Sickle cell Disease was first described by James B. Herrick in November 1910. Since its first record, it has been detected in many part of the world including Orissa.
Sickle Cell Disease is a chronic inherited disease transmitted as Mendelian recessive character. It is a disease of hemoglobin structure where the glutamic acid in the 6th position of Beta Chain is replaced by valine. This disease may be present either in homozygous state or in conjunction with other type of normal or abnormal haemoglobin. The clinically significant sickle cell haemoglobinopathy include Sickle Cell Trait, Sickle Cell Disease, Sickle Beta thalassemia, Sickle Cell ‘C' Disease, Sickle Cell ‘D’ disease and Sickle ‘0’ Arab disease etc. These may present with different clinical severity ranging from mild symptoms to fatal complications. They usually present as chronic haemolysis, Sickle Cell crisis, growth retardation, increased susceptibility for infection and variety of other acute and chronic, complications that produce multi system organ damage, disability and death. Their clinical severity depends upon presence of precipitating factors or association with other abnormal or normal haemoglobin variants.
The most important clinical presentation is Sickle Cell crisis. The Sickle Cell Crisis was defined by Diggs L.W. in 1965 as “a sharp turn on the course of the disease with rapid development of new symptoms not explained by any other cause". There are four types of crises, such as vaso-occlusive crisis, Aplastic crisis, Haemolytic crisis and Sequestration crisis. The Vaso-occulusive crisis is the commonest and is very painful. The Vaso-occlusive crisis is defined as sudden onset of excruciating pain in different parts of the body particularly extremities, chest, abdomen etc. due to occlusion of microcirculation by the sickled erythrocytes. The crises are precipitated by many factors like anoxia, infection, acidosis, dehydration, exposure to cold, pregnancy, emotional stress etc.
Despite substantial increase in knowledge in cellular, in pathological and physical basis of sickling phenomenon, there is some therapy available for prevention of crisis. There is some hope in gene replacement therapy and bone marrow transplantation in future and cure of the disease.
Currently accepted management of painful crisis includes.
1. Prophylactic measures to reduce the incidence or crisis and
2. Therapy to relieve- or reverse the established crisis by
a) Early detection and prompt management of precipitating factor- infection should be treated with suitable antibiotic, hypoxaemia with oxygen, acidosis with alkali and dehydration with adequate IV fluid.
b) Analgesics for control of pain
c) Stabilization of Red Blood Cell membrane
d) Vasodilatation to improve microcirculation
Many drugs like phenothiazine, Nitrates, Urea, Nicotinic acid, Dextran, alkali, Androgen, Aspirin, Desmopressin acetate, 5 azacytidine etc. have been tried with partial or no benefit and none of them are also safe. New compounds continue to be sought, that might interfere with sickling and be useful clinically. Aspartame is the only agent that can prevent sickling and reverse sickling tested in-vitro and in-vivo so far (Manion et al, 2001). Therefore this study is undertaken to know the efficacy of drug (Aspartame) in sickle cell disease and sickle cell crisis.
A glucose analogue aspartame (L. aspartyl L. Phenylalanine) a sweetener prepared from 2 amino acids -  - aspartic acid and L-phenylalanine is appears to be beneficial effects in sickle cell disease and sickle cell crisis. This drug can prevent fibril formation and / or interaction with or by getting inserted into the EF acceptor site and prevent the  - helix that contain valine  from its delectation binding to the EF acceptor site and thus obstruct sickling. A possibility of functional interaction of intracellular biopolymerization may occur appears to be possible mechanism (Manion et al, 2001).

1.


ABSTRACT:

Pseudoxanthoma elasticum is a rare inherited disorder of connective tissue, characterized by general elastorrhexis of the elastic tissue in the dermis, the blood vessels and Bruch membranes of the eye.

KEYWORDS:
Pseudoxanthoma elasticum (PXE), Angioid streaks, Bruch’s membrane, Connective tissue, Haematuria.

CASE REPORT:
A 55 years Hindu female presented with complain of recurrent haematuria for 6 months, diminished vision for one year and weakness of left half of the body since 3 years. She had attended menopause and was under Enalapril (5 mg) since 1 year for hypertension. No history of diabetes, tuberculosis or CAD. No suggestive family history.

On examination the patient was of average built with BP 130/80mmHg (both upper limbs) , pulse rate 80/min, regular (Brachial) good volume while diminished pulsation of both radial, ulnar, posterior tibial and dorsalispedis arteries. Both carotids, axillary, femoral and popliteal artery pulsations were well felt. She was mild anaemic without icterus, cyanosis, clubbing or lymphadenopathy. JVP was not raised. Thyroid was normal. Chest examination revealed vesicular breath sounds without any added sounds. Cardiovascular system examination revealed normal apex with normal heart sounds, without any murmur. P/A examination was normal without any renal brui. On CNS examination the cranial nerves, motor, sensory systems were normal without any cerebellar signs or meningeal signs. On examination of the skin, there were laxed skin with yellowish Xanthomatous lesions over neck and upper chest (Fig. 1, 2). Eye examination revealed vision 6/9 (Lt) and 6/6(Rt) and fundoscopy showed macular choroiditis with angioid streaks on left side (Fig. 3).
Routine Investigation Showed: FBS - 82mg%, PPBS – 104mg%, Blood Urea 20 mg%, Serum Creatinine 1.08mg%, ESR - 20mm/1 hour, DC N72, L25, E3, M0, B0, and TLC - 8000/mm3, Lipid Profile of serum were Sr. Total cholesterol -160mg%, TGS -108mg%, HDLC -48mg%, LDLC- 92mg% and VLDL-C -21mg%, Urine analysis showed proteinuria(+) and 10-15 RBC/HPF and RBC casts. Mantoux test was 18mm , ECG was normal.

ECHO Showed: Mitral value thickened, EF – 65%, Aorta – 32 mm, MACS – 17 mm, LA – 42mm.

Skin Biopsy Revealed: Epidermis was normal and dermis showing accumulation of basophilic mucoid material and collagen bundles. There was occasional macrophages and multinucleated giant cells compatible with pseudoxanthoma elasticum.

Colour Doppler study of kidney and renal arteries showed normal kidney size , shape, echo structure and punctate calcific areas on both renal cortex. Both renal arteries and interlobar arteries and aorta showed normal Doppler profile.

Doppler study of upper and lower limb arteries showed:-

Upper Limb: B/L subclavian , axillary, brachial , radial , ulnar arteries were anechoic with normal caliber and showing loss of normal triphasic blood flow with low resistance blood flow in them.
Lower limb: B/L femoral , popliteal and dorsalis pedis arteries were normal caliber with speaks of arterial calcifications seen in arterial wall at places and with loss of normal triphasic blood flow with low resistance.
Aorta and iliac arteries: Showed normal in caliber and size with normal spectrum of blood flow and no thrombus or stenosis. The patients was diagnosed to be a case of Pseudoxanthoma Elasticum with complications leading to peripheral vascular , renal and retinal involvement.

Treatment given: Capsule E, Tab Pentoxyphyllin and advised diet restriction , regular follow up.


DISCUSSION:
Pseudoxanthoma elasticum is a rare disease occurring in about 1 in every 160,000 population. Females are frequently affected. The basic defect lies in the elastic tissue. Typically it is first noticed during adolescence as yellow orange bumps on the side of neck. This entity has been observed in India and has been reported sporadically from all regions.

Aetiology:
Pseudoxanthoma elasticum is caused by genetic mutations that are inherited in either a dominant or recessive mode. A person with recessive form of the disease (most common) must posses two copies of the PXE gene to be affected, and therefore must have received one from each parent. In dominant form , one copy of the defective gene is sufficient to cause the disease. In some cases, a person with dominant form inherits abnormal gene from a parent with PXE, more commonly, the mutation , arise as a spontaneous change in the genetic material of the affected person. These cases are called “ Sporadic” and do not affect parents or sublings , although each child of a person with sporadic PXE has a 50% risk to inherit the condition.

Actual genetic defect is caused by different mutations or deletion in a single gene called ABCC-6 (also known as MRP6) located on chromosome 16. Although responsible gene has been identified, how it causes PXE is still unknown1.

It has been suggested that defects on glycosaminoglycans or proteoglycans might play a role in pathogenesis, bends of chondroitin sulphate, dermatan sulphate and hyaluronic acid are increased in the areas of calcification2.

An abnormality in cysteine proteinase of the fibroblasts has been demonstrated. It seems likely that an abnormal glycosaminoglycan secreted by fibroblasts is deposited on the surface of the elastic fibres and leads to fragmentation and calcification.


Pathology:
In skin lesions the elastic fibres in the mid dermis are clumped, degenerated, fragmented and swollen and abnormal fibres stains positively for calcium. The collagen fibres are also abnormal being split into small fibres. Similar changes occur in connective tissues of the media and intima of blood vessels, Bruch membrane of the eye and the endocardium and pericardium. Calcification has been reported in pulmonary and other visceras3.

Vascular involvement is generalized but may involve predominantly the larger arteries, the mesenteric , renal and visceral arteries or those of the extremities. Calcification of internal elastic lamina of the arteries leads to vascular obstruction.

CLINICAL FEATURES:
Skin changes: Lesion are small (1-3 mm in diameter), yellowish papule arranged on linear or reticular pattern and eventually forming plaques. Telangiectasia may be present. Areas involved are – fold of groin, arms, neck, axillary folds, armpits, perineum and mucous membrane. Skin is soft, lax, wrinkled and may hang in folds.
Eye: Angioid streaks represent defect or cracks in Bruch’s membrane. Angioid streaks are irregular jagged, curvilinear lines that radiate from the region of the optic nerve into the more peripheral retinal tissue. Other findings in PXE include salmon spots (areas of tissue atrophy) optic disc drusen (calcified deposits within the optic nerve head) and crystalline bodies (small yellow round subretinal lesions) and choroids neovascularization presented with visual loss (70%). If haemorrhage and choroiditis develops it may lead to blindness4.

Cardiovascular Changes:
• There may be intermittent claudication, diminished peripheral pulses, accelerated altheroma with hypertension5.
• Death commonly result from cerebral haemorrhage, coronary occlusion (angina/MI) or massive haemorrhage into the gut5.
• Cardiomyopathy and mitral value prolapse (5-8%) has been reported.

Associated abnormalities: May be associated with Osteitis deformans (Pagets disease) Osteoectasia, sickle cell disease, Marfan’s Syndrome and perforating elastosis.

Diagnosis:
Diagnostic criteria for Pseudoxanthoma elasticum (from Lewohl et al)6.
Major Criteria:
1. Flexural yellow cobblestone lesions.
2. Characteristic histopathological features of lesional skin using elastic tissue and calcium stains (e.g Van Gieson and Von Kossa).
3. Angioid streaks in the retina.

Minor Criteria:
1. Characteristic histological changes in non-lesional skin.
2. Family history of PXE in first degree relatives.
• It should be suspected in cases without skin lesions by obliterative arterial disease of early onset and unexplained gastrointestinal haemorrhage.
Management:
• The important aspect of treatment is to ensure that complications from blood vessels involvement are prevented or dealt with speedily by the appropriate specialist. Regular follow up with a specialist vascular surgeon and/or cardiologist is recommended.
• There is currently no effective treatment for skin lesions, but the appearance may be improved by plastic surgery.
• Restriction of dietary calcium has been tried with some benefits , but controversial.
• Laser photocoagulation, may be helpful in preventing further bleeding at the back of the eye.
• Genetic counseling may be helpful.
• Propranolol – to prevent development of aortic dilatation.


CONCLUSION:
Though incidence of haematuria is reported earlier in some cases, our case primarily presented with haematuria along with other usual complications. The probable mechanisms is due to microvascular involvement of kidney and urinary tract.

REFERENCE:
1. L Frank Glass/Shelli Marks, BS: Department of Internal Medicine and Pathology, Vuniversity of South Florida College of Medicine –Nov 2003 – 05.
2. Pasquali – Ronchette L, Pincellinc et al – Arch dermatol. Res 1986, 278, 386-92.
3. Goodmen RM, Simth E W, Paton D et al – “PXE”: Clinical and histopathological study medicine, 1963, 42, 297- 334.
4. Vitreous –Retina – Macula Consultant of New York – Angioid streaks and pseudoxanthoma elasticum.
5. Parker J C, Firedman –Kien AE, Levin et al . NEJM 1964/Kundrotus L, Novak J et al ; GI bleeding in PXE Am J Gastroenterol , 1988.
6. Lebwohl et al ; J Am Aacd Dermatol, 1994.

.

ABSTRACT

Symmetric peripheral gangrene (SPG) is a rare clinical presentation in case of falciparum malaria. Few cases have been so far reported from India and abroad. Here we report such a case from this hospital and discuss the pathophysiology and management.

KEY WORDS

Symmetric peripheral gangrene (SPG)
Falciparum malaria
Disseminated intravascular coagulation (DIC)

INTRODUCTION

SPG is an uncommon clinical condition characterized by sudden onset of symmetric dry gangrene of acral distribution without any evidence of vasculitis or arterial obstruction. This has been described in conditions like infections most commonly bacterial (meningococcal, streptococcal, Pneumococcal, E.coli septicaemia) and viral (varicella and viral gastroenteritis), low output states like myocardial infarction, shock, CCF or use of drugs like vasopressin and ergot and other conditions like polymyalgia rheumatica,cryoglobinaemia. In all these conditions DIC has been the basic pathogenesis (90%)9.

The incidence of DIC and SPG in cases of falciparum malaria has rarely been reported as one of its multiple complication1.


CASE REPORT
A 15 years boy from Raigarh (C.G.) admitted to this hospital in last week of December 2005 with history of fever associated with chill and rigor (20 days), sudden blackening of distal parts of fingers, toes of all limbs , tip of nose and lateral part of pinna of both ears (15 days) and altered sensorium for 3 days. He was treated at the local hospital with I/V fluid, antibiotic and decadron , without any improvement.

There was no history of joint pain, trauma, sore throat, spontaneous bleeding, thromboembolic episode or any relevant disease like SCD, HTN, DM. He was a student in a residential school without habit of smoking or alcohol. There was no relevant family history.

On examination the patient was stuporous with Temperature 1000F , pulse – 100/min , regular low volume and all the peripheral pulsations well felt without brachiofemoral delay. BP was 110/70 mm of Hg (both U/L), with moderate pallor and features of dehydration. There was no icterus , clubbing, lymphadenopathy or thyromegaly. Cardiovascular and Respiratory system revealed no abnormality. There was no hepatosplenomegaly. Neurological examination revealed mild neck rigidity with diminished DTJ and plantar was flexor. Examination of skin and digits showed blackening of tip of nose (Fig.1), both ear pinna on lateral aspects (Fig 2) and distal parts of toes and fingers of all limbs (dry gangrene) (Fig 3 & 4). There was clear line of demarcation between the healthy and affected parts.

Investigation on the day of admission showed
Hb: 6.2 gm%
DC : N - 48, E-2, L-48, M-2, B-0
TLC: 9800/mm3
TPC: 60,000/mm3
RBS : 116mg%
B. Urea : 96mg%
Serum Creatinine : 1.5mg%
Blood smear : Showed P.falciparum rings and gametocytes
LFT :
Serum Bilirubin : Total 0.78mg%
Direct 0.26mg%
SGOT: 39U/L
SGPT : 36U/L
Alkaline phosphatase: 50U/L
Electrolytes: Serum Na+ - 138meq/L
Serum K+ - 3.6meq/L
Serum Ca++ - 8.5 mg/dl
Prothrombin time (PT) – 16 second (control 12.5)
Activated partial thromboplastin time (aPTT) 29.5 seconds (control – 28)
Fibrinogen : 187mg/dl (N : 250-450mg/dl)

The patient was treated with injection Artesunate, injection Ceftriaxone 2gm I/V BID,injection Omnacortil, Injection Ranitidin 8 hourly, I/V fluid and tablet Zilast (Cilostazol 100mg BID) with care of the skin , bladder, bowel and maintaining nutrition. He was stabilised on 2nd day and gained consciousness and there was clinical improvement. Two units of whole blood transfusion given.

On further investigation urine analysis was normal and haemoglobin electrophoresis was AA (to exclude SCD – common in this belt). USG of abdomen and pelvis was normal. Test for antinuclear factor, LE cell, Rheumatoid factor, VDRL were negative, Test for cryoglobulin was normal. Coagulation profile (Antineutrophil cytoplasminc antibodies, Antinuclear antibodies, anti double standard DNA, complement –3 , complement – 4) was normal. Serum uric acid was 3.9 mg/dl.

Echocardiography did not reveal any thrombi or vegetation. The Doppler study of the vessels demonstrated normal flow pattern upto digital arteries in all four limbs.

Biopsy of an affected area of the skin showed thrombi in dermal capillaries without any evidence of vasculitis.

Blood could not be tested for fibrin degradation products (FDPs). However evidence of DIC was seen in skin biopsy.

Gradually the patient improved. Full anti-malarial course was given and antibiotic was given for 7 days. Zilast was continued and omnacortil was gradually tapered. Slowly the gangrenous parts improved and patient was discharged on 12th day. No surgical intervention was required.

DISCUSSION
SPG has been reported in various medical conditions including falciparum malaria1, 7, 4, 2, 6,12. Our patient had no clinical or laboratory evidence of other causes like sepsis, vasospastic condition, ergot or other drugs. There was no evidence of vasculitis, cryoglobulinaemia, polycythemia or thrombocythaemia. The common pathogenic mechanisms of SPG is DIC9. All the cases reported had evidence of DIC.

Reduced fibrinogen level, thrombocytopenia, prolonged PT, prolonged aPTT and histopathological evidence of microvascular thrombi indicate the presence of DIC in this patient1.

Alteration of coagulation and fibrinolytic system in falciparum malaria is well recognized5. A functionally active but controlled coagulatory state exists in falciparum malaria even in uncomplicated cases5. Elevation of FDPs reflecting the ongoing fibrinolysis have been documented11. Heavy parasitaemia triggering the coagulation pathway10, alteration in the lipid distribution across the surface membrane of the parasitized erythrocytes activating the intrinsic coagulation cascade8 and activation of complement system5 have been postulated as possible mechanism for DIC in falciparum malaria. Sequestration of the parasitised erythrocytes in the microcirculation by molecular interactions with endothelial receptors, mainly intracellular adhesion molecule10 – 1(ICAM – 1) may occur. Rosetting of the healthy erythrocytes around parasitised red cells may occur and these multicellular aggregates further exacerbate the vascular obstruction caused by sequestration3.

DIC is encountered in less than 10% of patients with cerebral malaria3 and manifest as spontaneous bleeding from gum and GIT. But in a review of 71 cases of SPG and DIC significant bleeding complications were not recorded9.

Our patient who had no other cause of peripheral gangrene made satisfactory recovery on specific antimalarial therapy supporting the observation that falciparum malaria was the triggering mechanism for the DIC and subsequent SPG.

CONCLUSION

In conclusion we report that falciparum malaria may present as peripheral dry gangrene and this possibility though uncommon must be taken into consideration while encountering patients in endemic areas.

REFERENCE
1. Anuradha S, Prabhash K,Shome DK et al . Symmetrical peripheral gangrene and falciparum malaria an interesting association. JAPI 1999; 47(7): 733-5.
2. Arya TVS, Singh SP, Singh DK. Bilateral foot gangrene occurring in falciparum malaria. JAPI 1990; 38: 30 (Abstract).
3. Bradley D, Newbold CI, Warell DA. Malaria in Oxford Test Book of Medicine. Weatherall DJ Ledinqham JGG and Warrell Da (eds) Oxford University Press Inc. New York 1996; 1 : 835-63.
4. Chittichai P, Chiekrul N, Davis TM. Peripheral gangrene in nofatal paediatric cerebral malaria: a report of two cases. Southeast Asian Trop Med Public Health 1991; 22: 190 – 4.
5. Clemens R, Pramoolsinsap C, Lorenz R et al . Activation of coagulation cascade in severe falciparum malaria through the intrinsic pathway.Br. J. Haemat. 1984; 87,100-05.
6. Jain D, Srivastava S, Singhal SS. A rare presentation of falciparum malaria . JAPI 1995; 43: 582.
7. Kochar DK, Shubhakaran , Kumawat B et al. A patient with falciparum malaria and bilateral gangrene of the feet who developed arrhythmia/ventricular fibrillation after quinine therapy. Quart J Med 1998 (Corrosp)246.
8. Mohanty D, Marwah N, Gosh K et al. Vascular occlusion and disseminated intravascualr coagulation in falciparum malaria. Br. Med J 1985; 290: 15-6.
9. Molos MA, Hall JC. Symmetrical peripheral gangrene and disseminated intravascualr coagulation. Arch Dermatol 1985; 121: 1059-61.
10. Philips RE, Looareesuwan S, Warrell DA Et al . The importance of anemia in cerebral and uncomplicated falciparum malaria: role of complications dyserythripoiesis and iron sequestration. Quart J Med 1986; 58: 305 – 23.
11. Rojanasthein S, Surakamolleart V, Boonpucknavig S et al . Hematological and coagulation studies in malaria. J. Med Assoc. Thai 1992; 75 (supplele-1):190-4.
12. Sharma BD, Gupta B. Safdarjung Hospital, JIACM 2002, 3(3): 297 – 9.

ABSTRACT:
Hydatid cysts are due to parasitic infection caused by the cestode tapeworm Echinoccocus. In humans the hydatid disease commonly involves the liver (75%) & the lungs (15%). The remaining (10-15%) cases involve the other organs of the body-kidney, spleen, heart, brain, bones, pancreas, breast, ovaries, scrotum, thyroid gland, inguinal canal & soft tissues.The disseminated intra-peritoneal hydatid disease is a very rare finding1. We report such a case wherein the abdominal cavity is seen to contain multiple hydatid cysts .Hydatid cysts were also found in the left scrotum, lungs, liver & spleen.

KEY WORDS:
Hydatid cyst, Echinococcus, Peritoneal hydatidoses, Scrotum

CASE REPORT:
A 42 years Hindu male presented with complaints of left scrotal swelling for 6 months, progressive distention of abdomen for 1 year & generalized weakness for 1 ½ years. He had past history of hydatid disease 13 years back, for which cystectomy was done in 1994. He was not taking any drugs. There is no history suggestive of diabetes mellitus, hypertension, tuberculosis, coronary artery disease or history of Filariasis.

On examination, patient was of thin built with blood pressure 110/70 mmHg (both upper limb), pulse rate 84/min (Regular), Respiratory rate of 24/min and temperature of 37oC. He had diminished vesicular breath sounds in both lower lung fields. His abdomen was distended. On inspection, dilated veins were present over the abdomen with flow below upwards. There was a mid line supraumblical scar mark. Flanks were full and contour was irregular. Umblicus was central and everted (Figure 4). On palpation, there was no local rise of temperature, no tenderness, no fluid thrill and shifting dullness. There were multiple ill defined cystic masses all over the abdomen of varying size. There was bilateral scrotal mass which was soft and non-tender with increased scrotal volume. The liver was not enlarged and spleen was not palpable. On auscultation, bowel sound was normal, no bruit heard. Cardiovascular system and central nervous system examinations were within normal limit.

ROUTINE INVESTIGATIONS:
Hb%-10.4gm%, TLC-12,000/mm3, N50E28L22, ESR-48mm(1st hours), FBS-74mg/dl, Blood urea-31mg/dl, Sr creatinine-1.58mg/dl, Sr Na+-143meq/lt, Sr K+-4.9meq/lt, Urine analysis-normal study,ECG-normal.

LIVER FUNCTION TESTS:
Sr Billirubin (total)-0.89mg/dl, Direct-0.22mg/dl, Indirect-0.67mg/dl, SGOT-26.39IU/lt, SGPT-18.40IU/lt, Sr Alkaline phosphatase-149.38IU/lt, HBsAg-negative, Anti HCV Ab-negative.

ULTRASOUND (ABDOMEN & PELVIS):
Multiple hydatid cysts of liver, spleen, left scrotum & through out abdomen, varing from size 1 mm to 6 mm, B/L moderate Hydrocele (Figure 3).

CHEST X-RAY (PA-VIEW):
Circular opacity of size 8x2cm in right basal zone (? hydatid cyst).

C.T.SCAN (ABDOMEN):
Multiple hydatid cyst of liver, spleen, B/L lower lobes of lungs, involving mesentery & retoperitoneal region. Nonvisualization of RT kidney
(? replaced by hydatid cysts) (Figure 1, 2).

C.T.SCAN OF BRAIN: Normal

IMMUNOLOGICAL TEST:
Echinococcus antibody titer - 1:64 (Normal 1:32)

TREATMENT GIVEN:
Surgical resection of the cysts was not possible. Albendazole-400 mg PO BD for life long (with monthly monitoring of Liver function Tests) given. On first two follow ups there was decrease in the abdominal distension & the liver function test was normal.

DISCUSSION:
Hydatid disease is a parasitic infection caused by the Echinococcus granulosus. The dogs are the definite host and the adult worms are found in their small intestine. Human get infected either by contact with the definitive host or by consuming vegetables and water, contaminated with the hydatid ova2. Hydatid disease is endemic in the cattle grazing areas like India, Pakistan, Middle-East, Africa, South America, and New-zealand1. The close association of people with sheep and dogs and the unavailability of clean potable water supplies in India make it a region endemic to disease. Majority of the cases of Hydatid disease seen come from rural areas or people who have settled in urban centers after spending life in villages. Most of the people acquire the disease during their childhood, but do not present with the clinical signs and symptoms until late adult hood. The natural progression of an untreated cyst may include calcification and death of the cyst; however, more frequently the cyst gradually enlarges3.

The liver (75%) and the Lungs (15%) is the commonest site of involvement, although no site in the body may be completely immune from it4. This atypical and rare presentation of the disease may be seen in kidneys (3%), usually the upper and the lower pole of the kidney may be involved. The spleen may be involved in about 4% of the cases and is associated with splenomegaly, fever and abdominal pain4. Cerebral Hydatid cysts occur in only 2% of all the cases reported. The region of the middle cerebral artery distribution specially the parietal lobe is most frequently involved. Cardiac Hydatid cyst is very rare (0.02-2%) and most commonly affects the left ventricular chamber specially the left ventricle in 50%-60% of cases4. The other sites that have been reported to be involved are bones, pancreas, breast, ovaries, scrotum, thyroid glands, inguinal canal and soft tissues.

Hydatid cysts can also be found rarely in the peritoneum1. Most of these cases are the result of traumatic or surgical rupture of a hepatic, splenic or mesenteric cyst. The prevalence of peritoneal hydatid cysts in cases of abdominal Hydatid disease is approximately 13%. In our case the patient had already undergone cystectomy and it is likely that these findings may be associated to previous surgical rupture, although spontaneous rupture of micro cysts into the peritoneum may also occur in about 12% of the cases1. The hydatid cysts may resemble a multiloculated mass filling the entire peritoneal cavity. Such a condition is referred to as peritoneal hydatidoses .

Hydatid cyst may be solitary or multiple. The type of the imaging modality used depends on the site and the size of the hydatid cyst. Ultrasonogarphy (USG) is the first line of screening for abdominal hydatidosis and it is especially useful for detection of cystic membrane, septa, and hydatid sand. CT scan best demonstrates cyst wall calcification and cyst infection. CT scan imaging is also the modality of choice in peritoneal seedling1. The CT scan shows well defined solitary or multiple cysts that may be thin walled or thick walled. A hydatid cyst typically demonstrates a high attenuation value at unenhanced CT even without calcification. Multivesicular cysts can depict a typical honeycomb pattern. The septa represent the walls of the daughter cysts housed within the mother cyst. A “wheel spoke” pattern can be observed when the daughter cysts are separated by hydatid matrix1.

There are different types of serological tests which can be carried out for the diagnosis, screening and follow up of patients with hydatid disease. These include the immunoelectrophoresis, enzyme-linked immunosorbent assay (ELISA), latex agglutination and indirect haemagglutination (IHA) test 4. The diagnosis of HD can thus be established with the help of radiologic and serologic finding4. The diagnosis is also easier when the lesion has multiple locations involving different organs or when daughter cysts, germinal membrane detachment and calcification are present 2.

Surgery is the mainstay of treatment for hydatid cysts of the Liver. Laparotomy is the most common surgical approach6. Liver resection and pericystectomy are procedures that resect the closed cysts with a wide safety margin; however they are considered too radical procedures for hydatid cyst removal. Conservative procedures such as cystectomy and omentoplasty for hydatid disease should be the standard surgical procedure because of their safety, simplicity, and effectiveness in fulfilling the surgical treatment criteria of hydatid disease6. The peritoneal hydatidosis has also been successfully surgically removed with similar conservative procedures5, 7.

CONCLUSION:
Symptomatic or large cysts should be surgically treated. In cases suspected of having peritoneal spillage, antihelminthic drugs should be administered8. In addition, small asymptomatic cysts, some daughter cysts, and peritoneal secondary cysts and splenic cysts may also be effectively treated with Albendazole8.

REFERENCES:

1. Pedrosa I, Saiz A, Arrazola J, Ferreiros J, Pedrosa CS. Hydatid disease: radiologic and pathologic features and complications. Radiographics 2000; 3:795-817.
2. Polat P, Kantarci M, Alper F, Suma S, Koruyucu MB, Okur A.: Hydatid Disease from Head to Toe. Radiographics 2003; 23:475-94.
3. Ammann RW, Eckert J. Cestodes. Echinococcus. Gastroenterol Clin North Am 1996; 3:655-89.
4. Husen YA, Nadeem N, Aslam F, Bhaila I. Primary splenic hydatid cyst: a case report with characteristic imaging appearance. J Pak Med Assoc 2005; 5:219-21
5. Karavias DD, Vagianos CE, Kakkos SK, Panagopoulos CM, Androulakis JA. : Peritoneal echinococcosis. World J Surg 1996; 20:337-40.
6. Buttenschoen K, Carli Buttenschoen D. Echinococcus granulosus infection: the challenge of surgical treatment. Langenbecks Arch Surg 2003; 4:218-30.
7. Hamamci EO, Besim H, Korkmaz A. Unusual locations of hydatid disease and surgical approach. ANZ J Surg 2004; 5:356-60
Balik AA, Celebi F, Basglu M, Oren D, Yildirgan I, Atamanalp SS. Intra-abdominal extrahepatic

ABSTRACT:
Organophosphorus induced delayed neuropathy (OPIDN) is a delayed sequel of organophosphorus poisoning, occurs rarely1,2,6 after an acute cholinergic crisis and is confused with Guillain Barre’ Syndrome (GBS) or other causes of polyneuropathy. We report one case of OPIDN which we managed conservatively with steroids & we found improvement of CMAP (Compound Muscle Action Potential) within one month.

KEYWORDS:
Organophosphorus (OP), OPIDN, Axonal degeneration, neuropathic target esterase (NTE), Pralidoxim (PAM).

INTRODUCTION:
OPIDN refers to delayed effects of organophosphorus poisoning (OP poisoning), occurs due to binding of esterase enzyme called neuropathic target esterase (NTE)2,3 and cause predominant axonal degeneration (dying back axonopathy5) and minor demylenation7. Typically patient presents 3-5 weeks after OP poisoning with lower extremity weakness, bilateral foot drop, glove and stocking type of sensory loss5. Present case study documents one case of OPIDN due to tri Ortho cresyl phosphate poisoning after one month of cholinergic crisis and prevention of OPIDN is by early treatment of cholinergic crisis with PAM (before organophosphorus compound ages), steroids and other supportive measures (e.g splintage, physiotherapy and carbamazepine for neuropathic pain).

CASE REPORT:
A 19 year male presented to the hospital with complains of tingling sensation and weakness of lower limbs and hands 15 days back. He was apparently alright 15 days back, had 4 episodes of loose motion which subsided with medication. Then he had tingling sensation over lower limbs and hands and weakness of lower limbs followed by weakness and clumsiness of both hands. Weakness was progressive and in one week the patient was not able to walk. No history of fever, dog bite, vaccination, previous similar episode, contact, diabetes, leprosy was elicited.

Allegedly he took insecticides and suffered from acute cholincrgic crisis one and half month ago for which he was hospitalized for 11 days and recovered. On general examination the patient was conscious, afebrile with pulse rate 80/min, BP 126/80mm Hg without any other positive findings. CNS examination revealed intact cranial nerves, wasting of hypothenar, thenar (Fig. 1), calf and peroneal muscles of limbs (Fig. 2). Hypotonia involving flexor and extensor of ankle, weakness of abductor pollicis berevis, adductor pollicis and oppones pollicis seen. Long flexors and extensors of digits were normal. Lower limbs evertor, invertor, flexor and extensor of ankle were 0/5 power on both sides. Extensor and flexor of knee and hip were normal. Supinator jerk was diminished, ankle jerk was absent on both sides. Rest deep tendon jerks were normal. Plantar was nonresponsive both sides. There was in-coordinated movement, Rhomberg's test was positive and gait was high stepping. Sensory examination revealed all modalities diminished below ankle and wrist bilaterally. Peripheral nerves were normal.

Laboratory investigation revealed:
o Hb 12.7 gm%, TLC 10,700/mm3, DC N-69 L-30 E-l, ESR 8mm/lst hr, FBS 85 mg% .
o Serum Na'-132meq/lt, Serum K-4.8meq/lt, Serum urea -28mg%, Serum creatinine -1.18 mg%.
o HIV ELISA - Negative, CSF study showed TLC 3/mm3 (all lymphocytes) RBC absent, Glucose 61mg%, Protein 27 mg%, TB ELlSA- Negative.

NERVE CONDUCTION STUDY:
Initial Nerve Conduction Study:
Motor - Compound muscle action potential (CMAP) was absent in bilateral Median, Common peroneal nerve (CPN) , bilateral posterior tibial nerve (PTN).
CMAP in bilateral ULNAR - Amplitude less than normal, velocity in right ulnar less than normal , Left ulnar velocity within the normal limits.
Sensory - In bilateral Median Velocity was reduced, Right ulnar velocity was reduced no potential in Right sural, left Sural velocity and amplitude within normal limit.

Repeat Nerve conduction Study: (After one month)
CMAP- left median no potential, Right median small amplitude potential
Velocity in the above is reduced
Conduction in bilateral ulnar as before
No CMAP in bilateral CPN and bilateral PTN
Sensory as before

DISCUSSION:
Chronic complication of OP poisoning are neurobehavioral and poly-neuropathy1. Sensory motor polyneuropathy or OPIDN typically ocours after 3 to 5 weeks of exposure where motor deficit dominates the clinical picture5. Patient initially complains of tingling sensation over extremities, symmetric lower extremity weakness, and leg cramping and calf pain. Atrophy of calf muscles, ataxia and bilateral foot drop gradually ensues. It may progress to cause truncal weakness. Cranial nerves and autonomic system are not involved3. Sensory symptoms resolve over months. In mild cases motor symptoms may resolve over 15 months or may not resolve at all3. Severe cases may develop spasticity due to spinal cord involvement in the form of diffused spinal cord atrophy predominantly of thoracic spine2,5. Neuropathology of OPIDN demonstrates that large distal neurons tend to be affected first. There is slowing and stoppage of axonal flow, blockage transport of protein and other substances as well as demyelination7. Axonal degeneration precedes demyelination and there is "dying back" axonopathy5. Site of OP attack is a membrane bound target esterase called neuropathic target esterase (NTE)2,3. Function of NTE is not known. It is present in brain, spinal cord and peripheral nerve6, lymphocytes4 where specific OP binds and ages1 by losing 1 carbon and forming P-O carbon linkage. Critical mass of 70% of NTE must be inhibited to cause clinical symptom6. The delay in symptoms is due to the fact that not all axons will degenerate at the same time and nerve may continue to function until significant number of axons is degenerated.

OPIDN diagnosis is made by clinical and neurophysiologic examination and ruling out other possibilities. Currently platelet, RBC and lymphocyte NTE inhibition for confirming neuropathic potential of organophosphorus is under study . Use of hen test as screening test of neurotoxicity is flawed1.

Treatment of OPIDN is conservative and can be prevented by early and prolonged use of PAM. Tingling sensation over palm and sole responds to carbamazepine5.

REFRENCE:
1. Angelo Moretto et al: Poisoning by organophosphorus insecticides and sensory neuropathy; J. Neurol. Neurosurg. Psychiatry: 1998;64;463-468.
2. Cnia-Chang Chuang et al: Delayed Neuropathy and Myelopathy after Organophosphate Intoxication: NEJM, Volume 347:1119-1121 October 3, 2002 Number 14.
3. J. Mirandal et al : Muscular Strength and vibration thresholds during two years after acute poisoning with organophosphate insecticides. Occupational and Environmental Medicine BMJ 2004; 61: e4.
4. M. Lotti et al: Inhibition of lymphocyte neuropathy target esterase predicts the development organophosphate induced delayed polyneuropathy:J. Arch of Toxicology, Vol 59/3 Oct 1986, Pg 176-179.
5. R. Hierons and M.K. Johnson : Clinical and Toxicological investigations of a case of delayed neuropathy in man after acute poisoning by an organophosphorus pesticide: J Arch of Toxicology, Issue Volume 40, Number 4/Deceber , 1978.
6. Singh H, Sharma N: Neurological Syndromes Following organo-phosphate poisoning, Year 2000 , Neurology India, Volume 48, issue 4, Page 308-13.
7. Versik P et al: Chronic Toxic Neurophaty in Qualis: British Lek Letsy 106 (10), 293 – 296, 2005.