Eating disorder in a 6-year-old Asian girl with ethyl malonic adipic aciduria

Accurate data are not available for the prevalence of eating disorders amongst the Asian population in Britain. Only a handful of cases have been reported in the literature [Bhadrinath (1990). British Journal of Psychiatry, 156, 565–568.] suggested that it is an uncommon phenomenon despite Dolan's recent finding [Dolan, Lacey, & Evans (1990). British Journal of Psychiatry, 157, 523–528.] that there were elevated Eating Attitudes Test (EAT) scores in a sample of young Asian adults compared with Caucasians. We report a case of an Asian girl with a rare inborn error of metabolism and an eating disorder. © 1993 by John Wiley & Sons, Inc.     

Clinical responses with T lymphocytes targeting malignancy-associated κ light chains

BACKGROUND. Treatment of B cell malignancies with adoptive transfer of T cells with a CD19-specific chimeric antigen receptor (CAR) shows remarkable clinical efficacy. However, long-term persistence of T cells targeting CD19, a pan–B cell marker, also depletes normal B cells and causes severe hypogammaglobulinemia. Here, we developed a strategy to target B cell malignancies more selectively by taking advantage of B cell light Ig chain restriction. We generated a CAR that is specific for the κ light chain (κ.CAR) and therefore recognizes κ-restricted cells and spares the normal B cells expressing the nontargeted λ light chain, thus potentially minimizing humoral immunity impairment.METHODS. We conducted a phase 1 clinical trial and treated 16 patients with relapsed or refractory κ⁺ non-Hodgkin lymphoma/chronic lymphocytic leukemia (NHL/CLL) or multiple myeloma (MM) with autologous T cells genetically modified to express κ.CAR (κ.CARTs). Other treatments were discontinued in 11 of the 16 patients at least 4 weeks prior to T cell infusion. Six patients without lymphopenia received 12.5 mg/kg cyclophosphamide 4 days before κ.CART infusion (0.2 × 10⁸ to 2 × 10⁸ κ.CARTs/m²). No other lymphodepletion was used.RESULTS. κ.CART expansion peaked 1–2 weeks after infusion, and cells remained detectable for more than 6 weeks. Of 9 patients with relapsed NHL or CLL, 2 entered complete remission after 2 and 3 infusions of κ.CARTs, and 1 had a partial response. Of 7 patients with MM, 4 had stable disease lasting 2–17 months. No toxicities attributable to κ.CARTs were observed.CONCLUSION. κ.CART infusion is feasible and safe and can lead to complete clinical responses.TRIAL REGISTRATION. ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00881920","term_id":"NCT00881920"}}NCT00881920.FUNDING. National Cancer Institute (NCI) grants 3P50CA126752 and 5P30CA125123 and Leukemia and Lymphoma Society (LLS) Specialized Centers of Research (SCOR) grant 7018.     

Understanding the nature of apraxia of speech: Theory,analysis, and treatment

Researchers have interpreted the behaviours of individuals with acquired apraxia of speech (AOS) as impairment of linguistic phonological processing, motor control, or both. Acoustic, kinematic, and perceptual studies of speech in more recent years have led to significant advances in our understanding of the disorder and wide acceptance that it affects phonetic - motoric planning of speech. However, newly developed methods for studying nonspeech motor control are providing new insights, indicating that the motor control impairment of AOS extends beyond speech and is manifest in nonspeech movements of the oral structures. We present the most recent developments in theory and methods to examine and define the nature of AOS. Theories of the disorder are then related to existing treatment approaches and the efficacy of these approaches is examined. Directions for development of new treatments are posited. It is proposed that treatment programmes driven by a principled account of how the motor system learns to produce skilled actions will provide the most efficient and effective framework for treating motorbased speech disorders. In turn, well controlled and theoretically motivated studies of treatment efficacy promise to stimulate further development of theoretical accounts and contribute to our understanding of AOS.     

The quality of care for Medicare patients with peptic ulcer disease

OBJECTIVE: The aim of this study was to examine quality of care for hospitalized Medicare beneficiaries with peptic ulcer disease. METHODS: Collaborating with five Peer Review Organizations, we used 1995 Medicare claim files to select samples of inpatients with a principal diagnosis of peptic ulcer disease. Quality of care indicators developed by content experts included percentages for ulcer patients tested for Helicobacter pylori (H. pylori); biopsied patients who received tissue tests; H. pylori-positive patients who received appropriate therapy; and ulcer patients screened for preadmission nonsteroidal anti-inflammatory drug (NSAID) use and counseled about risks. RESULTS: Of 2,644 patients eligible for medical record review, 56% were tested for H. pylori, and 73% of those testing positive were treated appropriately; 84% of patients with endoscopic biopsies received a tissue test for H. pylori; 74% of patients were screened for preadmission NSAID use, 24% had documented counseling of NSAID use, and only 2% had documented counseling on the ulcer risk of NSAID use. Statistically significant regional variation occurred in four of six quality indicators. Outpatient records were reviewed for 529 patients to document prior outpatient H. pylori in this population; only 2% (n = 12) were tested for H. pylori in the year before admission. CONCLUSIONS: Opportunities exist to improve quality of care by testing for and treating H. pylori in hospitalized Medicare beneficiaries with peptic ulcer disease and to improve screening for NSAIDs and counseling on ulcer risks.     

Role of cystourethrography in the preoperative evaluation of stress urinary incontinence in women

Thirty-two women with stress urinary incontinence and 27 control continent patients with pelvic relaxation underwent a detailed clinical and urodynamic evaluation of the lower urinary tract. All patients underwent a standard chain urethrocystographic evaluation to detect anatomic pathology of the lower urinary tract. Urethrocystographic study included an evaluation of the posterior and anterior urethral angle, funneling of the proximal urethra on straining, the position of the urethrovesical junction and flattening of the bladder base. No differences were seen in the incidence of radiographic findings in women with pelvic relaxation with or without stress urinary incontinence. All five cystographic criteria were similar in the continent and stress incontinence patients. Static urethrocystography cannot differentiate women with and without stress urinary incontinence from among those with pelvic relaxation and thus should not be relied upon in the evaluation of women with urinary incontinence.     

Theophylline treatment in the extubation of infants weighing less than 1,250 grams: a controlled trial

The role of theophylline in weaning infants weighing less than 1,250 g at birth from mechanical ventilation was evaluated. Infants were randomized into control or theophylline treatment groups when they required minimal ventilatory support (peak inspiratory pressure 12 cm H2O, positive end-expiratory pressure 2 cm H2O, rate 12 breaths per minute, and FiO2 less than 0.3), and they were extubated 24 hours later. Infants required reintubation if they had (1) PaCO2 greater than 55 mm Hg and pH less than 7.20, (2) FiO2 greater than 0.5, or (3) apnea associated with a heart rate less than 100 beats per minute that required frequent stimulation (more than 20 episodes during a 16-hour period). Among 32 infants (birth weight less than 1,000 g) who reached minimal ventilatory support before seven days after delivery, 13 of 18 (72%) control infants required reintubation, whereas only four of 14 (28%) theophylline-treated infants required reintubation. On the other hand, among infants (birth weight less than 1,000 g) who reached minimal ventilatory support after seven days following delivery, only one of six (17%) of the control group required reintubation and no improvement could be seen with theophylline treatment. Similarly, among control infants (birth weight 1,001 to 1,250 g), only ten of 45 (23%) required reintubation after reaching low intermittent manditory ventilation settings. In summary, most infants recovering from respiratory distress syndrome who had birth weights (1) greater than 1,000 g or (2) less than 1,000 g and who were older than seven days could be successfully extubated from minimal ventilatory support without theophylline treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Elevation of arterial potassium during acute systemic hypoxia is abolished by alkalosis

BACKGROUND: Small elevations in plasma potassium evoke vasodilation in the peripheral circulation. Systemic hypoxia elevates arterial potassium and also modifies arterial pH. AIMS: We examined the interaction between pH and potassium in blood during systemic hypoxia and the effect of pH on the uptake/release of potassium in the peripheral tissues. METHODS: Anesthetized dogs were ventilated with air plus oxygen for normoxia or air plus nitrogen for hypoxia. Some animals received intravenous sodium bicarbonate to elevate pH by 0.1 units. Arterial plasma potassium concentration was measured in normoxia and hypoxia. A rat gracilis muscle was perfused with normoxic Krebs buffer and the potassium content of the venous outflow was compared during perfusion at pH 7.4, 6.8, or 7.8. RESULTS: In dogs with an arterial pH of 7.40-7.45, systemic hypoxia elevated the arterial potassium by 1 mmol/L. An arterial pH of 7.55 did not alter the basal potassium concentration, but it abolished the hypoxia-induced increase. In rat muscle, reduction of the perfusate pH from 7.4 to 6.8 reduced arterial perfusion pressure from 8.73 to 7.32 kPa and venous potassium from 6.6 to 5.2 mM. Elevation of perfusate pH to 7.8 decreased the arterial perfusion pressure from 8.44 to 6.95 kPa but did not affect venous potassium. CONCLUSIONS: The hypoxia-induced elevation of arterial potassium is abolished by increasing the pH to 7.55. This is not due to enhanced potassium uptake into peripheral tissues at high pH. Red blood cells are suggested as the most likely source of the potassium released in hypoxia.     

Biotinidase catalyzes debiotinylation of histones

Summary Background Posttranslational modifications of histones play important roles in processes such as regulation of gene expression and DNA repair. Recently, evidence has been provided that histones in human cells are modified by covalent attachment of biotin. Aim of the study To determine whether the reverse process (debiotinylation of histones) occurs in biological samples and whether debiotinylation is an enzyme-mediated process; and to characterize the enzyme that mediates debiotinylation of histones. Methods Plasma and lymphocytes from healthy adults and a biotinidase-deficient patient were used as sources of debiotinylating enzymes. Debiotinylation of histones by plasma and lymphocyte proteins was measured using a colorimetric 96-well plate assay. Results Histones were debiotinylated rapidly if incubated with human plasma or lysates of lymphocytes. The following observations are consistent with the hypothesis that debiotinylation is an enzyme-mediated process: (i) Hydrolysis was slower at 4 °C compared to 37 °C; (ii) debiotinylating activity was destroyed when biological samples were heated at 90 °C for 30 min preceding incubation with biotinylated histones; and (iii) rates of debiotinylation were pH dependent. Rates of histone debiotinylation were significantly decreased in biotinidase-deficient samples. Conclusion Debiotinylation of histones in human samples is an enzyme-mediated process that is at least partly catalyzed by biotinidase. Received: 27 September 2001, Accepted: 6 January 2002     

Effect of parietal lobe lesions on saccade targeting and spatial memory in a naturalistic visual search task

The eye movements of two patients with parietal lobe lesions and four normal observers were measured while they performed a visual search task with naturalistic objects. Patients were slower to perform the task than the normal observers, and the patients had more fixations per trial, longer latencies for the first saccade during the visual search, and less accurate first and second saccades to the target locations during the visual search. The increases in response times for the patients compared to the normal observers were best predicted by increases in the number of fixations. In order to investigate the effects of spatial memory on search performance, in some trials observers saw a preview of the search display. The patients appeared to have difficulty using previously viewed information, unlike normal observers who benefit from the preview. This suggests a spatial memory deficit. The patients' deficits are consistent with the hypothesis that the parietal cortex has a role in the selection of targets for saccades, in memory for target location.