Large Size Microneedle Patch to Deliver Lidocaine through Skin

Purpose

Current topical treatments using lidocaine (LD) for analgesia have limited applications due to their delayed analgesic actions, resulted from slow drug permeation through skin. The aim of this study is to fabricate a large size microneedle (MN) array patch containing LD, with fast onset of action, for the treatment of acute and chronic pain.

Methods

The MN patch was developed through photolithography and tested for its mechanical characteristics. In vitro and in vivo skin permeation, plasma pharmacokinetics, histology and skin irritation testing have also been performed for the MN patches.

Results

The MN have a mechanical strength of 10–30 N and more than 90% of the microneedles on the patch penetrated skin. It was shown that LD permeated through skin within 5 min of patch application. Subsequently, the in vivo skin permeation study using a porcine model showed that LD administrated by the MN patch was able to achieve the therapeutic level locally within 10 min and sustained for 8 h. It shows most of the drug diffuses perpendicularly against skin, with little lateral diffusion. After skin permeation LD remains within skin and unquantifiable amount of LD was found in the plasma of the pigs. Minor skin irritations were observed after 6 h of microneedle contact. However, the skin irritations resolved within 1 day following the removal of MN patch.

Conclusion

The large size MN patches showed fast onset and sustained delivery of LD through skin, potentially useful to increase the application scope of topical LD for pain management.

     

Periosteo-Temporofascial flap for cavity obliteration - first Indian study

Healing of the mastoid cavtiycompletely is the desired result after a mastoid surgery. Even after the Sade’s principles’ of the complete disease clearance, adequate lowering of the facial ridge, good meatoplasty and closure of the perforation of the tympanic membrane are fallowed, the complete healing of tike mastoid cavity is sometimes net the end result. According to various surgeons, the incidence of discharging mastoid cavity after a open cavity mastoid surgery is between /0-60%-H The usual techniques of obliteration of the mastoid cavity to decrease the size of the mastoid cavity, unusually has good healing results due to good vascularity. The failure ta the early detectmn 0/disease recurrence and risk of sudden appearance of intra-cranial complications are the most important disadvantages of the technique. We undertook a study in SO randomly chosen patients of Unsafe CSOM. Twenty five underwent obliteration of the mastoid cavity with Periosteo-Temporofascial flap, which is based on branches of posterior auricular artery and rest twenty five underwent non-obliteration of the mastoid cavity. Tfie results between the two groups were compared in terms of healing of the mastoid cavity and hearing gain after operation. Very good results in terms of healing of the cavity were seen after obliteration surgery. The rate of healing of the cavity was much faster after obliteration. The additional advantage with the flap is the see-through character of the cavity lining, which would lead to early detection of the disease recurrence. No significant increase in the hearing was seen in the obliterated patients as compared to non-obliterated cases.     

Improved diagnosis of actively bleeding aneurysm on CT angiography using delayed CT images

Computed tomographic angiography (CTA) is being increasingly utilized in the non-invasive diagnosis of aneurysmal subarachnoid hemorrhage (SAH). There are emerging reports of diagnosis of active aneurysmal bleeding on CTA, furthering our understanding of imaging features of active extravasation on cross-sectional studies. We demonstrate imaging characteristics of two such cases of active contrast extravasation from intracranial aneurysms. Additionally, we demonstrate that delayed CT images greatly improve the confidence of this diagnosis by demonstrating pooling of contrast in the subarachnoid space. Prompt recognition and management can improve prognosis of this potentially lethal condition.     

The monomeric alpha beta form of the insulin receptor exhibits much higher insulin-dependent tyrosine-specific protein kinase activity than the intact alpha 2 beta 2 form of the receptor.

The relationship between the structure of the insulin receptor and its kinase activity was studied on the purified receptor treated with different concentrations of dithiothreitol. An enhanced autophosphorylation of the beta subunit (Mr, 90,000) was observed on NaDodSO4/PAGE under reducing conditions when the receptor was treated with 0.1-0.75 mM dithiothreitol in the presence of 1 microM insulin. Since we have previously observed (unpublished data) that incubation of the purified receptor with 1 mM dithiothreitol completely reduced an intact form of the receptor, alpha 2 beta 2, to free alpha subunit (Mr, 125,000) and beta subunit, the population of disulfide-linked complexes of the receptor after the dithiothreitol treatment was analyzed by NaDodSO4/PAGE under nonreducing conditions. The same receptor preparations were assayed for tyrosine kinase activity by using an exogenous substrate. Treatment of the receptor with dithiothreitol significantly enhanced both basal and insulin-dependent kinase activity. The kinase activity was enhanced 12- to 37-fold at concentrations of 0.5-0.75 mM dithiothreitol in the presence of 1 microM insulin. The amount of alpha 2 beta 2, alpha beta, and beta forms in each dithiothreitol-treated receptor preparation was quantified and compared with its kinase activity. These studies clearly indicate a correlation between the appearance of an alpha beta form and an increase in kinase activity. Therefore, we conclude that the alpha beta form of the insulin receptor exhibits much higher kinase activity than the intact receptor in the alpha 2 beta 2 form.     

Total serum immunoglobulin E levels in a case–control study in asthmatic/allergic patients, their family members, and healthy subjects from India

BACKGROUND: Total immunoglobulin E (IgE) is an important indicator of allergic disorders. However, its role in allergic patients in India has not been evaluated in relation to atopic status for a reference range as compared with healthy subjects. OBJECTIVE: The aim of the study was to establish serum IgE levels in a diseased group, study its relationship with atopy, and to compare the same with healthy volunteers in Indian subjects. METHODS: Four hundred and eighty asthmatics/allergic patients, 100 first-degree relatives of asthmatics, and 120 unrelated normal healthy volunteers from Delhi region were recruited for the study. Atopy was established by family history and skin test to common indigenous allergens and, total and specific IgE measurements. Statistical analysis was performed with the help of SPSS software program. RESULTS: The mean IgE levels were the highest in asthmatic patients and the lowest in the control healthy group. IgE was significantly high in the male than the female healthy volunteers (P<0.05), but not in the diseased group. Prosopis juliflora among pollen allergens and Alternaria alternata among fungal allergens were important sensitizers in allergic patients with 34.7% and 17.7% skin positivity, respectively. Atopic status and asthma were found to be the best predictor of IgE, which was highly significant (r(2)=0.239, P<0.00001). However, at 95% confidence interval as many as 50% of asthmatic patients had their IgE values in the normal range. CONCLUSION: The IgE levels in Indian allergic patients is significantly related to atopy, but due to wide overlap of IgE levels in patients and healthy subjects, its diagnostic significance in Indian population seems to be limited.     

Recurrent and aggressive chondroblastoma of the pelvis with late malignant neoplastic changes

A case of chondroblastoma involving the left ischium, lower wing of left ilium and inferior ramus of left pubis is presented. The tumor showed aggressive features and repeated recurrences over a 30-year period and ultimately developed the cytologic features of a malignant neoplasm. However, no metastases have developed.     

Is DNA ploidy of prognostic significance in stage I cutaneous melanoma?

Recent studies have suggested that the presence of DNA aneuploidy in stage I cutaneous melanoma carries a poor prognosis. To see if our experience correlated with these reports, we used DNA analysis by flow cytometry of propidium iodide-stained nuclei disaggregated from formalin-fixed paraffin-embedded tissue of biopsy specimens to retrospectively study 55 patients who had cutaneous stage I melanomas. The patients had been treated from 1977 to 1987 with a mean follow-up of 5.4 years. Thirty-nine (71%) of the 55 histograms were diploid, and 16 (29%) of the histograms were aneuploid. DNA content was significantly associated with other conventional prognostic factors, including growth pattern, ulceration, pathologic stage, tumor thickness, and Clark's level. DNA aneuploidy was significantly related to disease-free survival and predicted a poorer prognosis (p less than 0.05), but when stratified for tumor thickness it lost significance. A multivariate discriminant function analysis of 12 factors in melanoma showed six factors to be independently significant in determining prognosis. DNA content (p = 0.034) ranked fifth in importance behind growth pattern (p less than 0.001), ulceration (p less than 0.001), thickness (p = 0.001), and pathologic stage (p less than 0.005). DNA content, although significantly associated with conventional prognostic factors and disease-free survival, is not the best indicator of biologic behavior of melanomas in this study. Further investigation into its usefulness is necessary before DNA content can become a routine diagnostic modality in the work-up of stage I cutaneous melanomas.     

Magnetization transfer MR imaging correlation with histopathology in intracranial tuberculomas

OBJECTIVE: The purpose of this study was to correlate the differences in the magnetization transfer (MT) ratios of different components of the tuberculoma with histopathology and to see whether MT or conventional MR imaging correlates better with histopathology. METHODS: MT T1 and conventional spin echo MR imaging was performed in six patients with intracranial tuberculomas. The tuberculomas were excised as a single mass and ex vivo MR imaging was performed using the same protocol. The gross histopathology was compared with in vivo imaging with respect to the MR signal intensity (MT ratio) in all six specimens. RESULTS: The size of the tuberculomas was larger on MT T1-weighted images compared to T2-weighted images and matched the gross measurements of each specimen. The MT hyperintense rim matched the cellular component of the tuberculoma that was masked on T2-weighted images because of the associated perifocal oedema. The cellular component had a lower MT ratio compared to the necrotic components. CONCLUSION: The outer hyperintense rim and hyperintense strands are due to the cellular infiltrate, noncaseating granulomas, and gliosis while the hypointense core represents solid caseation. The cellular outer rim shows lower MT ratio compared to the core of the tuberculoma. Histological correlation of the cellular and necrotic components of tuberculomas is best shown with MT T1 imaging.