Antimicrobial resistance: Causes and impact on public health in developed and developing countries

Antibiotic-resistance (AR) has become an alarming issue, posing threats to public health in terms of mortality and economic loss. The drivers of AR include environmental contamination from varied sources, ultimately making its way into our drinking water and food. Other factors include reckless use of antibiotics by the uneducated health workers, unhygienic situation of the hospitals, overconsumption and careless discharge of medicines by the general populace, injudicious use of antibiotics in the livestock, and indiscriminate disposal of untreated pharmaceutical wastes into the municipal water have caused several health hazards, such as “AR in infants,” respiratory disorders, and cancer. Furthermore, the sewage treatment process itself augments the antimicrobial resistance crisis. Hence, it is an alarming issue which must be taken care at the global level as well as the national level.

Contribution of insulin resistance to decreased baroreceptor sensitivity & cardiometabolic risks in pre-obesity & obesity

Background & objectives: Although insulin resistance (IR) is a known complication in obesity, the physiological mechanisms linking IR with cardiometabolic risks in obesity have not been well studied. This study was conducted to assess the difference in cardiovascular (CV) risk profile in IR and non-IR (NIR) conditions, and contribution of IR to cardiometabolic risks in pre-obese and obese individuals. Methods: Basal CV, blood pressure variability, autonomic function test and cardiometabolic parameters were recorded in pre-obese (n=86) and obese (n=77) individuals during 2012 and 2015. The association of altered cardiometabolic parameters with homeostatic model for IR (HOMA-IR) in pre-obese and obese groups and with baroreceptor sensitivity (BRS) in IR and NIR groups was calculated by appropriate statistical analysis. Results: Decreased BRS, a known CV risk and cardiometabolic parameters were significant in IR (pre-obese and obese) group compared to the NIR group. Sympathovagal imbalance in the form of increased sympathetic and decreased parasympathetic activities was observed in individuals with IR. There was no significant difference in the level of independent contribution of HOMA-IR to cardiometabolic parameters in pre-obese and obese groups. Adiponectin and inflammatory markers had an independent contribution to BRS in IR group. Interpretation & conclusions: Findings of the present study demonstrated that the intensity of cardiometabolic derangements and CV risk were comparable between IR, pre-obese and obese individuals. Pro-inflammatory state, dyslipidaemia and hypoadiponectinaemia might contribute to CV risk in these individuals with IR. IR could possibly be the link between altered metabolic profile and increased CV risks in these individuals independent of the adiposity status.

Diabetic nonketotic hyperosmolar state: interesting imaging observations in 2 patients with involuntary movements and seizures.

We report two patients of diabetic nonketotic hyperosmolar state presenting acutely with "self-limiting hemichorea - hemiballismus" and "generalized convulsive status epilepticus". CT scan in both the patients revealed a hyperdense nonenhancing basal ganglia. Magnetic resonance imaging brain of patient 1 showed it to be hyperintense on T1W image and iso-hyper intense on T2W image, minimally enhancing with contrast injection.

Management of neurodegenerative disorders: Parkinson's disease and Alzheimer's disease.

Neurodegenerative disorders result from premature progressive degeneration of specific neurons, and manifest as diseases or syndromes with varied combinations of cognitive, motor, sensory and autonomic dysfunctions. The management involves pharmacotherapy as well as non-pharmacological measures and also to lessen the burden of the care-givers. The medications available for medical treatment are: Levodopa, dopamine agonists, amantadine, anticholinergics, enzyme inhibitors, etc. Advanced Parkinson's disease is concerned with management of motor complications and non-motor complications. Recently surgical treatment is a great option for managing motor complication. Orthostatic hypotension, gait distiurbances, emotional and psychiatric problems, sleep disturbances can be managed and had been discussed in brief. Currently there is no medication available for the cure of Alzheimer's disease. The specific medications claimed to improve patient's well being and cognition include cholinesterase inhibitors, N-methyl-D-aspartate receptor antagonist, anti-oxidants, and anti-amyloid therapy. While medical and surgical treatments for Parkinson's disease have revolutionised the management, still drug therapy for Alzheimer's disease is dismal.

Clinical features, assessment and treatment of essential tremor.

Essential tremor is the most common of the movement disorders, being 20 times more common than Parkinson's Disease. It is characterised by postural and kinetic tremor which maximally affects the hands. It can be assessed by physiological techniques, subjective clinical methods, objective clinical methods and handicap/disability scales. Accelerometry, spirography and handwriting assessment, volumetry and handicap/disability questionnaires are commonly used methods. Primidone and propranolol are the first-line drugs. Several second-line drugs have been identified. Surgical techniques include lesioning or stimulation of the ventral lateral thalamus. Alcohol and botulinum toxin A are found to reduce tremor amplitude as well.

Modulation of feeding and drinking behaviour by catecholamines injected into nucleus caudatus in rats.

Lesions of nucleus caudatus have been documented to produce adipsia and aphasia in rats. Injection of dopamine into this nucleus has been shown to facilitate water intake in rats. But, reports are not available on the effects of intracerebral injection of epinephrine and norepinephrine on feeding and drinking behaviour in animal models. Therefore, in the present study the effect of adrenaline and noradrenaline injected into nucleus caudatus on food and water intake in rats was assessed. 24 h basal food and water intakes were recorded in Wistar rats and were found to be 12.37 +/- 0.20 g and 22.04 +/- 0.27 ml respectively. Stainless steel cannulae were implanted stereotaxically into the nucleus caudatus. Four different doses (0.1 microgram, 0.5 microgram, 1 microgram, and 2 micrograms) of adrenaline and noradrenaline were injected into the nucleus caudatus through the implanted cannulae in separate groups of animals and their 24 h food and water intakes were recorded following these injections. No change in food and water intake was observed following the administration of different doses of adrenaline. A significant increase in 24 h food intake reaching a maximum of 16.03 +/- 0.15 g at 2 micrograms dose, without change in water intake was observed following administration of different doses of noradrenaline. The noradrenaline-facilitated food intake was blocked when noradrenaline was injected following injection of phentolamine, an alpha-receptor blocker. The bilateral lesions of nucleus caudatus resulted in a significant and sustained inhibition of food (8.98 +/- 0.17 g) and water intake (19.12 +/- 0.16 ml). These observations suggest that nucleus caudatus is involved in regulation of food and water intakes in rats. Noradrenaline-facilitated food intake is mediated by alpha-receptors. Adrenaline does not affect these ingestive behaviours when injected into the nucleus caudatus in rats.

Modulation of feeding and drinking behaviour by catecholamines injected into nucleus accumbens in rats.

Nucleus accumbens is proposed as one of the centers in the neural circuitry involved in the regulation of feeding and drinking behaviour in rats. Injection of dopamine and angiotensin-II into this nucleus has been documented to affect water and food intake in rats. Reports on the effect of intracerebral injection of catecholamines on feeding and drinking behaviour in animal models are conflicting. Therefore, in the present study the effect of adrenaline and noradrenaline injected into nucleus accumbens on food and water intake in rats was assessed. 24 h basal food and water intakes were recorded in Wistar rats and were found to be 12.3 +/- 0.46 g and 21.7 +/- 1.03 ml respectively. Stainless steel cannulae were implanted stereotaxically into the nucleus accumbens. Four different doses (0.1 microgram, 0.5 microgram, 1 microgram, and 2 micrograms) of adrenaline and noradrenaline were injected into the nucleus accumbens through the implanted cannulae in different group of animals and their 24 h food and water intakes were recorded following these injections. No change in food and water intake was observed following the administration of different doses of adrenaline. A significant increase in 24 h water intake reaching a maximum of 28.88 +/- 1.45 ml at 1 microgram dose, without change in food intake was observed following administration of different doses of noradrenaline. The noradrenaline-facilitated water intake was blocked when noradrenaline was injected following injection of phentolamine, an alpha-receptor blocker. The bilateral lesions of nucleus accumbens resulted in a significant and sustained inhibition of water intake (16.61 +/- 0.67 ml) without change in food intake. These observations suggest that noradrenaline facilitates water intake without affecting food intake when injected into the nucleus accumbens in rats and the dipsogenic effect of noradrenaline is mediated by alpha-receptors. Adrenaline does not affect these ingestive behaviours when injected into the nucleus accumbens in rats.

Patterns of prescriptions and drug use in two tertiary hospitals in Delhi.

The study was carried out to assess prescribing trends in outpatients at Dr. R.P. Centre for Ophthalmic Sciences (RPC) and other OPD's of All India Institute of Medical Sciences (AIIMS) and Safdarjung hospitals, two premier hospitals in Delhi. Prescriptions of 500 patients were audited and analysed under heads of average number of drugs per patient, percentages of drugs prescribed by generic name, antibiotics, injections, drugs from WHO recommended essential drug list, availability of drugs etc. using WHO basic drug indicators. Prescription analysis showed that 75 to 95% drugs were prescribed from essential drug list. The average number of drugs per prescription was 1.42 to 4.07. Percentage of antibiotics prescribed varied from 14.39% to 22.28%. The use of injections was from nil to 4.4%. Availability of drugs was however, not satisfactory. Though maximum drugs were prescribed from essential drug list, the results indicate that there is a considerable scope for improving prescribing habits according to rational drug use and to provide a feed back to hospital authority for making maximum number of drugs available to the patients.

Early onset cerebellar ataxia with retained tendon reflexes (EOCA) and olivopontocerebellar atrophy (OPCA): a computed tomographic study.

Computed tomographic (CT) studies in olivopontocerebellar atrophies (OPCA) and 'early onset cerebellar ataxia with retained tendon reflexes (EOCA)' are few and vary widely in methodology and criteria for cerebellar and brainstem atrophy. In this prospective study, CT scan observations on 26 patients (EOCA-11, OPCA-15) were compared with 31 controls using qualitative and quantitative assessment of cisterns, ventricles and atrophy of brain. Vermian and/or cerebellar hemispheric (predominantly anterior) atrophy was present in 80.8% and both were equally common. Cerebral cortical atrophy (26.9%) and leukoariosis (15.4%) were less frequently seen. Statistically significant atrophy of pons, brachium pontis, cerebellum and midbrain was noted in patient group. No significant differences were observed between EOCA and OPCA groups. Evidence of atrophy did not correlate with either the duration of illness or the severity of cerebellar ataxia in both the groups. The severity of brainstem atrophy in 14 patients with and 12 patients without abnormal brainstem auditory evoked response did not differ significantly. This study highlights the methodology of CT evaluation for brainstem and cerebellar atrophy, draws attention to cerebral atrophy and emphasizes the lack of significant differences in CT morphology between OPCA and EOCA patients.

Early onset cerebellar ataxia with retained tendon reflexes: a clinical, electrophysiological and computed tomographic study.

Fourteen patients of Early Onset Cerebellar Ataxia with retained tendon reflexes (EOCA) were prospectively evaluated clinically, electorphysiologically and with CT scan. Their age and duration of symptoms were 18.6 +/- 8.3 years and 7.8 +/- 5.1 years respectively. High consanguinity (91.7%) and positive family history (76.9%) suggested autosomal recessive inheritance. Apart from cerebellar signs and brisk knee jerks in all, other important findings were abnormal ocular movements (mostly impaired saccades) in 92.8%, Babinski's sign (78.6%), brisk ankle jerks (64.3%), spasticity in lower limbs (50%) and impairment of proprioceptive sensations (50%). Neuropsychological tests, done in 12 patients, were abnormal in all. Abnormalities of electroneuromyographic studies were universal, motor conduction parameters (85.7%) being more affected than sensory (78.6%). One or more modalities of evoked potentials were abnormal in 71.4%, that of brainstem auditory evoked response being most frequent (50%), followed by posterior tibial somatosensory evoked potential (SSEP) (46.1%) and median SSEP and visual evoked potential (30.8% each). CT scan (n = 12) showed atrophy of brainstem (91.7%), cerebellar hemisphere and/or vermis (83.3%) and cerebral cortex (33.3%). There was no correlation between the duration of disease and degree of disability or abnormalities of nerve conduction and CT parameters. The rationality of the diagnosis of this recently recognised entity of 'EOCA' in Indian context is discussed.

An outbreak of viral hepatitis in a housing complex of north Calcutta.

In a housing complex of North Calcutta, a sudden outbreak of hepatitis occurred between September 1988 and January 1989. Of 620 residents, 8.5 per cent were affected. Majority of the cases occurred among the adult population and the case fatality rate was 3.8 per cent. The epidemic was common source with peak incidence in the month of November. The source of infection was most likely drinking water supplied by the Municipal Corporation which was found to be contaminated by faecal coli. Epidemic was suspected to be caused by enterically transmitted Non A Non B hepatitis virus as the serological testing of all 18 blood samples were negative for anti-HAVIgM titre and only one sample was positive for HBsAg.

Proton liberation in the pre-steady state phase of creatine kinase.

Numerous stereochemical and kinetic investigations on the reaction pathway of creatine kinase (CK) suggest that this enzymic reaction proceeds via direct in-line transfer of phosphate between participating substrates and to date there has been no chemical evidence for any plausible intermediate between enzyme-substrate and enzyme-product complexes. By following the absorption pattern of a pH sensitive dye (o-cresol sulphonaphthalein) in a stopped flow module we have studied transient pH changes in the backward reaction of CK. While the rapid mixing of ADP and CK gives no pH transient, that of phosphocreatine (PCr) and CK gives H+ liberation with kapp of 62.8 sec-1. The magnitude of proton release is one H+ per monomer of CK. Mixing of PCr+CK with ADP does not give any detectable pH transient and the reaction immediately proceeds to steady phase. The mixing of ADP+CK with PCr again gives a release of 1.2 H+ per monomer of CK with kapp of around 67.2 sec-1 before the reaction proceeds to steady phase where there is absorption of one H+ per ADP transphosphorylated. The results obtained, therefore, indicate the involvement of proton deficient E.PCr and E.ADP.PCr complexes in the pathway of CK.