Mitochondrial DNA sequence diversity in bipolar affective disorder

OBJECTIVE: Point mutations in mitochondrial DNA (mtDNA) are one mechanism that could explain the apparent excess maternal transmission of bipolar affective disorder observed in some families. The authors sequenced the mtDNA from probands with bipolar disorder and tested nucleotide variants for association with the disorder. METHOD: The entire 16.5 kilobase mitochondrial genome was sequenced in nine unrelated probands selected from large pedigrees with exclusively maternal transmission of bipolar affective disorder. Compared to a reference sequence, variants were detected at 107 nucleotide positions. Fifteen variants of possible pathogenic significance were selected for further study. These variants were assayed in 93 unrelated probands with bipolar I, bipolar II, or schizoaffective-manic disorder and 63 comparison subjects, all of whom were classified into the major groups comprising the European mtDNA haplotype structure (haplogroups).RESULTS: The major European haplogroups were represented at the expected frequencies among both probands and comparison subjects. There was no significant difference between probands and comparison subjects in the frequency of any variant, although odds ratios >2 or <0.5 were observed for four variants. Frequencies of these four variants were similar in probands and haplogroup-matched comparison subjects. The results of all comparisons were essentially unchanged when probands from families with an apparently paternal transmission pattern were excluded.CONCLUSIONS: The results demonstrate that bipolar affective disorder occurs across all of the major European mtDNA haplogroups but do not reveal any point mutations that explain excess maternal transmission of the disorder.     

Diagnostic accuracy of the palliative prognostic score in hospitalized patients with advanced cancer.

PURPOSE: To evaluate the predictive accuracy of the Palliative Prognostic (PaP) score in patients with advanced cancer under the care of an oncologist. PATIENTS AND METHODS: The PaP score was calculated in 100 consecutive patients with advanced cancer hospitalized under the care of a medical or radiation oncologist at a university teaching hospital in Australia. The attending oncologist predicted the survival duration for the purpose of the scoring. The positive predictive value of the PaP score was evaluated. Survival analysis was performed to compare the survival of the three prognostic groups. RESULTS: Assessable survival data were available for 98 patients. The overall median survival was 12 weeks (interquartile range, 7 to 25 weeks). The PaP score divided the heterogeneous patient sample into three isoprognostic groups related to the chance of surviving 1 month, with 64 patients in group A (> 70% chance), 32 patients in group B (30% to 70% chance), and four patients in group C (< 30% chance). The estimated median survival of the three groups was 17 weeks (95% CI, 12 to 26 weeks), 7 weeks (95% CI, 4 to 12 weeks), and less than 1 week (95% CI, < 1 to 3 weeks), respectively. These survival differences were highly significant (log-rank test of trend, chi1(2) = 25.65; P < .0001). The 1-month survival of the groups was 97%, 59%, and 25%, respectively. CONCLUSION: When oncologists' survival estimates are used, the PaP score is able to identify accurately three isoprognostic patient groups, irrespective of the cancer type. The PaP score may help reduce the uncertainty of formulating a prognosis in patients with advanced cancer.     

The effects of ulnar axial malalignment on supination and pronation

BACKGROUND: Forearm fractures are common injuries in both adults and children. Despite efforts to obtain anatomical alignment, axial rotational malunions occur, resulting in a decreased range of motion and a poor appearance. The objective of this study was to quantify loss of forearm rotation after simulation of ulnar malunions in supination and pronation. METHODS: Six fresh-frozen cadaveric upper extremities (mean age at the time of death, 79.4+/-2.8 years) were used to quantify loss of forearm rotation after simulation of axial rotational malunions of the ulna. First, maximum forearm rotation in supination and pronation was measured at torques of 6.8, 13.6, and 20.4 kilograms-centimeter applied with use of a custom jig. Following a midshaft ulnar osteotomy, a custom adjustable internal fixation plate was used to simulate axial rotational malunions of the ulna of 0, 15, 30, and 45 degrees in both directions. Measurements in supination and pronation were then repeated at the prespecified torques. Analysis of variance, with a p value of 0.05, was used for statistical analysis. RESULTS: In all instances, a decrease in forearm rotation after simulation of the ulnar rotational malunion was accompanied by an increase in rotation in the opposite direction. Supination and pronation were significantly influenced, whereas the total arc of rotation was not affected by ulnar rotational malunion. At a torque of 20.4 kilograms-centimeter, pronation malunions of 15, 30, and 45 degrees resulted in a mean loss of supination (and standard error of the mean) of 5+/-1, 11+/-1, and 20+/-1 degrees, respectively, and supination malunions of 15, 30, and 45 degrees resulted in a mean loss of pronation of 4+/-1, 10+/-2, and 18+/-4 degrees, respectively. The ratio of the simulated rotational malunion to the loss of motion was larger than one. CONCLUSIONS: Ulnar rotational malunions do not lead to a significant change in the total arc of forearm rotation. Instead, loss of motion in one direction is accompanied by increased motion in the opposite direction. Even with a 45-degree ulnar rotational malunion, forearm rotation decreases no more than 20 degrees.     

Calcified occlusion of the right coronary artery in Kawasaki disease: evidence of myocardial ischaemia using cardiac technetium-99m-tetrofosmin perfusion single-photon emission computed tomography.

We report the case of a 14-year-old boy who developed Kawasaki disease at 5 months of age. The patient developed severe aneurysmal disease of both the left and right coronary arteries. He eventually developed total calcified occlusion of the right coronary artery despite long-term treatment with aspirin. Catheterisation showed no antegrade flow into the right coronary artery, with retrograde flow from the left coronary system into the right coronary. At the most recent follow-up he was asymptomatic, with normal exercise tolerance and a negative exercise stress test. Single-photon emission computed tomography (SPECT) myocardial perfusion imaging was carried out during stress and at rest using intravenous persantine (dipyridamole) and technetium-99m tetrofosmin. During stress, there were prominent left ventricular apical and anteroseptal defects, which normalised at rest. SPECT during stress and at rest may detect subclinical ischaemia and influence further management options in such patients.     

Pharyngolaryngeal, neck, and jaw discomfort after anesthesia with the face mask and laryngeal mask airway at high and low cuff volumes in males and females

BACKGROUND: There is controversy over (1) the relative incidence of sore throat between the face mask (FM) and laryngeal mask airway (LMA), (2) the efficacy of LMA intracuff pressure reduction as a mechanism for minimizing sore throat, and (3) the relative incidence of sore throat with the LMA between males and females. In a randomized double-blind study, the authors compared laryngopharyngeal, neck, and jaw discomfort with the FM and LMA at high and low cuff volumes in males and females. METHODS: Three hundred adult patients were randomly assigned to three equal-sized groups for airway management: (1) the FM, (2) the LMA with a fully inflated cuff (LMA-High), or (3) the LMA with a semi-inflated cuff (LMA-Low). Anesthesia was administered with propofol, nitrous oxide, oxygen, and isoflurane. In the FM group, a Guedel-type oropharyngeal airway and jaw thrust were used only if necessary. In the LMA groups, cuff inflation was achieved with either 15 or 30 ml for the size 4 (females) and 20 or 40 ml for the size 5 (males). The LMA was removed when the patient was awake. Patients were questioned 18-24 h postoperatively about surgical pain, sore throat, sore neck, sore jaw, dysphonia, and dysphagia, and about whether they were satisfied with their anesthetic. RESULTS: The incidence of sore throat was lower in the FM (8%) than the LMA-High (42%) and LMA-Low (20%) groups (both: P < or = 0.02). The incidence of sore neck was higher for the FM (14%) than the LMA-High group (6%; P = 0.05) but similar to the LMA-Low group (8%). The incidence of sore jaw was higher in the FM (11%) than the LMA-High (3%) and LMA-Low (3%) groups (both: P = 0. 02). There were no differences among groups for surgical pain or dysphonia. The incidence of dysphagia was lower in the FM (1%) than the LMA-High group (11%; P = 0.003), but similar to the LMA-Low group (1%). The incidence of sore throat and dysphagia was lower in the LMA-Low group than the LMA-High group for both males and females (all: P < or = 0.04). There were no differences in discomfort levels between males and females in any group. Two patients from the FM group and one from the LMA-High group were not satisfied with their anesthetic. These complaints were unrelated to postoperative morbidity. CONCLUSION: The LMA causes more sore throat and dysphagia but less jaw pain than the FM. Sore throat and dysphagia are more common with the LMA if the initial cuff volume is high. There are no differences in discomfort levels between males and females. However, these discomforts do not influence patient satisfaction after LMA or FM anesthesia.     

Breast magnetic resonance imaging: An essential role in malignant axillary lymphadenopathy of unknown origin

The aim of this retrospective case series was to assess the role of breast MRI in the investigation of ‘occult’ malignancy, and the associated potential to influence patient management. Between January 2000 and March 2004, 18 patients, who presented with axillary lymphadenopathy, most likely due to ‘occult’ breast cancer, were examined with MRI of the breast. The results showed 12 true positives, four true negatives, and two false positives. This gave an overall sensitivity of 85.7% and an overall accuracy of 86.7%. In those in whom malignancy was identified on MRI and subsequently proven histologically, 78% of these cancers were identified, and localized by preoperative MRI‐guided sonography. In addition, 55% of these patients were eligible for conservative surgery. As such, MRI of the breast is highly sensitive for the detection of mammographically and clinically occult breast cancer. The use of MRI enables a preoperative diagnosis to be made in a high percentage of patients and may allow retrospective targeted ultrasound localization. Definitive surgical planning, including the option of breast conservation, is made possible with the result of the MRI examination.     

Diagnosis of pulmonary embolism: Ventilation perfusion scintigraphy versus helical computed tomography pulmonary angiography

The present study compared the accuracy of ventilation perfusion scintigraphy (VQS) and CT pulmonary angiography (CTPA) for the diagnosis of pulmonary embolism. This was a prospective observational study of 112 patients with suspected pulmonary embolism (PE) who could be studied with both investigations within 24 h. Results were compared to final diagnosis at completion of 6-month follow up, using receiver operating characteristic (ROC) analysis. Pulmonary embolism was diagnosed in 27 referred patients (24%). The sensitivity and specificity of VQS and CTPA were similar to that reported from the literature. A normal VQ scan had the highest negative predictive value (100%), while a high-probability VQ scan had the highest positive predictive value (92%). There was no overall difference (area under the ROC curve (AUC)) between VQS (AUC (95% CI) = 0.82 (0.75,0.89)) and CTPA (AUC = 0.88 (0.81,0.94)) for the diagnosis of PE. Among patients with abnormal chest X-rays, CTPA (AUC 0.90 (0.83,0.97)) appeared somewhat better than VQS (AUC 0.78 (0.68,0.88)) but this difference did not reach statistical significance. In this instance, CTPA is at least as accurate as VQS and may provide an opportunity to make alternative diagnoses.     

The injured elderly in the trauma intensive care unit

The injured elderly patient in the ICU presents many challenges. Demographic changes in western society will dramatically increase the patient population in question, and new, older, subsets are growing. The association of severe injury, preinjury comorbidity, and the aging process narrows the ability of the patient to respond to the stress of injury. When compared with younger patients, the elderly have greater mortality, morbidity, and higher costs. Age alone, however, does not predict outcome. Although aggressive or maximally supportive care is advocated, controlled data supporting this approach are lacking. Significant economic, sociologic, and ethical issues confront the care providers in almost every case. Continued and heightened study of all aspects of our injured elders focusing on the determinants of outcome is required. A realistic appraisal of the limitations of care and a reassessment of the financial implications of providing extended care are critical to the continuing ability to respond to this growing need.