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Background Lingual linear lesions (LLLs) are the oral linear lesions located on the dorsum, lateral borders, and/or ventral surface of tongue. It has been suggested that LLLs might be an early clinical sign of vitamin B12 deficiency. Here, a retrospective study was conducted to further investigate and validate the association between LLL and vitamin B12 deficiency. Methods Based on the clinical examination, patients with LLLs were enrolled and analyzed retrospectively. Data regarding clinical and laboratory features were obtained. Follow-up was done at least 6 months following appropriate supplementation therapy. Results A total of 57 patients, consisting of 20 males and 37 females with a mean age of 59.12 years (range, 18-80), were enrolled in this study. The hematological examination revealed that 56 (98.25%) of the 57 patients had severe serum vitamin B12 deficiency, and the other 1 patient had a borderline low level of vitamin B12 . All the enrolled patients responded well to cobalamin replacement therapy. Conclusion LLLs might be a clinical sign strongly suggestive of severe vitamin B12 deficiency.

Background Low endogenous testosterone has been associated with increased cardiovascular risk in men. Objectives To determine the prevalence of low serum testosterone level (TT) in a cohort of male US career firefighters and to examine its relation with left ventricular wall thickness (LVWT). Materials and Methods We conducted a cross‐sectional study among 341 career firefighters, (age: 37.5 ± 10.3 years; BMI: 28.9 ± 4.5 kg/m2), who underwent an occupational medical screening examination. TT quartiles were determined, and LVWT distribution among them was plotted. Then, TT values were categorized as low (916 ng/dL). To further investigate the association of mildly decreased TT on LVWT, we divided the borderline group into borderline‐low (264‐319 ng/dL) and borderline‐high (320‐399 ng/dL) ranges. LVWT values were classified as low LVWT when

Antithrombin deficiency diagnostics by first-line activity tests suffer from a lack of sensitivity sometimes resulting in diagnostic uncertainty. We here present a case of a woman with recurrent pregnancy loss who was screened for inherited thrombophilia. Antithrombin activity was borderline low, resulting in uncertainty about the correct diagnosis. Using a mass spectrometry-based test, the antithrombin protein of the patient was characterized at the molecular level and a heterozygous p.Pro73Leu mutation was identified. The mutation, also known as antithrombin "Basel," increases the risk of venous thromboembolism and obstetric complications. This case is illustrative of current antithrombin deficiency screening, in which diagnoses may be missed by traditional diagnostics. Next-generation protein diagnostics by mass spectrometry provides molecular insight into the proteoforms present in vivo. This information is essential for laboratory specialists and clinicians to unambiguously diagnose patients and will aid in evolving healthcare from traditional to precision diagnostics.

Von Willebrand Disease (VWD) is considered the most common inherited bleeding disorder. It has multiple subtypes and a primary symptom of mucocutaneous bleeding. Some researchers in this field speculate that inherited disorders of platelet function may be as common but underdiagnosed due to the difficulty of accessing testing. The diagnostic approach for this disease has evolved as new instruments and diagnostic testing have become available. The ISTH-Bleeding Assessment Tool is a validated instrument that is used to screen patients referred for bleeding symptoms for further laboratory testing. The three main screening tests used in the diagnosis of VWD include von Willebrand Factor (VWF) antigen, platelet-dependent VWF activity, and factor VIII activity. Improvements in laboratory assays discussed include changes in how traditional assays are performed as well as the addition of new laboratory assays. The role of genetic testing and management of patients with borderline low von Willebrand factor are also discussed.

Model Study: Cross-sectional study, exploratory, descriptive and quantitative character. Objective: To evaluate quality of life (QL), Quality of sleep and Burnout Syndrome (SB) in multi professional residents along the residence. Methodology: 60 multi professional residents were analyzed, of which 24 were freshmen residents, attending the first week of the program (RIN), 18 at the end of the first year (R1) and 18 at the end of the second year (R2). The application of the WHOQOL-BREF was performed Sleep Quality Index of Pittsburgh and Maslach Burnout Inventory (MBI). Results: Quality of sleep decreased over the residence and was identified less involvement in all areas of QL for RIn. As for the isolated dimensions of MBI, R1 showed a higher number of residents with emotional exhaustion (EE) high and professional fulfillment (RP) low and R2 depersonalization (DE) high. Two individuals of R2 showed the SB; R2 also excelled in completing a criterion. R1 had a higher percentage of subjects at risk. Most RIn there has been no classification in any of the dimensions. The average of the results of EE was high for R2, R1 and borderline low for RIn. Conclusions: Considering 1ue the physical and emotional exhaustion can be understood as a gradual process that can lead to illness, QL impairment and services, points to an increasing need to propose solutions to better planning and organization of work, for improvements in the general conditions, contributing to better health of residents

Selenium is a very important micronutrient. Food is the major source for selenium uptake and the average blood levels is seen to be highly affected by dietary habits as selenium levels in food naturally depend on the kind of soil they are grown upon and in processed foods its levels depend on fortification. Deficiency of this vital nutriment needs to be assessed to understand deficiency prevalence.A total number of 529,461 subjects were tested for their blood selenium levels. The study cohort consisted of 284,189 males and 245,272 females respectively. Average blood selenium levels have been analyzed across both the genders using the analytical platform of Inductively Coupled Plasma - Mass Spectrometry.For borderline low analysis of selenium, values of/= 105 μg/L were considered. The total frequency of borderline low recorded in our study was 3.7%. The average blood selenium levels and further geographical highlights have been included and discussed.Our report is an effort to create awareness about the less discussed micronutrient necessity to be tested in the Indian scenario.

Summary Exon 28 polymorphism p.D1472H is associated with significantly lower von Willebrand Ristocetin cofactor activity (VWF:RCoF) to von Willebrand antigen (VWF:Ag) ratio compared to normal, but has been reported as not conferring haemorrhagic risk. The impact of this polymorphism while assessing symptomatic patients for von Willebrand disease (VWD) has not been previously analysed. We retrospectively reviewed charts of children with clinically significant bleeding and abnormal VW panel who underwent VW exon 28 analysis. Twenty-three of 63 patients studied had p.D1472H. Of these 23 patients, 6 with borderline low VWF:RCo were given provisional diagnosis of VWD type 1 by treating physicians, which could be alternatively explained as due to the effect of p.D1472H. None of the patients with low VWF:RCo, decreased VWF:RCo/VWF:Ag ratio and p.D1472H had VWD type 2M mutations identified. This study illustrates the challenge in diagnosing VWD using ristocetin-based VW assay in symptomatic patients with p.D1472H.

We sought to determine the role of sex hormone-binding globulin in patients with male infertility.We retrospectively reviewed the records of 168 males seen at a fertility clinic from 2012 to 2014 to investigate the accuracy of total testosterone in the biochemical diagnosis of hypogonadism using calculated bioavailable testosterone as the reference value. We used multivariable analysis to assess sex hormone-binding globulin as an independent predictor of infertility.Computations using calculated bioavailable testosterone as a standard in the measurement of definitive biochemical hypogonadism (less than 156 ng/dl) revealed 81% sensitivity, 83% specificity, 81% positive predictive value and 82% negative predictive value for diagnosing hypogonadism with total testosterone alone. Of the 90 men with total testosterone greater than 300 ng/dl, 20% had low bioavailable testosterone less than 156 ng/dl, 52% had borderline low bioavailable testosterone less than 210 ng/dl and only 48% could be considered biochemically eugonadal according to calculated bioavailable testosterone. Of the 80 patients with total testosterone less than 300 ng/dl, 19% had free testosterone levels greater than 6.5 ng/dl and, thus, could be considered to be eugonadal. By a magnitude similar to that of follicle-stimulating hormone, sex hormone-binding globulin independently predicted decreased sperm concentration (p = 0.0027) and motility (p = 0.0447). After excluding men with azoospermia, only sex hormone-binding globulin levels differed significantly in classically hypogonadal men (group 1-total testosterone less than 300 ng/dl) and those missed but hypogonadal (group 2-calculated bioavailable testosterone less than 210 ng/dl) (p = 0.0001). At a more stringent cutoff of calculated bioavailable testosterone less than 156 ng/dl, sperm motility was significantly different for groups 1 and 2 (p = 0.014).Adding sex hormone-binding globulin to total testosterone serum testing facilitates more accurate diagnosis with free testosterone and calculated bioavailable testosterone, and clinical implications of decreased semen parameters to a magnitude similar to that of follicle-stimulating hormone. This warrants further study of the role of sex hormone-binding globulin in male infertility.

This study was carried out to investigate the effect of a new microbiological preparation Vetom 21.77 containing spore-mycelial biomass of Duddingtonia flagrans on hematological and biochemical parameters of broilers. The drug was administered for 3 months. A total number of 105 five-day-old broilers (Hubbard F15) were allocated to four test groups, where birds received the preparation in doses of 2, 5, 50 and 300 µl/kg bodyweight, and a control group with no treatment. Blood samples were collected 1.5 and 3 months after the beginning of the experiment for biochemical and hematological analysis. According to the results obtained, administration of the microbiological drug was followed by positive changes in the immunity of treated broilers. The preparation seems to have stimulating effect on their metabolic processes. There was no negative effect of the drug on the physiological state of the birds. In the course of the experiment, neither disease indications, nor mortality were detected in the birds, excluding deaths caused by the required slaughter. There were no treatment-related allergic reactions, even at the highest daily dose, as exemplified by almost borderline low eosinophil levels observed in treated broilers over the study period. No clinically relevant results were detected in serum biochemical profile.

Summary Repeating normal laboratory tests can waste resources. This study aimed to quantify unnecessary repeat haematinic tests taken from the elderly in a district general hospital. Haematinic tests (ferritin, B12, serum folate) from patients age ≥70 years were reviewed for repeat tests during an 8-week period. Questionnaires were given to doctors to establish when the considered repeating a ‘borderline low normal’ result to be clinically justifiable. 7.7% of all haematinic tests were repeat tests and of these, the majority (83%) was performed following a previously normal result. Thirteen of 24 doctors believed repeating a normal result at the bottom of the normal range (‘borderline low normal’) was justifiable. After excluding ‘borderline low normal’ results, 6.0% (at minimum) of repeat tests were done following a previous normal result and were unnecessary. This audit showed that there are a significant number of unnecessary repeat haematinic tests being performed.

Glomangiopericytoma is a rare vascular neoplasm characterized by a pattern of prominent perivascular growth. A 72-year-old woman was admitted to our clinic complaining of nasal obstruction, frequent epistaxis, and facial pain. A reddish tumor filling the left nasal cavity was observed on endoscopy and treated with endoscopic excision. Microscopically, closely packed cells interspersed with numerous thin-walled, branching staghorn vessels were seen. Glomangiopericytoma is categorized as a borderline low malignancy tumor by WHO classification. Long-term follow-up with systemic examination is necessary due to high risk of recurrence.

TRYMS is a multicentre, randomised, double-blinded, parallel group, placebo controlled phase IV trial in young male cancer survivors with low testosterone levels. The trial is designed to investigate whether testosterone treatment for 26 weeks will result in a reduction of truncal fat mass and increase in participant-reported physical functioning scores. The general consensus worldwide is that testosterone levels ≤12nmol/L are deemed to be low; however a previous study of 200 healthy volunteers found that testosterone≤10nmol/L would be deemed to be low. The trial team considered only including patients with testosterone≤10nmol/L but acknowledged this would leave an evidence gap for patients with testosterone between 10-12nmol/L. Therefore TRYMS was designed to determine whether testosterone replacement is effective in men with low testosterone and with borderline low testosterone by powering the study to look at each subgroup individually. A sample size of 268 participants was required after accounting for imbalanced recruitment to the subgroups. However, opening TRYMS took longer than anticipated and recruitment was substantially slower than expected; the trial design was adapted to combine the subgroups for primary analysis, reducing the minimum sample size to 112 participants. The trial was granted a recruitment extension and continued to recruit beyond the minimum sample size to maximise precision of the treatment effect estimates in each subgroup; this analysis is exploratory but still considered useful to inform clinical practice. This adaption of the trial design was a pragmatic approach for a trial struggling with recruitment, whilst still able to provide clinically useful results.

Glomangiopericytoma is classified as a borderline low malignancy tumor but recurrence rate is reported to be about 16.8%-30%, probably caused by the lack of radical resection.(1) It is a rare tumor arising from pericytes surrounding capillaries. The tumor has a predilection for the nasal cavity and paranasal sinuses. We report a case of glomangiopericytoma with an aim to present how it can invade and destroy both maxillary bones and lower part of nasal cavity. Due to its dimensions the tumor required extensive resection within tumor-free margins. On the basis of immunohistochemical staining the tumor was diagnosed as glomangiopericytoma. Strict follow-up of 16 months after radical resection revealed no recurrence of the tumor.

Objective—To compare serum total thyroxine (T4) concentrations obtained with an in-house ELISA and a validated radioimmunoassay (RIA). Design—Laboratory trial. Sample Population—50 canine and 50 feline serum samples submitted for measurement of total T4 concentration with the RIA; samples were selected to represent a wide range of concentrations (< 6 to 167 nmol/L). Procedure—Results of the ELISA and RIA were compared by calculating correlation coefficients, examining linearity, determining bias and precision, and evaluating clinical interpretations. Results—Correlation coefficients for results of the 2 methods were 0.84 for the canine samples and 0.59 for the feline samples. Examination of bias plots revealed large variations in ELISA results, compared with RIA results. For the feline samples, the ELISA consistently overestimated total T4 concentration obtained with the RIA. When results of the 2 methods were categorized (low, borderline low, normal, borderline high, or high), results were discordant for 24 (48%) and 29 (58%) of the canine samples and for 18 (36%) and 28 (56%) of the feline samples (depending on whether borderline high ELISA results were considered normal or high). Reliance on results of the ELISA would have led to inappropriate clinical decisions for 31 (62%) canine samples and 25 (50%) feline samples. The ELISA coefficients of variation for the pooled canine and feline samples were 18 and 28%, respectively. Conclusions and Clinical Relevance—Substantial discrepancies between ELISA and RIA results for T4 concentrations were detected. Thus, we concluded that the in-house ELISA kit was not accurate for determining serum total T4 concentrations in dogs and cats. (J Am Vet Med Assoc 2002;221:243–249)

Many patients presented with borderline low blood pressure (BP= 90-100mmHg) due to (1) internal bleeding, (2) bleeding in the retroperitoneal space during intervention, (3) sepsis or (4) dehydration. These patients present with borderline low BP. The question is: Which test can predict which patient

Euthyroid sick syndrome is related to profound changes in thyroid metabolism induced by nonthyroidal diseases. To determine whether children with newly diagnosed Hodgkin disease might present thyroid abnormalities and to establish their predictive value, the authors performed regular thyroid function testing. Seven children (5 M, 2 F) with a mean age of 10.4 years (range: 4.6-15 years) at diagnosis were studied for a period of 6.9 years (4.2-10.5 years). Five patients presented at diagnosis with euthyroid sick syndrome characterized by borderline low thyroxine circulating levels (T3 0.8-1.3 ng/mL, FT3 1.5-1.7 pg/mL) and mildly raised TSH (4.6-5 microU/mL). Thyroid function turned normal within 6 months of therapy. Subsequently, 3 children developed overt hypothyroidism (T4 35-40 ng/mL, FT4 2-7 pg/mL, TSH 5.5-11 microU/mL) requiring substitution therapy. Euthyroid sick syndrome was not associated with a poorer outcome in terms of survival or long-term thyroid consequences. Thyroid function testing should be performed routinely at diagnosis and thereafter in children with Hodgkin disease to detect subtle abnormalities.

DOI: 10.1200/JCO.2012.43.1908 For the last decade, I have traveled monthly to Juneau, Alaska, to see patients who have oncology or hematology problems and are referred to me by their primary care provider. Although Juneau is Alaska’s state capital, it is located in southeast Alaska and is surrounded by mountains, glaciers, and the sea, so it is accessible only by boat or a 2-hour flight from either Anchorage or Seattle. The medical community of primary care providers in Juneau is strong, but the population of only 31,000 precludes the full-time presence of many medical specialties, including oncology and hematology. In collaboration with the local medical community and hospital, we can treat patients with many hematologic and oncologic diagnoses in Juneau, but conditions that require intensive supportive care or complex multispecialty care necessitate transfer to Anchorage or to the lower 48 states, most frequently to Seattle. The following story will sound familiar to most of my medical colleagues, but I thought it nevertheless remarkable and indicative of some of the issues that we face daily in serving our patients. Recently, on the first of my three heavily booked clinic days in Juneau, I received a call from a local family physician about a patient who had been found to be pancytopenic during a preoperative evaluation before spinal stenosis surgery. Despite an already full schedule, I asked the office staff to add him on at the end of the day. The patient appeared to be the picture of health, savefordocumentedslowprogressionofpancytopenia over the preceding 3 months. The diagnosis was not obvious, so a marrow examination was needed. The office staff worked diligently and uncomplainingly behind the scenes to rearrange my schedule for the second day in Juneau so that I would be able to perform the marrow biopsy that afternoon. The only time that the procedure could be shoehorned into the calendar would be just a little too late to meet the deadline for the daily courier who takes specimens from Juneau to Seattle for special studies, so the samples would not go out until the following day. That would have to be adequate. The next day, additional laboratory data were returned. The only other abnormalities were a markedly elevated D-dimer and a borderline low fibrinogen level, which suggested disseminated intravascular coagulation.Butwhy?ThenIrecalledthat thepatienthad a digital papillary adenocarcinoma of the finger resected 5 years previously, and I wondered if he might now have metastatic disease in his marrow. The bone marrow biopsy went well and was completed quickly, and the technologist rushed up to the laboratory in hopes of still catching the courier. The day after the bone marrow biopsy, I met the patient and his wife in the office (somehow that visit was also worked into my schedule). I informed them that, unfortunately, the initial marrow stain was not adequate to make a diagnosis, but I promised that I would keep track of the patient’s situation, although I was returning to Seattle that evening. I also told them that he might need care outside of Juneau. I learned thathehadbeenpleasedwithpreviouscare thathehad receivedat theUniversityofWashingtoninSeattle,but he had family in southern California and might prefer to go there if a longer stay was anticipated. The next morning, back in Seattle, I received a call from the Juneau hospital pathologist. A better stain of the marrow aspirate was suggestive of acute promyelocytic leukemia (APL), and that diagnosis had already been confirmed by the Seattle reference laboratory on the basis of immunohistochemical stains. (Yes, somehow the specimen did get to the courier in time to be flown out on the afternoon of the marrow examination!) As most readers of Journal of Clinical Oncology know, patients with APL have an 80% to 90% chance of cure if they start modern therapy in a timely fashion, but also a 10% to 30% chance of early death before or in the initial days of therapy, usually as a result of devastating thrombohemorrhagic complications. In fact, I have been involved as an expert witness in two recent Seattle-area malpractice cases in which a plaintiff family contended, with some justification, that a loved one died because appropriate therapy for APL was not initiated promptly. It seemed that the next steps would be relatively simple. APL is a medical emergency, so we needed to start the patient promptly on the medication that must be started quickly (all-trans-retinoic acid [ATRA]) to prevent the thrombohemorrhagic complications, and we needed to get him to Seattle to start definitive chemotherapy. JOURNAL OF CLINICAL ONCOLOGY A R T O F O N C O L O G Y VOLUME 30 NUMBER 31 NOVEMBER 1 2012

A new study shows that low and high maternal levels of free T4 during pregnancy are associated with reduced IQ and cortex and grey matter volumes in offspring. Do these findings herald change for the clinical management of pregnant women with borderline low or high normal levels of T4?

We report the syndrome of inappropriate antidiuresis as a much earlier side-effect of carbamazepine administration in a 29-year Nigerian female patient with generalized tonic-clonic seizures. Although asymptomatic, the biochemical abnormality improved after discontinuation of carbamazepine. Hyponatraemia developed after rechallenge with controlled release carbamazepine. The authors suggest that serum sodium levels be carried out before commencement of carbamazepine and caution be used in prescribing carbamazepine to patients with low or borderline low sodium values.

Background Mediastinal widening is a common finding on chest radiograph, and can be caused by numerous conditions. Most of these diseases have grave prognosis if accompanied by chest pain, and require immediate attention. However, mediastinal lipomatosis is a very benign condition caused by deposition of adipose tissue in the mediastinum. Case presentation We present a case of a morbidly obese female patient who presented to emergency department with a fall. She had mediastinal widening on chest radiograph, and borderline low voltage on electrocardiogram. On computed tomography, mediastinal lipomatosis was evident. Conclusion Obesity is a major epidemic in United States, and can lead to deposition of fat in the chest. Mediastinal lipomatosis is very benign condition, which rarely causes grave consequences.

Objectives. In 2004, the Ontario Society of Clinical Chemists (OSCC) held an invitational multidisciplinary workshop to establish the most reliable, cost-effective approach to the biochemical assessment of hypogonadism in men. Methods. Specialists across Canada in clinical biochemistry, endocrinology, family medicine and urology were invited to participate in this workshop which included individual presentations and a consensus component addressing two challenge statements: 1) ‘Determinations for total testosterone (TT) are equivalent to those for bioavailable testosterone (BAT) or calculated BAT (cBAT) or free testosterone (FT) (by analogue radioimmunoassay or equilibrium dialysis) or calculated FT (cFT)’; 2) ‘There is no good evidence that borderline low testosterone concentrations in men should be treated’. The main outcomes were to identify what agreement exists in Canada, what issues were still controversial, and what research remains to be addressed. Results. Six recommendations based on expert opinion addressed these main themes: investigate with morning total testosterone (TT) followed by repetition and reflexive testing of sex hormone binding globulin (SHBG) if testosterone is 8– 15 nmol/L with automatic calculation of cBAT; discontinue the use of analogue free testosterone assays; and definitive methods and standards must be available to ensure standardized results. Conclusions. Total testosterone is a reliable marker for the initial investigation of men presenting with symptoms of hypogonadism; cBAT is a reasonable follow-up test in patients with equivocal biochemical or consistent symptomatic findings.

Persons who have developed acute flaccid paralysis following infection with wild-type polioviruses or vaccine-associated paralytic poliomyelitis usually excrete polioviruses for only a few weeks. However, some patients with paralytic poliomyelitis have had prolonged excretion of polioviruses for periods of up to 10 years after onset of disease. Most prolonged excretors have been identified in industrialized countries. We studied 348 patients 2-28 years old in Ethiopia, Pakistan and Guatemala with residual paralytic poliomyelitis to determine if they had IgA or IgG deficiency or persistent poliomyelitis excretion at least 1 year after onset of disease. None of the 348 affected individuals had IgG deficiency or persistent poliovirus excretion. One child had borderline low serum IgA concentration. Since we did not study children under 2 years of age, persons born with IgG deficiency disorders may have died in developing countries where replacement immunoglobulin therapy is not readily available. Nevertheless, persistent poliovirus excretion among persons 2 years of age and older with residual paralytic poliomyelitis is uncommon in developing countries.

To investigate bone mineral status in children with verified cow milk allergy for more than 4 yr compared with a large reference population of 343 local healthy controls. Whole body bone mineral content (BMC), projected bone area and bone mineral density (BMD) were determined by dual energy x-ray absorptiometry in nine children (8-17 yr old, one girl and eight boys). All children had cow milk allergy for more than 4 yr. All children had asthma and was treated with corticosteroids. BMC and BMD were reduced for age (p < 0.01). Height for age was significantly reduced (p < 0.01), indicating 'short' bones. BMC for bone area was borderline reduced (p = 0.05), indicating reduced bone mineralization. The growth of the children was reduced compared with there parents and siblings (p < 0.01), and the bone age was retarded (mean 1.4 yr, p < 0.01). Calcium consumption calculated from food intake was about 25% of the recommended. All laboratory tests were normal. Short bones were the main reason for reduced BMC and BMD for age in children with cow milk allergy, but a borderline low BMC for bone area indicated reduced bone mineralization of the bones. A supplementation of calcium to children with cow milk allergy is recommended.

In recent years, we have come a long way from categorizing all ankle-brachial indices (ABIs) above 0.90 as normal. Both borderline low and high ABIs present significant risk ([1][1]). In this issue of the Journal , Arain et al. ([2][2]) at the Mayo Clinic document the risk of a high ABI with the

A relationship between folate and neuropsychiatric disorders has been inferred from clinical observation and from the enhanced understanding of the role of folate in critical brain metabolic pathways. Depressive symptoms are the most common neuropsychiatric manifestation of folate deficiency. Conversely, borderline low or deficient serum or red blood cell folate levels have been detected in 15–38% of adults diagnosed with depressive disorders. Recently, low folate levels have been linked to poorer antidepressant response to selective serotonin reuptake inhibitors. Factors contributing to low serum folate levels among depressed patients as well as the circumstances under which folate and its derivatives may have a role in antidepressant pharmacotherapy must be further clarified.

A 50-year-old woman presented with pain and tenderness in the right flank. Urogram and ultrasound demonstrated the presence of an 8-mm calculus in the right kidney. There were persistently elevated serum calcium levels ranging from 10.7-11.4 mg/dL (normal range: 8.5-10.5) and borderline low serum phosphate levels of 2.4-2.9 mg/dL (normal range 2.5-4.5). Serum albumin levels were normal. The patient's parathormone levels were elevated and a diagnosis of primary hyperparathyroidism was made. An MRI of the neck failed to reveal evidence of parathyroid pathology. Tc-99m sestamibi imaging demonstrated no abnormal parathyroid tissue in the neck, but clearly showed an abnormal focus in the anterior mediastinum.

The authors assessed 20 carbamazepine-treated patients for the development of hyponatremia. None of the patients had readings below 135 meg/liter of sodium before carbamazepine therapy, but five (25%) did have such readings after carbamazepine therapy. Three of these patients developed frank symptoms of hyponatremia within 1-3 months of the start of therapy. In one patient, hyponatremia developed after rechallenge with carbamazepine. The authors suggest that caution be used in prescribing carbamazepine to patients with low or borderline low sodium values.

To define further the factor VIII abnormality in acquired von Willebrand's disease, we performed immunoelectrophoresis of factor VIII antigen, as well as quantitative measurements of the antigen, factor VIII procoagulant activity and von Willebrand factor activity on plasma from an affected 57-year-old man who also had a poorly differentiated lymphocytic lymphoma. No evidence for an inhibitor against factor VIII procoagulant activity or von Willebrand factor activity was detected, but immunoelectrophoresis showed none of the less anodic forms of factor VIII antigen. There were concomitant decreases in total antigen (0.19 U per milliliter) and von Willebrand factor levels (0.12 U per milliliter). Factor VIII-procoagulant activity was borderline low (0.45 U per milliliter). Correction of both the abnormal immunoelectrophoresis pattern and the quantitative abnormalities followed radiotherapy of the lymphoma. The factor VIII abnormalities might have resulted from binding or destruction of theless anodic forms of factor VIII antigen by the malignant lymphocytes.

We have studied a family in which the mother has PKU and has had six pregnancies, three untreated and three treated with a low-phenylalanine diet begun during the first or second trimester. The three nonphenylketonuric offspring from two of the untreated pregnancies are mentally retarded and microcephalic. The two nonphenylketonuric offspring from two of the treated pregnancies are also microcephalic and have low or borderline low intelligence. One untreated pregnancy resulted in spontaneous abortion. One treated pregnancy resulted in stillbirth at seven months. It is not certain that dietary treatment of maternal PKU during pregnancy, when begun after conception, is sufficient to protect the fetus. This therapy may have to be ongoing at the time of conception for optimal fetal protection.

Assessments were made of 945 consecutive hospital patients with regard to a relation between borderline low thyroid function (recognised by a slightly raised thyroid stimulating hormone), thyroid autoimmunity, serum cholesterol, and coronary heart disease. Men and women with a thyroid autoimmunity, serum cholesterol, and coronary heart disease. Men and women with a thyroid stimulating hormone of 4.0 mU/l or over had a higher prevalence of coronary heart disease than did age-matched controls, and this difference was significant in women. The excess of coronary heart disease was not explained by an excess of other risk factors such as a high cholesterol, hypertension, smoking, and diabetes. Women with thyroid antibodies had a slightly higher prevalence of coronary heart disease despite the unexpected finding of a lower serum cholesterol. The data point to an association between borderline thyroid function and autoimmunity and coronary heart disease which is not mediated through a raised serum cholesterol.

Normochromic anaemia was diagnosed in two brothers in early infancy. At the time of this report they were aged 10 (M.H.) and 12 (T.H.) years. A defect of the atrial septum was found in both patients. They had slight skeletal malformations. Their haemoglobin values have remained constantly at the level of about 100 g/l and the RBC count at about 3.5 x 10(12)/l. At repeated examinations, both the patients and their parents had low or borderline low erythrocyte enolase levels. Erythropoietin levels were normal and so were numerous other laboratory tests, including analysis for abnormal haemoglobins. The condition could represent a mild form of chronic congenital hypoplastic anaemia.

The purpose of this study was to ascertain the cause for seasonal variations of donor deferral. Deferred donors and monthly temperatures from 1981 to 1984 were tallied and analyzed. Temperatures were categorized at 10-degree intervals from 15 degrees F to 75 degrees F. Donors failing the hemoglobin screening then underwent a microhematocrit evaluation. Of the 65,531 donors seen at this blood center, 4537 were deferred, for an annual deferral rate of 6.7 to 7.2 percent (p less than 0.1). Deferrals for low hematocrit were significantly higher for both sexes at and above 45 degrees F. Similar experiences were also observed in 79,563 donors who came to the bloodmobiles over 19 months in 1983 and 1984. The percentages of deferrals at the blood center for low hematocrit in 1984 were 1.22, 2.6, and 3.5 for men and 6.7, 11.3, and 13.2 for the women at monthly average temperatures of 15.1 to 45 degrees F, 45.1 to 65 degrees F, and 65.1 to 75 degrees F, respectively. These differences of deferral rates are significant (p less than 0.05-0.001). Although other personal demographics remained constant, more of the donors deferred in this study had also been deferred in the past. The climatic changes had a significant effect on the blood composition that resulted in the deferral of blood donors with a borderline low hematocrit.

We have studied a family in which the mother has PKU and has had six pregnancies, three untreated and three treated with a low-phenylalanine diet begun during the first or second trimester. The three nonphenylketonuric offspring from two of the untreated pregnancies are mentally retarded and microcephalic. The two nonphenylketonuric offspring from two of the treated pregnancies are also microcephalic and have low or borderline low intelligence. One untreated pregnancy resulted in spontaneous abortion. One treated pregnancy resulted in stillbirth at seven months. It is not certain that dietary treatment of maternal PKU during pregnancy, when begun after conception, is sufficient to protect the fetus. This therapy may have to be ongoing at the time of conception for optimal fetal protection.

To the Editor.— In the QUESTIONS AND ANSWERS section of the Sept 5, 1986, issue of JAMA , a physician 1 wrote for advice regarding the appropriate diagnostic workup for two 8-year-old boys with recurrent otitis media and sinusitis. He had already obtained quantitative immunoglobulin measurements, demonstrating borderline low levels of IgG and IgM in both patients and IgA levels of 60 mg/dL (0.60 g/L) and 10 mg/dL (0.10 g/L), respectively. One boy in addition had been found to have an adequate antibody response to tetanus toxoid. We are concerned that the response to this inquiry was misleading in several respects. First, it was stated that both boys had "significant deficiencies in IgA level." The level of 60 mg/dL (0.60 g/L) is within two standard deviations from the mean for an 8-year-old and presents no significant concern. While an IgA level of 10 mg/dL (0.10 g/L) in the second patient might

Top of pageAbstract Local immunoglobulin production was evaluated in 11 children with borderline low serum IgA concentration (3–22 mg/100 ml) by studying immunoglobulin-containing cells in jejunal and rectal mucosa and by measuring immunoglobulins in intestinal juice and saliva. Most patients had increased susceptibility to infections. The total amount of immunoglobulin producing cells was normal. The IgA-IgM cell ratio was reversed in 6 cases, viz. in both the jejunal and rectal mucosa in one, and in one or the other in 5 patients. This reversed cell ratio was usually associated with the lowest serum IgA levels, below 6 mg/100 ml. IgA was detected in all secretions studied except for the jejunal juice of one patient. We conclude, that some of the children with borderline low serum IgA concentration do have definitive functional impairment of the mucosal IgA system. This is indicated by relative increase in the IgM-cell population in the mucosal surfaces.