EVA implants for controlled drug delivery to the inner ear.

This study evaluated the potential of poly(ethylene vinyl acetate) (EVA) copolymers as matrix formers in miniaturised implants, allowing to achieve controlled drug delivery into the inner ear. Due to the blood-cochlea barrier, it is impossible to reliably deliver a drug to this tiny and highly sensitive organ in clinical practice. To overcome this bottleneck, different EVA implants were prepared by hot melt extrusion, altering the vinyl acetate content and implant diameter. Dexamethasone was incorporated as a drug with anti-inflammatory and anti-fibrotic activity. Its release was measured into artificial perilymph, and the systems were thoroughly characterised before and after exposure to the medium by optical and scanning electron microscopy, SEM-EDX analysis, DSC, X-ray powder diffraction, X-ray microtomography and texture analysis. Notably, the resulting drug release rates were much higher than from silicone-based implants of similar size. Furthermore, varying the vinyl acetate content allowed for adjusting the desired release patterns effectively: With decreasing vinyl acetate content, the crystallinity of the copolymer increased, and the release rate decreased. Interestingly, the drug was homogeneously distributed as tiny crystals throughout the polymeric matrices. Upon contact with aqueous fluids, water penetrates the implants and dissolves the drug, which subsequently diffuses out of the device. Importantly, no noteworthy system swelling or shrinking was observed for up to 10 months upon exposure to the release medium, irrespective of the EVA grade. Also, the mechanical properties of the implants can be expected to allow for administration into the inner ear of a patient, being neither too flexible nor too rigid.

Drug release from PLGA microparticles can be slowed down by a surrounding hydrogel.

This study aimed to evaluate and better understand the potential impact that a layer of surrounding hydrogel (mimicking living tissue) can have on the drug release from PLGA microparticles. Ibuprofen-loaded microparticles were prepared with an emulsion solvent extraction/evaporation method. The drug loading was about 48%. The surface of the microparticles appeared initially smooth and non-porous. In contrast, the internal microstructure of the particles exhibited a continuous network of tiny pores. Ibuprofen release from single microparticles was measured into agarose gels and well-agitated phosphate buffer pH 7.4. Optical microscopy, scanning electron microscopy, differential scanning calorimetry, X-ray powder diffraction, and X-ray µCT imaging were used to characterize the microparticles before and after exposure to the release media. Importantly, ibuprofen release was much slower in the presence of a surrounding agarose gel, e.g., the complete release took two weeks vs. a few days in well agitated phosphate buffer. This can probably be attributed to the fact that the hydrogel sterically hinders substantial system swelling and, thus, slows down the related increase in drug mobility. In addition, in this particular case, the convective flow in agitated bulk fluid likely damages the thin PLGA layer at the microparticles' surface, giving the outer aqueous phase more rapid access to the inner continuous pore network: Upon contact with water, the drug dissolves and rapidly diffuses out through a continuous network of water-filled channels. Without direct surface access, most of the drug "has to wait" for the onset of substantial system swelling to be released.

The African AIDS case definition and HIV serology in medical in-patients at Komfo Anokye Teaching Hospital, Kumasi, Ghana.

In 914 consecutive medical admissions to Komfo Anokye Teaching Hospital, the prevalence of infection with Human Immunodeficiency Virus type I (HIV-I) and Human Immunodeficiency Virus type 2 (HIV-2) was 12.6%. The prevalence in females was twice that found in males. The infection rate was maximum in the age group 25-29 years for females (45%) and 30-34 years for males (29%). There were 7 cases infected with HIV-2 alone, 55 cases infected with HIV-I alone and 53 cases with dual infection. The cases with HIV-2 infection tended to be older than those with HIV-I infection. For detecting HIV seropositivity in our patients the World Health Organization recommended case definition for AIDS in Africa gave a sensitivity of 32%, a specificity of 93% and a positive predictive value of 42%. The case definition gave the highest specificity and positive predictive values when cases of tuberculosis were not included in the analysis.

PIP: During November 1989-January 1990 in Ghana, medical officers clinically examined and took blood samples from 914 consecutive admissions to Komfo Anokye Teaching Hospital in Kumasi to determine seroprevalence of HIV and different clinical features of HIV infection as well as to assess the value of the World Health Organization (WHO) clinical case definition for AIDS. 12.6% of the admissions were infected with HIV-1 and/or HIV-2. Females were more than two times likely to be infected with HIV than males (17.6% vs. 8.8%). Overall, 25-29 year old women had the highest HIV infection rate (45%). 30-34 year old men had the highest HIV infection rate among males. 56.5% of HIV-infected females and 30.4% of HIV-infected males were infected with both HIV-1 and HIV-2. 7 cases (5 females and 2 males) were infected with just HIV-2. Their ages ranged from 35 to 75 years. When the researchers applied the WHO clinical case definition to all HIV seropositive cases, they found its sensitivity to be 32%, specificity to be 93%, and positive predictive value to be 42%. Sputum-positive tuberculosis (TB) accounted for much of the false positives (28/53). 15% of the 76 sputum positive TB cases were HIV infected. When the researchers excluded all confirmed or suspected TB cases from the analysis, the specificity and positive predictive value increased to a maximum of 97% and 61%, respectively; sensitivity was 28%. Many HIV seropositive cases were not diagnosed with HIV infection either by the case definition or clinically by ward physicians. They probably were asymptomatic. Clinicians should suspect patients diagnosed with pneumonia or meningitis to be HIV infected, as was the case in this study (20% and 17% of HIV seropositive cases who were case definition negative, respectively).

Pyogenic meningitis in the tropical rain-forest of Kumasi, Ghana

Pyogenic meningitis is a common and often fatal disease in the tropical rain-forest of Ghana. A study conducted in Komfo Anokye Teaching Hospital; Kumasi; in the Ashanti Region; shows that meningitis is endemic in this community. Its incidence increases in the dry season with the peak in January and February. It is much more common in large families where 4 or more people sleep in a small room with poor ventilation. It is more common in men than in women with ratio 1.8:1. The main complication is cranial nerve damage (III; IV and VIII). The mortality rate is unacceptably high in the two groups: Strep. pneumoniae 41 per cent and N. meningitidis 16 per cent