Capsaicin pretreatment modifies hydrogen sulphide-induced pulmonary injury in rats.

One of the major target organs of hydrogen sulphide gas is the lung. Exfoliation of upper respiratory epithelia and pulmonary edema are prominent effects. Various neuropeptides contained in afferent C-fibres are intimately associated with the epithelia of the conducting airways and are liberated upon exposure to noxious gases. We sought to determine their role in the pathogenesis of hydrogen-sulphide-induced pulmonary injury by pretreating rats with the neurotoxin, capsaicin, which is known to ablate a subpopulation of vagal afferent C-fibres. Groups of capsaicin and saline (control) pretreated Fischer 344 rats were exposed to an edemogenic concentration of hydrogen sulphide (525-559 mg/m3) for 4 hr. Mortality was significantly greater (p less than 0.01) in the capsaicin treated rats (12/12) compared to the control animals (2/12). Pulmonary injury was also more severe in the capsaicin pretreated animals as assessed by lung water content, histological grade of pulmonary edema and protein in the broncho-alveolar fluid. Animals depleted of substance P exhibited a significantly greater (p less than 0.01) degree of bronchial epithelial cell exfoliation and ulceration following exposure to hydrogen sulphide. These experiments indicate that capsaicin sensitive sensory nerves may play a major role in pulmonary defense against the effects of inhaled toxic gases such as hydrogen sulphide.     

Sensitivity, specificity, and predictive values of the Limulus lysate assay for detection of exclusion of gonococcal cervicitis

The Limulus amoebocyte lysate (LAL) assay was evaluated for its ability to detect or exclude gonococcal cervicitis in two groups of women. The first (positive) group consisted of 100 untreated women who were referred to the venereal disease clinic with culture-proven gonococcal cervicitis. The second (negative) group consisted of 50 normal volunteers who were evaluated on two separate occasions. In the first group, Gram stains and repeat cervical cultures were 53 and 93% sensitive, respectively. In the second group, Gram stains and cultures were negative. For the LAL assay, ectocervical mucus was removed with a sponge, and a depyrogenated cotton-tipped swab was then used to collect endocervical specimens. The swab was placed in 1 ml of diluent (1:1 dilution), and serial twofold dilutions were made and tested for endotoxin by the LAL assay. Incubation was carried out at 37 degrees C for 30 min; positive or negative results were indicated by gelation or lack of gelation, respectively. At a dilution of 1:256, sensitivity and specificity of the LAL assay were 57 and 99%, respectively. The positive predictive values ranged from 36.5 to 97.4% for theoretical prevalence rates of 1 to 40%. At a dilution of 1:8, the sensitivity and specificity were 100 and 78%, respectively. At this dilution, the negative predictive value was 100% regardless of the prevalence rate. Thus, these preliminary results show that at the higher dilution, the LAL assay was comparable to Gram stain in diagnostic accuracy of gonococcal cervicitis, and if used as a screening test at the lower dilution, a negative LAL assay would exclude women without gonococcal cervicitis.     

Leukemia following chemotherapy for ovarian cancer

An international collaborative group of cancer registries and hospitals identified 114 cases of leukemia following ovarian cancer. We investigated the possible etiologic role of chemotherapy, radiotherapy, and other factors, using a case-control study design, with three controls matched to each case of leukemia. Chemotherapy alone was associated with a relative risk of 12 (95 percent confidence interval, 4.4 to 32), as compared with surgery alone, and patients treated with both chemotherapy and radiotherapy had a relative risk of 10 (95 percent confidence interval, 3.4 to 28). Radiotherapy alone did not produce a significant increase in risk as compared with surgery alone. The risk of leukemia was greatest four or five years after chemotherapy began, and the risk was elevated for at least eight years after the cessation of chemotherapy. The drugs cyclophosphamide, chlorambucil, melphalan, thiotepa, and treosulfan were independently associated with significantly increased risks of leukemia, as was the combination of doxorubicin hydrochloride and cisplatin. Chlorambucil and melphalan were the most leukemogenic drugs, followed by thiotepa; cyclophosphamide and treosulfan were the weakest leukemogens, and the effect per gram was substantially lower at high doses than at lower doses. The extent to which the relative risks of leukemia are offset by differences in chemotherapeutic effectiveness is not known.     

MRI evaluation of topical heat and static stretching as therapeutic modalities for the treatment of eccentric exercise-induced muscle damage

The aim of this study was to monitor the effects of topical heat and/or static stretch treatments on the recovery of muscle damage by eccentric exercise. For this purpose, 32 untrained male subjects performed intense eccentric knee extension exercise, followed by 2 weeks of treatment (heat, stretch, heat plus stretch) or no treatment (control, n=8/group). Isometric strength testing, pain ratings, and multi-echo magnetic resonance imaging of the thigh were performed before and at 2, 3, 4, 8, and 15 days following the exercise. Increased T2 relaxation time, muscle swelling, pain ratings, and strength loss confirmed significant muscle damage during the post-exercise period. Pain ratings and muscle volume recovered to baseline by 15 days, although muscle strength remained lower [77 (4) vs. 95 (3) kg pre-exercise, mean (SE)] and T2 values higher [32.2 (0.8) vs. 28.6 (0.2) ms pre-exercise]. Our results indicate that heat and/or static stretching does not consistently reduce soreness, swelling or muscle damage. The practical implication of our findings is that clinicians should be aware that prescribing heat and/or static stretching following intense eccentric or unaccustomed exercise will not enhance the recovery of damaged muscles.     

A simple index relating clinical activity in Crohn's disease with T cell activation: hematocrit, frequency of liquid stools and urinary neopterin as parameters

Crohn's disease is characterized by alternating acute and quiescent periods. Several indices for activity of the inflammatory process have been proposed to have criteria for prognosis of the clinical course and therapeutic efficacy. Neopterin is specifically released from human monocytes-macrophages after induction by interferon-gamma secreted from activated human T lymphocytes. Thus, urinary neopterin excretion is elevated in diseases involving activation of cellular immunity. Fifteen clinical and laboratory parameters, including urinary neopterin levels, collected from 35 visits of patients with Crohn's disease, were compared using multiple linear regression analysis with a simple clinical activity index as reference. Prediction of clinical activity was best with the combination of hematocrit, weekly number of liquid stools and neopterin. A simple triple-parametric Crohn's disease activity index was established on the basis of this result. Its quality was tested on independent data obtained from 25 repeat visits of 13 of these patients. A comparison with the well-known Crohn's Disease Activity Index (CDAI) was performed. The results obtained with the proposed activity index were slightly better than those with the eight-parametric CDAI for the data from the first as well as from the repeat visits. We conclude that our simple index is a reliable and easily accessible measure for clinical activity in patients with Crohn's disease.     

HPRT-APRT-deficient mice are not a model for lesch-nyhan syndrome

Complete hypoxanthine-guanine phosphoribosyl-transferase (HPRT) deficiency in humans results in the Lesch-Nyhan syndrome which is characterized, among other features, by compulsive self-injurious behavior. HPRT-deficient mice generated using mouse embryonic stem cells exhibit none of the behavioral symptoms associated with the Lesch- Nyhan syndrome. Administration of drugs that inhibit adenine phosphoribosyltransferase (APRT) in HPRT-deficient mice has produced the suggestion that deficiency of APRT in combination with HPRT- deficiency in mice may lead to self-mutilation behavior [C.L. Wu and D.W. Melton (1993) Nature Genet. 3, 235-240]. To test this proposition, we bred HPRT-APRT-deficient mice. Although the doubly-deficient mice excrete adenine and its highly insoluble derivative, 2,8- dihydroxyadenine, which are also associated with human APRT deficiency, additional abnormalities or any self-injurious behavior were not detected. Thus, APRT-HPRT-deficient mice, which are devoid of any purine salvage pathways, show no novel phenotype and are not a model for the behavioral abnormalities associated with the Lesch-Nyhan syndrome as previously suggested.      

Diagnostic accuracy of bone scintigraphy in the assessment of cardiac transthyretin-related amyloidosis: a bivariate meta-analysis

Purpose

Cardiac transthyretin-related amyloidosis (ATTR) is a progressive and fatal cardiomyopathy. The diagnosis of this disease is frequently delayed or missed due to the limited specificity of echocardiography. An increasing amount of data in the literature demonstrate the ability of bone scintigraphy with bone-seeking radiopharmaceuticals to detect myocardial amyloid deposits, in particular in patients with ATTR. Therefore we performed a systematic review and bivariate meta-analysis of the diagnostic accuracy of bone scintigraphy in patients with suspected cardiac ATTR.

Methods

A comprehensive computer literature search of studies published up to 30 November 2017 on the role of bone scintigraphy in patients with ATTR was performed using the following search algorithm: (a) “amyloid” OR “amyloidosis” AND (b) “TTR” OR “ATTR” OR “transthyretin” AND (c) “scintigraphy” OR “scan” OR “SPECT” OR “SPET” OR “bone” OR “skeletal” OR “skeleton” OR “PYP” OR “DPD” OR “HMDP” OR “MDP” OR “HDP”. Pooled sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR?) and diagnostic odds ratio (DOR) of bone scintigraphy were calculated.

Results

The meta-analysis of six selected studies on bone scintigraphy in cardiac ATTR including 529 patients provided the following results: sensitivity 92.2% (95% CI 89–95%), specificity 95.4% (95% CI 77–99%), LR+ 7.02 (95% CI 3.42–14.4), LR? 0.09 (95% CI 0.06–0.14), and DOR 81.6 (95% CI 44–153). Mild heterogeneity was found among the selected studies.

Conclusion

Our evidence-based data demonstrate that bone scintigraphy using technetium-labelled radiotracers provides very high diagnostic accuracy in the non-invasive assessment of cardiac ATTR.

     

Molecular diagnosis of non-deletion SMA patients using quantitative PCR of SMN exon 7

The telomeric survival motor neuron (SMN^T gene is a valuable molecular diagnostic tool for childhood-onset spinal muscular atrophy (SMA) as homozygous deletions of SMN^T exon 7 (Δ7SMN^T) are present in ∼94% of patients. In this report, we provide the first comprehensive study of 32 unrelated non-deletion SMA patients. Quantitative polymerase chain reaction (PCR) studies established that 90% had two intact copies of SMN^T exon 7 suggesting that that these patients do not have 5q SMA. Once 5q SMA is confirmed, the SMN^T gene can be screened for subtle mutations. Using single strand conformation analysis, we identified two missense mutations (P245L and Y272C) in exon 6 of the SMN^T gene of two SMA patients shown to have a single copy of SMN^T exon 7. Y272 is most likely critical for SMN^T function as it is target for recurring mutations and is associated with type I SMA. These results emphasize the need for dosage analysis in the differential diagnosis of 5q SMA in non-deletion patients, consistent with extensive clinical heterogeneity and some genetic heterogeneity in this disease. Homozygosity or heterozygosity for a Δ7SMN^T allele confirms the diagnosis of 5q SMA with greater precision than clinical examination alone. Received July 14, 1997; Revised and Accepted July 15, 1997     

Mental health and social security: the case of the Incapacity Benefit in Northern Ireland

Although mental illness affects people from all income levels, a significant proportion of discharged psychiatric patients rely heavily on the benefit system. Therefore, changes in benefit entitlement are of great concern to these people who already find this system difficult to use. In the summer of 1995, using both focus groups and individual interviews, the views of 35 individuals with mental health problems and of five organizations involved in advocacy work were sought on the introduction of the Incapacity Benefit. These views raised serious questions about the extent to which the benefit system meets the needs of claimants with mental health problems, on the relevance of the models of disability used in sickness benefits, and on the impact of the Incapacity Benefit and the Job Seeker's Allowance on people with mental health problems and confirmed the need for further research.     

The role of the family for behavioral outcome in children and adolescents following traumatic brain injury

This study assessed the behavioral outcome of 51 children with traumatic brain injury (TBI) up to 2 years following injury. Children with severe injuries, but not those with mild or moderate injuries, were reported by parents to have a greater incidence of behavior problems following TBI. Regression analyses indicated that the presence of a partner for the primary caregiver of the child and the acute emotional reaction of the parent to the injury were both predictive of child behavioral outcome, although not by 2-year follow-up. These findings suggest that parental coping resources may impact on the development of child behavioral sequelae following TBI, emphasizing the role of the family in the child's response and the importance of supportive intervention.