Quantitation of human in vitro megakaryocytopoiesis by radioimmunoassay

The isolation and characterization of human megakaryocyte growth factors has been hampered because evaluation of megakaryocyte growth in semisolid medium requires both lengthy incubation and visual quantitation. In addition, colony formation requires cell division, while most regulation of platelet production may involve individual, nonproliferating differentiating megakaryocytes. We have developed a radioimmunoassay (RIA) that makes use of an iodinated murine monoclonal antibody (MoAb) specific for platelet/megakaryocyte glycoprotein IIb/IIIa (GPIIb/IIIa) to measure megakaryocyte production in liquid marrow culture. This assay is sensitive to 3 X 10(3) platelets (roughly 30 megakaryocytes) and linear up to 1 X 10(6) platelets, and thus it provides a useful range for quantitating megakaryocyte production in in vitro marrow culture. Significant differences (threefold to fivefold) in megakaryocyte/platelet-specific GPIIb/IIIa complex are detected between stimulated and unstimulated marrow cultures by day 7, although antigen accrual in stimulated cultures continues through at least day 16. Conditions that promote megakaryocyte growth in semisolid medium (ie, aplastic plasma and PHA-LCM) have also been facilitory in liquid culture. This rapid and sensitive assay for cell-bound GPIIb/IIIa should facilitate recognition and isolation of megakaryocyte and platelet growth factors.     

The place of high-dose BEAM therapy and autologous bone marrow transplantation in poor-risk Hodgkin's disease. A single-center eight- year study of 155 patients

Although high-dose chemotherapy and autologous bone marrow transplantation (ABMT) are increasingly being used for the treatment of relapsed and resistant Hodgkin's disease, there have been few large, single-center studies reported with adequate follow-up to allow full evaluation of this therapeutic modality. We present 155 poor-risk Hodgkin's disease patients who received high-dose BEAM (BCNU, etoposide, cytosine arabinoside, and melphalan) chemotherapy and ABMT who have been studied over a period of 8 years. All patients had either not attained a remission on mechlorethamine, vincristine, procarbazine, prednisone-type therapy and had poor prognostic features at presentation, not attained a complete remission or relapsed within 1 year of an initial alternating regimen, or not attained remission with two or more lines of treatment. At the time of ABMT the relapse status of the patients was as follows: 46 patients were primarily refractory to induction therapy, 7 were good partial responders, 52 were in first relapse, 37 in second relapse, and 13 in third relapse. Seventy-eight patients had chemoresistant disease, 33 had chemosensitive disease at the time of ABMT, and 44 were untested for chemosensitivity at latest relapse. The procedure related mortality in the first 90 days post-ABMT of 10% overall. At 3 months 43 patients (28%) were assessed as complete responders, 72 patients had a partial response (46%), and 24 patients (16%) had no response or progression of disease. However, by 6 months, 53 (24%) patients were assessed as complete responders and 51 (33%) patients had nonprogressive disease. Forty-five patients had received radiotherapy post-ABMT to residual masses (41 patients) or to previous sites of bulk disease (4 patients). The actuarial overall and progression-free survival at 5 years was 55% and 50%, respectively. On multivariate analysis patients with bulk (masses > 10 cm), heavily pretreated patients (those receiving three or more lines of treatment) and females had a significantly poorer prognosis. Relapse status was also significant for progression-free survival in that patients in second (60%) and third relapse (70%) had a better prognosis than those in first relapse (44%) or with primary refractory disease (33%). Response to prior chemotherapy did not predict for progression-free survival. These results enable comparisons to be made between high-dose chemotherapy with ABMT and conventional dose salvage therapy. Furthermore, although the results as a whole are highly encouraging, certain groups carry an unfavorable prognosis.     

Prospective Study of TMVR Using Balloon-Expandable Aortic Transcatheter Valves in MAC: MITRAL Trial 1-Year Outcomes

ObjectivesThe aim of this study was to evaluate 1-year outcomes of valve–in–mitral annular calcification (ViMAC) in the MITRAL (Mitral Implantation of Transcatheter Valves) trial.BackgroundThe MITRAL trial is the first prospective study evaluating the feasibility of ViMAC using balloon-expandable aortic transcatheter heart valves.MethodsA multicenter prospective study was conducted, enrolling high-risk surgical patients with severe mitral annular calcification and symptomatic severe mitral valve dysfunction at 13 U.S. sites.ResultsBetween February 2015 and December 2017, 31 patients were enrolled (median age 74.5 years [interquartile range (IQR): 71.3 to 81.0 years], 71% women, median Society of Thoracic Surgeons score 6.3% [IQR: 5.0% to 8.8%], 87.1% in New York Heart Association functional class III or IV). Access was transatrial (48.4%), transseptal (48.4%), or transapical (3.2%). Technical success was 74.2%. Left ventricular outflow tract obstruction (LVOTO) with hemodynamic compromise occurred in 3 patients (transatrial, n = 1; transseptal, n = 1; transapical, n = 1). After LVOTO occurred in the first 2 patients, pre-emptive alcohol septal ablation was implemented to decrease risk in high-risk patients. No intraprocedural deaths or conversions to open heart surgery occurred during the index procedures. All-cause mortality at 30 days was 16.7% (transatrial, 21.4%; transseptal, 6.7%; transapical, 100% [n = 1]; p = 0.33) and at 1 year was 34.5% (transatrial, 38.5%; transseptal, 26.7%; p = 0.69). At 1-year follow-up, 83.3% of patients were in New York Heart Association functional class I or II, the median mean mitral valve gradient was 6.1 mm Hg (IQR: 5.6 to 7.1 mm Hg), and all patients had ≤1+ mitral regurgitation.ConclusionsAt 1 year, ViMAC was associated with symptom improvement and stable transcatheter heart valve performance. Pre-emptive alcohol septal ablation may prevent transcatheter mitral valve replacement–induced LVOTO in patients at risk. Thirty-day mortality of patients treated via transseptal access was lower than predicted by the Society of Thoracic Surgeons score. Further studies are needed to evaluate safety and efficacy of ViMAC.     

The effect of aging on the association between coronary heart disease risk factors and carotid intima media thickness: An analysis of the Atherosclerosis Risk in Communities (ARIC) cohort

Objective

Aging decreases the strength of association between established coronary heart disease (CHD) and its risk factors. Carotid intima media thickness (IMT) is a widely used surrogate for coronary artery disease, which we hypothesized has a similar diminishing age-mediated strength of association with CHD occurrence and prevalence of its risk factors.

Methods and results

Data from the Atherosclerosis Risk in Communities (ARIC) cohort of 14,562 individuals aged 45 to 64 (mean follow up nine years) was stratified into two age groups, 45–54 and 55–64 years, within each of ARIC's four examination visits (n = 14,562; 13,622; 7869; 6628 for visits 1 to 4, respectively). Cross-sectional and longitudinal analyses with multiple linear and logistic regression modeling were used to compare the relationships between carotid IMT (the mean of six far wall sites from the right and left carotid bifurcation, common and internal carotid arteries with imputation of missing data) and the risk factors of smoking, hypertension, hypercholesterolemia, diabetes, and obesity with age. The strength of the associations between carotid IMT and most risk factors were qualitatively stronger across successive visits and within each visit, these associations were stronger in the older, as compared to the younger, age group.

Conclusions

In a large cohort followed for nearly one decade, our hypothesis that age attenuates the association of CHD risk factors and carotid IMT was not supported by ARIC data. Rather, we found that associations between carotid IMT and CHD risk factors remained stable with advancing age, contrary to the relationship between risk factors and CHD outcomes with age. These findings suggest that there is efficacy to continued risk factor management in the elderly.     

Meeting the commitments of the ICPD Programme of Action to young people

Some of the commitments nations have made in international agreements, notably in the ICPD Programme of Action (1994) and the resolution of the UN Committee on Population & Development (2012), to young people include: realisation of the right to education and attainment of a secondary school education; delaying marriage beyond childhood and ensuring free and full choice in marriage-related decisions; exercise of the right to health, including access to friendly health services and counselling; access to health-promoting information, including on sexual and reproductive matters; acquisition of protective assets and agency, particularly among girls and young women, and promotion of gender equitable roles and attitudes; protection from gender-based violence; and socialisation in a supportive environment. These are crucial for a successful transition to adulthood with reference to sexual and reproductive health outcomes. This paper assesses the extent to which these commitments have been realised, drawing from available studies conducted in the 2000s in developing countries. It concludes that while some progress has been made in most of these aspects, developing countries have a long way to go before they can be said to be helping their young people achieve a successful sexual and reproductive health-related transition to adulthood.     

Intracervical versus vaginal misoprostol for cervical dilatation prior to operative hysteroscopy—a comparative study

Background

Hysteroscopic surgery requires pre-operative cervical ripening to facilitate adequate dilatation of the cervix for insertion of operative hysteroscope. This study was conducted to compare the efficacy of intracervical misoprostol with vaginal misoprostol in achieving cervical ripening before operative hysteroscopy.

Methods

In this randomised comparative study conducted at a tertiary care teaching hospital, 56 patients needing operative hysteroscopy were divided into two groups of 28 patients, one for intracervical misoprostol and the other for vaginal misoprostol. Four hundred microgram of misoprostol was inserted on the night before and in the morning of operative hysteroscopy intracervically in group I and vaginally in group II.

Results

Primary outcome measure was number of patients achieving 7 mm preoperative dilatation of cervix. Largest Hegar dilator that could be passed into the uterine cavity past the internal optic sheath without resistance was noted in each case. Mean cervical dilatation prior to operative hysteroscopy was calculated. In addition, incidence of slipping of vulsellum and cervical laceration was also noted. Time to achieve full cervical dilatation was recorded. In 23/28 cases of group I and 5/28 in group II, size 7 Hegar dilator could be passed without effort. Mean cervical dilatation was 7.5 mm in group I and 5.7 mm in group II. Slipping of the vulsellum and cervical lacerations were seen in significantly less patients in group I. Mean time to achieve cervical dilatation to 10 mm was 43.39 seconds in group I and 103.96 seconds in group II (P<0.0001).

Conclusion

Intracervical administration of misoprostol is an effective method of achieving cervical ripening for easy cervical dilatation up to 10 mm prior to operative hysteroscopy.Key Words: cervical ripening, intracervical administration, misoprostol, operative hysteroscopy     

Angelchik prosthesis with oesophageal adenocarcinoma: our surgical approach

The Angelchik prosthesis is an incomplete doughnut-shaped device composed of silicone elastomer used in the treatment of gastro-oesophageal reflux disease (GORD). It is used to encircle the lower oesophagus at the gastro-oesophageal junction (GOJ). The ease of the operation led to the insertion of over 25,000 such prostheses world-wide. However, a variety of major complications including intractable dysphagia, prosthesis migration and gastric erosion required a quarter of these devices to be removed. Development of adenocarcinoma in patients with Angelchik prosthesis is a rare occurrence. This article describes two patients who developed adenocarcinoma above their prosthesis and whose cardio-oesophagectomy was technically challenging due to the formation of a dense inflammatory capsule around the prosthesis. Our surgical approach to curative oesophageal resection with the Angelchik prosthesis in situ is also discussed.     

Favourable Long-term Results with the End-to-Side Jejunoileal Bypass

Background: Although jejunoileal bypass (JIB) causes longstanding weight loss, it is no longer recommended as a surgical treatment of morbid obesity due to adverse effects. Methods: JIB was performed on 87 morbidly obese subjects with a mean age of 35 years. Complete followup on 95% of the patients included monitoring weight, metabolic parameters and liver biopsies up to 25 years postoperatively. Results: The mean (± sd) Body Mass Index (BMI) was reduced from 41.5 ± 5.8 kg m⁻² preoperative, to 26.7 ± 3.8 kg m⁻² at 2 years and 29.7 ± 3.9 kg m⁻² at 16 years follow-up. More than 60% loss of initial excess weight was achieved by 88% of the patients at four years and by 75% at 16 years follow-up. Reversal of the bypass was performed in 3% of the patients and revisions in 8% of the patients. There was no 30-day hospital mortality but there was one (1%) late bypass-related death. Complications included urinary calculi in 39% of the patients, electrolyte disturbances in 25% and transient liver failure in 5.5%. Liver biopsies taken more than 13 years postoperatively in 44 patients revealed no cirrhosis. All patients were normoglycemic and normolipemic at follow-up. Conclusions: The majority of the patients have an acceptable weight reduction, few serious adverse effects but several beneficial effects after more than 16 years. The JIB deserves a reconsideration as an alternative in obesity surgery.