Time-dependent changes of insufficiency fractures of the sacrum: intraosseous vacuum phenomenon as an early sign

Sacral insufficiency fractures develop over a period of time and show time-dependent changes. We report on 15 CT examinations of 5 patients with early-stage insufficiency fractures of the sacrum. In 4 patients only irregular sclerosis without distinct fracture lines was present in 7 of 8 fractures. Of these 4 patients; 3 exhibited intraosseous gas inclusions in a ventral part of a lateral mass; 5 of 8 fractures disclosed a ventral cortical break. When distinct fracture lines had developed in 1 patient, intraosseous vacuum phenomenon had disappeared. Fracture lines evolve over weeks to months and show central bone absorption. The fractures can heal as demonstrated in 4 of 6 fractures in 3 patients, can persist over 1 year without significant changes or can progress to pseudoarthrosis with bone destruction similar to neuropathic joint disease. Intraosseous vacuum phenomena can persist to this stage. Intraosseous vacuum phenomenon is recognized as a potential finding in the early stage of sacral insufficiency fracture, which also is true for irregular sclerosis and ventral cortical disruption. Correspondence to: A. Stäbler     

Dose response, coasting, and differential fiber vulnerability in human toxic neuropathy: a prospective study of pyridoxine neurotoxicity.

We administered either 1 or 3 g/d of pyridoxine (vitamin B6) to five healthy volunteers and repeatedly followed serum pyridoxal phosphate levels, clinical symptoms and signs, quantitative sensory thresholds (QSTs), and sural nerve electrophysiology. Pyridoxine was discontinued at the first sign of either clinical or laboratory abnormality. In all subjects, sensory symptoms and QST abnormalities occurred concurrently. Subjects receiving higher doses became symptomatic earlier than low-dose subjects. Elevation of thermal QSTs preceded or exceeded that for vibration in the three low-dose subjects; vibration and thermal QST became abnormal simultaneously in the higher-dose subjects. A reduction in the amplitude of the sural sensory potential lagged behind QST changes in two of three subjects. Symptoms continued to progress ("coasting") for 2 to 3 weeks despite stopping pyridoxine administration and the return of serum pyridoxal phosphate levels to normal. This study suggests that (1) there is a clear dose-percent relationship for pyridoxine-induced neuropathy, (2) QST is a sensitive measurement for detecting early peripheral neuropathy; QST abnormalities may precede changes in nerve conduction studies, (3) coasting appears unrelated to persistently elevated blood levels of the toxin, and (4) a dose-dependent vulnerability may exist among nerve fibers of different caliber when exposed to an axonal toxin, such as pyridoxine.     

The role of atmospheric pressure variation in the development of spontaneous pneumothoraces

It has been postulated that spontaneous pneumothoraces (SP) develop because of rupture of subpleural blebs, and that atmospheric pressure changes (delta AP) may be contributory. A 5-year retrospective analysis of SP admissions was carried out to determine if delta AP do play a role in SP development. Using a 36-yr record of hourly delta AP, a normative background for delta AP was constructed. A fall in AP below the fifth, or a rise above the ninety-fifth percentile during these time periods, was classed as "unusual." Atmospheric pressure changes in the 4 days prior to SP were analyzed. The expected frequency of SP occurring by chance, if no relationship to delta AP existed, was also calculated. A total of 192 cases of SP was analyzed. Traumatic pneumothoraces were excluded. The majority of cases (72%) had been exposed to at least one "unusual" delta AP in the 4 days prior to onset of symptoms. Among those with four or more "unusual" exposures, SP occurrence was significantly more frequent than expected by chance alone (p less than 10(-10]. A strong positive association between delta AP and SP was not found in all cases, as delta AP are unlikely to be the only causative factor for SP. This finding of a relationship with ambient pressure changes lends support to the theory that SP develop as a result of rupture of subpleural blebs.     

Studies of the mechanism of tolerance induced by short-term immunosuppression with cyclosporine in high-risk corneal allograft recipients. I. Analysis of CTL precursor frequencies

Transplantation of unmatched allogeneic corneas into highly vascularized recipient eyes under the cover of short-term immunosuppression with cyclosporine enables permanent engraftment. The aim of this study was to further elucidate the mechanism(s) underlying this tolerant state. In eight "high-risk" cornea recipients the clone sizes of donor-specific and third-party reactive cytotoxic T cell precursors were assessed by limiting dilution analyses before and at three and six months after transplantation. Acquired allograft tolerance in these patients was not accompanied by clonal reduction of donor-specific CTL-p, whereas in the case of an irreversible rejection the donor-specific CTL pool size was significantly enlarged. This donor-specific CTL-p increase could already be seen two months before clinical manifestation. These patterns differed from that of tolerant renal transplant patients, in whom marked and donor-specific reduction of CTL-p was observed. During rejection identical patterns with increasing donor-specific CTL-p frequencies were seen in both groups of patients. We conclude that induction of tolerance by short-term CsA to unmatched cornea grafts is not caused by clonal reduction of the effector precursor cell pool.     

Evaluation of long-term safety of the anti-IgE antibody, omalizumab, in children with allergic asthma.

OBJECTIVE: To evaluate the long-term effects of the anti-IgE antibody omalizumab in children with asthma. METHODS: This was a 28-week, double-blind, randomized, placebo-controlled trial with a 24-week open-label extension. In the core trial 225 children (ages 6 to 12 years) with moderate-to-severe allergic asthma requiring inhaled beclomethasone dipropionate (BDP) received omalizumab every 2 or 4 weeks, and 109 received placebo. BDP dosage was stable for weeks 1 to 16, then reduced during weeks 17 to 24 using strict safety criteria. The lowest dose for optimal asthma control was maintained for 4 more weeks. During the 24-week extension, all patients (n = 309) received open-label omalizumab in addition to other asthma medications. One-year safety data were analyzed. RESULTS: The incidence of adverse events in patients treated with omalizumab for 52 weeks was similar to those treated for 28 weeks in the core trial, which was generally comparable with placebo. In the 52-week omalizumab group, upper respiratory tract infection and headache were the most frequently reported adverse events (47.1% and 42.7%, respectively). Eleven patients (4.9%) reported urticaria, which resolved spontaneously or with antihistamine, except for 1 patient who was discontinued because of severe urticaria. No anaphylactic reactions or adverse events suggestive of serum sickness or immune complex formation occurred. No anti-omalizumab antibodies were detected in any of the children. There is no evidence that new or more serious adverse events occur with long-term omalizumab treatment. CONCLUSIONS: Long-term treatment with omalizumab is safe and well tolerated in children with allergic asthma.     

Development and validation of school-based asthma and allergy screening instruments for parents and students.

BACKGROUND: The increasing morbidity attributable to asthma among school-aged children suggests the potential utility of school-based asthma screening programs. OBJECTIVE: We report our efforts to develop and validate culturally sensitive and clinically useful screening questionnaires (parent and child versions) for asthma and allergies among urban US school children. METHODS: Instrument development was accomplished through literature review, expert medical and child developmental input, focus group feedback, and a rigorous trial of the instruments in a public school setting. Questionnaires were distributed to 2,800 children and their families in an urban public school system (grades kindergarten through 6). Validity was evaluated by blinded comparison of results against a standardized clinical evaluation in 107 children, with final designations determined by an expert panel. RESULTS: Questionnaires pertaining to 2,083 children were returned (participation rate of 74%). A moderate level of agreement was observed between parent and student questionnaire responses (r values = 0.36 to 0.50; P values < 0.001). The highest frequency of asthma-like symptoms was reported for African-American boys and the lowest for Caucasian girls. The items from the parent questionnaire that best predicted asthma were "breathing problems" (occurring rarely or more; odds ratio 12.8; 95% confidence interval, 4.5 to 36.1) and "problems coughing" (sometimes or more; odds ratio 9.7; 95% confidence interval, 3.6 to 26.5). Considering the presence of cough (sometimes or more) and/or breathing problem (rarely or more) yielded a sensitivity of 80%; a specificity of 75%, a positive predictive value of 50%, and a negative predictive value of 92%. Similar levels of prediction were observed for the items "trouble breathing" and "noisy breathing" as directly reported by the students. Allergic rhinitis was best predicted by report of a runny/stuffy no se (sometimes or more; sensitivity of 83%, specificity of 61%).Allergic conjunctivitis was best predicted by "itchy eyes." CONCLUSIONS: Administration of a school-based questionnaire is feasible, with a high response rate and excellent internal consistency. A high sensitivity and acceptable specificity was achieved by using one to two questions for asthma, allergic rhinitis, and allergic conjunctivitis. Among the children in grades 2 or above, comparable levels of prediction could be achieved with the student or parent version.     

Menstrual cycle and appetite control: implications for weight regulation

Hormonal fluctuations associated with the menstrual cycle influence appetite control and eating behaviour. Energy intake varies during the reproductive cycle in humans and animals, with a periovulatory nadir and a luteal phase peak. Patterns of macronutrient selection show less consistency but a number of studies report carbohydrate cravings in the premenstrual phase, particularly in women with premenstrual syndrome. The cyclical nature of food cravings are frequently, but not invariably, associated with depression. Fluctuations in appetite, cravings and energy intake during the menstrual cycle may occur in parallel with cyclical rhythms in serotonin, which can be accompanied by affective symptoms. The premenstrual phase can be considered as a time when women are especially vulnerable to overconsumption, food craving and depression; this is often associated with low serotonin activity.