rh30 and GC3/C1 cells, respectively. In cells exposed to drug/pH(e) combinations that resulted in 50% reduction in colony forming potential, the steady state levels of [3H]MPCU were similar (range 8.8 +/- 0.9 to 10.56 +/- 0.6 nmol/10(6) cells). These results demonstrate that decrease of pH(e) significantly enhanced the uptake of MPCU accumulation into an FCCP/azide-sensitive compartment, and cytotoxicity of this agent. These data further support the hypothesis that sequestration of diarylsulfonylureas into the FCCP/azide-sensitive compartment (probably mitochondria) was associated with its cytotoxicity. The role of pH(e) in determining therapeutic selectivity of diarylsulfonylureas is discussed.

Spectrophotometric determination of circulating cholinesterases in rats.

A spectrophotometric assay was established to determine circulating levels of cholinesterase (ChE) in the whole blood of rats. A commercially available ChE reagent set was obtained and the suggested procedure modified to quantify and correct for the activity resulting from nonenzymatic hydrolysis of the substrate. The stability of ChE as well as the effect of sampling site, exercise, and carbamate administration were evaluated. The ChE activity of blood drawn from a jugular cannula (central sample) was less than that drawn from a lateral tail vein (peripheral sample), but percent change in activity between sampling times was not different between the two sites. Cholinesterase in carbamate-inhibited blood was not stable and had to be assayed soon after sampling. Therefore, if the assay is performed soon after sampling, rat whole blood ChE activity may be determined spectrophotometrically, and the blood may be sampled either peripherally or centrally.

Short-term release cues to stop-consonant place of articulation in child speech.

In recent work Blumstein and Stevens (J. Acoust. Soc. Am. 66, 1001-1017 (19179); 67, 648-662 (1980) have proposed that the short-term onset spectra at stop-consonant releases provide invariant cues for the perception of place of articulation, and that the salient acoustic characteristics of these cues can be characterized by a set of templates. The present study investigated the suitability of these templates for characterizing place of articulation in utterance-initial voiced stop consonants produced by two children 71-75 weeks old in spontaneous discourse. The overall correct categorization rate for the templates was 65%, with 70% correct categorizations for the bilabial template, 85% for the alveolar template, and 40% for the velar template. The results of a perceptual study in which listeners were asked to identify place of articulation for computer-edited 15-, 25-, 40-, and 135-ms samples of the initial parts of these utterances were compared with the results of the template matching study. Although listeners' identification of place of articulation was at well above chance level on even the 15-ms tokens, there was no correlation between the results of the template-matching study and the perceptual data. The perceptual data thus indicate that short-term onset cues exist in the spontaneous speech of children at an early stage of language development, however, these cues do not appear to be adequately characterized by the Blumstein-Stevens templates.

Effects of twinning on lactation and days open in Holsteins.

Effects of twinning on lactation and days open in Holsteins were studied from calving records compiled by member surveys of Eastern Artificial Insemination Cooperative. Records of cows with 305-day mature-equivalent records from the Northeast Dairy Records Processing Laboratory were grouped according to whether the twin calving was associated with dystocia. Records of each cow that had a twin calving were paired with records of a single-calving control herdmate. In the twin group of 175 cows associated with dystocia, twin pregnancy had no effect on production; milk and fat production in the lactation initiated by twinning was depressed (137 kg and 7 kg) although not significantly; and days open following twin calving was increased. In the twinning group of 367 cows with no dystocia at twinning, milk and fat production were depressed by 285 kg and 14 kg in the lactation initiated by the twinning. Days open after twinning were increased by about 22 days. These results indicate a negative economic effect of twinning on lactation performance in Holstein cattle. Increased rates of twinning via selection or artificial induction of twinning dairy cattle appear not to be desirable.