Cystinuria and its treatment: 25 years experience at St. Bartholomew's hospital

Summary Cystinuria is an inherited condition affecting the active transport of the diamino acids cystine, ornithine, lysine and arginine across the renal tubule and the small intestine. The only clinical effect is the production of urinary tract stones and if these can be prevented the affected individuals can lead a normal life. In many people cystine stones can be dissolved and new stone formation prevented by a high fluid intake, but if this does not succeed regular treatment with penicillamine will do so. Although many side-effects have been described with penicillamine treatment it is rare for them to be severe enough to prevent its use in patients with cystinuria. Since the clinical effects of cystinuria can be prevented by either a high fluid intake or by penicillamine it is important to make the diagnosis in affected individuals as soon as possible and cystinuria should therefore be considered in all people (regardless of age) who form urinary stones.     

The intravascular contribution to fmri signal change: monte carlo modeling and diffusion-weighted studies in vivo

Understanding the relationship between fMRI signal changes and activated cortex is paramount to successful mapping of neuronal activity. To this end, the relative extravascular and intravascular contribution to fMRI signal change from capillaries (localized), venules (less localized) and macrovessels (remote, draining veins) must be determined. In this work, the authors assessed both the extravascular and intravascular contribution to blood oxygenation level-dependent gradient echo signal change at 1.5 T by using a Monte Carlo model for susceptibility-based contrast in conjunction with a physiological model for neuronal activation-induced changes in oxygenation and vascular volume fraction. The authors compared our Model results with experimental fMRI signal changes with and without velocity sensitization via bipolar gradients to null the intravascular signal. The model and experimental results are in agreement and suggest that the intravascular spins account for the majority of fMRI signal change on T₂^*-weighted images at 1.5 T.     

A case-control study of multiple myeloma and occupation

Lifetime job histories from a population-based, case-control study were analyzed to investigate the relationship between multiple myeloma and employment in various occupations and industries. Interviews were obtained from 89% (692) of eligible incident cases and 83% (1683) of eligible controls. An elevated risk was observed among persons ever employed as painters [odds ratio (OR) + 2.1, 95% confidence interval (CI) + 1.2–3.6], particularly for those employed for 10 or more years (OR + 4.1, 95% CI + 1.8–10.4). A small excess risk was observed among agricultural workers employed for 10 or more years (OR + 1.3, 95% CI + 1.0–2.2), with a higher relative risk observed among farm laborers (OR + 1.8, 95% CI + 1.0–4.0). Among agricultural workers who reported having been highly exposed to pesticides, the OR was 5.2 (95% CI + 1.6–21.1). Some evidence, based on smaller numbers, was also found to support an association with firefighting and employment in the petroleum- and coal-products manufacturing industries. Little evidence was found to support the previously noted association with wood exposure, and no evidence for an association with employment in the rubber or petroleum refining industries was found. This study lends further support to previously reported associations between multiple myeloma and employment among painters and agricultural workers. © 1993 Wiley-Liss, Inc.     

Chronic brief restraint decreases in vivo binding of benzodiazepine receptor ligand to mouse brain

This study examines the effects of chronic brief restraint on in vivo benzodiazepine (BZD) receptor binding in mouse brain. Three groups of mice were used. Mice in group 1 were neither restrained nor injected (ACUTE control). Mice in group 2 were restrained for 5–6 s by grabbing the back skin and holding the subject upside-down at a 45° angle as if to be injected (CHRONIC SHAM control) for 7 d. Mice in group 3 (CHRONIC SALINE) received daily single intraperitoneal (ip) injections of saline (5 mL/kg) for 7 d. On d 8 BZD receptors were labeled in vivo by administration of 3 μCi [³H]flumazenil (ip). The levels of ligand bound in vivo to cerebral cortex (CX), cerebellum (CB), brain stem (BS), striatum (ST), hippocampus (HP), and hypothalamus (HY) were determined. Results indicated that the level of binding was significantly (p<0.01) lower by 30–50% (depending on the brain region) in saline-injected or sham control groups compared to acute control animals. Furthermore, the values for sham control were similar to the saline-treated group. Our data suggest that exposure to chronic mild restraint produces a decrease in in vivo binding of [³H]flumazenil in mouse brain and supports the hypothesis that chronic mild stress produces a decrease in BZD receptor binding sites.     

Application of Solid-State Nuclear Magnetic Resonance (NMR) to the Study of Skin Hydration

The solid-state nuclear magnetic resonance (NMR) technique of carbon-13 cross-polarization/magic angle spinning (CP/MAS) has been successfully used to obtain high-resolution spectra of whole-thickness, hairy rat skin and to characterize the influence of hydration on the efficiency of cross-polarization and the proton spin-lattice relaxation time in the rotating frame (T1H). Spectra obtained with hydrated samples, which were obtained with 50% more accumulations, had comparable signal-to-noise ratio relative to spectra obtained with dried skin, indicating a disordering effect with the presence of water. The integrated area of spectra of low-shifted peaks rose more rapidly with increasing contact time relative to the high-shifted peaks for both hydrated and dried skin. In addition, the carbonyl intensity of the hydrated skin relative to dried skin reached a maximum at shorter times, reflecting an efficient relaxation mechanism of the protons. The shift of the peak maximum to shorter mixing times quantitatively reflects the interaction of the protons of water with the carbonyl moiety.     

Transformation of alveolar type 2 cells to type 1 cells following exposure to NO2.

This research was undertaken to study the fate of Type 2 cells after they have divided. To accomplish this, male rats were exposed to NO₂ to increase the number of dividing Type 2 cells. Dividing cells were labeled with ³H-TdR and studied with autoradiographic techniques in the electron microscope for up to 14 days after labeling. The results show that initially most of the ³H-TdR labeled cells were Type 2. However, by 2 days there was a decrease in frequency of labeled Type 2 cells and a large increase in labeled Type 1 cells. The new frequencies of labeled alveolar epithelial cells were stable from 2 through 14 days. This evidence supports the interpretation that Type 2 cells may transform into Type 1 cells. In addition, it was shown that under the conditions of this experiment: (1) the time for transformation was about 2 days, and (2) during this process an intermediate cell type was present.     

Which treatment for whom for ADHD? Moderators of treatment response in the MTA

Using receiver operating characteristics, the authors examined outcome predictors (variables associated with outcome regardless of treatment) and moderators (variables identifying subgroups with differential treatment effectiveness) in the Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder (ADHD; MTA). Treatment response was determined using parent- and teacher-reported ADHD and oppositional defiant symptoms, with levels near or within the normal range indicating excellent response. Among 9 baseline child and family characteristics, none predicted but 3 moderated treatment response. In medication management and combined treatments, parental depressive symptoms and severity of child ADHD were associated with decreased rates of excellent response; when these 2 characteristics were present, below-average child IQ was an additional moderator. No predictors or moderators emerged for behavioral and community comparison treatments. The authors discuss conceptual and clinical implications of research on treatment moderators.     

Asthma and the diver

Self-contained underwater breathing apparatus (scuba) diving has grown in popularity, with nearly 9 million sport divers in the United States alone. Approximately 7% of the population has been diagnosed with asthma, which is similar to the percentage of divers admitting they have asthma. Numerous concerns exist regarding subjects with asthma who choose to participate in recreational diving. Among these concerns are pulmonary barotrauma, pneumomediastinum, pneumothorax, arterial gas embolism, ear barotrauma, sinus barotrauma, and dental barotrauma. Despite these concerns, a paucity of information exists linking asthma to increased risk of diving complications. However, it has long been the norm to discourage individuals with asthma from participating in recreational scuba diving. This article examines the currently available literature to allow for a more informed decision regarding the possible risks associated with diving and asthma. It examines the underlying physiological principles associated with diving, including Henry’s law and Boyle’s law, to provide a more intimate understanding on physiological changes occurring in the respiratory system under compressive stress. Finally, this article offers a framework for guiding the patient with asthma who is interested in scuba diving. Under the right circumstances, the patient with asthma can safely participate in recreational diving without apparent increased risk of an asthma-related event.     

How do topical nasal corticosteroids improve sleep and daytime somnolence in allergic rhinitis?

Therapy for rhinitis improves sleep quality and symptoms of daytime sleepiness. This improvement with therapy may be secondary to anti-inflammatory effects, leading to a reduction of inflammatory mediators, or to a mechanical reduction of congestion directly leading to improvement in sleep disturbance. We combined our data from 3 placebo-controlled studies of intranasal corticosteroids in patients with perennial rhinitis to determine whether a correlation between the reduction of congestion and improved sleep and daytime somnolence existed. The pooled data of budesonide, flunisolide, and fluticasone demonstrated significantly decreased nasal congestion, sleep problems, and sleepiness in treated patients. The data demonstrated a correlation between a reduction in nasal congestion and an improvement of sleep (P < .01) and daytime somnolence (P = .01). Thus, topical intranasal corticosteroids should be used to decrease nasal congestion and to improve sleep and daytime somnolence in patients manifesting these symptoms.