Identifying patients with depression in the primary care setting: a more efficient method

OBJECTIVE: To determine if there is a core subset of depressive symptoms that could be used to efficiently diagnose depression after administering the 2-item PRIME-MD a screening questionnaire for depression. METHODS: One thousand patients selected randomly and by convenience from 4 primary care clinics were assessed by PRIME-MD and completed a questionnaire measuring the following validation variables: functional status and well-being, disability days, somatic symptoms, depression severity, suicidal thoughts, health care utilization, and the physician-patient relationship. RESULTS: Four symptoms (sleep disturbance, anhedonia, low self-esteem, and decreased appetite) accounted for virtually all the depression symptom-related variance in functional status and well-being, with 8.3% of patients having 2 of these symptoms and 8.2% having 3 or 4 of these symptoms. There was excellent agreement between diagnosis based on core symptoms and major depression (K= 0.77; overall accuracy rate, 94%). There were significant differences (P<.001) among patients with negative depression screen, 0 to 1, 2, and 3 to 4 core symptoms with scores on each of the validation variables getting progressively worse in these 4 groups. A cutoff point of 2 core symptoms identified all but 3 patients with major depression and an additional 5% of the entire sample without major depression who were significantly (P<.05) worse than patients without depression on each of the validation variables. CONCLUSION: A strategy that includes the use of a 2-item depression screener followed by the evaluation of 4 core depressive symptoms is an efficient and effective way of identifying and classifying primary care patients with depression in need of clinical attention.     

Lipid and lipoprotein profiles in children with familial hypercholesterolaemia: effects of therapy

In 71 children with familial hypercholesterolaemia the effect of dietary and/or medical treatment was evaluated. Initial total cholesterol and low density lipoprotein (LDL)-cholesterol levels were significantly lower in children who were consecutively treated by diet (Step-One-Diet) than in those who received additional medication. By dietary treatment, the median total cholesterol level (236.5 mg/dl; range 210-510 mg/dl) was reduced by 7.4% and the median LDL-cholesterol level (162 mg/dl; range 126-423 mg/dl) by 9.9%. By dietary and medical therapy, the median total cholesterol level (330 mg/dl; range 270-424 mg/dl) was reduced by 29.7% and the median LDL-cholesterol level (263 mg/dl; 192-333 mg/dl) by 25.9%. High density lipoprotein (HDL)-cholesterol and HDL 3 remained unchanged. HDL 2 showed a significant decrease of 15.6% up to 27 mg/dl (13-42 mg/dl) on medical treatment. Apolipoprotein A I levels did not change during therapy. Initial apolipoprotein B levels were significantly higher in children who were treated by diet and medication and were reduced by 28.9% by combined therapy. In 28 patients (39.4%) an excess of lipoprotein (a) was detected. Regarding the apolipoprotein E phenotype, 32.2% of the patients carried the risk gene epsilon4 in a hetero- or homozygous form. CONCLUSION: Early dietary and/or medical treatment in hypercholesterolaemic children significantly ameliorates the lipoprotein status. The pretherapy lipoprotein status seems to prognosticate the effectiveness of therapy.     

Core mutations that promote the calcium-induced allosteric transition of bovine recoverin

Recoverin is a small calcium binding protein involved in regulation of the phototransduction cascade in retinal rod cells. It functions as a calcium sensor by undergoing a cooperative, ligand-dependent conformational change, resulting in the extrusion of the N-terminal myristoyl group from a hydrophobic pocket. To test the role of certain core residues in tuning this allosteric switch, we have made and characterized two mutants: W31K, which replaces Trp31 with Lys; and a double mutant, I52A/Y53A, in which Ile52 and Tyr53 are both replaced by Ala. These mutations decrease the hydrophobicity of the myristoyl binding pocket. They are thus expected to make sequestering of the myristoyl group less favorable and destabilize the Ca2+-free state. As predicted, the myristoylated forms of the mutants exhibit increased affinity for Ca2+, whether monitored by equilibrium binding of 45Ca2+ (Kd = 17.2, 7.9, and 8.1 microM for wild type, W31K, and I52A/Y53A, respectively) or by the change in tryptophan fluorescence associated with the conformational change (Kd = 17.9, 3.6, and 4.4 microM for wild type, W31K, and I52A/Y53A, respectively). The mutants also exhibit decreased cooperativity of binding (Hill coefficient = 1.2 and 1.0 for W31K and I52A/Y53A vs 1. 4 for wild type). Binding of the mutant proteins to rod outer segment membranes occurs at lower Ca2+ concentrations compared to wild-type protein (K1/2 = 5.6, 2.2, and 1.0 microM for wild type, W31K, and I52A/Y53A, respectively). The unmyristoylated forms of the mutants exhibit biphasic Ca2+ binding curves, nearly identical to that observed for wild type. The binding data for the two mutants can be explained by a concerted allosteric model in which the mutations affect only the equilibrium constant L between the two allosteric forms, T (the Ca2+-free form) and R (the Ca2+-bound form), without affecting the intrinsic binding constants for the two Ca2+ sites. Two-dimensional NMR spectra of the Ca2+-free forms of the mutants have been compared to the wild-type spectrum, whose peaks have been assigned to specific residues (1). Many resonances assigned to residues in the C-terminal domain (residues 100-202) in the wild-type spectrum are identical in the mutant spectra, suggesting that the backbone structure of the C-terminal domain is probably unchanged in both mutants. The N-terminal domain, in which both mutations are located, reveals in each case numerous changes of undetermined spatial extent.     

Melanoma arising from the mucosal surfaces of the head and neck

Oral mucosal malignant melanoma is a rare disease. We reviewed 30 years of data from a tumor registry and identified 65 patients who had head and neck melanomas. Two thirds (43) of the 65 patients were identified as male, with the mean age in the sixth decade. Of the 65 patients, only 6 had melanoma that arose from the oropharyngeal mucosa. Of the lesions involving the oral mucosa, each lesion manifested itself as a mass or was associated with symptoms of discomfort; only one third (2) of the lesions were pigmented. The clinician must carefully examine the head, neck, and oral cavity, and any pigmented lesion that is not recognized as a specific entity, such as amalgam tattoo, should be biopsied. The more common presentation of amelanotic malignant melanoma requires a high index of suspicion for masses identified in the mouth and requires biopsy for definitive diagnosis. The prognosis for oral mucosal malignant melanoma is poor.     

Testing the equivalence of translations of widely used response choice labels: results from the IQOLA Project. International Quality of Life Assessment

The similarity in meaning assigned to response choice labels from the SF-36 Health Survey (SF-36) was evaluated across countries. Convenience samples of judges (range, 10 to 117; median = 48) from 13 countries rated translations of response choice labels, using a variation of the Thurstone method of equal appearing intervals. Judges marked a point on a 10-cm line-representing the magnitude of a response choice label (e.g., "good" relative to the anchors of "poor" and "excellent"). Ratings were evaluated to determine the ordinal consistency of response choice labels within a response scale; the degree to which differences between adjacent response choice labels were equal interval; and the amount of variance due to response choice label, country, judge, and interaction between response choice label and country. Results confirmed the hypothesized ordering of response choice labels; the percentage of ordinal pairs ranged from 88.7% to 100% (median = 98.2%) across countries and response scales. Examination of the average magnitudes of response choice labels supported the "quasi-interval" nature of the scales. Analysis of variance (ANOVA) results supported the generalizability of response choice magnitudes across countries; labels explained 64% to 77% of the variance in ratings, and country explained 1% to 3%. These results support the equivalence of SF-36 response choice labels across countries. Departures from the assumption of equal intervals, when observed, were similar across countries and were greatest for the two response scales that are recalibrated under standard SF-36 scoring. Results provide justification for scoring translations of individual items using standard SF-36 scoring; whether these items form the same scales in other countries as they do in the United States is evaluated with tests of scaling assumptions.     

The murine neutrophil-chemoattractant chemokines LIX, KC, and MIP-2 have distinct induction kinetics, tissue distributions, and tissue-specific sensitivities to glucocorticoid regulation in endotoxemia

Lipopolysaccharide-induced CXC chemokine (LIX) is a novel murine neutrophil-chemoattractant CXC chemokine cloned as a glucocorticoid-attenuated response gene. We investigated LIX message expression in an acute endotoxemia model. LIX message peaks later than KC or macrophage inflammatory protein-2 (MIP-2) and remains elevated longer in almost all tissues. Induced LIX message expression in heart is 5- to 6-fold greater than in lung and spleen, and 20-fold greater than in liver. In contrast, KC expression is equal in heart, lung, and liver, whereas MIP-2 expression is strongest in the lung. Glucocorticoid regulation of these genes also differs. Endotoxemia-induced LIX message expression in the lung is markedly enhanced in adrenalectomized mice and strongly attenuated by dexamethasone, whereas lung KC and MIP-2 expression are unaffected by glucocorticoids. It is surprising to note that endotoxemia-induced brain expression of LIX (but not KC or MIP-2) is increased by dexamethasone. These observations suggest that LIX may have biological roles distinct from KC and MIP-2.     

Guided tissue regeneration in Class II furcation involved maxillary molars: a controlled study of 8 split-mouth cases

The purpose of this study was to clinically evaluate the effectiveness of polytetrafluoroethylene membranes in the healing of interproximal Class II furcation defects in maxillary molars using a surgical treatment technique based on the principles of guided tissue regeneration. Eight subjects with similar bilateral Class II furcation lesions on the mesial aspect of maxillary first molars participated in this study. Patients received initial therapy consisting of oral hygiene instructions, scaling and root planing, and occlusal adjustment if necessary. Clinical parameters evaluated included plaque index, sulcular bleeding index, probing depth, attachment level, gingival recession, and open horizontal and vertical furcation fill. An acrylic occlusal stent was used to assure reproducibility of measurements. Experimental sites received a polytetrafluoroethylene membrane following surgical exposure of the furcation. Control sites were treated in the exact same manner but without a membrane. Membranes were removed at 6 weeks after the first surgery. Reentry surgeries were performed at 9 months. Postsurgical results showed a significant improvement in probing depth, attachment level, and open horizontal furcation fill for both groups when compared to baseline values, with experimental sites performing significantly better than controls. Control sites showed a slight loss in open vertical furcation fill while experimental sites remained unchanged. This study suggests that guided tissue regeneration using polytetrafluoroethylene membranes is of some but limited value in the treatment of maxillary molar interpoximal Class II furcation lesions.     

Monteggia fractures in adults

The records concerning ten consecutive years of experience with Monteggia fractures in adult patients at a level-one trauma center were retrospectively reviewed. Forty-eight patients who had been followed for a minimum of two years (average, 6.5 years; range, two to fourteen years) were identified. There were twenty-five women and twenty-three men, and the average age was fifty-two years (range, eighteen to eighty-eight years). According to the classification of Bado, there were seven type-I, thirty-eight type-II, one type-III, and two type-IV injuries. Twenty-six patients (68 percent) who had a Bado type-II fracture had an associated fracture of the radial head; ten of these patients also had a fracture of the coronoid process as a single large fragment. The ulna was fixed with a tension band-wire construct supplemented with screws in three patients (all of whom had a Bado type-II fracture). An ulnar diaphyseal fracture was fixed with an intramedullary Steinmann pin in one patient. The remaining patients had fixation with a plate and screws. The fracture of the radial head was treated with either complete or partial excision of the fragments in twelve patients (with replacement with a silicone prosthesis in two), open reduction and internal fixation in ten patients, and no intervention in four patients. Nine patients, all of whom had a Bado type-II fracture, needed a reoperation within three months after the initial operation; five had revision of a loose ulnar fixation device, three had resection of the radial head, and one had removal of a wire that had migrated from the radial head into the elbow articulation. Other important complications included proximal radioulnar synostosis in three patients, ulnar malunion in three, posterolateral rotatory instability of the ulnohumeral joint in one, and instability of the distal radioulnar joint in one. At the most recent follow-up examination, which was performed after all of the reoperations and reconstructive procedures had been done, the average score according to the system of Broberg and Morrey was 86 points (range, 15 to 100 points). The result was excellent for eighteen patients, good for twenty-two, fair for two, and poor for six. Six of the eight patients who had an unsatisfactory (fair or poor) result had had a Bado type-II fracture with a concomitant fracture of the radial head. These unsatisfactory results were related to a malunited fracture of the coronoid process in two patients, a proximal radioulnar synostosis in one, a malunited fracture of the coronoid process and a proximal radioulnar synostosis in one, a malunion of the ulna in one, and painfully restricted rotation of the forearm after operative fixation of a comminuted fracture of the radial head in one. The other two unsatisfactory results were in a patient who had had a Bado type-I fracture and in one who had had a Bado type-IV fracture. The results of the present series are much better than those reported in most earlier studies, suggesting that stable anatomical fixation of the ulnar fracture (including associated fracture fragments of the coronoid process) with a plate and screws inserted with use of current techniques of fixation leads to a satisfactory result in most adults who have a Monteggia fracture. The posterior (Bado type-II) fracture is the most common type of Monteggia fracture in adults. Problems with the elbow related to fractures of the coronoid process and the radial head, which are common with Bado type-II Monteggia fractures, remain the most challenging elements in the treatment of these injuries.