Hepatitis E: An Underdiagnosed,Emerging Infection in Nonendemic Regions

Although hepatitis E virus (HEV) is the primary cause of enterically transmitted acute hepatitis and jaundice in developing countries, locally acquired HEV infections are increasing in nonendemic countries. As such, HEV is emerging as an underdiagnosed cause of infection. This report describes three clinically variable cases of HEV infection with unusual clinical presentations. These cases highlight the fact that HEV should be considered in the differential diagnosis of patients with unexplained hepatitis (acute or chronic) with or without extrahepatic manifestations. HEV should also be considered in patients with persistently elevated liver enzymes who have not travelled to known HEV-endemic regions. Lack of knowledge among physicians and an absence of standardized diagnostic tests may result in increased morbidity and mortality from HEV infection.     

Complications associated with central venous catheters inserted in critically ill neonates

OBJECTIVE: To assess the incidence and spectrum of complications associated with central venous catheter (CVC) placement in the critically ill infant. DESIGN: A prospective study of all babies hospitalized in a neonatal intensive care unit (NICU) from January 1989 to December 1989. Potential risk factors associated with infection were evaluated by a case-control comparison. SETTING: Conducted at a university-affiliated, tertiary care community hospital. PATIENTS: Neonates requiring intensive care and a central venous catheter. Controls consisted of noninfected babies. RESULTS: Of 263 critically ill neonates, only 13 (4.9%) required a CVC insertion. Seventeen CVCs were placed in these 13 neonates for a total duration of 600 days (median, 32 days/cannula). Fifteen (88%) of these cannulas had one or more complications during its catheter life including dislodgement or leakage (53%), occlusion or thrombosis (47%), infections (29%), or minor bleeding (12%). Five babies (29%) developed 6 episodes of bloodstream infection including 3 sporadic cases due to Staphylococcus epidermidis and a cluster of fungemia due to Malassezia furfur associated with lipid emulsion therapy. Infants with a CVC-associated infection were a younger gestational age (24 weeks versus 32 weeks, p = .04) and weighed less at birth (580 g versus 1285 g, p = .02). The overall rate of bloodstream infection was one episode per 100 days of catheter use. CONCLUSIONS: CVCs may be lifesaving to a critically ill neonate, but complications occur frequently. Use must be restricted to infants in whom alternate delivery routes of intravenous therapy or support are otherwise unavailable.     

Clericuzio type poikiloderma with neutropenia is distinct from Rothmund-Thomson syndrome

Two siblings from a consanguineous family presented with a poikiloderma of limbs and face, plantar keratoderma, and toenail pachyonychia. Neutropenia and neutrophil dysfunction with impairment of the respiratory burst and bacterial killing resulted in frequent respiratory tract infections. A bronchocentric granulomatous pneumonia was a fatal complication. The clinical presentation is consistent with Clericuzio type poikiloderma with neutropenia. Literature review identified several additional probable patients. Genetic linkage analysis excluded the locus of the RECQL4 gene, mutations in which have been described in some patients with the Rothmund-Thomson poikiloderma syndrome. This report confirms the clinical and genetic identity of the Clericuzio type of poikiloderma with neutropenia syndrome.     

Clinical validation of a new real-time PCR assay for detection of enteroviruses and parechoviruses, and implications for diagnostic procedures.

BACKGROUND: Enteroviruses (EV) and parechoviruses (HPeV) are the most common causes of aseptic meningitis, encephalitis and sepsis-like syndrome in neonates. Detection by nucleic acid amplification methods improves patient management. OBJECTIVE: Development of a real-time PCR assay on a LightCycler for simultaneous detection of EV, HPeV and an internal control to monitor inhibition. STUDY DESIGN: We investigated the value of the new assay, prospectively, in a variety of samples from patients suspected of having viral meningitis or sepsis-like syndrome. RESULTS: The assay detected 64 EV serotypes and HPeV types 1-4. Of 186 patients, 63 (33.9%) were EV positive and 18 (9.7%) HPeV positive in one or more samples. In 43 of 159 feces and 6 of 57 throat samples viral culture and PCR were positive. With real-time PCR 27 extra EV and 19 HPeV positives were found. Blood and CSF were present from 33 patients. In 19 patients blood and CSF were positive, one was only positive in CSF, two were only positive in blood, 11 were negative. From 96 patients CSF and/or blood samples were tested and compared to results in throat and/or feces samples. Forty patients were EV-PCR and 14 HPeV-PCR positive in blood and/or CSF. All of these were confirmed by a positive PCR for the respective virus in feces and/or throat. CONCLUSIONS: Simultaneous detection of EV and HPeV with this two-step real-time PCR is specific, faster and more sensitive than viral culture. All systemic infections (blood or CSF positive) were confirmed in feces. Culture is no longer necessary for clinical diagnosis and should only be performed on PCR-positive samples to obtain isolates for typing purposes. Application of this assay is an important improvement for patient management since the outcome of the analysis is available within the time frame of clinical decision-making.     

Views of Dutch general practitioners about premenstrual symptoms: A qualitative interview study

BackgroundGeneral practitioners (GPs) encounter women suffering from premenstrual symptoms. Often women with premenstrual problems experience little understanding from GPs. Views of GPs will influence their approach to these women and their care. Insight into these views is lacking but could help in designing educational programmes for GPs.ObjectivesTo explore the views of Dutch GPs towards aetiology, diagnostic process, and preferred treatment of premenstrual symptoms.MethodsIn 2017, we conducted a qualitative, semi-structured, interview survey among 27 GPs, varying in age, gender, and practice setting.ResultsImportant themes emerged from the interviews: ‘no need for a symptom diary,’ ‘PMS defined as illness’ exclusively in case of disruption of normal functioning, and ‘symptomatic treatment’ as preferred approach. Most GPs considered PMS to be a physiological phenomenon, with taking history as an adequate diagnostic tool. Almost all GPs regarded a normal cyclical hormonal cycle as causal; many also mentioned the combination with personal sensitivity. Some pointed to a dividing line between physiological condition and illness if women could not function normally in daily life. Lastly, the approach GPs preferred was focussing on relieving symptoms of individual patients. In addition to explaining the hormonal cycle and lifestyle advice, all GPs advocated oral contraceptives, and if necessary psychological support. GPs expressed negative feelings about prescribing antidepressants.ConclusionGPs considered physiological changes and personal sensitivity as aetiological factors. We recommend more training to improve GPs knowledge and more insight into the burden of women with PMS. A symptom diary is an essential diagnostic tool for GPs.     

An immunocytochemistry study comparing the occurrence of neuroactive substances in the nervous system of cercariae and metacercariae of the eye flukeDiplostomum spathaceum

The nervous system of two larval stages (cercariae, metacercariae) of eye flukeDiplostomum spathaceum was investigated immunocytochemically by the application of antisera to the amino acid glutamate and to neuropeptides isolated from invertebrates (Mollusca) and from vertebrates to whole-mount preparations. In cercariae, positive immunoreactivity (IR) was observed with antisera raised against Catch-relaxing peptide (CARP), FMRFamide, -caudodorsal cell peptide (-CDCP), substance P, vasotocin, and vasopressin. In metacercariae, in addition to positive staining with these antisera, the ones raised against glutamate, APGWamide, caudodorsal cell hormone I (CDCH-I), and small cardiac peptide B (SCP_B) also gave positive IR in the nervous system. In the two larval stages the most extensive pattern of IR was observed with anti-FMRFamide and anti-CARP. In the nervous system of metacercariae the same immunoreactive neurosubstances appeared to be present as in that of cercariae. The increase in the variety of immunoreactive neurosubstances in the more complex nervous system of metacercariae is discussed in relation to parasite development and to host adaptation.     

A quantitative study in the rat on the relationship between imipramine levels in brain and serum

Serum and brain levels of the tricyclic antidepressant drug imipramine (IMI) were studied in the rat under a variety of conditions. IV doses (range 1 nmol kg^-1 to 15 mol kg^-1, 350 ng–5mg kg^-1) and administered 5 min before death, were linearly correlated with IMI levels in serum, frontal cortex, and cerebellum. In this experiment, the highest levels of IMI were achieved in the frontal and occipital cortex and the lowest levels were found in the brain stem. The regional distribution was more even in rats pretreated with thiopental or -hydroxybutyric acid, drugs that alter cerebral blood flow. After 20 min or more, tracer amounts of IMI injected IV to IMI-pretreated rats [1 or 17 days, daily dose 2×36 mol kg^-1 (10 mg kg^-1), last dose 89 mol kg^-1 (25 mg kg^-1), 2–3 h before death] exhibited a distribution pattern in serum and various brain regions similar to that of the unlabeled drug. In the latter experiments, content (per volume) of the tracer or unlabeled IMI was more than 25-fold higher in various brain areas than in serum. It is concluded that despite large differences in drug levels in serum or brain, a close relationship is maintained under the conditions studied.deceased     

Intratumoral administration of recombinant human interleukin 12 in head and neck squamous cell carcinoma patients elicits a T-helper 1 profile in the locoregional lymph nodes.

The objective of this Phase II study was to evaluate the pharmacodynamic and immune effects of intratumorally administered recombinant human interleukin-12 (IL-12) on regional lymph nodes, primary tumor, and peripheral blood. Ten previously untreated patients with head and neck squamous cell carcinoma were injected in the primary tumor two to three times, once/week, at two dose levels of 100 or 300 ng/kg, before surgery. We compared these patients with 20 control (non-IL-12-treated) patients. Toxicity was high, with unexpected dose-limiting toxicities at the 300 ng/kg dose level. Dose-dependent plasma IFN-gamma and IL-10 increments were detected. These cytokine levels were higher after the first injection than after the subsequent injections. A rapid, transient reduction in lymphocytes, monocytes, and all lymphocyte subsets, especially natural killer cells, was observed, due to a redistribution to the lymph nodes. In the enlarged lymph nodes of the IL-12-treated patients, a higher percentage of natural killer cells and a lower percentage of T-helper cells were found compared with control patients. The same pattern was detected in the infiltrate in the primary tumor. Real-time semiquantitative PCR analysis of peripheral blood mononuclear cells in the peripheral blood showed a transient decrease of T-bet mRNA. Interestingly, the peripheral blood mononuclear cells in the lymph nodes showed a 128-fold (mean) increase of IFN-gamma mRNA. A switch from the Th2 to a Th1 profile in the lymph nodes compared with the peripheral blood occurred in the IL-12-treated patients. In conclusion, in previously untreated head and neck squamous cell carcinoma patients, recombinant human IL-12 intratumorally showed dose-limiting toxicities at the dose level of 300 ng/kg and resulted in measurable immunological responses locoregionally at both dose levels.