Implementation of an outbreak response vaccination campaign with typhoid conjugate vaccine - Harare, Zimbabwe, 2019.

Introduction: Typhoid fever is a public-health problem in Harare, the capital city of Zimbabwe, with seasonal outbreaks occurring annually since 2010. In 2019, the Ministry of Health and Child Care (MOHCC) organized the first typhoid conjugate vaccination campaign in Africa in response to a recurring typhoid outbreak in a large urban setting. Method: As part of a larger public health response to a typhoid fever outbreak in Harare, Gavi approved in September 2018 a MOHCC request for 340,000 doses of recently prequalified Typbar-TCV to implement a mass vaccination campaign. To select areas for the campaign, typhoid fever surveillance data from January 2016 until June 2018 was reviewed. We collected and analyzed information from the MOHCC and its partners to describe the vaccination campaign planning, implementation, feasibility, administrative coverage and financial costs. Results: The campaign was conducted in nine high-density suburbs of Harare over eight days in February-March 2019 and targeted all children aged 6 months-15 years; however, the target age range was extended up to 45 years in one suburb due to the past high attack rate among adults. A total of 318,698 people were vaccinated, resulting in overall administrative coverage of 85.4 percent. More than 750 community volunteers and personnel from the MOHCC and the Ministry of Education were trained and involved in social mobilization and vaccination activities. The MOHCC used a combination of vaccination strategies (i.e., fixed and mobile immunization sites, a creche and school-based strategy, and door-to-door activities). Financial costs were estimated at US$ 2.39 per dose, including the vaccine and vaccination supplies (US$ 0.79 operational costs per dose excluding vaccine and vaccination supplies). Conclusion: A mass targeted campaign in densely populated urban areas in Harare, using the recently prequalified typhoid conjugate vaccine, was feasible and achieved a high overall coverage in a short period of time.

Towards Q-PCR of pathogenic bacteria with improved electrochemical double-tagged genosensing detection.

A very sensitive assay for the rapid detection of pathogenic bacteria based on electrochemical genosensing has been designed. The assay was performed by the PCR specific amplification of the eaeA gene, related with the pathogenic activity of Escherichia coli O157:H7. The efficiency and selectivity of the selected primers were firstly studied by using standard Quantitative PCR (Q-PCR) based on TaqMan fluorescent strategy. The bacteria amplicon was detected by using two different electrochemical genosensing strategies, a highly selective biosensor based on a bulk-modified avidin biocomposite (Av-GEB) and a highly sensitive magneto sensor (m-GEC). The electrochemical detection was achieved in both cases by the enzyme marker HRP. The assay showed to be very sensitive, being able to detect 4.5 ng microl(-1) and 0.45 ng microl(-1) of the original bacterial genome after only 10 cycles of PCR amplification, when the first and the second strategies were used, respectively. Moreover, the electrochemical strategies for the detection of the amplicon showed to be more sensitive compared with Q-PCR strategies based on fluorescent labels such as TaqMan probes.

ANALYSIS OF BAROREFLEX FUNCTION BY MEANS OF MATHEMATICAL MODEL.

Re-evaluation of all functions of baroreflex by means of a simple mathematical model of circulation was the aim of the present study. The following states are modelled: 1. Rest. 2. Immediately after baroreceptor denervation. 3. Several days after denervation. 4. Physical exercise before denervation. 5. Physical exercise several days after denervation. Despite the same cardiac contractility and the same vasodilatation in working muscles as before denervation the cardiac output is by one third lower after baroreceptor denervation. In conclusion, a model simulation revealed the common regulation of blood pressure and blood volume by baroreflex and kidneys as a primary function of baroreflex.

Non-syntenic amplification of MDM2 and MYCN in human neuroblastoma.

Amplification of the MYCN gene is a well documented genetic alteration of aggressively growing human neuroblastomas. Through cytogenetic studies we have identified neuroblastoma cell lines which, in addition to amplified MYCN, carry amplified DNA not harbouring MYCN. In situ hybridization of biotinylated total genomic DNA to metaphase chromosomes of normal human lymphocytes by reverse genomic hybridization revealed the amplified DNA to be derived from chromosome 12 band q13-14. Subsequent filter analyses showed a 20- to 40-fold amplification of the MDM2 gene, located at 12q13-14, both in three cell lines and in an original tumor, in addition to amplified MYCN. As the apparent consequence of amplification abundant MDM2 protein was present, a part of which was complexed with p53.

Thallium kinetics in rat cardiac transplant rejection.

Cardiac transplant rejection is a very complex process involving both cellular and vascular injury. Recently, thallium imaging has been used to assess acute transplant rejection. It has been suggested that changes in thallium kinetics might be a sensitive indicator of transplant rejection. Accordingly, thallium kinetics were assessed in vivo in acute untreated rat heterotopic (cervical) transplant rejection. Male Lewis rats weighing 225-250 g received heterotopic heart transplants from syngeneic Lewis rats (group A; n = 13), or allogeneic Brown Norway rats (group B; n = 11). Rats were imaged serially on the 2nd and the 7th postoperative days. Serial cardiac thallium content was determined utilizing data collected every 150 sec for 2 hr. The data were fit to a monoexponential curve and the decay rate constant (/sec) derived. By day 7 all group B hearts had histological evidence of severe acute rejection, and demonstrated decreased global contraction. Group A hearts showed normal histology and contractility. However, thallium uptakes and washout of the two groups were the same. Peak thallium uptake of group B was +/- 3758 1166 counts compared with 3553 +/- 950 counts in the control group A (P = 0.6395); The 2-hr percentage of washout was 12.1 +/- 1.04 compared with 12.1 +/- 9.3 (P = 1.0000); and the decay constant was -0.00002065 +/- 0.00001799 compared with -0.00002202 +/- 0.00001508 (P = 0.8409). These data indicate that in vivo global thallium kinetics are preserved during mild-to-severe acute transplant rejection. These findings suggest that the complex cellular and extracellular processes of acute rejection limit the usefulness of thallium kinetics in the detection of acute transplant rejection.

A one-way, valved, atrial septal patch in the management of postoperative right heart failure. An animal study.

Patients who undergo surgical repair of congenital heart defects that are characterized by hypoplastic right ventricle or pulmonary hypertension are at high risk for the development of postoperative right heart failure. To minimize this risk, a new one-way, valved, atrial septal patch was developed that serves as an artificial one-way foramen ovale. The feasibility of this device was tested in five dogs in which reversible right heart failure had been induced. Use of the one-way valved patch significantly improved right ventricular performance and reduced right ventricular hydrostatic pressures. The interatrial pressure gradient was reduced from 10 +/- 3.5 mm Hg during right heart failure to 4.4 +/- 1.4 mm Hg. When the device was opened, cardiac output increased significantly. This hemodynamic improvement was achieved at the expense of systemic arterial desaturation, which was, however, well tolerated. When the state of right heart failure was reversed, the one-way valved patch spontaneously closed, allowing no interarterial shunting. The results of this experimental trial suggest that this device can play a useful role in selected patients in whom postoperative right heart failure can be anticipated after surgical repair of certain congenital heart defects.

Aprotinin improves myocardial recovery after ischemia and reperfusion. Effects of the drug on isolated rat hearts.

The effects of aprotinin, a protease inhibitor, on the ischemic and nonischemic isolated rat heart was investigated with the use of the modified Langendorff model. During phase I of the study, hearts were perfused with either low-dose aprotinin (10(5) KIU/L), high-dose aprotinin (10(6) KIU/L), or normal saline solution added to modified Krebs-Henseleit solution. No statistically significant differences in contraction amplitude, contractility, coronary flow, and wet/dry heart weight ratio were observed among the three groups of hearts. In phase II, hearts were exposed to a 40-minute period of global ischemia at 31 degrees C. Ischemic arrest was induced by warm cardioplegia. Before ischemia and during cardioplegia, hearts were perfused with either aprotinin 10(6) KIU/L (n = 10) or normal saline solution (n = 10) for 30 minutes. On reperfusion, recovery of hearts treated with aprotinin was significantly better than that of control hearts, as reflected by better contractility (analysis of variance, p = 0.011), higher coronary flow (p < 0.025), and lower creatine kinase levels (p < 0.05). No statistically significant differences in contraction amplitude were observed between the two groups. When the effect of ischemia within each group of hearts was analyzed, the preserving effect of aprotinin was even more pronounced. In the control group, ischemia caused a decrease in contractility (p < 0.025) and a decrease in oxygen consumption (p = 0.006); by contrast, in the aprotinin group the preischemic values were maintained. Accordingly, we conclude that aprotinin at concentrations up to 10(6) KIU/L has no deleterious effect on normally perfused hearts and has a significant protective effect on the ischemic heart when used in high doses in the preischemic period.

A one-way valved atrial septal patch: a new surgical technique and its clinical application.

Patients who undergo surgical repair of congenital heart defects, characterized by a hypoplastic right ventricle or high pulmonary vascular resistance, are at high risk for the development of postoperative right heart failure. This risk may discourage the surgical team from carrying out a biventricular or complete repair in such patients. To reduce the risk for right heart failure, we developed a one-way, valved, atrial septal patch to serve as an artificial one-way foramen ovale and tested it in an animal model. By permitting right-to-left shunt, this device decompresses the failing right ventricle and maintains systemic cardiac output. The device has been used in 15 patients divided into three different groups: group 1 (n = 8), patients with a hypoplastic right ventricle and pulmonic stenosis or atresia, seven of whom underwent a biventricular repair; group 2 (n = 5), patients with evidence of pulmonary disease after longstanding left-to-right shunt caused by a correctable atrial or ventricular septal defect, all of whom had a complete repair; group 3, two patients with acute right heart failure in whom the device was used as a last option of treatment to wean them from cardiopulmonary bypass. This article presents our data in regard to the use of the one-way, valved, atrial septal patch and the indications for its clinical use.

Partial distal pancreatectomy with a hand-held CO2 laser. An experimental study.

Partial distal pancreatectomy was performed in dogs with CO2 laser. Results were compared with those obtained with use of diathermy and scalpel. Postoperative hyperamylasemia appeared in all the animals. The highest peaks in the laser and scalpel groups were found on the fifth postoperative day, after which they gradually returned to normal; the highest levels appeared in the diathermy group on the 21st day, and returned to normal only after 56 days. Pancreatography showed a sealed duct in the laser and diathermy groups although no duct ligation was performed. Histological study of the laser group disclosed initial thermal injury at the cut section with no damage to the nearby parenchyma, followed later by a smooth, thin scar. In the diathermy and scalpel groups, the injured zone became enlarged later by active parenchymal and interlobular inflammation in the underlying tissue.

The development of the cholinergic system in rat hippocampus following postnatal x-irradiation.

Postnatal X-irradiation of the rat hippocampus results in a marked reduction in the number of the postnatally developing granular neurons in the dentate gyrus and also caused a marked increase in the specific activity of acetylcholinesterase (AChE) and choline acetyltransferase (CAT) and a slight but consistent increase in the activity per whole hippocampus of AChE. The effect of irradiation on the granular neurons and on the cholinergic enzymes was found to be dose and age dependent. Drastic increase in specific enzymatic activities is also observed in the irradiated cerebellum whose granular neurons differentiate postnatally and to a lesser extent in the cerebral cortex in which cell formation is accomplished prior to birth. Staining for AChE activity revealed enhanced staining in the molecular layer and the hilar zone of the irradiated dentate gyrus, and in the striatum lucidum of area CA3 which corresponds to the projection area of the mossy fibers. Enhanced staining in area CA1 and subiculum was noticed especially in the supra- and infrapyramidal layers. Biochemical analysis demonstrated that AChE and CAT activities were 140-180% higher in the subareas of the irradiated vs non-irradiated hippocampus. The development and distribution of the postsynaptic muscarinic receptors in the irradiated hippocampus by [3H]quinuclidinyl benzilate (QNB)-binding were also studied. It was found that the elimination of the postnatally formed neurons does not appear to change the developmental pattern of the [3H]QNB-binding sites but reduced receptor level to about 75% of control to adulthood. Measurements of the [3H]QNB-binding in the subareas within the hippocampus revealed marked reduction in the specific [3H]QNB-binding in the molecular layer of the dentate gyrus but not in other subareas. However, the reduction in [3H]QNB-binding sites in the dentate is not as drastic as the reduction in the number of granular neurons. It is suggested that muscarinic sites may be located on early formed neurons, non-cholinergic afferents, or glial elements in this area.

Cholinergic binding sites in rat hippocampal formation: properties and ontogenesis.

The hippocampal formation of the rat contains two types of membrane-bound cholinergic binding sites, as revealed by specific binding of [3H]quinuclidinyl benzilate (QNB) or of a-[125I]bungarotoxin (a-Btx). The sites differ in pharmacological profile, sensitivity to detergents and ontogenesis. The major binding site (about 17 pmol per adult hippocampus) is of a muscarinic nature, and binds [3H]QNB with an on-rate of 2 x 10(6) M-1 sec-1 and an apparent KD of 0.4 nM. This binding is displaced by low concentrations of muscarinic ligands but not of nicotinic ligands. The earliest increase in binding level is detected at about day 4 postnatal and a sharp increase in total binding takes place between days 10 and 15. Total binding continues to increase gradually about 3-fold until an age of about 7 weeks, at a rate resembling that of acetylcholinesterase. a-Btx-binding sites (about 0.6 pmol per adult hippocampus) display a nicotinic profile with an on-rate constant for a-[125I]Btx of 6 x 10(4) M-1 sec-1 and an apparent KD of 2 nM. Ontogenesis of these sites clearly differs from that of muscarinic sites and acetylcholinesterase. Absolute binding reaches mature levels at an age of 12--14 days postnatal, and binding per tissue protein is higher during the first postnatal days than at maturity. It appears that the level of toxin-binding sites attains mature values before the major synaptogenetic events in the area are completed.

Early septal lesion: effect on the development of the cholinergic system in rat hippocampus.

The development of the cholinergic system in the rat hippocampal formation was studied following lesion of the septal region at an age 2--4 days postnatal (i.e. the lesion was performed prior to the establishment of the septohippocampal connections). The steep increase in acetylcholinesterase (AChE) level, that under normal conditions takes place during the second and the third week postnatal, was not observed in early lesioned animals, and AChE level at maturity was about 30% of control. AChE level of adult-lesioned animals was about 15% of control, suggesting an age-dependent plasticity in response to the lesion. Early deafferentation did not seem to alter the pattern of development of muscarinic binding sites as measured by specific binding of [3H]quinuclidinyl benzilate ([3H]QNB). Total [3H]QNB bound per hippocampus of adult, early-lesioned animals was about 70% of control, but this reduction could be accounted for by the atrophy observed in the hippocampal formation following early lesion. Binding of [3H]QNB per protein in early lesioned animals did not differ from normal. Thus the development and the level of muscarinic binding sites in the hippocampal formation do not seem to depend upon normal establishment of presynaptic contacts.

In vivo modulation of the number of muscarinic receptors in rat brain by cholinergic ligands.

Administration of the muscarinic agonist oxotremorine led to a decrease in the number of muscarinic receptors, as determined by specific binding of [3H]quinuclidinyl benzilate ([3H]QNB), in several rat brain regions both during development and at maturity. In contrast, administration of the muscarinic antagonist scopolamine led to an increase in the number of [3H]QNB-binding sites in various brain regions. Scopolamine also prevented the decrease in the number of [3H]QNB-binding sites induced by administration of an organophosphorus drug. The results are compatible with the hypothesis that the number of brain muscarinic receptors, or at least of a sub-class of them, is regulated by their transmitter.

Sperm motility index: a new parameter for human sperm evaluation.

OBJECTIVE: The study was performed to evaluate the correlation between sperm motility index, a novel parameter of semen quality, and routine semen analysis parameters by microscopic evaluation. DESIGN: Sperm motility index was measured by an electro-optical device, the Sperm Quality Analyzer (United Medical Systems Inc., Santa Ana, CA). Human semen samples covering the whole span of qualities were analyzed prospectively and simultaneously by both methods. SETTING: Samples were collected from patients referred to university hospital infertility clinics. PATIENTS, PARTICIPANTS: Nine hundred sixty-eight semen samples of 812 patients and healthy men were analyzed. MAIN OUTCOME MEASURE(S): Sperm motility index is a measurement of optical density fluctuations caused by motile cells; therefore, a positive correlation was anticipated between its values and semen motility parameters. RESULTS: Sperm motility index values demonstrated statistically significant correlation with motile cell concentration, total cell concentration, and percent motile cells. They were also shown to reliably represent semen quality assessment obtained by two experienced andrologists. CONCLUSIONS: The sperm motility index provides a reliable and objective reflection of semen motility parameters and quality.

Structural modification and cryopreservation of porcine heart valves for xenotransplantation with reduced immunity.

BACKGROUND AND AIM OF THE STUDY: In order to provide valved xenografts with reduced immunity, yet durability comparable with that of homografts, a method for endothelial cell removal was developed. METHODS: Adult porcine valved pulmonary conduits were isolated, washed and incubated in trypsin-EDTA solution. The endothelial cells were flushed free with a stream of culture medium, and the xenografts cryopreserved. Grafts were thawed after three months, and evaluated structurally. RESULTS: Macroscopic inspection of the grafts revealed no cracks or other morphological damage. Light microscopy revealed mildly edematous changes, and the elastic layers appeared to be preserved. Incubation with trypsin-EDTA solution consistently removed the entire endothelial layer, without obvious damage to the underlying tissues. CONCLUSION: With care and appropriate timing, the xenograft endothelium can be selectively removed, leaving the underlying tissue intact. This process may allow further structural manipulations to improve the durability of these grafts.

Outcome and risk factors in octogenarians undergoing open-heart surgery.

BACKGROUND AND AIM OF THE STUDY: Increasing numbers of elderly (aged > 80 years) patients are being referred for cardiac surgery, and results for coronary artery bypass grafting (CABG) are generally better than for combined CABG and valve replacement. METHODS: During the past 55 months, 77 octogenarians underwent cardiac intervention in our institution. Forty-five patients (mean age 82.5 years) underwent CABG alone; surgery was elective in 33% of patients and 2.7 +/- 1.0 grafts per patient were performed. Thirty-two patients (mean age 82.4 years) underwent combined CABG and valve surgery (28 aortic, four mitral); 2.1 +/- 0.8 grafts per patient were performed and 65% of cases were emergencies. RESULTS: In patients undergoing CABG alone, the operative mortality rate was 2% and rose to 4% (n = 2) at the end of follow up. Mean NYHA functional class improved significantly from 3.5 +/- 0.5 to 1.4 +/- 0.3 after surgery (p < 0.05) and most patients reported marked improvement in their quality of life. In CABG + valve surgery patients, the operative mortality rate was 6% (n = 2) and reached 18% by the end of follow up. In these patients the complication rate was 24% and mean hospitalization stay 11.0 +/- 2.9 days, while mean NYHA functional class improved from 3.4 +/- 0.6 to 1.2 +/- 0.5. Data analysis revealed that mitral regurgitation combined with coronary artery disease (p < 0.03) and prolonged cross-clamping time (p < 0.01) were the most important independent factors for mortality. CONCLUSION: This study confirms that, in selected elderly patients, combined CABG and cardiac surgery can achieve good postoperative results.

Induction of controlled cardiac tamponade in the management of massive unexplained postcardiotomy bleeding. Case report and review of the literature.

Massive unexplained bleeding is a catastrophic complication of open heart surgery. The following paper describes a successful attempt to terminate such a hemorrhage by induction of controlled cardiac tamponade which caused augmentation of mediastinal pressure without hemodynamic decompensation, thereby aiding in hemostasis. This modality has not previously reported. Few events in clinical medicine are so ominous as the major unexplained hemorrhage. Diffuse bleeding from multiple transected small vessels may be controlled by mechanical techniques which apply pressure directly over the bleeding area. However, where the mediastinum is the source of bleeding, application of such a direct pressure with a closed chest, is both technically difficult and potentially risky. Reported attempts to stop bleeding by increasing the mediastinal pressure included the induction of pneumothorax, and the increase of positive end expiratory pressure (PEEP) has been published. To the best of our knowledge, a deliberate induction of controlled cardiac tamponade in order to terminate prolonged unexplained massive postcardiotomy hemorrhage has not been reported so far.

Role of protease inhibition in myocardial preservation following ischemia and reperfusion.

Aprotinin, a naturally occurring protease inhibitor, in concentrations of 10(6) KIU/L was found to have no effect on myocardial performance in normally perfused isolated rat hearts, before ischemia. Given during the preischemic period, the drug had a significant protective effect on the reperfused hearts, following cardioplegic ischemia: better contractility upon reperfusion (p < 0.011), faster decline of the ischemic contracture, higher coronary flow (p < 0.025), lower AV-difference (p < 0.05), and lower CPK levels (p < 0.01).

Massive arterial air embolism during cardiopulmonary bypass.

Massive arterial air embolism occurred in two patients during 1250 open heart operations. Emergency measures led to complete recovery in both cases. Flow reversal, hypothermia and anti-oedema measures may be adequate in some clinical situations for total recovery after this catastrophic accident.

Mechanical, biochemical, and structural effects of vitamin D deficiency on the chick heart.

The effects of vitamin D deprivation on the chick heart were investigated from three aspects: cardiac contractility (+/- dP/dT), intracellular high-energy phosphorus compounds, and structural differences. Four-week-old vitamin D-deficient chicks were divided into four groups: Group A served as the normal group and received subcutaneous injections of cholecalciferol; Groups B and C were vitamin D-deficient hearts but perfused differently; Group D received daily subcutaneous injections of 5 micrograms of 1,25(OH)2D3. When the isolated spontaneously beating hearts (modified Langendorff preparation) were perfused with Krebs-Henseleit (KH) solution containing a calcium concentration of 2.5mM, the myocardial contractility of the vitamin D-deficient hearts was significantly increased when compared with group A. After the isolated heart had beaten for one hour, the myocardial contractility in the vitamin D-deficient hearts was found to decline to significantly lower values. Presacrifice administration of 1,25(OH)2D3 improved cardiac performance. Vitamin D deficiency resulted in an enhanced rate of decline of the intracellular high-energy phosphorus compounds. No differences were found in the microscopic study. These observations suggest that vitamin D has a role in cardiac function.