A brief history of testicular organoids: from theory to the wards.

In recent years, researchers have successfully generated many human and mammalian organoid models, including organoids representing the intestine, prostate, ovary, bladder, liver, and brain. Therefore, organoids have become an important research model in the fields of regenerative medicine, drug research, and gene therapy, acting as a bridge between in vivo and in vitro experiments. In addition, testicular organoids (TOs) represent the highest level of in vitro culture of spermatogenic cells in a simulated testicular environment. However, the generation of TOs is still in the early stages, and there is still much room for improvement in dealing with the many challenges and prospects to achieve the goal of TOs that simulate the testicular microenvironment in vitro or even reconstruct the process of spermatogenesis without the need to reconstruct seminiferous tubules. We review the brief history of TO generation and some major strategies for functional applications of TOs, which are the main concerns of our clinicians and laboratory researchers.

Cardiac abnormalities and facial anthropometric measurements in children from the Free State and Northern Cape provinces of South Africa with chromosome 22q11.2 microdeletion.

INTRODUCTION: Microdeletions of chromosome 22 are common and have a prevalence of at least 1/4 000. Cardiac abnormalities, abnormal facial features and palatal abnormalities are frequently present in these patients. AIM: To describe the cardiac lesions and selected measurable facial features in children from the Free State and Northern Cape presenting at the Cardiology Unit of the Universitas Academic Hospital complex in Bloemfontein. METHODS: This was a prospective study in which patients with abnormal facial characteristics were tested using a fluorescence in situ hybridisation (FISH) probe for the 22q11.2 microdeletion. Forty children tested positive for the microdeletion. All patients underwent an echocardiogram and where possible, facial anthropometric measurements were performed. RESULTS: The median age at diagnosis was 3.6 years (range 0.04 years, i.e. 2 weeks to 16.2 years). Tetralogy with or without pulmonary atresia was diagnosed in 43% (n = 17) of the children and truncus arteriosus in 20% (n = 8). A rightsided aortic arch was present in 43% (n = 17) of the patients. Mid-facial height was slightly longer (median = 1.0; range -0.5 to 3.3) and width narrower (median = -1.4; range -2.2 to 0.1) than normal. Ear height and width were notably small compared to normal, with median -scores = -3.3 (range -4.8 to -2.6) and = -2.4 (range -3.4 to -1.4), respectively. CONCLUSIONS: Microdeletions of chromosome 22q11 are present in children from the Free State and Northern Cape. Conotruncal cyanotic heart lesions, especially tetralogy with or without pulmonary atresia and truncus arteriosus were the most frequent congenital cardiac diagnoses. A right-sided aortic arch was also commonly present in these children. Facial features varied and small ears were the most noteworthy anthropometric feature. A right-sided aortic arch with or without a congenital cardiac lesion, a long, narrow mid-face and small ears should alert the physician to the possibility of a microdeletion on the long arm of chromosome 22.

Strong coupling of nonlinear electronic and biological oscillators: reaching the "amplitude death" regime.

Interaction between an electronic and a biological circuit has been investigated for a pair of electrically connected nonlinear oscillators, with a spontaneously oscillating olivary neuron as the single-cell biological element. By varying the coupling strength between the oscillators, we observe a range of behaviors predicted by model calculations, including a reversible low-energy dissipation "amplitude death" where the oscillations in the coupled system cease entirely.

Treatment of mesothelioma in Bloemfontein, South Africa.

OBJECTIVE: Two different surgical methods for treating mesothelioma (pleurectomy and pleuro pneumonectomy) were reviewed. METHODS: This was a retrospective study from 1976 to 2001. Forty-six patients, aged 35-80 years, received one of the following procedures: pleurectomy (n=29), or pleuro pneumonectomy (n=17). Pleurectomy was indicated in symptomatic patients with pain or pleural effusion while pleuro pneumonectomy was indicated in patients with Butchart stage I or II disease and an acceptable cardiopulmonary reserve. Patients received either chemotherapy, radiation, or in combination after surgery. RESULTS: The mortality rate was 3.8% for pleurectomy patients and 5.8% for pleuro pneumonectomy patients. The median survival rate for pleurectomy patients was 9 months, and 12 months for pleuro pneumonectomy patients. Pleuro pneumonectomy patients experienced less morbidity and had a shorter hospital stay than pleurectomy patients. CONCLUSIONS: Improved survival was obtained with both procedures. Morbidity was higher in the patients who underwent pleurectomy. Important prognostic factors include tumor stage, tumor histology, duration of symptoms, and weight loss or pain as a presenting symptom. Patients with a low tumor stage, epithelial histology, absence of pain or weight loss, and a longer onset of symptoms had the best survival rate. A trend towards improved survival in patients undergoing pleuro pneumonectomy and receiving radiation as adjuvant therapy was observed.

True acquired left ventricular aneurysms in childhood.

AIM: True left ventricular aneurysms are rarely encountered in childhood. Etiological factors are varied and often indeterminable. There is a paucity of literature detailing the surgical techniques used to repair pediatric aneurysms. METHODS: Three children aged 21 months, 19 months and 5 years with true left ventricular aneurysms underwent surgical repair in our unit. The clinical details, surgical technique, histological review, hospital outcome and short term follow-up is discussed. RESULTS: Two patients underwent repair of their aneurysms by means of the Cooley endoaneurysmorraphy technique, and 1 patient underwent repair using the aneurysm resection and linear plication technique. Histological examination revealed tuberculosis to be the etiological factor in one patient, while a non-specific vasculitis was present in the other 2 patients. Immediate postoperative course was uneventful and all 3 patients were discharged from hospital within one week. Two patients were recatheterized during follow-up visits. All patients were asymptomatic at 1 year follow-up. Echocardiography demonstrated good left ventricular function with disappearance of preoperative mitral regurgitation. CONCLUSION: Pediatric left ventricular aneurysms may be successfully repaired using standard operative techniques. These techniques render excellent short-term RESULTS: Longer follow-up is needed to fully evaluate the outcome of these children.

Eating disorders: current concepts.

OBJECTIVE: To review for the community pharmacist common eating disorders and suggest strategies for pharmacist-directed patient education. DATA SOURCES: Current literature. DATA SYNTHESIS: Women are much more likely than men to develop eating disorders, and Western culture's emphasis on thinness contributes to the prevalence of eating disorders in the United States. Regardless of the type, all eating disorders are rooted in emotions, often traced to problems during adolescence. Anorexia nervosa patients continually set and strive to obtain lower goal weights to the point that their general well-being is compromised. Bulimia nervosa is characterized by excessive eating followed by purging that is an apparent attempt to relieve the tension and guilt associated with the initial overeating. Rather than directly dealing with tension and anger, a patient suffering from binge eating overindulges in food. Most overeaters are aware that excess weight is detrimental to their health, but they cannot control their overeating behavior. CONCLUSION: In treating eating disorders, it is important to address patients' emotional and psychological needs as well as physical symptoms. Patients often need encouragement to seek and continue treatment, and pharmacists are in an ideal position to provide that support.

Features of unusual metastases from prostate cancer.

A retrospective study of CT examinations on 508 patients with prostate carcinoma was performed in order to document the presence or absence of uncommon nodal and extranodal metastases according to pre-defined criteria. 45 atypical metastases were demonstrated in 36 patients. There were 23 atypical nodal metastases including unusual distribution (19/23), large volume (7/23) and atypical morphology or contrast enhancement pattern (8/23). 22 atypical extranodal metastases included orbit/skull base (11), pulmonary (4), liver (3), intracranial (2), ocular (1) and adrenal (1). Atypical prostate carcinoma metastases are usually encountered in the presence of known advanced disease but can be the presenting feature of malignancy or the only sign of distant spread. Knowledge of atypical manifestations of metastatic disease will reduce diagnostic delay, allow accurate staging and lead to the effective and timely delivery of appropriate treatment.

Evaluation by magnetic resonance imaging of the inferior vena cava in patients with non-seminomatous germ cell tumours of the testis metastatic to the retroperitoneum.

OBJECTIVE: To assess the role of magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) in evaluating suspected occlusion of the inferior vena cava (i.v.c.) in patients with abdominal nodal metastases from non-seminomatous germ cell tumours, thus giving information that may be helpful in planning surgery and for determining the need for anticoagulant therapy. PATIENTS AND METHODS: Five patients with abdominal nodal metastases in whom occlusion of the i.v.c. was suspected on computed tomography (CT) were imaged using a 1.5 T MRI scanner. The MRI findings were compared with those from CT. RESULTS: The MR images successfully and clearly detected partial and total occlusions of the i.v.c. by both intraluminal thrombus and extrinsic compression. The technique also clearly detected extensive collateral venous circulation in several cases and in one a cavernous transformation of the i.v.c. In all patients, the MRI studies provided better information than that from CT. CONCLUSION: MRI, and particularly MRA, is a comparatively new technique that is non-invasive and offers the potential of evaluating vascular structures with no need for ionizing radiation or contrast media. This technique, if available, should be chosen for imaging the i.v.c. in patients suspected of having compression or occlusion of the i.v.c.

The relationship between resource constraints and physician problem solving. Implications for improving the process of care.

OBJECTIVES: Research suggests that physicians will engage in more vigilant problem-solving under conditions of resource constraints than under conditions of resource slack. Increased vigilance related to physicians' clinical strategies enhances care by disposing physicians toward more optimal care choices. The authors examine whether pressures for clinical resource constraints encourage increased and sustained vigilance in problem-solving among cardiologists treating acute myocardial infarction. METHODS: The physician problem-solving process is reconstructed from the medical records of all eligible cases of acute myocardial infarction treated by the physician sample set over a 6-year period. The sample period encompasses phases of both resource slack and resource constraints. The Herfindahl index is used to measure the relative amount of vigilant problem-solving activity exhibited in each of five major tactical areas of the physician care strategies in each year of the study. RESULTS: The results support the hypothesis that resource constraints initially promote a shift to increased vigilance in physician problem-solving. Only one of the five major tactical areas, however, is characterized by sustained vigilance over time. The other areas are, instead, associated with a substantial reduction in vigilant activity after the initial peak period. CONCLUSIONS: The results suggest that resource constraints do set the stage for improved clinical decision-making. Sustained vigilance, however, appears to apply only to those portions of the care strategy for which the physician can draw a clear link between optimizing clinical activity and reducing resource consumption. For those portions of the care strategy for which the physician cannot establish a clear link, ongoing pressures to conserve resources results in reduced vigilance and a potential reduction in quality of clinical decision-making.

Ruptured abdominal aortic aneurysms--prognostic indicators and complications affecting mortality. A local experience.

Although elective abdominal aortic aneurysm (AAA) repair can be done with a less than 5% mortality rate, ruptured AAAs have a 32-85% mortality rate. The aims of this study were: (i) to identify prognostic factors affecting mortality; (ii) to identify and assess the impact of postoperative complications on mortality; and (iii) to try to identify a subgroup of patients who would not benefit from surgery. The records of 54 patients presenting with ruptured AAAs were reviewed; 49 of these patients were operated on, 43 of them males and 6 females (mean age 67 years). The operative mortality rate was 44%, most patients who died doing so in the intensive care unit. In 14 cases AAA was diagnosed before rupture--6 of these patients died. Factors that had a significant effect on mortality were: (i) associated ischaemic heart disease--83% of these patients died postoperatively; (ii) the degree of shock on admission--66% of patients with a blood pressure on admission of 85 mmHg or less died; and (iii) the number of postoperative complications per patients--those with 2 or more complications had an 83% mortality rate. Factors that did not correlate statistically with mortality were age, time interval to surgery, volume and composition of intra-operative fluid therapy, and length of surgery. The most important correctable error was failure to operate electively. From the factors assessed it was not possible clearly to identify a subgroup of patients in this study who should have been excluded from surgery.

A study of dental anxiety in a Belfast population.

BACKGROUND AND DESIGN: This study was undertaken to assess the levels and behavioural consequences of dental anxiety in a Belfast population. Fear is associated with poor attendance, leading to neglect and so Northern Ireland, with the highest caries rate in the United Kingdom, seemed a good place to examine dental anxiety and its relation to dental health status. A questionnaire was used to examine the prevalence and accompanying effects of dental anxiety. The results were statistically analysed.

An evaluation of the antirhinoviral activity of acetylfuran replacements for 3-methylisoxazoles. Are 2-acetylfurans bioisosteres for 3-methylisoxazoles?

As a probe of the 3-methylisoxazole portion of our broad-spectrum antipicornaviral series, a panel of 2-acetylfuran analogues was prepared as replacements for the 3-methylisoxazole ring. Comparison of the two series showed remarkable similarity in potency, spectrum of activity, logP, and electrostatic parameters. X-ray studies of 21b bound to human rhinovirus-14 showed that the 2-acetyl group adopted a syn conformation and the carbonyl oxygen acts as a hydrogen bond acceptor with ASN219 in much the same way as the nitrogen of the isoxazole. The importance of the syn conformation and the hydrogen-bonding capability was confirmed by the reduced antiviral activity of the 2-methylfuran and 2-formylfuran analogues. From the results of this study, it is apparent that the syn-2-acetylfuran ring is acting as a bioisostere for the 3-methylisoxazole.

Structural characterization of the micelle-vesicle transition in lecithin-bile salt solutions.

Small-angle neutron scattering (SANS) and dynamic light scattering (QLS) are used to characterize the aggregates found upon dilution of mixed lecithin-bile salt micelles. Molar ratios of lecithin (L) to taurocholate (TC) studied varied from 0.1 to 1, and one series contained cholesterol (Ch). Mixed aggregates of L and taurodeoxycholate (TDC) at ratios of 0.4 and 1 were also examined. In all cases the micelles are cylindrical or globular and elongate upon dilution. The radius of the mixed micelles varies only slightly with the overall composition of lecithin and bile salt which indicates that the composition of the cylindrical micelle body is nearly constant. The transition from micelles to vesicles is a smooth transformation involving a region where micelles and vesicles coexist. SANS measurements are more sensitive to the presence of two aggregate populations than QLS. Beyond the coexistence region the vesicle size and degree of polydispersity decrease with dilution. Incorporation of a small amount of cholesterol in the lipid mixture does not affect the sequence of observed aggregate structures.

Oxadiazoles as ester bioisosteric replacements in compounds related to disoxaril. Antirhinovirus activity.

A series of 1,2,4-oxadiazoles has been prepared as ester bioisosteres and tested against 15 human rhinovirus serotypes, and the MIC80, the concentration which inhibits 80% or 12 of the serotypes tested, was determined. Homologation of the alkyl group attached to the oxadiazole ring resulted in a reduction in activity with increased chain length. Introduction of hydrophilic groups in this position rendered the compounds inactive. Increasing the length of the side chain attached to the isoxazole ring resulted in an increase in activity. Replacement of the methyl with alkoxyalkyl substituents retained activity; however, introduction of a hydroxyl group on to the side chain reduced activity. Compound 8a, where both the isoxazole and oxadiazole rings were substituted with methyl groups, was one of the most active compounds in the series. A comparison was made between 8a and the two isomeric oxadiazoles 41 and 46, and an attempt was made to explain the difference in activity by examining electrostatic potential maps and by an energy profiling study. No conclusive results were obtained from these studies.

Case report: multiple intra-cranial metastases from a prolactin-secreting pituitary tumour.

Only seven cases of metastatic prolactin-secreting pituitary tumour have been reported in world literature. The metastases were intra-cranial in five cases and extra-cranial in two cases. We report a further case with multiple intra-cranial metastases in the supra-tentorial compartment. Histologically, both primary and metastatic tumours were benign with strongly positive immuno-histochemical staining for prolactin. Our case exemplifies the inconsistent correlation between the histopathological appearance and biological behaviour of malignant pituitary tumours.

Case report: the transabdominal ultrasound appearances of a colovesical fistula.

When the clinical manifestations of colovesical fistulae lack diagnostic features, significant diagnostic delay may result. The literature contains conflicting recommendations regarding the optimal method of imaging such fistulae. We describe the transabdominal ultrasound appearances of a colovesical fistula and review the relevant literature. The identification of the ureteric orifices with their associated urinary jets and the use of abdominal compression are essential components of the technique.

Renal artery embolization with ethanol and gelfoam for the treatment of ureteric fistulae with one year follow-up.

Two patients with ureteric fistulae who were unfit for reconstructive surgery were treated by renal ablation using intra-arterial ethanol, gelfoam fragments and in one case coils. In both cases the fistulae dried-up on the same day and both patients are well and normotensive a year later. Our conclusion is that renal ablation by arterial embolization with ethanol can be a valuable alternative to surgery to treat ureteric fistulae in patients who are poor surgical risks.

Outpatient treatment of hyperemesis gravidarum with stimulus control and imagery procedures.

Hyperemesis gravidarum is a frequent illness among women in their first trimester of pregnancy. This study evaluated the use of an outpatient behavioral approach to treat hyperemesis in four women. The subjects, all health care professionals, were treated with stimulus control and imagery procedures in an A-B design, with follow-up. The results demonstrated the clinical effectiveness of outpatient behavioral treatment procedures in the management of mild/moderate hyperemesis gravidarum.