p‐Synephrine,ephedrine, p‐octopamine and m‐synephrine: Comparative mechanistic,physiological and pharmacological properties

Confusion and misunderstanding exist regarding the lack of cardiovascular and other adverse health effects of p‐synephrine and p‐octopamine relative to ephedrine and m‐synephrine (phenylephrine) which are known for their effects on the cardiovascular system. These four molecules have some structural similarities. However, the structural and stereochemical differences of p‐synephrine and p‐octopamine as related to ephedrine and m‐synephrine result in markedly different adrenergic receptor binding characteristics as well as other mechanistic differences which are reviewed. p‐Synephrine and p‐octopamine exhibit little binding to α‐1, α‐2, β‐1 and β‐2 adrenergic receptors, nor are they known to exhibit indirect actions leading to an increase in available levels of endogenous norepinephrine and epinephrine at commonly used doses. The relative absence of these mechanistic actions provides an explanation for their lack of production of cardiovascular effects at commonly used oral doses as compared to ephedrine and m‐synephrine. As a consequence, the effects of ephedrine and m‐synephrine cannot be directly extrapolated to p‐synephrine and p‐octopamine which exhibit significantly different pharmacokinetic, and physiological/pharmacological properties. These conclusions are supported by human, animal and in vitro studies that are discussed.     

Clinical,histological and immunohistochemistry characteristics of cornea in the sequelae stage of chronic vernal keratoconjunctivitis

Purpose:To report the clinical outcomes and histopathological and immunohistochemistry (IHC) features in eyes with the sequelae stage of vernal keratoconjunctivitis (VKC).Methods:Investigative study of corneal samples obtained following surgical intervention for vision restoration in four eyes of three patients with VKC. Patient 1 (an 11-year-old boy) had deep anterior lamellar keratoplasty in both eyes, Patient 2 (a 24-year-old male) underwent superficial keratectomy followed by penetrating keratoplasty, and Patient 3 (a 22-year-old male) underwent penetrating keratoplasty. The corneal samples retrieved after surgical intervention were assessed for histology features and immunohistochemistry (IHC) studies.Results:The grafts were clear till the follow-up of 2–18 months. Histopathology of all four corneal samples showed epithelial hyperplasia, absent Bowman layer, thick hyalinized stromal lamellae, vascularization, and chronic inflammatory cells such as lymphocytes and plasma cells. IHC showed strong expression of CK 3 in both eyes of Patient 1 and no expression in Patients 2 and 3. The marker for limbal stem cells, ABCG2, was absent in all four samples; however, p63α was expressed strongly in Patients 2 and 3, moderately in the right eye of Patient 1, and marginally expressed in the left eye of Patient 1.Conclusion:The eyes in the sequelae stage of VKC (having corneal scarring and 360° hypertrophied limbus) can be managed favorably with keratoplasty and amniotic membrane transplantation without allogenic/cadaveric stem cell transplantation. The expression of transient progenitor cells in the scarred corneas of VKC patients in the sequelae stage suggests that the limbal stem cell dysfunction is more likely partial and self-renewal of limbal stem cells is a plausibility in these eyes.     

Medical negligence or diagnostic conundrum? A medico-legal case study

India is a signatory to the UN backed Consumer Protection Resolution, and has enacted the Consumer Protection Act in 1986 to promote and protect the rights of consumers. A land-mark judgment of the Supreme Court of India in 1996, has paved the way for a number of lawsuits involving the public sector, including an eminent tertiary care medical institution. The case described in this study was filed with the State Consumer Dispute Redressal Commission in June 2000. The complainant was a fifty year old female who noticed a lump in her right breast; which was diagnosed as malignant by fine needle aspiration cytology (FNAC); and was treated by surgery and adjuvantradio-therapy (brachytherapy). Subsequently, the tissue sent for histo-pathological study was reported to be 'benign phyllodes tumour'; which was confirmed by other centres in India and the UK. The complaint filed for total damages amounting to Rupees 19 lacs (approx. 27,300 UK pounds) along with interest from the date of operation. Review of the relevant literature suggests that phyllodes tumour of the breast has various sub-types;and even borderline cases can develop malignancy at a later date. It is also clear that false positive cases had been reported previously in cases diagnosed by FNAC. Finally, avenues to minimise litigation through in-house mechanisms and a new concept of mediation have been explored.     

Effects of intranasal administration of norethisterone on folliculogenesis, cervical mucus, vaginal cytology, endometrial morphology and reproductive-endocrine profile in women.

The effects of intranasal administration of norethisterone (NET) on menstrual cycle length, folliculogenesis, serum levels of estradiol, FSH, LH and progesterone, vaginal cytology, cervical mucus and endometrial morphology were studied in 8 volunteers (age 28 to 39 years, weighing between 46 and 54 kg). The study period comprised 4 consecutive menstrual cycles. In the first cycle (pretreatment cycle), only the vehicle (alcohol, propylene glycol, water; 3:3:4) was sprayed intranasally (100 microliters in each nostril), using a metered nebulizer, once daily from day 3 to the last day of menstrual cycle. In the next two cycles (treatment cycles), NET (300 micrograms/day) was administered once daily, starting from day one of menstrual cycle, between 9 and 10 a.m. The fourth cycle was a post-treatment cycle in which the volunteers were monitored for recovery. Blood samples (about 5 ml each) were collected once daily from day 8 to 24 and thereafter on alternate days until the last day of cycle during all the 4 cycles. Levels of estradiol, FSH, LH and progesterone were measured in the serum samples by radioimmunoassay methods. Cervical mucus samples and vaginal smears were collected once daily starting from day 7 or 8 of each cycle until the mucus was very scanty. Serial pelvic ultrasonography was performed starting from day 7 or 8 until the growing follicle disappeared or throughout the cycle in case a growing follicular cyst was observed. Endometrial aspirates were collected once around day 22 in each cycle and processed for routine histological examination.