Management of malaria: recent trends.

In the present day scenario of resurgence of infectious diseases, malaria compounded with problems of multi drug resistance, assumes paramount importance. A combination of artemisinine derivatives with other effective anti-malarial drug remains the most effective form of treatment against the falciparum malaria which is most lethal form of disease. Oral chloroquin in the dose of 25 mg base/kg over 48 hours is effective in infections due to P. vivax, P. ovale P. malariae and chloroquine sensitive P. Falciparum. For chloroquine resistant P. vivax and multidrug resistant falciparum malaria, a combination of Quinine with doxycycline or clindamycin for 5-7 days, Quinine with singlt dose sulfadoxine-pyrimethamine combination. Mefloquine with artemeter or artesunate for 3 days, artesunate with doxycycline or clindamycin for 7 days and Otovaquin with proguanil for 3 days have been found to be effective. Primiquin as a hypnozoticide for 5-10 days is mandatory for preventing relapse in cases of P. vivax, P. Ovale and P. malariae. Death due to complicated malaria can be as high as 75% if case diagnosis is delayed or the patient arrives late. The artemisinine based rectal suppositories can be very effective in home/village setting in patients who can not be given oral anti malarial, though not yet approved for use in our country. In ICU settings, properly administered loading dose of quinine has proved to be effective and safe in almost all therapeutic trials including our study on Indian patients. Frequent blood glucose monitoring is mandatory. Parentral artemisinine with oral mefloquine is an effective alternative to quinine based therapy. The cerebral malaria management in the ICU setting includes monitoring fluid and electrolyte balance so as to maintain a CVP of 5 cm of water and pulmonary arterial occlusive pressure at less than 15 mm of mercury. In renal failure haemofiltration is ideal. Mefloquine is safe in second and third trimester of pregnancy. Exchange transfusion, haemopheresis and plasmapheresis are new techniques in the treatment of gravely ill patients with PF malaria especially when parasitemia exceeds 10%.

Distal spinal muscular atrophy.

Spinal muscular atrophies (SMA) are clinically heterogenous group of motor system disorders characterised by progressive pure lower motor neuron involvement. The distal form of SMA is an extremely rare disorder, which presents in the adults and has a relatively slow progression with almost no effect on the patients' life-span. Differential diagnosis of this syndrome include other forms of neuromuscular disorders with peroneal muscular atrophy like hereditary motor sensory neuropathy (HMSN) and distal myopathies, which need exclusion before confirming this rare entity. We present a young male with this disorder and briefly discuss the theoretical aspects.

A fatal case of systemic brucellosis.

A 65 years man presented with fever, drenching sweats, progressive dyspnoea, backache and weight loss. On examination, he had wide pulse pressure, clubbing, retinal hemorrhages, aortic and mitral regurgitation, hepatosplenomegaly, lower spinal tenderness and bilateral basal crepitations. Transthoracic 2D-echocardiography showed a large vegetation on the aortic valve. Antibody titers for brucella were positive. X-ray spine was suggestive of brucella spondylitis. Early surgical intervention was planned and the patient was given combination antibiotic therapy. The course was complicated by renal failure and the patient succumbed while being taken up for surgery.

Carbon monoxide poisoning.

OBJECTIVES: We studied the clinical profile and autopsy findings of carbon monoxide (CO) poisoning encountered at a hospital located at the altitude of 5,000 ft above mean sea level. METHODS: Clinical and postmortem findings in 25 and 15 cases of accidental CO poisoning respectively were evaluated. The diagnosis was made on circumstantial evidences, definite history of "Bukhari" burning and positive Kunkel's test for carboxyhaemoglobin (COHb). Detailed routine investigations including pulse oxymetry, X-ray chest and electrocardiographical monitoring was carried out in all the 25 patients. Oxygen (100%) via an endotracheal tube in all the comatosed patients and by conventional non-rebreathing plastic face masks was the mainstay of treatment. All patients were monitored and followed up for any delayed neurological sequelae. RESULTS: Most of the patients were young adults and the duration of exposure varied between three to eight hours. The initial diagnosis was stroke in three, seizure in one, encephalitis in two and ischaemic heart disease (IHD) in four. Neurological and respiratory signs and symptoms were noted in 19 and 18 of 25 patients respectively. SPO2 measured by pulse oxymetry was normal in all cases. ECG was suggestive of IHD in four patients. No delayed neurological sequelae was noted in any patients. Autopsy revealed deep red discoloration of skin and serous membranes in 80%, pulmonary oedema in 100% and cerebral oedema with widespread multiple pin point haemorrhages mainly in thalamus and globus pallidus in 40%. CONCLUSION: A high level of suspicion and routine history about the kind of indoor heating, specially in cold climate areas during winter will help in early diagnosis and decrease the incidence of misdiagnosis of CO poisoning. Oxygen (100%) or hyperbaric oxygen, if available should be administered without waiting for COHb levels to decrease morbidity and mortality.

Near drowning in cold water.

Drowning and near drowning is a common cause of accidental death all over the world; specially in road traffic accidents over bridges, swimming pool and boat tragedies. Cold water drowning resulting in hypothermia can lead to instant death before actual drowning. Five cases of near drowning (ND) in cold water, who presented with varied clinical picture like coma with decerebrate rigidity and fixed dilated pupils, hypertension with coma and delayed pulmonary oedema (Secondary drowning) are reported. Energetic management with continuous positive airway pressure was very rewarding in all patients with ND except in one who had transient organic psychosis persisting for two weeks followed by minimal cognitive defect in the form of slow mentation, lack of drive and mild irritability (Bender Gestald Test Score of 53). We have tried to analyse some of the clinical features of ND and the sequel associated with it. The management as well as recent developments in the field are also discussed.

Near drowning in cold water.

Drowning and near drowning is a common cause of accidental death all over the world; specially in road traffic accidents over bridges, swimming pool and boat tragedies. Cold water drowning resulting in hypothermia can lead to instant death before actual drowning. Five cases of near drowning (ND) in cold water, who presented with varied clinical picture like coma with decerebrate rigidity and fixed dilated pupils, hypertension with coma and delayed pulmonary oedema (Secondary drowning) are reported. Energetic management with continuous positive airway pressure was very rewarding in all patients with ND except in one who had transient organic psychosis persisting for two weeks followed by minimal cognitive defect in the form of slow mentation, lack of drive and mild irritability (Bender Gestald Test Score of 53). We have tried to analyse some of the clinical features of ND and the sequel associated with it. The management as well as recent developments in the field are also discussed.

The circadian pattern of ischaemic heart disease events in Indian population.

A circadian variation of the onset of almost all ischaemic heart disease (IHD) manifestations with an increased incidence between 6:00 a.m. to 12:00 noon has been reported in several publications during the last decade. This study included 605 patients of various IHD subgroups, i.e., acute Q-wave myocardial infarction (n = 174), unstable angina (n = 266), non-Q myocardial infarction (n = 67), acute pulmonary oedema (n = 35) and sudden cardiac death (n = 63) proven to be due to IHD by electrocardiogram and/or autopsy. In overall, 33.55% (p < 0.0001) of patients had the IHD events with an increased frequency between 6:00 a.m. To 12:00 noon (2nd quarter of the day.) The distribution in the remaining, 1st 3rd and 4th quarters was 22.64%, 20.99% and 22.80%, respectively. Similar circadian rhythm (2nd quarter peak) was seen in males (n = 486), females (n = 119), patients ages < 60 years (n = 388), patients without past history of IHD (n = 434) and in those not on any medications (n = 359). However in patients with past history of IHD and diabetics, the circadian distribution did not differ from the random and the cases were distributed almost evenly in all the four quarters of the day. 39.08% of all the acute Q wave myocardial infarction (A-QMI), 33.45% of unstable angina and 36.5% of sudden cardiac deaths also occurred between 6:00 a.m. and 12:00 noon. However 51.42% cases of acute pulmonary oedema were encountered in the 4th quarter of the day and patients with non Q-myocardial infarction (non-QMI) did not show any particular pattern in relation to circadian rhythm. Thus it was inferred that in Indian population too the circadian pattern of IHD manifestations are similar to other population studies and morning appears to be the time, when the triggers (transient precipitating risk factors) that lead to these events are likely to be prominent. Study of these triggers and/or early morning pathophysiological changes may go a long way in understanding ischaemic heart disease and suggesting possible means of prevention.

The changed clinical spectrum of malaria due to drug resistance.

The clinical spectrum of 14 cases of Plasmodium falciparum malaria (PF) who received empirical treatment and suffered from initial prolonged mild illness culminating into severe complicated malaria are presented. The empirical treatment (ET) consisted of adequate doses of chloroquine in 9, chloroquine with pyrimethamine-sulphadoxine combination in 3 and pyrimethamine-sulphadoxine alone in 2 cases. Moderate fever and weakness persisted for 7 to 28 days leading to anaemia and progressive hepatosplenomegaly in all patients. Other clinical features noticed included jaundice in 5, sudden shock with pulmonary oedema in 4, cerebral malaria and renal failure in 3 each and multiorgan in 4 cases. Subsequent investigations revealed PF rings in 9 cases, mixed PF and vivax infection in 3 and PF gametocytaemia only in 2 patients. Seven patients received quinine, 4 quinine with doxycycline and 3 were given quinine followed by injection artemether. Exchange transfusion was carried out in two cases. Four patients died. The empirical treatment with first line antimalarials alters the clinical profile of resistant PF, makes it milder temporarily, delays in confirming the diagnosis and leads to high mortality. There is urgent need for more diligent early workup for these patients who linger on with moderate pyrexia, progressive hepatosplenomegaly, anaemia and jaundice after ET till better diagnostic methods are available to avoid the prolonged illness and high mortality.

Prolactin and cortisol levels in seizure disorders.

Levels of prolactin (PRL) and cortisol were estimated to find out the acute effects of generalised tonic clonic seizures (GTCS), partial seizures and pseudoseizures in 60, 18 and 9 patients respectively. Prolactin levels were estimated at 20, 60 and 120 minutes whereas, cortisol was estimated at 20, 60, and 120 minutes postictally. Cortisol and PRL estimation was also done in 10 healthy controls and 11 patients of epilepsy during interictal phase. Serum PRL levels were elevated (> 25 ng/ml) in 68.33% of GTCS and 11.11% of partial seizure cases. The peak levels were achieved in first 30 minutes after the seizures with a gradual return to base line during subsequent one hour. None of the patients with pseudoseizure showed any rise in serum PRL levels. The interictal PRL levels were normal in all the epileptics. Plasma cortisol levels were elevated during 60 to 120 minute postictal period in 45% of GTCS, 55.55% of partial seizures and 66.66% of pseudoseizure patients. Cortisol appears to be non-selectively triggered by all stressful events but postictal PRL estimation can help in differentiating pseudoseizures from GTCS. While an elevated PRL indicates the occurrence of grandmal seizure, a normal postictal PRL level does not always exclude epileptic seizure, specially a partial seizure.

The roles of myoglobin, MB iso-enzyme of creatine phosphokinase and aspartate aminotransferase in serum in the acute phase of myocardial infarction.

The diagnostic value of serum myoglobin as compared to MB iso-enzyme of creatine phosphokinase and aspartate aminotransferase was investigated in 25 patients admitted on suspicion of acute myocardial infarction with a duration of symptoms less than 6 hours. In group 1 (acute myocardial infarction group), the first blood sample, obtained at a mean time of 3.27 hours after onset of infarction, invariably showed increased myoglobin (mean 2.6-fold normal) whereas MB iso-enzyme of creatine phosphokinase and aspartate aminotransferase were often normal. Peak myoglobin values occurred earlier than peak serum MB iso-enzyme of creatine phosphokinase values. The highest peak values of serum myoglobin were found in patients with extensive myocardial infarction. In group 2 (non-acute myocardial infarction or control group) serial determinations of serum myoglobin, serum MB iso-enzyme of creatine phosphokinase and aspartate aminotransferase were within normal limits. Hence the importance lies with the early detection of serum myoglobin in acute myocardial infarction.

Experience on loading dose--quinine therapy in cerebral malaria.

Twelve cases of cerebral malaria due to plasmodium falciparum, treated with loading dose of quinine (20 mg/kg salt in 500 ml of 5% glucose infused IV in 4 hrs) are compared with eleven age and sex matched cases treated with conventional dose of 10 mg/kg. The parasite clearance rate was significantly faster in loading dose group. There was no difference in recovery time: the interval between the initiation of treatment to full recovery of consciousness in both groups. One patient had pretreatment hypoglycaemia and two cases in the conventional dose group developed hypoglycaemia during therapy. One patient died in conventional dose group due to multi-organ failure. Two litres blood exchange transfusion was also tried for this case. Mild cinchonism occurred in two cases after loading dose while this was observed only in one case in conventional dose group. There was no significant hypotension or ECG changes in any patient. Loading dose of quinine seems to be well tolerated and may clear parasitaemia faster in case of malaria due to Plasmodium falciparum (PF).

Ranitidine for the prevention of complications following endoscopic sclerotherapy for esophageal varices.

Thirty one patients with significant esophageal variceal bleed were allocated alternately to receive endoscopic sclerotherapy along with ranitidine 300 mg daily or endoscopic sclerotherapy alone till eradication of varices. The mean sclerotherapy sessions, time and volume of sclerosant required for obliteration of varices were similar for the two groups. The esophageal varices were eradicated in all the patients except three in sclerotherapy alone group. There was statistically significant reduction in frequency of post sclerotherapy mucosal ulcers (P < 0.05) after addition of ranitidine to sclerotherapy. Rebleeding was not only significantly reduced (P < 0.05) in the sclerotherapy with ranitidine group but was minor and did not even require blood transfusion. In sclerotherapy alone group rebleeding was controlled by surgery in two patients and one died due to massive bleeding. The results of this study suggest a beneficial role of ranitidine in reducing post sclerotherapy mucosal ulcers and rebleeding. This effect of ranitidine emphasises the role of acid-pepsin in pathogenesis of these ulcers and its associated morbidity.