Changes in Lower Leg Anterior Compartment Pressure Before,During, and After Creatine Supplementation

OBJECTIVE: To determine if 35 days of creatine supplementation (Cr) followed by 28 days of no supplementation altered lower leg anterior compartment pressure (ACP) at rest and after exercise. DESIGN AND SETTING: Subjects were divided into 2 treatment groups: (1) high dose (0.3 g Cr.kg body mass(-1).d(-1) for 7 days followed by 0.03 g Cr.kg body mass(-1).d(-1) for 28 days), or (2) low dose (0.03 g Cr.kg body mass(-1).d(-1) for 35 days). After 35 days, supplementation was terminated, and no Cr was ingested for 28 days. SUBJECTS: Sixteen physically active, healthy, college-aged males (O(2)max = 47.6 +/- 5.1 mL.kg(-1).min(-1)). MEASUREMENTS: At baseline, 7 days and 35 days of supplementation, and 28 days postsupplementation, ACP was measured preexercise and immediately, 1, 5, 10, and 15 minutes postexercise after a treadmill run at 80% O(2)max. RESULTS: For ACP, there was no significant group-by-time interaction, but there was a significant time effect for group when the data were combined. ACP was significantly increased at preexercise, immediately postexercise, and 1, 5, and 10 minutes from baseline to 7 days. ACP remained significantly elevated from baseline at 35 days immediately postexercise and 1 minute postexercise. After 28 days of no supplementation, ACP began to return to presupplementation levels, with only the 1-minute postexercise measurement significantly elevated from baseline. CONCLUSIONS: Creatine supplementation increased ACP at rest and after exercise, and ACP began to return to normal after 28 days of no supplementation.     

Long QT syndrome with a high mortality rate caused by a novel G572R missense mutation in KCNH2

In a four-generation family with long QT syndrome, syncopes and torsades de pointes ventricular tachycardia (TdP) were elicited by abrupt awakening in the early morning hours. The syndrome was associated with a novel KCNH2 missense mutation, G572R, causing the substitution of a glycine residue at position 572, at the end of the S5 transmembrane segment of the HERG K(+)-channel, with an arginine residue. This segment is involved in the channel pore and the mutation may cause a reduction in the rapidly activating delayed rectifier K+ current (Ikr), or changed gating properties of the ion channel, leading to prolonged cardiac repolarization. The electrocardiograms of affected persons showed prolonged QT interval and notched T waves. Despite treatment with atenolol, 200 mg twice daily, the proband still experienced TdP episodes. Three untreated relatives of the proband died suddenly, and unexpectedly, at 18, 32, and 57 years of age. The G572R mutation is thus associated with a high mortality rate, and the clinical presentation illustrates that some mutations may not be controllable by just beta-blockade.     

Effect of the 21-aminosteroid,U-74389F,on hyperoxic lung injury in rats

Hyperoxia (>95% oxygen) in rats caused an increase in lung weight and an accumulation of fluid in the thorax. The mean lung wet weight of air-breathing controls at 60 h was 1.2±0.01 g, and that of vehicle-treated, oxygen-exposed animals was 2.45±0.05 g. Treatment with the 21-aminosteroid U-74389F, 3, 10, and 30 mg/kg twice daily throughout oxygen exposure, produced 8, 42, and 18% inhibition of the oxygen-induced increase in lung weight, respectively. However, U-74389F did not inhibit the hyperoxia-induced accumulation of neutrophils in bronchoalveolar lavage fluid.

No pleural fluid could be aspirated from the thorax of air-breathing controls. The volume of pleural fluid in oxygen-exposed, vehicle-treated animals and animals treated with 3, 10, and 30 mg/kg U-74389F b.i.d. was 6.5±0.9, 2.6±0.6, 0.8±0.3, and 1.3±0.5 ml, respectively.

U-74389F or its biologs are of potential value for the treatment of lung diseases in which oxidant damage has been implicated.

     

Whey hydrolysate compared with cow's milk-based formula for weaning at about 6 months of age in high allergy-risk infants: effects on atopic disease and sensitization

Ninety-one high atopy-risk infants were prospectively followed up to 18 months of age with regard to the development of allergic/atopic manifestations and sensitization. They were randomized into one of two feeding groups, i.e., a hydrolyzed, ultrafiltered cow's milk whey formula, Profylac® ( n = 32), or an ordinary cow's milk formula ( n = 39), for 12 months, started after exclusive breast-feeding for 0–9 (median 6.0) months. Lactating mothers avoided milk, egg, and fish, as did the infants up to 12 months of age. Twenty of the 91 infants were breast-fed exclusively for more than 9 months and regarded as a control group. All infants were followed-up by questionnaires, physical examinations, skin prick tests, and determination of serum total IgE and cow's milk-specific IgE. The frequency of allergic/atopic disease was similar in the three groups. However, all three infants who developed cow's milk allergy with skin symptoms belonged to the cow's milk formula group. The skin prick test with whey hydrolysate was negative in all, while with cow's milk it was positive in eight infants. Growth was similar in the three groups. The study comprises too few infants to allow us to make statistically based statements. However, the difficulties encountered and the limited effects obtained by the use of whey hydrolysate at weaning at about 6 months of age made us conclude that we can spare high atopy-risk families this extra burden.     

Relation of psychological vulnerability factors to posttraumatic stress disorder symptomatology in bone marrow transplant recipients

OBJECTIVE: Prior research suggests that the diagnosis and treatment of cancer can result in the development of symptoms of posttraumatic stress disorder (PTSD). Based on Lazarus and Folkman's model of stress, the current study examined whether trauma appraisals, coping, social support, and social constraint were associated with the severity of PTSD symptoms in cancer patients who had undergone bone marrow transplantation (BMT). METHODS: Participants were 23 males and 79 females treated with BMT an average of 20 months previously (range = 3-62 months). Past and current psychiatric diagnoses were assessed through a structured clinical interview. PTSD symptomatology and other psychological variables were assessed using standardized self-report measures. RESULTS: Results indicated that 5% of participants met diagnostic criteria for current PTSD. Participants reported an average of three to four symptoms of PTSD (range = 0-16). Univariate analyses confirmed predictions that increased PTSD symptomatology would be associated with more negative appraisals of the BMT experience, greater use of avoidance-based coping strategies, lower levels of social support, and greater social constraint (p < .05). Regression analyses indicated that each of these variables accounted for significant (p < .05) variability in PTSD symptomatology above and beyond relevant demographic and medical variables. CONCLUSIONS: Results of the present study confirm and extend prior research regarding the prevalence of PTSD and PTSD symptoms among patients treated for cancer. In addition, the study identified a set of theoretically derived psychological characteristics that seem to place patients at risk for greater PTSD symptomatology after BMT.     

Identification and Characterization of a 29-Kilodalton Protein from Mycobacterium tuberculosis Culture Filtrate Recognized by Mouse Memory Effector Cells

Culture filtrate proteins from Mycobacterium tuberculosis induce protective immunity in various animal models of tuberculosis. Two molecular mass regions (6 to 10 kDa and 24 to 36 kDa) of short-term culture filtrate are preferentially recognized by Th1 cells in animal models as well as by patients with minimal disease. In the present study, the 24- to 36-kDa region has been studied, and the T-cell reactivity has been mapped in detail. Monoclonal antibodies were generated, and one monoclonal antibody, HYB 71-2, with reactivity against a 29-kDa antigen located in the highly reactive region below the antigen 85 complex was selected. The 29-kDa antigen (CFP29) was purified from M. tuberculosis short-term culture filtrate by thiophilic adsorption chromatography, anion-exchange chromatography, and gel filtration. In its native form, CFP29 forms a polymer with a high molecular mass. CFP29 was mapped in two-dimensional electrophoresis gels as three distinct spots just below the antigen 85 complex component MPT59. CFP29 is present in both culture filtrate and the membrane fraction from M. tuberculosis, suggesting that this antigen is released from the envelope to culture filtrate during growth. Determination of the N-terminal amino acid sequence allowed cloning and sequencing of the cfp29 gene. The nucleotide sequence showed 62% identity to the bacteriocin Linocin from Brevibacterium linens. Purified recombinant histidine-tagged CFP29 and native CFP29 had similar T-cell stimulatory properties, and they both elicited the release of high levels of gamma interferon from mouse memory effector cells isolated during the recall of protective immunity to tuberculosis. Interspecies analysis by immunoblotting and PCR demonstrated that CFP29 is widely distributed in mycobacterial species.     

HLA-DP and bonemarrow transplantation: DP-incompatibility and severe acute graft versus host disease

Thirteen recipients of HLA-haploidentical, DR compatible bone marrow (BM) and the corresponding BM donors were HLA-DP typed using primed lymphocyte typing (PLT). Severe acute GVHD (greater than or equal to grade 2) developed within 3 months after BM-transplantation in all of eight recipients of DP incompatible BM, but in none of five recipients of DP-compatible BM. This difference was highly significant (p less than 0.001, Fisher's exact test). Moreover, severe acute GVHD was significantly increased in recipients of haploidentical, DR compatible, but DP incompatible BM as compared to severe acute GVHD in 88 recipients of HLA-identical BM (p less than 0.0001). In contrast, there was no difference in acute GVHD between recipients of haploidentical, DR and DP compatible BM and recipients of HLA-identical BM. The data presented here provide strong evidence for the first time that HLA-DP antigens play a role as transplantation antigens.