Ketoacidotic Coma Research Articles

Pediatric Multisystem Inflammatory Syndrome in a Patient with a Coma with a Hyperosmolar Component in the Manifestation of Type 1 Diabetes Mellitus: Clinical Case

Background. Due to the rarity of the combination of emergence diabetes mellitus type 1 (DM1), COVID-19, and multisystem inflammatory syndrome, each reported case represents valuable experience and increases the awareness of medical professionals. Clinical case description. A 7-year-old boy was admitted to the intensive care unit with a diagnosis of diabetes mellitus type 1, first identified. On day 2, ketoacidotic coma with a hyperosmolar component developed, a positive polymerase chain reaction (PCR) test for SARS-CoV-2 was obtained, and a picture of subarachnoid hemorrhage was described according to CT scans of the brain. On day 3, macrohematuria, peripheral edema, pasty complexion were noted; the clinical picture and laboratory examination data corresponded to a “cytokine storm” with the development of multiple organ failure. On day 5, tonic-clonic seizures and bloody discharge from the nasopharynx were noted. On day 6, a negative PCR test for SARS-CoV-2 was obtained, on chest X-rays there was a heterogeneous decrease in pneumatization in the basal sections on both sides, and bilateral hydrothorax. On day 9, meningeal symptoms were noted. On day 14, a repeated episode of a convulsive attack was registered, and changes in the brain according to MRI results were regarded as an inflammatory demyelinating lesion against the background of the course of multisystem inflammatory syndrome and DM or as posterior reversible encephalopathy (PRES syndrome). Against the background of the appointment of immunomodulatory, anticoagulant, antibacterial, antiviral therapy, positive dynamics was noted in the child's condition. On day 18, the patient in a stable condition of moderate severity was transferred to the Department of Pediatric Endocrinology for further treatment. After 14 days, the child was discharged from the hospital in a satisfactory condition. Conclusion. This case report may confirm the risk of developing multisystem inflammatory syndrome in children with DM1 and COVID-19, which requires an interdisciplinary approach and the appointment of therapy included in the standards of management of children with multisystem inflammatory syndrome.

STUDY OF NON TRAUMATIC COMA IN CHILDREN AT TERTIARY HOSPITAL.

Introduction: Non-traumatic coma can have varied etiology and clinical characteristics. These may determine the management and outcome of the patients. We aimed to study the etiology and outcomes of children diagnosed and treated for non-traumatic coma in our hospital. Methodology: Medical records of children aged 2 months to 18 years, diagnosed with non-traumatic coma from January 2020 till December 2020 were reviewed retrospectively. The nal outcome was determined by patient's death or neurological condition at the time of discharge. Results: In the present study, out of 45 patients of NTC, 44% of the patients were in the age group 2 months to 5 years, 31% in 6 years to 12 years and 24% in 13 years to 18 years and 42% were Males & 57% were Females. In etiology, Infectious and Non-infectious causes contributed equally. Among the infectious causes, the most common ones were acute encephalitis (22%), acute pyogenic meningitis (9%), TBM (9%) and remaining infectious causes contributed to 9%. Among the non-infectious causes, diabetic ketoacidotic coma (22%), epileptic encephalopathy and metabolic encephalopathy contributed to 7% each. In outcome of the sample of 45 patients, 39 (87%) were discharged home and mortality was observed in 6 (13%). Among the total patients discharged (87%), 53% were neurologically normal, 7% had mild disability, 9% had moderate disability and 18% had severe disability. In our study, mortality was 3% in children with moderate brain injury, 33% mortality in children with severe brain injury (p value < 0.01). Conclusions: In our study, mortality rate was high with severe brain injury as compared to mild and moderate brain injury as assessed by GCS at admission.

Carbohydrate balance in the perioperative period

Background. Deep and multifaceted disorders during the perioperative period can lead to severe metabolic disorders that are life-threatening and require immediate care. Such conditions include the disorders of carbohydrate metabolism (CHM).
 Objective. To describe CHM disorders in the perioperative period and the possibility of their correction.
 Materials and methods. Analysis of literature sources on this topic.
 Results and discussion. The pathogenesis of CHM disorders in the perioperative period includes such links as the impact of surgical stress and/or infections, relative insulin deficiency, increased production of ketone bodies etc. Grades of CHM disorders include compensation (normoglycemia, aglucosuria), subcompensation (moderate glycemia (up to 13.9 mmol/L), slight glucosuria), and decompensation (high glycemia, significant glucosuria, ketone bodies). The main tasks of preoperative preparation in patients with CHM disorders include CHM normalization, correction of volemic disorders, maximum compensation of renal function, prevention and treatment of infectious complications. Glycemic levels in perioperative CHM disorders are highly variable and are not always associated with the severity of the condition, although glycemia >30 mmol/L is usually associated with severe diabetic ketoacidosis. Surgery is one of the triggers of stress hyperglycemia (for patients without diabetes, the glucose level in these cases is 7.7-11.0 mmol/L). In the treatment of persistent hyperglycemia in hospitalized patients, insulin therapy should be initiated, starting from a blood glucose threshold of 10.0 mmol/L. The target is 7.8-10.0 mmol/L. Ketoacidotic coma is an absolute contraindication to surgery due to concomitant severe water-electrolyte disorders. Surgery for vital indications can be performed only after restorative measures in 3-4 hours after recovery of consciousness and reduction of glycemia to <15 mmol/L. Only profuse, life-threatening bleeding can be the basis for reducing the time and volume of preoperative preparation of a patient with diabetes decompensation. Criteria of readiness for surgery include normal or close to normal blood glucose levels, adequate hydration and elimination of ketoacidosis. In patients with severe diabetes, relative compensation (8.8-10.0 mmol/L) can be used as a criterion. Most researchers recommend transitioning patients with impaired CHM to simple insulin injections before surgery. Insulin concentration is important for wound healing and prevention of purulent complications. Sodium bicarbonate or Soda-Bufer (“Yuria-Pharm”) can be used to correct metabolic acidosis. Ketogenesis should be eliminated with xylitol (Xylate, “Yuria-Pharm”). Routine glucose use in critically ill patients has been abandoned.
 Conclusions. 1. Many patients in the perioperative period develop CHM disorders, which worsen the course of the underlying disease. 2. The main tasks of preoperative preparation in patients with CHM disorders are CHM normalization, correction of volemic disorders, maximum compensation of renal function, prevention and treatment of infectious complications. 3. In the treatment of persistent hyperglycemia in hospitalized patients, insulin therapy should be started, starting from the glycemic threshold of 10.0 mmol/L. 4. Ketoacidotic coma is an absolute contraindication to surgery due to concomitant severe water-electrolyte disorders. 5. Criteria of readiness for surgery include normal or close to normal blood glucose levels, adequate hydration and elimination of ketoacidosis. 6. Sodium bicarbonate or Soda-Bufer can be used to correct metabolic acidosis. 7. Ketogenesis should be eliminated with Xylate.

Unique options for the correction of carbohydrate metabolism disorders

Background. Deep and versatile disorders in case of acute diseases can lead to severe metabolic disorders that are life-threatening and require immediate care. Such conditions include carbohydrate metabolism disorders (CMD): ketoacidosis, non-diabetic ketoacidosis, ketoacidotic and hyperosmolar coma, hypoglycemic syndrome, hypoglycemic and lactic acid coma.
 Objective. To describe the possibilities of CMD correction.
 Materials and methods. Analysis of literature sources on this topic; own study involving 126 patients with CMD. Patients were prescribed classic and balanced crystalloids (1200-1400 ml per day), in case of ketoacidosis – Xylate (6-8 ml/kg/day), in case of hyperosmolar conditions – Volutenz (400-600 ml per day).
 Results and discussion. Necessary laboratory tests in CMD include the assessment of glycemia, potassium, sodium, urea, creatinine, acid-base status, ketonemia, ketonuria; clinical blood test; blood culture and antibiotic sensitivity determination (according to the indications). It should be noted that the level of glycemia in diabetic ketoacidosis (DKA) can vary from a slight increase to a severe hyperglycemia. In case of the clinical picture of advanced ketoacidosis the semiquantitative analysis can reveal 3-4 pluses of ketonuria. However, the nitroprusside method allows to determine acetoacetic acid only, whereas the severe DKA is characterized by the more pronounced increase in the content of β-oxybutyric acid. It may create the preconditions for the underdiagnosis of ketoacidosis. Due to certain features of the analysis, ketosis is usually diagnosed in a decompensated state. Therefore, first of all, it is necessary to be rely by a clinical condition of the patient. Infusion therapy (IT) for DKA involves the use of 0.9 % NaCl solution or Ringer’s solution. If the patient has hypernatremia, 0.45 % NaCl solution is administered. During the first 30-60 minutes of treatment one should administered 1 liter of these solutions. Subsequently, the infusion is continued at a rate of 4-14 ml/kg/h until the glucose level reaches <12 mmol/L, then the infusion should be continued with 5 % glucose solution. IT must be performed with caution in elderly patients and people with heart failure. In addition to IT, insulin therapy (0.1 U/kg/h) is prescribed for DKA, followed by dose adjustment to ensure a decrease in blood glucose concentration at a rate of 2-3 mmol/L. Acidosis is corrected by IT and insulin therapy. Treatment of severe acidosis (pH <7.0) with bicarbonate requires dose adjustment under acid-base control. Xylitol (Xylate, “Yuria-Pharm”) is the main antiketogenic solution. It enters the pentose phosphate metabolism, increases the intensity of glycolysis, enhances glycogen production in the liver and stimulates insulin secretion. On the background of Xylate use, the content of β-oxybutyrate in the urine is halved in 5 hours, and the level of acetone – decreases in 2.5 times in 2 hours. Xylate reduces lactate levels and normalizes tissue perfusion. The unique effects of Xylate include pronounced antiketogenic effect, correction of metabolic acidosis, role as a non-insulin-independent energy source, correction of water-electrolyte balance, and hydration. Evaluation of the effectiveness of therapy in patients with DKA should include regular monitoring of neurological status. If deterioration is observed, cerebral edema, stroke, infectious diseases of the central nervous system, traumatic brain injury, hyperosmolar condition should be excluded. In the latter case, it is advisable to enter a hypotonic solution of 0.45 % NaCl. Because the use of such solutions is associated with a risk of cerebral edema, most recommendations prefer isotonic solutions.
 In the own study, the described above IT scheme helped to reduce the total volume of infusions, increase diuresis, improve consciousness on the 3rd day of treatment, and reduce the length of stay in the intensive care unit.
 Conclusions. 1. Many patients develop CMD, which worsen the course and prognosis of the underlying disease. 2. The use of IT should be started at the first signs of DKA. 3. Modern antiketogenic agent Xylate affects the pathogenesis of CMD and has an additional energy effect.

Disorders of carbohydrate metabolism in critical conditions

Background. Carbohydrate metabolism disorders (CMD) include ketoacidosis and ketoacidotic hyperglycemic coma, non-diabetic ketoacidosis, hyperosmolar coma, hypoglycemic syndrome and hypoglycemic coma, lactic acid coma. The main factors in the development of CMD are newly diagnosed diabetes mellitus (DM) or inadequate therapy of previously diagnosed DM, infectious processes, acute diseases (myocardial infarction, strokes, pancreatitis, renal failure, severe burns, thyrotoxicosis), use of certain drugs (calcium channel blockers, osmotic and thiazide diuretics, propranolol, chemotherapeutic drugs), alcohol or cocaine abuse.
 Objective. To describe the course and management of patients with CMD.
 Materials and methods. Review of the available literature on this issue.
 Results and discussion. CMD in critical conditions leads to the development of hyperglycemia, hyperketonemia, metabolic acidosis, dehydration, hyperosmolarity, electrolyte imbalance, arising against the background of the underlying disease, being masked by it and worsening the patient’s condition. When diagnosing ketoacidosis, one should focus primarily on the clinical condition of the patient, because the test for ketonuria does not reflect the actual level of ketone bodies in the urine. CMD therapy should include rehydration (infusion therapy – IT), insulin therapy, partial correction of severe metabolic acidosis, use of antiketogenic drugs, compensation of electrolyte disorders and elimination of the CMD causes. Isotonic NaCl solution or Ringer solution must be used for IT. Elderly patients and patients with heart failure should be treated with caution, with a possible dose reduction of 50 %. In case of hyperglycemia, insulin therapy (intravenous bolus 0.15 IU/kg, then infusion 0.1 IU/kg/h) is prescribed to ensure a reduction in glucose concentration by 2-3 mmol/L per hour. To correct metabolic acidosis, hydrocarbonate solutions are prescribed under the control of acid-base status (ABS). If it is not possible to determine ABS, in the presence of clinical signs of ketoacidosis, it is possible to prescribe Soda-Bufer (“Yuria-Pharm”) up to 300 ml. Xylitol (Xylate, “Yuria-Pharm”) is the main antiketogenic solution. It reduces the amount of free fatty acids, which oxidize to acetyl-CoA, acts as an insulin-independent energy source, increases the intensity of glycolysis and glycogen production, stimulates insulin secretion. If the patient has a fasting blood glucose level >13.9 mmol/L, nausea, vomiting, dizziness, drowsiness, dry skin and dry mouth, Kussmaul’s breathing, frequent urination, or a patient with diabetes is scheduled for surgery, it is advisable to prescribe xylitol-containing solution. Xylate should be prescribed for various CMD (hyperglycemia, dehydration, hypokalemia, ketoacidosis). Another area of CMD treatment is the normalization of potassium levels, which should be started in the conditions of normokalemia, because CMD are characterized by an initial increase and subsequent decrease in potassium content. The latter should be maintained at 4-5 mmol/h with tight monitoring every 2 hours firstly and then every 4 hours.
 Conclusions. 1. Many patients in the intensive care unit develop CMD. 2. CMD in critical conditions involve the development of hyperglycemia, hyperketonemia, metabolic acidosis, dehydration, hyperosmolarity, and electrolyte imbalance. 3. CMD therapy should include rehydration, insulin therapy, partial correction of severe metabolic acidosis, use of antiketogenic drugs, compensation of electrolyte disorders and elimination of the CMD causes. 4. Isotonic NaCl solution, Ringer solution, insulin therapy, hydrocarbonate solutions, xylitol, potassium preparations are used in CMD therapy.

Epidemiology of acute diabetes complications (coma) according to the Federal Diabetes register of the Russian Federation (2013–2016)

Background: Despite the improvement in the quality of diabetes care in the Russian Federation (RF), coma remain one of the causes of death in patients with diabetes.
 Aim: To assess dynamic of epidemiological characteristic of acute complications in adult patients with T1D and T2D in 201316.
 Materials and methods: The database of the Russian Federal Diabetes register (81 regions). The indicators of coma for 201316 were estimated for 10000 adult patients with diabetes (18 years).
 Results: In 2016, the prevalence of coma in RF was 225.9 with T1D and 11.6/10000 adults with T2D. For the period from 2007 the prevalence of ketoacidotic coma decrease three times in T1D, 4 times for T2D.Totally in 2016, 165 new cases of coma for both types of diabetes were registered, an average of 0.4/10000 adults. Interregional differences in the prevalence of coma were observed 04.2/10000 adults. The frequency of new cases of coma has a tendency to decrease: 0,90,4/10000 adults: T1D 5.73.4, T2D 0.60.2/10000 adults. When evaluating the structure of coma, redistribution is evident in their form. So in 2016 the proportion of hypoglycemic coma increased to 40.7%, and ketoacidotic coma decreased to 56.6% in T1D. With T2D, the difference expressed in a lesser degree. The mean duration of diabetes at the time of coma development increased with T1D from 3.89.1 years, with T2D 3.57.0 years. The maximum frequency of development of coma is recorded with the diabetes duration more than 30 years, regardless of the type. The patients age at the time of coma development in T1D increased to 27.5 years old, and in T2D it was 60.4 years, it didnt change significantly. The assessment of glycemic control showed a significant improvement: a decrease in the proportion of patients with HbA1c 9.0% (23% with T1D, 8.8% with T2D), an increase with HbA1c 7% (32.4% and 51.7%, respectively). The average value of HbA1c in 2016 with T1D 8.21%, with T2D 7.48%.
 Conclusions: It is established that the dynamics of the frequency of development of coma in 201316 in adult patients with diabetes in the RF has a stable tendency to decrease: 1.5 times with T1D and more than 3 times with T2D. It can be assumed that this is due to the improvement in the quality of diabetes care and glycemic control in general, as well as the use of modern medicines. Attention is required to draw to the high frequency of coma in T1D, the development of coma with a longer duration of diabetes, an increase in the proportion of patients with hypoglycemic coma. Significant interregional differences in the frequency of coma registration require additional analysis.

Clinical case of late diagnosed diabetes in ketoacidotic coma III in teenager: lessons to be learned

Clinical case of late diagnosed diabetes in ketoacidotic coma III in teenager: lessons to be learned

Clinical Case of Late Diagnosed Diabetes in Ketoacidotic Coma III in Teenager: Lessons to be Learned

Clinical Case of Late Diagnosed Diabetes in Ketoacidotic Coma III in Teenager: Lessons to be Learned

Management of Diabetic Ketoacidosis in Patients with Diabetes Type I

Background: DKA is the leading cause of mortality among pediatric age and young adults with T1D, responsible for almost 50% of all fatalities in diabetic patients younger than 24 years of age. Goals of DKA management include optimization of volume status, hyperglycemia and ketoacidosis, electrolyte abnormalities, and potential precipitating factors. Methodology: we conducted this review using a comprehensive search of MEDLINE, PubMed, and EMBASE, January 1987, through February 2017. The following search terms were used: ketoacidosis, management of diabetic ketoacidosis, type I diabetic patients’ emergency complication, fluid replacement in DKA, insulin therapy approach. Aim: in this review, we aim at evaluating the various ways of approaching patients who suffer from type-one diabetes during ketoacidosis and keto-acidotic coma. We will try to understand the triggers and pathophysiology behind this condition, and explore ways to prevent them. Conclusion: prompt diagnoses, aggressive treatment, and education of patient and their care providers about prevention strategies must be implemented. Also, more studies are required in the area of preventing health complications due to these types of diseases to effectively manage DKA in the future.

BIOCHEMICAL INDICES OF VITREOUS HUMOR IN DIAGNOSIS OF DISEASES

Aim. The aim of the study was to carry out the biochemical analysis of vitreous humor for the development of the methods of postmortal differential diagnosis of diabetes mellitus comas. Materials and methods. In the vitreous humor of 378 patients suffering in the life time from diabetes mellitus, the following indices were determined: glucose, lactate, ketone bodies, «average molecular weight» peptides content. Results. Vitreous humor glucose content higher than 17 mmol/l proves hyperglycemic coma; at the same time, glucose content higher than 9,0 mmol/l and lower than 17 mmol/l is typical for precomatose status. In case of ketoacidotic coma, vitreous humor ketonic content is higher than 4,0 mmol/l, but in case of hyperosmolar ketoacidotic coma (hyperglycemia + ketoacidosis) ketonic bodies content is higher than 2,5 mmol/l and glucose content exceeds 7,0 mmol/l. Absence of glucose and vitreous humor lactate content lower than 10 mmol/l testifies the presence of hypoglycemic coma. Conclusions. The methods for postmortal differential diagnosis of diabetic comas and endogenous intoxication syndrome were developed.

Insulin.

Insulin.

Interesting Development in the Pathophysiology of Diabetic Ketoacidotic Coma

The identification of acetoacetic and beta-hydroxybutyrie acids in the urine of comatose patients with diabetic ketoacidosis at the end of the nineteenth century has led to the opinion that these two acids are the cause of lethal coma in diabetes mellitus (therefore the name “ketoacidotic coma”). In the following decades also other organic acids have been identified in such patients (up to date 34); there are no reports on the dependency of these 34 acids on insulin. Knowledge has emerged that acidosis (=low blood pH), regardless what is the acid (or acids), impairs utilization of glucose in brain cells: this could explain development of coma in patients with very low blood pH. The positive consequence of this development could be that increase and normalization of the very low blood-pH would be followed by recovery from coma to full alertness. Clinical reports have confirmed that infusions of alkalizing solutions resulted in recovery of comatose patients with diabetic ketoacidosis (=zero lethality).

A case of instantaneous rigor?

The question of whether instantaneous rigor mortis (IR), the hypothetic sudden occurrence of stiffening of the muscles upon death, actually exists has been controversially debated over the last 150 years. While modern German forensic literature rejects this concept, the contemporary British literature is more willing to embrace it. We present the case of a young woman who suffered from diabetes and who was found dead in an upright standing position with back and shoulders leaned against a punchbag and a cupboard. Rigor mortis was fully established, livor mortis was strong and according to the position the body was found in. After autopsy and toxicological analysis, it was stated that death most probably occurred due to a ketoacidotic coma with markedly increased values of glucose and lactate in the cerebrospinal fluid as well as acetone in blood and urine. Whereas the position of the body is most unusual, a detailed analysis revealed that it is a stable position even without rigor mortis. Therefore, this case does not further support the controversial concept of IR.

Coma diabeticum

Diabetic coma is an endocrinological emergency leading to severe metabolic crisis with electrolyte disturbance, dehydration and disturbance of consciousness up to coma in patients with diabetes mellitus. In many cases it involves the first manifestation of diabetes mellitus. A distinction is made between hyperosmolar diabetic coma that mainly occurs in type 2 diabetes with relative lack of insulin and results in severe dehydration, and diabetic ketoacidosis on the other hand, which mainly develops in type 1 diabetes with absolute insulin shortage. In the latter case, a shifted acid-base balance and metabolic acidosis are the main pathophysiologic processes. Mixed forms may occur, both relating to pathophysiology or the underlying type of diabetes. Thus, ketoacidotic coma may also occur in progredient type 2 diabetes with complete dysfunction of β-cells.

Alkali Therapy in Patients with Metabolic Acidosis

To the Editor: In his review Acid-Base Disorders in lCU Patients, Oh1) writes in the summary on p 66 treatment target is not the acidosis, but the underlying condition causing acidosis. In contrast to this statement, Edge et al.2) have concluded that the immediate cause of coma in patients with acidosis is the very low blood pH. The glycolytic enzyme phosphofructokinase is pH dependent, as its activity is decreasing with decreasing pH, and, thus, glucose utilization in brain cells is impaired3). For the readers of Electrolyte Blood Press it would be perhaps interesting to know, why the author did not comment the paper of Edge et al.2). On p 69, the author writes HCO3- therapy does not improve the outcome in diabetic ketoacidosis ... Life-threatening is the most severe stage of diabetic ketoacidosis, coma. If the treatment of diabetic ketoacidotic coma included also infusions of alkalizing solutions, lethality was zero %, e g4). Without alkalizing solutions, lethality was up to 100%, e g5). Again, it would be perhaps interesting to know why the author did not comment the papers of Wagner et al.4) and Basu et al.5).

Different Clinical Presentation in Siblings with Mitochondrial Acetoacetyl-CoA Thiolase Deficiency and Identification of Two Novel Mutations

Mitochondrial acetoacetyl-CoA thiolase (T2) catalyzes 2-methylacetoacetyl-CoA cleavage into acetyl-CoA and propionyl-CoA in isoleucine catabolism and interconversion between acetyl-CoA and acetoacetyl-CoA in ketone body metabolism. T2 deficiency is a rare metabolic disease of autosomal recessive inheritance. The disorder is characterized by intermittent ketoacidotic episodes. The onset of clinical symptoms is in the infant or toddler period. The frequency of episodes declines with age, stopping before adolescence. Here we report two siblings with this disorder. The proband (GK65) is a French girl born from non-consanguineous parents. She presented several ketoacidotic episodes with 5 hospitalizations from age 2 to 4 years, the first of them complicated by ketoacidotic coma. Minor episodes, which are generally provoked by infections or high protein intake, still persist at age of 16 years. Molecular analysis of the T2 gene has revealed the compound heterozygosity of c.578T>C (M193T) and IVS8+5g>t. The latter mutation results in skipping of exon 8. In contrast, the younger brother (GK65b) had a unique ketoacidotic crisis at the age of 6 years that is the oldest-age first crisis among T2-deficient patients reported thus far. Despite the mild phenotype, he carried the same T2 gene mutations as his sister (GK65). Furthermore, T2 catalytic activity and T2 protein were not detected in the fibroblasts derived from GK65 and GK65b. In conclusion, the siblings with the same T2 gene mutations present different clinical severity. Diagnostic testing for asymptomatic siblings is important in the management of T2-deficient families.

Long-term posaconazole treatment and follow-up of rhino-orbital-cerebral mucormycosis in a diabetic girl

To demonstrate that the 2-yr clinical follow-up of our patient strongly suggests that long-term therapy with posaconazole (POS) is safe and beneficial in treatment and prevention of relapses of, otherwise fatal, central nervous system mucormycosis. Mucormycosis is a very rare opportunistic mycotic infection of diabetic children. We present the 30-month follow-up of a 12-yr-old girl affected by diabetic ketoacidotic coma, complicated by rhinocerebral mucormycosis and successfully treated with POS at the initial daily dose of 5 mg/kg t.i.d. with fatty food for 3 wk, followed by a daily dose of 10 mg/kg in four doses for 2 months and then 20 mg/kg/d in four doses for 16 months and in two doses for further 5 months. The previous amphotericin B, granulocyte colony-stimulating factor, hyperbaric oxygen and nasal and left maxillary sinus surgical debridement therapy was ineffective in stopping the progression of the infection to the brain. The patient improved within 10 d with reduced ocular swelling and pain, and 6 months after therapy stop, she is in good health and cultures are sterile. This article demonstrates that POS may be a useful drug in mucormycosis in children. We also strongly draw the attention to the main preventive procedure against invasive fungal infection that is the correct management of antidiabetic therapy that prevents the predisposing temporary neutrophils activity deficit, contributing to a better survival rate of diabetic children.

Acidocétose diabétique d’évolution fatale : serait-ce un MODY3 (maturity-onset diabetes of the young de type 3) ?

Ketoacidotic coma is one of the possible diabetes mellitus first symptoms. It results from complete or relative lack of insuline and is often associated with type 1 diabetes. The authors report a case of a 45-years old woman with inaugural diabetes of which atypical features have motivated the study of MODY gene (maturity-onset diabetes of the young). Gly574ser polymorphism in the HNF-1alpha gene was found, in homozygous state, and the question of the responsibility of this polymorphism in this diabete is asked.

Human Sco1 and Sco2 Function as Copper-binding Proteins

The function of human Sco1 and Sco2 is shown to be dependent on copper ion binding. Expression of soluble domains of human Sco1 and Sco2 either in bacteria or the yeast cytoplasm resulted in the recovery of copper-containing proteins. The metallation of human Sco1, but not Sco2, when expressed in the yeast cytoplasm is dependent on the co-expression of human Cox17. Two conserved cysteines and a histidyl residue, known to be important for both copper binding and in vivo function in yeast Sco1, are also critical for in vivo function of human Sco1 and Sco2. Human and yeast Sco proteins can bind either a single Cu(I) or Cu(II) ion. The Cu(II) site yields S-Cu(II) charge transfer transitions that are not bleached by weak reductants or chelators. The Cu(I) site exhibits trigonal geometry, whereas the Cu(II) site resembles a type II Cu(II) site with a higher coordination number. To identify additional potential ligands for the Cu(II) site, a series of mutant proteins with substitutions in conserved residues in the vicinity of the Cu(I) site were examined. Mutation of several conserved carboxylates did not alter either in vivo function or the presence of the Cu(II) chromophore. In contrast, replacement of Asp238 in human or yeast Sco1 abrogated the Cu(II) visible transitions and in yeast Sco1 attenuated Cu(II), but not Cu(I), binding. Both the mutant yeast and human proteins were nonfunctional, suggesting the importance of this aspartate for normal function. Taken together, these data suggest that both Cu(I) and Cu(II) binding are critical for normal Sco function.

L’imagerie dans la mucormycose rhinocérébrale

Purpose Rhinocerebal mucormycosis is a rare life threatening fungal infection observed in immunocompromised patients. We report six cases of patients with rhinocerebral mucormycosis confirmed histologically. Our study confirms the necessity of early diagnosis when clinical and CT findings are suggestive. Materials and Methods This is a retrospective study including 6 diabetic patients (3 women and 3 men) aged from 28 and 63 years. Five patients had ethmoiditis evolving for a few days (3 to 5 days), and one patient was in an ketoacidotic coma and had a severe infectious syndrome with purulent rhinorrhea evolving for 4 days. All of our patients underwent computed tomography (CT) scan of the paranasal sinuses. MRI was performed in two patients with neurological findings. Results Unilateral ethmoido-maxillary sinusitis was noted in 5 cases. Only one case of pansinusitis was found. All patients presented orbital involvement. Cerebral involvement was noted in 4 cases (cerebral venous thrombosis: 2 cases; abscess: 2 cases; cerebral ischemia: 2 cases). The diagnosis of mucormycosis was based on endonasal biopsy. When available, MRI allowed a more precise evaluation of the orbital and cerebral extension. Conclusion Mucormycosis is an opportunist mycosis due to mucoralis fungus. It is very invasive with a highly aggressive potential in diabetic or immunocompromised patients. Imaging study particularly CT scan, plays an important role in diagnosis especially to evaluate cerebral extension.