Describes a case of leucine-rich, glioma-inactivated protein 1 (LGI1) limbic encephalitis presenting with generalised tonic-clonic seizures, confusion, memory loss, and syndrome of inappropriate ...antidiuretic hormone secretion (SIADH), with minimal sodium response to fluid restriction, but rapid normalisation after immunotherapy, suggesting a pathogenic role of the LGI1 antibodies in the induction of SIADH. Source: National Library of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.
Three-dimensional printing of implants allows the ability to produce implants and interfaces which theoretically better mimic “normal” bone behaviour, leading to a possible reduction in stress ...shielding thus maintaining bone mineral density (BMD). This issue was not investigated in vivo using bone scan and different bearings; therefore, we did a prospective study aiming to answer: 1) is there a loss of BMD around the 3D printed trabecular titanium cup, when compared to the native hip?; 2) does liner type influence the BMD changes around the acetabulum when a 3D printed trabecular titanium cup is used?
BMD changes around the acetabulum are not influenced by the liner type, and the cup will be associated with a reduction in BMD when compared to the native hip.
This is a prospective observational study of patients receiving a primary total hip arthroplasty. A 3D printed trabecular titanium uncemented acetabular component was used in all cases. All patients received a ceramic femoral head, with either a ceramic or polyethylene acetabular liner. BMD measurements using DXA were performed at 6 weeks, 6, 12 and 24 months after surgery to evaluate remodeling changes. The 3 acetabular regions of interest (ROI) of DeLee and Charnley were used for serial comparisons of peri-acetabular BMD. The study was powered as a non-inferiority study with the principle variables compared using a two-step repeated analysis of variance.
A total of 48 consecutive patients were included in the study, with all patients completing their 2 year follow-up. There were no failures, revisions or complications within this cohort. We found no statistically significant difference in the BMD change scores between the operated and the native hip in any of the 3 ROI zones. We found no differences in BMD scores when comparing ceramic to polyethylene acetabular liners, head sizes and BMI.
This study shows a similar pattern of BMD behaviour around a 3D printed cup when compared to the contralateral native hip. We were unable to show a clinical or radiological difference between the bearing material, head size, or BMI when used with this type of acetabular component.
III; prospective comparative study.
The relation between the plasma level of 25-hydroxyvitamin D3, the main metabolite of sun-induced vitamin D, and myocardial infarction (MI) was investigated in a community-based case-control study. ...Some 179 MI patients presenting to hospital within 12 hours of the onset of symptoms were individually matched with controls by age, sex and date of blood collection. MI patients had significantly lower mean 25-hydroxyvitamin D3 levels than controls (32.0 versus 35.5 nmol/L; p = 0.017), with the case-control differences being greatest in winter and spring. The relative risk of MI for subjects with 25-hydroxyvitamin D3 levels equal to or above the median was 0.43 (95% confidence limits = 0.27, 0.69) compared to subjects below the median. The decrease in MI risk associated with raised vitamin D3 levels was observed in all seasons. These results provide support for the hypothesis that increased exposure to sunlight is protective against coronary heart disease.
Despite being a classical growth disorder, pituitary gigantism has not been studied previously in a standardized way. We performed a retrospective, multicenter, international study to characterize a ...large series of pituitary gigantism patients. We included 208 patients (163 males; 78.4%) with growth hormone excess and a current/previous abnormal growth velocity for age or final height >2 s.d. above country normal means. The median onset of rapid growth was 13 years and occurred significantly earlier in females than in males; pituitary adenomas were diagnosed earlier in females than males (15.8 vs 21.5 years respectively). Adenomas were ≥10 mm (i.e., macroadenomas) in 84%, of which extrasellar extension occurred in 77% and invasion in 54%. GH/IGF1 control was achieved in 39% during long-term follow-up. Final height was greater in younger onset patients, with larger tumors and higher GH levels. Later disease control was associated with a greater difference from mid-parental height (r=0.23, P=0.02). AIP mutations occurred in 29%; microduplication at Xq26.3 – X-linked acrogigantism (X-LAG) – occurred in two familial isolated pituitary adenoma kindreds and in ten sporadic patients. Tumor size was not different in X-LAG, AIP mutated and genetically negative patient groups. AIP-mutated and X-LAG patients were significantly younger at onset and diagnosis, but disease control was worse in genetically negative cases. Pituitary gigantism patients are characterized by male predominance and large tumors that are difficult to control. Treatment delay increases final height and symptom burden. AIP mutations and X-LAG explain many cases, but no genetic etiology is seen in >50% of cases.
Genetic studies suggest a diabetes susceptibility locus on human chromosome 20, near the melanocortin receptor-3 (MC3-R) gene. We examined the MC3-R as a candidate gene for type 2 diabetes in 12 ...members of a large Maori kindred with multiple affected members. The coding region of the MC3-R gene was sequenced for both diabetic and non-diabetic individuals. Two separate single base pair substitutions were found in the MC3-R coding sequence and these resulted in amino acid changes, Lysine6Threonine and Isoleucine81Valine. Neither of these MC3-R variants tracked with the presence of diabetes. Furthermore, the variant and wild type MC3-R showed similar functional coupling to adenylyl cyclase. A polymorphic marker (D20S32e) close to the human MC3-R (hMC3-R) coding sequence was investigated in a 60-member pedigree for association with diabetes and other metabolic parameters. There was an association between D20S32e genotype and fasting insulin (P=0.0085) and the insulin resistance index, HOMA-R (P=0.0042). An association was also found between genotype and HDL levels during oral glucose tolerance testing (P=0.0037). These associations were independent of BMI, age, gender and diabetes. Our data do not support a role for variations in the coding region of the hMC3-R in the development of type 2 diabetes in this Maori kindred, but suggest that a locus on chromosome 20q, close to D20S32e, may contribute to both insulin secretion and action in the Maori kindred.
Pituitary and thyroid autoimmunity can be triggered by pregnancy. We report the first association of combined growth hormone (GH) and prolactin secretion deficiency due to autoimmune damage to GH- ...and prolactin-secreting cells in a patient with postdelivery lactation failure, presenting subsequently with primary autoimmune hypothyroidism.
A 34-year-old woman presented with lactation failure following the delivery of her first child. She had a family history of hypothyroidism without a history of pituitary dysfunction. Physical examination did not show any abnormal findings. Laboratory investigations showed normal gonadotropin levels after the restoration of normal menstrual cycles following pregnancy, normal basal and stimulated cortisol levels, but an impaired GH response to insulin-induced hypoglycemia, and low basal prolactin and insulin-like growth factor-1 concentrations. Thyroid function was normal when initially investigated three months after delivery, but five months later, marked primary hypothyroidism (thyrotropin levels >100 mIU/L) occurred. Immunological investigation revealed the presence of antipituitary antibodies, identified by double immunofluorescence and targeting GH- and prolactin-secreting cells. Antithyroid antibodies, in the normal range three months postpartum, became significantly elevated when the hypothyroidism appeared. Autoimmune hypophysitis is responsible for selective or multiple pituitary-hormone deficiencies, sometimes involving thyrotropin secretion and causing secondary hypothyroidism, but usually associated with hyperprolactinemia. To our knowledge, this is the first observation of autoimmune hypopituitarism involving deficient growth hormone and prolactin secretion in a patient with lactation failure after delivery, subsequently followed by severe primary autoimmune hypothyroidism, thus falling into an unusual constellation of autoimmune polyendocrine syndrome type 3.
Considering the well-known relationship between pregnancy and autoimmunity, an early postdelivery immunological and functional investigation in women presenting with disorders of lactation may be useful to detect potential pituitary and thyroid dysfunction even at a subclinical stage.
Background: Insulin‐like growth factor‐I (IGF‐I) and IGF binding protein‐3 (IGFBP‐3) appear to influence the growth of breast cancer cells in vitro, and epidemiological studies suggest higher serum ...IGF‐I levels increase the risk of breast cancer. IGF‐I and IGFBP‐3 have therefore been measured in women with advanced breast cancer to determine if changes in serum levels predict the response to treatment by chemotherapy.
Methods: Serum IGF‐I and IGFBP‐3 levels were measured in 14 patients before and after 1 week of chemotherapy. Changes in serum levels were compared with duration of survival.
Results: Mean basal serum levels of IGF‐I and IGFBP‐3 were not significantly different between patients with advanced breast cancer and controls or women with early breast cancer. Serum IGFBP‐3 fell significantly 1 week after initiation of chemotherapy. Patient survival was not significantly related to baseline IGF‐I or IGFBP‐3 levels, but when the fall in serum levels 1 week after starting treatment was expressed either as absolute change or as a percentage of baseline, those individuals with a decrease in IGFBP‐3 greater than the median had significantly poorer survival (median survival 5.5 months vs 18 months). These results were independent of other prognostic variables such as previous disease‐free survival, and were also unaffected by the change in serum albumin with treatment. The fall in IGF‐I and IGFBP‐3 with chemotherapy mainly occurred in those with hepatic metastases, but prediction of survival was explained solely by the extent of the fall in IGFBP‐3.
Conclusions: This preliminary study has shown that serum IGFBP‐3 falls significantly following initiation of chemotherapy and the extent of reduction significantly predicts the response to treatment.
Terminal deletions of chromosome 10p result in a DiGeorge-like phenotype
that includes hypoparathyroidism, heart defects, immune deficiency, deafness
and renal malformations. Studies in patients with ...10p deletions
have defined two non-overlapping regions that contribute to this complex phenotype.
These are the DiGeorge critical region II (refs 1, 2), which is located on 10p13-14, and the region for the
hypoparathyroidism, sensorineural deafness, renal anomaly (HDR) syndrome (Mendelian Inheritance in Man number 146255), which
is located more telomeric (10p14-10pter). We have
performed deletion-mapping studies in two HDR patients, and here we define
a critical 200-kilobase region which contains the GATA3 gene.
This gene belongs to a family of zinc-finger transcription factors that are
involved in vertebrate embryonic development. Investigation
for GATA3 mutations in three other HDR probands identified one nonsense
mutation and two intragenic deletions that predicted a loss of function, as
confirmed by absence of DNA binding by the mutant GATA3 protein. These results
show that GATA3 is essential in the embryonic development of the parathyroids,
auditory system and kidneys, and indicate that other GATA family members may
be involved in the aetiology of human malformations.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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