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Biomedical subjects

F Hawkins

Publications and source records attributed to F Hawkins.

At least 37 records · Page 2Linked to original sources

Calcitonin, etidronate, and calcidiol treatment in bone loss after cardiac transplantation.

Cardiac transplantation is associated with severe bone loss caused by glucocorticoids, immunosuppressive treatment, and other factors. Treatment protocols for the prevention of bone loss is being studied. Forty patients who underwent cardiac transplantation were randomly given calcitonin (n = 13; 100 UI/d, nasal route), etidronate (n = 14; cyclical treatment 400 mg p.o./d/2 weeks/3 months), or calcidiol (n = 13; 32,000 IU/weekly) therapy for at least 18 months. Serum parameters (Ca, P, alkaline phosphatase, osteocalcin, intact PTH), urinary calcium, and vertebral mineral density (VMD; L2-L4, DXA Hologic QDR 1000) were measured immediately before treatment and after 6, 12, and 18 months of therapy after cardiac transplantation. Patients with cardiac transplantation had a VMD significantly lower than age and sex-matched Spanish controls. Prevalence of osteoporosis (Z-score below -2 SD) was 30%. Osteocalcin levels increased at 6, 12, and 18 months of treatment in the three groups. After 18 months of treatment, VMD increased significantly in the calcidiol 4.9%, vs. -1.19% and -0.19% in the calcitonin and etidronate groups, respectively. A lower incidence of fracture was found in patients treated with calcidiol during the study. In summary, we have found in this open randomized study that calcidiol was the most effective drug in the prevention and treatment of bone loss in patients after cardiac transplantation.

Alkaline Phosphatase↗

Identification and characterization of the mouse obesity gene tubby: a member of a novel gene family.

The mutated gene responsible for the tubby obesity phenotype has been identified by positional cloning. A single base change within a splice donor site results in the incorrect retention of a single intron in the mature tub mRNA transcript. The consequence of this mutation is the substitution of the carboxy-terminal 44 amino acids with 24 intron-encoded amino acids. The normal transcript appears to be abundantly expressed in the hypothalamus, a region of the brain involved in body weight regulation. Variation in the relative abundance of alternative splice products is observed between inbred mouse strains and appears to correlate with an intron length polymorphism. This allele of tub is a candidate for a previously reported diet-induced obesity quantitative trait locus on mouse chromosome 7.

Adaptor Proteins, Signal Transducing↗

[the early diagnosis of the vertical transmission of the human immunodeficiency virus type 1. The evaluation of diagnostic tests].

BACKGROUND: The early diagnosis of vertically transmitted human immunodeficiency virus infection cannot be based on the presence of specific serum antibodies since those of the maternal IgG class pass the placenta and may be detected in children for up to 18 months. Based on this fact, the aim of this study was to evaluate other techniques for early diagnosis of the infection applicable from birth in 306 children of infected mothers. METHODS: The production of in vitro antibodies, virus culture and polymerase chain reaction (PCR) were used. The sensitivity of the techniques was estimated in the 40 children diagnosed with human immunodeficiency virus infection and specificity was determined in the 266 uninfected children. RESULTS: The sensitivity for the production of in vitro antibodies was 62.0% at 3 months and 94.7% at 6 months; 90.4% and 88.2%, respectively, for the viral culture and 92.3% and 94.1%, respectively, for the PCR. The specificity of all the cases was higher than 89.4% although varied in relation to age. CONCLUSIONS: The combination of several diagnostic techniques provides better performance for the early diagnosis of vertical transmission of the human immunodeficiency virus. Given that viral culture takes longer to provide results and is more expensive, it is less recommendable for routine use, although the form of viral replication may be useful to establish the prognosis.

Aging↗

Calcitonin and bisphosphonates treatment in bone loss after liver transplantation.

Osteopenia is a major complication of orthotopic liver transplantation (OLT). However, no effective therapy for bone disease has been defined. We have studied vertebral bone mineral density (VMD) and fasting serum markers of bone formation [bone gla protein (BGP), procollagen I carboxyterminal peptide (PICP)] and metabolism (serum Ca, P, intact parathyroid hormone (iPTH), 25OHD3 and 1,25(OH)2D3) in 120 patents after OLT. VMD was measured by dual-energy X-ray absorptiometry (DXA) using a Hologic QDR 1000 densitometer on two occasions, 12 months apart. Patients with OLT had a VBD significantly lower compared with age- and sexed-matched Spanish controls (P < 0.05). Prevalence of osteoporosis (Z score below -2 SD) was 35.8%. Serum BGP (8.6 +/- 0.7 ng/ml) and PICP (222.9 +/- 81.9 ng/dl) were higher than those of controls. However, serum calcium, phosphorus, iPTH, 25OHD3, and 1,25(OH)2D3 were within normal range. Patients with osteoporosis were randomly treated with 40 IU/day of calcitonin i.m. (Diatin, Ferrer Int. Laboratories) (n = 17) or 400 mg p.o., 15 days every 3 months, of sodium ethiodronate (Difosfen, Rubio Laboratories) (n = 23). All patients received 500 mg/12 hours of elemental calcium p.o. After 12 months of treatment, a significant increment of vertebral mineral density (VMD) was observed (6.4% and 8.2%, respectively). Serum BGP and PICP values remained elevated without a difference between the two drugs. Our results indicate that antiresorptive drugs may be of benefit in the high turnover osteoporosis of OLT recipients.

Adult↗

Prognostic value of immunological data, in vitro antibody production, and virus culture in vertical infection with HIV-1.

The prognostic value of immunological indices, in vitro antibody production, and virus culture pattern at 3 months of age was estimated in 35 infants infected by HIV-1 from a cohort of 298 babies born to HIV-1 seropositive mothers and followed up from birth. At 1 year old, 15 of these infants were classified as stage P-1 (according to the Centers for Disease Control classification) seven were P-2A, and seven had AIDS. Significantly higher CD8 percentages, lower percentages and absolute value of CD4, and lower CD4/CD8 ratios at 3 months were observed in infants with severe symptoms at 1 year of age when compared with those who were asymptomatic at this age. Seventy seven per cent of infants with a 'rapid' virus culture when 3 months old had developed AIDS or had died by 1 year of age and only 8% of those with 'slow' virus culture had AIDS when 1 year old. Moreover, 100% of those who were asymptomatic at 1 year had a slow virus culture at 3 months. Significant statistical association was found between the virus replication pattern at 3 months and the clinical stage at 1 year of age.

Acquired Immunodeficiency Syndrome↗

[Cushing's syndrome associated with a metastatic medullary carcinoma of the thyroid. A report of 2 cases and a review of the literature].

An ectopic Cushing syndrome (CS) caused by a medullary thyroid carcinoma (MTC) is an exceptional observation. Two patients are here reported with metastatic MTC, who developed CS two years after the thyroid cancer was diagnosed. A review is also made of clinical and biochemical characteristics of cases with MTC associated with ectopic CS reported in the literature and it is concluded that the cortico-adrenal function in follow-up should be monitored in patients with this type of cancer.

Aged↗

Spinal bone mass after long-term treatment with L-thyroxine in postmenopausal women with thyroid cancer and chronic lymphocytic thyroiditis.

This study investigated the effect of long-term treatment upon bone density with L-Thyroxine in postmenopausal women compared with untreated postmenopausal women with climacteric symptoms. We measured spinal bone density in three groups (n = 84) of postmenopausal women: (A) those treated with TSH-suppressive doses of L-Thyroxine for a medium of 5 years after removal of thyroid cancer; (B) those on L-Thyroxine treatment for a median of 9 years after being diagnosed with chronic lymphocytic thyroiditis (CLT); and (C) those with no thyroid disease or other known pathology and without any treatment. There were no differences in dietary calcium intake and daily activity between untreated and L-Thyroxine-treated women. Measurements of bone mineral density were performed at spine level L1-L4 using a dual X-ray densitometer and serum thyroid-stimulating hormone (TSH), thyroid hormones, and bone markers (serum osteocalcin, procollagen I, urinary calcium), and PTH levels were assayed and found to be within normal ranges. Women receiving L-Thyroxine after thyroid cancer had slightly higher FT4 levels compared with women who had CLT and lower TSH levels, with serum T4 and T3 levels normal and similar in both groups. No significant differences were found in spinal bone density after L-Thyroxine treatment between Groups A and B and compared with Group C. Bone loss according to 2 SD below reference standards (age and sex matched) was found in the 12.9% of L-Thyroxine-treated patients versus 22.6% of untreated women. No correlation was found between bone loss and thyroid hormone levels and duration of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗

Bone density and turnover in Addison's disease: effect of glucocorticoid treatment.

Osteoporosis is a well-known side-effect of chronic treatment with glucocorticoids. We have studied vertebral bone mineral density (BMD) and biochemical markers of bone metabolism in 30 patients diagnosed of Addison's disease (AD) to determine the effect of long-term replacement treatment with hydrocortisone (30 mg/day) or prednisone (7.5 mg/day). Lumbar bone mineral density was measured with dual energy X-ray absorptiometry in L-1-4 in two occasions, separated by 12 months. BMD in premenopausal women and men with AD was similar to healthy controls and postmenopausal women had slightly lower results. Rate of change of bone density followed up over a period of 12 months was -0.82%. Bone loss was not influenced by duration or type of steroid treatment. Biochemical parameters, serum calcium, alkaline phosphatase, osteocalcin, procollagen type I, PTH and 25(OH)vitamin D were within normal limits. Our results show that in patients with AD, after replacement with low doses of glucocorticoids there is no significative trabecular bone loss neither modifications in bone formation markers.

Absorptiometry, Photon↗

Both class I and class II HLA antigens are thyroid cancer susceptibility factors.

It has been established that HLA antigens are susceptibility factors for different cancers, including thyroid tumors. However, the diversity and sometimes weak and contradictory associations found have frequently led to the view that the HLA and tumorigenesis links might be the result of statistical errors. However, it has recently been established that it is indeed a currently complex and unexplained but real phenomenon, which may be crucial in preventing several types of cancer. In the present work we have found in a relatively large series of thyroid cancer patients (n = 161) that both HLA class I (B35) and class II (DR11) antigens are susceptibility factors only in the papillary tumor group of patients, B35 association p value is found at the limit of significance (pc(120) = 0.05); the follicular group did not show any HLA association, suggesting that the etiopathogenesis of each type of cancer is different. HLA-B35 and DR11 are not working together to induce tumorigenesis and each of them seems to confer susceptibility by using different pathways or by being markers of distinct neighboring susceptibility genes. DR4 has also been found in 86% (n = 6) of Hürthle cell carcinoma. No association has been found between HLA and disease activity. HLA mechanisms of association to cancer are discussed and a world-wide HLA/tumorigenic study is proposed to obtain a clear picture of the puzzling and controversial susceptibility markers found in different tumors and in different ethnic groups.

Disease Susceptibility↗

Is there a place for urinary growth hormone measurement?

The evaluation of growth hormone (GH) secretion is an important problem in pediatric endocrine practice. The diagnosis of GH insufficiency is based on the finding of a "blunted" GH response to GH provocative tests or on the demonstration of a decreased endogenous secretion. From a practical point of view, these methods are uncomfortable, expensive and time consuming. Recently, very sensitive specific assays to measure human GH in urine have been developed. We present a discussion of available data on these tests in order to estimate their role in the evaluation of a short or slowly growing child. The present available assays allow measuring very low levels of GH in a small sample of untreated urine. The main limitations of urinary GH measurement are the intrasubject variability, wide normal range, overlapping results in several GH secretory states and lack of information on GH pulsatility. However, most of these limitations also apply to other tests of GH secretion. The advantage of urinary GH tests is that they provide, in an easy procedure, information on serum GH concentration. There is good correlation between urinary and serum GH concentration and several findings suggest that urinary GH excretion reflects changes in plasma GH levels during the period of urine collection. Therefore, the usefulness of urinary GH measurement is that of a simpler and cheaper screening method for assessing integrated serum GH concentration in clinical practice.

Adult↗

Lack of preferential transmission of diabetic HLA alleles by healthy parents to offspring in Spanish diabetic families.

HLA-DR3 or -DR4 segregation distortion to normal or insulin-dependent (ID) diabetic offspring of 108 Spanish families whose parents were healthy was not observed; however, DR3 or DR4 ID offspring is significantly increased in the present study, since parents were chosen after tracing ID children. These results are discrepant with those found by others in families with diabetic parents in other ethnic groups. These conflicting data could be due to sampling errors or segregation distortion. Thus, ethnic group differences in a genetic (T/t-like) or metabolic mechanism might confer advantages to DR3- or DR4-bearing gametes from ID diabetic parents, but segregation distortion might only affect certain HLA DR3 or DR4 extended haplotypes which are frequent and characteristic for certain ethnic groups (i.e. B8-DR3-BfS-C4AQOB1 and Bw62-DR3-BfS-C4A383 in most caucasians) but not for other haplotypes in other ethnic groups (Spaniards; B18-DR3-BfF1-C4A3BQO and BwX-DR4-BfX-C4AXBX).

Adolescent↗

[Serum osteocalcin and bone turnover in hyperthyroidism].

In hyperthyroidism an increased bone turnover may appear, essentially due to a higher bone resorption. In order to evaluate this complication we have measured the serum levels of Osteocalcin (BGP) in 41 patients, mean age 43 +/- 18 (+/- SD) years. BGP is a protein synthesized by osteoblasts which may be employed as an specific and non-aggressive marker of bone turnover. Serum BGP was significantly increased in these patients with respect to normals (6.2 +/- 4.2 vs 3.7 +/- 1.3 ng/ml). The total group was divided according to BGP values higher and lower than 3.7 ng/ml, emerging two groups with BGP 7.9 +/- 3.8 (n = 30) y 2.2 +/- 1.2 ng/ml (n = 11), respectively. There were not differences between these two groups regarding to thyroid hormones or other data of mineral metabolism. In the total group, only serum BGP and T3 were correlated. Our results suggest the existence of a double effect of hyperthyroidism on bone, as well as a temporal dissociation between thyroid synthesis and bone metabolism.

Adult↗

Study of bone loss in diabetes mellitus type 1.

While people with type 1 diabetes mellitus (DM) often have bone deficiency, the relation between this deficiency and the duration or control of diabetes remains controversial. To assess the possibility of such an interrelationship, we studied parameters relating to mineral metabolism (Ca, P, alkaline phosphatase, Mg, PTH, and hydroxyproline (OHP)); bone remodeling (osteocalcin); diabetic control (HbA1c); and radiological study of the second metacarpal of the left hand and of bone age in 87 children with type 1 DM. The mineral parameters were not abnormal among the diabetics. Diabetic children had similar levels of fasting osteocalcin as normals (10.05 +/- 4.9 vs. 9.79 +/- 3.34 ng/ml, mean +/- SD); this did not differ by sex. The bone age fell within two standard deviations of the mean, and 9.5% of the diabetics had a bone mass deficit (less than the mean cortical thickness) greater than 2 SD. There was no correlation between osteocalcin and Ca, P, glycemia, HbA1c, PTH, Mg, or OHP. Our results do not support any association between bone mass loss and the severity or duration of type 1 diabetes. Bone turnover, measured by serum osteocalcin, was normal. Therefore the pathogenesis of osteopenia in type 1 DM remains unclear, and requires further investigation.

Alkaline Phosphatase↗

[Study of bone involvement in hypothyroidism determining the blood levels of osteocalcin].

Several bone abnormalities, characterized by a decreased bone turnover, may develop in patients with hypothyroidism. We have used the measurement of serum Osteocalcin (BGP), a protein synthesized by osteoblasts and proposed as a marker of bone formation, in order to elucidate the bone status in 62 hypothyroid patients, mean age 52 +/- 15 (SD) years. As a group, BGP results in hypothyroidism were not different from normal (3.6 +/- 3.2 vs 3.7 +/- 1.3 ng/ml). However, we were able to differentiate 3 groups: 1) patients with significantly lower BGP values (p less than 0.01) (primary hypothyroidism and total thyroidectomy with body scan); 2) patients with antithyroid drugs had significantly higher BGP levels (p less than 0.05); 3) in the other groups (post-1311, post-surgery, and insufficiently treated hypothyroidism) BGP values were within normal limits. In the total group BGP was significantly correlated with T3T, TSH, alkaline phosphatase and age. Lower serum BGP values in some etiologic groups of hypothyroidism may reflect a greater pathologic effect on the bone in these patients, with a decrease in bone formation.

Aged↗

Fine needle aspiration biopsy in the diagnosis of thyroid cancer and thyroid disease.

Fine needle aspiration biopsy (FNAB) performed for diffuse and nodular goiter in the past 5 years, was evaluated in 1399 cases. Surgery was performed on the basis of FNAB cytologic diagnosis that was positive or suggestive of malignancy and/or a suggestive clinical history. Surgery also was performed in cases of cold nodules with negative FNAB results that did not respond to 6 months of suppressive thyroxine therapy. A correlation of cytologic findings with histologic findings was possible in 415 patients who underwent surgery: the evaluation of FNAB results yielded better results when suspicious cytologic findings were considered to be positive (2.4% false-negative, 86.3% sensitivity) rather than negative (6.5% and 65.7%, respectively). FNAB has become a useful procedure in the study and diagnosis of thyroid diseases. It is a simple, rapid diagnostic procedure that may be used to expedite the management of malignant lesions.

Biopsy, Needle↗