A systematic review on Piper longum L.: Bridging traditional knowledge and pharmacological evidence for future translational research.

ETHNOPHARMACOLOGICAL RELEVANCE: Piper longum, commonly referred as 'Pippali', has found its traditional use in India, Malaysia, Singapore and other South Asian countries as an analgesic, carminative, anti-diarrhoeic, immunostimulant, post childbirth to check postpartum hemorrhage and to treat asthma, insomnia, dementia, epilepsy, diabetes, rheumatoid arthritis, asthma, spleen disorder, puerperal fever, leprosy etc. AIM OF THE REVIEW: This review offers essential data focusing on the traditional use, phytochemistry and pharmacological profile of Piper longum thereby identifying research gaps and future opportunities for investigation on this plant. MATERIALS AND METHODS: This systematic survey was accomplished as per the PRISMA guidelines. The information was collected from books, and electronic search (PubMed, Science Direct, Lilca and Scielo) during 1967-2019. RESULTS: Many phytochemicals have been identified till date, including alkaloids as its major secondary metabolites (piperine and piperlongumine), essential oil, flavonoids and steroids. These exhibit a wide range of activities including anti-inflammatory, analgesic, anti-oxidant, anti-microbial, anti-cancer, anti-parkinsonian, anti-stress, nootropic, anti-epileptic, anti-hyperglycemic, hepatoprotective, anti-hyperlipidemic, anti-platelet, anti-angiogenic, immunomodulatory, anti-arthritic, anti-ulcer, anti-asthmatic, anthelmintic action, anti-amebic, anti-fungal, mosquito larvicidal and anti-snake venom. CONCLUSION: Amongst various activities, bioscientific clarification in relation to its ethnopharmacological perspective has been evidenced mainly for anti-amebic, anthelminthic, anti-tumor and anti-diabetic activity. However, despite traditional claims, insufficient scientific validation for the treatment of insomnia, dementia, epilepsy, rheumatoid arthritis, asthma, spleen disorder, puerperal fever and leprosy, necessitate future investigations in this direction. It is also essential and critical to generate toxicological data and pharmacokinetics on human subjects so as to confirm its conceivable bio-active components in the body.

Ultraviolet-A1 phototherapy in Asian skin: A review of 159 cases in Singapore.

BACKGROUND: Ultraviolet-A1 phototherapy has been used to treat many inflammatory dermatoses. AIMS: To determine the efficacy and safety of ultraviolet-A1 phototherapy in Asian skin. MATERIALS AND METHODS: We performed a review of records of patients undergoing ultraviolet-A1 phototherapy at our dermatology unit in Singapore from January 2007 to January 2011. Their electronic medical records were reviewed and a standardized questionnaire was filled up for data collection and tabulation. Chi-square or Fisher's exact tests were used to compare the difference in response between various groups for each characteristic. P value of < 0.05 was considered statistically significant. RESULTS: Our study comprised of 159 patients, of which 103 were patients with hand and foot eczema, 21 with atopic dermatitis, 17 with scleroderma and the remaining with miscellaneous dermatoses. Of these patients, 47.6% of patients with hand and feet eczema had good response after 10 sessions, which increased to 75% after 20 sessions and to 84.6% after 30 sessions. After 10 sessions, 47.6% of patients with atopic dermatitis had good response, which increased to 66.7% after 20 sessions. After 30 sessions, all the three remaining patients with atopic dermatitis experienced good response. For patients with scleroderma, only 11.8 and 10% had good response after 10 and 20 sessions, respectively, which increased to 40% after 30 sessions. LIMITATIONS: Limitations of our study include its retrospective design and, consequently, the lack of standardized treatment protocol, as well as subjective assessment in terms of clinical improvement. CONCLUSIONS: Ultraviolet-A1 phototherapy appears to be efficacious for the treatment of hand and foot eczema as well as atopic dermatitis. However, in patients with scleroderma, the response was partial and needed a longer duration of treatment.

The social transformation of Singapore medicine through 55 years of the SMJ.

The Singapore Medical Journal (SMJ) has in the past 55 years reflected the phenomenal socioeconomic progress of Singapore. Publications in the pre-independent years were mainly on diseases like cholera, diphtheria, leprosy, tetanus and worm infestation. In the new millennium, the research papers included molecular genetics, health economics, obesity, Internet medicine, cancer, cosmetic surgery and palliative medicine. The annual SMA Lecture published in the SMJ provides an ethical compass for doctors to remind them of primum non nocere.

Topical photodynamic therapy in the treatment of basal cell carcinoma in Singaporean Chinese patients.

BACKGROUND: Topical photodynamic therapy has been used for the treatment of superficial and nodular basal cell carcinomas, with varying cure rates. AIMS: This study aims to evaluate the effectiveness of topical photodynamic therapy in the treatment of superficial and nodular basal cell carcinomas in Asian patients treated at the National Skin Centre, Singapore. MATERIALS AND METHODS: A retrospective analysis of Asian patients with histologically confirmed basal cell carcinomas and treated with photodynamic therapy was performed. RESULTS: Eight Chinese patients, with an equal gender distribution and mean age of 83.4 years were included. Five of eight basal cell carcinomas were superficial while the remaining three were nodular. The basal cell carcinomas were located in the head and neck in seven patients. The overall clearance rate at 3 months was 87.5% while the clearance rate for superficial and nodular basal cell carcinomas was 100% and 66.6% respectively at 3 months. At 12 months, the overall clearance rate was 85. 7%. LIMITATIONS: This is a retrospective analysis with small patient numbers. CONCLUSIONS: In this small series of eight Asian patients, topical photodynamic therapy has been shown to be effective and generally well-tolerated in the treatment of basal cell carcinomas, particularly of the superficial subtype. However, larger studies are needed to evaluate its overall efficacy in Asian patients.

Identification of the leprosy agent Mycobacterium lepromatosis in Singapore.

BACKGROUND: A new leprosy-causing species, namely Mycobacterium lepromatosis, was discovered recently to be the cause of diffuse lepromatous leprosy (DLL) in Mexico. It is unknown whether this organism exists beyond Mexico. METHODS: We sought to determine the identity of the mycobacteria in the skin tissue of two patients from Singapore who died of DLL. DNA was extracted from archived biopsy tissue, and conserved polymerase chain reaction primers were used to amplify and sequence two to three mycobacterial genes in each skin sample. RESULTS: Both M. lepromatosis and the well-known leprosy agent Mycobacterium leprae were identified in each DLL skin sample. The M. lepromatosis gene sequences from the Singapore cases matched 99.9% with the known Mexican M. lepromatosis strain, but they only matched the corresponding M. leprae sequences by 89.2%. CONCLUSIONS: The new species M. lepromatosis exists beyond Mexico and is the cause of DLL in Singapore. It may cause dual infections along with M. leprae in endemic areas. Archived skin biopsy can be used to differentiate the leprosy agents.

Skin cancers at Tertiary Referral Skin Hospital in Singapore.

BACKGROUND: Skin cancer is the seventh most common cancer in Singapore. This study was performed to determine the pattern of skin cancers seen in a tertiary referral skin hospital. METHODS: Histologically confirmed skin cancers, seen between 1980 and 1991, were analyzed according to age, sex, race, site, and presence/absence of preexisting skin conditions. RESULTS: Of a total of 520 patients, the commonest skin cancer was basal cell carcinoma (BCC) (36.5%), followed by squamous cell carcinoma (SCC) (24.4%), Bowen's disease (16.7%), and mycosis fungoides (9.0%). Malignant melanomas (2.7%) were rare. The sharp increase (26.2%) in BCC in the recent 3 years was largely contributed by a fivefold increase of non-resident Caucasian patients with BCC. All types of skin cancers were more common in Chinese (78.1%) and less frequent in the more pigmented races (9.4%). The men to women ratio was 1.72:1. The peak age distribution was in the 51-70-year group, with the exception of mycosis fungoides (31-50 years). The commonest site involved in BCC was the head and neck (67.0%) and in Bowen's disease the trunk (33.3%). Squamous cell carcinoma was found on the head and neck and the lower extremities with equal frequency (29.3%) and 46.2% of all SCC on the lower extremities occurred in leprosy patients with chronic trophic ulcers. Of patients with Bowen's disease involving the nonsunexposed parts (trunk and upper extremities), 42.6% had probable arsenic exposure evident either from the history or clinical examination. Malignant melanomas were commonly located on the foot (71.4%). CONCLUSIONS: The commonest skin cancers seen were BCC, SCC, Bowen's disease, and mycosis fungoides. There were differences in the site distribution of SCC, Bowen's disease, and malignant melanomas in our study when compared to studies in Caucasians.

Evaluation of a multidrug therapy programme of leprosy control.

MDT programmes for leprosy control have two objectives, controlling leprosy in populations and controlling leprosy in individuals. Evaluation of such programmes needs to address both objectives and this can be done by a review of the trends in key indicators and by site visits. Site visits are more expensive and should be done less frequently, but they can reveal issues not apparent in routinely produced statistics. Evaluation on an annual basis is the responsibility of programme managers and programme funders. Evaluation by programme staff themselves should be encouraged and supported. Evaluation of an MDT programme's effectiveness in controlling leprosy in a population should be by analysis of case detection as a proxy for incidence. Prevalence rates will continue to be monitored because of the WHO elimination goal, but these do not reflect disease transmission. Case detection is a proxy measure of incidence and depends on consistency in case detection activities. Case detection data by age, gender, mode of detection, disability ratio and lepromatous (MB) rate need to be analysed over at least 5 years and preferably 10 years to give an indication of trends in incidence. Caution is needed, however, as the pattern seen when case detection deteriorates may resemble the pattern expected when transmission is reduced. The site visit is important in this situation in allowing examination of the case detection activities, as well as in looking for new, undetected cases in the population.(ABSTRACT TRUNCATED AT 250 WORDS)

Histoid leprosy in Singapore.

Histoid leprosy is a rare variant of lepromatous leprosy. This is the first documented case of histoid leprosy in Singapore. The patient was diagnosed as borderline leprosy in 1973, remained untreated and progressed to lepromatous leprosy. The characteristic histoid lesions were firm pruriginous nodules on the dorsum of his feet. The histology showed a pseudocapsulated tumour with fibroblasts and histiocytes filled with lepra bacilli. Electron microscopy showed fibroblasts, macrophages with bacilli and plasmacytoid cells with active endoplasmic reticulum. He was found to be dapsone-resistant and the lesions cleared with clorphazimine. Immunological defects were not detected.

Erythema nodosum leprosum in Singapore.

Erythema Nodosum Leprosum (ENL) or Type II reaction is an immune complex syndrome seen in multibacillary leprosy. 20 patients with histological confirmation of ENL in leprosy were studied from 1982 to 1986. These patients had a range of clinical signs, from fever, tender dusky nodules, bullae, ulcers to lymphadenopathy, arthralgia and neuritis. The four major histological patterns are: a) classical pattern showing heavy infiltrations of neutrophils in three cases, b) sub-epidermal bulla pattern with marked oedema of the upper dermis, and collections of neutrophils in five cases, c) vasculitis pattern, affecting superficial and mid-dermal vessels, leading to epidermal necrosis, bulla formation and ulceration. Dilated vessels, congestion, lumenal fibrin clots and fibrinoid necrosis of vessels were seen, d) non-specific picture in nine cases with mild oedema, infiltration with neutrophils, and two cases with minimal reaction had chronic ENL with clinical vasculitis. All the five cases with vasculitis showed C1q, C3 and fibrinogen in the vessels. Comparing ENL reactions reported in Asia, our pattern is similar to that of Malaysians with the majority showing sub-epidermal oedema. Vasculitis is more common in India. Oedema with collagen necrosis as seen in acute ENL with iritis in New Guinea. The Lucio's phenomenon was not seen in any of the countries in Asia.

Leprosy in Singapore.

The incidence of leprosy in Singapore is declining over the past 20 years. More than one third of new cases are now over 50 years while no child under 5 years has been affected since 1970. Male to female ratio is 2:1. Indians are more significantly affected compared to the other races and a higher proportion has tuberculoid leprosy. Tuberculoid leprosy accounts for 50.4% of cases seen during the past decade. Case detections from household contacts is still worthwhile as it accounts for 3% to 13.5% of the yearly incidence of the disease. The first four cases of dapsone resistance was confirmed in 1969. Since then the yearly incidence of clinically diagnosed dapsone resistant cases averaged 2.9 per thousand. Hence, various regimens of multiple drug therapy have been instituted.

Imported communicable diseases in Singapore.

Most communicable diseases in Singapore have been brought under control and some eliminated. In recent years, an increasing proportion of the reported cases turned out to be imported. Between the period 1977 and 1982, 96% of malaria, 44% of paratyphoid, 32% of typhoid, 20% of leprosy, 11% of acute viral hepatitis, 7% of dengue fever/dengue haemorrhagic fever and 7% of cholera were imported. About 10% of the notified tuberculosis cases were non-residents while all the sporadic cases of poliomyelitis (except in 1977) and diphtheria (except in 1982) were contracted outside Singapore. The majority of the infections originated from Southeast Asia and the Indian subcontinent. The main groups of population with imported infections were local residents who travelled to the endemic areas without taking adequate preventive measures, foreign contract workers, and foreign seeking medical treatment in Singapore. Whether or not these imported cases would spread the infection to others in the community and cause epidemics depend on the virulence of the pathogen introduced, the susceptibility of the population and the environmental conditions which favour transmission of infection. Measures taken to reduce the risk of transmission include provision of a high standard of environmental sanitation, epidemiological surveillance to detect and eliminate the focus of infection; maintenance of a high level of herd immunity through immunisation; health education of the medical practitioners and of the public on the need for personal prophylaxis when travelling overseas; and screening of foreign contract workers and returning residents in special situations.

HLA and skin disease in the Chinese.

The HLA associations in skin diseases among the Chinese were reviewed. Tuberculoid leprosy was associated with B17 (RR = 4.1). This HLA association was reinforced in the finding of excess HLA haplotype sharing among affected siblings in multiple case families. In psoriasis the associations were with A1, AW30 and B13. The relative risk associated with AW30, B13 was 16.1. In SLE, mild patients were associated with B13 (RR = 3.7) and severe patients with B17.

Factors influencing the outcome of health campaigns: a case study in Singapore.

Singapore, located in South-east Asia, enjoys a high standard of health care. However, certain diseases are still of major concern to the health authorities, who feel these could be more easily controlled if the public were more aware of their modes of transmission. A "Combat infectious diseases" campaign was therefore launched to educate the public on food-borne diseases (cholera, enteric fever), malaria, dengue/dengue haemmorrhagic fever, leprosy, tuberculosis, and sexually transmitted diseases (syphilis, gonorrhoea). Educational activities in the form of talks, film shows and exhibitions in schools, community centres and other institutions were carried out over a 15-month period. This paper analyzes some of the factors which affected the results of the campaign, as revealed by a health survey conducted in a selected lower-middle income urban community, where sub-groups of the adult population (aged above 15) were tested to assess their health knowledge. Findings indicate that educational level, age of respondents and language proficiency--four languages are used in Singapore--seem to be the three variables that affect the likelihood of the respondents' receptivity to campaign information.