Impact of the coronavirus disease 2019 (COVID-19) pandemic on the presentation of paediatric acute appendicitis: an observational study.

AIM: To determine whether there were differences in the clinical presentation of patients imaged to evaluate for acute appendicitis in 2020 compared to 2019 with the hope that this information might better identify patients who should undergo imaging work-up and those who should not. MATERIALS AND METHODS: This retrospective observational study included patients <18 years who were evaluated for appendicitis between 1 March and 31 May 2019 and 2020. A total of 465 patients were stratified by final diagnosis (appendicitis versus not appendicitis) and compared based on presenting symptoms, physical examination findings, vital signs, and laboratory test results. RESULTS: Symptoms and physical examination findings that were significant in the positive cohort in both years included right lower quadrant pain, pain with movement, migration of pain, right lower quadrant tenderness, and peritoneal findings. Reporting upper respiratory symptoms was an independent predictor of negative results among all patients and in 2019. Both negative cohorts were more likely to have negative physical examinations. Anorexia and nausea/vomiting were more likely among positive cases in 2019 whereas diarrhoea was more likely among positive cases in 2020. CONCLUSIONS: The COVID-19 pandemic did not significantly change the presenting features of acute appendicitis. The results of the present study emphasise the importance of the physical examination. The ambiguity of symptoms that mimic gastroenteritis justifies imaging in these patients.

Discrimination of the local orientation structure of spiral Glass patterns early in human visual cortex.

The local orientation structure of a visual image is fundamental to the perception of spatial form. Reports of reliable orientation-selective modulations in the pattern of fMRI activity have demonstrated the potential for investigating the representation of orientation in the human visual cortex. Orientation-selective voxel responses could arise from anisotropies in the preferred orientations of pooled neurons due to the random sampling of the cortical surface. However, it is unclear whether orientation-selective voxel responses reflect biases in the underlying distribution of neuronal orientation preference, such as the demonstrated over-representation of radial orientations (those collinear with fixation). Here, we investigated whether stimuli balanced in their radial components could evoke orientation-selective biases in voxel activity. We attempted to discriminate the sense of spiral Glass patterns (opening anti-clockwise or clockwise), in which the local orientation structure was defined by the placement of paired dots at an orientation offset from the radial. We found that information within the spatial pattern of fMRI responses in each of V1, V2, V3, and V3A/B allowed discrimination of the spiral sense with accuracies significantly above chance. This result demonstrates that orientation-selective voxel responses can arise without the influence of a radial bias. Furthermore, the finding indicates the importance of the early visual areas in representing the local orientation structure for the perception of complex spatial form.

Effect of Systemic Therapies on Outcomes following Vertebroplasty among Patients with Multiple Myeloma.

BACKGROUND AND PURPOSE: The role of vertebroplasty in patients with myeloma remains relatively undefined. Accordingly, we sought to better define the efficacy of vertebroplasty for myeloma-associated fractures and determine the effect of procedure timing relative to the initiation of systemic therapy on outcomes and complication rates. MATERIALS AND METHODS: Clinical, laboratory, and medication data were retrieved for 172 patients with multiple myeloma treated with vertebroplasty since October 2000. Quantitative outcome data (Roland-Morris Disability Questionnaire [scale, 0-24] and the Numeric Rating Scale [0-10] for pain at rest and with activity) were collected immediately pre- and postoperatively and at 1 week, 1 month, 6 months, and 1 year following vertebroplasty. Patients with ≥50% improvement on the Numeric Rating Scale and ≥40% improvement on the Roland-Morris Disability Questionnaire were classified as "responders." Peri- and postoperative complications were also collected. RESULTS: Significant median improvement in the Roland-Morris Disability and rest and activity Numeric Rating Scale scores (15, 2, and 6 points, respectively; P < .0001) persisted at 1 year without significant change from the immediate postoperative scores (P > .36). Patients on systemic therapy at the time of vertebroplasty were more likely to achieve "responder status," compared with patients not on systemic therapy, for the Numeric Rating Scale pain at rest score (P < .01) and the Roland-Morris Disability Questionnaire score (P < .003), with no difference in complication rates (χ2 = 0.17, P = .68). CONCLUSIONS: Vertebroplasty is an effective therapy for patients with myeloma with symptomatic compression fractures. Favorable outcomes are more likely to be achieved when spinal augmentation is performed after systemic therapy is initiated. Complication rates were not affected by the timing of systemic therapy.

RNA-Sequencing Analysis of Messenger RNA/MicroRNA in a Rabbit Aneurysm Model Identifies Pathways and Genes of Interest.

BACKGROUND AND PURPOSE: Rabbit aneurysm models are used for the testing of embolization devices and elucidating the mechanisms of human intracranial aneurysm growth and healing. We used RNA-sequencing technology to identify genes relevant to induced rabbit aneurysm biology and to identify genes and pathways of potential clinical interest. This process included sequencing microRNAs, which are important regulatory noncoding RNAs. MATERIALS AND METHODS: Elastase-induced saccular aneurysms were created at the origin of the right common carotid artery in 6 rabbits. Messenger RNA and microRNA were isolated from the aneurysm and from the control left common carotid artery at 12 weeks and processed by using RNA-sequencing technology. The results from RNA sequencing were analyzed by using the Ingenuity Pathway Analysis tool. RESULTS: A total of 9396 genes were analyzed by using RNA sequencing, 648 (6.9%) of which were found to be significantly differentially expressed between the aneurysms and control tissues (P < .05; false-discovery rate, <0.01; fold change, >2 or <.5). Of these genes, 614 were mapped successfully, 143 were down-regulated, and 471 were up-regulated in the aneurysms as compared with controls. Using the same criteria for significance, 3 microRNAs were identified as down-regulated and 5 were identified as up-regulated. Pathway analysis associated these genes with inflammatory response, cellular migration, and coagulation, among other functions and pathologies. CONCLUSIONS: RNA-sequencing analysis of rabbit aneurysms revealed differential regulation of some key pathways, including inflammation and antigen presentation. ANKRD1 and TACR1 were identified as genes of interest in the regulation of matrix metalloproteinases.

Modulation of mu, kappa and delta opioid receptors in the rat brain by isoflurane and enflurane.

This study was done to investigate whether inhalational anesthetics modulated the binding of specific ligands to opioid receptors in the brain of the rat. The effect of isoflurane and enflurane on the binding of specific ligands to various subtypes of opioid receptors in vitro was studied. Isoflurane inhibited the binding of [3H]naloxone to opioid receptors by 50% in the spinal cord, midbrain and cortex at 22, 49 and 50 mM, respectively. Enflurane was more potent than isoflurane in inhibiting the binding of [3H]naloxone. Scatchard analysis of the binding of [3H]naloxone, done in the presence of therapeutic level (5 mM) of isoflurane, suggested that it did not affect the KD (1.3 nM) but decreased the Bmax by 41% in the cortex. Isoflurane and enflurane, at large doses (30-50 mM), inhibited the binding of [3H]ethylketo-cyclazocine (EKC) to kappa receptors in midbrain, cortex and spinal cord. At a smaller dose (5 mM), they increased the binding of EKC in spinal cord. The binding of the analogs of enkephalin [3H]DSTLE(Tyr-D-Ser-Gly-Phe-Leu-Thr-enkephalin) to delta receptors and [3H]DAGO (Tyr-D-Ala-Gly-Methyl-Phe-Glyol-enkephalin) to mu receptors in the midbrain and cortex was inhibited by isoflurane at a significantly smaller concentration than the binding of [3H]naloxone, indicating that the binding of peptides was more susceptible to the inhibition by inhalational anesthetics than the binding of alkaloids, such as naloxone or EKC. These results suggest that the modulation of opioid receptors by inhalational anesthetics is a function of both the nature of the ligand and the tissue used for the receptor binding.(ABSTRACT TRUNCATED AT 250 WORDS)

Strain distribution of mice in discriminated Y-maze avoidance learning: genetic and procedural differences.

The current study was conducted to characterize discriminated avoidance learning in mice by using a Y-maze task. In Experiment 1, the task parameters were manipulated, including the amount of time spent in the start arm, the amount of time to make the avoidance response, and the intertrial interval (ITI) using C57 x SJL F1 hybrid mice. Avoidance performance was significantly improved with longer times to avoid the shock and longer ITIs. In Experiment 2, mice from 4 inbred strains (BALB/cByJ, DBA/2J, C57BL/6J, and SJL/J), an F1 hybrid (C57 x SJL), and 1 outbred strain (CD1) were tested with various ITIs. Strain differences were observed in avoidance learning, with BALB, DBA, C57 x SJL and CD1 mice showing significantly better avoidance learning than C57 mice, which were better than SJL mice. These data demonstrate that Y-maze performance is significantly influenced by the genetic background of the mouse and the parameters of the task.

The effects of cocaine on operant responding for food in several strains of mice.

The availability of numerous genetically homogenous mouse strains permits the analysis of genetic influences on behavior and also behavioral sensitivity (responsivity) to drugs of abuse. The current study was conducted to characterize discriminated operant responding for food in four inbred strains (Balb/cByJ, DBA/2J, C57BL/6J, SJL/J), an F1 Hybrid (C57BL/6xSJL), and one outbred strain (CD1) of mouse. The effect of cocaine on this operant behavior was also examined. Initially, all animals were trained to nosepoke for food on a continuous reinforcement schedule. The minimum response requirement for reinforcement was increased every 5 days until the animals were responding on an FR-15 schedule of reinforcement. All strains increased operant responding as the schedule of reinforcement was raised. However, significant differences in response rate and discrimination learning were observed among the various strains of mice. Cocaine administration reduced operant responding for food in Balb/cByJ, C57BL/6J, C57BL/6xSJL/J and CD1 mice at a dose of 15.0 mg/kg, whereas higher doses were required in DBA/2J mice (30.0 mg/kg) and SJL/J mice (56.0 mg/kg). These results suggest that operant performance and the effect of cocaine on this behavior is differentially influenced by genetic make-up.

Computed tomography-guided pudendal block for treatment of pelvic pain due to pudendal neuropathy.

BACKGROUND: Severe pelvic pain secondary to pudendal neuropathy can be treated with repeated local anesthetic nerve blocks or with surgical decompression of the nerve. Computed tomographic (CT) needle guidance to identified reliable anatomic points might be useful for improved success rates. TECHNIQUE: A CT scan is used to determine baseline anatomy and identify the sacrospinous process. A metallic marker is used to create a perpendicular pathway from the sacrospinous process upward to the skin surface, where a local anesthetic is injected. A 22-gauge, 5-inch needle is inserted downward in a perpendicular direction to the target. Deep penetration and direction are confirmed by serial CT scans. Medication is injected and the needle is removed. EXPERIENCE: Twenty-six women with diagnoses of pudendal neuropathy were treated with injection therapy once per month, for five total treatments each. About three-quarters experienced improvement. There were no complications in this series. Outcomes were gratifying considering the complex patient population, all having failed multiple therapeutic trials. CONCLUSION: We believe this technique warrants further evaluation and application in instances where noninvasive therapy of pudendal neuropathy is indicated.

Effects of the combination of skin cooling and hyperpnea of frigid air in asthmatic and normal subjects.

To investigate whether reducing integumental temperature influences pulmonary mechanics and interacts with inhaling cold air, 10 normal and 10 asthmatic subjects participated in a three-part trial in which cooling the skin of the head and thorax and isocapnic hyperventilation of frigid air were undertaken as isolated challenges and then administered in combination. Integumental cooling for 30 min caused airway obstruction to develop in both populations [change in 1-s forced expiratory volume (delta FEV1) asthmatic subjects = 10% ; normal subjects = 6%)]. Hyperventilation, however, only affected the asthmatic subjects (delta FEV1 asthmatic subjects = 18%; normal subjects = 3%). In contrast to expectations, the combined challenge did not produce a summation effect (delta FEV1 asthmatic subjects = 21%; normal subjects = 7%). These data demonstrate that the skin of the trunk and head is cold sensitive and when stimulated causes similar degrees of bronchial narrowing in both normal subjects and patients with airway disease independent of any ventilatory effect. They also indicate that cooling of the skin does not add to the obstructive consequences of hyperpnea.

Cardiopulmonary response to extracorporeal venous CO2 removal in awake spontaneously breathing dogs.

The ventilatory response to a reduction in mixed venous PCO2 has been reported to be a decrease in breathing even to the point of apnea with no change in arterial CO2 partial pressure (PaCO2), whereas a recent report in exercising dogs found a small but significant drop in PaCO2 (F. M. Bennett et al. J. Appl. Physiol. 56: 1335-1337, 1984). The purpose of the present study was to attempt to reconcile this discrepancy by carefully investigating the cardiopulmonary response to venous CO2 removal over the entire range from eupnea to the apneic threshold in awake, spontaneously breathing normoxic dogs. Six dogs with chronic tracheostomies were prepared with bilateral femoral arteriovenous shunts under general anesthesia. Following recovery, an extracorporeal venovenous bypass circuit, consisting of a roller pump and a silicone-membrane gas exchanger, was attached to the femoral venous cannulas. Cardiopulmonary responses were measured during removal of CO2 from the venous blood and during inhalation of low levels of CO2. Arterial PO2 was kept constant by adjusting inspired O2. The response to venous CO2 unloading was a reduction in PaCO2 and minute ventilation (VE). The slope of the response, delta VE/delta PaCO2, was the same as that observed during CO2 inhalation. This response continued linearly to the point of apnea without significant changes in cardiovascular function.(ABSTRACT TRUNCATED AT 250 WORDS)

Acral lentiginous melanoma of the oral cavity.

Lentiginous melanomas may be classified clinicopathologically as either lentigo maligna melanomas or acral lentiginous melanomas. Lentigo maligna melanoma is generally characterized by its slow rate of growth, lateness of metastasis, and relatively good prognosis. Acral lentiginous melanoma, while demonstrating a radial growth phase which is histologically similar to that of lentigo maligna, appears biologically more similar to superficially spreading malignant melanoma once the vertical growth phase supervenes. Mucous membrane melanomas with lentiginous characteristics are likely to be aggressive lesions with a marked propensity for metastasis and a uniformly poor prognosis, much like the acral lentiginous type of melanoma. It would seem, therefore, that superficial melanomas of the oral mucous membranes with a lentiginous pattern should best be termed acral lentiginous melanomas instead of lentigo maligna melanomas so as to more accurately predict their true biologic potential. An amelanotic case is presented which we believe illustrates this point.

Verrucous carcinoma of the oral cavity.

Since verrucous carcinoma was first identified as a distinct clinicopathologic entity, a great deal of confusion has developed in interpreting the proper criteria for diagnosis. Various authors, therefore, have developed considerably different concepts of the features that make this lesion a unique variant of squamous cell carcinoma. Consequently, there is great confusion in the literature as to the appropriate therapeutic approach, the incidence of recurrence, and the frequency of anaplastic transformation of verrucous carcinoma. The literature was reviewed to identify all cases of verrucous carcinoma of the oral cavity that appear to meet the clinical and histopathologic criteria for this lesion as originally set forth by Ackerman. The problems encountered in arriving at the diagnosis of verrucous carcinoma are discussed. Cases with at least a 1-year reported follow-up were grouped according to the primary modality of therapy employed and were evaluated as to the effectiveness of the initial therapy. The frequency of anaplastic transformation following radiation therapy is also addressed.

Overexpression of p53 protein is common in premalignant head and neck lesions.

In order to determine whether or not the p53 gene is involved in the malignant transformation of the head and neck carcinoma HNSCC, we have analyzed archival specimens from 527 primary head and neck lesions and 27 corresponding lymph node metastases. Nuclear p53 protein was present in 107 of 190 (56%) dysplasias, 61 of 102 (60%) carcinoma in situ (CIS), and 262 of 493 (53%) carcinomas. The p53 score did not increase significantly with progression of these lesions from dysplasia to CIS and to carcinoma. All 357 normal samples of head and neck tissues were negative. The majority of the 172 sets of premalignant and malignant lesions displayed concordant p53 staining patterns. The staining was incongruous in only six cases. The p53 staining results were congruent in all 27 pairs of primary and metastatic (lymph nodes) tumors. These data strongly suggest that p53 protein could be altered in a very early phase of the head and neck tumorigenesis and is maintained during tumor progression and metastatic spread. Mutations in p53 were examined in 11 cases that exhibited high levels of p53 protein as detected by immunohistochemistry using PAb 1801 MAb. Mutation analysis was performed by direct sequencing of the PCR amplification products of exons 5 through 8, which contain greater than 90% of p53 mutations found in tumors. Three of 11 HNSCC had mutations at codon 130 (C to A), 193 (A to T), 283 (G to C), respectively. No mutations were found in the other 8 samples within the regions examined. However, they may have mutations in unsequenced regions of p53 or may have wild type protein that accumulates for other reasons.

The role of the p53 gene in the malignant transformation of pleomorphic adenomas of the parotid gland.

Pleomorphic adenoma (PA), the most common neoplasm of the parotid gland in adults, undergoes malignant transformation in only two to six percent of cases. In order to determine whether or not the p53 gene is involved in the malignant transformation of PA of the parotid gland, we have analyzed archival specimens from four patients with carcinoma ex-pleomorphic adenoma (CEPA) by immunohistochemistry and sequencing of the amplified DNA. Tissue specimens from each patient contained both the CEPA and the precursor PA. Immunostaining revealed that while all CEPA were p53 positive, only one of the four precursor PA was positive for p53. In this case, DNA was isolated from both the PA and CEPA and exons five through eight were amplified using the polymerase chain reaction. The same p53 mutation (single base substitution) was found in both the PA and the CEPA at codon 248. Adjacent normal tissue contained the wild-type p53 sequence. To our knowledge, this is the first report of the same p53 point mutation in both a PA and the associated CEPA of the parotid. These results strongly suggest a role for p53 gene mutation in the malignant transformation of some PA of the parotid gland.

Management of chronic pelvic pain.

Anyone who has managed chronic pain patients well understands the need for patience and unconditional positive support for the patient. It is most imperative that the physician and the entire health care team continue to be optimistic in spite of repeated failures of different treatment regimens. It is important to keep the patient informed continually of the problems encountered and the different treatment regimens used (Fig. 8). To keep the patient motivated to seek eventual solutions to the problems is one of the key elements in chronic pelvic pain therapy for the pain specialist. Do not underestimate the power of patient involvement in her own disease process. Some of the most common errors made by physicians are the underestimation of the patient's interest and intelligence in understanding the medical aspects of the pain disorder, lack of communication with the patient in regard to new findings and the effect they have on the course of the patient's treatment, and the lack of outward expressions of sincerity and concern about an individual patient's condition.

Anesthetic considerations in the presence of intrapartum emergencies.

Acute fetal distress requires that the anesthesiologist use his skills and knowledge to achieve a safe anesthetic effect for both mother and infant. Techniques should be individualized in a manner dictated by the situation, and those techniques that least affect the fetus and maternal-fetal interrelationships should be employed. The anesthesiologist must be able to apply regional or general techniques with equal facility and to select agents of the least toxicity and threat to the maternal-fetal relationship. The possibility of perinatal asphyxia is remote when the induction and maintenance of anesthesia are carried out efficiently and carefully. For a fetus that is already stressed, however, injudiciously managed anesthesia can be a serious problem. Finally, because the anesthesiologist administered the anesthetic, he must also be prepared to effectively institute immediate neonatal resuscitative measures in the first five to ten minutes of extrauterine life.

Performance studies of an enzyme-linked immunosorbent assay for detecting Staphylococcus aureus antibody in bovine milk.

An enzyme-linked immunosorbent assay (ELISA) for detecting Staphylococcus aureus antibody in bovine milk samples was examined for repeatability. A set of 51 bovine milk samples from 4 universities with confirmed culture results was assembled, and a panel of 30 milk samples was randomly selected. When the selected panel was tested at the collection laboratory, there was 97% agreement between the ELISA and the culture test. The panel was tested with the ELISA by the 4 university laboratories. Results were scored by both visual and optical density reader methods. When compared to reference ELISA results, the university laboratory ELISA results showed an agreement of 99.8% for negative samples, 98% for positive samples, and 99% for all samples. Additional studies on 19 milk samples that cultured positive for bacteria other than S. aureus showed 100% specificity. Overall comparison of ELISA and culture results showed high agreement between the 2 techniques. Disagreement appeared to result from explainable differences in antibody and bacterial levels and not from errors in either of the 2 techniques.

Study of humidification potential of a heat and moisture exchanger in tracheotomized dogs.

Though a heat and moisture exchanger (HME) has been used in clinical practice following a tracheotomy on a limited basis, no work has been done to document the humidification potential of an HME in this situation. Eighteen dogs underwent tracheotomy and were killed at either 1 day (nine dogs) or 10 days (nine dogs) postoperatively. Following the tracheotomy, the animals were divided into three groups according to the type of humidification received: ambient conditions, warm mist, or HME. The tracheal mucosa was studied for histologic changes in the cilia, the epithelium, submucosal reaction, and mucus production at the level of the carina. The results were significant (p = .02) for the interaction of the experimental type and method of treatment in their effect on the histologic changes noted at the carina. The study supports the use of an HME as an alternative for long-term humidification in a patient with a tracheotomy.

Pyostomatitis vegetans associated with ulcerative colitis. Temporary clearance with fluocinonide gel and complete remission after colectomy.

Pyostomatitis vegetans is a rare condition characterized by pustules that affect the oral mucosa. It is consistently associated with inflammatory bowel disease and is usually resistant to treatment. We present the case of a 65-year-old white man with pyostomatitis vegetans that was associated with ulcerative colitis and adenocarcinoma of the colon. Fluocinonide gel resulted in a complete but temporary clearance of the lesions. Complete remission was achieved immediately after a total colectomy.

Radiographic method for anatomic study of the teat canal: changes between milking periods.

Radiographs of the teat canal (papillary duct) of 14 Holstein-Friesian cows were made immediately after removal of the milking machine and at 2, 4, 6, and 8 hours. The distal, middle, and proximal diameters of the canal were dilated when the machine was removed. The distal and the middle parts of the teat canal were more dilated than the proximal part of the canal. Two hours later, the canal was constricted in the 3 areas. During the next 6 hours, the canal dilated-the greatest kilation being at the proximal paet of the teat canal. The average lenght of the teat canal remained unchanged. Apparently, microorganisms can easily pass through the teat canal when it is dilated at the end of machine milking and for up to 2 hours after milking.