Juvenile, adult and late-onset systemic lupus erythematosus: a long term follow-up study from a geographic and ethnically homogeneous population.

OBJECTIVES: This paper aims to identify clinical and serological differences, damage accrual and mortality, in juvenile, adult and late-onset SLE. METHODS: We conducted our study with patients fulfilling SLE classification criteria taken from the Hospital Gregorio Marañon Autoimmune Systemic Rheumatic Diseases' Registry (1986 to 2012). Clinical characteristics, laboratory data and therapies used during the course of the disease were analysed with patients divided into 3 groups: juvenile-onset (≤ 18 years), adult-onset (19-50) and late onset (>50 years). RESULTS: Four hundred and forty-five patients were included. Renal disease and cutaneous manifestations were more frequent in the juvenile-onset group at disease onset. During follow-up, juvenile-onset group presented a higher incidence of renal disease, malar rash, Raynaud's phenomenon, cutaneous vasculitis, and neuropsychiatric manifestations than the other two groups. Arthritis and lymphopoenia were more frequent in the adult-onset group. Arterial hypertension and neoplasm were more frequent in the late-onset group. Low serum complement, anti-dsDNA, anti-U1RNP and anti-Sm antibodies were more common in the juvenile-onset group. Patients with late-onset SLE had more damage accrual. Thirty-seven patients (8.3%) died during the study. All-cause mortality was significantly higher in the late-onset group. Age at disease onset >50 years was an independent risk factor for damage accrual (OR, 2.2; 95%CI, 1.1-4.6; p=0.029) and mortality (OR, 2.6; 95%CI, 1.1-6.3; p=0.03). CONCLUSIONS: We found significant differences in clinical and serological profiles between juvenile, adult and late-onset SLE. The most significant of which was a higher prevalence of neuropsychiatric and renal complications as well as different autoantibody signatures for the juvenile-onset group.

Discrepancies in identification of left atrial enlargement using left atrial volume versus left atrial-to-aortic root ratio in dogs.

BACKGROUND: Left atrial size is prognostically important in dogs with myxomatous mitral valve disease (MMVD). HYPOTHESIS/OBJECTIVES: To compare the level of agreement in identification of left atrial enlargement (LAE) between the left atrial-to-aortic root ratio (LA : Ao) and left atrial volume using the biplane area-length method indexed to body weight (LA Vol/BW). ANIMALS: Sixty dogs with MMVD and 22 normal dogs were prospectively studied with 2-dimensional echocardiography. METHODS: The upper limit of normal for LA Vol/BW was defined as 1.1 mL/kg. LA : Ao was deemed normal if ≤1.5. To define overall disease severity, each dog was assigned a mitral regurgitation severity score (MRSS) based on echocardiographic parameters that did not include left atrial size. ACVIM staging also was utilized. RESULTS: Of 60 affected dogs, 20 were ACVIM Stage B1, 25 were Stage B2, and 15 were Stage C. LA Vol/BW identified LAE in 12 cases in which LA : Ao was normal; 7 of these were Stage B1 and 5 were Stage B2. This diagnostic disagreement was significant (P = .00012). Of the 12 cases in which diagnostic discrepancies were identified, 5/5 of the B2 dogs and 3/7 B1 dogs had a moderate MRSS, whereas 4/7 B1 dogs had a mild MRSS. No diagnostic discrepancies between LA : Ao and LA Vol/BW were apparent in dogs with a severe MRSS. CONCLUSIONS AND CLINICAL IMPORTANCE: This study shows evidence of diagnostic disagreement between LA : Ao and LA Vol/BW for assessment of LAE. LA Vol/BW may be superior to LA : Ao for identification of mild LAE.

Effects of urea formaldehyde condensation polymer treatment of flaxseed on ruminal digestion and lactation in dairy cows.

Flaxseed is a potent source of the n-3 fatty acid α-linolenic acid (ALA), yet most ALA is lost during ruminal biohydrogenation when ground flaxseed is fed to ruminants. Heat processing and urea formaldehyde condensation polymer (UFCP) treatment of flaxseed were investigated as possible means of protecting ALA from ruminal degradation. Ground flaxseed (GF), heated ground flaxseed (HGF), or UFCP-treated ground flaxseed (UFCPGF) were incubated for 0, 4, 8, and 12h in 4 ruminally cannulated multiparous lactating Holstein cows. Compared with GF, HGF and UFCPGF decreased ruminal disappearance of dry matter, crude protein, and ALA. Pepsin-digestible protein remaining after 12h of ruminal incubation was greater for UFCPGF and HGF than for GF. Twenty-four lactating Holstein cows (207 ± 37 d in milk, 668 ± 66 kg of body weight, and 1.33 ± 0.56 lactations) were then used in a randomized complete block design experiment with a basal feeding period to assess effects of flaxseed treatment on ALA enrichment of plasma and milk as well as lactational performance. No evidence existed that supplementation of HGF and UFCPGF affected dry matter intake, milk fat content, milk protein content, or energy-corrected milk yield, but UFCPGF marginally decreased milk yield compared with HGF. Plasma concentration of ALA was not affected by treatment. Concentrations of n-3 fatty acids and conjugated linoleic acids in milk fat were increased by UFCPGF relative to HGF, but ALA yield was not affected. Taken together, in situ results suggest that heat-treated flaxseed, with or without UFCP treatment, slowed ruminal disappearance of ALA. Feeding UFCP-treated flaxseed failed to alter ALA content of plasma or milk ALA yield relative to heating alone.

Additive feeding inhibitory and aversive effects of naltrexone and exendin-4 combinations.

OBJECTIVE: One developing strategy for obesity treatment has been to use combinations of differently acting pharmacotherapies to improve weight loss with fewer adverse effects. The purpose of this study was to determine whether the combination of naltrexone (Nal), an opioid antagonist acting on the reward system, and exendin-4 (Ex-4), a glucagon-like peptide 1 agonist acting on satiety signaling, would produce larger reductions in food intake than either alone in rats. Because the anorectic potencies of both compounds have been associated with nausea and malaise, the influence of these drug combinations on the acquisition of a conditioned taste aversion (CTA) was also determined. METHODS: In Experiment 1, the acute anorectic effects of Nal (0.32-3.2 mg kg(-1); intraperitoneally (i.p.)) and Ex-4 (1-10 µg kg(-1); i.p.) were assessed alone or in combination. Combinational doses were further investigated by the repeated daily administration of 1 mg kg(-1) Nal+3.2 µg kg(-1) Ex-4 for 4 days. In Experiment 2, both compounds alone or in combination were used as unconditioned stimuli in a series of CTA tests. RESULTS: Nal and Ex-4, alone or in combination, suppressed food intake in a dose-dependent manner, and the interaction on food intake between Nal and Ex-4 was additive. In the CTA paradigm, Nal (1 mg kg(-1)) alone did not support acquisition, whereas a CTA was evident with doses of Ex-4 (1 or 3.2 µg kg(-1)). Combinations of Nal and Ex-4 also resulted in a more rapid and robust acquisition of a CTA. CONCLUSION: Given that the Nal and Ex-4 combination produces additive effects on not only food intake reduction but also food aversion learning, this specific drug combination does not have the benefit of minimizing the adverse effects associated with each individual drug. These data suggest that it is necessary to evaluate both the positive and adverse effects at early stages of combinational drug development.

Enteric methane emissions and lactational performance of Holstein cows fed different concentrations of coconut oil.

To determine if dietary medium-chain fatty acids (FA; C(8) to C(14)) may mitigate enteric methane emissions, 24 cows were blocked by body size (n=2) and randomly assigned to 1 sequence of dietary treatments. Diets were fed for 35 d each in 2 consecutive periods. Diets differed in concentrations of coconut oil (CNO; ~75% medium-chain FA): 0.0 (control) or 1.3, 2.7, or 3.3% CNO, dry matter basis. The control diet contained 50% forage (74% from corn silage), 16.5% crude protein (60% from rumen-degradable protein), 34% neutral detergent fiber (NDF; 71% from forage), and 28% starch, dry matter basis. Data and sample collections were from d 29 to 35 in environmentally controlled rooms to measure methane (CH(4)) production. Methane emitted was computed from the difference in concentrations of inlet and outlet air and flux as measured 8 times per day. Control cows emitted 464 g of CH(4)/d, consumed 22.9 kg of DM/d, and produced 34.8 kg of solids-corrected milk/d and 1.3 kg of milk fat/d. Treatment with 1.3, 2.7, or 3.3% dietary CNO reduced CH(4) (449, 291, and 253 g/d, respectively), but concomitantly depressed dry matter intake (21.4, 17.9, and 16.2 kg/d, respectively), solids-corrected milk yield (36.3, 28.4, and 26.8 kg/d, respectively), and milk fat yield (1.4, 0.9, and 0.9 kg/d, respectively). The amount of NDF digested in the total tract decreased with increased dietary CNO concentrations; thus, CH(4) emitted per unit of NDF digested rose from 118 to 128, 153, and 166 g/kg across CNO treatments. Dietary CNO did not significantly affect apparent digestibility of CP but increased apparent starch digestibility from 92 to 95%. No FA C(10) or shorter were detected in feces, and apparent digestibility decreased with increasing FA chain length. Coconut oil concentrations of 2.7 or 3.3% decreased yields of milk FA C(14). The highest milk fat concentration (3.69%; 1.3% CNO) was due to the greatest yields of C(12) to C(16) milk FA. Milk FA concentrations of C(18:2 trans-10,cis-12) were related to increased dietary CNO concentrations and presumably to depressed ruminal NDF digestion. Moderate dietary CNO concentrations (e.g., 1.3%) may benefit lactational performance; however, CNO concentrations greater than or equal to 2.7% depressed dry matter intake, milk yield, milk fat yield, and NDF utilization. If mitigation of enteric CH(4) emissions is due to decreased digestion of dietary NDF, then this will lessen a major advantage of ruminants compared with nonruminants in food-production systems. Thus, CNO has limited use for enteric CH(4) mitigation in lactating dairy cows.

A novel obesity model: synphilin-1-induced hyperphagia and obesity in mice.

AIMS: The pathogenesis of obesity remains incompletely understood and the exploration of the role of novel proteins in obesity may provide important insights into its causes and treatments. Here, we report a previously unidentified role for synphilin-1 in the control of food intake and body weight. Synphilin-1, a cytoplasmic protein, was initially identified as an interaction partner of alpha-synuclein, and has implications in Parkinson's disease pathogenesis related to protein aggregation. SUBJECTS AND METHODS: To study the in vivo role of synphilin-1, we characterized a human synphilin-1 transgenic mouse (SP1) by assessing synphilin-1 expression, plasma parameters, food intake and spontaneous activity to determine the major behavioral changes and their consequences in the development of the obesity phenotype. RESULTS: Expression of human synphilin-1 in brain neurons in SP1 mice resulted in increased food intake, body weight and body fat. SP1 mice also displayed hyperinsulinemia, hyperleptinemia and impaired glucose tolerance. Pair-feeding SP1 mice to amounts consumed by non-transgenic mice prevented the increased body weight, adiposity, hyperinsulinemia and hyperleptinemia demonstrating that these were all the consequences of increased food intake. Transgenic expression of synphilin-1 was enriched in hypothalamic nuclei involved in feeding control, and fasting-induced elevated endogenous synphilin-1 levels at these sites, suggesting that synphilin-1 is an important player in the hypothalamic energy balance regulatory system. CONCLUSION: These studies identify a novel function of synphilin-1 in controlling food intake and body weight, and may provide a unique obesity model for future studies of obesity pathogenesis and therapeutics.

The E3 ubiquitin ligase specificity subunit ASB2beta is a novel regulator of muscle differentiation that targets filamin B to proteasomal degradation.

Ubiquitin-mediated protein degradation is the main mechanism for controlled proteolysis, which is crucial for muscle development and maintenance. The ankyrin repeat-containing protein with a suppressor of cytokine signaling box 2 gene (ASB2) encodes the specificity subunit of an E3 ubiquitin ligase complex involved in differentiation of hematopoietic cells. Here, we provide the first evidence that a novel ASB2 isoform, ASB2beta, is important for muscle differentiation. ASB2beta is expressed in muscle cells during embryogenesis and in adult tissues. ASB2beta is part of an active E3 ubiquitin ligase complex and targets the actin-binding protein filamin B (FLNb) for proteasomal degradation. Thus, ASB2beta regulates FLNb functions by controlling its degradation. Knockdown of endogenous ASB2beta by shRNAs during induced differentiation of C2C12 cells delayed FLNb degradation as well as myoblast fusion and expression of muscle contractile proteins. Finally, knockdown of FLNb in ASB2beta knockdown cells restores myogenic differentiation. Altogether, our results suggest that ASB2beta is involved in muscle differentiation through the targeting of FLNb to destruction by the proteasome.

Detection of anovulation by heatmount detectors and transrectal ultrasonography before treatment with progesterone in a timed insemination protocol.

Our objective was to determine the accuracy of identifying noncycling lactating dairy cows before the application of a timed artificial insemination (AI) protocol [with or without progesterone supplementation via a controlled internal drug-release (CIDR) insert and 2 different timings of AI] by using heatmount detectors and a single ovarian ultrasound examination. At 6 locations in the Midwest, 1,072 cows were enrolled in a Presynch protocol (2 injections of PGF(2alpha) 14 d apart), with the second injection administered 14 d before initiating the Ovsynch protocol (injection of GnRH 7 d before and 48 h after PGF(2alpha) injection, with timed AI at 0 or 24 h after the second GnRH injection). Heatmount detectors were applied to cows just before the first Presynch injection, assessed 14 d later at the second Presynch injection (replaced when activated or missing), and reassessed at initiation of the Ovsynch protocol. Ovaries were examined for the presence of a corpus luteum (CL) by ultrasound before the initiation of treatment. Treatments were assigned to cows based on the presence or absence of a CL detected by ultrasound: 1) no CL + no CIDR; 2) no CL + CIDR insert for 7 d; and 3) CL present. Further, alternate cows within the 3 treatments were assigned to be inseminated concurrent with the second GnRH injection of Ovsynch (0 h) or 24 h later. Pregnancy was diagnosed at 33 and 61 d after the second GnRH injection. By using low (<1 ng/mL) concentrations of progesterone in serum as the standard for noncycling status, heatmount detectors were activated on a large percentage of noncycling cows (>60%), whereas the single ultrasound examination incorrectly classified noncycling cows only 21% of the time. Conversely, cycling cows (progesterone > or =1 ng/mL) were correctly identified 70 to 78% of the time by heatmount detectors, but 85 to 92% were correctly identified by ultrasound. Overall accuracy of heatmount detectors and ultrasound was 71 and 84%, respectively. Application of progesterone to cows without a CL at the time of the first injection of GnRH reduced the incidence of ovulation but increased the proportions of pregnancies per AI at d 33 or 61 compared with nontreated cows without a CL at the onset of the Ovsynch protocol. Percentages of cows pregnant and pregnancy survival did not differ for cows having a CL before treatment compared with those not having a CL and treated with progesterone. Compared with no response, when a follicle ovulated in response to the first GnRH injection, percentage of cows becoming pregnant after the timed AI increased from 33.3 to 41.6%. Timing of AI at 0 or 24 h after the second GnRH injection did not alter pregnancies per AI, but cows having luteal activity before treatment had improved pregnancies per AI compared with noncycling cows. We conclude that identifying noncycling cows by ultrasound was more accurate than by heatmount detectors. Subsequent progesterone treatment of previously cycling cows not having a CL at the onset of Ovsynch increased the proportion of pregnant cows, equal to that of cows having a CL but not treated with progesterone.

Systemic high blood pressure and inner ear dysfunction: a preliminary study.

OBJECTIVE: To assess the association between inner ear dysfunction and retinal vascular changes related to systemic arterial hypertension. DESIGN: A comparative, cross-sectional and observational study. SETTING: Primary care. MAIN OUTCOMES MEASURES: Hearing and vestibular symptoms evaluated by a standardized questionnaire; cochlear function evaluated by audiometry and distortion product otoacoustic emissions; vestibular function evaluated by oculomotor and bithermal caloric tests and vascular retinal compromise evaluated by ophthalmoscopy (according to the modified Scheie classification). RESULTS: Forty-two subjects participated in the study, 21 with and 21 without arterial hypertension, age and sex matched; with no history of diabetes mellitus and with normal glucose levels and normal blood lipids. Although patients with hypertension reported vertigo more frequently than control subjects, conventional oculomotor and bithermal caloric tests showed no difference between the two groups. Patients with hypertension showed deterioration of hearing thresholds at 8 kHz and, compared with normotensive subjects, a higher frequency of abnormal otoacoustic emissions (P = 0.01). According to Scheie classification, 43% (95% CI: 33-53%) of the patients showed second degree retinal vascular compromise and 24% (95% CI: 15-33%) of them showed first degree compromise. The degree of the vascular retinal compromise was significantly correlated with the hearing thresholds at 8 kHz (Spearman's correlation coefficient 0.45, P = 0.002) and it was also consistent with the absence of otoacoustic emissions at frequencies between 4 and 8 kHz. CONCLUSION: The results of this preliminary study suggest that patients with systemic arterial hypertension may have cochlear dysfunction associated with the vascular disease because of hypertension, which could be silent and without clear evidence of vestibular dysfunction.

Optimizing ovulation to first GnRH improved outcomes to each hormonal injection of ovsynch in lactating dairy cows.

Ovulatory response to the first GnRH of Ovsynch is the critical determinant for successful synchronization of ovulation in dairy cows. Our objective in this study was to develop a pre-Ovsynch treatment that increased the percentage of cows that ovulated in response to the first GnRH injection of Ovsynch. To accomplish our goal, we evaluated a hormonal strategy that consisted of PGF2alpha and GnRH before the first GnRH of Ovsynch. Lactating dairy cows (n = 137) were assigned to receive either no treatment before Ovsynch (control) or 25 mg of PGF2alpha (PreP) followed 2 d later by 100 microg of GnRH (PreG), administered 4 (G4G), 5 (G5G), or 6 (G6G) d before initiating the Ovsynch protocol. Transrectal ultrasonography was performed to assess follicular size and resulting ovulation, and blood samples were collected to measure circulating concentrations of progesterone and estradiol immediately before each hormonal injection. Cows were inseminated at a fixed time 16 h after final GnRH of Ovsynch. Pregnancy diagnosis was performed 35 d later by palpation per rectum of uterine contents. Proportion of cows that ovulated to first GnRH of Ovsynch was 56.0, 66.7, 84.6, and 53.8% for G4G, G5G, G6G, and controls, respectively, and was greater for G6G than for control cows. Luteolytic response to PGF2alpha of Ovsynch was greater in all treated than control cows (92.0, 91.7, 96.2, and 69.2% for G4G, G5G, G6G, and control, respectively). Synchronization rate to Ovsynch was greater (92 vs. 69%, respectively) in G6G than in control cows. In addition, cows that ovulated in response to first GnRH of Ovsynch had greater response to PGF2alpha of Ovsynch (92.7 vs. 77.1%, respectively) and greater synchronization rate to the overall protocol (87.9 vs. 62.9%, respectively) than those that did not ovulate. Concentrations of progesterone at PGF2alpha of Ovsynch, and estradiol and follicle size at final GnRH of Ovsynch, were identified as significant predictors of probability of pregnancy 35 d after artificial insemination. In summary, a PGF2alpha-and-GnRH based pre-Ovsynch strategy consisting of a 6-d interval between PreG and first GnRH of Ovsynch resulted in a greater ovulatory and luteolytic response to first GnRH and PGF2alpha of Ovsynch, respectively, compared with control cows. This, in turn, optimized synchronization rate to Ovsynch.

Corticotropin-releasing factor neurones of the central nucleus of the amygdala mediate locus coeruleus activation by cardiovascular stress.

Hypotensive stress engages corticotropin-releasing factor (CRF) release within the rat locus coeruleus (LC), which activates LC neurones, initiating norepinephrine release in forebrain and activation of forebrain electroencephalographic activity. This study identified CRF afferents to the LC that are engaged during hypotensive stress. One of two potential CRF afferents, the central nucleus of the amygdala (CNA) or bed nucleus of the stria terminalis (BNST), was electrolytically lesioned and LC activation during hypotensive stress was quantified. Neither lesion altered LC spontaneous discharge rate or activation by intra-LC administered CRF. By contrast, LC activation by hypotensive stress was greatly attenuated in CNA-lesioned, but not BNST-lesioned, rats. Hypotensive stress-induced changes in transcriptional activation were immunohistochemically identified in CRF neurones that were retrogradely labelled from the LC region. c-fos immunoreactivity was prevalent in the paraventricular nucleus of the hypothalamus (PVN), CNA and BNST. However, only the PVN contained a substantial number of neurones that were doubly immunolabelled for CRF and c-fos, and few of these were retrogradely labelled from the LC. By contrast, immunoreactivity for the phosporylated form of cyclic AMP response-element binding protein (PCREB) was prevalent in CRF neurones in the CNA and BNST. Moreover, approximately one-third of the PCREB-expressing CRF neurones in the CNA were retrogradely labelled from the LC. These electrophysiological and anatomical findings implicate the CNA as a primary source of CRF that activates the LC during hypotensive stress. Additionally, CREB phosphorylation, rather than c-fos induction, is associated with hypotensive activation of CRF-CNA neurones that project to the LC.

Laparoscopic pericystectomy for liver hydatid cysts.

BACKGROUND: The laparoscopic approach for managing of liver echinococcosis is a controversial issue because of scarce experience worldwide. The aim of this report is to describe the technical details of our laparoscopic method and present our results. METHODS: Consecutive cases of liver echinococcosis managed by laparoscopic surgery are reported. Thoracic x-ray and abdominal ultrasound had been performed previously. The following aspects were considered as selection criteria: unique cyst located in segments III, IV, V, VI, and VIII; diameter less than 7 cm; and no evidence of infection or calcification. An evacuating puncture was performed, germinative membrane removed, and pericystectomy performed, which extirpated the pericystic structure with the surrounding liver parenchyma. Specimens were removed in a plastic bag through one of the ports. Surgical morbidity, hospital stay, time until return to work, and evidences of hydatid recurrence were measured. RESULTS: Surgery was performed on eight patients (5 women and 3 men) with a mean age of 44.9 years (range, 22-83 years) who had a liver hydatid cyst with a mean diameter of 6.6 cm (range, 5-7 cm). During a mean follow-up period of 30 months (range, 23-44 months), no morbidity or hydatid recurrence were verified. Hospital stay was 2 days in all cases, and return to work was within 15 days. CONCLUSION: This laparoscopic technique, applied with selective criteria, can be a useful alternative for treating patients with liver hydatidosis because its results are comparable with those for open surgery studies involving similar follow-up time.

Vitamin A controls epithelial/mesenchymal interactions through Ret expression.

Mutations or rearrangements in the gene encoding the receptor tyrosine kinase RET result in Hirschsprung disease, cancer and renal malformations. The standard model of renal development involves reciprocal signaling between the ureteric bud epithelium, inducing metanephric mesenchyme to differentiate into nephrons, and metanephric mesenchyme, inducing the ureteric bud to grow and branch. RET and GDNF (a RET ligand) are essential mediators of these epithelial-mesenchymal interactions. Vitamin A deficiency has been associated with widespread embryonic abnormalities, including renal malformations. The vitamin A signal is transduced by nuclear retinoic acid receptors (RARs). We previously showed that two RAR genes, Rara and Rarb2, were colocalized in stromal mesenchyme, a third renal cell type, where their deletion led to altered stromal cell patterning, impaired ureteric bud growth and downregulation of Ret in the ureteric bud. Here we demonstrate that forced expression of Ret in mice deficient for both Rara and Rarb2 (Rara(-/-)Rarb2(-/-)) genetically rescues renal development, restoring ureteric bud growth and stromal cell patterning. Our studies indicate the presence of a new reciprocal signaling loop between the ureteric bud epithelium and the stromal mesenchyme, dependent on Ret and vitamin A. In the first part of the loop, vitamin-A-dependent signals secreted by stromal cells control Ret expression in the ureteric bud. In the second part of the loop, ureteric bud signals dependent on Ret control stromal cell patterning.

[Lack of sensitivity to per-anesthetic malignant hyperthermia in 32 patients who developed neuroleptic malignant syndrome]. / Absence de sensibilité à l'hyperthermie maligne peranesthésique chez 32 patients ayant développé un syndrome malin des neuroleptiques.

The aim of this study was to verify whether a relationship exists between neuroleptic malignant syndrome (NMS) and anaesthetic-induced malignant hyperthermia (MH) or not. The in vitro halothane-caffeine tests were performed on muscle tissue obtained from 32 patients with documented NMS episodes. The diagnosis of NMS relied on Levenson's criteria. The results, expressed in accordance with the criteria of the European MH Group, defined 29 subjects as MH non-susceptible. Three patients were classified as MH equivocal. These findings demonstrate the lack of any link between NMS and MH. Therefore, patients with a history of NMS are not likely to be at risk of developing MH and special measures against MH are not required for anaesthesia in these patients.

Fiber-type caffeine sensitivities in skinned muscle fibers from humans susceptible to malignant hyperthermia.

BACKGROUND: The response to contracture tests may depend upon the relative proportion of muscle fiber types within the muscle specimen. To determine whether a difference in fiber-type caffeine sensitivities exists between malignant hyperthermia susceptible (MHS) and malignant hyperthermia-nonsusceptible (MHN) skeletal muscle, we compared the fiber-type caffeine sensitivities in chemically skinned muscle fibers dissected from vastus lateralis muscle from 15 MHS and 16 MHN patients. METHODS: Muscle fiber type was determined in each fiber by the difference in strontium-induced tension measurements and in 36 fibers, after contracture testing, by ATPase enzyme histochemistry. Caffeine sensitivity was defined as the threshold concentration inducing more than 10% of the maximal tension obtained with a calcium 1.6 x 10(-2) mM solution. RESULTS: Significant difference in the mean (+/- SD) caffeine sensitivity was found between type I MHS fibers (2.63 +/- 0.85 mM) versus type II MHS fibers (3.47 +/- 1.2 mM) and between type I MHN fibers (5.89 +/- 1.8 mM) versus type II MHN fibers (10.46 +/- 2.6 mM). The mean (+/- SD) caffeine sensitivities for a given muscle fiber type (I or II) were different between groups of MHS and MHN patients. Both type I and II MHS fibers had significantly lower caffeine sensitivities, and this increase in caffeine sensitivity was significantly smaller in type I than in type II fiber. CONCLUSIONS: The current study indicates that a truly MHS patient cannot have a false-negative result solely related to abnormal type II fibers contained in a given muscle strip. Although the occurrence of a very high proportion of type I fibers in MHN human muscle could result in a false-positive contracture outcome, such an occurrence is expected to be rare.

Surgical correction of severe Peyronie's disease without plaque excision.

We report 7 cases of severe Peyronie's disease treated with a modified surgical technique of the one described in 1989. This second version consists of making only one I-shaped incision on the dorsal face of the penis, in order to relax and create a defect in the tunica albuginea, which is then covered with a patch of human lyophilized dura mater. The plastic and sexual results were identical to the ones described previously, but the operative time was shortened. This type of surgery is indicated to correct severe angulation and shortening of the penis in men with normal sexual lives.