Ambulatory Hysteroscopy in Abnormal Uterine Bleeding: A Tertiary Care Hospital Perspective

Background: To avoid delays in outpatient facilities for managing benign gynecological conditions like abnormal uterine bleeding (AUB), there is a need to evaluate the usage of unconventional methods like outpatient hysteroscopy. Objectives: To evaluate the usage of outpatient diagnostic hysteroscopy in women with abnormal uterine bleeding. Methods: An observational study was conducted at the Obstetrics and Gynecology Department of Combined Military Hospital, Kharian. The study included 56 women having AUB with or without a history of failed medical treatment. The study participants underwent outpatient diagnostic hysteroscopy. Diagnostic hysteroscopy was done under the local para-cervical block in the Outpatient department. Procedure indications, outcome and biopsy findings were recorded on predesigned proformas. Results: Median age of the study participants was 44 years. The most common indications for diagnostic hysteroscopy were postmenopausal bleeding (34%) and heavy menstrual bleeding (28%). Hysteroscopy outcomes included endometrial biopsy (34%), discharge with no biopsy (25%), further test and evaluations required (21%), and admission due to failed outpatient procedures (20%). Sixty-two percent of the study participants had normal biopsy findings while other biopsy findings included polyps (20%), fibroids (14%) and endometrial hyperplasia (4%). Nine percent had unsuccessful hysteroscopy due to patient refusal to proceed. Conclusion: Outpatient hysteroscopy can be helpful in the early and rapid diagnosis of women with abnormal uterine bleeding.  

Synthesis, Characterization and Biological Activities of Isocoumarins, Triazoles, Thiadiazoles and Indolinones

The work presented in this thesis consists of the synthesis, characterization, and biological screening of heterocyclic compounds. For convenience, the work has been divided into two parts, part one is related to the compounds containing oxygen atom in the heterocyclic ring whereas part two refers to the compounds containing nitrogen and/ or sulphur atoms in the heterocyclic ring. Part one of this thesis is related to the synthesis, characterization and biological activity of some heterocyclic compounds containing oxygen in the ring. These compounds include some naturally and unnaturally occurring substituted isocoumarins and 3,4-dihydroisocoumarins. The synthesis of naturally occurring isocoumarin Thunberginol B is reported, in which 3,5-dimethoxyhomophthalic acid is a key intermediate for the synthesis of Thunberginol B. It was synthesized efficiently in five steps from 3,5-dimethoxybenzaldehyde via a series of reactions including synthesis of 3,5-dimethoxycinnamic acid, 3-(3′,5′- dimethoxyphenyl)propionic acid, cyclization of 3-(3′,5′-dimethoxyphenyl)propionic acid to 5,7-dimethoxy-1-indanone and oxidative decomposition of methyl 2- hydroxy-2-(5,7-dimethyoxy-1-oxo-1H-inden-2(3H)-ylidene)acetate dimethoxyhomophthalic acid. 3,4-Dimethoxybenzoylchloride from 3,4-dimethoxybenzoic acid condensation with to 3,5- was prepared on reaction with thionyl chloride which on 3,5-dimethoxyhomophthalic acid afforded 3-(3'',4''- dimethoxyphenyl)-6,8-dimethoxyisocoumarin. Complete demethylation of 3-(3'',4''- dimethoxyphenyl)-6,8-dimethoxyisocoumarin with hydrobromic acid in acetic acid gave 3-(3'',4''-dihydroxyphenyl)-6,8-dihydroxyisocoumarin (Thunberginol B). In addition to above, some unnaturally occurring halogenated isocoumarins and their 3,4-dihydrodrivatives were also synthesized. The difluorophenyl- and dichlorophenylisocoumarins by condensation of homophthalic acid with an appropriate acid chloride. Alkaline hydrolysis of the isocoumarins yielded corresponding keto-acids, which on reduction give the corresponding racemichydroxy-acids. 3,4-Dihydroisocoumarins were obtained from these racemic hydroxy-acids by cyclodehydration using acetic anhydride. All the synthesised compounds were identified using their IR, 1 H NMR and mass spectral data. In many cases 13 C NMR and elemental analysis data were employed to support the characterization. In each case, a plasible mass fragmentation pattern is suggested. The synthesized compounds were screened for their antifungal, antibacterial, herbicidal, insecticidal, fungicidal, anti- metastatic, brine shrimp lethality, antioxidant, anti -inflammatory, antiviral, anti- HIV, anti-HBV and anticancer activities and in some cases, very fascinating results were obtained which were then published in different international journals. These synthetic schemes have tremendous potential for further synthesis of novel biological active compounds. Part two of the thesis describes the synthesis and biological screening of some, hitherto unreported, isatin derivatives (Indolinones), 1,4-disubstituted thiosemicarbazides and their related 2,5-disubstituted-1,3,4-thiadiazoles and 4,5- disubstituted-3H-1,2,4-triazole-3-thiones. Indolinones were formed by the direct condensation of hydrazides with halogenated isatins. Triazoles were formed by intramolecular dehydrative cyclization of thiosemicarbazides in basic media while thiadiazoles were formed in acidic media, which is an intermediate during the synthesis of various heterocyclic compounds. Thiosemicarbazides were formed by aldol type condensation reaction of acid hydrazides and isothiocyanates. Isothiocyanates were formed by the reaction of anilines with carbon disulphide in ammonium hydroxide solution to yield ammonium dithiocarbamate, an intermediate which on oxidation with lead nitrate yield isothiocyanate. Acid hydrazides were formed by the reaction of esters of carboxylic acid with hydrazine hydrate and esters were formed by refluxing carboxylic acid in methanol in catalytic amount of carboxylic acids. As a result of these synthetic schemes, thirty new indolinones, ten disubstituted-1,3,4-thiadiazoles and twenty disubstituted 1,2,4-triazole-3-thiones were synthesized. The characterization ofthese synthesized compounds was carried out by IR, 1 H NMR, 13 C NMR, elemental analysis, Mass spectral data and XRD analysis. The synthesized compounds were screened for their antifungal, antibacterial, herbicidal, insecticidal, fungicidal, plant growth regulatory activity and antiviral activities.