Magseed placement before neoadjuvant chemotherapy to facilitate subsequent breastconserving surgery - a single-centre audit.

BACKGROUND: A radio-opaque clip is placed in all patients planned for breast-conserving surgery (BCS) receiving neoadjuvant chemotherapy (NACT) to localise the tumour bed in case response to chemotherapy makes later localisation impossible. A tumour that was localised with a radio-opaque clip before NACT will then need a second localisation procedure, after the completion of NACT to aid BCS. The two most commonly used methods are hookwire and radioguided occult lesion localisation. Magseed®, a newly available technology consisting of a small magnetic seed, has now become available. The seed is placed instead of a radio-opaque clip before the start of or during NACT and can remain in place until the time of BCS. METHODS: A retrospective cohort study was performed, collecting data on patients who had a Magseed placed before or during NACT from December 2018 to February 2020. RESULTS: Twenty-one Magseed devices were placed into the breasts of 20 patients, 18 under ultrasound guidance, and three under stereotactic guidance. The average breast volume of individuals who had seeds placed was 1 532 g ± 869 g. The duration that the seeds were in situ was 138 days ± 45 days. All preoperatively placed seeds were retrieved at the surgery with no observed migration outside the tumour bed. CONCLUSION: Magseed placement before NACT is a safe and technically simple technique that can be done under ultrasound guidance in the majority of cases. It has the advantage of being a single procedure with an associated reduction in time off work and travel cost to the patient, as well as flexibility in terms of the time of placement.

Carrier-Envelope Phase-Dependent Strong-Field Excitation.

We present a joint experimental-theoretical study on the effect of the carrier-envelope phase (CEP) of a few-cycle pulse on the atomic excitation process. We focus on the excitation rates of argon at intensities in the transition between the multiphoton and tunneling regimes. Through numerical simulations, we show that the resulting bound-state population is highly sensitive to both the intensity and the CEP. The experimental data clearly agree with the theoretical prediction, and the results encourage the use of precisely tailored laser fields to coherently control the strong-field excitation process. We find a markedly different behavior for the CEP-dependent bound-state population at low and high intensities with a clear boundary, which we attribute to the transition from the multiphoton to the tunneling regime.

A case of secondary syphilis manifesting as a pulmonary pseudo-tumour with nephrotic syndrome.

The global incidence of primary and secondary syphilis is increasing in high-risk groups. However, pulmonary syphilis remains exceedingly rare with less than 30 cases recorded since 1967. Of these cases, none have recorded the presence of both pulmonary and renal involvement with nephrotic syndrome. Diagnosis of pulmonary syphilis remains a challenge, and there is no consensus on treatment. We report a case of a 46-year-old male with secondary pulmonary syphilis and concomitant nephrotic syndrome.

CD68-positive tumour associated macrophages, PD-L1 expression, and EBV latent infection in a high HIV-prevalent South African cohort of Hodgkin lymphoma patients.

A higher proportion of CD68-positive tumour associated macrophages (TAMs) has been associated with poorer outcomes in HIV-negative patients with Hodgkin lymphoma (HL), but whether this is true in HIV-positive patients with HL is not known. In this study, we investigated the number of CD68-positive TAMs and expression of programmed cell death-ligand 1 (PD-L1) in lymph node specimens from HL patients and correlated expression with clinical features (HIV status, disease severity and survival) and histopathological features (EBV latent positivity and subtype of HL). We stained archived lymph node specimens from 77 patients diagnosed with HL for CD68 and PD-L1. Stains were graded as: CD68 low (≤25%), CD68 high (>25%), PD-L1 low (≤50%), and PD-L1 high (>50%). Expression levels were correlated with the clinical and histopathological features using bivariate and multivariate analyses. Survival was analysed by overall and progression-free survival. Thirty-four of the 77 included patients (44%) were HIV-positive. EBV latency was detected in 97% of HIV-positive HL patients and in 14% of HIV-negative HL patients. A high CD68 score was associated with lower median haemoglobin levels (9.4 vs 11.4 g/dL; p=0.02), platelet numbers (262 vs 424 cells ×109/L; p=0.01), and lymphocyte numbers (0.99 vs 1.70 cells ×109/L, p=0.01) and a trend towards advanced disease (international prognostic score ≥4; hazard ratio 2.4; confidence interval 0.89-6.47; p=0.08). HIV status did not affect CD68 or PD-L1 expression. A higher proportion of CD68-positive TAMs was found in samples that were EBV-positive. HIV positivity and EBV negativity correlated with poorer survival. CD68 and PD-L1 expression were not predictive of survival. High CD68 expression was associated with EBV positivity but not HIV positivity and did not predict adverse outcomes. PD-L1 expression was unaffected by HIV status or EBV positivity and did predict adverse outcomes.

Relativistic Nondipole Effects in Strong-Field Atomic Ionization at Moderate Intensities.

We present a detailed experimental and theoretical study on the relativistic nondipole effects in strong-field atomic ionization by near-infrared linearly polarized few-cycle laser pulses in the intensity range of 10^{14}-10^{15} W/cm^{2}. We record high-resolution photoelectron momentum distributions of argon using a reaction microscope and compare our measurements with a truly ab initio fully relativistic 3D model based on the time-dependent Dirac equation. We observe counterintuitive peak shifts of the transverse electron momentum distribution in the direction opposite to that of laser propagation as a function of laser intensity and demonstrate an excellent agreement between the experimental results and theoretical predictions.

Plasma plumes produced by laser ablation of Al with single and double pulse schemes.

We generated and characterized plasma with single and double picosecond laser pulses to study the plume dynamics and to control the plasma properties. The double pulse scheme was found to be superior for generating a homogeneous plasma. Lateral expansion was prominent in irradiation schemes wherein the energy in the first pulse is lower than or equal to that of the second pulse. The velocities of the fast and slow species were found to be nearly equal with the emission counts corresponding to slow species being larger for the single pulse compared to the double pulse.

The common fibular nerve (and its branches) in fetuses / El nervio fibular comun (y sus ramos) en fetos

The common fibular nerve (CFN), is a branch of the sciatic nerve (SN) that exits the popliteal fossa and is located at the tuberculum of the fibula. At the tuberculum of the fibula, the CFN bifurcates into deep (DFN) and superficial (SFN) fibular nerves. Forty fetuses were micro-dissected to (i) describe the course of the CFN in relation to the tuberculum and neck of the fibula in fetuses; (ii) describe the branches, distribution and relation of the DFN and SFN to muscles within the anterolateral compartment of the leg. The CFN, DFN and SFN were present in all specimens dissected; the CFN measured a mean length (mm) of 16.03 and 16.69 on the right and left sides respectively. Bifurcation of the CFN related to the tuberculum of fibula (right; left) - above 20/80 (25%); 14/80 (17.5%); below 6/80 (7.5%); 10/80 (12.5%) and at the tuberculum 54/80 (67.5%); 56/80 (70%). The DFN bifurcated into medial and lateral branches in 68/80 (85%) and 54/80 (67.5%) on the right and left sides, respectively. The SFN bifurcated into a medial branch in 78/80 (97.5%) and 76/80 (95%) on right and left sides, respectively and a lateral branch in 78/80 (97.5%) and 76/80 (95%) on right and left sides, respectively. The course and distribution of the CFN, DFN and SFN were consistent with the literature reviewed and descriptions found in standard anatomical textbooks. However, our findings show that the DFN has a variable number of branching patterns, which is unique to this fetal study and an intermediate branch of the SFN which was recorded in 3/80 cases.

El nervio fibular común (NFC), es un ramo del nervio isquiático (NI) que sale de la fosa poplítea y se ubica a nivel de la cabeza de la fíbula. A ese nivel, el NFC se bifurca en los nervios fibular profundo (NFP) y superficial (NFS). Cuarenta fetos fueron micro disecados para (i) describir el curso del NFC en relación con la cabeza y cuello de la fíbula en fetos; (ii) describir los ramos, distribución y relación del NFP y NFS con los músculos dentro del compartimento anterolateral de la pierna. El NFC, NFP y NFS estuvieron presentes en todos los especímenes disecados; el NFC presentó una longitud promedio de 16,03 y 16,69 (mm) en el lado derecho e izquierdo, respectivamente. La bifurcación del NFC se relacionó con la cabeza de la fíbula del lado derecho e izquierdo: por encima en 25% y 17,5%; por debajo 7,5% y 12,5 % y a nivel de la cabeza en 67,5 % y 70%. El NFP se bifurcó en ramos medial y lateral en un 85% en el lado derecho y 67,5% en el izquierdo. El NFS se bifurcó en una ramo medial en el 97,5% y 95% en los lados derecho e izquierdo, respectivamente, y un ramo lateral en el 97,5% y 95% del lados derecho e izquierdo, respectivamente. El curso y distribución del NFC, NFP y NFS coincidieron con la literatura revisada y textos de anatómia normal. Sin embargo, observamos que el NFP tiene un número variable de patrones de ramificación, único para este estudio fetal y un ramo intermedio del NFS que fue visto en 3/80 casos.

Effectiveness of a nurse facilitated cognitive group intervention among mild to moderately-depressed-women in KwaZulu-Natal, South Africa.

OBJECTIVE: The purpose of the study was to determine the effectiveness of a nurse-facilitated-cognitive-group (NFCG) intervention as an adjunct to antidepressant medication, in mild to moderately, depressed women. METHOD: This was a quasi-experimental, nonequivalent, control group design study. A sample of 30 consenting participants was selected from an urban, community psychiatric clinic, and the participants were randomly allocated to the control and the intervention groups. The effectiveness of the intervention was measured using the Beck Depression Inventory (BDI). RESULTS: After six weeks of implementation of the NFCG intervention, there was a decrease in the BDI scores of the intervention group, and an increase in the BDI scores in the control group (CG) - but the difference in scores was not significant (Student's t-test=1.076, p=0.291). After 12 weeks of the group intervention, the BDI scores for the intervention group, showed a considerable reduction in their levels of depression, whilst the participants of the control group had a further increase in their scores. There was a statistically significant difference between the groups, with respect to the BDI scores (p<0.001). The Friedman test indicated that the mean BDI scores, were statistically significant (p<0.001) within the intervention group, meaning that the BDI scores improved, at the end of the intervention for all the participants. Analysis of the BDI scores, using the Friedman test, showed that there was no improvement in the control group (p=0.597). CONCLUSION: The NFCG intervention, as an adjunct to antidepressant medication, contributed to a reduction in depressive symptoms.

Enhancing drug incorporation into tetracycline-loaded chitosan microspheres for periodontal therapy.

PURPOSE: To identify optimal formulation parameters for enhancing the incorporation of tetracycline hydrochloride into chitosan microspheres for periodontal therapy. METHODS: Tetracycline-loaded chitosan microspheres were prepared by ionotropic gelation. Various formulation parameters (salt form of drug, aqueous phase pH, anion structure, inorganic salts and electrolytes, preparation method) were investigated for their influence on drug incorporation efficiency. Microspheres were assessed in terms of drug entrapment and content, microsphere recovery, particle size and morphology. RESULTS: Although drug incorporation efficiency was increased marginally, the use of a dihydrate form of the drug was not considered feasible due to the lowered microsphere recovery and higher costs. A decrease in the aqueous pH from 9 to 6 enhanced drug incorporation efficiency without an adverse effect on microsphere morphology. The use of inorganic salts/electrolytes and other approaches of microsphere preparation did not significantly enhance drug incorporation efficiency and these approaches also adversely affected microsphere morphology. The ionotropic preparation method in terms of the drug loading technique significantly affected drug incorporation efficiencies. CONCLUSIONS: This study has shown that formulation variables can be exploited in order to enhance the incorporation of a water soluble drug into chitosan microspheres using the ionotropic gelation technique. Based on a comparison of all results obtained with the different approaches, the modification of the aqueous phase to pH 6 was identified as the most feasible approach.

Statistical optimisation of the mucoadhesivity and characterisation of multipolymeric propranolol matrices for buccal therapy.

A Box-Behnken experimental design was employed to optimise a polymeric blend for the preparation of propranolol HCl matrices with maximum mucoadhesivity and was thereafter modified for achieving controlled drug release. The quantitative effects of the polymers used i.e. poly(acrylic acid) (PAA) and poly(vinyl pyrrolidone) (PVP) on mucoadhesion could be predicted using polynomial equations. A formulation of 20% PAA, 20% CMC and 20% PVP was identified for maximising mucoadhesivity and obtaining a controlled drug release profile. Reproducibility of the optimal formulation in terms of mucoadhesivity and controlled drug release was confirmed. The optimal formulation was characterised in terms of mucoadhesivity, release kinetics, swelling/erosion, hydration dynamics and surface pH. From the model fitting analyses, drug release was found to be diffusion, polymeric relaxation and erosion based with the former two being more dominant over erosion. This was in agreement with the erosion and swelling studies which showed swelling and erosion occurring in the tablet matrix. Textural profiling showed initial rapid hydration, which could be beneficial for enhanced mucoadhesivity. Surface pH of the multipolymeric matrices was similar to salivary pH and did not show extremes in changes over the test period. The optimal preparation of multipolymeric propranolol matrices identified in this study shows potential for buccal administration.

Aggressive fibromatosis--impact of prognostic variables on management.

OBJECTIVE: To determine the impact of prognostic variables on local control in patients with aggressive fibromatosis treated with or without radiation. MATERIALS AND METHODS: Forty-two patients presenting to the combined sarcoma clinic at Johannesburg Hospital with aggressive fibromatosis from 1990 to 2003 were analysed retrospectively. There were 14 males and 28 females. The lesions involved the head and neck in 6 cases (14%), the thorax in 6 (14%), the extremities in 19 (45%) and the abdomen in 11 (26%). Thirty-seven patients (88%) presented to the clinic for the first time, whereas 5 (12%) had recurrent disease at presentation. Fifteen patients (36%) underwent excision only, 15 (36%) had excision followed by postoperative radiation, 8 (19%) had biopsy only, and 4 (9%) had radiation only. The median dose of radiation was 60 Gy (range 9 - 70 Gy). RESULTS: One patient had local failure following excision and postoperative radiation therapy. The local control was 100% for surgery alone and 86% for surgery followed by postoperative radiation at > or = 24 months. On univariate analysis, age, sex, positive margins, primary or recurrent presentation, site of involvement and initial treatment did not affect local control significantly. Eight of 19 patients (42%) receiving radiation developed severe moist desquamation following treatment, and all these patients had doses of 60 Gy or more. CONCLUSION: Surgery with or without radiation therapy gave excellent local control. The addition of radiation therapy to surgery as well as other known prognostic parameters did not impact on local control. The morbidity of radiation treatment is considerable, as noted in this series, and adjuvant radiation therapy should therefore be considered only in situations where the risk of recurrence and the morbidity of re-excision are high.

Aggressive fibromatosis - impact of prognostic variables on management : general surgery

Objective. To determine the impact of prognostic variables on local control in patients with aggressive fibromatosis treated with or without radiation. Materials and methods. Forty-two patients presenting to the combined sarcoma clinic at Johannesburg Hospital with aggressive fibromatosis from 1990 to 2003 were analysed retrospectively. There were 14 males and 28 females. The lesions involved the head and neck in 6 cases(14); the thorax in 6 (14); the extremities in 19 (45) and the abdomen in 11 (26). Thirty-seven patients (88) presented to the clinic for the first time; whereas 5 (12) had recurrent disease at presentation. Fifteen patients (36) underwent excision only; 15 (36) had excision followed by postoperative radiation; 8 (19) had biopsy only; and 4 (9) had radiation only. The median dose of radiation was 60 Gy (range 9 - 70 Gy). Results. One patient had local failure following excision and postoperative radiation therapy. The local control was 100for surgery alone and 86for surgery followed by postoperative radiation at 24 months. On univariate analysis; age; sex; positive margins; primary or recurrent presentation; site of involvement and initial treatment did not affect local control significantly. Eight of 19 patients (42) receiving radiation developed severe moist desquamation following treatment; and all these patients had doses of 60 Gy or more. Conclusion. Surgery with or without radiation therapy gave excellent local control. The addition of radiation therapy to surgery as well as other known prognostic parameters did not impact on local control. The morbidity of radiation treatment is considerable; as noted in this series; and adjuvant radiation therapy should therefore be considered only in situations where the risk of recurrence and the morbidity of re-excision are high

Optimisation and characterisation of bioadhesive controlled release tetracycline microspheres.

A Box-Behnken experimental design was employed to statistically optimise the formulation parameters of a tetracycline microsphere preparation for maximum bioadhesivity and controlled drug release. The quantitative effect of the formulation parameters at different levels on bioadhesion and drug release could be predicted using polynomial equations. A formulation comprising of 3% (w/w) chitosan, 10% (w/w) tetracycline HCl and 9% (w/v) tripolyphosphate was identified for maximising bioadhesivity and obtaining controlled drug release. The optimal microsphere preparation was subsequently characterised in terms of hydration dynamics, release kinetics, antimicrobial activity, thermal properties, morphology and surface pH. Kinetic models revealed that drug release followed Fickian diffusion while textural analysis showed minimal hydration over the test period. Antimicrobial studies showed that the drug concentrations in the in vitro release samples were above the minimum concentration of drug required for inhibition of Staphylococcus aureus growth. Thermal analyses showed a possible interaction between the drug and polymer. Scanning electron microscopy confirmed the integrity of the microspheres and identified the morphological changes following drug release. Surface pH of the microspheres was similar to salivary pH and did not show extremes in changes over the test period.

Characterization of captopril sublingual permeation: determination of preferred routes and mechanisms.

Although sublingual captopril has been used clinically to treat hypertensive emergencies, a mechanistic understanding of sublingual permeation will facilitate the optimization of drug delivery. A correlation of sublingual steady-state flux with donor captopril concentration in a porcine model showed the absence of saturability and suggested a passive diffusion permeation mechanism. A simultaneous evaluation of permeability and partition coefficient demonstrated that the paracellular route is the predominant pathway for sublingual permeation. The enhancement factors of specific ion permeabilities in the presence of tight junction perturbants indicated that although the paracellular pathway is preferred by the ionized species of captopril, the lipophilic transcellular pathway is preferred by the neutral, un-ionized species.

A mechanistic analysis to characterize oramucosal permeation properties.

The hypotheses of this study are that the permeation of ionizable molecules follows the pH-partition theory, that the preferred transport pathway for penetrants depends on their charge status and that transport resistance is related to the membrane-coating granules (MCG). Transcellular resistance is believed to be proportional to the volume of MCG in the intracellular space while paracellular resistance is believed to result from the extrusion of the lipid contents of the MCG into the intercellular space. Nicotine, an ionizable model compound with two pK(a) values (3.4 and 8.2), was chosen as a molecular probe to investigate the pH-partition theory on permeation through porcine oramucosae, to characterize the differences in permeability among various oramucosae, and to explore the preferred transport pathways of each nicotine species through oramucosae. The pH-partition theory was proved from the observations that permeability, partition coefficient and diffusivity of nicotine varied as a function of pH. The keratinized gingiva was found to have greater permeability than the non-keratinized buccal and sublingual mucosae. The neutral nicotine species had a higher permeability than the ionized species due to its higher partition coefficient and diffusivity. A mechanistic analysis (permeability ratio-pH profile) was conducted to determine the preferred transport pathway of each nicotine species. The permeability of neutral nicotine was found to be proportional to the occupied volume of MCG in the intracellular space. This indicates that the preferred transport pathway for neutral nicotine is transcellular. As the solution pH was decreased, and a greater fraction of nicotine became protonated, the transport of hydrophilic, charged nicotine species along the intercellular pathway was preferred.

Novel methods of insulin delivery: an update.

Conventional insulin therapies involve multiple daily subcutaneous injections. However, the resultant disposition of insulin and blood glucose differs considerably from that following the physiological secretion of pancreatic insulin. A variety of alternative routes/methods have been investigated to improve systemic insulin delivery. Peroral and nasal insulin administration have demonstrated good potential for the treatment of diabetes. Facilitated transdermal delivery has also enjoyed success in promoting the systemic delivery of insulin. In addition, pulmonary, buccal, and ocular insulin administration have been shown to decrease serum glucose concentrations. Other methods that have been investigated for their potential in systemic insulin delivery include rectal, vaginal, and uterine routes.

In vitro characterization of a controlled-release chlorpheniramine maleate delivery system prepared by the air-suspension technique.

Non-pareil cores were spray-coated with a chlorpheniramine maleate (an alkylamine antihistamine) layer and a Eudragit NE30D overcoat in a Wurster air-suspension apparatus. In vitro dissolution studies demonstrated that drug release was a function of polymer membrane thickness. Polyethylene glycol 6000, as a hydrophillic additive, increased the in vitro release of chlorpheniramine maleate from the pellets. Pellets coated with 8.30% Eudragit NE30D, 0.50% talc and 1.00% polyethylene glycol 6000 were found to display desirable controlled release characteristics for chlorpheniramine maleate over the 8-h testing period, which were also comparable with that of Dykatuss capsules. The controlled release pellets exhibited first-order release characteristics for chlorpheniramine maleate. Reproducibility of the manufacturing conditions employed in the study were confirmed thus ensuring reproducibility of drug release characteristics between batches of chlorpheniramine maleate pellets. Drug release from the pellets was shown to be independent of the dissolution method and medium used. Pellets displayed no significant change in drug release characteristics relative to the initial drug release data when stored for 12 weeks at room temperature (20 +/- 2 degrees C) and for 8 weeks at a low temperature (5 +/- 1 degrees C). However, pellets stored at 37 degrees C with 80% relative humidity and at 40 +/- 2 degrees C showed a slower in vitro drug release after 8-week storage and therefore failed to maintain their initial drug release profile.

Biomembrane permeation of nicotine: mechanistic studies with porcine mucosae and skin.

In the present study, the permeation and partitioning of nicotine as a function of pH was investigated with various regions of skin and absorptive mucosae that were freshly excised from domestic pigs. As an ionizable compound (pKa values of 3.04 and 7.84), nicotine in solutions of different pH values provides a model for determining the influence of the charge status of a molecule on permeation. The permeation of nicotine across porcine mucosae and skin followed zero-order kinetics. The rate of permeation was dependent on donor solution pH and increased exponentially as the pH increased. With an exception of the nasal mucosa, which showed similar permeabilities for all species of nicotine, the permeability of nicotine across various skin and mucosal specimens was significantly higher (p < 0.001) for the un-ionized species (NN) than for the ionized species (NNH+, NH+NH+). It was also seen that un-ionized nicotine molecules were more permeable through absorptive mucosae (nasal, buccal, sublingual, and gingival) than through skin (abdominal, dorsal, thigh, and ear pinna). Partition studies were performed and the results further confirmed that biomembrane permeation of nicotine follows the pH-partition theory.

Microencapsulated Eudragit RS30D-coated controlled-release pellets: the influence of dissolution variables and topographical evaluation.

The air suspension technique was employed to prepare Eudragit RS30D-coated controlled-release pellets of salbutamol. Drug release in dissolution studies can be dependent on the dissolution method and medium used. Thus, the aim of this study was to investigate the influence of various dissolution methods and dissolution medium pH values on drug release from a batch of pellets which displayed controlled drug-release characteristics over an 8-h period in deionized water using the rotating basket method. In vitro testing using the official USP XXII (rotating basket and rotating paddle) and non-official (rotating bottle) methods showed drug release to be independent of the method used. The prepared pellets displayed pH-dependent drug-release characteristics when tested in hydrochloric acid (pH 1.5), phosphate buffer (pH 6.8) and deionized water (pH 7.2). Also, in vitro testing, which exposed the pellets to a changing pH gradient that simulated the gastrointestinal pH conditions following oral administration, was used to confirm the drug-release characteristics. The results showed controlled-release characteristics to be maintained, with the drug being released over an 8-h period. Scanning electron microscopic evaluation proved useful in the elucidation of the physical characteristics of the controlled-release pellets as well as in the identification of a possible mode of drug transfer into the dissolution medium.

Management of 240 cases of liver abscess.

The clinical features and surgical management of 240 cases of liver abscess admitted during a period of five years are presented. Incidence of liver abscess was 0.20 per cent of hospital admissions. A peak age incidence in the 4th decade, male preponderance, pain and fever were the striking features. The majority of the abscesses were localised to a single lobe (90.0%). The abscess was sited in the right lobe in 75.1 per cent, in the left lobe in 18.3 per cent and in both lobes in 6.7 per cent. Elevation and limitation of movement of the right dome of the diaphragm was present in 89.5 per cent of cases. Depending upon therapeutic response, aspiration or/and surgical drainage was undertaken. Aspiration was done in 169 patients and surgical drainage in 63 patients. Management of pyogenic liver abscess included early operative intervention preceded by appropriate antibiotic therapy. Surgical intervention is required less often in amoebic abscess and is recommended only after amoebicidal therapy. Open drainage is recommended for the cases associated with complications, left lobe abscess and big abscess.