Changes in retinoblastoma gene expression during cervical cancer progression

The role of tumour suppressor genes in the development of human cancers has been studied extensively. In viral carcinogenesis, the inactivation of suppressor proteins such as retinoblastoma (pRb) and p53, and cellular oncogenes overexpression, such as c-myc, has been the subject of a number of investigations. In uterine-cervix carcinomas, where high-risk human papillomavirus (HPV) plays an important role, pRb and p53 are inactivated by E7 and E6 viral oncoproteins, respectively. However, little is known about the in situ expression of some of these proteins in pre-malignant and malignant cervical tissues. On the other hand, it has also been demonstrated that c-myc is involved in cervical carcinogenesis, and that pRb participates in the control of c-myc gene expression. By using immunostaining techniques, we investigated pRb immunodetection pattern in normal tissues, squamous intraepithelial lesions (SILs) and invasive carcinomas from the uterine cervix. Our data show low pRb detection in both normal cervical tissue and invasive lesions, but a higher expression in SILs. C-Myc protein was observed in most of the cellular nuclei of the invasive lesions, while in SILs was low. These findings indicate a heterogeneous pRb immunostaining during the different stages of cervical carcinogenesis, and suggest that this staining pattern could be a common feature implicated in the pathogenesis of uterine-cervix carcinoma.     

Cross neutralization of SARS-CoV-2 omicron subvariants after repeated doses of COVID-19 mRNA vaccines

We have measured the humoral response to messenger RNA (mRNA) vaccines in COVID-19 naïve and convalescent individuals. Third doses of mRNA COVID-19 vaccines induced a significant increase in potency and breadth of neutralization against SARS-CoV-2 variants of concern (VoC) including Omicron subvariants BA.1, BA.2, and BA.2.12.1, that were cross-neutralized at comparable levels and less for BA.4/5. This booster effect was especially important in naïve individuals that only after the third dose achieved a level that was comparable with that of vaccinated COVID-19 convalescents except for BA.4/5. Avidity of RBD-binding antibodies was also significantly increased in naïve individuals after the third dose, indicating an association between affinity maturation and cross neutralization of VoC. These results suggest that at least three antigenic stimuli by infection or vaccination with ancestral SARS-CoV-2 sequences are required to induce high avidity cross-neutralizing antibodies. Nevertheless, the circulation of new subvariants such as BA.4/5 with partial resistance to neutralization will have to be closely monitored and eventually consider for future vaccine developments.     

Immunosuppression in Behçet's disease Clinical management and long-term visual outcome

The authors review the visual prognosis of 44 patients with Beh?et's disease referred to the Ophthalmology and Rheumatology Departments (Hospital S. Jo?o-one of the two major referral centers in Northern Portugal), due to ocular complaints or for routine examination, in the last ten years. All fulfilled the clinical criteria for diagnosis of Beh?et's disease. Twenty-six were male and 18 female, with mean age 37 years (range 23-66). The mean evolution time since the first clinical manifestations was ten years (range 1-21). Aphthous stomatitis (100%) and genital ulcers (77.3%) were the initial manifestations preceding eye involvement. HLA-B(51)(5) was present in 27 of 36 typed patients (75%). Ocular manifestations were present in 33 patients (75%)-22 patients with panuveitis, eight with hypopyon, four with chronic anterior uveitis and three with episcleritis. Mean age of onset of ocular complications was 32 years (range 20-54). Retinal vaso-occlusive vasculitis was diagnosed in 26 patients (22 with panuveitis and four with posterior uveitis). To prevent ocular relapses, all needed immunosuppression with corticosteroids (drops, depo or systemic), combined with cyclosporine A (CsA) (5 mg/kg/day) in 13 patients and with chlorambucil or cyclophosphamide in six patients, when sight threatening uveitis had previously been refractory to treatment with systemic steroids. The 13 patients under CsA were observed for a period ranging from eight months to five years. Lowdose CsA was found to abrogate the intraocular inflammation, was well tolerated and had no major adverse effects. Regardless of the type of treatment, 21% (14/66) of the eyes lost useful vision five to ten years after initial diagnosis.     

Case-control analysis of clostridium difficile-associated diarrhea on a gynecologic oncology service

Objective: The incidence, morbidity, and risk factors associated with Clostridium difficile-associated diarrhea (CDAD) were studied in a group of gynecologic oncology patients.Methods: A case-control analysis of gynecologic oncology patients with CDAD was carried out from August 1986 through January 1989 in a university medical center.Results: One hundred twenty-three stool samples were tested for C. difficile using the CDT latex agglutination test (Marion Diagnostics, Kansas City, MO). Thirty episodes of CDAD developed in 23 patients. From August 1986 through July 1988, the incidence was stable at 1.5 episodes/100 admissions. From August 1988 through January 1989, the incidence increased to 9.9 episodes/100 admissions (P = 0.005). Compared with patients with nonspecific antibiotic-associated diarrhea, the study patients were hospitalized longer prior to the development of symptoms (mean 15.2 vs. 9.2 days, P = 0.006) and were admitted more frequently with diarrhea (37% vs. 11%, P = 0.015). The rates of surgery, chemotherapy, and radiation therapy were similar. Fever (57% vs. 14%, P < 0.001), abdominal pain (40% vs. 6%, P < 0.001), bloody stools (27% vs. 3%, P = 0.006), and leukocytosis (64% vs. 26%, P = 0.011) were more common among the study cases. The duration, indication, and number of antibiotics administered were similar, though once started, the mean time to symptoms was longer in the study cases (13.7 vs. 6.1 days, P = 0.004). Seven relapses, 1 death, and 1 unplanned colostomy occurred among women with CDAD.Conclusions: C. difficile is a serious cause of nosocomial morbidity in gynecologic oncology patients. Diarrhea developing after antibiotic exposure is more likely to be associated with C. difficile in patients whose symptoms develop several days after completing antibiotics and in patients with a history of CDAD.     

Epidemiology of dengue and hemorrhagic dengue in Santiago, Cuba 1997]

A dengue epidemic that Cuba reported in 1997 registered more than 500,000 cases of dengue fever produced by viral serotype 1. In 1981, there was an epidemic of dengue hemorrhagic fever produced by serotype 2 of the virus. This time 344,203 clinical cases were reported, 10,312 of which were severe cases of hemorrhagic fever that led to 158 fatalities (101 of them among children). The reintroduction of dengue, and specifically of dengue viral serotype 2 (Jamaica genotype), was quickly detected in January 1997 through an active surveillance system with laboratory confirmation of cases in the municipality of Santiago de Cuba, in the province of the same name. The main epidemiological features of this outbreak are reported in this paper. A total of 3,012 cases were reported and serologically confirmed. These included 205 cases classified as dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), 12 of which were case fatalities (all among adults). Secondary infection with dengue virus was one of the most important risk factors for DHF/DSS. Ninety-eight percent of the DHF/DSS cases and 92% of the fatal cases had contracted a secondary infection. It was the first time dengue hemorrhagic fever was documented as a secondary infection 16 to 20 years after initial infection. Belonging to the white racial group was another important risk factor for DHF/DSS, as had been observed during the 1981 epidemic. During the most recent epidemic it was demonstrated that the so called "fever alert" is not useful for early detection of an epidemic. Measures taken by the country's public health officials prevented spread of the epidemic to other municipalities plagued by Aedes aegypti.     

Modulation of adrenergic receptors during left ventricular hypertrophy development and after regression by captopril.

The objective of this study was to analyze adrenergic receptors during cardiac hypertrophy development, after establishment of cardiac hypertrophy and after regression of cardiac hypertrophy by an angiotensin-converting enzyme inhibitor. Left ventricular hypertrophy (LVH) was induced by abdominal aortic stenosis. After surgery, plasma norepinephrine concentrations (PNE) and left ventricular adrenergic receptors from rat hearts subjected to aortic stenosis were assessed during cardiac hypertrophy development (at 3, 7, 15, and 30 days of aortic stenosis), once cardiac hypertrophy had been established (7 and 14 weeks after the stenosis) and after regression of cardiac hypertrophy by an antihypertensive dose (200 mg/kg/day) of captopril. The presence of LVH was observed from day 7 after stenosis. PNE had significantly increased after 15 days but returned to control values 30 days after surgery. The density of alpha1-adrenoceptors was found to decrease with development of hypertrophy. Once hypertrophy had been established, 7 weeks from stenosis, PNE was not different from control; however, the density of alpha1-adrenoceptors continued to diminish, whereas PNE and the density of beta-adrenoceptors were no different from control values. Fourteen weeks after stenosis, a significant decrease in PNE was recorded, and no change in alpha1- but an increase in beta-adrenoceptors was observed. LVH was reversed by treatment with captopril; PNE was similar in control and stenosed treated animals. The density of alpha1-adrenoceptors was decreased when compared with control animals, and no change in the density of beta-adrenoceptors was observed with treatment. In conclusion, a decrease of alpha1-adrenoceptors was associated with LVH development and earlier stages of established cardiac hypertrophy. Later stages of established cardiac hypertrophy were characterized by no change in alpha1- and an increase in beta-adrenoceptors. Treatment with captopril induced LVH regression and decreased the number of alpha1-adrenoceptors without any change in beta-adrenoceptors.     

Congenital bladder diverticulum and Ehlers-Danlos syndrome: an unusual association

The existence of a vesical diverticulum in the context of a congenital connective tissue disorder such as Ehlers-Danlos syndrome led us to consider the possibility of a relationship. Four types of diverticula can be found in the literature: congenital, acquired, iatrogenic and syndrome-associated. Within the later, Ehlers-Danlos syndromes type IV and IX, even type V, are associated to the existence of vesical diverticula. The potential spontaneous rupture of the diverticulum is a typical feature, as well as post-surgery relapse. The attitude towards such diverticula should be one of watchful waiting, and simple, plasty-free diverticulectomy on the bladder's neck is indicated when performing a surgical procedure.     

Analysis of anti-reflux surgery failure

Recurrent gastroesophageal reflux following fundoplication is a challenging problem, because it is usually refractory to medical treatment and a second, technically difficult, antireflux operation is required. Different factors that may contribute to surgery failure have been identified in children. We present 8 cases who underwent redofundoplication after failed procedures, from a total number of 96 patients operated on due to gastroesophageal reflux. Four patient's had their initial fundoplication performed at our institution. Six patients were neurologically impaired, six had chronic pulmonary disease, and two had esophageal atresia. The main presenting symptoms were recurrent vomiting (n = 8) and aspiration (n = 4). Gastroesophageal reflux was confirmed by barium swallow and endoscopy. Operative findings showed wrap breakdown in two cases, warp breakdown associated with hiatal hernia in five, wrap breakdown associated with paraesophageal hernia in two cases, and paraesophageal hernia with normal wrap in one. A second Nissen procedure were performed in five cases, whereas a Collis-Nissen gastroplasty was realized in three with a short esophagus. Six patients had a successful outcome remaining symptom free, one has severe disphagia, and one has recurrent vomiting. In our experience, patients with recurrent gastroesophageal reflux disease should undergo an antireflux procedure tailored to specific anatomic or functional abnormalities.     

Glandular cystic cystitis

Cystic-glandular cystitis is considered as part of the urothelial pre-neoplastic proliferative abnormalities. This group includes atypical hyperplasia. Von Brunn's nidus, and cystitis cystica. They are a consequence of the changes experienced at the urothelium level in response to inflammation, irritation or carcinogens. Diagnosis is mainly based in the pathoanatomical study of the biopsy obtained following endoscopic resection. The signs and symptoms it presents are varied and show a clear relationship to distribution and extension of cysts. Treatment is based in the removal of irritative factors. Cystectomy with urinary by-pass may be necessary if required by clinical evolution.