Citations

Pisotriquetral arthrosis in young patients is considered rare and the diagnosis may be difficult to distinguish from other ulno-carpal problems. 12 patients under 40 years of age (15 cases) who underwent pisiformectomy were reviewed at a mean of 41 months. Patients with a good history of trauma and a positive response to intra-articular local anaesthetic injection did well. Others with an indefinite history and bilateral symptoms did not do so well. Trispiral tomography is the radiological investigation of choice.

Muscle physiological cross-sectional area, as defined and measured by dividing the volume of the muscle by its fibre length, is proportional to the maximum strength of the muscle. It is one of the important parameters when considering muscle mechanics in sports science and, clinically in tendon transfer procedures. This study reports that tendon cross-sectional area correlated well with the physiological cross-sectional area of associated muscles.

AbstractEighty‐nine patients underwent adrenal exploration for Cushing's syndrome at our institution during the period 1970–1979. On the basis of clinical and histological findings related to the initial adrenal operation, patients were divided into 6 major subgroups: (a) adrenocortical adenoma; (b) adrenocortical carcinoma; (c) proven ectopic ACTH adrenocortical hyperplasia; (d) Cushing's disease; (e) uncertain diagnostic group (probably ectopic ACTH syndrome—site unknown); and (f) “non‐ACTH‐dependent” hypercortisolism due to micronodular hyperplasia.Results of pathologic examination included 25 adrenal adenomas, 15 adrenocortical carcinomas, 40 bilateral adrenocortical hyperplasias, and a single case of micronodular hyperplasia. The postoperative mortality rate was 5.6%, and significant morbidity occurred in 40% of patients. Four of the 5 patients who died within 30 days of operation were in the subgroups with adrenal carcinoma (2 patients) and Cushing's disease (2 patients). Survival in patients with adrenocortical adenomas was significantly decreased at 2 years (relative adrenocortical insufficiency?), but thereafter, it paralleled the expected survival. Patients with the ectopic ACTH syndrome and adrenocortical carcinoma had significantly decreased survival, with only one‐third of carcinoma patients alive 2 years postoperatively. The survival of patients with Cushing's disease was lower than expected at both 5 and 10 years.These results confirm that the diagnosis of patients with endogenous hypercortisolism is usually straightforward and accurate, surgical intervention in this group of patients is still accompanied by significant short‐term mortality and morbidity, and long‐term survival in all subgroups is decreased.

The basis for ethnicity-related distinctions in gonadotropin secretion are unknown but may have important populational and physiological implications. In male contraceptive trials, exogenous testosterone and progestins suppress spermatogenesis to a greater degree in Asian than Caucasian men. In addition, iv infusion of testosterone inhibits LH release more in Asian than Caucasian volunteers. We test the converse postulate that experimental reduction of androgen-dependent negative feedback by way of the steroidogenic inhibitor combination ketoconazole/dexamethasone will unveil ethnicity-related mechanisms of regulated LH secretion in young men. LH release was monitored by sampling blood every 10 min for 24 h followed by immunoradiometric assay, model-free pulse detection, an entropy (regulatory) statistic, and cosine regression. Statistical comparisons revealed that healthy young Asian and Caucasian men maintain comparable baseline concentrations of LH, testosterone, estradiol, SHBG, and molar testosterone to SHBG ratios. In contrast, the two ethnic groups differ prominently in each of basal, pulsatile, entropic, and 24-h rhythmic LH adaptations to short-term androgen withdrawal. Therefore, we postulate that physiological nonuniformity of sex steroid-dependent negative feedback in particular may contribute to populational diversity in LH regulation.

Patent ductus arteriosus (PDA) is a common congenital heart disease that results when the ductus arteriosus, a muscular artery, fails to remodel and close after birth. A syndromic form of this disorder, Char syndrome, is caused by mutation in TFAP2B , the gene encoding a neural crest-derived transcription factor. Established features of the syndrome are PDA, facial dysmorphology, and fifth-finger clinodactyly. Disease-causing mutations are missense and are proposed to be dominant negative. Because only a small number of families have been reported, there is limited information on the spectrum of mutations and resulting phenotypes. We report the characterization of two kindreds (K144 and K145) with Char syndrome containing 22 and 5 affected members, respectively. Genotyping revealed linkage to TFAP2B in both families. Sequencing of TFAP2B demonstrated mutations in both kindreds that were not found among control chromosomes. Both mutations altered highly conserved bases in introns required for normal splicing as demonstrated by biochemical studies in mammalian cells. The abnormal splicing results in mRNAs containing frameshift mutations that are expected to be degraded by nonsense-mediated mRNA decay, resulting in haploinsufficiency; even if produced, the protein in K144 would lack DNA binding and dimerization motifs and would likely result in haploinsufficiency. Examination of these two kindreds for phenotypes that segregate with TFAP2B mutations identified several phenotypes not previously linked to Char syndrome. These include parasomnia and dental and occipital-bone abnormalities. The striking sleep disorder in these kindreds implicates TFAP2B-dependent functions in the normal regulation of sleep.

Abstract The physiology of early-diastolic filling comprises ventricular performance and fluid dynamical principles. Elastic recoil and myocardial relaxation rate determine left ventricular early diastolic performance. The integrity of left ventricular synchrony and geometry is essential to maintain the effect of their timely action on early diastolic left ventricular filling. These factors not only are prime determinants of left ventricular pressure decay during isovolumic relaxation and immediately after mitral valve opening; they also instigate the generation of a sufficient intra-ventricular pressure gradient, which enhances efficient early diastolic left ventricular filling. Accurate assessment of diastolic (dys)function by non-invasive techniques has important therapeutic and prognostic implications but remains a challenge to the cardiologist. The evaluation of left ventricular relaxation by the standard Doppler echocardiographic parameters is hindered by their preload dependency. The colour M-mode velocity propagation of early diastolic inflow (Vp) correlates with intra-ventricular pressure gradients and is a largely preload independent index of ventricular diastolic performance. In this article, the physiologic background, utility and limitations of this promising new tool for the study of early diastolic filling are reviewed.

Abstract Pheochromocytomas are rare catecholamine-producing neuroendocrine tumors that are usually benign, but which may also present as or develop into a malignancy. Predicting such behavior is notoriously difficult and there are currently no curative treatments for malignant tumors. This report follows from a workshop at the Banbury Conference Center, Cold Spring Harbor, New York, on the 16th–18th November 2003, held to review the state of science and to facilitate future progress in the diagnosis and treatment of malignant pheochromocytoma. The rarity of the tumor and the resulting fragmented nature of studies, typically involving small numbers of patients, represent limiting factors to the development of effective treatments and diagnostic or prognostic markers for malignant disease. Such development is being facilitated by the availability of new genomics-based tools, but for such approaches to succeed ultimately requires comprehensive clinical studies involving large numbers of patients, stringently collected clinical data and tumor samples, and interdisciplinary collaborations among multiple specialist centers. Nevertheless, the well-characterized hereditary basis and the unique functional nature of these neuroendocrine tumors provide a useful framework that offers advantages for establishing the pathways of tumorigenesis and malignancy. Such findings may have relevance for understanding the basis of other more common malignancies where similar frameworks are not available. As the relevant pathways leading to pheochromocytoma are established it should be possible to take advantage of the new generation of drugs being developed to target specific pathways in other malignancies. Again the success of this will require well-designed and coordinated multicenter studies.

Purpose This multicenter, open-label, phase II study was undertaken to assess the antitumor activity and safety of the oral mitogen-activated extracellular signal regulated kinase kinase (MEK) inhibitor, CI-1040, in breast cancer, colon cancer, non-small-cell lung cancer (NSCLC), and pancreatic cancer. Patients and Methods Patients with advanced colorectal, NSCLC, breast, or pancreatic cancer received oral CI-1040 continuously at 800 mg bid. All patients had measurable disease at baseline, a performance status of 2 or less, and adequate bone marrow, liver, and renal function. Expression of pERK, pAkt, and Ki-67 was assessed in archived tumor specimens by quantitative immunohistochemistry. Results Sixty-seven patients with breast (n = 14), colon (n = 20), NSCLC (n = 18), and pancreatic (n = 15) cancer received a total of 194 courses of treatment (median, 2.0 courses; range, one to 14 courses). No complete or partial responses were observed. Stable disease (SD) lasting a median of 4.4 months (range, 4 to 18 months) was confirmed in eight patients (one breast, two colon, two pancreas, and three NSCLC patients). Treatment was well tolerated, with 81% of patients experiencing toxicities of grade 2 or less severity. Most common toxicities included diarrhea, nausea, asthenia, and rash. A mild association (P < .055) between baseline pERK expression in archived tumor specimens and SD was observed. Conclusion CI-1040 was generally well tolerated but demonstrated insufficient antitumor activity to warrant further development in the four tumors tested. PD 0325901, a second generation MEK inhibitor, has recently entered clinical development and, with significantly improved pharmacologic and pharmaceutical properties compared with CI-1040, it may better test the therapeutic potential of MEK inhibition in cancer.

Objective. The development of this review article evolved from a National Kidney Foundation consensus conference on recent advances in the importance of evaluating and treating proteinuria. From this conference, a series of recommendations for the evaluation of adults with proteinuria was published. Because specific pediatric aspects of the problem were outside the scope of the original National Kidney Foundation publication, an ad hoc committee of 6 pediatric nephrologists who were active participants in the National Kidney Foundation conference was established to provide primary care physicians with a concise, up-to-date reference on this subject. Methods. The recommendations that are given represent the consensus opinions of the authors. These are based on data from controlled studies in children when available, but many of the opinions are, by necessity, based on uncontrolled series in children or controlled trials performed in adults, because controlled trials in children have not been performed to evaluate many of the treatments described. Results and Conclusions. These recommendations are intended to provide primary care physicians with a useful reference when they are faced with a young child or teenager who presents with proteinuria, whether this is mild and asymptomatic or more severe, leading to nephrotic syndrome.