The crisis facing printed medical literature. Acid paper

Medicine strives to preserve the achievements of the past for the benefit of future clinicians and scientists. However, the paper on which medical journals are printed is steadily and irreversibly decaying. Since the late 1800s, most medical journals have been published on paper prepared with acids. In recent years, publishers, authors, and archivists have become aware of the destructive effects of acid decay on medical journals. Though the cause of deterioration is well understood, the choice of a remedy is still controversial. Remedies include acid-free paper, computerization, deacidification, and microfilm. These techniques are reviewed for their reliability, comprehensiveness, and cost-effectiveness. Microfilm is recommended above other techniques as the most immediately promising solution. The authors propose that publishers be required by law to submit archival quality microfilm as a condition for copyright protection.     

Bündelhaar-Follikulitis

Zusammenfassung Bei der Bündelhaar-Follikulitis (tufted hair folliculitis) handelt es sich um eine durch Staphylococcus aureus verursachte, chronisch entzündliche und vernarbende Haarbodenerkrankung, die charakterisiert ist durch das umschriebene Auftreten von Bündelhaaren. Histopathologisch findet sich eine perifollikul?re Entzündung im oberen Bereich der Haarfollikel unter Aussparung der tiefen Follikelanteile. Innerhalb der Entzündungsareale münden mehrere Haare aus getrennten Haarwurzeln in ein gemeinsames Infundibulum mit dilatiertem Ostium. Das Krankheitsbild ist als eine Erscheinungsform der Folliculitis decalvans capillitii Quinquaud anzusehen, bei der die Auffassung besteht, da? die Infektion mit Staphylococcus aureus den pathogenetischen Initialfaktor darstellt, und Besonderheiten der Follikelanatomie und Immunantwort die individuelle Morphologie bestimmen: Dabei ist anzunehmen, da? die Ausbildung fl?chig atropher Narben mit vollst?ndigem Untergang der Hautanhangsgebilde (im Falle der Folliculitis decalvans) oder das Auftreten von Haarbündeln (im Falle der Bündelhaar-Follikulitis) von der Tiefe und dem Destruktions-Potential des Entzündungsinfiltrates abh?ngen. Die Behandlung der Bündelhaar-Follikulitis ist nicht ganz unproblematisch: Die prolongierte und wiederholte Gabe staphylokokken-wiksamer Antibiotika vermag den Krankheitsverlauf zu stabilisieren. Bereits vorhandene Haarbündel mit einer besonders hohen Rezidivneigung sollten aber – wie im vorgestellten Fall – nach M?glichkeit chirurgisch exzidiert werden.

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Summary A case of tufted hair folliculutis presenting as circumscribed, tender and inflamed areas in the occiput with residual tufted follicles in a 28-year old man is reported. Tufted hair folliculitis is a characteristic localized scarring bacterial folliculitis of the scalp due to Staphylococcus aureus. Histopathological studies reveal perifollicular inflammation around the upper portions of the follicles sparing the hair root level. Within areas of inflammation, several follicles converge toward a common follicular duct with a widely dilated opening. Currently, tufted hair folliculitis is considered a variant of folliculitis decalvans of Quinquaud. Staphylococcal infection is believed to be an initial causative factor, and underlying differences in follicular anatomy or host response may be important in determining which reaction pattern occurs in an affected individual. The development of atrophy with loss of adnexal structures (in folliculitis decalvans) or of hair tufts (in tufting folliculitis) may depend upon the depth and destructive potential of the inflammatory process. The therapeutic approach is problematic; prolonged treatment with oral antibiotics may stabilize the disease, but good and at times more definitive results (as in the presented case) have been reported after radical surgical excision of the involved areas.

Eingegangen am 2. April 1996 Angenommen am 7. Juni 1996     

Altered Excitability of the Motor Cortex after Minor Head Injury Revealed by Transcranial Magnetic Stimulation

Summary This study attempts to find out whether the motor evoked potential (MEP) elicited by single pulse and slow-rate (1 Hz) repetitive transcranial magnetic stimulation (TMS) can disclose concealed subclinical impairments in the cerebral motor system of patients with minor head injury. The motor response to single pulse TMS (STMS) of the patient groups was characterized by significantly higher threshold compared with that of the control group. The central motor conduction time, as well as the peripheral conduction time were normal in all patients pointing to cortical impairment. Two main patterns of MEP changes in response to repetitive TMS (RTMS) were observed in the patient group. A. – progressive decrease of the MEP amplitude throughout the stimulation session to a near complete abolition. B. – irregularity of the amplitude and the waveform of the MEP in a chaotic form. The MEP latency remained stable during the whole stimulation session. The MEP abnormalities recovered gradually over the period of a few months. The higher threshold of the motor response to STMS and the abnormal patterns of the MEP to RTMS seem to reflect transient impairment of cortical excitability or “cortical fatigue” in patients who sustained minor head injures. Further study is needed to evaluated the extent and the pathophysiological mechanisms of the central nervous system fatigue phenomenon following head injury.     

Differential effects of interleukin-12, interleukin-15, and interleukin-2 on human immunodeficiency virus type 1 replication in vitro.

Cytokines may have clinical utility as therapeutic agents for human immunodeficiency virus type 1 (HIV-1) infection and as an adjuvant for vaccines. The effect of interleukin-12 (IL-12) and IL-15 on in vitro HIV-1 replication was investigated. IL-12 and IL-15 at doses up to 10 ng/ml had little effect on basal HIV-1 p24 antigen production by chronically HIV-infected T (ACH-2) and monocytic (U1) cell lines. For ACH-2 cells stimulated with phorbol 12-myristate 13-acetate (PMA; 50 ng/ml), IL-12 and IL-15 significantly increased p24 antigen production by 20 and 30%, respectively (n = 6). In contrast, IL-12 and IL-15 (10 ng/ml) treatment of PMA-stimulated U1 cells decreased p24 antigen production by 16 and 15%, respectively (n = 6). We next studied the effect of IL-12 and IL-15 on HIV-infected peripheral blood mononuclear cells (PBMCs). In 10 HIV-seropositive patients' PBMCs cocultured with mitogen-activated HIV-seronegative donor cells, two patterns of p24 antigen production were observed in response to IL-2: low (p24 antigen production < 10(3) pg/ml; n = 8) and high (p24 antigen production > 10(3) pg/ml; n = 2) response. For the low-response pattern, IL-12 and IL-15 increased viral replication by 97-fold and 100-fold, respectively (P = 0.05 and 0.004, respectively). For the high-response pattern, both IL-12 and IL-15 suppressed HIV replication. The effect of IL-2, IL-12, and IL-15 on acute in vitro infection by HIV-1JRCSF was also examined. IL-12 did not increase p24 antigen production above basal levels while IL-2 and IL-15 significantly enhanced p24 antigen production (by approximately 2-fold). In conclusion, IL-12 and IL-15 may have differential effects on latent and acute HIV infection, and their ability to enhance HIV production may depend on cell activation. Thus, the use of these cytokines may be dictated by the clinical state of the patient.     

Predicting schizophrenia outcome with self-report measures of family interaction

This study is based on 18 patients admitted to a psychiatric hospital with a DSM-III-R diagnosis of schizophrenia who currently were living with one or both parents. Patients and parents completed several questionnaire, including the Parental Bonding Index (PBI), the Family Environment Scale (FES), the Hostility and Direction of Hostility Questionnaire (HDHQ), and the Brief Symptoms Inventory. Observer ratings of patients' symptoms also were made. Outcome was predicted best by patients' ratings of mothers on the PBI and by mothers' scores on the HDHQ Criticism of Others scale. Other significant outcome predictors were the number of previous admissions to hospital, patients' scores on the HDHQ Projected Hostility scale and the FES Expressiveness scale, and fathers' scores on the FES Achievement-Orientation scale.     

Abnormal seasonality of schizophrenic births A specific finding?

Summary The unusual finding of an abnormal seasonal distribution of schizophrenic births, showing an excess of 10% in the winter or spring months and an equal deficit in the summer or autumn months, cannot be explained by artefacts. It has not yet been established whether the finding is specific to schizophrenia. We observed an excess of schizophrenic births of some 10% in March to May, significant at the 5% level, and a deficit of approximately the same size in June to August on the birth data of first-admission patients with the clinical diagnosis of schizophrenia. The data, obtained from the Mannheim Psychiatric Case Register, were compared with those of the Mannheim population and a control group matched by birth year and sex. The total population of mentally retarded children aged 7 to 16 years from the Mannheim population showed an excess of some 20% in April to June and an equal deficit in the last two quarters of the year, compared with the Mannheim population of the same birth years. The finding was not significant, but allowance must be made for the low case number of 415. We also compared 3409 first-admission patients with depressive syndromes (ICD 296 and 300.4) and 5615 first-admission patients with the diagnosis of neurosis and personality disorders (ICD 300–302, except 300.4, and 305–309) from the Mannheim Case Register with a control population and a parallel control group. Depressed males showed an excess of births in March to May, which was significant at the 1% level; the birth peak for females was smaller and not significant. The same findings were obtained for the category of neurosis and personality disorders, i.e. an excess of about 10% in March to May for males, significant at the 1% level, and a non-significant excess for females. Our findings are awaiting replication. Causal explanations will be discussed with great reservation. The procreational hypothesis, assuming those factors that lead to an equidirectional seasonal pattern of births with a slight deviation from the average of a year in the general population, to be reinforced in the disease categories mentioned, is regarded as the most simple and plausible explanation. It is based on the assumption that some of the parents of individuals suffering from schizophrenia, mental retardation or probably also some other mental disorders running from generation to generation, have a higher threshold in partner-seeking behaviour, which is overcome more easily in the summer months with the consequence of increased pregnancies.     

Modulation of action potential duration by inhibition of the transient outward current in sheep cardiac Purkinje fibers

In sheep cardiac Purkinje fibers concentration-dependent inhibition of transient outward current (i_to) by 4-aminopyridine (4-AP, 3-1000 mol/l) was recorded with the two-microelectrode voltage-clamp technique, and correlated effects on action potential duration measured at — 70 mV (APD-70) were investigatigated.Half-maximal inhibition of i_to-amplitude occurred at 15 mol/l 4-AP. The drug exhibited no major effect on voltage-dependent control of inactivation but reduced the maximally available i_to-current. At different activation frequencies (0.05 Hz, 0.25 Hz, 1 Hz) an equal amount of i_to-current, measured as percentage of the respective control, was inhibited by 4-AP. The APD-70 was on the average increased by 4-AP (3–500 mol/l) in a concentration-dependont manner up to 151 % of control. The drug-induced prolongation, measured as percentage of the respective control, was independent of stimulation frequency (0.05 Hz, 0.25 Hz, 1 Hz). Prolongation of APD-70 was on the average more pronounced for short action potentials (APD-70<150 ms: 169 % of reference) than for longer ones (APD-70 150–300 ms: prolongation to 117 % of reference; 500 mol/l 4-AP; 0.25 Hz stimulation rate). Few long control signals (APD-70 >300 ms) were shortened by 4-AP. These results indicate that inhibition of i_to-current by appropriate drugs will result in a reduction of inhomogeneity of action potential duration.     

Hereditary disorders of the protein C system in central artery and branch arteriolar occlusions]

BACKGROUND: Resistance to activated protein C (APC) is the most common hereditary defect in patients with venous thrombosis. There are conflicting reports on the prevalence of APC resistance in patients with arterial thrombosis, e.g. coronary arteries, compared to the APC resistance prevalence among the normal population. The prevalence of APC resistance in branch retinal artery occlusion (BRAO) and central retinal artery occlusion (CRAO) is unknown. PATIENTS AND METHODS: 29 consecutive patients with arterial retinal occlusions (BRAO, n = 12; CRAO, n = 17) were included in this prospective study over a 23-months-period. We searched for APC resistance, protein C or S deficiencies, as well as for acquired vascular risk factors. Factor-V-deficient plasma and genetic analysis with a PCR method were employed for APC resistance determination. Protein C and protein S activity were determined with functional tests. RESULTS: APC resistance was found in 3 of 29 patients (10.3%). Two of these patients had BRAO and one patient CRAO. Comparing this prevalence to the APC resistance prevalence within the normal population (9%), the difference was not statistically significant. 27 patients (93.1%) had one or more vascular risk factors (arterial hypertension = 19 [65.5%], hyperlipidaemia = 14 [48.2%], smoking = 7 [24.1%], diabetes mellitus = 5 [17.2%], carotid artery stenosis = 5 [17.2%]). CONCLUSIONS: We could not find an increased prevalence of APC resistance in patients with CRAO or BRAO when compared to the normal population.     

Retinal vascular occlusion and deficiencies in the protein C pathway.

PURPOSE: To report abnormalities in the protein C pathway and other vascular occlusion risk factors in patients with retinal vascular occlusion. METHODS: In a study, we investigated 76 consecutive patients who had in-patient evaluation of venous or arterial retinal vascular occlusion. All patients underwent comprehensive tests for coagulation disorders including determinations of protein C, protein S, lupus anticoagulants, and resistance to activated protein C and were screened for vascular disease risk factors. Resistance to activated protein C was confirmed by a polymerase chain reaction method to detect the specific factor V R506Q mutation. For comparative purposes, we also screened 209 consecutive inpatients with deep vein thrombosis from the same geographic region for resistance to activated protein C as well as protein C and protein S deficiencies. RESULTS: Ten (29%) of 35 patients with central retinal vein occlusion (CRVO) had factor V R506Q mutation. The factor V R506Q mutation was detected in four (19%) of 21 patients with branch retinal vein occlusion. The higher frequency in factor V R506Q mutation compared with the expected 9% mutation prevalence in a white population was highly significant for the central retinal vein occlusion group but not for the branch retinal vein occlusion group. In all patients with resistance to activated protein C, the factor V R506Q mutation was detected; 16 were heterozygous, one homozygous. No cases of lupus anticoagulants, protein C, or protein S deficiencies were detected. Forty (19%) of 209 patients with deep vein thrombosis were carriers of the factor V R506Q mutation. CONCLUSIONS: The prevalence of the factor V R506Q mutation is similar in patients with central retinal vein occlusion and patients with deep vein thrombosis and represents a relevant risk factor. Screening for this mutation is therefore recommended in all patients with central retinal vein occlusion.     

Inhibition of potassium outward currents and pacemaker current in sheep cardiac Purkinje fibres by the verapamil derivative YS 035

Summary The electrophysiologic mode of action and potency of the verapamil derivative YS 035 (N,N-bis-(3,4-dimethoxyphenethyl)-N-methyl amine) were investigated in sheep cardiac Purkinje fibres. Action potential duration measured at a repolarization level of –60 mV (APD-60) and membrane currents recorded with the two-microelectrode voltage-clamp technique were evaluated. At 10 mol/l YS 035 APD-60 was increased to about 115% of reference. Prolongation measured as percentage of the respective control exhibited on the average no dependence on stimulation frequency (0.17–2 Hz). At 100 mol/l membrane became depolarized to about –50 mV and action potentials could no longer be elicited. Further study was focussed on effects on outward currents, mostly activated at a frequency of 0.05 Hz. Transient outward current (i_to) was completely blocked at 100 mol/l and half-maximal inhibition occurred at about 14 mol/l. Inwardly rectifying potassium current (i_K1) was reduced to 47% of reference at 100 mol/l. An initially activating outward current at positive membrane potentials (i_inst) was reduced to 73% at 100 mol/l. Time-dependent (delayed) outward current (i_K) was on the average not affected up to 100 ol/l. Besides inhibition of repolarizing outward currents YS 035 completely blocked pacemaker current (i_f) at 100 mol/l and half-maximal reduction was achieved at 5 mol/l. YS 035 (1–100 mol/l) did not clearly affect time constants of activation at selected test potentials (I_K: +35 mV; i_f: –90 mV) or inactivation (i_to: 0 mV). Voltage-dependent control mechanisms of currents (it_to, i_f) were not influenced by YS 035 but the amount of available current was reduced.In conclusion, the verapamil derivative YS 035 inhibited pacemaker current and potassium outward currents which correlated to a prolongation of cardiac action po tentials. Electrophysiological actions of the compound favour it to be tested in vivo as an antiarrhythmic drug candidate. Send offprint requests to U. Borchard at the above address