Necrotizing fasciitis: a deadly infection

Necrotizing fasciitis (NF) is a life-threatening condition, consisting of a soft-tissue infection with rapidly progressive, widespread fascial necrosis. NF may be caused by a wide variety of microbes. Indeed, NF may be an infection of one species of bacteria or may be polymicrobial. Prompt diagnosis and treatment are essential. Surgical debridement and antibiotic therapy are the primary treatment options.     

Abnormal Schwann Cell-Axon Interaction In EBF-2 "Knock Out" Mice

Sometimes standard sensory nerve conduction studies show normal results in patients with definite symptoms of sensory polyneuropathy. This is usually explained because standard neurophysiological tests evaluate only large myelinated fibers and do not assess the slowest conducting fibers, more distal segments of the nerves and tactile receptors. Tactile stimulation is a test, not routinely available, that assesses the function of tactile receptors and conduction of fibers that are depolarized by these receptors. During conventional sensory nerve conduction studies (in patients and healthy subjects) through surface electrodes, where we slowly increased the intensity of the stimulus, we occasionally observed a sensory response characterized by a particular morphology with two peaks. After several experiments (performed in the neurophysiological laboratories of Catholic University of Rome and of University of Uppsala) we argued that the double component of the response is the expression of the stimulation of tactile receptors (and depolarization of their related fibers). Therefore an electrical stimulation through conventional EMG equipment allows us to assess function of tactile receptors (and related nerve fibers). This observation may have important diagnostic application in clinical practice to evaluate suspected polyneuropathies negative to neurophysiological conduction studies.     

A predictive model combining human epididymal protein 4 and radiologic features for the diagnosis of ovarian cancer

Objective

Ovarian cancer is the leading cause of death in women with gynecologic cancer. CA125 is the commonly used biomarker in the diagnosis of ovarian cancer, but has limitations in both sensitivity and specificity. Human Epididymal secretory protein (HE4) is a promising biomarker and is included in the Risk of Ovarian Malignancy Algorithm (ROMA) score, which is suggested to further increase the diagnostic accuracy than either marker alone. However, information from ultrasound and CT-scan is not included in this algorithm. This study evaluated the diagnostic accuracy of HE4 in the pre-operative diagnosis of ovarian cancer and the predictive values of biomarkers, ultrasound and CT-scan and combinations hereof.

Methods

HE4 and CA125 were measured in 361 subjects (34 benign, 147 ovarian cancer and 180 controls). Sensitivity, specificity and area under the curve (AUC) for CA125, HE4, ROMA and RMI scores were calculated using the receiver operating characteristic (ROC) methodology. The additional predictive value of ultrasound or CT-scan to the individual markers was analyzed using logistic regression.

Results

The sensitivity in predicting ovarian cancer of CA125 was 91% and of HE4 90%. The specificity was 65% and 97% respectively. HE4 demonstrated the highest discrimination (ROC-AUC = 0.96), compared to ROMA, RMI and CA125 (AUC = 0.95, 0.89 and 0.90 respectively). ROMA did not improve when it was combined with different ultrasound factors. The presence of intra-abdominal metastasis on CT-scan improved the discriminative potential of HE4 (p = 0.0004).

Conclusion

HE4 in combination with CT-scan may be incorporated in the diagnostic work-up in women with a pelvic mass.     

Nerve sparing radical hysterectomy: latest developments and historical perspective

Autonomic nerve damage during surgery is thought to play a crucial role in the aetiology of bladder dysfunction, sexual dysfunction and colorectal motility disorders which are seen in patients after radical hysterectomy. In order to prevent these complications, Japanese gynaecologists introduced a surgical technique with preservation of the pelvic autonomic nerves in the 1960s. In the 1980s the first English paper was published. Since then several surgical approaches have been described, i.e. liposuction, electrical stimulation to locate nerves intra-operatively and laparoscopically assisted techniques. Recently, more attention is being paid to the importance of sparing the sympathetic hypogastric nerve. All authors report results on small cohorts of patients. The incidence of urinary dysfunction seems very low after nerve sparing. Sparing the autonomic nerves during radical hysterectomy seems feasible and safe in both Japanese and Western patients. Literature review does not provide strong clues for a compromised radicality and cure due to nerve sparing. Future larger clinical trials will have to decide whether the technique of nerve sparing radical hysterectomy could be implemented as a standard treatment for cervical cancer patients.     

DMBT1 expression is down-regulated in breast cancer

Background  

We studied the expression of DMBT1 (deleted in malignant brain tumor 1), a putative tumor suppressor gene, in normal, proliferative, and malignant breast epithelium and its possible relation to cell cycle.     

Human papillomavirus type 16-positive cervical cancer is associated with impaired CD4+ T-cell immunity against early antigens E2 and E6

Cervical cancer is the possible outcome of genital infection with high-risk human papillomavirus (HPV) and is preceded by a phase of persistent HPV infection during which the host immune system fails to eliminate the virus. Fortunately, the majority of genital HPV infections are cleared before the development of (pre)malignant lesions. Analysis of CD4+ T-helper (Th) immunity against the E2, E6, and E7 antigens of HPV16 in healthy women revealed strong proliferative E2- and E6-specific responses associated with prominent IFN-gamma and interleukin 5 secretion. This indicates that the naturally arising virus-induced immune response displays a mixed Th1/Th2 cytokine profile. Of all HPV16+ cervical cancer patients, approximately half failed to mount a detectable immune response against the HPV16-derived peptides. The other half of the patients showed impaired HPV16-specific proliferative responses, which generally lacked both IFN-gamma and interleukin 5. This indicates that the HPV16-specific CD4+ T-cell response in cervical cancer patients is either absent or severely impaired, despite a relatively good immune status of the patients, as indicated by intact responses against recall antigens. It is highly conceivable that proper CD4+ T-cell help is important for launching an effective immune attack against HPV because infection of cervical epithelia by this virus is, at least initially, not accompanied by gross disturbance of this tissue and/or strong proinflammatory stimuli. Therefore, our observations concerning the lack of functional HPV16-specific CD4+ T-cell immunity in patients with cervical cancer offer a possible explanation for the development of this disease.     

Adrenomyeloneuropathy--report on a family.

A family is reported in which there is one case of adrenomyeloneuropathy, one case of Addison's disease and at least three heterozygous females with spastic paraparesis and peripheral neuropathy. Adrenomyeloneuropathy has not been reported previously in Scandinavia. The differences in the clinical picture between the sexes and at different ages are emphasized. Elevation of the levels of very-long-chain fatty acids in plasma is a characteristic feature of the disease and confirms the diagnosis. Some recent reports in the literature seem to provide some hope that the clinical manifestations of adrenomyeloneuropathy/adrenoleukodystrophy may be prevented.     

EVALUATION OF THE EFFECTIVENESS OF TREATMENT ON ADULT HEIGHT PROGNOSIS IN DISORDERS WITH ADVANCED AND RETARDED BONE AGE Height and Height Velocity related to Chronological or to Bone Age

Different growth parameters and their graphical presentation in disorders with advanced and retarded bone age are discussed. Their usefulness for the evaluation of the effect of treatment on growth and maturation is compared. In precocious puberty, more information is obtained when height is plotted against bone age instead of chronological age. It is more reasonable from a physiological standpoint to plot height velocity against bone age rather than chronological age. For the evaluation of the efficiency of treatment on adult height prognosis in precocious puberty, two possibilities are proposed: height velocity expressed as height increment per bone age year, or the quotient height age increment/bone age increment. However, where skeletal maturation is severely retarded, as in hypopituitary growth retardation, these growth parameters should be related in the conventional way to chronological age, rather than to bone age.     

Tiredness in Dutch family practice. Data on patients complaining of and/or diagnosed with "tiredness"

BACKGROUND: Research including patients from the entire tiredness spectrum in family practice is needed. OBJECTIVES: Our aim was to provide routine family practice data on (i) relationships between the RFE (reason for encounter) and the diagnosis "tiredness"; (ii) duration, number of encounters and family physician's (FP's) interventions in episodes of care of tiredness; and (iii) sex/age and co-morbidity of patients diagnosed with "tiredness". METHODS: Routine episode of care data from the Transition Project, coded comprehensively with the International Classification of Primary Care (ICPC), were used. (i) A 16 year database (1985-2000, 58 FPs, 504 145 episodes of care, 168 550 patient years) for calculating "prior probabilities" with (diagnostic) odds ratios. (ii) A "basic population" extracted from that 16 year database of patients listed for an entire 4 year period (1997-2000; n = 12 292). RESULTS: The RFE tiredness resulted in a variety of diagnoses, but most frequently (43%) in "tiredness". Most odds ratios were low or negative. Of episodes of care of tiredness, 90% started with the RFE tiredness; 72% required one encounter only, and 90% lasted <6 months. In the 4 year period, 21% of patients first presented with tiredness, and 12% were diagnosed with tiredness; both groups were skewed towards women. Average co-morbidity in tired patients (16.6) was higher than in other visiting patients (10.4), and contained more tiredness-related conditions. FPs' interventions were mainly blood test, physical exam and advice; few referrals occurred. CONCLUSIONS: For many diagnoses, the RFE tiredness hardly contributes to the Bayesian posterior probability. FPs react differently to the RFE tiredness in cases in which they diagnose the patient with "tiredness" from how they react in other cases. The characteristics of ICPC and the Dutch health care system resulted in a full integration of tiredness as an RFE and as a freestanding episode of care in the context of family practice.