Citations

Uterine dehiscence is the incomplete separation of the myometrium at a uterine scar site, usually from a previous cesarean section. Because membranes remain intact, the prognosis for both mother and fetus is generally good. However, labor contractions may lead to progression and a complete uterine rupture, which can be catastrophic. The combination of abdominal pain, previous cesarean section, and the sonographic finding of ballooning membranes should suggest the diagnosis of uterine dehiscence.

AbstractAs refinement of technetium‐99m 2‐methoxyisobutyl isonitrile‐scintigraphy (MIBI)‐scintigraphy of parathyroid glands has continued since its initial use in 1989, the sensitivity, specificity, and overall accuracy of the technique have improved greatly, approaching 100% for larger, solitary adenomas. Preoperative use of sestamibi scintigraphy has become commonplace and allows surgeons the option of a minimally invasive, or focused approach for their patients with primary hyperparathyroidism. Intraoperative use of the gamma probe based on sestamibi localization has not caught on due to lesser accuracy, cumbersome gamma probes, small doses of radiation exposure for patients and staff, and the greater accuracy and current confidence in intraoperative parathormone (PTH) monitoring. However, with the potential for smaller and more accurate gamma probes that truly assist in localizing abnormal parathyroid glands, the potential for cost reduction by shortening operative times, avoiding expensive PTH assays, and eliminating the need for pathologic analysis, gamma scintigraphy may yet become a viable option for many parathyroid surgeons.

AbstractChildhood papillary thyroid carcinoma is associated with more locally aggressive and more frequent distant disease than its adult counterpart. Recurrence rates tend to be higher in children, but cause‐specific mortality remains low. Optimal initial treatment of childhood papillary thyroid carcinoma should include total or near‐total thyroidectomy and central compartment node clearance. Modified neck dissections should be performed for biopsy‐proven lateral neck disease. Every effort should be made to maintain parathyroid and laryngeal nerve function. Radical neck dissections are to be avoided. Radioiodine remnant ablation (RRA), appropriate thyroid hormone suppressive therapy (THST), and judicious use of therapeutic doses of 131I are applied to achieve a disease‐free status, which is most often confirmed by negative neck ultrasonography, negative whole‐body scan (either withdrawal or recombinant human thyroid‐stimulating hormone‐stimulated), and extremely low levels of serum thyroglobulin. Appropriate utilization of 131I, THST, repeat surgery, external beam radiotherapy, and rarely chemotherapy may provide long‐term palliation and some cures in patients with recurrent/persistent disease. Follow‐up should be lifelong, and the care of children after age 17 should subsequently be transferred to adult‐care endocrinologists with expertise in managing thyroid neoplasia. Optimal surgical management can be achieved if adequate operations are routinely carried out by “high‐volume” thyroid surgeons with expertise in the care of children. Nowhere is a multidisciplinary approach (endocrinologists, surgeons, nuclear medicine physicians, pediatricians, pathologists, oncologists) more critical than in the long‐term management of papillary thyroid carcinoma that presents during childhood.

Abstract The present study tests the intuition that successful aging in men is marked by: 1) impaired feedforward by endogenous LH concentrations (con) of testosterone (Te) secretion (sec); and/or 2) attenuated feedback by unmanipulated Te con of LH sec. The goal was to assess both implicit linkages analytically without disrupting normal pathway coupling. This strategy required: 1) assay of paired LH and Te con sampled every 10 min for 24 h in 13 older (O) (ages 60–78 yr) and 13 young (Y) (ages 18–30 yr) men; 2) deconvolution-based estimation of LH and Te sec rates; 3) lag-specific cross-correlation analyses of the relationships between LH and Te con and sec; and 4) statistical contrasts by age stratum. Salient outcomes were: 1) O and Y men maintain comparable LH con drive of Te sec, viz maximal r = +0.51 and r = +0.52, respectively, at an optimal time lag of 50 min (both P < 0.001 against random LH and Te associations); 2) elderly subjects exhibit reduced Te con inhibition of LH sec [minimal r = −0.008 (O) vs. r = −0.10 (Y), P < 0.01 at a time lag of 40 min]; 3) mean (24-h) LH con do not differ by age; and 4) molar Te/sex hormone-binding globulin con are lower in the elderly than in Y individuals (P < 0.01). In conclusion, noninvasive analyses predict that attenuation of endogenous Te feedback restraint on the hypothalamo-pituitary unit may be an early biological marker of adaptive changes in the GnRH-LH-Te ensemble axis in the healthy O male.

▪ Abstract The assembly of the cystic fibrosis transmembrane regulator (CFTR) chloride channel is of interest from the broad perspective of understanding how ion channels and ABC transporters are formed as well as dealing with the mis-assembly of CFTR in cystic fibrosis. CFTR is functionally distinct from other ABC transporters because it permits bidirectional permeation of anions rather than vectorial transport of solutes. This adaptation of the ABC transporter structure can be rationalized by considering CFTR as a hydrolyzable-ligand-gated channel with cytoplasmic ATP as ligand. Channel gating is initiated by ligand binding when the protein is also phosphorylated by protein kinase A and made reversible by ligand hydrolysis. The two nucleotide-binding sites play different roles in channel activation. CFTR self-associates, possibly as a function of its activation, but most evidence, including the low-resolution three-dimensional structure, indicates that the channel is monomeric. Domain assembly and interaction within the monomer is critical in maturation, stability, and function of the protein. Disease-associated mutations, including the most common, ΔF508, interfere with domain folding and association, which occur both co- and post-translationally. Intermolecular interactions of mature CFTR have been detected primarily with the N- and C-terminal tails, and these interactions have some impact not only on channel function but also on localization and processing within the cell. The biosynthetic processing of the nascent polypeptide leading to channel assembly involves transient interactions with numerous chaperones and enzymes on both sides of the endoplasmic reticulum membrane.

AbstractThe etiology, prognosis, and optimal management of primary gastric carcinoids remain controversial. Records of 36 consecutive patients with gastric carcinoid (15 men) were reviewed retrospectively between 1975 and 1990. Follow‐up was complete in 97% of cases. Mean age at diagnosis was 58.4 years (range 24–82 years). The clinical presentations included anemia (72%), pain (69%), and carcinoid syndrome (11%). Associated autoimmune and endocrine abnormalities were common and included atrophic gastritis (67%), pernicious anemia (58%), hypothyroidism (39%), diabetes (19%), Addison's disease (6%), and hyperparathyroidism (6%). Lesions were nonantral in 78%, involving only the corpus in 42%, the fundus in 28%, and only the antrum in 8%; 42% were multiple. Urinary 5‐hydroxyindoleacetic acid (5‐HIAA) and serum gastrin levels were elevated in 17% and 50% of those tested, respectively. Histologic examination revealed that 28% of lesions were ≥2 cm, and 33% had liver metastases on presentation or developed them during follow‐up. Eight patients (22%) died of tumor with a median survival of 39 months. The presence of metastases, atypical histology, serosal involvement, and size > 2 cm were adverse prognostic factors. In patients without hypergastrinemia (n=6), 66% developed metastases, 60% had elevated 5‐HIAA, and 50% died of carcinoid tumor. In sharp contrast, those patients with hypergastrinemia and “typical” gastric carcinoids (n=15), metastases and death did not occur (p<0.003 and p < 0.005, respectively, compared with eugastrinemic patients). In the latter group (hypergastrinemia and typical histology), pernicious anemia was common (73%); solitary lesions and serosal penetration were seen comparatively less often (33% versus 100%, p<0.005 and 0% versus 33%, p<0.05, respectively); and no lesion measured > 2.0 cm compared to 66% in the group without elevated gastrin (p<0.002). No patient with hypergastrinaemia had elevated levels of 5‐HIAA. Overall survival at 5 and 10 years was 58% and 28%, respectively. Survival was 80% at 5 and 10 years in the hypergastrinemic group. Gastric carcinoid tumors that are histologically atypical, large (>2 cm), or present without elevated gastrin are potentially lethal and require aggressive therapy. In contrast, gastric carcinoids with typical histology and hypergastrinemia are rarely lethal, and conservative management with local excision and close observation is appropriate.