Female circumcision (female genital mutilation): a problem for brachytherapy in cervical cancer

Female circumcision is a traditional practice common in African countries. It involves partial or total removal of external female genitalia. It has led to many complications, in particular, the scarring of the external genitalia. The consequence is a very narrow introitus making the intracavitary brachytherapy treatment component difficult when these women develop cancer of cervix. We present two such cases from our institution. Our aim is to make the radiation and gynecological oncologists, both in developed and developing countries, aware of this practice and the problems they can encounter in the management of such cases. Intracavitary brachytherapy is an important component in the potentially curative role of radiation therapy for cervical cancer. Every effort should be made to ensure that the sequelae of genital mutilation does not deprive these women of the same standard of care as the general population.     

Favourable outcome in sclerotherapy for bleeding oesophageal varices in schistosomiasis: Results in 30 patients

Abstract Thirty consecutive patients with bleeding oesophageal varices secondary to schistosomal liver disease received injection sclerotherapy. These formed a part of a prospective study, to evaluate the role of sclerotherapy in the treatment of bleeding oesophageal varices due to different aetiological factors in patients seen at the Gastroenterology Unit, Riyadh Armed Forces Hospital, Saudi Arabia, between December 1980 and July 1984.
Schistosomiasis is endemic in parts of Saudi Arabia. Sclerotherapy has a special place in schistosomal liver disease as liver function is well preserved in this disease. The new antischistosomal drugs are effective and may halt the progress of the disease. However, in many patients portal hypertension with bleeding oesophageal varices is found at diagnosis. Of the patients with schistosomiasis, 63.3% were Group A Child's Classification. Oesophageal varices have been eradicated in 11 cases during the mean follow-up period of 28 months (range 3-44 months). Four patients were referred for surgery because of bleeding gastric varices, two of whom died following operation. One patient, who was also hepatitis B surface antigen positive, died due to re-bleeding from gastric varices. The remaining 25 patients had no recurrence of bleeding and their liver function remained satisfactory.
Surgical procedures for oesophageal varices in schistosomiasis carry the risk of peri-operative and postoperative morbidity and mortality. In contrast, complications following sclerotherapy are minor compared to surgical procedures and none of our patients had any serious sclerotherapy complications.     

Cardiac Tamponade,Sever Hypothyroidism and Acute Respiratory Distress Syndrome (ARDS) with COVID-19 Infection

A 21-years-old with Down syndrome presented with respiratory distress. Initial investigations revealed a cardiac tamponade. On further evaluation, he had positive coronavirus disease-2019 (COVID-19), severe chest infection and severe hypothyroidism. He responded well to urgent pericardiocentesis, levothyroxine, hydrocortisone and tocilizumab.     

Identification of an oncogenic form of the thrombopoietin receptor MPL using retrovirus-mediated gene transfer

Thrombopoietin and its receptor (MPL) are important regulators of megakaryopoiesis. We have identified an activating mutation of MPL using a combination of a retrovirus-mediated gene transfer and polymerase chain reaction-driven random mutagenesis. This point mutation causes a single amino acid substitution from Ser498 to Asn498 in the transmembrane region and abrogates factor-dependency of all interleukin-3-dependent cell lines tested. Murine interleukin-3- dependent Ba/F3 cells expressing the mutated but not the normal form of MPL were tumorigenic when transduced into syngeneic mice. Analysis of intracellular signaling pathways indicated that the mutant MPL protein constitutively activated two distinct signaling pathways, SHC-Raf-MAPK and JAK2-STAT3/STAT5.     

Exploring the utility of whole‐exome sequencing as a diagnostic tool in a child with atypical episodic muscle weakness

The advent of whole‐exome next‐generation sequencing (WES) has been pivotal for the molecular characterization of Mendelian disease; however, the clinical applicability of WES has remained relatively unexplored. We describe our exploration of WES as a diagnostic tool in a 3½‐year old female patient with a 2‐year history of episodic muscle weakness and paroxysmal dystonia who presented following a previous extensive but unrevealing diagnostic work‐up. WES was performed on the proband and her two parents. Parental exome data was used to filter potential de novo genomic events in the proband and suspected variants were confirmed using di‐deoxy sequencing. WES revealed a de novo non‐synonymous mutation in exon 21 of the calcium channel gene CACNA1S that has been previously reported in a single patient as a rare cause of atypical hypokalemic periodic paralysis. This was unexpected, as the proband's original differential diagnosis had included hypokalemic periodic paralysis, but clinical and laboratory features were equivocal, and standard clinical molecular testing for hypokalemic periodic paralysis and related disorders was negative. This report highlights the potential diagnostic utility of WES in clinical practice, with implications for the approach to similar diagnostic dilemmas in the future.     

Development of an instrument for the identification of frail older people as a target population for integrated care

Background

Primary care is increasingly interested in the identification of frailty, as it selects the target population for integrated care. However, instruments for the identification of frailty specifically validated for use in primary care are scarce. This study developed the Easycare Two-step Older persons Screening (Easycare-TOS), which provides a valid, efficient, and pragmatic screening procedure to identify frail older people.

Aim

This paper aims to describe the development of the Easycare-TOS and the data from the pilot studies.

Design and setting

Observational pilot study in seven academic GP practices in and around Nijmegen, The Netherlands.

Method

The Easycare-TOS was developed in a cyclic process with the input of stakeholders. In every cycle, the requirements were first defined, then translated into a prototype that was tested in a pilot study. The Easycare-TOS makes optimal use of prior knowledge of the GP, and the professionals’ appraisal is decisive in the frailty decision, instead of a cut-off score. Further, it considers aspects of frailty, as well as aspects of the care context of the patient.

Results

The pilot data have shown that after step 1, two-thirds of the patients do not need further assessment, because they are judged as not frail, based on prior knowledge of the GP. The overall prevalence of frailty in this pilot study is 24%. Most professionals who participated in the pilot studies considered the time investment acceptable and the method to be of added value.

Conclusion

The Easycare-TOS instrument meets the predefined efficiency, flexibility, and acceptability requirements for use as an identification instrument for frailty in primary care.     

Tissue-specific dysregulation of 11beta-hydroxysteroid dehydrogenase type 1 and pathogenesis of the metabolic syndrome

Glucocorticoids are important regulators of glucose, lipid and protein metabolism, acting mainly in the liver, adipose tissue and muscle. Chronic glucocorticoid excess is associated with clinical features, such as insulin resistance, visceral obesity, hypertension, and dyslipidemia, which also represent the classical hallmarks of the metabolic syndrome. Elevenbeta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1), a key intracellular enzyme which catalyses the conversion of inactive cortisone to active cortisol, has been implicated in the development of the metabolic syndrome. The shift of this reaction towards cortisol generation may lead to tissutal overexposure to glucocorticoids even with normal circulating cortisol levels. The most robust evidence in support of a pathogenetic role of this enzyme in the development of the metabolic syndrome has been reported in experimental animals, whereas results of human studies are less convincing with several case control and cross-sectional studies showing an association between with 11beta-HSD-1 setpoint and individual features of the metabolic syndrome. However, recent data suggest a tissue-specific rather than systemic alteration of this shuttle, with down-regulation in liver but up-regulation in adipose tissue and skeletal muscle of obese subjects. New techniques based on direct tissutal estimates of cortisol/cortisone ratios are clearly needed to precisely assess the role of enzyme in all target tissues. If confirmed, these results would prompt the development of selective and tissue-specific 11beta-HSD-1 inhibitors to decrease insulin resistance and treat the metabolic syndrome, thus contrasting the harmful effects of glucocorticoid excess in peripheral tissues.     

Chronic Viral Hepatitis in Thalassemic Liver Disease: A Long-Term Study in Patients with Acute Hepatitis with Nontransfusion-Dependent Thalassemia Minor

To evaluate the effective role of hepatitis viruses in thalassemic (Th) liver disease, we carried out a long-term study in 42 subjects with nontransfusion-dependent Th minor hospitalized for an episode of acute viral hepatitis. 10 patients had serologic evidence of hepatitis A, 23 of hepatitis B and 9 of hepatitis non-A, non-B. In the follow-up chronic hepatitis was detected histologically in 5/23 patients with hepatitis B and 5/9 with hepatitis non-A, non-B. All hepatitis A patients recovered completely. The prevalence in 7 out of 10 patients with chronic hepatitis of piecemeal necrosis and of inflammatory changes over hepatic siderosis and fibrosis evidenced a determinant role of chronic viral infection in the development of liver damage in these patients. Thus, heterozygous nontransfusion-dependent Th patients seem to have a high risk of developing a chronic inflammatory liver disease especially after an episode of non-A, non-B hepatitis. Therefore, in our geographical area, chronic hepatitis of viral origin should be taken into account, among other pathogenetic factors, in many cases of cryptogenic thalassemic liver disease.