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Biomedical subjects

D M McCarthy

Publications and source records attributed to D M McCarthy.

At least 19 recordsLinked to original sources
PubMed1996

A randomized study of VAD therapy with either concurrent or maintenance interferon in patients with newly diagnosed multiple myeloma.

This randomized study was designed to determine whether response to VAD chemotherapy could be prolonged by using rh alpha-2b-interferon (IFN) at a dose of 3 mU three times per week, either concurrently with VAD (VIC) or as maintenance after completion of VAD (VIF). Maintenance IFN was given for 9 months in order for the duration of IFN therapy to be similar in both groups. 72 patients were randomized between December 1988 and August 1993. The majority of patients had poor prognostic features. The objective response rate was similar in each arm, 78% in VIF and 77% in VIC. Of the 56 responders, 33 have relapsed, three died in remission, and 18 proceeded to high-dose therapy, withdrew for other reasons or were lost to follow-up and were censored from analysis at the relevant time point. Only two patients remain in remission (both in partial remission). Median PFS was 15 months for both VIF and VIC, compared with 16.5 months for a historic control group treated with VAD alone (n.s.). The estimated median survival in VIF was 43 months and in VIC 22 months, compared with 45 months in the historic controls (n.s.). These findings indicate that neither maintenance nor concurrent IFN prolongs response to VAD.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

The pronator quadratus: a distinct forearm space?

The pronator quadratus sign is associated with fractures of the distal radius and ulna and is believed to be due to accumulation of fluid within the pronator quadratus muscle. This anatomic study based on dye injection and x-ray film examination shows that the pronator quadratus occupies a distinct forearm space without intramuscular communication.

Cadaver↗
PubMed1995

Effect of partial laceration on the structural properties of the canine FDP tendon: an in vitro study.

The appropriate management of partially lacerated digital flexor tendons in zone 2 is controversial. Tenorrhaphy has been advocated by some on the basis of improving tendon gliding function, whereas others have recommended foregoing tenorrhaphy because of the negative impact of repair on the tensile strength of the tendon. In light of this division, we undertook a study of the effect of varying degrees of partial laceration on the structural properties of the canine flexor digitorum profundus tendon. Lacerations up to 90% of the tendon cross-sectional area were surgically fashioned. We conclude that the structural properties of the tendon are increasingly adversely affected as laceration size increases. However, based on previous estimates of in vivo forces, even tendons with up to 60% cross-sectional area involvement may be strong enough to withstand an early active mobilization regimen. Further, we conclude that neither calipers nor naked-eye estimates provide a reliable means of assessing the extent of tendon laceration.

Animals↗
PubMed1995

Self-reported drinking and alcohol-related problems among early adolescents: dimensionality and validity over 24 months.

OBJECTIVE: Researchers rely on adolescents' self-reports of alcohol consumption and alcohol-related problems, despite little evidence concerning their validity. We assessed the reliability and validity of adolescents' self-reports, employing collateral validation and focusing on the understudied transitional years of early adolescence. METHOD: Subjects were 214 boys and 247 girls who participated in school-wide surveys that assessed drinking, drunkenness and alcohol-related problems each year for 3 years. These measures were validated by collateral (peer) reports and by separate, 7-day drinking calenders. Internal consistency and test-retest reliability were also assessed. RESULTS: Results replicated findings with older adolescents that drinking/drunkenness and alcohol-related problems fall on two partially overlapping dimensions. Scales assessing each dimension had moderate to high internal consistency and high test-retest stability. Correlations with collateral reports were relatively strong for the drinking/drunkenness scale, moderate for a dichotomous variable reflecting the presence or absence of alcohol-related problems, and more modest for the alcohol-related problems scale. Correlations with diary reports of drinking behavior were strong for drinking/drunkenness. Results generally replicated across gender and over time. CONCLUSIONS: Researchers can have some confidence in the reliability and validity of early adolescents' survey self-reports, particularly of alcohol consumption (alcohol-related problems occurred with low base rates, perhaps limiting validity coefficients). Because drinking/drunkenness and alcohol-related problems shared 30% of their variance, factors other than consumption (e.g., personality factors) apparently influenced the experience of alcohol-related problems.

Adolescent↗
PubMed1995

Mechanisms of mucosal injury and healing: the role of non-steroidal anti-inflammatory drugs.

Biological insights into injurious effects of non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin (ASA), on mucosal protection and repair, are largely from studies of acute injury. That chronic ulceration is similar is not established. NSAIDs directly injure tissues, including endothelia, and at the same time impair the operation of many of the processes that normally contribute to mucosal protection, whatever the injurious agent. Many protective processes are mediated through prostaglandins, whose synthesis is abolished by inhibition of the constitutive isoenzyme, cyclooxygenase I (COX I) or Prostaglandin H-Synthase1 (PGHS1). The aims of therapy are aimed at inhibiting the inducible isozyme cyclooxygenase II (COX II) or prostaglandin-H Synthase2 (PGHS2), which contributes to prostanoid synthesis at sites of inflammation. Newer NSAIDs, selectively inhibiting COX II, promise to revolutionize the treatment of inflammatory disease while reducing mucosal injury. Meanwhile, there is increasing evidence that direct injury to both mucosae and endothelia is mediated by free-radical species, exacerbated by reduced blood flow, and by the local release of inflammatory and other mediators, which accentuate vascular leakage and hemorrhage, and cause intravascular aggregation of blood elements, stasis, hypoxia, and additional free-radical injury. The NSAIDs also inhibit epithelial cell division and the angiogenesis critical to healing and repair.

Animals↗
PubMed1995

Quality of Life: a critical assessment.

There is increased recognition that Health-Related Quality of Life (HRQOL) or Health Status (HS) is important and, together with other outcome measures, highly relevant to evaluating both the impact of diseases, and the individual and societal benefits/costs of different interventions, management strategies and health policies: yet many problems remain. While the methodology of HS assessment has been extensively studied and greatly improved, implementation has lagged in practice and in clinical research. Resources have been forthcoming for studies which promise increased profit (e.g., marketing advantage) or cost-containment, but funding has been scarce when the focus is on quality of care, patient utility, or health issues such as screening, monitoring or disease prevention. There are well-defined limitations associated with various assessment instruments, with interpretation of scores, and with the lack of relationship between disease activity and overall HRQOL. For these reasons, to date, HS assessment has not been clearly shown to be useful to physicians or to benefit patient outcomes to a degree sufficient to justify the burden of widespread use. Physicians remain cautious of the processes, especially with those aspects that relate to values, autonomy, equity, legal liability and potential for abuse.

Attitude of Health Personnel↗
PubMed1995

Stimulation of goblet cell mucous secretion by activation of nerves in rat conjunctiva.

An epithelial debridement wound, as a stimulus to the cornea, causes conjunctival goblet cell mucous secretion in that eye. To determine if this stimulation of secretion is neurally mediated, rats were anesthetized and the local anesthetic lidocaine (1%) or buffer alone was administered topically and/or subconjunctivally for 15 min. A corneal epithelial debridement wound was made in one eye. The contralateral eye served as the control. After 5-120 min, animals were sacrificed and inferior bulbar conjunctival buttons removed. Mucus in the goblet cells was stained with Alcian blue and periodic acid-Schiff's reagent to indicate mucin-containing goblet cells. The number of mucin-containing goblet cells/0.16 mm2 was determined by light microscopy; a decrease in number indicated an increase in mucous secretion. Stimulation by corneal wounding induced goblet cell mucous secretion in that eye. Secretion was observed as rapidly as 5 min after stimulus and for as long as 120 min. Topical application of lidocaine, subconjunctival injection of lidocaine, or a combination of both inhibited wound-induced stimulation of mucous secretion. We conclude that conjunctival goblet cell mucous secretion can be neurally mediated and could serve as an immediate response to protect the ocular surface.

Administration, Topical↗
PubMed1995

Localization of nerves adjacent to goblet cells in rat conjunctiva.

Neural stimulation of the cornea induces conjunctival goblet cell mucous secretion. Immunofluorescence microscopy was used to determine if nerves are present near conjunctival goblet cells and what types of nerves are present. In euthanized rats, the local anesthetic lidocaine (1%) was placed topically on the ocular surface for 10 min to prevent goblet cell mucous secretion. The ocular surface tissues were removed and either fixed in formaldehyde and then frozen, or frozen first and then post-fixed in formaldehyde. Tissue was sectioned and nerves localized by indirect immunofluorescence microscopy, using antibodies to synaptophysin (indicates nerve, independent of type), vasoactive intestinal peptide (VIP, indicates parasympathetic nerves), tyrosine hydroxylase (TH, indicates sympathetic nerves), dopamine beta-hydroxylase (DBH, indicates sympathetic nerves), phenylethanolamine-N-methyltransferase (PNMT, indicates sympathetic nerves), and calcitonin gene-related peptide (CGRP, indicates sensory nerves). Goblet cells were identified by phase-contrast microscopy. Synpatophysin-containing nerves were present in the basolateral region of conjunctival goblet cells clusters. Nerve fibers immunoreactive to VIP were found in the conjunctiva along the epithelial-stromal junction and around the basolateral aspect of goblet cell clusters. Nerve fibers immunoreactive to TH and DBH were detected surrounding goblet cells and in the conjunctival stroma. Nerve fibers immunoreactive to CGRP were detected in the epithelium and at the epithelial stromal junction, but were not localized near goblet cell clusters. CGRP-containing nerve fibers were also detected in the conjunctival stroma under the epithelium. We conclude that efferent parasympathetic and sympathetic, but not afferent sensory, nerves appear to be located adjacent to conjunctival goblet cell clusters. Activation of efferent parasympathetic and sympathetic nerves could directly stimulate conjunctival goblet cell mucous secretion. Antidromic activation of afferent sensory nerves releasing neurotransmitters could stimulate goblet cell secretion by a paracrine mechanism.

Animals↗
PubMed1995

A cadaveric and radiologic assessment of catheter placement for the measurement of forearm compartment pressures.

The diagnosis of compartment syndrome is essentially a clinical one. In recent years, much interest and research has focused on the development of intracompartmental pressure monitoring devices to help in the diagnosis of this condition. Proper placement of the catheter is essential for accurate monitoring, because an incorrect result is potentially more dangerous than no reading at all. In the forearm, measurement in the flexor digitorum profundus is thought to be a more sensitive way of assessing rising pressure. One of the risks of catheter placement is inadvertent damage to a neurovascular structure, particularly when monitoring pressures in deeper muscle bellies. Standard anatomic texts and outpatient magnetic resonance scans of the forearm were studied to define a safe pathway for the introduction of a catheter into the volar forearm. An approach from the midline to the ulna, between the tendons of the flexor carpi radialis and palmaris longus, seemed the safest. Ten cadaveric forearms had 100 cc of gastrograffin injected into the deep forearm through a dorsal approach. The median and ulnar nerves were cannulated with a fine wire from the elbow to the wrist. Two cannulae were passed, using the suggested approach, at 2 locations between the wrist and the mid forearm. All limbs then were scanned with computed tomography, and the images were reviewed. In all forearms, the cannulae passed between the median and ulnar nerves into the belly of the flexor digitorum profundus and posed no risk to the neurovascular structures.

Cadaver↗
PubMed1994

Left ventricular assist without thoracotomy: clinical experience with the Dennis method.

A method to provide left ventricular circulatory assistance without thoracotomy was developed and implemented in 2 patients. The left atrium is cannulated from the neck by passing a catheter across the interatrial septum (Dennis technique) using fluoroscopic and echocardiographic imaging. To facilitate ambulation, the arterial catheter is connected to the right axillary artery. Left atrial to axillary arterial flow is produced by a centrifugal pump. Two patients were perfused at 2.7 to 3.5 L/min for 5 and 6.5 days. One patient had successful coronary angioplasty during perfusion and remains alive 1 year later. The other patient died of sepsis and anuria that preceded implementation of circulatory assistance. The Dennis method of continuous left ventricular circulatory assistance avoids thoracotomy, requires a minimal operation, is portable and inexpensive, uses widely available equipment, and is particularly suitable for patients in cardiogenic shock after acute myocardial infarction. The method is safe and cost-effective, and merits wider application in selected patients.

Angioplasty, Balloon, Coronary↗
PubMed1994

Evidence that iron stores regulate iron absorption--a setpoint theory.

To evaluate the concept of a predetermined "setpoint" for iron stores, 20 healthy elderly individuals (12 blood donors and 8 nondonors) were studied to examine the effects of changes in iron stores on iron absorption. Oral iron-absorption tests revealed a statistically significant increase (P < 0.001) in iron absorption in donors, 7.4 +/- 3.6% (mean +/- SD) compared with 2.5 +/- 1.4% in nondonors. In a comparison of percent iron absorption with changes in baseline iron stores, a statistically significant correlation was noted (r2 = 0.702, P < 0.001). Thus, reductions in iron stores were correlated with increases in iron absorption. Basal gastric acid output was found to be within normal limits (1.62-10.20 mmol/h) in all elderly subjects and unrelated to iron stores. These findings are consistent with iron absorption being regulated according to the degree of depletion of iron stores from predonation values and is consistent with a proposed setpoint theory of iron stores.

Absorption↗
PubMed1993

Maintenance therapy for peptic ulcer--who needs it?

Until recently, peptic ulcer disease implied lifelong susceptibility to symptomatic, asymptomatic or complicated ulcer recurrences. Only about 50% of the ulcers seen endoscopically ever become symptomatic. Asymptomatic ulcers appear clinically unimportant, except in the setting of aspirin (ASA) or NSAID use, where they may lead without warning to fatal complications. Until recently, ulcer disease could not be cured medically: no drug has been shown to prevent ulcer complications occurring in patients taking ASA/NSAIDs. Low-dose maintenance therapy with H2-antagonists reduces recurrences and complications, but is expensive and requires indefinite use. Other anti-ulcer drugs have not been studied enough to conclude with confidence that they are similarly effective. Over 80% of recurrences are infrequent and can be treated when they occur n 20% of ulcer patients have 3 recurrences/yr, ulcer complications, or such poor health that recurrence might prove fatal. Ulcers recurring during maintenance therapy rarely complicate and heal with increasing and maintaining dosage. Eradication of H. Pylori (HP) infection, while difficult, abolishes most recurrences without maintenance therapy. Maintenance therapy is therefore indicated principally when HP can not be eradicated. Surgery is rarely required for uncomplicated disease.

Adult↗
PubMed1993

Mixed haplotypes and autoimmunity.

Why do (NZB x NZW)F1 mice develop an autoimmune lupus-like syndrome? The second exons of the class II genes of NZB and NZW are identical to their counterparts of H-2d and H-2u haplotypes. Several lines of evidence suggest that this allows the production of a mixed haplotype molecule, I-E alpha dE beta z, and that this molecule plays a key role in the development of autoimmunity.

Amino Acid Sequence↗
PubMed1992

Rhinocerebral mucormycosis following bone marrow transplantation.

Rhizopus oryzae was the causative organism in a fatal case of rhinocerebral and then pulmonary mucormycosis in a patient cured of her underlying leukaemia by bone marrow transplantation. We discuss the risk factors involved and the need for maintaining a high index of suspicion of fungal infection in the late post-transplant period.

Adult↗
PubMed1992

The long-term results of enzymic fasciotomy.

We reviewed ten hands in nine patients who had enzymatic fasciotomy for Dupuytren's contracture, with an average follow-up of 6.5 years. While all patients were initially satisfied with the results, the disease recurred quite rapidly to pre-operative levels in seven patients over the subsequent two to three years.

Dupuytren Contracture↗
PubMed1992

Nonsteroidal anti-inflammatory drugs--the clinical dilemmas.

Physicians using nonsteroidal anti-inflammatory drugs (NSAIDs) are concerned that effective anti-inflammatory doses cause few gastrointestinal side effects. Among the causes of discontinuing therapy, upper gastrointestinal symptoms and the development of 'ulcer' complications are major concerns; endoscopic findings in asymptomatic users are not. Initial symptoms, poorly correlated with endoscopic findings, are relieved by anti-ulcer drugs and ameliorate with time of NSAID use in most patients. Symptoms accompanied by epigastric tenderness, or unrelieved by H2 antagonists, or resulting in cessation of NSAID therapy are more predictive of underlying ulcers. Complications probably arise in several ways, including as hemorrhages due to interference with platelet function, and as complications due to exacerbations of underlying ulcer disease or of ulcers caused by the NSAIDs. Pathogenesis and effective prophylaxis (yet to be established) may therefore vary in different patients, a clinical dilemma.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1991

Sucralfate.

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Cross Infection↗