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BackgroundLanadelumab demonstrated efficacy in preventing hereditary angioedema (HAE) attacks in the phase 3 HELP Study.ObjectiveTo assess time to onset of effect and long-term efficacy of lanadelumab, based on exploratory findings from the HELP Study.MethodsEligible patients with HAE type I/II received lanadelumab 150 mg every 4 weeks (q4wks), 300 mg q4wks, 300 mg q2wks, or placebo. Ad hoc analyses evaluated day 0-69 findings using a Poisson regression model accounting for overdispersion. Least-squares mean monthly HAE attack rate for lanadelumab was compared with placebo. Intrapatient comparisons for days 0-69 versus steady state (days 70-182) used a paired t test for continuous endpoints or Kappa statistics for categorical endpoints.ResultsOne hundred twenty-five patients were randomized and treated. During days 0-69, mean monthly attack rate was significantly lower with lanadelumab (0.41-0.76) vs placebo (2.04), including attacks requiring acute treatment (0.33-0.61 vs 1.66) and moderate/severe attacks (0.31-0.48 vs 1.33, all P ≤ .001). More patients receiving lanadelumab vs placebo were attack free (37.9%-48.1% vs 7.3%) and responders (85.7%-100% vs 26.8%). During steady state, the efficacy of lanadelumab vs placebo was similar or improved vs days 0-69. Intrapatient differences were significant with lanadelumab 300 mg q4wks for select outcomes. Lanadelumab efficacy was durable-HAE attack rate was consistently lower vs placebo, from the first 2 weeks of treatment through study end. Treatment emergent adverse events were comparable during days 0-69 and 70-182.ConclusionProtection with lanadelumab started from the first dose and continued throughout the entire study period.

Background: Acquired cold urticaria (ACU) is a form of physical urticaria that has been treated with first-generation antihistamines; there is a paucity of data regarding second- and third-generation antihistamines for the treatment of ACU., Objective: To perform a systematic review of the literature to determine the efficacy of second- and third-generation antihistamines in the treatment of ACU., Methods: Data were extracted via a MEDLINE search of the literature between 1950 and May 2009. We included double-blind, randomized, placebo-controlled studies comparing the treatment of patients with ACU with second- and third-generation antihistamine medications vs placebo., Results: Overall, 98 patients were identified from 4 included studies. Two trials indicated that second- and third-generation antihistamines significantly eliminated the presence of wheals after treatment vs placebo (odds ratio [OR], 8.88; 95% confidence interval [CI], 4.35 to 18.13). Two trials demonstrated a reduction in wheal area after treatment with a second- or third-generation antihistamine compared with placebo (mean difference, -347.99 mm2; 95% CI, -489.43 to -206.54 mm2). Two trials demonstrated significant elimination of pruritus with second- or third-generation antihistamine treatment vs placebo (OR, 10.44; 95% CI, 4.39 to 24.84). All 4 studies assessed the tolerability of a second- or third-generation antihistamine vs placebo and found an increased rate of adverse events (OR, 3.04; 95% CI, 1.53 to 6.06), although the complaints were mild., Conclusions: The newer, less-sedating antihistamines seem to be effective in the treatment of ACU in terms of their ability to significantly reduce the presence of wheals and pruritus after cold exposure. These medications are usually well tolerated, with only mild adverse effects.

With differing treatment guidelines available from many sources, collaborating advanced practice nurses and physicians at this facility recognized the need for one clear, acceptable set. Survey results show that clinicians incorporate all or most of the guidelines into practice (91%).

Extra genetic material that is euchromatic is generally regarded to be associated with phenotypic abnormalities. However, recent studies suggest that this is not always the case. Chromosome analysis was performed on amniotic fluid cells from a 37-year-old phenotypically normal patient referred for advanced maternal age. All the cells analysed showed a karyotype of 46,XY,1p+. The 1p+ chromosome had extra genetic material of uncertain origin in chromosome band region 1p21-->31. Chromosome analysis on the father revealed a normal 46,XY male karyotype. The mother's karyotype showed the same 1p+ chromosome. C and Q banding, as well as silver staining studies, in both the mother and the fetus support the interpretation that the extra chromosomal material was euchromatic in nature. This 1p+ chromosome may be characterized as a euchromatic heteromorphism. Euchromatic heteromorphisms not associated with phenotypic abnormalities have been reported for chromosomes 9 and 16. To the best of our knowledge, this is the first report involving this type of cytogenetic anomaly on chromosome number 1 in a phenotypically normal mother and infant.

Bladder catheterization is widely employed for laparoscopic cholecystectomy. Fifty consecutive laparoscopic cholecystectomies were performed without bladder catheterization. Patients were asked to void shortly before induction of anesthesia to ensure that the bladder was empty. Postoperative bladder catheterization for urinary retention was required in 3 of the 50 patients. Routine bladder catheterization for laparoscopic cholecystectomy is unnecessary, and its elimination will reduce costs, urethral trauma, and nosocomial urinary tract infections.

The sequence of centromere separation of mitotic chromosomes derived from lymphocytes of 17 individuals of various ages was studied. A comparison of the mean CSI (centromeric separation index) values for individual chromosomes in the complement indicated a significant difference between the older and the younger subjects only with regard to the chromosome nos. 6, 11, and 19 in both sexes and the X chromosome exclusively in the female. With age, chromosome no. 6 in both males and females and the X chromosome in females showed premature centromeric separation whereas chromosome nos. 11 and 19 in both males and females displayed delayed centromeric separation. Our study, therefore, indicates that changes in the sequence of centromeric separation of certain chromosomes do occur in lymphocytes during chronological aging in humans.

The relative effect of five commonly used culture media (MEM, BME, McCoy's 5A, M199 and HMEM) on the population doubling level (PDL), nuclear volume and nuclear morphology was examined during in vitro senescence of WI-38 human fetal fibroblasts. Statistical analyses showed that cells grown in M199 had a significantly lower PDL than that of cells cultured in any other medium. The PDL in McCoy's 5A was significantly lower compared to that in BME, MEM and HMEM. Cells grown in BME, MEM and HMEM showed similar PDL. It was found that the nuclei of aged cells grown in M199 were significantly larger in volume than cells aged in any other medium. The average increases in nuclear volume of cells during aging in BME, MEM and McCoy's 5A were statistically equivalent. The increase in nuclear volume in HMEM was significantly smaller than that of cells aging in M199 and was longer than that of cells aging in BME or MEM. Linear regression analysis showed that there was a linear increase in nuclear volume as a function of PDL for cells aged in all five media. However, the rate of increase in nuclear volume with increasing PDL varied from medium to medium. There was no significant difference between media on induction of abnormal nuclear morphology as related to PDL. The relative effects of all five media were not uniform on the three cellular parameters investigated during in vitro aging of WI-38 cells. It is, therefore, suggested that one should keep this medium differential in mind to allow meaningful comparison of possible changes in various morphological parameters during in vitro senescence of diploid human fibroblasts such as WI-38.

It has been suggested that patients sustaining blunt chest injury severe enough to result insignificant bony injury to the thorax may have traumatic aneurysms of the thoracic aorta in the absence of th widened mediastinum on plain film. To test the validity of this hypothesis, we performed aortograms on 14 patients with severe blunt chest injury but an otherwise normal chese X-ray. None of these patients was found to have an aortic injury. By contrast, of 21 patients with severe chest injury and a widened mediastinum who underwent thoracic aortography eight were found to have traumatic aneurysms of the thoracic aorta. These results suggest that in the absence of a widened mediastinum, severe chest wall injury is not an indication for aortography.

The brainstem auditory evoked response (BAER) was evaluated as an aid in the early diagnosis and prognosis of 17 comatose blunt head-injury patients. Click stimuli (60 dBSL, 10/sec) were presented monaurally through headphones. BAER's were recorded between Cz and ipsilateral mastoid; contralateral mastoid ground. No BAER waves occurred in three "brain-dead" patients. Two patients with initially abnormal BAER's did not show improvement in followup recordings, and died of their brain injuries. Recovery occurred in 12 patients with normal followup BAER's, regardless of whether initial BAER's had been abnormal (three patients) or normal (nine patients). Apparently, initial BAER's (mean, 31 hours postinjury) can be abnormal as the result of reversible damage. Followup BAER's (3 to 6 days postinjury) did correspond with patient outcome at a time when clinical prognoses were often uncertain. BAER's aided diagnostically in determining the extent of brainstem damage and the effectiveness of treatment.

Nine patients on intermittent mandatory ventilation (IMV) and continuous positive airway pressure (CPAP) were allowed to breathe spontaneously at varying end expiratory pressure-end inspiratory pressure (EEP-EIP) gradients up to 10 cm H2O. There was no change in the mean cardiac output and oxygen delivery despite a lowered mean airway pressure (MAWP) when the gradient was increased. Three patients were uncomfortable at the higher gradients and another manifested evidence of fatigue of the muscles of respiration by raising her arterial PCO2 (PaCO2) and intrapulmonary shunt (Qs/Qt). In view of the difficulty experienced by some patients and lack of improvement in cardiac outputs (CO) during spontaneous inspiration when the EEP-EIP gradient is raised from zero to 5 and 10 cm H2O, it is recommended that the variation in airway pressure during spontaneous breaths while a patient is on CPAP be minimized.

Philadelphia (Ph) chromosome negative chronic myeloid leukemia (CML) can be distinguished from clinically similar disorders on the basis of the presence of rearrangement of the breakpoint cluster region (bcr) of chromosome 22. We have identified six patients with Ph-negative CML, each with bcr rearrangement. Apparently normal karyotypes were observed in two cases, and a third contained a rearrangement that did not appear to involve chromosomes 9 or 22. The other three cases had translocations involving chromosome band 9q34 but no case contained the common derivative chromosome 9pter----9q34::22q11----22qter. One case appeared to contain either a deletion of an unrearranged bcr locus in approximately 50% of cells or duplication of rearranged bcr, both 5' and 3' of the chromosome 22 breakpoint. Considerable complexity exists in the types of genetic changes that can juxtapose bcr and the c-abl oncogene in CML. Based on the molecular and cytogenetic analyses of these and other cases described in the literature, we conclude that most cases of true Ph-negative CML arise from submicroscopic genetic exchanges rather than masking of simple t(9;22)(q34;q11) translocations by secondary rearrangements.

The relative effect of five commonly used culture media (MEM, BME, McCoy's 5A, M199 and HMEM) on the average nucleolar number/cell, the average volume/nucleolus and the total nucleolar volume/cell was examined during in vitro senescence of WI-38 human fetal fibroblasts. Statistical analyses show that cells aging in MEM show a higher number of nucleoli/cell than that of cells aging in any other medium. For cells aging in the other four media, there are no significant differences in the average number of nucleoli/cell. Linear regression analysis shows that in all cases there is a linear decrease in the average number of nucleoli/cell as a function of PDL. Statistical analyses show that the average volume/nucleolus is significantly greater for cells aging in M199 than in any other medium. Cells aging in HMEM show smaller average nucleolar volume than cells aging in M199, but display larger volumes than that of cells aged in BME, McCoy's 5A, or MEM. Cells aging in BME and McCoy's 5A media show no significant difference among each other in terms of average nucleolar volume, but a difference in this parameter is noted in cells aging in BME and MEM. A linear regression analysis shows that the average volume/nucleolus increases linearly as a function of age for cells grown in all five media. Analysis of the total nucleolar volume/cell in the five media shows that cells aging in M199 and HMEM are not significantly different from each other in terms of this variable, but show significantly larger volumes than those of cells aging in BME, McCoy's 5A and MEM. Cells aging in BME, McCoy's 5A and MEM display no significant difference with regard to this parameter. Linear regression analysis shows a positive linear relationship between the PDL and the total nucleolar volume/cell. The relative effects of all five media are not the same on the three cellular variables studied during in vitro aging of WI-38 cells. We, therefore, suggest that one should note this medium differential in order to allow meaningful comparison of results on possible changes in various morphological parameters during in vitro senescence of diploid human fibroblasts.

Thirty consecutive patients sustaining splenic injury from blunt abdominal trauma were evaluated as to the feasibility of performing splenorrhaphy rather than splenectomy. Twenty-four patients were over 14 years of age. The procedure to be performed was decided intraoperatively. Twelve patients required a splenectomy, and 18 patients had all or a portion of the injured spleen salvaged. The two groups were similar in age, mechanism of injury, and associated injuries. Nine of the 18 salvaged spleens required only debridement and the topical application of Avitene for hemostasis. The remaining nine patients required more extensive procedures including hemisplenectomy (three) and partial splenectomy (three); three patient patients required oversewing of bleeding splenic surfaces and the ligation of vessels without removal of splenic tissue. There were no differences in the number of blood transfusions required by the two groups. There were no postoperative complications resulting from the splenorrhaphy. Sixteen of the 18 who underwent splenorrhaphy were studied postoperatively by spleen scan. In all cases functioning splenic tissue was found consistent with the operative findings and procedure.

This report presents a patient with bilateral scapular fractures resulting from an accidental electric shock (440 volt, 60 cps current). This appears to be a previously unreported injury. A postulated mechanism of injury is discussed.

Two patients who sustained severe anorectal trauma from "fist fornication" were treated by irrigation, colostomy, drainage, antibiotics, and primary repair of the rectum and anal sphincters without complications. Both had complete return of continence. Primary sphincter repair is advocated for these and similar anorectal injuries.