Overweight/obesity and chronic health conditions in older people with intellectual disability in Ireland.

BACKGROUND: This study examines overweight/obesity and chronic health conditions (CHCs) in older people with intellectual disability (ID). METHODS: Data for this cross-sectional observational study emanated from Wave 2 of the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing, a longitudinal study assessing the health and well-being of older Irish adults with ID aged ≥40 years across all levels of ID. Participation involves an interview process and collation of objective health measures. In this study, body mass index (BMI) (n = 572), used as a measure of weight status, was examined with clustered doctor's diagnosed CHCs. Descriptive analysis was conducted where counts (n) and proportions (%) were used to summarise the variables univariately, while cross-tabulations were used for bivariate summary into counts and proportions. With overweight/obesity prevalence established and patterns described using logistical regression, Pearson's chi-squared test was used to test for significant associations. RESULTS: Overweight/obesity identified in 69% of participants occurred with greater frequency in women (72%). A higher percentage of participants aged <50 years (72.5%) were overweight/obese than those aged 50-64 (70%) and 65+ (61.4%). Level of ID and residence type were significantly associated with weight status (P < 0.001), with overweight/obesity more prevalent in mild (85.7%) than moderate (72%) or severe/profound ID (51.4%). Of those who lived independently/with family, 78.4% were overweight/obese, as were 74% living in a community group home (P < 0.001). Almost all overweight/obese participants' waist measurements were in the substantially increased risk of metabolic disease waist measurement category (92%, P < 0.001). Logistical regression used to model CHCs on BMI showed significant association between BMI and gastrointestinal tract [odds ratio (OR) = 0.57, P < 0.008, 95% confidence interval (CI) = (0.37; 0.86)], respiratory condition [OR = 8.95, P < 0.004, 95% CI = (2.57; 56.72)] and musculoskeletal disorders [OR = 0.40, P < 0.001, 95% CI = (0.25; 0.63)]. CONCLUSIONS: The findings illustrate the strong cross-sectional association between overweight/obesity and CHCs. These findings suggest a need to prioritise weight status as a health risk to people with ID as they age.

Outcomes of renal replacement therapy in the critically ill with COVID-19.

OBJECTIVE: To describe outcomes of critically ill patients with COVID-19, particularly the association of renal replacement therapy to mortality. DESIGN: A single-center prospective observational study was carried out. SETTING: ICU of a tertiary care center. PATIENTS: Consecutive adults with COVID-19 admitted to the ICU. INTERVENTION: Renal replacement therapy. MAIN VARIABLES OF INTEREST: Demographic data, medical history, illness severity, type of oxygen therapy, laboratory data and use of renal replacement therapy to generate a logistic regression model describing independent risk factors for mortality. RESULTS: Of the total of 166 patients, 51% were mechanically ventilated and 26% required renal replacement therapy. The overall hospital mortality rate was 36%, versus 56% for those requiring renal replacement therapy, and 68% for those with both mechanical ventilation and renal replacement therapy. The logistic regression model identified four independent risk factors for mortality: age (adjusted OR 2.8 [95% CI 1.8-4.4] for every 10-year increase), mechanical ventilation (4.2 [1.7-10.6]), need for continuous venovenous hemofiltration (2.3 [1.3-4.0]) and C-reactive protein (1.1 [1.0-1.2] for every 10 mg/L increase). CONCLUSIONS: In our cohort, acute kidney injury requiring renal replacement therapy was associated to a high mortality rate similar to that associated to the need for mechanical ventilation, while multiorgan failure necessitating both techniques implied an extremely high mortality risk.

OBJETIVO: Describir los resultados de pacientes críticamente enfermos con COVID-19, especialmente la asociación de la terapia de reemplazo renal con la mortalidad. DISEÑO: Estudio observacional, prospectivo y unicéntrico. ÁMBITO: En la unidad de cuidados intensivos (UCI) de un centro de atención terciaria. PACIENTES: Pacientes adultos con COVID-19 ingresados de forma consecutiva en la UCI. INTERVENCIÓN: Administración de terapia de reemplazo renal. VARIABLES DE INTERÉS PRINCIPALES: Datos demográficos, antecedentes médicos, gravedad de la enfermedad, tipo de oxigenoterapia, datos analíticos y uso de terapia de reemplazo renal para generar un modelo de regresión logística que describa factores de riesgo independientes de la mortalidad. RESULTADOS: De los 166 pacientes, el 51% recibieron ventilación mecánica (VM) y el 26% requirió terapia de reemplazo renal (TRR). La mortalidad hospitalaria global fue del 36%, frente al 56% en el caso de los pacientes que requirieron TRR y el 68% en el subconjunto de pacientes que necesitó tanto VM como RTT. Un modelo de regresión logística señala cuatro factores de riesgo independientes de la mortalidad: edad (OR ajustada: 2,8 [IC del 95%: 1,8-4,4] por cada incremento de 10 años), ventilación mecánica (4,2 [1,7-10,6]), necesidad de hemofiltración venovenosa continua (HVVC) (2,3 [1,3-4,0]), y proteína C reactiva (1,1 [1,0-1,2] por cada incremento de 10 mg/L). CONCLUSIONES: En nuestra cohorte, la lesión renal aguda que necesita TRR se asocia con una mortalidad similarmente elevada a la de los pacientes que requieren VM, y la insuficiencia multiorgánica que hace necesarias ambas intervenciones se asocia con un riesgo de mortalidad extremadamente alta.

Surgical Parathyroidectomy Services

Aims Retrospectively audit our experience with surgical parathyroidectomy over a 5 year period from the beginning of 2013 to June 2018. Methods Hospital In-patient Enquiry (HIPE) data, NIMIS radiology and theatre logs were used to identify the study cohort of a single specialist parathyroid surgeon. Demographic data plus pre and post-op calcium and parathyroid Hormone (PTH) levels were analysed. Data were coded and entered into SPSS 24 statistical software package for analysis. Results Thirty-one surgical parathyroidectomy cases were identified comprising four male and twenty seven females. Average age was 59.81 years (SD 14.75). The median pre-op and post-op calcium levels were 2.81[elevated] (Range 2.37-4.06 mmol/L) and 2.42[normal] (2.16-3.31 mmol/L) respectively and were statistically significant therapeutic reductions (p<0.05). The median pre-op and post-op PTH levels were 168.0[elevated] (Range 69-3171 pg/ml) and 41.7 [normal] (7.30-1628 pg/ml) respectively. All patients were discharged on post op day 1. Conclusion Parathyroidectomy is a safe and cost-effective treatment for PHPT in University Hospital Waterford.

Biallelic mutations in mitochondrial tryptophanyl-tRNA synthetase cause Levodopa-responsive infantile-onset Parkinsonism.

Mitochondrial aminoacyl-tRNA synthetases (mtARSs) are essential, ubiquitously expressed enzymes that covalently attach amino acids to their corresponding tRNA molecules during translation of mitochondrial genes. Deleterious variants in the mtARS genes cause a diverse array of phenotypes, many of which involve the nervous system. Moreover, distinct mutations in mtARSs often cause different clinical manifestations. Recently, the gene encoding mitochondrial tryptophanyl tRNA synthetase (WARS2) was reported to cause 2 different neurological phenotypes, a form of autosomal recessive intellectual disability and a syndrome of severe infantile-onset leukoencephalopathy. Here, we report the case of a 17-year-old boy with compound heterozygous mutations in WARS2 (p.Trp13Gly, p.Ser228Trp) who presented with infantile-onset, Levodopa-responsive Parkinsonism at the age of 2 years. Analysis of patient-derived dermal fibroblasts revealed decreased steady-state WARS2 protein and normal OXPHOS content. Muscle mitochondrial studies suggested mitochondrial proliferation without obvious respiratory chain deficiencies at the age of 9 years. This case expands the phenotypic spectrum of WARS2 deficiency and emphasizes the importance of mitochondrial protein synthesis in the pathogenesis of Parkinsonism.

An exploration of the bone health of older adults with an intellectual disability in Ireland.

BACKGROUND: Many risk factors have been confirmed for poor bone health among the general population including age, gender and corticosteroid use. There is a paucity of investigation among people with intellectual disability; however, research points to differing risks namely anti-epileptic medication use, Down syndrome and poor behaviour lifestyle. METHODS: Data was extracted from the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing in Ireland. In total, 753 participants took part, and data was gathered on participants' health status, behavioural health, health screenings and activities of daily living. The prevalence of osteoporosis and related risk factors were specifically examined. RESULTS: Overall, 8.1% reported a doctor's diagnosis of osteoporosis with over 20% reporting history of fracture. Risk identified included older age (P < 0.0001), female gender (P < 0.0001), difficulty walking (P < 0.0001) with older age and being female the stronger predictors for osteoporosis, odds ratio = 6.53; 95% confidence interval 2.82-15.11 and odds ratio = 4.58; 95% confidence interval 2.29-9.17, respectively. There was no gender difference regarding the level of fractures; however, epilepsy and anti-epileptic medication were strong predictors. Overall, 11.1% attended for bone screening diagnostics. CONCLUSION: Despite low levels of reported doctor's diagnosis of osteoporosis risk factor prevalence was high. Considering the insidious nature of osteoporosis and the low levels of diagnostic screening, prevalence could be possibly higher.

Antimicrobial-resistant Faecal Organisms in Algae Products Marketed as Health Supplements.

Dietary supplements are increasingly popular in Irish society. One of these is blue-green algae which is used with a variety health benefits in mind. A batch of Chlorella powder was found to be contaminated with Salmonella species in Ireland in 2015. This prompted additional testing of a total of 8 samples of three different products (Chlorella, Spirulina and Super Greens), for other faecal flora and antimicrobial resistance in any bacteria isolated. All 8 samples cultured enteric flora such as Enterococci, Enterobacteriaceae and Clostridium species. Antimicrobial susceptibility testing revealed one isolate with extended-spectrum ?-lactamase (ESBL) activity and one with carbapenemase activity. Clinicians caring for vulnerable patients should be aware of the potential risk of exposure to antimicrobial resistant bacteria associated with these products.

The conversion of allenes to strained three-membered heterocycles.

This article reviews methods for converting allenes to strained, three-membered methylene heterocycles, and also covers the reactivity of these products. Specifically, the synthesis and reactivity of methylene aziridines, allene oxides/spirodiepoxides, methylene silacyclopropanes, methylene phosphiranes, and methylene thiiranes are described, including applications to the synthesis of complex molecules. Due to the primary focus on heterocyclic motifs, the all-carbon analogue of these species (methylene cyclopropane) is only briefly discussed.

Outcomes of renal replacement therapy in the critically ill with COVID-19.

OBJECTIVE: To describe outcomes of critically ill patients with COVID-19, particularly the association of renal replacement therapy to mortality. DESIGN: A single-center prospective observational study was carried out. SETTING: ICU of a tertiary care center. PATIENTS: Consecutive adults with COVID-19 admitted to the ICU. INTERVENTION: Renal replacement therapy. MAIN VARIABLES OF INTEREST: Demographic data, medical history, illness severity, type of oxygen therapy, laboratory data and use of renal replacement therapy to generate a logistic regression model describing independent risk factors for mortality. RESULTS: Of the total of 166 patients, 51% were mechanically ventilated and 26% required renal replacement therapy. The overall hospital mortality rate was 36%, versus 56% for those requiring renal replacement therapy, and 68% for those with both mechanical ventilation and renal replacement therapy. The logistic regression model identified four independent risk factors for mortality: age (adjusted OR 2.8 [95% CI 1.8-4.4] for every 10-year increase), mechanical ventilation (4.2 [1.7-10.6]), need for continuous venovenous hemofiltration (2.3 [1.3-4.0]) and C-reactive protein (1.1 [1.0-1.2] for every 10mg/L increase). CONCLUSIONS: In our cohort, acute kidney injury requiring renal replacement therapy was associated to a high mortality rate similar to that associated to the need for mechanical ventilation, while multiorgan failure necessitating both techniques implied an extremely high mortality risk.

Immunization with soluble BDC 2.5 T cell receptor-immunoglobulin chimeric protein:antibody specificity and protection of nonobese diabetic mice against adoptive transfer of diabetes by maternal immunization.

The BDC 2.5 T cell clone is specific for pancreatic beta-cell antigen presented by I-Ag7, and greatly accelerates diabetes when injected into 10-21-d-old nonobese diabetic (NOD) mice. The BDC 2.5 T cell receptor (TCR) has been solubilized as a TCR-IgG1 chimeric protein. All NOD mice immunized against BDC 2.5 TCR-IgG1 produced antibodies recognizing TCR C alpha/C beta epitopes that were inaccessible on the T cell surface. 56% of the mice produced antibodies against the BDC 2.5 clonotype that specifically blocked antigen activation of BDC 2.5 cells. We have used the adoptive transfer model of diabetes to demonstrate that maternal immunization with soluble TCR protects young mice from diabetes induced by the BDC 2.5 T cell clone.

Optimising the management of concurrent symphyseal/parasymphyseal and bilateral extracapsular condylar fractures using three-dimensional printing.

PURPOSE: Three-dimensional (3D) printing plays an important role in the diagnosis and treatment planning of many elective procedures in oral and maxillofacial surgery (OMFS). 3D printers and the associated print materials are now within the price range of most maxillofacial units, requiring less work to be sent out to commercial printers. Whilst their use in the planning of elective procedures is commonplace, acute trauma is an area where 3D printing remains underutilised. The successful management of complex fracture patterns such as concomitant symphyseal/parasymphyseal and bilateral condylar fractures often warrants this approach. METHODS: Freeware digital processing and manipulation software packages were used to view and segment structures from computed tomography (CT) data. Thereafter, fractures were digitally reduced. 3D printed models were produced from the digitally reduced models, allowing preoperative custom adaptation of osteosynthesis plates, facilitating accurate fracture fixation intraoperatively. RESULTS: For less than one hundred pounds sterling (STG), a 3D printer (with print material) capable of producing a model of sufficient quality can be purchased. The use of freeware digital processing software allows digital manipulation of CT data. Production of 3D models and plate adaptation can be carried out within hours after CT examination. CONCLUSIONS: The construction of digitally reduced 3D models and custom adapted plates enables the surgeon to achieve accurate fixation of complex fracture patterns in theatre which is clearly of benefit to patients. The potential for reduced theatre time also renders this approach more desirable, making this a worthwhile investment despite the additional non-clinical time associated with training and initial expenditure.

Tubular lysosomes accompany stimulated pinocytosis in macrophages.

A network of tubular lysosomes extends through the cytoplasm of J774.2 macrophages and phorbol ester-treated mouse peritoneal macrophages. The presence of this network is dependent upon the integrity of cytoplasmic microtubules and correlates with high cellular rates of accumulation of Lucifer Yellow (LY), a marker of fluid phase pinocytosis. We tested the hypothesis that the efficiency of LY transfer between the pinosomal and lysosomal compartments is increased in the presence of tubular lysosomes by asking how conditions that deplete the tubular lysosome network affect pinocytic accumulation of LY. Tubular lysosomes were disassembled in cells treated with microtubule-depolymerizing drugs or in cells that had phagocytosed latex beads. In unstimulated peritoneal macrophages, which normally contain few tubular lysosomes and which exhibit relatively inefficient transfer of pinocytosed LY to lysosomes, such treatments had little effect on pinocytosis. However, in J774 macrophages and phorbol ester-stimulated peritoneal macrophages, these treatments markedly reduced the efficiency of pinocytic accumulation of LY. We conclude that a basal level of solute accumulation via pinocytosis proceeds independently of the tubular lysosomes, and that an extended tubular lysosomal network contributes to the elevated rates of solute accumulation that accompany macrophage stimulation. Moreover, we suggest that the transformed mouse macrophage cell line J774 exhibits this stimulated pinocytosis constitutively.

Meanings and feelings of (Im)mobility in later life: Case study insights from a 'New Mobilities' perspective.

Understandings of mobility and immobility shape research and responses to late life. Yet, the underlying assumptions about mobility often remain fixed on ideas of function and physical ability. The 'new mobilities' paradigm shifts this analysis by focusing on the importance and experience of mobility as a thing in itself rather than a means to an end, and to the complex enactments that operate across a range of relationships, settings, sites, and contexts. This paper provides insight from an embedded case study method comprised of fifteen exploratory interviews with older people at three social locations, including 5 individuals considered 'frail', 5 people who are aging with a disability, and 5 older people who self-identify as 'active'. Considered together and in contrast, the findings from these three distinct but related embedded case sites, viewed from a 'new mobilities' perspective, can help to understand (im)mobility as an embodied experience that is situated within and across social and political contexts, and can explicate how relations of power enhance the mobility of some, and the immobility of others. We conclude that the 'new mobilities' approach introduces ideas to overcome limitations of distance, movement, and place, and in doing so, serves to redefine what it means to be mobile while aging.

Anti-CD25 treatment and FOXP3-positive regulatory T cells in heart transplantation.

The interleukin-2 receptor alpha chain (IL-2Ra, CD25) plays a major part in shaping the dynamics of T cell populations following immune activation, due to its role in T cell proliferation and survival. Strategies to blunt the effector responses in transplantation have been developed by devising pharmaceutical agents to block the IL-2 pathways. However, such strategies could adversely affect the CD25(+)FOXP3(+)T regulatory (T reg) populations which also rely on intereukin-2 signaling for survival. The present study shows that a cohort of heart allograft recipients treated with Daclizumab (a humanized anti-CD25 antibody) display FOXP3 expression patterns consistent with functional T regulatory cell populations. High levels of FOXP3 were observed to correlate with lower incidence of and recovery from acute rejection, as well as lower levels of anti-donor HLA antibody production. Therefore, T reg populations appear fully functional in patients treated with Daclizumab, even when 5 doses were administered. By comparison, patients treated with fewer doses or no Daclizumab had a higher incidence of acute rejection, antibody production and graft failure. Therefore, our data indicates that Daclizumab treatment does not interfere with the generation of regulatory T cells and has a beneficial effect on heart allograft survival.

Pharyngeal flap and obstructive apnea: maximizing speech outcome while limiting complications.

OBJECTIVE: To assess speech results and rate of obstructive sleep apnea using a modified, superiorly based pharyngeal flap performed after staged adenotonsillectomy in a group with velopharyngeal insufficiency. METHODS: In this nonrandomized, retrospective case series (July 1, 1996, through June 30, 2003), patients were mainly children referred to a multispecialty craniofacial clinic. Patients underwent staged adenotonsillectomy 2 months before width-customized pharyngeal flap surgery. Short flaps were created high above the level of the palate, just long enough to reach the nasal surface. Donor sites were closed by superior advancement of the inferior posterior pharyngeal wall tissue. Cardiopulmonary and oximetry data were analyzed for immediate obstructive apnea. Speech results and airway symptoms were assessed at 6-month and yearly follow-up examinations. RESULTS: In the 54 consecutive patients who underwent staged adenotonsillectomy, no apnea occurred immediately after surgery. Long-term clinical examination revealed 4 cases of loud snoring. Polysomnographic results were negative in all cases. Complications included 3 cases of bleeding, 1 requiring transfusion. Velopharyngeal insufficiency was eliminated in 94% of patients. CONCLUSION: Complications related to obstructive sleep apnea have been significantly reduced while maintaining excellent speech results by a staged approach of removing tonsils and adenoids and by creating a short, high, wide, superiorly based pharyngeal flap with superior advancement of the inferior posterior wall to close the donor site.

Upper airway asymmetry in velo-cardio-facial syndrome.

OBJECTIVE: Various forms of asymmetry have been recognized as a feature of velo-cardio-facial syndrome (VCFS). This study was implemented to determine the frequency of anatomic and functional asymmetry of the velum, pharynx and larynx in children with VCFS. METHODS: Individuals with VCFS underwent prospective, blinded analysis by an expert panel who assessed the velum, pharynx and larynx with multi-view videofluoroscopy (MVF) and nasopharyngolaryngoscopy (NPL). The VCFS group was compared to an age-matched group of normal individuals. Eight different parameters were assessed in both groups for functional and anatomic symmetry including: velar elevation, adenoid size, posterior pharyngeal wall size, carotid pulsations, epiglottis size and shape, arytenoid size, true vocal cord size and true vocal cord motion. RESULTS: One hundred and twenty-one subjects with VCFS and 20 normal individuals underwent examination. Children with VCFS showed significantly more asymmetry compared to the normal group (69% versus 20%, P=0.01) with greatest differences seen with palatal motion, posterior pharyngeal wall size and epiglottis shape. On average, subjects with VCFS had three asymmetric parameters versus one parameter in the normal group. CONCLUSION: Asymmetric development of the pharynx and larynx in children with VCFS appears to be a distinct clinical feature of this syndrome. This finding may provide an important diagnostic clue for patients presenting with subtle features of the 22q11.2 microdeletion. These developmental abnormalities may increase the risk of speech impairment, aspiration and airway obstruction in affected individuals.

Bronchiolitis obliterans organizing pneumonia in a patient with non-Hodgkin's lymphoma following R-CHOP and pegylated filgrastim.

Bronchiolitis obliterans organizing pneumonia (BOOP) presents with fever, dyspnoea, pleuritic chest pain and hypoxia. The diagnosis can be made from radiological appearances on chest radiograph and CT scan correlated with histological findings following biopsy. We present a 52-year-old gentleman undergoing treatment for high grade non-Hodgkin's lymphoma who developed respiratory symptoms during chemotherapy. BOOP was diagnosed and he responded well to oral prednisolone. The cause of BOOP is often not certain. However, in this case we suspect pegylated filgrastim or rituximab as possible agents.

A simplified, data-constrained approach to estimate the permafrost carbon-climate feedback.

We present an approach to estimate the feedback from large-scale thawing of permafrost soils using a simplified, data-constrained model that combines three elements: soil carbon (C) maps and profiles to identify the distribution and type of C in permafrost soils; incubation experiments to quantify the rates of C lost after thaw; and models of soil thermal dynamics in response to climate warming. We call the approach the Permafrost Carbon Network Incubation-Panarctic Thermal scaling approach (PInc-PanTher). The approach assumes that C stocks do not decompose at all when frozen, but once thawed follow set decomposition trajectories as a function of soil temperature. The trajectories are determined according to a three-pool decomposition model fitted to incubation data using parameters specific to soil horizon types. We calculate litterfall C inputs required to maintain steady-state C balance for the current climate, and hold those inputs constant. Soil temperatures are taken from the soil thermal modules of ecosystem model simulations forced by a common set of future climate change anomalies under two warming scenarios over the period 2010 to 2100. Under a medium warming scenario (RCP4.5), the approach projects permafrost soil C losses of 12.2-33.4 Pg C; under a high warming scenario (RCP8.5), the approach projects C losses of 27.9-112.6 Pg C. Projected C losses are roughly linearly proportional to global temperature changes across the two scenarios. These results indicate a global sensitivity of frozen soil C to climate change (γ sensitivity) of -14 to -19 Pg C °C(-1) on a 100 year time scale. For CH4 emissions, our approach assumes a fixed saturated area and that increases in CH4 emissions are related to increased heterotrophic respiration in anoxic soil, yielding CH4 emission increases of 7% and 35% for the RCP4.5 and RCP8.5 scenarios, respectively, which add an additional greenhouse gas forcing of approximately 10-18%. The simplified approach presented here neglects many important processes that may amplify or mitigate C release from permafrost soils, but serves as a data-constrained estimate on the forced, large-scale permafrost C response to warming.

Re-epithelialization of porcine skin by the sweat apparatus.

The behavior of the keratinocyte during the initial stages of cutaneous wound repair has been the subject of intense investigation. Most of these studies have focused on the lateral edges of wounds as the source of activated keratinocytes. Less attention has been directed towards elucidating the role of the appendageal structures as sources of keratinocytes for re-epithelialization, particularly the sweat apparatus. Surgical wounds of specific depths were created in pig skin, above and below hair follicles, and wound healing was allowed to take place in a setting in which lateral ingrowth of keratinocytes by migration was prevented. In this manner, all re-epithelialization occurred from residual appendageal structures. In those wounds where only sweat gland elements remained, an epithelium formed that had clinical, morphologic, and protein electrophoretic features closer to palmar/plantar or mucosal-like epithelia. In contrast, wounds that retained elements of the hair follicle healed faster and the resultant epithelium clinically, morphologically, and biochemically resembled the surrounding nonwounded epidermis. These findings establish that the sweat apparatus is capable of re-epithelializing the skin surface after a major cutaneous wound, but may not be capable of mimicking the epidermis.

Glucose stimulates IGF-I gene expression in C6 glioma cells.

Glucose stimulates expression of the insulin-like growth factor I (IGF-I) gene in cultured C6 glioma cells. This stimulation is specific, as the expression of other genes, including those encoding hypoxanthine guanine phosphoribosyl transferase (HPRT) and ubiquitin, is not similarly affected by glucose. IGF-I gene expression is also stimulated by lactate, suggesting that the stimulatory effect is mediated by a product of glycolysis. Additional results indicate that the abundance of IGF-I mRNA is considerably higher in stationary confluent cells than in log-phase growing cells. This regulation is also specific for IGF-I, as HPRT mRNA is regulated in the opposite direction.