Molecular weight diversity among murine class I antigens: both the mature cell surface forms and the unglycosylated polypeptides vary significantly in molecular weight

The molecular weights of the fully glycosylated cell surface form and the unglycosylated polypeptide of five murine class I antigens (H-2Kb, Db, TL, Qa-1.1, and Qa-2) were compared by SDS-PAGE. Significant molecular weight diversity was observed for both forms among these molecules. The size of the fully glycosylated forms ranged from approximately 52,000 daltons (H-2Db) to 41,000 daltons (Qa-2), whereas the unglycosylated polypeptides ranged from 43,000 daltons (H-2Kb and TL) to 33,000 daltons (Qa-2). The magnitude of the size variation observed in the unglycosylated polypeptides implies that there are differences in the gene organization, RNA processing or post-translational modifications of various class I glycoproteins.     

Risk factors for positive findings in patients with high‐grade T1 bladder cancer treated with transurethral resection of bladder tumour (TUR) and bacille Calmette‐Guérin therapy and the decision for a repeat TUR

Study Type – Therapy (case series) Level of Evidence 4

OBJECTIVE

To determine factors predictive of positive findings at the 3‐month follow‐up evaluation (after transurethral resection of bladder tumour [TUR] and bacille Calmette‐Guérin [BCG] therapy) in patients with initial high‐grade (HG)T1 bladder cancer, and to assess the depth of lamina propria (LP) invasion and effectiveness of BCG therapy.

PATIENTS AND METHODS

In all, 138 patients with initial HGT1‐transitional cell carcinoma (TCC) were prospectively assigned, after TUR + BCG and according to depth of LP invasion, to a postBCG‐TUR (T1b) or cystoscopy/cytology (T1a) at 3 months. Any finding at 3 months was considered positive. The predictive value of 11 clinical and pathological variables was assessed by chi‐squared, Mann–Whitney U and multivariate logistic regression.

RESULTS

Of the 138 patients (14 women, mean age 69 years), 42% had T1a and 58% T1b TCC. Tumour size and carcinoma in situ (CIS) were significantly associated with positive findings and present in 26% (36/138) of the patients. The postBCG‐TUR (T1b cases), was positive in 31% (25/80), including seven infiltrating tumours. On multivariate analysis, again a tumour size of >3 cm (odds ratio, OR, 7.02) and associated CIS (OR 5.4) were significantly related to a positive postBCG‐TUR. A secondary finding was that at 20.3 months; patients with T1a TCC, who did not undergo a repeat TUR, did not have increased progression; only 3% (two of 58) had progressed compared with 21% (17/80) of those with T1b/c TCC (P < 0.002).

CONCLUSIONS

In initial HGT1‐TCC, tumour size and CIS were predictive factors of positive findings at 3 months after the initial TUR + BCG therapy. Patients with HGT1‐TCC invading the LP (T1b TCC) had a seven times higher risk of a positive repeat TUR if the initial tumour was >3 cm and a five‐fold increased risk if associated with CIS. The repeat TUR after BCG therapy allowed confirmation of complete resection and pathological evaluation of the BCG response. Although data are still preliminary, the strategy of performing a repeat TUR only in cases with LP involvement, i.e. T1b TCC, did not increase the risk of progression in cases with T1a TCC.     

NovoTTF-100A versus physician's choice chemotherapy in recurrent glioblastoma: A randomised phase III trial of a novel treatment modality

PurposeNovoTTF-100A is a portable device delivering low-intensity, intermediate frequency electric fields via non-invasive, transducer arrays. Tumour Treatment Fields (TTF), a completely new therapeutic modality in cancer treatment, physically interfere with cell division.MethodsPhase III trial of chemotherapy-free treatment of NovoTTF (20–24 h/day) versus active chemotherapy in the treatment of patients with recurrent glioblastoma. Primary end-point was improvement of overall survival.ResultsPatients (median age 54 years (range 23–80), Karnofsky performance status 80% (range 50–100) were randomised to TTF alone (n = 120) or active chemotherapy control (n = 117). Number of prior treatments was two (range 1–6). Median survival was 6.6 versus 6.0 months (hazard ratio 0.86 [95% CI 0.66–1.12]; p = 0.27), 1-year survival rate was 20% and 20%, progression-free survival rate at 6 months was 21.4% and 15.1% (p = 0.13), respectively in TTF and active control patients. Responses were more common in the TTF arm (14% versus 9.6%, p = 0.19). The TTF-related adverse events were mild (14%) to moderate (2%) skin rash beneath the transducer arrays. Severe adverse events occurred in 6% and 16% (p = 0.022) of patients treated with TTF and chemotherapy, respectively. Quality of life analyses favoured TTF therapy in most domains.ConclusionsThis is the first controlled trial evaluating an entirely novel cancer treatment modality delivering electric fields rather than chemotherapy. No improvement in overall survival was demonstrated, however efficacy and activity with this chemotherapy-free treatment device appears comparable to chemotherapy regimens that are commonly used for recurrent glioblastoma. Toxicity and quality of life clearly favoured TTF.     

Portal vein thrombosis: Insight into physiopathology, diagnosis, and treatment

Portal vein thrombosis (PVT) is a relatively common complication in patients with liver cirrhosis, but might also occur in absence of an overt liver disease. Several causes, either local or systemic, might play an important role in PVT pathogenesis. Frequently, more than one risk factor could be identified; however, occasionally no single factor is discernable. Clinical examination, laboratory investigations, and imaging are helpful to provide a quick diagnosis, as prompt treatment might greatly affect a pa...     

Towards a new paradigm of microscopic colitis: Incomplete and variant forms

Microscopic colitis (MC) is a chronic inflammatory bowel disease that has emerged in the last three decades as a leading cause of chronic watery diarrhoea. MC classically includes two main subtypes: lymphocytic colitis (LC) and collagenous colitis (CC). Other types of histopathological changes in the colonic mucosa have been described in patients with chronic diarrhoea, without fulfilling the conventional histopathological criteria for MC diagnosis. Whereas those unclassified alterations remained orphan for a long time, the use of the term incomplete MC (MCi) is nowadays universally accepted. However, it is still unresolved whether CC, LC and MCi should be considered as one clinical entity or if they represent three related conditions. In contrast to classical MC, the real epidemiological impact of MCi remains unknown, because only few epidemiological studies and case reports have been described. MCi presents clinical characteristics indistinguishable from complete MC with a good response to budesonide and cholestiramine. Although a number of medical treatments have been assayed in MC patients, currently, there is no causal treatment approach for MC and MCi, and only empirical strategies have been performed. Further studies are needed in order to identify their etiopathogenic mechanisms, and to better classify and treat MC.     

Pre-treatment with hyperbaric oxygenation reduces bubble formation and platelet activation

Abstract Bubble formation and platelet activation are major factors contributing to decompression sickness. We hypothesized that pretreatment with hyperbaric oxygen immediately before a dive may reduce bubble formation and platelet activation in humans. Five healthy volunteer subjects (1 female and 4 males; age, 33.6±2.9 years; height, 170±3 cm; weight, 71±8 kg, body mass index, 24.5±22.0 kg/m²) participated in this study with a 4-day protocol. On day 1, a multiplace hyperbaric chamber was used to compress all subjects with air to 4 atmosphere absolute (ATA) for 25 minutes; they were then decompressed to surface pressure at a rate of 10 m/min. Once surface pressure was reached, they were monitored with precordial ultrasonic Doppler at 20 min, 50 min and 80 min. Venous blood samples were obtained immediately before and after pressure exposure. On day 2, all subjects were compressed at 1.6 ATA for 45 min with 100% oxygen; they were then decompressed to surface pressure at a rate of 10 m/min. As soon as they reached surface pressure, they were immediately exposed to the same compression-decompression protocol as day 1; blood samples were taken after the second pressure exposure. Platelet activation was examined before and after exposure. On days 3 and 4, we inverted the protocol to minimize the influence of the first immersion on bubble formation. In comparison to the standard compression protocol, compression after hyperbaric oxygenation led to significantly reduced bubble numbers and platelet activation (11.4%±0.7% vs. 5.4%±0.5%, p<0.05). This study shows that hyperbaric oxygenation pretreatment significantly reduces decompression-induced bubble formation and platelet activation. Hyperbaric oxygenation pretreatment may reduce the risk of decompression sickness in at-risk activities.     

Adenosine and its analogue (-)-N6-R-phenyl-isopropyladenosine modulate anterior pituitary adenylate cyclase activity and prolactin secretion in the rat

The effect of adenosine and its analogue (-)-N6-R-phenylisopropyladenosine (PIA) on both anterior pituitary adenylate cyclase activity and prolactin secretion was examined in the rat. Adenosine inhibited basal adenylate cyclase activity in a dose-dependent manner and also reduced the stimulation of the enzyme by vasoactive intestinal peptide (VIP). Likewise, in primary cultures of anterior pituitary cells, adenosine decreased prolactin secretion in both basal and VIP-stimulated conditions. In perifusion experiments, adenosine also inhibited prolactin release in both basal and TRH-stimulated conditions. PIA produced a biphasic pattern of response of basal adenylate cyclase activity, being inhibitory at low and stimulatory at high concentrations. In VIP-stimulated conditions, low concentrations of PIA inhibited both adenylate cyclase activity and prolactin release from primary cultures of pituitary cells, while no additive stimulatory effect was seen at high concentrations. Similarly, low concentrations of PIA reduced both basal and TRH-stimulated prolactin release from perifused pituitaries, while increasing PIA concentrations restored prolactin release. These data show that adenosine affects basal and stimulated prolactin secretion from anterior pituitary cells. Adenosine receptors seem to be coupled to the adenylate cyclase system in the anterior pituitary gland, suggesting a possible relationship between the effect of adenosine on adenylate cyclase activity and prolactin secretion.     

Laparoscopic hysterectomy in a case of male pseudohermaphroditism with persistent Mullerian duct derivatives

We describe laparoscopic diagnosis and treatment for a case of dysgenetic male pseudohermaphroditism with persistent Mullerian ducts. The patient, a 32 year old man, with a history of surgery for hypospadias and cryptorchidism during childhood, was referred because of anejaculation. He was of short stature, with male external genitalia composed of a small penis and hypoplastic testis (1 ml right, 6 ml left side). Plasma follicle stimulating hormone (FSH) was high (17 mUI/ml), testosterone low (1.9 ng/ml), and his karyotype was 46,XY. Pelvic ultrasound, nuclear magnetic resonance (NMR) and genitography disclosed a uterine-like structure with cavity communicating with the urethra. Laparoscopy and urethrocystoscopy confirmed the presence of a 4 cm uterus, which was removed endoscopically at the same time. A biopsy of the left gonad was also performed. The uterus contained endometrial tissue and was fibrotic. Histology of the left gonad showed spermatocytic arrest. We diagnosed dysgenetic male pseudohermaphroditism. Laparoscopy, in our opinion, is an optimal tool to diagnose and treat abnormal sexual conditions.