Initially Detected Research Articles

Single Nucleotide Polymorphism-Based Real-Time PCR Screening Assay for Rapid Tracking of Bacterial Infection Clusters To Complement Whole-Genome Sequencing Efforts during Outbreak Investigations.

Infection clusters of multidrug-resistant bacteria increase mortality and entail expensive infection control measures. Whereas whole-genome sequencing (WGS) is the current gold standard to confirm infection clusters, PCR-based assays targeting cluster-specific signatures, such as single nucleotide polymorphisms (SNPs) derived from WGS data, are more suitable to initially screen for cluster isolates within large sample sizes. Here, we evaluated four software tools (SeqSphere+, RUCS, Gegenees, and Find Differential Primers) regarding their efficiency to find SNPs within WGS data sets that were specific for two bacterial monospecies infection clusters but were absent from a WGS reference data set comprising several hundred diverse genotypes of the same bacterial species. Cluster-specific SNPs were subsequently used to establish a probe-based real-time PCR screening assay for in vitro differentiation between cluster and noncluster isolates. SeqSphere+ and RUCS found 2 and 24 SNPs for clusters 1 and 14 and 24 SNPs for cluster 2, respectively. However, some signatures detected by RUCS were not cluster specific. Interestingly, all SNPs identified by SeqSphere+ were also detected by RUCS. In contrast, analyses with the remaining tools either resulted in no SNPs (with Find Differential Primers) or failed (Gegenees). Design of six cluster-specific real-time PCR assays enabled reliable cluster screening in vitro. Our evaluation revealed that SeqSphere+ and RUCS identified cluster-specific SNPs that could be used for large-scale screening in surveillance samples via real-time PCR, thereby complementing WGS efforts. This faster and simplified approach for the surveillance of bacterial clusters will improve infection control measures and will enhance protection of patients and physicians. IMPORTANCE Infection clusters of multidrug-resistant bacteria threaten medical facilities worldwide and cause immense health care costs. In recent years, whole-genome sequencing (WGS) has been increasingly applied to detect and to further control bacterial clusters. However, as WGS is still expensive and time-consuming, its exclusive application for screening and confirmation of bacterial infection clusters contributes to high costs and enhanced turnaround times, which many hospitals cannot afford. Therefore, there is need for alternative methods that can enable further surveillance of bacterial clusters that are initially detected by WGS in a faster and more cost-efficient way. Here, we established a system based on real-time PCR that enables rapid large-scale sample screening for bacterial cluster isolates within 7 days after the initial detection of an infection cluster, thereby complementing WGS efforts. This faster and simplified surveillance of bacterial clusters will improve infection control measures and will enhance protection of patients and physicians.

Utility of magnetic resonance imaging in determining treatment response and local recurrence in nasopharyngeal carcinoma treated curatively

BackgroundTo determine the optimal timing of the first Magnetic Resonance Imaging (MRI) scan after curative-intent radiotherapy (RT) for nasopharyngeal carcinoma (NPC), and evaluate the role of MRI in surveillance for locoregional recurrence (LRR).MethodsPatients with non-metastatic NPC treated radically who had at least one post-treatment MRI (ptMRI) done were included for analysis. ptMRI reports were retrospectively reviewed and categorised as complete response (CR), partial response/residual disease (PR) or indeterminate (ID). Patients with LRR were assessed to determine if initial detection was by MRI or clinical means. Univariable and multivariable Cox proportional hazard regression analysis were performed to identify independent factors associated with CR on ptMRIs.ResultsBetween 2013 and 2017, 262 eligible patients were analysed, all treated with Intensity Modulated Radiotherapy (IMRT). Median time from end of RT to the first ptMRI was 93 days (range 32–346). Of the first ptMRIs, 88 (33.2%) were CR, 133 (50.2%) ID, and 44 (16.6%) PR. A second ptMRI was done for 104 (78.2%) of 133 patients with ID status. In this group, 77 (57.9%) of the subsequent MRI were determined to be CR, 21(15.8%) remained ID and 6 (4.5%) PR. T1 tumour stage and AJCC stage I were associated with increased CR rates on first ptMRI on multivariable analysis. ID status was more likely at 75–105 days (3 months +/− 15 days) vs 106–135 days (4 months +/− 15 days) post RT (OR 2.13, 95% CI 1.16–4.12, p = 0.024). LRR developed in 27 (10.1%) patients; 20 (74.1%) were initially detected through MRI, 3 (11.1%) by nasoendoscopy and 2 (7.4%) by PET-CT.ConclusionMRI is useful for detecting local recurrence or persistent disease after curative-intent treatment. Most patients will need more than one ptMRI to arrive at a definitive status. The rate of ID ptMRI may be reduced by delaying the first scan to around 4 months post RT.

Susceptibility Profile of Aedes aegypti L. (Diptera: Culicidae) from Montclair, California, to Commonly Used Pesticides, With Note on Resistance to Pyriproxyfen.

The peridomestic anthropophilic Aedes aegypti L. (Diptera: Culicidae) is originated from the wild zoophilic subspecies Aedes aegypti formosus in sub-Saharan Africa, and currently has a broad distribution in human-modified environments of the tropics and subtropics worldwide. In California, breeding populations were initially detected in 2013 in the cities of Fresno, Madera, and San Mateo, and now can be found in 188 cities of 12 counties in the state. Recent genetic studies suggest that this species invaded California on multiple occasions from several regions of the United States and northern Mexico prior to initial detection. As an invasive species and vector for numerous arboviruses, Ae. aegypti is a primary target of surveillance and control in California. In southern California city of Montclair, a population was identified in September 2015, from which a short-term colony was established in an insectary. The susceptibility of this field population to commonly used pesticides with various modes of action, including 15 formulations against larvae and four against adults, was determined, in reference to a susceptible laboratory colony of the same species. No resistance was shown to most pesticides tested. However, tolerance or reduced susceptibility to spinosad, spinetoram, diflubezuron, and fipronil was detected, and modest levels of resistance to pyriproxyfen (resistance ratio = 38.7-fold at IE50 and 81.5-fold at IE90) was observed. Results are discussed based on the field usage and modes of action of the pesticides tested. Strategic selection and application of pesticides against this population of Ae. aegypti in the urban environments should be taken into consideration.

Utilization of a handheld metal detector protocol to reduce radiation exposure in pediatric patients with esophageal coins

ObjectiveThe primary objective of this study is to assess the utility of a handheld metal detector for identification and surveillance of patients with known esophageal coin ingestion to reduce repeat x-rays and associated radiation exposure. MethodsProspective study of children presented to the emergency department with esophageal coins confirmed by an initial x-ray were enrolled. The otolaryngology team used the handheld metal detector to detect and localize the coin on patient. If admitted for observation, the metal detector was used to ensure coin persistence prior to going to operating room for removal. No further x-rays were done if same location is confirmed. ResultsA total of 19 patients (10 months-14 years) with 20 esophageal coins were enrolled. 14 patients (73.7%) were initially detected in the emergency department by the metal detector. 11 (58%) asymptomatic patients admitted for period of observation, repeat x-rays were avoided in 10 (90.9%) patients prior to removal in the OR. All proximal esophageal coins were detected with the metal detector. There were 5 (26.3%) patients who failed initial detection of coin, and all of these were in the mid-distal esophageal location with depth from skin >7 cm. ConclusionA handheld metal detector is rapid, cost-effective surveillance tool to reduce exposure to radiation from repeated x-rays in patients with esophageal coins. In contrast to all prior published studies, which did not objectively examine depth, the distance of the coin from skin surface appears to be a major limitation. Parents have provided positive feedback on the protocol.

Detection of exhaled carbon dioxide following intubation during resuscitation at delivery

ObjectivesEnd tidal carbon dioxide (ETCO2) monitoring can facilitate identification of successful intubation. The aims of this study were to determine the time to detect ETCO2 following intubation during resuscitation of...

Serendipity in the Diagnosis of Pheochromocytoma

Pheochromocytomas are increasingly being discovered incidentally on imaging studies performed without clinical suspicion of the existence of an adrenal lesion. We aimed to determine the rate of diagnosis of adrenal pheochromocytoma as an incidental finding during a recent 7-year period. We obtained the Department of Pathology database to study all the patients at our institution with newly diagnosed pheochromocytomas in the 7-year period from 2005 to 2011 to determine the clinical presentation and the means of diagnosis. In 40 (70.2%) of the 57 patients, an adrenal pheochromocytoma was detected in an imaging study performed without suspicion of an adrenal lesion. There were 13 chest computed tomography studies-8 to evaluate for possible pulmonary emboli. Other indications included abdominal pain or discomfort (n = 8), trauma (n = 3), abnormal liver function tests (n = 3), suspect renal artery stenosis (n = 3), hematuria (n = 2), colitis (n = 2), and 4 miscellaneous indications. Our study documents that the commonest current means of initial detection of pheochromocytoma is by serendipitous discovery. In 16 of our 40 patients with serendipitously discovered pheochromocytomas, there were no clinical symptoms of pheochromocytoma; these were true incidentalomas. More than two thirds of the new cases of pheochromocytoma were detected by serendipity (found during studies not performed to evaluate for pheochromocytoma), approximately one third were true incidentalomas (pheochromocytomas in patients without symptoms). In a 7-year period at a single institution, 40 patients, 70% of new cases of surgically proven pheochromocytoma, were initially detected by serendipity. Sixteen patients, 40% of those incidentally discovered represented true examples of "incidentalomas."

Presentation of early-stage non-small cell lung cancer (NSCLC) without radiographic screening: End of an era?

e17506 Background: In contrast to other common malignancies, screening for lung cancer is currently not recommended. However, recent evidence suggests that computed tomography (CT)-based screening of select populations may decrease lung cancer mortality. We determined how screening would impact current presentation patterns of early stage disease. Methods: Retrospective analysis of patients diagnosed with stage 1-2 NSCLC from 2000-2009 at the University of Texas Southwestern Medical Center. Data were obtained from tumor registries and medical records. Associations between baseline characteristics and the reason for and type of imaging were assessed using univariate analysis and multivariate logistic regression. Results: A total of 412 patients were included in the analysis. Mean age was 67 years, 49% were men, 70% were white, and 79% had stage I disease. Only 52% were age 55-74 years and had 30+ pack-year smoking history and would therefore have met criteria for the National Lung Screening Trial (NLST). Reason for initial imaging was symptoms in 51%, follow-up of other medical conditions in 43%, and lung cancer screening in 6%. Dominant symptoms were cough/hemoptysis (36%), dyspnea (29%), and chest pain (15%). Chest x-ray was the initial imaging modality in 57%, with CT scans accounting for almost all other cases. Reason for imaging was significantly associated with race (P<0.001), socioeconomic status (P=0.005), and stage (P<0.001), with non-white patients, indigent patients, and those diagnosed with stage 2 disease more likely to present with symptoms. Type of imaging was associated with reason for imaging (P<0.001), year of diagnosis (CXR 67% 2000-2004 vs. 49% 2005-2009; P<0.001), and disease stage (P=0.005). Conclusions: Symptoms remain the dominant reason for initial detection of early stage NSCLC, particularly among underrepresented populations. The proportion of early stage NSCLC initially detected by CT scan, principally for follow-up of other medical conditions, has increased markedly in recent years. If widespread lung cancer screening is implemented, these patterns may persist, as only half of patients currently diagnosed with early stage NSCLC meet NLST eligibility criteria.

Mre11 Nuclease Activity and Ctp1 Regulate Chk1 Activation by Rad3ATR and Tel1ATM Checkpoint Kinases at Double-Strand Breaks

Rad3, the Schizosaccharomyces pombe ortholog of human ATR and Saccharomyces cerevisiae Mec1, activates the checkpoint kinase Chk1 in response to DNA double-strand breaks (DSBs). Rad3(ATR/Mec1) associates with replication protein A (RPA), which binds single-stranded DNA overhangs formed by DSB resection. In humans and both yeasts, DSBs are initially detected and processed by the Mre11-Rad50-Nbs1(Xrs2) (MRN) nucleolytic protein complex in association with the Tel1(ATM) checkpoint kinase and the Ctp1(CtIP/Sae2) DNA-end processing factor; however, in budding yeast, neither Mre11 nuclease activity or Sae2 are required for Mec1 signaling at irreparable DSBs. Here, we investigate the relationship between DNA end processing and the DSB checkpoint response in fission yeast, and we report that Mre11 nuclease activity and Ctp1 are critical for efficient Rad3-to-Chk1 signaling. Moreover, deleting Ctp1 reveals a Tel1-to-Chk1 signaling pathway that bypasses Rad3. This pathway requires Mre11 nuclease activity, the Rad9-Hus1-Rad1 (9-1-1) checkpoint clamp complex, and Crb2 checkpoint mediator. Ctp1 negatively regulates this pathway by controlling MRN residency at DSBs. A Tel1-to-Chk1 checkpoint pathway acting at unresected DSBs provides a mechanism for coupling Chk1 activation to the initial detection of DSBs and suggests that ATM may activate Chk1 by both direct and indirect mechanisms in mammalian cells.

The Performance of Computed Tomography (CT) Scans or Ultrasound Has No Clinical Relevance in Treatment of Patients with Chronic Lymphocytic Leukemia (CLL): Results of a Metaanalysis from Three Phase III Studies of the German CLL Study Group (GCLLSG).

Introduction: Staging of CLL is based on simple methods to estimate the prognosis of CLL at the time point of diagnosis. Both, the Rai and Binet staging systems, are based on physical examination and peripheral blood count. According to the recently updated IWCLL guidelines for CLL (Hallek et al., Blood, 2008) no radiological examinations are needed for staging and response evaluation outside clinical trials. Previously, it was shown that CT scans add no benefit to the response criteria defined by the National Cancer Institute (NCI) (Byrd et al., 2007). However, it is still unclear, how much additional information can be gained by using CT scans by routine at pretherapeutic evaluation and during follow-up phase. Therefore the GCLLSG initiated a metaphase analysis based on the results of three phase III studies (CLL4, CLL5 and CLL8 protocol of the GCLLSG), in order to evaluate the clinical relevance of CT scans on disease outcome.Patients: A total of 1372 patients (pts) receiving first line therapy for CLL within a phase III trial of GCLLSG were included in this analysis. 362 pts younger than 65 years were included in the CLL4 trial, 193 pts older than 64 years in the CLL5 trial and 817 pts with normal renal function and a comorbidity score ≤ 6 were included in the CLL8 trial. 100 pts received chlorambucil, 257 fludarabine (F), 590 F plus cyclophosphamide (FC) and 408 FC plus rituximab. Response as well as progression during later follow-up was assessed according to the NCI-WG criteria (Cheson et al., Blood 1996). CT scan or other radiological examinations were not performed by routine, but were recommended at pretherapeutic staging, interim and final staging and during the follow-up phase, if clinically indicated.Results: The median follow up time for pts alive in the CLL4 trial was 54 months (mo), 40 mo in CLL5 and 27 mo in CLL8 (overall 31 mo). During follow-up a total of 11.103 CT scans, 22.728 ultrasounds as well as 2.350 chest x-rays were performed in 1372 pts. In contrast, 59.742 physical examinations were performed either additionally to radiological examination or alone. In a first step we evaluated the number of pts for whom the radiological examination was crucial in order to reconcile progressive disease (PD) according to the NCI criteria. A total 491 pts were considered as progressive during treatment or follow-up. In 100 pts the definition of PD by the treating physician could not be confirmed by a strict, independent application of the NCI-WG criteria and were therefore excluded from the analysis. In the remaining 391 pts PD was clinical apparent in 326 (83%), while CT scans were relevant for the decision of PD in 39 pts (10%) only and ultrasound in 26 pts (7%). In a next step we assessed the number of pts for whom CT scan or ultrasound had a clinical consequence by initiating relapse treatment because of bulky disease (defined as a lymph node of > 5 cm) in the thorax or abdomen. Out of 176 pts receiving relapse treatment due to PD, in only 2 pts (1%) the retreatment decision was based on the result of the CT scan or ultrasound: in these pts a new bulk was detected by radiological examination, while physical examination and blood count were normal. Moreover, an initially detected bulky disease by radiological examination had no prognostic value as well. Pts with initially detected bulky disease showed a higher rate of complete remissions in comparison to pts without bulky disease (29% versus 22%, p = 0.02). Interestingly, no difference in overall response rates (86% versus 89%, p = 0.2), as well as progression free survival (36 versus 39 months, p = 0.2) and overall survival (OS) (median OS not reached vs. 85 months, p = 0.08) was assessed.Conclusion: These data from 1372 patients included in three prospective phase III trials show that the use of CT scans has no apparent clinical benefit for the evaluation of PD or the decision to initiate relapse treatment in the follow-up phase of CLL. In 1% of the relapse treatment receiving pts only the result of the CT scan was crucial for retreatment decision. Moreover, the initial detection of bulky disease by CT scan or ultrasound had no prognostic impact. Our data suggest that physical examination and blood count remain the methods of choice for clinical follow-up of patients with CLL.

Sensitivity of respiratory virus culture when screening with R-mix fresh cells.

Use of R-Mix Fresh Cells has been shown to be a rapid and sensitive method for the detection and identification of respiratory viruses. We prospectively evaluated the impact of incorporation of R-Mix shell vials on the sensitivity and time to detection of seven respiratory viruses recovered in a comprehensive culture during the course of an entire respiratory season in a high-volume clinical laboratory. In this study, R-Mix shell vials were used as part of the culture of 3803 respiratory specimens. A total of 428 respiratory viruses were recovered. Staining of R-Mix vials after overnight incubation allowed initial detection of 274 of 279 influenza viruses, 33 of 38 parainfluenza viruses, 35 of 51 adenoviruses, and 52 of 60 respiratory syncytial viruses (RSVs). The time to reporting of all positive cultures after in-lab specimen receipt was 2.9 days on average and those initially detected in R-Mix cells were reported in 2.3 days on average. A combination of direct fluorescent-antibody (DFA) staining and virus culture was performed on a subset of 711 respiratory specimens. Of 152 viruses identified, 57 were observed only with DFA testing (55 RSV and 2 influenza A viruses) and 31 were recovered only in cell culture. After overnight incubation, R-Mix cells detected 87.1% of respiratory viruses not observed by DFA testing and 96.9% of viruses positive by both methods. The sensitivities of DFA testing and R-Mix cells for identification of influenza viruses were 70.5% and 96.7%, respectively. The R-Mix method detected influenza virus in 18 samples that were negative by DFA testing.

Screening for retinoblastoma: presenting signs as prognosticators of patient and ocular survival.

To correlate 3 common presenting signs of retinoblastoma with patient and ocular survival and to assess the efficacy of current pediatric screening practices for retinoblastoma. A retrospective study was conducted of 1831 retinoblastoma patients from our center (1914-June 2000). Patient survival (excluding deaths from other primary neoplasms) and ocular survival (presenting eyes) rates were calculated and analyzed using the Kaplan-Meier method. Leukocoria correlated with excellent patient survival (>86%, 5 years) but poor ocular survival in unilateral (4%, 5 years) and bilateral patients (29%, 5 years). A total of 308 (19%) of 1654 patients presented with strabismus: patient survival was excellent (90%, 5 years), and ocular survival was poor (17%, 5 years) yet better than leukocoria. Patients who had a family history of retinoblastoma and were clinically screened for retinal tumors from birth were diagnosed younger (8 months of age) and earlier (Reese Ellsworth group 1 = 26 [58%] of 45) and had better ocular survival than nonscreened patients with a family history. More patients were initially detected by family/friends (1315 [80%] of 1632) than pediatricians (123 [8%] of 1632) or ophthalmologists (156 [10%] of 1632). Most US children whose retinoblastoma is diagnosed initially present with leukocoria detected by a parent, despite routine pediatric screening for leukocoria via the red reflex test. Initial disease detection at the point of leukocoria or strabismus correlated with high patient survival rates and poor ocular survival rates for the presenting eye. Saving eyes and vision requires disease recognition before leukocoria, as demonstrated by the better ocular salvage rate among patients who had a positive family history and received clinical surveillance via early, routine dilated funduscopic examinations by an ophthalmologist.

A primary CNS lymphoma in spontaneous remission for 3.5 years after initial detection of the lesions by MRI

We describe the clinicopathological features of a patient with an autopsy-proven primary CNS lymphoma, who had a relatively long remission period after onset. A 61-year-old man experienced disorientation and gait disturbance. A ventriculoperitoneal shunt operation was performed, based on the diagnosis of hydrocephalus due to aqueductal stenosis, after which his symptoms subsided. Three months later, T2-weighted magnetic resonance imaging (MRI) revealed high-intensity lesions in the corpus callosum and tectum. However, he remained asymptomatic for the next three and a half years, during which periodic MRI studies constantly detected the lesions. At the age of 65 years, he suffered respiratory and consciousness disturbances, and his general condition gradually deteriorated. MRI studies disclosed that the callosal lesion had spontaneously disappeared, whereas the tectal lesion had developed to become an enhanced linear lesion with a tendency to spread on the dorsal side of the brain stem. Examination of the cerebrospinal fluid disclosed a markedly elevated beta2-microglobulin content, and a tentative diagnosis of malignant lymphoma was made. Steroid pulse therapy had little effect, and the patient died four years after presentation. Examination at autopsy disclosed a malignant, large B-cell lymphoma that had diffusely infiltrated the cerebrum and brain stem. In the corpus callosum, a small number of residual lymphoma cells were seen around the vessels. Therefore, the initially detected lesions in the corpus callosum and tectum might have been attributable to lymphoma, and the unusual clinical and radiological features of this case provide further information that might aid in diagnosis and help to ensure prompt treatment.

Transmission of hepatozoon canis to dogs by naturally-fed or percutaneously-injected Rhipicephalus sanguineus ticks.

Hepatozoon canis is an apicomplexan protozoan parasite of dogs, prevalent in Asia, Africa, and southern Europe. Experimental transmission of H. canis to dogs was performed with laboratory-reared Rhipicephalus sanguineus nymphs that fed on a naturally infected dog or were percutaneously injected with canine blood containing H. canis gamonts. Dogs were inoculated by oral ingestion of adult ticks containing H. canis oocysts. Transstadial transmission of H. canis was recorded, whereas transovarial transmission could not be demonstrated. Oocysts were detected in 85% of the adult ticks that had engorged as nymphs on an infected dog and in 61% of the adult ticks resulting from nymphs injected percutaneously with blood from the same dog. Nine of 12 dogs (75%) inoculated with naturally fed or percutaneously injected ticks became parasitologically positive, and all showed seroconversion. Meronts were initially detected in the bone marrow 13 days postinoculation and gamonts 28 days after infection. The variation in the time of initial detection of parasitemia among infected dogs and the rapid appearance of gamonts in dogs immunosuppressed with corticosteroids suggest that immune mechanisms play an important role in controlling H. canis parasitism. The artificial acquisition of Hepatozoon parasites by percutaneous injection of ticks, demonstrated here for the first time, may serve as a useful tool for studies on transmission, vector-host relationships, and the immunology of infection with Hepatozoon species.

Season of initial discovery of tumour as an independent variable predicting survival in breast cancer

The month of initial detection of tumour was recorded in 2,245 patients with breast cancer and correlated with survival over a follow-up period of 1.5-10 years. Women who initially detected their breast cancer in spring/summer had a significantly longer survival than those detecting their tumour at other times of the year. Overall, this relationship was independent of nodal status, tumour size and hormone receptor status. However, when patients were divided into groups the survival advantage was significantly associated with receptor status and age. Women aged greater than or equal to 50 years with ER-positive and PR-positive tumours who discovered their initial tumour in spring/summer had significantly better survival than those detecting their tumours at other times of the year. Survival was also longer in women aged less than 50 years with receptor-negative tumours who initially found their tumours in spring/summer compared with the rest of the year. This study suggests that the season of first detection of a breast cancer relates significantly to the later behaviour of the tumour, and may reflect seasonal changes in hormone dependent growth.

Hydrologic detection of abandoned wells near proposed injection wells for hazardous waste disposal

Deep saline aquifers are being used for disposal of hazardous liquid wastes. A thorough knowledge of the competency of such aquifers and their confining geologic beds in permanently isolating the hazardous substances is the key to successful disposal operations. Characterization of such systems, and in particular the detection of any conduit that may permit hydraulic communication between the host aquifer and nearby freshwater aquifers, must be carried out prior to the initiation of disposal projects. In deep, multi‐aquifer systems, leaky faults, abandonded wells, highly conductive fractures, or shear zones may all provide leakage paths. If not initially detected, such conduits may show no apparent effect until contaminants in the freshwater aquifer reach detectable levels at the discharge point. By then, of course, detection is generally too late. This paper is an attempt to address the problem of initial detection of improperly plugged or open abandoned wells. A new analytic solution has been derived to calculate the amount of leakage from an abandoned well and the corresponding drawdown at monitoring wells. A method is proposed that can be used to detect such deep abandoned wells in the area of influence of a proposed deep injection well in a multiple‐aquifer system.

Association between season of first detection of breast cancer and disease progression.

The season of recurrence of tumour was investigated by follow-up of 1324 patients with breast cancer and compared with the season of initial tumour detection. Unlike primary tumours, where an increased incidence of detection has previously been observed in late spring and early summer, there was no significant seasonal variation in the time of recurrence. However, women with oestrogen receptor positive or progesterone receptor negative primary tumours recurred significantly more frequently in the same season that their primary cancer was initially detected. Overall there was an increased frequency of recurrence one year from diagnosis. Women less than age 50 who initially found their tumour in winter or autumn had a significantly shorter disease-free interval before recurrence than those first detecting their tumour in summer or spring. This relationship was independent of nodal status and tumour size. Tumours initially detected in winter or autumn thus appeared to follow a more aggressive growth profile. This study indicates that the season of first detection of a breast cancer relates significantly to aspects of the future biologic behaviour of the tumour.

Theileria parva: Kinetics of infection in the lymphoid system of cattle

The kinetics of infection with Theileria parva in cattle were studied by examining the total cellularity and numbers of parasites in a range of lymphoid organs from animals killed at intervals during the course of the infection. With the dose of T. parva stabilate used, macroschizonts were initially detected in the drainage lymph node about 7 days after inoculation and death of the host resulted on Day 18–19. Associated with the initial detection of parasites, there was a marked increase in cellularity of the drainage lymph node and a more gradual and less pronounced increase in cellularity of the other lymphoid organs. From about Day 12 onward, there was a gradual decrease in the cellularity in all of the lymphoid organs, so that in animals examined in the terminal stages of the infection there was often cellular depletion. The pattern of these cellular changes was similar in groups of Boran and Friesian cattle, although both the increase in cellularity and the terminal depletion were more marked in the Friesians. Blood leukocyte counts in infected Boran started to drop as early as Day 7 of infection and by Day 14 had reached values less than 25% of normal. Quantitation of parasitic schizonts indicated that the numbers of parasites in the lymphoid organs do not increase in a simple exponential manner. Rather, there appears to be an early rapid increase in parasite numbers followed by a phase of less rapid multiplication. Because of the marked changes which occured in total cellularity of the lymphoid organs during the course of the infection, a significant discrepancy was found between the replication rate of the parasite as calculated using total numbers of parasites and that obtained using schizont index (SI). These results indicated that the use of SI, as described in previous studies, is not a reliable method of determining the replication rate of the parasite.

Initial detection of human chorionic gonadotropin in serum in normal human gestation

Human chorionic gonadotropin (HCG), with a radioimmunoassay system that specifically measures this hormone, and luteinizing hormone (LH) were measured in serum samples obtained daily from 3 women from about 10 to 30 days after the last menses in the cycle of conception. With the specific assay, it was found that HCG was initially detected from 1 to 3 days earlier than the first observable increase in radioimmunoassayable HCG-LH. HCG was detected initially in the peripheral serum 8 days after ovulation, soon after implantation.