Monoclonal antibodies reveal circulating growth hormone of high molecular weight not detectable by conventional assays

A radioimmunoassay based on a monoclonal antibody. Mc-ab 1, which was raised against growth hormone but cross-reacted with human placental lactogen yielded higher GH immunoreactivity levels in serum than one based on a polyclonal antiserum. This discrepancy was noted in subjects with normal GH secretion as well as in patients with GH insufficiency. To characterize this GH immunoreactivity detected by Mc-ab 1, affinity purification and molecular sieve chromatography of serum were performed. High molecular weight proteins with GH immunoreactivity were found with both techniques. These proteins were associated with carbohydrates. Affinity cross-linking showed specific binding of radiolabelled GH to high molecular weight proteins in the serum. After fractionation of serum, the GH immunoreactivity became detectable by the polyclonal antiserum assay as well as by an immunoradiometric assay. GH immunoreactive material with an approximate mass of 80 kD was subjected to isoelectric focusing. When GH immunoreactive fractions at pH 5 were re-chromatographed, GH immunoreactivity was recovered in the elution volume corresponding to monomeric GH. Our results show that sera from normal subjects as well as from patients with deficient GH secretion contain notable amounts of high molecular weight GH which is undetectable by antibodies generally used for GH measurements, but which can be revealed after fractionation of serum.     

Comprehensive Treatment of Periorbital Region with Hyaluronic Acid

The periorbital subunit is one of the first facial regions to show signs of aging, primarily due to volume depletion of the soft tissue and bony resorption. Surgical and office-based nonsurgical procedures form an important basis for periorbital rejuvenation. It is important to make a detailed clinical evaluation of the patient to indicate the most appropriate procedure to be performed. With the objective of showing a nonsurgical procedure for the rejuvenation of the periorbital area, the authors describe a technique of applying fillers in the upper and lower periorbital regions, paying attention to the anatomy of this facial region and the type of product to be used besides the expected results of the procedure and its possible adverse effects and complications. The nonsurgical rejuvenation of the periorbicular region with hyaluronic acid is a new and innovative technique. In the opinion of the authors, it is a great aesthetic impact area and consequently brings high satisfaction to patients.Maintaining a youthful and pleasant appearance of the face in today’s culture impacts quality of life in many patients. The facial contour remodeling is being revolutionized by new nonsurgical techniques.Facial aging is a complex and dynamic process. All people age differently as a result of imbalance, disharmony, and disproportion of the aging process between the overlying soft tissue and the underlying bony frameworks.1 The upper periorbital subunit is one of the first facial regions to show signs of aging, and even minor changes in its structure and volume can distort the perceived emotions and health of patients.2 An aesthetic and youthful upper periorbital subunit is characterized by a well-defined brow of appropriate height and shape, fullness of the upper periorbit, a crisp and well-defined upper eyelid crease, minimal skin excess, and good skin quality.3,4In the aging process of this facial area, one group of patients displays signs of aging due predominantly to soft tissue ptosis of the upper eyelid, requiring surgical excision. Another group presents with volume depletion of the soft tissue and bony resorption of the orbit. The loss of septal support, leading to brow prolapse and an exacerbation of upper eyelid fullness and congestion, can also contribute to the aging process. This appearance is characterized by deflation of the upper eyelid as well as hollowing and visibility of the supraorbital bony rim, leading to a sunken, hollow, and skeletonized orbit, which can make the patient appear sickly, anorexic, and old. In recent years, modern facial rejuvenation surgery has evolved toward volume restoration in addition to tissue suspension.2Comprehensive analysis of both soft tissue and bony structural changes are essential for the periorbital rejuvenation. Surgical procedures and office-based nonsurgical procedures form an important basis for periorbital rejuvenation, including cosmeceuticals, chemical peels, laser and light treatments, neurotoxins, and fillers. Improved understanding of the pathophysiology of aging and technical advancements in nonsurgical techniques has enabled us to achieve better and more comprehensive improvement for patients.5     

Delayed-type Necrosis after Soft-tissue Augmentation with Hyaluronic Acid

The growing use of dermal fillers, specifically the use of hyaluronic acid, can be explained by their effectiveness and versatility as well as their favorable safety profiles. Nevertheless, early and late complications with varying levels of severity may occur. The incidence of complications is low and the majority of adverse events are mild (edema, erythema, and local ecchymosis) and of limited duration. However, more severe events, such as ischemia and necrosis, may occur. The symptoms of ischemia can occur immediately after the injection or several hours after the procedure. Here, the authors report three cases of necrosis after hyaluronic acid injection with the first symptoms presenting only several hours after the procedure. The patients were treated immediately after the diagnosis. The aim of this review is to communicate the possibility of the delayed-type presentation of necrosis, present the signs and symptoms that lead to early diagnosis, and review the treatment possibilities of this severe complication.Dermal fillers have been injected with increasing frequency over the past three decades for soft-tissue augmentation by volume expansion in the management of the aging face. In 2012, there were about two million procedures using dermal fillers, according to the American Society of Plastic Surgeons, five percent more than in 2011 and 205 percent more than in 2000, second only to botulinum toxin type A. These minimally invasive and nonsurgical cosmetic procedures were the two most commonly performed in this range of time studied.1,2The growing use of dermal fillers, specifically the use of hyaluronic acid (HA), can be explained by their effectiveness and versatility as well as their favorable safety profiles. Nevertheless, early and late complications with varying levels of severity may occur. The incidence of complications is low and the majority of adverse events are mild (edema, erythema, and local ecchymosis) and of limited duration. However, more severe events, such as ischemia and necrosis, may occur.Injection necrosis is a rare, but important, complication associated with dermal fillers. Necrosis can be attributed to one of two factors—an interruption of vascular supply due to compression or frank obstruction of vessels by direct injection of the material into a vessel itself. The glabella is the injection site commonly believed to be at greater risk for necrosis, but it can also occur at the nasolabial fold.3 Risk factors for intravascular injection include site of application (deep injection of filler products at or near the site of named vessels), volume applied (larger amounts of product can cause a proportionally greater degree of arterial obstruction), and previous scarring (deep tissue scars may stabilize and fix arteries in place, making them easier to penetrate with small sharp needles).4The initial presentation of vascular events may include pain and discomfort disproportionate to what is typically experienced following filler treatments and clinical findings, including blanching, livedo pattern, or violaceous discoloration.4 Although many cases report this immediate post-injection presentation as the typical background seen in a necrosis event, there are few reports with the first symptom presenting only hours after augmentation. See Figures 1 through ​through3,3, where the authors present three cases of vascular compromise after soft-tissue augmentation with delayed-type presentation. Open in a separate windowOpen in a separate windowFigures 2Aand 2B.Case 2: Necrosis and secondary infection 48 hours after the HA injection (a). Discrete scars in the affected area after treatment (b). Open in a separate windowOpen in a separate windowFigures 1Aand 1B.Case 1: Edema, erythema, and progressive violaceous reticulated patch, livedoid area were observed on the left cheek 36 hours after the injection (a). Complete healing five days after hyaluronidase application and nine days after the HA injection (b). Open in a separate windowOpen in a separate windowFigures 3Aand 3B.Case 3: Necrosis and secondary infection 48 hours after the HA injection (a). Erythema, hipercromia, and discreet scars in the affected area after treatment (b).     

Radiography in acute ankle injuries: the Ottawa Ankle Rules versus local diagnostic decision rules

STUDY OBJECTIVE: We validate the Ottawa Ankle Rules and 2 Dutch ankle rules in distinguishing clinically significant fractures from insignificant fractures and other injuries in patients with a painful ankle presenting to the emergency department. METHODS: This prospective comparison of 3 ankle rules was conducted in the ED of a 580-bed community teaching hospital in Amsterdam from January 1998 to April 1999. Participants included 647 consecutive patients aged 18 years or older presenting with a painful ankle after trauma. All physicians received extensive and pictorial training on how to correctly score the respective items of the rules. The physician on call recorded these items derived from history and physical examination on a standardized data sheet. All patients subsequently underwent standard radiographic assessment. A radiologist and a trauma surgeon evaluated the radiographs blinded from the results of the data sheet form and the treatment given. The diagnostic performance of the 3 rules was measured in terms of sensitivity, specificity, and the reduction of radiographs. Receiver operating characteristic (ROC) curves were constructed, and the area under the ROC curves was calculated and compared. RESULTS: Seventy-four fractures were seen, of which 41 were clinically significant. The Ottawa Ankle Rules had a sensitivity of 98% for identifying clinically significant fractures; the local rules scored 88% and 59%, respectively. The potential savings in radiographs for the 3 decision rules were 24%, 54%, and 82%, respectively. The area under the ROC curve was better for both the local rules (0.84 and 0.83) compared with the Ottawa Ankle Rules (0.76). CONCLUSION: Because the identification of all relevant fractures is more important than a reduction in radiographs, the higher sensitivity of the Ottawa Ankle Rules makes these most suitable for implementation in The Netherlands.     

Accuracy of supplementary serologic testing for human T-lymphotropic virus types I and II in US blood donors. Retrovirus Epidemiology Donor Study

Blood donations in the United States have been screened for antibody to human T-lymphotropic virus type I (HTLV-I) by HTLV-I enzyme immunoassay (EIA) since November 1988. Specimens repeatedly found to be reactive by EIA undergo confirmation by supplementary serologic tests. We assessed the accuracy of blood center testing of 994 HTLV-I EIA repeat-reactive specimens in five US blood centers between November 1988 and December 1991. Of 410 confirmed HTLV-I/II donations, 407 (99.3%) were infected with HTLV-I/II, as determined by polymerase chain reaction (PCR) (403 cases) and by repeat serologic testing (4 cases). The three false- positive results occurred in the first year of testing. Of 425 HTLV- indeterminate specimens, 6 (1.4%) were found to be infected by PCR (5 with HTLV-II and 1 with HTLV-I). None of 159 confirmatory test-negative donations was PCR positive. Of HTLV-I/II-seropositive specimens, 80.2% to 95.4% could be typed as HTLV-I or HTLV-II by type-specific serologic assays. These results support recommendations that HTLV-I/II- seropositive donors should be advised that they are infected with HTLV- I, HTLV-II, or HTLV-I/II (depending on results of type-specific assays). HTLV-indeterminate donors should be advised that their results only rarely indicate HTLV infection. HTLV confirmatory test-negative donors should be reassured that they are not infected with HTLV-I or HTLV-II.     

Early oral feeding after pancreatoduodenectomy enhances recovery without increasing morbidity

Objective

The aim of this study was to evaluate whether a change in the routine feeding strategy applied after pancreatoduodenectomy (PD) from nasojejunal tube (NJT) feeding to early oral feeding improved clinical outcomes.

Methods

An observational cohort study was performed in 102 consecutive patients undergoing PD. In period 1 (n = 51, historical controls), the routine postoperative feeding strategy was NJT feeding. This was changed to a protocol of early oral feeding with on-demand NJT feeding in period 2 (n = 51, consecutive prospective cohort). The primary outcome was time to resumption of adequate oral intake.

Results

The baseline characteristics of study subjects in both periods were comparable. In period 1, 98% (n = 50) of patients received NJT feeding, whereas in period 2, 53% (n = 27) of patients did so [for delayed gastric empting (DGE) (n = 20) or preoperative malnutrition (n = 7)]. The time to resumption of adequate oral intake significantly decreased from 12 days in period 1 to 9 days in period 2 (P = 0.015), and the length of hospital stay shortened from 18 days in period 1 to 13 days in period 2 (P = 0.015). Overall, there were no differences in the incidences of complications of Clavien–Dindo Grade III or higher, DGE, pancreatic fistula, postoperative haemorrhage and mortality between the two periods.

Conclusions

The introduction of an early oral feeding strategy after PD reduced the time to resumption of adequate oral intake and length of hospital stay without negatively impacting postoperative morbidity.     

Australian consensus guidelines for the safe handling of monoclonal antibodies for cancer treatment by healthcare personnel

These consensus guidelines provide recommendations for the safe handling of monoclonal antibodies. Definitive recommendations are given for the minimum safe handling requirements to protect healthcare personnel. The seven recommendations cover: (i) appropriate determinants for evaluating occupational exposure risk; (ii) occupational risk level compared with other hazardous and non‐hazardous drugs; (iii) stratification of risk based on healthcare personnel factors; (iv) waste products; (v) interventions and safeguards; (vi) operational and clinical factors and (vii) handling recommendations. The seventh recommendation includes a risk assessment model and flow chart for institutions to consider and evaluate clinical and operational factors unique to individual healthcare services. These guidelines specifically evaluated monoclonal antibodies used in the Australian cancer clinical practice setting; however, the principles may be applicable to monoclonal antibodies used in non‐cancer settings. The guidelines are only applicable to parenterally administered agents.