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Pseudohypertriglyceridemia is an overestimation of serum triglyceride levels that may incorrectly lead to a diagnosis of hypertriglyceridemia. Glycerol kinase deficiency is a condition in which glycerol cannot be phosphorylated to glycerol-3-phosphate, resulting in elevated levels of serum glycerol. Laboratory assays that measure triglycerides indirectly may be affected by elevated glyerol levels and incorrectly report serum tryglyceride levels. We present a case of a novel missense mutation in the GK gene leading to isolated glycerol kinase deficiency and pseudohypertriglyceridemia in a male infant of a mother with gestational diabetes. This paper reviews glycerol kinase deficiency, describes the challenges in diagnosing pseudohypertriglyceridemia, and provides suggestions on improving diagnostic accuracy. Additionally, a potential maternal-fetal interaction between gestational diabetes and glycerol kinase deficiency is discussed.

At the University of Oklahoma Health Sciences Center Department of Pathology, we view excellence in training in clinical chemistry as an important element of our highly regarded clinical pathology residency training program. Over the years, this program has evolved into essential components that overall have proven to be most effective in producing high-quality clinical pathologists. These components are described below. ### Clinical Chemistry Training Overview Our chemistry resident teaching rotation consists of 14-week blocks (Table 1) that span 3 separate months of training in chemistry as well as other areas of the automated core laboratory, including phlebotomy, specimen processing and receiving, point-of-care testing, toxicology, endocrinology, hematology, coagulation, urinalysis, and specimen referral testing. The 3 separate months include introductory training (first-year residents), intermediate training (second-year residents), and advanced training (third- and fourth-year residents) in an effort to make our program progressive and therefore consistent with Accreditation Council for Graduate Medical Education (ACGME) (1) accreditation requirements. This progressive training “journey” allows a resident to gradually assume the role of a fully competent Laboratory Director. View this table: Table 1. Topics covered in a 14-week clinical chemistry residency training. The textbooks used for the chemistry rotation are The Professional Practice in Clinical Chemistry: A Review (2), Contemporary Practice in Clinical …

Background Activating autoantibodies (AAb) to adrenergic receptors (AR) have previously been reported in patients with postural tachycardia syndrome (POTS). These AAb may contribute to a final common pathway for overlapping disease processes, reflecting a possible autoimmune contribution to POTS pathophysiology. In prior studies, measurement of AAb activity was inferred from costly, low-throughput, and laborious physiological assays. In the present study, we developed and validated an alternative cell-based bioassay for measuring AAb activity in serum by means of pre-treatment with monoamine oxidase (MAO). Methods A total of 37 POTS patients and 61 sex-matched healthy control participants were included. Serum was pre-treated with MAO to remove endogenous catecholamines that could falsely inflate AR activation by AAb. A receptor-transfected cell-based bioassay was used to detect presence of α1AR-AAb and β1AR-AAb in serum. Results MAO effectively degraded catecholamines as demonstrated by suppression of norepinephrine-induced α1AR activation in POTS (6.4 ​± ​0.7 vs. 5.5 ​± ​0.9; P ​= ​0.044) and in controls (4.1 ​± ​0.5 vs. 3.9 ​± ​0.6; P ​= ​0.001). Mean activity values were greater in the POTS vs. Controls for α1AR-AAb (6.2 ​± ​1.2 vs. 5.3 ​± ​1.0; P ​, Highlights • Catecholamines can exist in stored frozen serum samples, even without antioxidants or preservatives. • MAO pre-treatment removes interference by endogenous catecholamines in serum. • POTS patients show elevated α1AR and β1AR activation by autoantibodies vs. Controls.

This article presents an overview of the curriculum deemed essential for trainees in pathology, with mapping to the Milestones competency statements. The means by which these competencies desired for pathology graduates, and ultimately practitioners, can best be achieved is discussed. The value of case (problem)-based learning in this realm, in particular the kind of integrative experience associated with hands-on projects, to both cement knowledge gained in the lecture hall or online and to expand competency is emphasized.

Respiratory distress syndrome causes morbidity and mortality of the newborn and is most often associated with premature birth. Laboratory testing can be helpful in establishing fetal lung maturity (FLM) status in situations when premature delivery may be necessary. In addition, the rising incidence of late-preterm births at >34 and =50 k/mm3.

We report a case of a false-positive HIV result in an apparently healthy pregnant woman. Since no prenatal HIV testing had been performed, we screened for HIV reactivity utilizing the Architect HIV-Ag/Ab Combo assay. Results obtained were inconsistent in that they were repeatedly HIV reactive on a single serum sample while nonreactive on a plasma sample. However, both sample types were nonreactive on the Advia Centaur HIV-1/O/2 and Oraquick assays. For further confirmation, an HIV-1 Western blot and viral load were performed; blot results were indeterminate while the viral load was undetectable. We concluded that the repeatedly reactive serum serology results were false-positive. While the cause of this false reactivity is not clear, most likely fibrin microclots in the serum sample interfered with the assay and thus accounted for the false positivity. Plasma may thus provide a more appropriate sample type when using the Architect assay, especially when testing pregnant women.

Delays in diagnosis and treatment of cardiac patients presenting in the Emergency Department with symptoms of acute coronary syndromes are associated with poorer patient outcomes; hence, the timely and accurate diagnosis in the Emergency Department now requires the 24/7 availability of real-time, rapid testing for cardiac markers. Cardiac troponin (cTnI) has emerged as the biomarker of choice to aid physicians in the diagnosis of acute myocardial infarction and moreover current guidelines call for cTnI results to be available to clinicians within 60 minutes of blood draw each and every time a cTnI is ordered.

Objectives: To develop a fully automated core laboratory, handling samples on a “first in, first out” real-time basis with Lean/Six Sigma management tools. Methods: Our primary goal was to provide services to critical care areas, eliminating turnaround time outlier percentage (TAT-OP) as a factor in patient length of stay (LOS). A secondary goal was to achieve a better laboratory return on investment. Results: In 2011, we reached our primary goal when we calculated the TAT-OP distribution and found we had achieved a Six Sigma level of performance, ensuring that our laboratory service can be essentially eliminated as a factor in emergency department patient LOS. We also measured return on investment, showing a productivity improvement of 35%, keeping pace with our increased testing volume. Conclusions: As a result of our Lean process improvements and Six Sigma initiatives, in part through (1) strategic deployment of point-of-care testing and (2) core laboratory total automation with robotics, middleware, and expert system technology, physicians and nurses at the Oklahoma University Medical Center can more effectively deliver lifesaving health care using evidence-based protocols that depend heavily on “on time, every time” laboratory services.

Background microRNAs are promising candidate breast cancer biomarkers due to their cancer-specific expression profiles. However, efforts to develop circulating breast cancer biomarkers are challenged by the heterogeneity of microRNAs in the blood. To overcome this challenge, we aimed to develop a molecular profile of microRNAs specifically secreted from breast cancer cells. Our first step towards this direction relates to capturing and analyzing the contents of exosomes, which are small secretory vesicles that selectively encapsulate microRNAs indicative of their cell of origin. To our knowledge, circulating exosome microRNAs have not been well-evaluated as biomarkers for breast cancer diagnosis or monitoring. Methods Exosomes were collected from the conditioned media of human breast cancer cell lines, mouse plasma of patient-derived orthotopic xenograft models (PDX), and human plasma samples. Exosomes were verified by electron microscopy, nanoparticle tracking analysis, and western blot. Cellular and exosome microRNAs from breast cancer cell lines were profiled by next-generation small RNA sequencing. Plasma exosome microRNA expression was analyzed by qRT-PCR analysis. Results Small RNA sequencing and qRT-PCR analysis showed that several microRNAs are selectively encapsulated or highly enriched in breast cancer exosomes. Importantly, the selectively enriched exosome microRNA, human miR-1246, was detected at significantly higher levels in exosomes isolated from PDX mouse plasma, indicating that tumor exosome microRNAs are released into the circulation and can serve as plasma biomarkers for breast cancer. This observation was extended to human plasma samples where miR-1246 and miR-21 were detected at significantly higher levels in the plasma exosomes of 16 patients with breast cancer as compared to the plasma exosomes of healthy control subjects. Receiver operating characteristic curve analysis indicated that the combination of plasma exosome miR-1246 and miR-21 is a better indicator of breast cancer than their individual levels. Conclusions Our results demonstrate that certain microRNA species, such as miR-21 and miR-1246, are selectively enriched in human breast cancer exosomes and significantly elevated in the plasma of patients with breast cancer. These findings indicate a potential new strategy to selectively analyze plasma breast cancer microRNAs indicative of the presence of breast cancer. Electronic supplementary material The online version of this article (doi:10.1186/s13058-016-0753-x) contains supplementary material, which is available to authorized users.

Noninvasive, transcutaneous bilirubin (TcB) measurement is an attractive option for neonates, but opinions about its usefulness vary among studies. We collected paired measurements of TcB and serum bilirubin (SB) in 343 term neonates using the BiliCheck meter (SpectRx, Norcross, GA) and 3 different SB methods. Correlations between SB and TcB were similar for all laboratory methods and TcB measurement sites. However, TcB bias varied depending on the comparison SB method and TcB measurement site. TcB bias also varied with race when measurements were done on the forehead but not when they were done on the sternum. Several factors must be considered before implementing TcB measurement: (1) Each laboratory instrument has its own unique relationship to TcB. (2) The chosen measurement site affects the relationship. (3) Race can affect TcB bias when the measurement is taken on the forehead. Properly used, TcB measurement, especially when taken from the sternum, can be a useful screening method for neonatal jaundice.

We compared a rapid, point-of-care multimarker protocol with a single and serial troponin I (TnI)-only protocol in 5,244 patients admitted to the emergency department with chest pain. The diagnosis of acute myocardial infarction (AMI) was based on a doubling myoglobin level accompanied by at least a 50% increase in the creatine kinase (CK)-MB level with no detectable TnI; a doubling of myoglobin level together with any detectable TnI; or a TnI level of 0.4 ng/mL (0.4 microg/L) or more, irrespective of myoglobin or CK-MB results. By using these new criteria, 145 of 148 cases were positive for AMI (positive predictive value [PPV], 92.4%) and 3 were negative, which were also negative by the core laboratory TnI assay. Twelve confirmed non-AMI cases were positive by the new protocol, with 10 of 12 confirmed by the core laboratory as positive for TnI. The negative predictive value (NPV) was 99.9% the overall diagnostic accuracy was 99.7%. The TnI-only protocol had a sensitivity of 68.2% with an NPV of 99.1%. With lower TnI-only cutoffs, 4 patients had false-negative results, and a PPV of 36.4% was observed. Our rapid multimarker protocol seems superior to a TnI-only approach for rapidly triaging patients with chest pain or AMI.

Laboratory medicine is undergoing tremendous change in recent years driven primarily by technology, regulations, reimbursement, and market forces. In this paradigm shift, the laboratory is under tremendous pressure to adapt to new requirements for critical care testing. Indeed, laboratories have entered the information age where chemical data is being extracted from specimens in totally automated fashion. In the past, laboratory data has played a more historical role in the care of critically ill patients, arriving at the bedside too late to be of significant use in the active, ongoing care of the patient. However, today's physicians taking care of critically ill patients now require that laboratory results are made available in real-time and, if possible, at the patient's point-of-care. Many new testing point-of-care testing (POCT) devices have been developed to address this need however often laboratories implement such distributed devices with little or no attention to the information technology requirements. In fact, as little as 10% of point-of-care testing is actually managed by the central laboratory computer hence critically importance results are not found on the patient's electronic medical record. In addition, the billing and management data for point-of-care testing is often handled manually with no plans to interface point-of-care devices to the laboratory billing and management systems. Because of recent improvements of information handling and interface capability, such shortcomings in data management are no longer acceptable. Indeed, the demands for laboratories to utilize information technology are such that those laboratories with no overall plan for data management of critical care testing will probably not survive this market-driven paradigm. We present a discussion of the various approaches to computerization of point-of-care testing including the advantages and the disadvantages of each approach.

The immediate post-HIV testing world of blood banking was a challenging time.1 Public concerns over blood safety fueled a tremendously powerful dynamic within the community to adopt testing and screening measures to deal with progressively more remote risks of transfusion-transmitted illnesses. Indeed, it was reasonable for patients to expect to receive untainted blood products in our hospitals. The result of this dynamic is now a safety profile for transfusion that begins to approach that of other low-risk activities of daily living, such as driving to the store or flying on a major airline.1,2 The firestorm of discussion and debate over each new risk, test, or screening method during the height of that era created a workable process by which to engage in this discussion, and has made the community keenly aware of the need to monitor for new risks. We are now generally more able to decide how, when, or if we should implement additional testing or screening measures to deal with those risks. That is not to say that this has come without considerable and even continuing controversy, but it has brought both the public and providers together to engage on the matter of expectations.1 The lessons learned from this era in blood banking should be studied and carefully considered as scrutiny of other aspects of medical care, and in particular laboratory testing and its risks (safety issues), come to light. Best practices, whether they are business models, software, or hardware tools, will rapidly become the standard of care, driven by a combination of legal, liability, regulatory, public perception, and payer pressures. Just as there was a race to adopt HIV antigen and then nucleic acid based testing (NAT) in the blood banking industry, there must be a rush to adopt a host of …

Foscarnet (trisodium phosphonoformate hexahydrate) is an antiviral agent used to treat cytomegalovirus disease in immunocompromised patients. One common side effect is acute ionized hypocalcemia and hypomagnesemia following intravenous administration. Foscarnet-induced ionized hypomagnesemia might contribute to ionized hypocalcemia by impairing excretion of preformed parathyroid hormone (PTH) or by producing target organ resistance. Prevention of ionized hypomagnesemia following foscarnet administration could blunt the development of ionized hypocalcemia. To determine whether intravenous magnesium ameliorates the decline in ionized calcium and/or magnesium following foscarnet infusions, MgSO 4 at doses of 1, 2, and 3 g was administered in a double-blind, placebo-controlled, randomized, crossover trial to 12 patients with AIDS and cytomegalovirus disease. Overall, increasing doses of MgSO 4 reduced or eliminated foscarnet-induced acute ionized hypomagnesemia. Supplementation, however, had no discernible effect on foscarnet-induced ionized hypocalcemia despite significant increases in serum PTH levels. No dose-related, clinically significant adverse events were found, suggesting that intravenous supplementation with up to 3 g of MgSO 4 was safe in this chronically ill population. Since parenteral MgSO 4 did not alter foscarnet-induced ionized hypocalcemia or symptoms associated with foscarnet, routine intravenous supplementation for patients with normal serum magnesium levels is not recommended during treatment with foscarnet.

Patient: 52-year-old Caucasian male. Chief Complaint: Increasing fatigue and weakness. History of Present Illness: Our patient presented for evaluation of an acute worsening of progressive weakness over the past month. He felt so weak that he almost “passed out.” He also reported an increased fluid intake and an increase in urinary output. There was no pain on urination or history of urinary tract infection. He denied chest pain, vision problems, nausea, diarrhea, and syncope. Family members were concerned that the patient was “wobbly” when he walked. While waiting in the emergency room, the patient experienced 2 tonic-clonic seizures. Past Medical History: Nephrolithiasis, hypertension, benign prostatic hypertrophy. Medication History: Lisinopril, potassium, Allopurinol, Flexeril. Social History: Denies alcohol and tobacco use. Physical Exam Findings: Blood pressure, 71/36 mm Hg; pulse, 115; respiratory rate, 22; and temperature, 36.9°C. The patient was awake and responsive but not oriented. The skin was dry and turgor was poor. The oral mucosa was also dry. The abdominal exam revealed mid-epigastric tenderness. Neurologic exam was nonfocal. Lung and cardiac exams were normal. Principal Laboratory Findings: Tables 1, 2, 3, 4 , and 5 . 1. What are this patient’s most striking clinical and laboratory test findings? 2. How do you explain these findings? 3. What is your differential diagnosis? 4. What additional laboratory test would be useful in confirming the diagnosis of this patient’s condition? 5. What laboratory tests might explain the precipitating event which caused this patient’s condition? 6. What is the most likely diagnosis? 7. What is the treatment and management of this disorder? 1. This patient has several important critical signs and symptoms that include seizure, lethargy, polydipsia, polyuria, hypotension, epigastric pain, and tachycardia. The …

Group A streptococcal infections, ranging from necrotizing fasciitis and myositis to toxic shock syndrome, have increased over the last 10 years. We developed the first primate model of necrotizing fasciitis and myositis. Thirteen baboons were inoculated intramuscularly with group A streptococci (GAS). Eleven animals survived foror = 11 days before sacrifice, and two animals died within 2 days. The site of inoculation of the survivors exhibited an intense neutrophilic influx (stage I), followed by a lymphoplasmacytic influx (stages II and III). This was accompanied by the appearance of markers of an acute and then a chronic systemic inflammatory response. In contrast, the site of inoculation of the two nonsurvivors exhibited intravascular aggregates of neutrophils at its margin with no influx of neutrophils and with extensive bacterial colonization. We conclude that GAS inoculation induces a local and systemic acute neutrophilia followed by a chronic lymphoplasmacytic response; failure, initially, of neutrophilic influx into the site of inoculation predisposes to systemic GAS sepsis and death; and this three-stage primate model approximates the human disease.

Areas other than the analytical process should be the focus of concern about quality issues in the laboratory because nearly 95% of errors occur at the nonanalytical front and back ends of the testing process. Until now, computer systems have been designed to handle the more predictable aspects of laboratory testing, necessitating that the infrequent and unpredictable data events be handled by manual systems. The manual systems are termed “workarounds” and indeed, because they occur sporadically, they are frequently not handled predictably. Here, I describe and give examples of an expert laboratory computer system that can be designed to handle both predictable and unpredictable data events without the use of manual workarounds. This expert system works in concert with a dynamic database allowing such data events to be detected in real time and handled predictably, thus providing a tool to address quality assurance issues throughout the testing process. The system performs up to 31 separate actions or tasks based on data events that in the past were handled by human workarounds.

Poor core laboratory performance that causes delays in diagnosis and treatment is an impediment to optimal patient care, particularly in high-volume patient care areas such as the emergency department (ED). To evaluate the impact of laboratory performance on patient care outcomes, we obtained data from 11 hospitals related to laboratory test turnaround time (TAT) parameters and ED patient throughput. We observed that the average length of stay (LOS) in the ED correlated significantly with the percentage of total laboratory outliers (R2 = 0.75; P < .01) and to a lesser extent the TAT means (R2 = 0.66; P < .01). Furthermore, improvements in laboratory performance during the study were associated with concurrent decreases in ED LOS. Although in the past, laboratories have focused on TAT means for performance assessment, our observations suggest that a more appropriate method of benchmarking might be to aggressively set clinically driven TAT targets and assess performance as the percentage of results achieving this goal.

Bioanalysis invited a selection of leading researchers to express their views on automation in the bioanalytical laboratory. The topics discussed include the challenges that the modern bioanalyst faces when integrating automation into existing drug-development processes, the impact of automation and how they envision the modern bioanalytical laboratory changing in the near future. Their enlightening responses provide a valuable insight into the impact of automation and the future of the constantly evolving bioanalytical laboratory.

Our goal was to recreate a passive hemagglutination inhibition (PHAI) test to diagnose brown recluse spider (BRS; Loxosceles reclusa) bite envenomation for treatment trials. Guinea pigs received intradermal injections of concentrated spider venom from the following species: Loxosceles reclusa, Argiope aurantia, Argiope trifasciata, Phidippus audax, and Lycosa frondicola. Skin lesion exudate was collected and tested with the BRS venom PHAI assay. From 51 separate collections of exudate, test sensitivity was 90% as long as 3 days after venom injection. Specificity was 100% with venom from the other spider species listed above in vivo (7 test samples) and in vitro (5 test samples), as well as with random bacterial exudate with and without added serial dilutions of BRS venom (10 test samples). The test was reproducible over repetitive assays to within one 10-fold dilution. A positive PHAI test result could function as an entry criterion for BRS bite victims in human treatment trials.

Glucosamine is used to treat osteoarthritis. In animals, the compound is known to cause insulin resistance, the underlying abnormality in type 2 diabetes mellitus. Insulin resistance in humans taking oral glucosamine in doses used for osteoarthritis has not been studied.Volunteer human subjects (n = 38) without known abnormality of glucose homeostasis had fasting serum glucose, insulin, and lipids determined before and after taking 1500 mg glucosamine by mouth every day for 6 weeks. Fasting insulin and glucose were used to calculate homeostasis model assessment (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI). Vascular elasticity was measured by pulse wave analysis. The paired Student's t test was used to compare baseline with posttreatment values. Pearson's correlation was used to determine the relation of baseline HOMA-IR with changes in other variables.We found a rise in HOMA-IR after 6 weeks of glucosamine (2.8 versus 3.2, P0.04). The fall in HOMA-IR among the subjects was statistically related to a higher baseline HOMA-IR by Pearson's correlation(P0.01). A rise in serum triglycerides and a rise in LDL cholesterol were statistically related to baseline HOMA-IR. Small artery elasticity fell, and the decrease was higher in those with the highest baseline HOMA-IR.Notwithstanding its efficacy remaining in question, glucosamine is widely used as treatment for osteoarthritis, which is a condition associated with both obesity and type 2 diabetes mellitus. Our data indicate that persons with underlying poorer insulin sensitivity are at risk for worsening insulin resistance and vascular function with the use of glucosamine in doses used to treat osteoarthritis.

Objective To analyze patients with “normal” baseline quick intraoperative parathyroid hormone (QPTH) levels during parathyroidectomy and to determine the prevalence of this finding, the usefulness of the assay in this situation, and to explain the possible causes for this phenomenon. Study design and setting Patients who underwent parathyroidectomy using QPTH in a tertiary hospital. Methods Retrospective analysis of 39 patients treated surgically for primary hyperparathyroidism using QPTH. Results Of the patients, 14 (36%) had normal baseline QPTH. 8 patients with localizing sestamibi scans had a single adenoma, and excision resulted in a mean decrease of 85.4% in QPTH. Six patients had nonlocalizing sestamibi scans, 1 patient had an 84% drop in QPTH level after removal of a single adenoma, and 5 patients had hyperplasia requiring ≥3 glands excision. At 11.36 months' mean follow-up, 13 patients (93%) were normocalcemic. Conclusions A “normal” baseline QPTH level was found in 36% of patients. A 50% decrease in QPTH remains predictive of biochemical cures in patients with localizing sestamibi scans. The likely explanation for this variability in “normal” levels between different assays is the variability in detection of the 7-84 PTH fragment, which results in an overestimation of the PTH level. Assays such as the QPTH, which are more sensitive for the biologically active PTH molecule [(1-84) PTH] than other laboratory PTH assays will tend to have lower PTH levels that can be within the normal range. EBM rating: B-3.

Increased proliferative activity of the renal tubular epithelium is thought to be a prerequisite for renal cyst formation by many investigators. However, in humans, the exact in vivo proliferation rate of epithelial cells lining these cysts is not known. In this study, which used immunohistochemical methods with an antibody to proliferating cell nuclear antigen (PCNA), the proliferation index (PI) (percentage of PCNA positive cell nuclei among epithelial cells lining the renal cysts) was determined in 10 cases of autosomal dominant polycystic kidney disease (ADPKD), 8 cases of autosomal recessive polycystic kidney disease (ARPKD), and 8 cases of acquired cystic kidney disease (ACKD). Cysts with proximal and distal nephron phenotype and cysts with markedly thickened basement membranes, as well as cysts lined by atrophic (flattened), "regular" (cuboidal or cylindrical), and hyperplastic epithelium, were evaluated separately. The overall PI of cyst epithelium (excluding hyperplastic cysts) was 2.58 in ADPKD, was 10.5 in ARPKD, and was 3.61 in ACKD. Overall, there were only minor differences in the PI between the various types of cysts. Cysts with hyperplastic epithelium in ACKD (unlike in ADPKD) showed a high PI (9.1). For comparison, the PI of two renal cell carcinomas occurring in two ACKD cases was also determined (13.70 and 8.67%). The PI of tubular epithelium in normal kidneys was only 0.22 to 0.33%, depending on the tubule segment. In contrast, in polycystic kidneys, those noncystic segments of the nephron from which the cysts are thought to originate (distal nephron (specifically collecting duct)) in ARPKD, primarily distal in ADPKD, proximal and distal in ACKD, had PI values similar to those of the cyst epithelium.(ABSTRACT TRUNCATED AT 400 WORDS)

In 10 normal term infants aged 52 +/- 2.5 hours, serum calcium, magnesium, phosphorus, ionized calcium, parathyroid hormone, and calcitonin were studied at 0, 1/2, 1, and 2 hours after administration of 1.77 +/- 0.08 gm/kg glucose orally over 20 minutes. In response to glucose administration, serum glucose concentration rose and serum P, Ca, and Mg concentrations fell. Serum PTH concentration rose significantly, and blood ionized Ca and pH were unaltered. Serum calcitonin was elevated, as compared with adult values, and did not change. We suggest that in neonates, as in adults, oral ingestion of glucose lowers serum Ca, Mg, and P, and a compensatory rise in serum PTH concentration maintains blood ionized Ca concentration.

We studied the hypotheses that serum calcium and blood ionized calcium would be low in acutely ill children and would rise with clinical improvement. In 15 children admitted to the pediatric intensive care unit, the blood ionized calcium level was 4.45 +/- 0.06 mg/dl (1.11 +/- 0.015 mmol/L) on entry versus 5.17 +/- 0.03 mg/dl (1.29 +/- 0.01 mmol/L) in control subjects (p less than 0.005), rose significantly on days 2 and 3, and was 5.12 +/- 0.04 mg/dl (1.28 +/- 0.01 mmol/L) at discharge (p less than 0.005). Changes in serum calcium level were similar, whereas serum magnesium and phosphorus levels were normal and did not change. Basal serum parathyroid hormone concentrations were elevated, rose further during the study, and were normal at discharge. Serum parathyroid hormone levels correlated inversely with blood ionized calcium levels, indicating that compensatory hyperparathyroidism occurs with low blood ionized calcium concentrations. Basal serum calcitonin values were evaluated on entry and decreased with clinical improvement. Serum calcitonin levels correlated significantly with low blood ionized calcium levels, indicating that hypercalcitoninemia may play a role in the pathogenesis of hypocalcemia in these children. Urine calcium excretion was not increased in the four children studied. We speculate that with clinical improvement, a rise in serum parathyroid hormone levels and a decline in serum calcitonin levels may help restore normocalcemia in these acutely ill children.

In very-low-birth-weight (VLBW) infants, we studied the hypotheses that in early neonatal hypocalcemia the serum parathyroid hormone (PTH) concentration would rise; the serum calcitonin (CT) concentration would decline; and, in response to intravenous (IV) calcium (Ca) infusion, the serum PTH concentration would be lowered; and the serum CT concentration would rise. Fifteen infants appropriate for gestational age (age, less than 32 weeks; birth weight, less than 1,500 g) were enrolled in the study. In eight infants in whom the serum Ca level declined to less than 6.0 mg/dL, changes in serum magnesium, phosphorus, PTH, CT, and whole blood ionized calcium (iCa) were evaluated on entry into the study, when serum Ca declined to less than 6.0 mg/dL, immediately after infusion of 18 mg/kg of elemental calcium as calcium gluconate, and at eight hours post-Ca infusion (+ 8 hr). The serum Ca concentration declined from 7.9 +/- 0.6 baseline (mean +/- SE) to 5.2 +/- 0.2 mg/dL pre-Ca infusion and rose to 9.17 +/- 0.74 mg/dL post-Ca infusion and 7.1 +/- 0.5 mg/dL at +8 hr post-Ca infusion. Whole blood iCa declined from 4.82 +/- 0.24 to 3.72 +/- 0.19 mg/dL pre-Ca infusion, rose to 6.68 +/- 0.32 mg/dL post-Ca infusion, and was 4.12 +/- 0.21 mg/dL at + 8 hr post-Ca infusion. The serum P concentration did not change significantly. The serum PTH concentration rose from 116 +/- 17 to 204 +/- 34 pmole/L pre-Ca infusion, declined to 149 +/- 22 pmole/L post-Ca infusion, and was 187 +/- 28 pmole/L at + 8 hr post-Ca infusion. The serum CT concentration was elevated and did not change significantly. Thus, in infants less than 32 weeks' gestation, the serum PTH level rises in early neonatal hypocalcemia and is suppressed by IV Ca infusion; the serum CT level is markedly elevated and is not altered in early neonatal hypocalcemia and does not rise further in response to IV Ca infusion in VLBW infants. We suggest that hypercalcitoninemia occurs in VLBW infants and that serum CT concentrations are unresponsive to changes in serum Ca.