The Mexican consensus on the treatment of hepatitis C. / Consenso Mexicano para el Tratamiento de la Hepatitis C.

The aim of the Mexican Consensus on the Treatment of HepatitisC was to develop clinical practice guidelines applicable to Mexico. The expert opinion of specialists in the following areas was taken into account: gastroenterology, infectious diseases, and hepatology. A search of the medical literature was carried out on the MEDLINE, EMBASE, and CENTRAL databases through keywords related to hepatitisC treatment. The quality of evidence was subsequently evaluated using the GRADE system and the consensus statements were formulated. The statements were then voted upon, using the modified Delphi system, and reviewed and corrected by a panel of 34 voting participants. Finally, the level of agreement was classified for each statement. The present guidelines provide recommendations with an emphasis on the new direct-acting antivirals, to facilitate their use in clinical practice. Each case must be individualized according to the comorbidities involved and patient management must always be multidisciplinary.

Incidence and severity of infections according to the development of neutropenia during combined therapy with pegylated interferon-alpha2a plus ribavirin in chronic hepatitis C infection.

The evolution of treatment of chronic hepatitis C virus infection has led to improved therapeutic efficacy. However, a major problem is the presence of side effects that require modification or withdrawal of drug therapy in 15-20% of cases. This could potentially influence the lack of sustained viral response in 50% of the cases. Side effects are common, even with pegylated interferon. This study aimed to assess the incidence and severity of infections based on the development of neutropenia associated with combined therapy with pegylated interferon-alpha2a plus ribavirin in 209 patients with chronic hepatitis C infection. All patients were administered pegylated interferon-alpha2a (180 microg/week) plus ribavirin (800 mg/day for 24 weeks in cases of nongenotype 1, or 1000-1200 mg/day for 48 weeks for genotype 1, according to whether patients weighed more or less than 75 kg). Patients with preexisting neutropenia of any cause or cirrhosis were excluded. Neutropenia was defined as a neutrophil count (NC) of <1500 cells/microl. Neutropenia was classified into three levels during treatment: 750

Chemiluminescence detection of ATP release from red blood cells upon passage through microbore tubing.

A novel approach for the determination of adenosine triphosphate (ATP) released from red blood cells (RBCs) after passage through microbore capillaries is described. ATP is often released from RBCs in vessels and has been linked to the production of nitric oxide, a known vasodilator. The system described here uses a syringe pump to deliver microliter flow rates (5-15 microl min(-1)) of reagent and sample through fused silica capillary tubing of varying dimensions (25-75 microm) to a photomultiplier tube. The released ATP is characterized by the detection of chemiluminescent emission from the luciferin-luciferase reaction. The amount of ATP released is directly proportional to the number of RBCs injected into the system. Results also suggest that the amount of released ATP decreases from 6.9 microM to 1.4 microM as the tubing diameter is increased from 25 microm to 75 microm. An investigation of capillary lengths ranging from 15 to 35 cm resulted in ATP concentrations of 1.5 microM to 2.4 microM being released. Results also indicate that increases in flow rate also induce increased amounts of ATP release. These results are consistent with those of previous systems attempting to model the physiological release of ATP from red blood cells.

On the diagnosis of hypoglycemia in car drivers--including a review of the literature.

Hypoglycemia may reach forensic relevance concerning the psychophysical ability of running a car and with respect to a possible imputability. Our retrospective study included anamnesis and clinical symptoms observed in drivers with impaired performance to point out correlations between biochemical parameters and the actual course of the disease and its sequelae on roadworthiness. Clinical-biochemical estimations were performed on glucose, lactic acid and ethanol including a toxicological screening. It is proposed to utilize the estimation of glucose and lactic acid (the so-called combined value) in blood samples taken on behalf of the police as an important hint to the actual state of glucose metabolism. The anamnesis and the symptomatology may complete the biochemical analyses.

Elevated homocysteine levels in alcohol withdrawal.

Ethanol exerts its behavioural effects largely by interacting with receptors for brain neurotransmitters. However, the molecular mechanisms involving these interactions and the pathogenesis of alcohol-withdrawal symptomatology are still not well understood. Until recently, no data were available about homocysteine (Hcy) levels in acute alcohol intoxication of chronic alcoholics and in patients undergoing withdrawal from alcohol. Hcy, blood-alcohol concentrations, vitamins B6, B12, and folate concentrations were assessed in 29 chronic alcoholics, who underwent withdrawal from alcohol. We observed increased Hcy levels in most patients. Hcy levels steadily decreased during the observation period. We postulate that hyperhomocysteinaemia and excitatory amino acid neurotransmitters, by their agonism at the N-methyl-D-aspartate receptor, may partly mediate alcohol-associated withdrawal symptomatology. The importance of assessing serum Hcy levels in order to detect methylation deficiency in patients with chronic alcoholism and for possible therapeutic strategies is discussed.

[Follow-up study after enteral manganese poisoning: clinical, laboratory and neuroradiological findings]. / Verlaufsbeobachtung nach enteraler Manganintoxikation. Klinische, laborchemische und neuroradiologische Befunde.

Manganese intoxication is an unusual, severe form of intoxication. This report deals with a patient now 80 years old who accidentally ingested a solution of potassium permanganate for a period of at least 4 weeks 14 years ago. Since then, the patient suffers from a mild parkinsonian syndrome and distally accentuated polyneuropathies. Psychiatric disorders, especially demential or depressive symptoms, were not observed. Manganese analysis of his hair still shows a clear increase in manganese concentration. The MRI of his brain showed no pathological changes, in particular none of those often described with symmetric signal elevation in T1 in the area of the basal ganglia. In this study, we present clinical, laboratory, and neuroradiological findings. Unusual in this case with a short exposition is the long duration and clinical improvement without L-dopa treatment.

[Phenomenology of ether administration. With a review of the literature]. / Zur Phänomenologie bei Etherapplikation. Mit einer Literaturübersicht.

A 45-year-old man was found dead lying on a sofa in his house. He had pulled a plastic bag over his head, the bag containing a pad of cotton-wool soaked with diethylether. Different aspects are discussed in this paper including a review of the literature: anamnesis, scene of death, utensils used for inhalation and autopsy findings. There are especially pointed out the results of chemical-toxicological analyses in many body compartments. Furthermore are interpreted the manners and the relations of the distribution of ether as well as possible effects on the consciousness. In consideration of other published cases, the analytical results concerning ether are discussed with regard to the presumed cause of death (e.g. asphyxia) and other potential competitive mechanisms.

Clinical and morphological aspects of death due to liquid nitrogen.

A 24-year-old student died while filling flasks with liquid nitrogen. The arms, legs and back were frozen and the face, ears and neck showed a dark red and livid colour with horizontal lines of demarcation. In the electrocardiogram, the heart showed asystolia followed by wide ventricular complexes. The patient was intubated orally as the situs of the larynx and pharynx showed no pathology findings. Cardiopulmonary resuscitation was carried out and terminated after 90 min. Unfortunately, the body temperature was not measured. The gas analysis of venous blood showed metabolic acidosis and oxygen deficiency. The student had worked alone with nitrogen, without opening the windows and without a working ventilation system. While filling the third flask he lost consciousness. As nitrogen does not cause characteristic prodromal signs he laid on the floor and was unable to help himself. The liquid nitrogen which was still escaping spread over the floor and vaporized. The student died from asphyxia due to oxygen deficiency in an atmosphere of nitrogen.

[Heavy metal incorporation as an unusual self-injury]. / Schwermetall-Inkorporation als ungewöhnliche Selbst(be)schädigung.

A 19-year-old man was admitted to hospital because of uncharacteristic neurologic symptoms. During the first examination morphologic alterations due to an injection of mercury into the left arm and the left side of the trunk were found. The dose and the manner of application were doubtful and suspected to be a case of self-infliction. The man informed the police only 7 months later because his relatives had finally persuaded him to do so. The description of the infliction by unknown perpetrators was full of contradictions. Initially the patient gave only an indistinct description. But later on, the number of details increased. At the same time there was a change in the characteristics of the perpetrator(s). Other differences existed concerning a loss of consciousness which should have been caused by a single stroke on an arm. Furthermore, the patient told about a swelling as big as an egg, provoked by an injection of liquid mercury. It could be shown by experiments that mercury can be injected into soft-tissue very simply and that it spreaded widely. Arguments for a self-injection were e.g. the technical possibility, the topography of the injection marks, and an easy handling of the syringe. A psychiatric examination furthermore revealed, that the patient had had periods of restriction of thinking, sometimes combined with a lack of appreciation.

Identification of fatty acid methyl esters (FAMEs) in postmortem tissue. A new marker of alcohol abuse?

Based on a method that combines thin layer chromatography and gas chromatography, it proved possible to detect postmortem fatty acid methyl esters (FAMEs) in human tissues (pancreas, liver, heart and adipose tissue). The highest concentrations were found in the pancreas, medium concentrations in the liver and adipose tissue and the lowest concentration in heart tissue. All tissues contained higher concentrations of unsaturated FAMEs than saturated FAMEs. In order to evaluate the influence of alcohol consumption on the formation of FAMEs, the decreased were divided into three groups: control group, chronic alcoholics (who were alcohol free at the time of death), and acutely alcohol-intoxicated subjects (so intoxicated at the time of death with no evidence of chronic alcohol abuse). In comparison to the control group, the organs of the chronic alcoholics showed only slight values, the tissues of the acutely intoxicated subjects were obviously higher. Based on the varying concentration distribution in the three groups, it seemed that postmortem differentiation of the alcohol consumption which existed before the time of death would be possible. After further investigation with a greater number of samples, FAMEs could become a useful supplement to existing alcohol markers in the future.

[Reliability of forensic evidence in breath alcohol analysis]. / Zur Frage der forensischen Beweissicherheit der Atemalkoholanalyse.

Drinking experiments were performed by using a device-combination appreciated by the German National Institut of Health (BGA) as being evidential and proposed as prototype for the future practice of breath-alcohol analysis. Comparing the breath- (BrAC) and blood alcohol-concentrations (BAC), however, there were relevant deviations. Our evaluation of the facts published Schoknecht demonstrated nevertheless distinct divergences in comparison to the blood alcohol determination: A BAC-nominal of 1% gave divergences of the nominal up to 0.25% resulted from the measured BrAC-values of Schoknecht on corresponding conversion. The divergences are distinctly above those that are tolerated by legislation according to previous standards for the blood alcohol determination. Consequently it requires further checking in standardized experiments and field experiments in order to be able to judge the practice usefulness; furthermore such further checking would have to be implemented by unconcerned institutions. Basing on these experiments an evidential breath-alcohol analysis for forensic purposes has not been established yet.

[Precision control in blood alcohol determination]. / Zur Präzisionskontrolle der Blutalkoholbestimmung.

The German supreme court (BGH [1]) summons that by proclaiming four or five single measuring values of every blood alcohol determination to prove that the resulting standard deviation lies under the highest amount stated in the official verdict of 1989 (10). On the one hand the control of the proceedings must be guaranteed by the successful participation of the ring tests, yet on the other hand the evidence to retroactively prove the accuracy of every blood alcohol determination from it's single values is always called for anew. In the example case the average value is 1.11 g/1000, the standard deviation is 0.036 g/1000. The standard deviation summoned by the BGH (1) is thereby exceeded. On account of the fundamental scientific regularies the parameter standard deviation is not qualified to retroactively verify the required accuracy of the procedure by means of the single values. The blood alcohol result in question can be used without proviso. A reduction of the present approved 10% variation of the single values is not significant. Only according to todays accuracy requirements does this limit nearly appear to be appropriate.

[Forensic assessment of questionable railway suicides]. / Zur rechtsmedizinischen Beurteilung fraglicher Eisenbahn-Selbstmorde.

Railway deaths only seldom give rise to extensive inquiries. For the police there exists no absolute necessity of differentiating between accident and suicide. The reason is that accidents usually do not result in criminal proceedings. For the railway embankment the normal traffic rules are unvalid, and the guilt of the engine driver usually cannot be proven. In consequence these cases very often are declared as suicides without adequate support. This leads to complications in the field of insurance law. Since the "prima facie" principle in these cases was dropped our medicolegal institutes are increasingly engaged with expert opinions dealing with the question of accident or suicide. According to literature only a straight decapitation is regarded as typical for a suicide. But such can be found rather seldom in reality. That was the reason for us to study our own cases and to examine whether there are additional patterns of morphological findings proving a suicidal action. The respective case circumstances and, if available, testimonies were included in our study as well as the special constructional peculiarities of the engine frontages which logically contribute to the appearance of injuries.

[Falsification of breath alcohol concentration measurement. An experimental and case report]. / Zur Verfälschung der Messung der Atemalkoholkonzentration. Ein experimenteller und kasuistischer Beitrag.

As a rule, in our comparison of breath alcohol and blood alcohol concentration levels both readings were in agreement. Nevertheless, we repeatedly observed readings showing significant differences for which there was no apparent explanation. In two cases where discrepancies were extreme (breath alcohol concentration greater than 2.0%; blood alcohol concentration, 0.0%) we discovered that the cause was sniffing. The effects of various pharmaceutical drugs were tested. Experimentally the inhalation of liquid gas resulted in ostensible breath alcohol concentration levels of more than 2%. These experiments were reproducible. Consequences for the exployment of alcohol breath testing devices are discussed.

Postnatal development of striatal neurotensin immunoreactivity in relation to clusters of substance P immunoreactive neurons and the "dopamine islands" in the rat.

Conventional immunoperoxidase preparations of the coronally sectioned brains of rats killed at various times during the early postnatal period revealed the distributions of tyrosine hydroxylase, substance P, and neurotensin immunoreactivities. At birth, patches of dense tyrosine hydroxylase immunoreactivity were present across the breadth of the rostral striatum, whereas patches displaying substance P immunoreactivity were present only in its lateral half, appearing in its medial half by about postnatal day 3. Neuronal neurotensin immunoreactivity was absent in the rostral striatum at birth, although some neurotensin immunoreactive cells were present in the tail of the caudate-putamen. Rostrally, neurotensin immunoreactive cells appeared first along the lateral margin of the caudate-putamen on postnatal day 3, became numerous there about day 5, spread medially into the striatum by day 7, and achieved their medialmost distribution by about day 10. Their numbers and those of substance P immunoreactive neurons diminished thereafter. Substance P immunoreactive patches, which contained numerous labeled neurons and "puncta," shared coextensive distributions with patches of dense tyrosine hydroxylase immunoreactivity, but interdigitated with neurotensin immunoreactive cell clusters. The neurotensin immunoreactive cell clusters lacked puncta, the light microscopic representation of axon terminals, or swellings. It is concluded that the patchy infrastructure of the striatum, which is established prior to birth, is substrate for the progression of separate "waves" of elevated neuronal peptide content, one reflecting substance P and a later one reflecting neurotensin. These proceed along rostromedialward trajectories to involve interdigitating neuronal domains.

[Methanol--an up-to-now neglected constituent of all alcoholic beverages. A new biochemical approach to the problem of chronic alcoholism]. / Methanol--Ein bisher verkannter Bestandteil aller alkoholischen Getränke. Eine neue biochemische Annäherung an das Problem des chronischen Alkoholismus.

Alcoholism is usually understood as ethanolism. There is some evidence that its oxidation product acetaldehyde may condense with endogenous amines to form tetrahydroisoquinoline (TIQ) and - tetrahydro-beta-carboline (THBC) alkaloids which ultimately might be responsible for addiction. In most animal experiments pure ethanol solutions were fed, but chronic alcoholics prefer normal alcoholic beverages, and it is widely ignored that all these beverages without exception also contain methanol. Its metabolite formaldehyde is a much more potent reaction partner for TIQ and THBC formation than acetaldehyde. As our findings in chronic alcoholics proved that these persons in contrast to healthy subjects are able to oxidize methanol despite high ethanol levels, there must be a continuous leakage of formaldehyde. And it seems possible that methanol plays a more significant role in the pathophysiology and possibly the etiology of chronic alcoholism than ethanol.