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Biomedical subjects

D Lynch

Publications and source records attributed to D Lynch.

At least 19 recordsLinked to original sources

The opiate addiction test: a clinical evaluation of a quick test for physical dependence on opiate drugs.

1. Mydriasis (pupil dilation) in response to conjunctivally applied naloxone hydrochloride has been demonstrated using an innovative electronic binocular pupillometer in 40 opiate dependent patients, on maintenance methadone treatment. 2. No pupillary response to naloxone was seen when an identical procedure was carried out in a control population of 12 healthy volunteers. 3. After a baseline measurement of pupil size, two drops of naloxone hydrochloride were instilled into the conjunctival sac of one eye. Serial binocular pupillometry was then carried out at 5, 10, 15, 20, 25, 30, 35, 40 and 45 min post-instillation. 4. Discriminant analysis between the control and patient groups showed that the false negative rate (error of misclassification to the wrong population) was lowest (20%) at 40 min post-eyedrop instillation, with no false positives in the control group. 5. The study has therefore shown an improvement in the previously reported false negative rate (25%) [1,2], of the conjunctival naloxone test of opiate dependence, with the use of our innovative electronic binocular pupillometer.

Adult

Anorexia nervosa in 'non-white' populations.

BACKGROUND: Comparisons were made between two groups of anorectic patients, 'non-white' and 'white', on a variety of clinical and social characteristics. METHOD: The study is based on a 34-year long database (1960-93) associated with a national tertiary referral centre. Thirty-six non-white patients meeting DSM-III-R criteria for anorexia nervosa (AN) and five with 'partial syndrome' are compared with a white group comprising 944 patients with full syndrome. RESULTS: The main finding is clinical similarity between the two groups, extending to social class and pathological patterns of family relationship. The non-whites are shorter in stature (P = 0.004) and report earlier menarche (P = 0.004); they are younger at presentation (P < 0.001), somewhat less emaciated, and practice veganism slightly more commonly; they less often acknowledge sensitivity to 'fatness' (P < 0.003). This sensitivity was exposed later whenever treatment involved substantial weight gain. The proportion of non-white cases accepted for assessment has not changed in respect of year of onset (around 6%) for the last 20 years, or year of presentation (around 6-7%) over the last 15 years. There was a tendency for non-white patients to be referred earlier in their illness. CONCLUSIONS: The clinical and background profiles of non-white and white anorectics are generally similar. The numbers arising and presenting have not changed recently. Non-white patients apparently have as ready access as white patients to assessment and treatment by us.

Adolescent

Risk factors at delivery and the need for skilled resuscitation.

A prospective study was devised to investigate how risk factors at delivery contribute to outcome at birth as measured by the type of resuscitation required ('skilled' or 'not skilled') and the Apgar score. In addition the number of unexpected 'crash calls' was recorded. In a 3-month sample, neonatologists attended 494 (38.6%) of 1279 deliveries. Of those attended, 188 (37.2%) required skilled resuscitation including 5 of 20 crash calls. Four risk factors at delivery were associated with skilled resuscitation: meconium, emergency caesarean section, prematurity and multiple births. Following the implementation of a revised resuscitation policy, a subsequent 3-month sample showed that 299 (24.8%) of 1206 deliveries were attended. A total of 175 (58.5%) required skilled resuscitation including 8 of 16 crash calls. The revised resuscitation policy, in our unit, proved to be safe and led to a reduction of attendance by neonatologists at deliveries.

Apgar Score

The expression of a NMDA receptor gene in guinea-pig myenteric plexus.

Muscle tension studies of guinea-pig ileum longitudinal muscle-myenteric plexus preparations suggest that the N-methyl-D-aspartate (NMDA) receptor may be present in the enteric nervous system. Therefore, we investigated the expression of a gene for the NMDA receptor in guinea-pig taenia coli. The gene product was amplified using polymerase chain reaction (PCR) and its synthesis localized using in situ hybridization. A NMDA receptor PCR product from the myenteric plexus was demonstrated with nearly identical sequence characteristics to that in the brain. In situ hybridization studies identified myenteric neurons which express NMDA receptor messenger RNA. Demonstration of the genetic expression of the NMDA receptor supports a role for glutamate as a neurotransmitter in the enteric nervous system.

Amino Acid Sequence

Characterization of the human CD27 ligand, a novel member of the TNF gene family.

CD27 is a lymphocyte-specific member of the TNF/NGF-R family that is highly induced on T cells after TCR stimulation, primarily on lymphocytes belonging to the unprimed CD45RA+ subset. However, after prolonged activation both in vivo and in vitro, CD27 expression is gradually switched off. In search of physiologic signals that influence CD27 expression, we found that B cell lines can mediate down-regulation of CD27 surface expression on activated T cells via direct cell-to-cell contact and that preincubation of activated T cells with CD27 mAbs prevented this modulation. Based on these observations, we hypothesized that a ligand for CD27L is expressed on B cell lines and that ligand interaction would result in down-modulation of the molecule from the T cell surface. To identify this putative CD27L, mAbs were raised against the Burkitt cell line Ramos and screened for their ability to block down-modulation of CD27 on activated T cells. Using this approach, we isolated a mAb, designated 2F2, that inhibits CD27 down-regulation in a dose-dependent manner. We demonstrate that this mAb recognizes CD27L as it 1) reacted to mouse fibroblasts expressing the recently cloned CD27L, a novel surface-expressed member of the TNF gene family, and 2) prevented binding of a soluble CD27-Fc construct to a CD27L expressing cell line. Down-regulation of CD27 from the T cell surface by recombinant CD27L was shown to be at least partially caused by release of soluble CD27. The 2F2 mAb enabled us to begin to analyze the biochemical properties, tissue distribution, and function of the CD27L on human cells. From cell lysates of 125I surface-labeled Burkitt cells a complex immunoprecipitation pattern with dominant bands of 29, 55, and 122 to 127 kDa was obtained using the 2F2 mAb. Phenotypical analyses showed that freshly isolated lymphocytes lacked CD27L expression, but that expression of the molecule could be induced after in vitro stimulation of T and B cells. No expression was found on cells of the myeloid lineage or on endothelial cells. Finally, blocking of naturally expressed CD27L by the 2F2 mAb exerted a potent inhibitory effect on the proliferation of T cells in response to allogeneic B cells and PHA. The data presented in this paper identify CD27 and its ligand as potentially important structures involved in cellular interactions between T and B lymphocytes.

Animals

Water content, lens hardness and cataract appearance.

Hardening of a cataractous lens is associated with the clinical appearance of brunescence and advancing age. Alterations in the nature and concentration of proteins, lens fibre compaction and other biochemical changes may all be contributing factors towards increased hardness. As the nucleus confers most of the rigidity to the lens and water content decreases towards the centre of the nucleus, the hardness might be thought to be related to total water content. To study the relationship between water content, hardness and the clinical appearance of cataract, 135 lenses were obtained from eyes undergoing extracapsular cataract surgery. The cataracts were assessed and classified pre-operatively. Lens hardness was determined by a specially designed guillotine and water content was measured by weighing the lens before and after desiccation. A regression analysis was carried out to look at the variation of lens water content with hardness, degree of nuclear sclerosis, extent of cortical and posterior subcapsular cataract, vacuolation and age. Multivariate analysis of data demonstrated a relationship between lens hardness and lens water content, degree of nuclear sclerosis and age (R2 = 0.59). An association could not be detected between lens water content and age, degree of nuclear sclerosis, extent of cortical and posterior subcapsular cataract and vacuoles. This study suggests that hardening of the lens is reflected by a respective decrease in water content. Increased hardness is associated with coloration and advancing age.

Adult

"Birds of a feather...": behavioral concordances and preferential personal attraction in children.

The purpose of this study was to assess the extent to which preferential personal attraction was associated with behavioral similarity among newly acquainted children. Participants included 69 focal children, selected from a sample of 236 7-year-old children who met, for the first time, in same-sex quartets (n = 59) for a free-play session. Within each of these quartets, a "discriminating child" was identified; this child expressed a clear preference for one of his or her playmates over one other of her or his quartet playmates. Preference was determined sociometrically after the children became acquainted during free play. The results indicated that "discriminating" children were more behaviorally similar to preferred playmates than to nonpreferred playmates both in terms of cognitive play style and social participation. Implications of the findings are discussed in terms of the relation to the acquaintanceship process.

Child

Laparoscopic cholecystectomy in the pregnant patient.

Laparoscopic cholecystectomy has rapidly replaced open cholecystectomy as the preferred surgical treatment of symptomatic cholelithiasis. Although the indications are similar for both procedures, some surgeons believe that pregnancy is a contraindication for the laparoscopic approach. Several recent reports in the literature have shown that laparoscopic cholecystectomy can be performed safely in the pregnant patient. A review of all patients who underwent laparoscopic cholecystectomy from January 1991 to January 1993 at Scott Air Force Base (AFB) and Edwards AFB was performed. Of 248 patients reviewed, four procedures were performed in the gravid patient. All patients were operated on during the second trimester of pregnancy. Laparoscopic cholecystectomy was successful in all four. Cholangiogram was performed in two patients. No postoperative morbidity was encountered (maternal or fetal). Twenty-one cases of laparoscopic cholecystectomy in the pregnant patient, with no fetal or maternal morbidity or mortality, have been reported in the literature to date. We conclude that in selected cases, laparoscopic cholecystectomy can be performed safely during pregnancy.

Adult

Interleukin-7 retroviruses transform pre-B cells by an autocrine mechanism not evident in Abelson murine.

In this study, we have constructed retroviral vectors expressing the interleukin-7 (IL-7) cDNA and have used infection with these retroviruses to express this cytokine endogenously in an IL-7-dependent pre-B-cell line. Infection with IL-7 retroviruses, but not with a control retrovirus, resulted in the conversion of the cells to IL-7 independence. The frequency at which this occurred, together with data on vector expression levels, indicated that secondary events were required for factor independence in this system. Southern analysis showed that the IL-7-dependent clones harbored unrearranged copies of the vector proviruses. The factor-independent cells produced variable quantities of IL-7 as measured by an IL-7-specific bioassay, and their proliferation could be substantially inhibited by a neutralizing antibody directed against IL-7, indicating that a classical autocrine-mechanism was responsible for their transformation. These IL-7-independent cells were tumorigenic, in contrast to the parental IL-7-dependent cells or those infected with a control vector. These results showed that IL-7 could participate in the malignant transformation of pre-B cells. However, neither of two Abelson murine leukemia virus (A-MuLV)-transformed pre-B-cell lines expressed detectable IL-7 mRNA, at a level of sensitivity corresponding to less than one molecule of mRNA per cell. Moreover, the proliferation of the A-MuLV transformants was unaffected by addition of the IL-7 antisera under conditions in which parallel experiments with IL-7 virus-infected cells resulted in greater than 70% growth inhibition. Thus, transformation of pre-B cells by A-MuLV was not associated with a demonstrable autocrine loop of IL-7 synthesis. These results show that IL-7 can participate in the malignant transformation of pre-B cells and suggest studies aimed at assessing the role of autocrine production of IL-7 in the generation of human leukemias and lymphomas.

Animals

Two outbreaks of Legionnaires' disease in Bolton Health District.

In 1988, there were two outbreaks of legionellosis in Bolton Health District. Altogether 37 cases of Legionnaires' disease and 23 cases of non-pneumonic legionellosis were identified. Twenty-five patients with Legionnaires' disease were associated with an engineering plant, 4 with Bolton town centre, and 8 with both the plant and town centre. Twenty-two people with non-pneumonic legionellosis were linked with the engineering plant and one with the plant and the town centre. A case-control study carried out among 37 employees with legionellosis and 109 control subjects at the plant showed that infection was associated with one of the 15 cooling towers on the site. Legionella pneumophila indistinguishable by serological and genetic typing methods was isolated from this cooling tower and from sputum samples from two patients. In the town centre, no one tower was linked with infection and L. pneumophila was not cultured from any of the nine towers identified. Control measures were implemented and to date there have been no further cases of legionellosis associated with Bolton Health District.

Adult

An outbreak of Salmonella saint-paul infection associated with beansprouts.

In March 1988, there was an outbreak of infection by a strain of Salmonella saint-paul with a distinctive antigenic marker. A total of 143 reports were received between 1 March and 7 June. Preliminary investigations suggested that raw beansprouts were a possible source of infection and a case-control study confirmed the association. S. saint-paul of the epidemic type was isolated from samples of beansprouts on retail sale in different cities in the United Kingdom and from mung bean seeds on the premises of the producer who was most strongly associated with cases. In addition, Salmonella virchow PT34 was isolated from samples of raw beansprouts and was subsequently associated with seven cases of infection. Four other serotypes of salmonella were also isolated from beansprouts. On 8 April the public were advised to boil beansprouts for 15 seconds before consumption, and the premises of the one producer associated with many cases were closed. As a result of these actions there was a significant decrease in the number of infections with S. saint-paul.

Adolescent

Thoracic manifestations of Wegener granulomatosis: diagnosis and course.

A combination of cytotoxic and corticosteroid therapy has dramatically improved the long-term survival of patients with Wegener granulomatosis. With extended survival, patients now experience diverse cardiopulmonary abnormalities that represent primary or secondary manifestations of the disease or that result from diagnosis and treatment. To evaluate these abnormalities, the authors reviewed the medical histories and chest radiologic findings of 19 patients with the histologic diagnosis of Wegener granulomatosis. In these patients thoracic images demonstrated parenchymal nodules or consolidations with cavitation, diffuse interstitial disease, mediastinal or hilar adenopathy, and isolated stenoses of the larynx or tracheobronchial tree. Intrathoracic relapse occurred in 18 cases; in one-third of these patients, findings at relapse differed from those at initial presentation. Complications from diagnosis or therapy occurred in nine patients. Pulmonary infection was the most frequent complication causing morbidity and was often clinically indistinguishable from the primary disease; it complicated relapse in five patients. The successful radiologic follow-up of patients with Wegener granulomatosis requires a consideration of the varied thoracic manifestations of both the primary disease and the complications of its treatment.

Adult

Pulmonary infiltrates associated with sulindac therapy.

Pulmonary infiltrates, cough, dyspnea, and fever developed in a 62-year-old woman with chronic degenerative arthritis who had been receiving sulindac therapy for six months. Her pulmonary signs and symptoms resolved upon withholding the drug. Inadvertent rechallenge resulted in rapid recurrence of respiratory symptoms and pulmonary infiltrates. This constellation of clinical findings provides strong evidence of isolated pulmonary reactions as a complication of sulindac therapy.

Drug Hypersensitivity

Case-control study of infections with Salmonella enteritidis phage type 4 in England.

OBJECTIVE: To determine the source of indigenous sporadic infection with Salmonella enteritidis phage type 4. DESIGN: Case-control study of primary sporadic cases identified by the Public Health Laboratory Service between 1 August and 30 September 1988. SETTING: PHLS Communicable Disease Surveillance Centre, Division of Enteric Pathogens, 11 PHLS laboratories, and 42 local authority environmental health departments in England. SUBJECTS: 232 Patients (cases) with confirmed primary sporadic infection, for 160 of whom (88 female) (median age 30 years, age range 4 months to 85 years) data were obtained by questionnaire about consumption of fresh eggs, egg products, precooked chicken, and minced meat in the three days and one week before onset of the symptoms. Up to three controls, matched for neighbourhood, age, and sex (if aged greater than 11 years), were asked the same questions for the same calendar period. MAIN OUTCOME MEASURE: Association of primary sporadic infection with consumption of suspected food items. RESULTS: Illness due to S enteritidis phage type 4 was significantly associated with consumption of raw shell egg products (homemade mayonnaise, ice cream, and milk drinks containing eggs) (matched p = 0.02) and shop bought sandwiches containing mayonnaise (matched p = 0.00004) or eggs (matched p = 0.02). Illness was also significantly associated with eating lightly cooked eggs (unmatched p = 0.02), but not soft boiled eggs, and precooked hot chicken (matched p = 0.006). Reported consumption of eggs was not appreciably different between cases and controls before or after the median date of interview. CONCLUSIONS: Fresh shell eggs, egg products, and precooked hot chicken are vehicles of S enteritidis phage type 4 infection in indigenous sporadic cases. Public health education and reduction in contamination of eggs and infection of poultry with S enteritidis are needed to reduce the incidence of human infection.

Adolescent