Functional characterization of peripheral blood lymphocytes in chronic HBsAg carriers

Increased proportions of suppressor/cytotoxic T cells have been identified in the peripheral blood of chronic HBsAg carriers and to investigate a possible relationship to T cell cytotoxicity against autologous hepatocytes, suppressor cell activity, viral replication and the histological type of disease, 42 consecutive HBsAg carriers undergoing a liver biopsy have been investigated. The proportion of suppressor/cytotoxic lymphocytes directly correlated with T cell cytotoxicity to autologous hepatocytes and both were higher in those with HBeAg in serum than in those with anti-HBe or those on corticosteroid therapy. There was no relationship to underlying histological classification. In contrast, suppressor cell regulation of IgG producing cells was unrelated to the proportion of suppressor/cytotoxic lymphocytes in peripheral blood or HBeAg status, but impaired function was associated with chronic hepatitis, particularly chronic active hepatitis. These data suggest that the increased proportion of suppressor/cytotoxic lymphocytes in the peripheral blood of HBsAg carriers represents an increase in the cytotoxic and not the suppressor cell subset and that this is a consequence of active viral replication and not of the severity of hepatic inflammation. Defective suppressor cell function may be one factor in the development of chronic active hepatitis, but is not reflected by alterations in the T4:T8 ratio.     

Pancreatic pseudocysts drained through a percutaneous transgastric approach

We describe a new method for the percutaneous drainage of pancreatic pseudocysts using a transgastric approach. We used this technique in three dogs and six patients for whom no other "safe" access route was available. The procedures were performed under US guidance alone or with US combined with fluoroscopy. No complications were observed.     

Approach to acute pharyngitis

The evaluation of the patient with a "sore throat" is deceptively complex. The clinician must first assess the potential for airway compromise. Specific risk factors, reviewed in this article, should be considered, including the presence of a pharyngeal membrane, immunocompromise, potential gonococcal exposure, and prior rheumatic fever.     

Urethral prolapse in children: insights into etiology and management

The pathophysiology of urethral prolapse has never been clearly elucidated. Following en bloc removal of the urethra, bladder, vagina, uterus and pelvic floor tissues from a 4-year-old burn victim with urethral prolapse at the time of death and from a female newborn cadaver, careful step-sectioning of the specimens at 5 mm. intervals for histological examination was performed. The anatomical defects of urethral prolapse noted were marked eversion of the urethral mucosa, vascular congestion of the "corpus spongiosum urethrae muliebris", and a cleavage plane between the inner longitudinal and outer circular-oblique smooth muscle layers of the urethra. We propose that urethral prolapse results from poor attachments between the smooth muscle layers of the urethra in association with episodic increases in intra-abdominal pressure. A clinical review of 12 cases revealed that at least 8 (67 per cent) had antecedent episodes of marked increases in intra-abdominal pressure. Obliteration of the cleavage plane between the smooth muscle layers is important for successful treatment of this lesion.     

How Are Indeterminate Pulmonary Nodules at Diagnosis Associated with Survival in Patients with High-Grade Osteosarcoma?

BackgroundPulmonary metastases are a poor prognostic factor in patients with osteosarcoma; however, the clinical significance of subcentimeter lung nodules and whether they represent a tumor is not fully known. Because the clinician is faced with decisions regarding biopsy, resection, or observation of lung nodules and the potential impact they have on decisions about resection of the primary tumor, this remains an area of uncertainty in patient treatment. Surgical management of the primary tumor is tailored to prognosis, and it is unclear how aggressively patients with indeterminate pulmonary nodules (IPNs), defined as nodules smaller than 1 cm at presentation, should be treated. There is a clear need to better understand the clinical importance of these nodules.Questions/purposes(1) What percentage of patients with high-grade osteosarcoma and spindle cell sarcoma of bone have IPNs at diagnosis? (2) Are IPNs at diagnosis associated with worse metastasis-free and overall survival? (3) Are there any clinical or radiologic factors associated with worse overall survival in patients with IPN?MethodsBetween 2008 and 2016, 484 patients with a first presentation of osteosarcoma or spindle cell sarcoma of bone were retrospectively identified from an institutional database. Patients with the following were excluded: treatment at another institution (6%, 27 of 484), death related to complications of neoadjuvant chemotherapy (1%, 3 of 484), Grade 1 or 2 on final pathology (4%, 21 of 484) and lack of staging chest CT available for review (0.4%, 2 of 484). All patients with abnormalities on their staging chest CT underwent imaging re-review by a senior radiology consultant and were divided into three groups for comparison: no metastases (70%, 302 of 431), IPN (16%, 68 of 431), and metastases (14%, 61 of 431) at the time of diagnosis. A random subset of CT scans was reviewed by a senior radiology registrar and there was very good agreement between the two reviewers (κ = 0.88). Demographic and oncologic variables as well as treatment details and clinical course were gleaned from a longitudinally maintained institutional database. The three groups did not differ with regard to age, gender, subtype, presence of pathological fracture, tumor site, or chemotherapy-induced necrosis. They differed according to local control strategy and tumor size, with a larger proportion of patients in the metastases group presenting with larger tumor size and undergoing nonoperative treatment. There was no differential loss to follow-up among the three groups. Two percent (6 of 302) of patients with no metastases, no patients with IPN, and 2% (1 of 61) of patients with metastases were lost to follow-up at 1 year postdiagnosis but were not known to have died. Individual treatment decisions were determined as part of a multidisciplinary conference, but in general, patients without obvious metastases received (neo)adjuvant chemotherapy and surgical resection for local control. Patients in the no metastases and IPN groups did not differ in local control strategy. For patients in the IPN group, staging CT images were inspected for IPN characteristics including number, distribution, size, location, presence of mineralization, and shape. Subsequent chest CT images were examined by the same radiologist to reevaluate known nodules for interval change in size and to identify the presence of new nodules. A random subset of chest CT scans were re-reviewed by a senior radiology resident (κ = 0.62). The association of demographic and oncologic variables with metastasis-free and overall survival was first explored using the Kaplan-Meier method (log-rank test) in univariable analyses. All variables that were statistically significant (p < 0.05) in univariable analyses were entered into Cox regression multivariable analyses.ResultsFollowing re-review of staging chest CTs, IPNs were found in 16% (68 of 431) of patients, while an additional 14% (61 of 431) of patients had lung metastases (parenchymal nodules 10 mm or larger). After controlling for potential confounding variables like local control strategy, tumor size, and chemotherapy-induced necrosis, we found that the presence of an IPN was associated with worse overall survival and a higher incidence of metastases (hazard ratio 1.9 [95% CI 1.3 to 2.8]; p = 0.001 and HR 3.6 [95% CI 2.5 to 5.2]; p < 0.001, respectively). Two-year overall survival for patients with no metastases, IPN, or metastases was 83% [95% CI 78 to 87], 65% [95% CI 52 to 75] and 45% [95% CI 32 to 57], respectively (p = 0.001). In 74% (50 of 68) of patients with IPNs, it became apparent that they were true metastatic lesions at a median of 5.3 months. Eighty-six percent (43 of 50) of these patients had disease progression by 2 years after diagnosis. In multivariable analysis, local control strategy and tumor subtype correlated with overall survival for patients with IPNs. Patients who were treated nonoperatively and who had a secondary sarcoma had worse outcomes (HR 3.6 [95% CI 1.5 to 8.3]; p = 0.003 and HR 3.4 [95% CI 1.1 to 10.0]; p = 0.03). The presence of nodule mineralization was associated with improved overall survival in the univariable analysis (87% [95% CI 39 to 98] versus 57% [95% CI 43 to 69]; p = 0.008), however, because we could not control for other factors in a multivariable analysis, the relationship between mineralization and survival could not be determined. We were unable to detect an association between any other nodule radiologic features and survival.ConclusionThe findings show that the presence of IPNs at diagnosis is associated with poorer survival of affected patients compared with those with normal staging chest CTs. IPNs noted at presentation in patients with high-grade osteosarcoma and spindle cell sarcoma of bone should be discussed with the patient and be considered when making treatment decisions. Further work is required to elucidate how the nodules should be managed.Level of EvidenceLevel III, prognostic study.     

p63 deficiency activates a program of cellular senescence and leads to accelerated aging

The p53 tumor suppressor plays a key role in organismal aging. A cellular mechanism postulated to drive the aging process is cellular senescence, mediated in part by p53. Although senescent cells accumulate in elderly individuals, most studies have relied on correlating in vitro senescence assays with in vivo phenotypes of aging. Here, using two different mouse models in which the p53-related protein p63 is compromised, we demonstrate that cellular senescence and organismal aging are intimately linked and that these processes are mediated by p63 loss. We found that p63(+/-) mice have a shortened life span and display features of accelerated aging. Both germline and somatically induced p63 deficiency activates widespread cellular senescence with enhanced expression of senescent markers SA-beta-gal, PML, and p16(INK4a). Using an inducible tissue-specific p63 conditional model, we further show that p63 deficiency induces cellular senescence and causes accelerated aging phenotypes in the adult. Our results thus suggest a causative link between cellular senescence and aging in vivo, and demonstrate that p63 deficiency accelerates this process.     

The relevance of pulse repetition rate and radiant exposure to the neurophysiological effects of low-intensity laser (820 nm/pulsed wave) irradiation upon skin temperature and antidromic conduction latencies in the human median nerve

The effects of low-intensity near-infra-red laser irradiation (820 nm; 1.5 and 9.0 J cm^–2; pulsed at 12 Hz, 73 Hz and 5 kHz) upon peripheral neurophysiology and skin temperature were investigated using antidromic conduction studies in the human median nerve in vivo. Healthy human volunteers (n = 90) were recruited and allocated randomly to either a control group (n=10) or one of eight experimental groups (two radiant exposures, 1.5 J cm^–2 and 9.0 J cm^–2 at one of three pulse repetition rates, 12 Hz, 73 Hz or 5 kHz, in addition to a placebo group for each radiant exposure;n = 10 all groups). Analysis of variance (ANOVA) demonstrated a significant (p0.05) decrease in skin temperature following irradiation at the lowest radiant exposure (1.5 J cm^–2) combined with pulse repetition rates of 73 Hz and 5 kHz, with the greatest effect at 73 Hz. These changes in skin temperature were coupled with increases in negative peak latency (NPL); ie changes in NPL were inversely related to changes in skin temperature. However, in contrast to the authors' previous findings using continuous wave (CW) laser irradiation, differences in NPL were not found to be significant. These findings, therefore, provide little evidence of the neuro-physiological effects of low-intensity infra-red irradiation at the dosage levels and pulse repetition rates used here.     

Analgesia after inguinal herniorrhaphy with laparoscopic inspection of the peritoneum in children. Caudal block versus ilioinguinal/iliohypogastric block

The authors prospectively evaluated the efficacy of caudal epidural block versus local infiltration combined with ilioinguinal/iliohypogastric block for analgesia after inguinal herniorrhaphy with laparoscopic inspection of the peritoneum. During standardized anesthetic care, 24 children were randomized to Group I (caudal epidural block with 1.2 mL/kg of 0.25% bupivacaine) or to Group II (local infiltration with an ilioinguinal/iliohypogastric block). Postoperative pain scores were significantly lower at all four evaluation points in Group I than in Group II. Patients in Group I had a significantly decreased requirement for supplemental intravenous fentanyl. Intra-operative requirements for isoflurane were decreased in Group I. The expired concentration of isoflurane was 0.4 +/- 0.1 (mean +/- SEM) in Group I and 1.5 +/- 0.3 in Group II. Time to extubation was 3.8 +/- 0.5 minutes in Group I and 8.2 +/- 1.1 minutes in Group II. The time from arrival in the postanesthesia care unit until discharge home was 113 +/- 3 minutes in Group I and 152 +/- 11 minutes in Group II. Caudal epidural block was more effective than local infiltration in controlling pain after herniorrhaphy with laparoscopy in children and resulted in earlier discharge home.     

Predictors of sun protective behaviors among school students

A random sample of students (N = 3,655) in Grades 7, 9, and 11 from 55 schools in Queensland (Australia) were surveyed about their sun protection knowledge, attitudes, and behaviors. An aggregate sun protection behavior index (SPBI) was developed from self-reported behaviors on a school day and a weekend day. Repeated measures regression analyses revealed that negative views of sun protection measures were associated with low scores on the SPBI, an association that was strongest among older students and in larger schools. Low perceived parental sun protective behaviors were associated with low SPBI ratings, and this association was greatest in small schools and on Saturdays. Older students had lower SPBI ratings, but their scores increased on Saturdays. Gender did not appear to be independently related to the SPBI after adjustment for the other variables. These findings reinforce the need for adolescent sun protection programs to address the complex interactions among psychological, social, and environmental factors that influence different subgroups of the student population.