Incidence of medullary thyroid carcinoma and Hirschsprung disease based on the cosmos database.

PURPOSE: Multiple endocrine neoplasia Type 2A (MEN2A) can occur with Hirschsprung disease (HD) due to mutation in the RET proto-oncogene, with the majority developing medullary thyroid carcinoma (MTC). Given the comorbidity, many parents have contacted us to share concerns and unfortunate experiences about the prevalence rates of MEN2A/MTC in patients with HD. The aim is to determine the prevalence rate of patients with HD and MEN2A or medullary thyroid carcinoma, respectively. METHODS: This is a cross-sectional study of the COSMOS database from January 01, 2017, to March 08, 2023. The database was searched for patients diagnosed with MEN2A, MTC, and HD. IRB exemption was provided (COMIRB #23-0526). RESULTS: The database contained 183,993,122 patients from 198 contributing organizations. The prevalence of HD and MEN2A was 0.00002%, and for HD and MTC was 0.000009%. One in 66 patients (1.5%) with MEN2A also had HD. One in 319 patients (0.3%) in the HD group had MEN2A. One in 839 patients (0.1%) within the HD population had MTC. CONCLUSION: The prevalence of MTC and HD or MEN2A and HD in the study population was low. Considering that almost all MEN2A patients have a positive family history, this data does not support the general genetic testing of HD patients.

Serum prealbumin, retinol-binding protein, transferrin, and albumin levels in patients with large bowel cancer.

In a study of the levels of serum prealbumin (PALB), retinol-binding protein (RBP), transferrin (TF), and albumin (ALB) in patients with large bowel cancer, critical values were established as (g/liter): PALB, 0.15; RBP, 40 X 10(-3); TF, 2.0; and ALB, 30. Values consistently below these were taken as a sign of malnutrition. The proteins in this system were interrelated and tended to show a similar pattern of change. Metastatic colon cancer caused a relatively small decline of ALB compared to the mean in tumor-free patients. PALB was the most sensitive indicator of nutrition, and its levels and rates of change had a prognostic significance. A rapid fall of PALB often occurred 2--3 months prior to the patients's death; this preterminal phase in ambulant patients was frequently heralded by a progressive rise in the level of C-reactive protein in the absence of any obvious infection.

Serum beta 2-microglobulin and human immunodeficiency virus infection.

Serum beta 2-microglobulin (beta 2-M) was measured in two prospectively evaluated groups of homosexual men in 1983 and 1985. Serum beta 2-M was raised in 64% of patients with HIV infection, but in only 6.7% of uninfected homosexuals. Depression of the total lymphocyte count was only clinically useful when it reached less than 1.0 X 10(9)/l. In further studies all patients with AIDS and AIDS-related complex (ARC) had raised levels of serum beta 2-M. Mean levels of beta 2-M did not differ between patients with persistent generalized lymphadenopathy (PGL) and asymptomatic HIV-infected patients. Raised serum levels of beta 2-M accompanied major immune dysfunction in HIV infection. Serum beta 2-M levels of greater than 3.0 mg/l in HIV-infected homosexual men were associated with progression to AIDS.

Clinical evaluation of serum tissue polypeptide-specific antigen (TPS) in non-small cell lung cancer.

M3 is an epitope of the tissue polypeptide antigen detectable in the serum by immunoradiometric assay. This epitope is referred to as tissue polypeptide-specific antigen (TPS). We examined the pretreatment TPS level of 160 non-small cell lung cancer (NSCLC) patients and 71 patients who suffered from non-malignant pulmonary diseases. The upper limit of normal values was 140 U/l. Using this cutoff, the sensitivity and specificity were 36 and 90%, respectively. The TPS was significantly higher in NSCLC patients with an advanced stage, a mediastinal lymph node involvement or a poor performance status. This level was significantly higher in the group of patients for whom the disease proved to progress during chemotherapy. In univariate analysis, patients with a high TPS level proved to have a shorter survival than patients with a TPS < or = 140 U/l. In Cox's model analysis, performance status, stage of the disease and serum TPS were the only significant prognostic variables. The low sensitivity of TPS precludes its use for diagnosis. However, the pretreatment TPS level adds information to the management of NSCLC inasmuch as it predicts a low sensitivity to chemotherapy and a poor prognosis.

The prognostic significance of acute phase proteins in patients with inoperable squamous cell carcinoma of the bronchus.

In 95 patients with inoperable squamous cell carcinoma of the bronchus, nine potential serum "markers" were analysed for their prognostic significance. Lactate dehydrogenase, alpha 1 HS-glycoprotein, ferritin, carcino-embryonic antigen and immunoglobulin E did not prove to be useful as prognostic indices. The erythrocyte sedimentation rate and the acute phase proteins alpha 1 acid glycoprotein, C-reactive protein and prealbumin were correlated with survival. After taking the performance status and tumour stage into account, C-reactive protein still proved to be a strong prognosticator. The clinical relevance of the acute phase proteins signifying a so-called "biochemical status" next to the "clinical status" is discussed.

Neuron-specific enolase can be used as the sole guide to treat small-cell lung cancer patients in common clinical practice.

Serum samples were collected from 115 small-cell lung cancer patients before each course of chemotherapy and during follow-up. Levels of neuron-specific enolase (NSE) were measured and compared to the clinical assessments of the course of the disease, which were done by the responsible physician without knowledge of NSE-values. The predictive accuracy of an increase or decrease of NSE for a major response (CR + PR), SD or PD was 98%. Importantly no false-positive rises of NSE were observed. On the basis of this large number of data it seems justified to conclude that in common clinical practice the treatment of small-cell lung cancer patients can be monitored by serial measurements of NSE alone.

Comparison of serum amyloid A protein and C-reactive protein concentrations in cancer and non-malignant disease.

Serum amyloid A (SAA) concentrations correlate well with C-reactive protein (CRP) concentrations. However, SAA is sometimes raised in disease when CRP is normal. This appears to occur more often in certain diseases such as rheumatoid arthritis, primary biliary cirrhosis and chronic active hepatitis. SAA concentrations did not distinguish between cancer with and without metastases as previously indicated, although mean concentrations were higher in more advanced tumours. Despite the higher sensitivity of SAA over CRP in the inflammatory response, SAA has little advantage over CRP in the assessment of malignant disease.

Serum alpha-thiol protease inhibitor concentrations in health and disease.

Serum alpha-thiol protease inhibitor (alpha-TPI) concentration was assayed by radial immunodiffusion in normal subjects, pregnant women, and in a wide variety of diseases. The normal concentration (448 (SD 75) mg/l) increased significantly (p less than 0.001) in pregnancy to 575 (89) mg/l, and in prostatic cancer treated by oestrogens to 666 (87) mg/l. Inconsistent changes were observed in inflammatory and malignant disease and in liver disease. A temporary pronounced fall of alpha-TPI was seen after burn injury, and a sustained fall after bone marrow transplantation. Crossed immunoelectrophoresis showed that the serum alpha-TPI occurred in two forms, with alpha 2 and alpha 1 electrophoretic mobilities. A heavy demand on this antiprotease may result in suppression of the alpha 1 form.

Isoelectric points of urinary light chains in myelomatosis: analysis in relation to nephrotoxicity.

Measurements of the isoelectric point (pI), sialic acid content, and polymerisation were made of 43 light chains isolated from the urine of patients with myelomatosis excreting large amounts of light chains. The pIs ranged from 3.5-9.5, and 23 were greater than 7.0. Sialylation was detected in 62% of light chains, and 69% showed microheterogeneity of charge. There was no clear association between the pI, sialylation, or polymerisation and the presence of renal failure, as assessed by serum creatinine concentrations. Light chains with pI spectrotype in the basic range, however, were found to produce more proximal tubular dysfunction than acidic light chains.

Serum beta 2-microglobulin and C reactive protein concentrations in viral infections.

Serum beta 2-microglobulin concentrations were assayed in a number of virus diseases. Infectious mononucleosis, cytomegalovirus, and influenza A were associated with pronounced increases in serum beta 2-microglobulin concentration. Smaller increases, with values generally less than 4 mg/l, were noted in other viral infections. Apart from in acute influenza A, the C reactive protein and beta 2-microglobulin responses were not associated.

C reactive protein: an aid to assessment and monitoring of acute pancreatitis.

An evaluation of C reactive protein as an indicator of the progress of acute pancreatitis has been made, and the data have been compared with the information given by the white cell count, erythrocyte sedimentation rate, and temperature and by two antiproteases--alpha 1 protease inhibitor and alpha 1 antichymotrypsin. The main value of C reactive protein is to provide a guide to the severity of the inflammation and to increase clinicians' awareness of the patient's enhanced risk of developing pancreatic collections when the C reactive protein concentration remains high (greater than 100 mg/l) at the end of the first week of the illness. In this respect C reactive protein concentrations are superior to white cell count, erythrocyte sedimentation rate, and temperature and the concentrations of antiproteases.

Changes in plasma beta 2 microglobulin concentrations after allogeneic bone marrow transplantation.

Plasma concentrations of beta 2 microglobulin (B2M), the light chain of the class I major histocompatibility complex, were measured serially in 26 patients undergoing allogeneic bone marrow transplantation (BMT). The concentrations fell after conditioning treatment, and recovered when the marrow was transplanted. Bacterial infection did not influence B2M concentration, but nine of 22 episodes of acute graft versus host disease were associated with raised concentrations. Increased plasma B2M concentrations were also a feature of eight episodes of chronic graft versus host disease, and these fell after treatment. Reactivation of herpes simplex, varicella zoster, or cytomegalovirus infections were also accompanied by raised B2M concentrations. Three patients with cytomegalovirus pneumonitis had high concentrations of plasma B2M, the rise starting between five and 22 days before onset of symptoms. Although it is non-specific, serial measurement of plasma B2M in patients undergoing BMT may be clinically useful in monitoring chronic graft versus host disease.

Proximal renal tubular function in myelomatosis: observations in the fourth Medical Research Council trial.

Proximal renal tubular function was studied in 522 consecutive patients entered into the Medical Research Council's fourth myelomatosis trial. Assessment was made at presentation after a 48 h period of hydration but before administration of chemotherapy. The most common abnormalities in the urine other than light chain proteinuria were raised concentrations of the low molecular weight proteins alpha 1-microglobulin and alpha 1-acid glycoprotein. These were usually accompanied by increases in urinary beta-N-acetyl-D-glucosaminidase concentrations. The concentration of these substances in the urine directly correlated with urinary free light chain output. This tubular proteinuria was seen whether or not patients had impaired glomerular function, as assessed by a rise in serum creatinine concentration. Urinary concentrations of retinol binding protein, however, were generally increased only when serum creatinine concentrations were raised. This applied even when there were high concentrations of light chains, alpha 1-microglobulin, alpha 1-acid glycoprotein, and beta-N-acetyl-D-glucosaminidase in the urine. There is therefore a selective tubular proteinuria in myelomatosis which is seen in almost all patients with urinary light chain values greater than 1 u/l. This proteinuria is generally reversible, when light chains no longer appear in the urine. Patients whose serum creatinine was greater than 200 mumol/l, however, had increased urinary output of retinol binding protein in addition to increased excretion of alpha 1-microglobulin, alpha 1-acid glycoprotein, and beta-N-acetyl-D-glucosaminidase. Tubular proteinuria in many of these patients presenting in renal failure persisted even when light chain output was reduced after chemotherapy.

Alpha-1-microglobulin: an indicator protein for renal tubular function.

A comparison of urinary alpha 1-microglobulin concentrations to the behaviour of other indicators of renal tubular disorders, beta 2-microglobulin, retinol-binding protein and N-acetyl-beta-D-glucosaminidase (NAG) has been made. In acute tubular disorders the concentrations of urinary beta 2M and RBP are highly correlated (r = 0.89) but this is less marked for alpha 1M and beta 2M (r = 0.55) and alpha 1M and RBP r = 0.48. NAG tends to run a parallel course to alpha 1M concentrations but lags behind the recovery of low molecular weight protein reabsorption following injury of the tubular cells. The concentrations of alpha 1M, and in particular its stability at low pH suggest that this protein may be useful in screening for tubular abnormalities and detecting chronic asymptomatic renal tubular dysfunction. Urinary alpha 1M greater than 15 mg/g creatinine is strongly suspicious of a proximal tubular dysfunction. The distinction between pure tubular proteinuria and mixed glomerular and tubular proteinuria requires further analysis.

Serum CA 125 antigen levels and disease severity in patients with endometriosis.

We wished to test whether there was a relationship between CA 125 levels and the severity of endometriosis that would allow CA 125 to be used to monitor disease progression. CA 125 levels were measured in 52 women with laparoscopically staged endometriosis and in eight women with normal pelvic findings at laparoscopy. There was a positive correlation (r = 0.63; P less than .0001) between disease severity and CA 125 levels. CA 125 was also elevated, compared with women with a normal pelvis, in patients with mild and moderate disease. There was no relationship between CA 125 levels and the day of the menstrual cycle. These results suggest that after malignancy has been excluded, CA 125 levels may offer a useful method of monitoring disease progress.

Biochemical markers in Hodgkin's disease and non-Hodgkin's lymphoma.

Vertical studies indicate that, in general, acute phase reactant proteins (APRP) reflect disease activity in both Hodgkin's disease and non-Hodgkin's lymphoma. Longitudinal studies of the selected APRP profile demonstrate the following: 1. The stable profile is characteristic of remission. 2. Considerable elevation of APRPs coincides with relapsed disease. 3. An unstable profile is a feature of relapsing disease and may give early warning of relapse. 4. Patients responding inadequately to treatment frequently have unstable APRP profiles.

A method to detect the in vitro modification of serum beta-2-microglobulin in health and disease.

The electrophoretically fast moving form of beta-2-microglobulin (alpha-B2m) was shown by crossed immunoelectrophoresis to be produced in vitro after incubation at room temperature and was not present in freshly drawn sera. A radioisotopic assay was developed to measure this conversion to alpha-B2m in sera from 14 healthy individuals and from 208 patients with benign and malignant disease. The activity was present in all the sera tested and the levels were significantly higher in sera from patients with small cell lung cancer, prostate cancer and in childhood lymphomas when compared to the level in normal sera.

The use of concanavalin A crossed immuno-affinoelectrophoresis to detect hormone-associated variations in alpha 1-acid glycoprotein.

alpha 1-Acid glycoprotein produces three peaks on crossed immuno-affinoelectrophoresis with concanavalin A in the first dimension, which is indicative of a degree of heterogeneity in the carbohydrate portion of this plasma glycoprotein. A different pattern, however, showing relatively less concanavalin A-binding material, is found in association with and after an increase in female sex hormone levels. Our observations strongly suggest a prolonged hormonal effect on the carbohydrate composition of alpha 1-acid glycoprotein, which may alter the metabolism or the function of the protein.

The evaluation of a new enzyme immunoassay for the measurement of prostatic acid phosphatase.

An enzyme immunoassay for prostatic acid phosphatase (PAP) has been assessed. An upper limit normal is set at 1.8 microgram/1. There is a very low incidence of raised levels in chronic diseases or cancers other than those of the prostate. Patients with well-controlled prostatic cancer have levels less than 1.8 microgram/1 and show little variation about their own mean. PAP can rise exponentially with a doubling time of 1-5 months. This assay is unlikely to increase the detection of asymptomatic prostatic cancer as 66% of T0-2NXM0 cases had PAP less than 1.8 microgram/1. The main advantages over routine enzyme assays are its sensitivity and accuracy in the lower range.

Serum beta 2-microglobulin in hepato-biliary diseases.

The levels of serum beta 2-m in hepato-biliary disease have been examined. Significant increase has been observed in various benign and malignant diseases of the liver, but not in jaundice due to acute pancreatitis. The age-dependent relationship of beta 2-m is present in controls, weaker in the malignant diseases and absent in the benign diseases. The level of beta 2-m is not influenced by jaundice. Serum beta 2-m levels have no role as a discriminant in liver disease.