Paediatric morphoea: a holistic review. Part 2: diagnosis, measures of disease activity, management and natural history.

Paediatric morphoea is a debilitating fibrosing disorder of uncertain aetiology, affecting the skin and subcutaneous tissues. Defining optimum management strategies in paediatric morphoea remains an ongoing challenge, owing to the varied presentations and a relative paucity of paediatric-specific studies. We performed a literature search on PubMed, MEDLINE and Google Scholar, using keywords such as 'pediatric morphea', 'juvenile localised scleroderma' and 'juvenile systemic sclerosis'. Relevant studies, including randomized trials, reviews of standard current guidelines and original research articles, were selected and results analysed before summarizing them. In Part 1 of this review, we described the epidemiology, aetiopathogenesis and clinical classification; in this part, we discuss the diagnosis, markers of disease activity, management and natural history in paediatric morphoea.

Uranium distribution in groundwater and assessment of age dependent radiation dose in Amritsar, Gurdaspur and Pathankot districts of Punjab, India.

A comprehensive study of seasonal variation of uranium distribution in groundwater of Amritsar, Gurdaspur and Pathankot districts of Punjab, India and assessment of associated radiological risks, chemical risks and effective radiation dose for different age groups, was conducted to determine its health impact on humans residing in these regions. Physicochemical parameters such as pH, EC, TDS, total hardness and contents of various anions such as carbonates/bicarbonates, chlorides, fluorides, nitrates, sulphates and phosphates in groundwater were also analysed to determine correlation between groundwater chemistry and uranium distribution. The average values of uranium concentration in ground water samples of Amritsar, Gurdaspur and Pathankot districts were found to be 8.6 µg L-1, 4.3 µg L-1 and 3.0 µg L-1, respectively, in pre-monsoon and 8.8 µg L-1, 4.9 µg L-1 and 3.4 µg L-1, respectively, in post-monsoon. The uranium concentration in majority of the ground water samples was found to be below the permissible limit of 30 µg L-1 recommended by World Health Organization (WHO, 2011). In all three districts, TDS, EC and bicarbonates were found to have positive correlation with observed uranium contents in both seasons. The annual effective dose due to ingestion of uranium through drinking water was found to be less than the prescribed limit of 100 µSv y-1 given by WHO (2004). Radiological and chemical toxicity risk assessment of uranium in groundwater was also carried out and found to be within the permissible values of 1.67 × 10-4 and 4.53 µg kg-1 day-1 respectively, recommended by Atomic Energy Regulatory Board (AERB, 2004).

Revisiting Metformin: Annual Vitamin B12 Supplementation may become Mandatory with Long-Term Metformin Use.

Monitoring of adverse drug reactions of a drug is a continuous process and runs through-out the life of a drug. Many rare adverse effects of a drug are documented after years of use; when a single case (signal generation) is reported leading subsequently to reporting of more cases. Deficiency of Vitamin B12 (vit B(12)) is a known sequel of prolonged metformin therapy. It was recommended to have annual measurement of serum vit B(12) levels in patients on long term metformin therapy way back in 1970 itself. After more than 50 years of use of metformin, we have come to know that metformin induced vit B(12) deficiency can cause neuropathy; forcing to change the recommendation from annual screening of vit B(12) levels to annual supplementation of vit B(12).

Methotrexate/narrowband UVB phototherapy combination vs. narrowband UVB phototherapy in the treatment of chronic plaque-type psoriasis--a randomized single-blinded placebo-controlled study.

BACKGROUND: Psoriasis is a chronic, recurring inflammatory disease affecting the skin, joints and nails that has a significant negative impact on the quality of life. Efficacy of combination of methotrexate/narrowband ultraviolet B (NBUVB) phototherapy in the treatment of psoriasis has been rarely assessed. OBJECTIVES: To compare the efficacy of methotrexate/NBUVB phototherapy combination vs. NBUVB phototherapy in the treatment of chronic plaque psoriasis. METHODS: Forty patients with chronic plaque-type psoriasis (body surface area involvement >10%) were randomized to receive either methotrexate/NBUVB phototherapy (group A) or placebo/NBUVB phototherapy (group B). End point of treatment was 75% reduction in Psoriasis Area and Severity Index (PASI) Score or upto 6 months, whichever was earlier. Patients were then followed up for a period of 12 weeks for assessment of relapse. RESULTS: Of 40 patients, 37 completed the treatment period and 29 both the treatment period and follow-up. PASI 75 was achieved in 19/20 patients in group A and 14/20 patients in group B (P < 0.04). The mean number of weeks(P = 0.001), the mean cumulative dose of NBUVB (P = 0.001) and the mean number of phototherapy sessions (P = 0.0001) required to achieve PASI 75 were significantly less in group A compared with group B. There was no significant difference in the number of patients who relapsed during the follow-up period (P = 0.68). CONCLUSION: Combination of methotrexate and NBUVB phototherapy provides more rapid clinical improvement compared with NBUVB monotherapy in the treatment for chronic plaque-type psoriasis.

Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options.

Free radicals are common outcome of normal aerobic cellular metabolism. In-built antioxidant system of body plays its decisive role in prevention of any loss due to free radicals. However, imbalanced defense mechanism of antioxidants, overproduction or incorporation of free radicals from environment to living system leads to serious penalty leading to neuro-degeneration. Neural cells suffer functional or sensory loss in neurodegenerative diseases. Apart from several other environmental or genetic factors, oxidative stress (OS) leading to free radical attack on neural cells contributes calamitous role to neuro-degeneration. Though, oxygen is imperative for life, imbalanced metabolism and excess reactive oxygen species (ROS) generation end into a range of disorders such as Alzheimer's disease, Parkinson's disease, aging and many other neural disorders. Toxicity of free radicals contributes to proteins and DNA injury, inflammation, tissue damage and subsequent cellular apoptosis. Antioxidants are now being looked upon as persuasive therapeutic against solemn neuronal loss, as they have capability to combat by neutralizing free radicals. Diet is major source of antioxidants, as well as medicinal herbs are catching attention to be commercial source of antioxidants at present. Recognition of upstream and downstream antioxidant therapy to oxidative stress has been proved an effective tool in alteration of any neuronal damage as well as free radical scavenging. Antioxidants have a wide scope to sequester metal ions involved in neuronal plaque formation to prevent oxidative stress. In addition, antioxidant therapy is vital in scavenging free radicals and ROS preventing neuronal degeneration in post-oxidative stress scenario.

Evaluation of the efficacy of albendazole against the larvae of Taenia solium in experimentally infected pigs, and kinetics of the immune response.

Cysticercosis, a disease of economic and public health importance, is caused by Cysticercus cellulosae, the metacestode stage of Taenia solium. Experimental induction of cysticercosis was achieved in young pigs by feeding an optimum dose of 20,000 T. solium (Indian strain) eggs after immunosuppression, to assess the effect of albendazole and development of the immune response to cysticercus antigens before and after treatment. Histopathological studies revealed the presence of cysticerei in liver, lungs and muscles. Treatment with albendazole at 15 mg kg-1 body weight daily for 30 days starting from day 0 or 15 days post-infection resulted in 100% cure rates. Increases in antibody titre to crude soluble extract and a Sephadek G-200 purified antigenic fraction of Cysticercus cellulosae were found on days 25, 40 and 55 post-infection in untreated pigs and those in which treatment started on day 15 post-infection, whereas no increase in antibody response was observed in pigs in which treatment started on day 0.

Effect of topical anaesthesia on the motor performance of vocal cords as assessed by tussometry.

Tussometry involves a continuous measurement of airflow produced by a cough manoeuvre displayed as an airflow-time wave. There is a rapid rise to its peak (cough peak flow rate) and the time taken to reach the peak (peak velocity time) is determined by the laryngeal opening at the onset of cough. Cough peak flow and peak velocity time were measured in 10 healthy volunteers before and after topical anaesthesia of the larynx with lignocaine 100 mg sprayed under indirect laryngoscopy. Adequacy of anaesthesia was established by touching the cords deliberately with a fibreoptic laryngoscope. All subjects had excellent anaesthesia of the larynx. However, cough peak flow rate and peak velocity time remained unchanged following topical anaesthesia. We conclude that topical anaesthesia of the larynx does not impair the motor performance of the vocal cords during a voluntary cough.

Altered course of Plasmodium berghei infection by nifedipine treatment.

The effect of nifedipine (a calcium channel blocker) on the course of P. berghei infection was examined. It was observed that mice receiving a daily dose of 0.015 mg/kg of nifedipine had significantly shorter prepatent, patent and survival periods as compared to untreated P. berghei-infected animals (p < 0.001). This shows that the calcium channel blockers, in addition to possessing the property of reversing drug resistance during combined therapy with chloroquine, may also alter the pathophysiology of malaria infection. The decreased resistance of the host to the invading parasite suggests that the effect of CCB on the host-parasite interaction in human malaria needs to be investigated further before CCB can be used in combination with chloroquine for the treatment of chloroquine-resistant malaria or for chemoprophylaxis.

Effect of nifedipine treatment on oxidative metabolism of peritoneal macrophages and neutrophils of Plasmodium berghei-infected mice.

The oxidative metabolism of peritoneal macrophages (PM) and neutrophils from nifedipine (calcium channel blocker)-treated, Plasmodium berghei (NK 65)-infected and normal infected Swiss Albino mice was studied. A significant fall in oxidative metabolism as evidenced by decreased chemiluminescence (CL) response (P less than 0.001) was recorded both in PM and neutrophils from nifedipine-treated mice compared to the control animals. When the oxidative metabolism of these phagocytes was studied after infection of the host, higher CL response was recorded from both PM and neutrophils isolated during the early course of infection (0-1 and 5-10% parasitaemia) when compared to uninfected mice (P less than 0.001). A similar pattern was observed in the case of nifedipine-treated and infected mice even though the CL response was much lower. The increasing parasite load not only resulted in subnormal CL response but also prolonged the time required for the phagocytes to exhibit peak oxidative activity both in normal infected and CCB-treated infected mice, but the time taken to show peak CL response was shortened following drug administration compared to controls. These observations revealed the profound in vivo effect of CCB on the functioning of phagocytic leucocytes and thereby questions the use of CCB in combination with chloroquine for reversal of drug resistance.

Humoral immune response of normal rhesus monkeys during primaquine administration.

Humoral immune response of normal rhesus monkeys was studied after giving a standard dose of primaquine. The drug did not effect the level of complement (C3) and its haemolytic activity. Levels of Immunoglobulin i.e. IgG, IgM & IgA and number of immunoglobulin secreting cells also remained unaffected. Results of this study suggested that primaquine did not suppress the immune status of the host and could be given safely to the malaria patients.

Sucralfate retention enemas in solitary rectal ulcer.

The conservative treatment of solitary rectal ulcer is generally unsatisfactory. Six patients, aged 27-54 years, with recurrent solitary rectal ulcer were treated with topical administration of sucralfate in a daily dose of 2 g twice a day for 6 weeks. Four patients experienced complete relief of symptoms and the remaining two patients had marked improvement. Although macroscopic healing of the ulcer was apparent in all, histologic improvement was not appreciable. Five of the six patients remain in remission during a follow-up period of 4-14 months (mean, 8 +/- 1.5 months). Recurrence was observed in one patient at 5 months, which satisfactorily resolved with sucralfate enemas. From these preliminary observations we infer that solitary rectal ulcer can be effectively treated with topical application of sucralfate.

Effect of nifedipine on Leishmania donovani infection in-vivo and in-vitro: chemiluminescence responses of peritoneal macrophages and neutrophils.

After peritoneal macrophages had been exposed to different concentrations of nifedipine (10-120 ng mL-1) there was a significant increase (P less than 0.001) in the percentage of Leishmania donovani infected macrophages compared with controls. Parasite load was also significantly increased (P less than 0.001) in nifedipine-treated, L. donovani infected, BALB/c mice, compared with untreated, infected mice, post-inoculation. Peak chemiluminescence responses were significantly depressed (P less than 0.001) in nifedipine-treated infected mice compared with untreated mice post-inoculation. It is suggested that availability of intracellular calcium is a factor in the defense mechanism of inflammatory cells in L. donovani infections.

Nifedipine prevents the pressor response to laryngoscopy and tracheal intubation in patients with coronary artery disease.

The efficacy of sublingual nifedipine, administered one minute before anaesthetic induction, in order to minimise the pressor response to laryngoscopy and tracheal intubation was studied in a group of 15 patients who underwent coronary artery bypass surgery. Another group of 15 similar patients served as control. Premedication consisted of oral diazepam 5-10 mg, intramuscular morphine 0.2 mg/kg and promethazine 0.4 mg/kg. Anaesthesia was induced with morphine 0.1-0.15 mg/kg and thiopentone 3-5 mg/kg. Laryngoscopy and tracheal intubation were facilitated with suxamethonium 1.5 mg/kg. A significant increase in blood pressure occurred during and after laryngoscopy and tracheal intubation in the control group. This increase was absent in the patients pretreated with nifedipine. The nifedipine group also maintained a lower rate-pressure-product than the control group during the period of study. It is concluded that nifedipine 10 mg is a useful pretreatment to prevent the pressor response to laryngoscopy and tracheal intubation in patients with coronary artery disease.

Characterization of seed storage proteins of urdbean (Vigna mungo).

Dehulled and defatted flour of urdbean (Vigna mungo), Var T-9, contained 25% protein with maximum contribution by globulins (63%). Albumins and glutelins contributed 12% and 21% respectively, whereas prolamins were present only in traces (1%). Globulins were further fractionated into legumin and vicilin type proteins which were present in the ratio of 4:1. All the protein fractions were heterogenous in nature as revealed by high performance liquid chromatography. SDS-polyacrylamide gel electrophoresis revealed the total protein sample to contain 21 different components with molecular weights ranging from 8.92 to 117.49 kd. Albumins, globulins, prolamins and glutelins resolved into 4, 8, 6 and 13 different sized components of molecular weights ranging from 10.23 to 25.53, 10.84 to 112.72, 10.33 to 51.52 and 8.91 to 112.72 kd, respectively. Amino acid analysis of all fractions revealed that glutamic acid was present in maximum concentration followed by aspartic acid and lysine. Just like other pulse proteins, the urdbean proteins were also deficient in sulphur containing amino acids.