Retrosternal herniation of transverse colon following minimal invasive esophagectomy causing dysphagia: A case report.

INTRODUCTION AND IMPORTANCE: Minimally invasive esophagectomy has emerged as the established standard for treating esophageal cancer. The gastric graft is usually placed in the posterior mediastinum or the retrosternal tunnel for reconstruction. Hiatal hernia occurrence is more common in the posterior mediastinal reconstruction and is more frequently observed in laparoscopic compared to open approach. On the other hand, retrosternal hernia is a rare complication that deserves greater attention, considering the increasing popularity of retrosternal reconstruction in esophageal cancer treatment. CASE PRESENTATION: We present the case of a 55-year-old male patient who underwent minimally invasive esophagectomy with retrosternal reconstruction using gastric conduit and cervical anastomosis. After four years, the patient experienced symptoms, including dyspnea and chest pain. CT scan revealed transverse colon herniation into the retrosternal tunnel. CLINICAL DISCUSSION: Our diagnosis was retrosternal herniation of the transverse colon. Although there was no sign of obstruction, the abundant colon in the retrosternal space caused mass effect symptoms. For that reason, we performed laparoscopic surgery to release the herniated organ and close the hernia hole. Postoperatively, the patient had a satisfactory recovery, and a follow-up CT scan confirmed the absence of any remaining herniated organs. CONCLUSION: While hiatal hernia is a well-known complication in minimally invasive esophagectomy, retrosternal hernia is a lesser-known entity. Surgical intervention is necessary to alleviate symptoms caused by herniation or address complications such as strangulation. The occurrence of retrosternal hernia warrants further attention and research in the future.

Are we closer to a standard of care for Richter's syndrome? Novel treatments on the horizon.

INTRODUCTION: The therapeutic landscape for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has significantly evolved over the past decade with dramatically improved outcomes with the introduction of targeted therapies. This unfortunately has not been the case for Richter transformation (RT), the histologic transformation to a more aggressive lymphoma, most typically diffuse large B-cell lymphoma (DLBCL). As such, RT continues to be one of the most challenging complications of CLL/SLL. Historically, RT has a poor response to treatment, with a minority reaching complete remission (CR) and overall survival (OS) being less than a year. AREAS COVERED: The focus of this review is to discuss the effectiveness of commonly used regimens, and review existing data for emerging regimens being examined in ongoing clinical trials to improve prognosis and outcomes in patients with RT. Despite extensive efforts to optimize therapies for RT, there is still no generalized consensus on either first-line treatment regimens or regimens in the relapsed/refractory setting. RT continues to carry a high mortality rate without durable response to current therapeutic agents. EXPERT OPINION: Ongoing and future research may identify novel treatment approaches that will eventually improve outcomes for patients with RT. The optimal care for RT patients is a clinical trial, when feasible.

Baseline Sequencing Surveillance of Public Clinical Testing, Hospitals, and Community Wastewater Reveals Rapid Emergence of SARS-CoV-2 Omicron Variant of Concern in Arizona, USA.

The adaptive evolution of SARS-CoV-2 variants is driven by selection for increased viral fitness in transmissibility and immune evasion. Understanding the dynamics of how an emergent variant sweeps across populations can better inform public health response preparedness for future variants. Here, we investigated the state-level genomic epidemiology of SARS-CoV-2 through baseline genomic sequencing surveillance of 27,071 public testing specimens and 1,125 hospital inpatient specimens diagnosed between November 1, 2021, and January 31, 2022, in Arizona. We found that the Omicron variant rapidly displaced Delta variant in December 2021, leading to an "Omicron surge" of COVID-19 cases in early 2022. Wastewater sequencing surveillance of 370 samples supported the synchronous sweep of Omicron in the community. Hospital inpatient COVID-19 cases of Omicron variant presented to three major hospitals 10.51 days after its detection from public clinical testing. Nonsynonymous mutations in nsp3, nsp12, and nsp13 genes were significantly associated with Omicron hospital cases compared to community cases. To model SARS-CoV-2 transmissions across the state population, we developed a scalable sequence network methodology and showed that the Omicron variant spread through intracounty and intercounty transmissions. Finally, we demonstrated that the temporal emergence of Omicron BA.1 to become the dominant variant (17.02 days) was 2.3 times faster than the prior Delta variant (40.70 days) or subsequent Omicron sublineages BA.2 (39.65 days) and BA.5 (35.38 days). Our results demonstrate the uniquely rapid sweep of Omicron BA.1. These findings highlight how integrated public health surveillance can be used to enhance preparedness and response to future variants. IMPORTANCE SARS-CoV-2 continues to evolve new variants throughout the pandemic. However, the temporal dynamics of how SARS-CoV-2 variants emerge to become the dominant circulating variant is not precisely known. Genomic sequencing surveillance offers unique insights into how SARS-CoV-2 spreads in communities and the lead-up to hospital cases during a surge. Specifically, baseline sequencing surveillance through random selection of positive diagnostic specimens provides a representative outlook of the virus lineages circulating in a geographic region. Here, we investigated the emergence of the Omicron variant of concern in Arizona by leveraging baseline genomic sequence surveillance of public clinical testing, hospitals, and community wastewater. We tracked the spread and evolution of the Omicron variant as it first emerged in the general public, and its rapid shift in hospital admissions in the state health system. This study demonstrates the timescale of public health preparedness needed to respond to an antigenic shift in SARS-CoV-2.

Opioid toxicity: histamine, hypersensitivity, and MRGPRX2.

Insights into the pathophysiology of many non-immune-mediated drug reactions referred to as toxicities, sensitivities, intolerances, or pseudoallergies have resulted from research identifying the mastocyte-related G-protein-coupled receptor (GPCR) member X2 (MRGPRX2), a human mast cell receptor mediating adverse reactions without the involvement of antibody priming. Opioid-induced degranulation of mast cells, particularly morphine, provoking release of histamine and other preformed mediators and causing hemodynamic and cutaneous changes seen as flushing, headache and wheal and flare reactions in the skin, is an example of results of MRGPRX2 activation. Opioids including morphine, codeine, dextromethorphan and metazocine as well as endogenous prodynorphin opioid peptides activate MRGPRX2 at concentrations causing mast cell degranulation. Unlike the canonical opioid receptors, MRGPRX2 shows stereochemical recognition preference for dextro rather than levo opioid enantiomers. Opioid analgesic drugs (OADs) display a range of histamine-releasing potencies from the strong releaser morphine to doubtful releasers like hydromorphone and the non-releaser fentanyl. Whether there is a correlation between histamine release by individual OADs, MRGPRX2 activation, and presence or absence of adverse cutaneous effects is not known. To investigate the question, ongoing research with recently pursued methodologies and strategies employing basophil and mast cell tests resulting from MRGPRX2 insights should help to elucidate whether or not an opioid's histamine-releasing potency, and its property of provoking an adverse reaction, are each a reflection of its activation of MRGPRX2.

Lower Plasma Albumin, Higher White Blood Cell Count and High-Sensitivity C-Reactive Protein are Associated with Femoral Artery Intima-Media Thickness Among Newly Diagnosed Patients with Type 2 Diabetes Mellitus.

Introduction: Low albumin levels, high levels of high-sensitivity C-reactive protein (hs-CRP), and high white blood cell count were risk factors for changes in arterial intima-media thickness (IMT). Femoral artery IMT damages were one of the common peripheral artery type 2 diabetes. This study was conducted to determine the association between femoral artery IMT and plasma albumin, hs-CRP levels, and white blood cell count in newly diagnosed patients with type 2 diabetes mellitus (nT2D). Materials and Methods: From January 2015 to May 2020, 306 patients with nT2D were recruited for this cross-sectional descriptive study at Vietnam's National Endocrinology Hospital. We measured IMT by Doppler ultrasound. Results: There was a statistically significant difference in albumin, hs-CRP levels, hs-CRP-to-albumin ratio, and white blood cell counts between three different IMT groups namely normal IMT, thick IMT, and atherosclerosis (p = 0.003, p = 0.001, p = 0.001 and p = 0.049, respectively). In the multivariate linear regression analysis, white blood cell count, and hs-CRP levels showed a significantly positive correlation to IMT (standardized B and p of 0.17, 0.015 and 0.163, 0.024, respectively), but albumin levels were a significantly negative correlation to IMT (standardized B = -0.151, p = 0.029). The multivariate logistic regression analysis showed that albumin (OR = 0.79, 95% CI 0.65-0.90, p = 0.018), hs-CRP (OR = 1.09, 95% CI 1.01-1.18, p = 0.026), and white blood cell count (OR = 1.36, 95% CI 1.03-1.81, p = 0.033) had correlation to atherosclerosis of femoral artery. Conclusion: Reduced plasma albumin, elevated hs-CRP, and white blood cell count associated with IMT increased the odds for atherosclerosis of femoral artery among nT2D.

Heparin-Mimicking Polymer-Based In Vitro Platform Recapitulates In Vivo Muscle Atrophy Phenotypes.

The cell-cell/cell-matrix interactions between myoblasts and their extracellular microenvironment have been shown to play a crucial role in the regulation of in vitro myogenic differentiation and in vivo skeletal muscle regeneration. In this study, by harnessing the heparin-mimicking polymer, poly(sodium-4-styrenesulfonate) (PSS), which has a negatively charged surface, we engineered an in vitro cell culture platform for the purpose of recapitulating in vivo muscle atrophy-like phenotypes. Our initial findings showed that heparin-mimicking moieties inhibited the fusion of mononucleated myoblasts into multinucleated myotubes, as indicated by the decreased gene and protein expression levels of myogenic factors, myotube fusion-related markers, and focal adhesion kinase (FAK). We further elucidated the underlying molecular mechanism via transcriptome analyses, observing that the insulin/PI3K/mTOR and Wnt signaling pathways were significantly downregulated by heparin-mimicking moieties through the inhibition of FAK/Cav3. Taken together, the easy-to-adapt heparin-mimicking polymer-based in vitro cell culture platform could be an attractive platform for potential applications in drug screening, providing clear readouts of changes in insulin/PI3K/mTOR and Wnt signaling pathways.

A mathematical model for predicting the transport process and quality changes during intermittent microwave convective drying.

Intermittent microwave convective drying (IMCD) is an advanced drying method where volumetric heating of samples drives the drying process. Understanding of the physical effects of IMCD on simultaneous heating and mass transfer as well as quality changes during IMCD is essential to predict accurately drying processes and quality attributes of end products. However, there is a lack of studies in this particular interest area. The aim of this research was to develop an IMCD model coupled with quality degradation kinetics by integrating a simultaneous heat and mass transfer model with Maxwell's equations for microwave heating and the chemical reaction kinetics model. The simulated results were compared with experimental results and a good agreement was observed. As it was found that power ratio (PR) had a vital role in altering quality attributes, different PR and drying conditions were considered to investigate the effects of IMCD on the drying kinetics. The simulated results showed that the model was capable of predicting accurately moisture and temperature distributions along with heath beneficial compounds, such as total phenolic content (TPC) and ascorbic acid (AA) as well as colour changes during IMCD processing. About 70% of AA was degraded during IMCD drying using PR of 1/3. However, losses were reduced when PR was reduced to 1/4 or 1/5. Likewise, TPC degraded significantly during the early stages (first 60 min) of IMCD processing but stabilised at later stages.

Quality of plant-based food materials and its prediction during intermittent drying.

In most drying processes, several physical, chemical and nutritional modifications take place in food products. Innovative drying techniques such as intermittent drying can enhance the quality of dehydrated products effectively and efficiently. Intermittent drying is a technique where drying conditions are changed through varying the drying air temperature, humidity, velocity, pressure, or even mode of heat input. This drying technique has been successfully applied to overcome the problems of conventional drying systems such as longer time consumption, case hardening, lower energy efficiency and poor-quality attributes. However, as the effect of intermittent drying on food quality is not yet well understood, a comprehensive study of quality change during intermittent drying is crucial. The main aim of this paper is to present a thorough review of the potential effect of intermittent drying methods on physical, chemical, nutritional, and stability characteristics of plant-based food material. It is found that application of intermittency using different drying systems has a significant effect on product quality and its stability. In addition, a comprehensive review on existing models of physio/biochemical kinetics for food drying is presented. Finally, the paper is concluded with the discussion of the current challenges and future directions of intermittent drying for producing high-quality dried food products.

Nutritional quality of heat-sensitive food materials in intermittent microwave convective drying.

BACKGROUND: The retention of health promoting components in nutrient-rich dried food is significantly affected by the dehydration method. Theoretical and experimental investigations reported in the literature have demonstrated that intermittent microwave convective drying (IMCD) can effectively improve the drying performance. However, the impact of this advanced drying method on the quality food has not been adequately investigated. DESIGN: A programmable NN-SD691S Panasonic inverter microwave oven (1100 W, 2450 MHz) was employed for the experiments. The microwave power level was set at 100 W and ran for 20 seconds at different power ratios and the constant hot air conditions was set to a temperature of 60°C and 0.86 m/s air velocity. OBJECTIVE: In this study, natural bioactive compounds (ascorbic acid and total polyphenol), water activity, colour and microstructure modifications which can occur in IMCD were investigated, taking kiwifruit as a sample. RESULTS AND DISCUSSION: The microwave (MW) power ratio (PR) had significant impact on different quality attributes of dried samples. The results demonstrate that applying optimum level MW power and intermittency could be an appropriate strategy to significantly improve the preservation of nutrient contents, microstructure and colour of the dried sample. The IMCD at PR 1:4 was found to be the ideal drying condition with the highest ascorbic acid retention (3.944 mg/g DM), lowest colour change (ΔERGB = 43.86) and a porous microstructure. However, the total polyphenol content was better maintained (3.701 mg GAE/g DM) at higher microwave density (PR 1:3). All samples attained a desirable level of water activity which is unsusceptible for microorganism growth and reproduction. CONCLUSION: Overall, IMCD significantly improved the drying performance and product quality compared to traditional convective drying.

Does adjuvant concurrent or sequential chemotherapy increase the radiation-related toxicity of vaginal brachytherapy for endometrial cancer patients?

PURPOSE: To compare radiation toxicity in endometrial cancer patients treated with adjuvant vaginal brachytherapy (VBT) vs. VBT with concurrent chemotherapy (CCT) or sequential chemotherapy (SCT) METHODS: We retrospectively analyzed 131 patients with endometrial cancer treated with VBT without external beam radiation therapy. Toxicities were graded according to the Common Terminology Criteria for Adverse Events v4.03. CCT was defined as VBT delivered between the first and last cycle of chemotherapy (CT); SCT was defined as VBT delivered before or after CT. RESULTS: Median followup was 36 months, with a 3-year survival rate of 88%. Of the 131 patients, 92 were treated with VBT alone, 34 with VBT and CCT, and 5 with VBT and SCT. The most common toxicity was vaginal stricture, with 30 (22.9%) patients affected. The distribution of toxicities was vaginal 28%, urinary 12%, rectal 11%, and fatigue 5%; none greater than Grade 2. Compared with patients treated with VBT alone, the addition of CT did not increase the chance of vaginal stricture formation (p = 0.84). The difference in system-specific toxicities between treatment modalities was not statistically significant. CONCLUSION: The most common pelvic toxicity from VBT is vaginal stenosis with other toxicities being infrequent and generally Grade 1. The addition of CT in a sequential or concurrent fashion did not increase the rate of pelvic toxicity from VBT alone.

Comparison of dosimetric and clinical outcomes between short- and long-channel cylinder applicators for vaginal brachytherapy in intermediate- and high-risk endometrial cancer.

PURPOSE: Vaginal brachytherapy (VBT) using a cylinder applicator is a standard treatment of intermediate- and high-risk endometrial cancer. We conducted a retrospective study of the dosimetric and clinical outcomes at our institution with 2 single-channel applicators in patients receiving VBT. METHODS AND MATERIALS: One hundred thirty-six patients with endometrial cancer treated from 2006 to 2016 receiving VBT after definitive surgery were evaluated. Two cylinders were used with the distal dwell position 7.1-12.8 mm from the apex varying by diameter (short channel), and 3.2 mm from the apex (long channel). We prescribed 18-26 Gy in 3-4 fractions at 0.5 cm depth. Measurements of the distance from the apex to the prescription isodose line were taken from CT imaging. Student's t test and the Wilcoxon rank-sum test were used with corrections for multiple comparisons. RESULTS: Patients had International Federation of Gynecology and Obstetrics 2009 Stage I-II disease (70 Stage IA, 58 Stage IB, 9 Stage II). Mean cylinder apex dose was 95.2% and 154.7% of prescription (p < 0.001), and mean distance from apex to the prescription isodose line was 0.54 mm and 3.5 mm (p < 0.001) for the short- and long-channel cylinders, respectively. There were no significant differences in any toxicity between cylinders. Four patients (2.9%) had vaginal recurrence, all of whom were treated with the short-channel cylinder. Cylinder type was not associated with vaginal recurrence (p = 0.27). CONCLUSIONS: A cylinder applicator with a distal dwell position closer to the apex results in higher doses to the vaginal cuff and increased D2cc to the bladder. All four recurrences were in the short-channel cylinder. Additional investigation into applicator design and impact on patient outcomes in larger cohorts with sufficient followup is warranted.

Multi-scale model of food drying: Current status and challenges.

For a long time, food engineers have been trying to describe the physical phenomena that occur during food processing especially drying. Physics-based theoretical modeling is an important tool for the food engineers to reduce the hurdles of experimentation. Drying of food is a multi-physics phenomenon such as coupled heat and mass transfer. Moreover, food structure is multi-scale in nature, and the microstructural features play a great role in the food processing specially in drying. Previously simple macroscopic model was used to describe the drying phenomena which can give a little description about the smaller scale. The multiscale modeling technique can handle all the phenomena that occur during drying. In this special kind of modeling approach, the single scale models from bigger to smaller scales are interconnected. With the help of multiscale modeling framework, the transport process associated with drying can be studied on a smaller scale and the resulting information can be transferred to the bigger scale. This article is devoted to discussing the state of the art multi-scale modeling, its prospect and challenges in the field of drying technology. This article has also given some directions to how to overcome the challenges for successful implementation of multi-scale modeling.

Adjuvant therapy in patients with clear cell endometrial carcinoma: An analysis of the National Cancer Database.

OBJECTIVE: To assess the impact of adjuvant treatment, sociodemographic and tumor factors on the survival of patients with non-metastatic clear cell endometrial carcinoma (CCC). METHODS: 4298 patients treated from 1998 to 2011 with Stage I-IVA CCC were identified within the National Cancer Database. FIGO 2009 staging system was used. Adjuvant groups included: hysterectomy (HYS); HYS+vaginal brachytherapy (VBT); HYS+chemotherapy (CT); HYS+external beam radiation therapy (EBRT); HYS+CT+EBRT; and HYS+CT+VBT. Univariable (UVA) and multivariable (MVA) frailty survival analyses were performed. RESULTS: On UVA, higher stage was associated with an increased risk of death. Compared to stage I-IA, the risk of death for stage IB was HR 1.75 (95% CI, 1.50-2.04; p<0.001), stage II was HR 1.77 (95% CI, 1.50-2.10; p<0.001), stage III-IIIB was HR 3.29 (95% CI, 2.86-3.80; p<0.001), stage IIIC-IIIC2 was HR 3.33 (95% CI: 2.94-3.77; p<0.001), and stage IVA was 8.59 (95% CI: 6.60-11.18; p<0.001). Other meaningful predictors of death included black race (p<0.001), public insurance (p<0.001), geographic education attainment (p=0.001), greater comorbidity score (p=0.001), increasing age (p<0.001), and increasing tumor size (p<0.001). After controlling for stage, insurance, race, education attainment, comorbidity score, age, and tumor size adjuvant treatment was not associated with decreased risk of mortality (p=0.26). CONCLUSION: Adjuvant therapy did not have a meaningful effect on survival in this sample from the National Cancer Center Database. Given the aggressive nature of the disease, clinical trials are required to determine the optimal adjuvant therapy in patients with non-metastatic CCC to improve clinical outcomes.

To enhance imaging performance of hybrid imaging systems by using two asymmetrical phase masks.

We propose the use of two asymmetrical phase masks combined with the subtracted imaging method to enhance the signal-to-noise ratio in wavefront coding systems. This subtracted imaging technique is similar to the variable pinhole diameter in confocal microscopy. Two different phase modulations of same phase masks are employed to promote the magnitude of the optical transfer function (OTF). The ratio factor is used to control the phase variation between two phase masks. The noise of decoded images is suppressed owing to the higher magnitude of the OTF than the wavefront coding systems with a phase mask. A tangent phase mask as an example is used to demonstrate our concept. Simulated results show that the performance promotion controls noise amplification of decoded images while maintaining a depth-of-field extension.

Adverse reactions to targeted and non-targeted chemotherapeutic drugs with emphasis on hypersensitivity responses and the invasive metastatic switch.

More than 100 drugs are used to treat the many different cancers. They can be divided into agents with relatively broad, non-targeted specificity and targeted drugs developed on the basis of a more refined understanding of individual cancers and directed at specific molecular targets on different cancer cells. Individual drugs in both groups have been classified on the basis of their mechanism of action in killing cancer cells. The targeted drugs include proteasome inhibitors, toxic chimeric proteins and signal transduction inhibitors such as tyrosine kinase (non-receptor and receptor), serine/threonine kinase, histone deacetylase and mammalian target of rapamycin inhibitors. Increasingly used targeted vascular (VEGF) and platelet-derived endothelial growth factor blockade can provoke a range of pathological consequences. Many of the non-targeted drugs are cytotoxic, suppressing haematopoiesis as well as provoking cutaneous eruptions and vascular, lung and liver injury. Cytotoxic side effects of the targeted drugs occur less often and usually with less severity, but they show their own unusual adverse effects including, for example, a lengthened QT interval, a characteristic papulopustular rash, nail disorders and a hand-foot skin reaction variant. The term hypersensitivity is widely used across a number of disciplines but not always with the same definition in mind, and the terminology needs to be standardised. This is particularly apparent in cancer chemotherapy where anti-neoplastic drug-induced thrombocytopenia, neutropenia, anaemia, vascular disorders, liver injury and lung disease as well as many dermatological manifestations sometimes have an immune basis. The most insidious of all adverse consequences of targeted therapies, however, are tumour adaptation, increased malignancy and the invasive metastatic switch seen with anti-angiogenic drugs that inhibit the VEGF-A pathway. Adverse reactions to 44 non-targeted and 33 targeted, frequently used, chemotherapeutic drugs are presented together with discussions of diagnosis, premedications, desensitizations and importance of understanding the mechanisms underlying the various drug-induced reactions. There is need for wide-ranging acceptance of what constitutes a hypersensitivity reaction and for allergists to be more involved in the diagnosis, treatment and prevention of chemotherapeutic drug-induced hypersensitivity reactions.

Antibiotic allergy: immunochemical and clinical considerations.

Antibiotics are among the most widely and heavily prescribed drugs, but despite this, allergic reactions to most groups of antibiotics are relatively uncommon-especially when compared with the number and frequency of type 1 hypersensitivity responses to the beta-lactams (ie, penicillins, cephalosporins, and, to a lesser extent, carbopenems). Still, there remains a steady flow of reports of allergic reactions to some topically used antibiotics (eg, rifamycin SV and bacitracin). Moreover, aminoglycosides (eg, neomycin and gramicidin) may be implicated more often than previously suspected. Despite advances in our understanding of the structural basis of the allergenicity of beta-lactam antibiotics, the insights have not readily transferred into routine use to improve diagnoses of reactions to individual penicillins and cephalosporins. This remains a challenge in drug allergy, as does the need for further chemical, immunologic, and clinical research on cephalosporin breakdown products and the so-called multiple antibiotic allergy syndrome.

Immunoglobulin E binding determinants on beta-lactam drugs.

PURPOSE OF REVIEW: Allergies to penicillins and cephalosporins remain an important clinical problem, but structural and immunochemical knowledge of the allergenic structures involved has tended to lag behind the heavy usage, consequent adverse reactions and introduction of new therapeutic members of these two families of antibiotics. Evidence of the increasing incidence of reactions to cephalosporins and to "minor" determinants of the beta-lactams is accumulating. Also, although numerous reports detail unique allergic recognitions of individual members of the two families, particularly the cephalosporins, information remains predominantly clinical. The present review summarizes the most recent advances in studies of structural aspects of beta-lactams as allergens. RECENT FINDINGS: For the cephalosporins, a pyrazinone allergenic degradation product of cefaclor and cephalexin has been identified and characterized. The widely used cephalosporin cephalothin was shown to cross-react allergenically with benzylpenicillin and the common cross-reacting structure was identified. The fine structural features on the amoxicillin molecule recognized by antibodies that distinguish "major" and "minor" determinants were identified, and steric factors were used to explain antibody recognition of the amoxicillin determinants. A recent study elucidated the molecular basis of some cases of the multiple drug allergy syndrome and its relationship to beta-lactam allergy. SUMMARY: Findings of the type described in the present review provide fundamental insights into the nature and size of antigenic determinants on "small" molecules such as drugs and other chemicals. At the clinical level, such structure/activity findings have implications for our understanding of drug allergenic cross-reactions, for selection for therapy of an appropriate member from a family of structurally related drugs and, ultimately, for desensitization of drug-allergic patients.