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Biomedical subjects

J Cohen

Publications and source records attributed to J Cohen.

At least 325 records · Page 18Linked to original sources
PubMed1999

Fourth branchial arch sinus: clinical presentation, diagnostic workup, and surgical treatment.

OBJECTIVES/HYPOTHESIS: Abnormalities of the fourth branchial arch are much less common than those of the second arch and present in a different manner. The authors report their experience with five cases of fourth arch sinuses. METHODS: Retrospective chart review of patients at a tertiary care center. RESULTS: All patients presented in the first or second decade of life, and all but one had left-sided neck involvement. Four patients presented with recurrent low neck inflammatory episodes, and one with respiratory compromise. Diagnostic studies performed included ultrasound, computed tomography (CT) scan, barium swallow, magnetic resonance imaging, and fine-needle aspiration. Barium contrast studies and CT scan were the most useful in demonstrating a fourth arch sinus tract preoperatively. Surgical treatment with an emphasis on complete exposure of the recurrent laryngeal nerve and exposure of the lateral piriform sinus to facilitate complete sinus tract excision was successful in all patients. CONCLUSION: The clinical history of recurrent low neck inflammatory episodes in young patients, especially on the left side, should raise the suspicion of this entity. Investigation using barium swallow in combination with CT scanning is useful. Excision of the sinus tract taking care not to injure the recurrent laryngeal nerve is curative.

Adolescent↗
PubMed1999

Impact of protease inhibitors on the outcome of human immunodeficiency virus-infected patients with chronic diarrhea.

OBJECTIVE: The effect of protease inhibitors on the outcome of chronic HIV-related diarrhea is unknown. The aim of this study was to compare the response to treatment of chronic HIV-related diarrhea, recurrence of diarrhea, and survival in a large cohort of individuals taking protease inhibitors to the outcome in similar patients not receiving protease inhibitors. METHODS: We reviewed the medical records of all patients referred between October 1993 and October 1996 at Bellevue Hospital for endoscopic evaluation of chronic HIV-related diarrhea after negative stool examination. Only patients presenting after December 1995 received protease inhibitor therapy. Follow-up data were obtained from chart review and direct telephone contact. The success of antidiarrheal therapy was compared between protease inhibitor and nonprotease inhibitor groups for patients receiving pathogen-specific therapy and for those with no pathogens found on endoscopy. RESULTS: Two hundred eighty-two of 307 patients evaluated for chronic diarrhea were followed for a mean of 69.9+/-34.1 weeks. Patients receiving protease inhibitors had a significantly higher rate of successful response to antidiarrheal therapy (62.0% vs 33.5%, p < 0.001). Protease inhibitors were associated with a significant decrease in stool frequency (4.8+/-4.5 vs 3.4+/-4.6 bowel movements per day, p = 0.01), an increase in weight (2.4+/-5.9 vs -1.6+/-6.2 kg, p < 0.001), a decrease in recurrence of diarrhea (34.8% vs 15.3%, p = 0.02), and a longer mean survival (148 vs 118 weeks, p = 0.002). CONCLUSIONS: Protease inhibitors significantly improve the outcome of antidiarrheal therapy and survival in patients with chronic HIV-associated diarrhea.

AIDS-Related Opportunistic Infections↗
PubMed1999

Growth-phase-dependent expression of virulence factors in an M1T1 clinical isolate of Streptococcus pyogenes.

The effect of growth phase on expression of virulence-associated factors was studied by Northern hybridization in an M1T1 clinical isolate of Streptococcus pyogenes. Expression of M protein, C5a peptidase, and capsule was maximal in the exponential phase of growth, while streptococcal pyrogenic exotoxins A and B and mitogenic factor were maximally expressed in later phases of growth.

Bacterial Proteins↗
PubMed1999

Protection against development of otitis media induced by nontypeable Haemophilus influenzae by both active and passive immunization in a chinchilla model of virus-bacterium superinfection.

Three separate studies, two involving active-immunization regimens and one involving a passive-transfer protocol, were conducted to initially screen and ultimately more fully assess several nontypeable Haemophilus influenzae outer membrane proteins or their derivatives for their relative protective efficacy in chinchilla models of otitis media. Initial screening of these antigens (P5-fimbrin, lipoprotein D, and P6), delivered singly or in combination with either Freund's adjuvant or alum, indicated that augmented bacterial clearance from the nasopharynx, the middle ears, or both anatomical sites could be induced by parenteral immunization with P5-fimbrin combined with lipoprotein D, lipoprotein D alone, or the synthetic chimeric peptide LB1 (derived from P5-fimbrin), respectively. Data from a second study, wherein chinchillas were immunized with LB1 or lipoprotein D, each delivered with alum, again indicated that clearance of nontypeable H. influenzae could be augmented by immunization with either of these immunogens; however, when this adjuvant was used, both antibody titers in serum and efficacy were reduced. A third study was performed to investigate passive delivery of antisera directed against either LB1, lipoprotein D, nonacylated lipoprotein D, or a unique recombinant peptide designated LPD-LB1(f)2,1,3. The last three antiserum pools were generated by using the combined adjuvant of alum plus monophosphoryl lipid A. Passive transfer of sera specific for LB1 or LPD-LB1(f)2,1,3 to adenovirus-compromised chinchillas, prior to intranasal challenge with nontypeable H. influenzae, significantly reduced the severity of signs and incidence of otitis media which developed (P </= 0.001). Collectively, these data indicate the continued merit of further developing LB1 and LPD-LB1(f)2,1,3 as components of vaccines for otitis media.

Amino Acid Sequence↗
PubMed1999

Heterotypic protection and induction of a broad heterotypic neutralization response by rotavirus-like particles.

The recognition that rotaviruses are the major cause of life-threatening diarrheal disease and significant morbidity in young children has focused efforts on disease prevention and control of these viruses. Although the correlates of protection in children remain unclear, some studies indicate that serotype-specific antibody is important. Based on this premise, current live attenuated reassortant rotavirus vaccines include the four predominant serotypes of virus. We are evaluating subunit rotavirus vaccines, 2/6/7-VLPs and 2/4/6/7-VLPs, that contain only a single VP7 of serotype G1 or G3. In mice immunized parenterally twice, G3 virus-like particles (VLPs) induced a homotypic, whereas G1 VLPs induced a homotypic and heterotypic (G3) serum neutralizing immune response. Administration of three doses of G1 or G3 VLPs induced serum antibodies that neutralized five of seven different serotype test viruses. The inclusion of VP4 in the VLPs was not essential for the induction of heterotypic neutralizing antibody in mice. To confirm these results in another species, rabbits were immunized parenterally with two doses of 2/4/6/7-VLPs containing a G3 or G1 VP7, sequentially with G3 VLPs followed by G1 (G3/G1) VLPs, or with live or psoralen-inactivated SA11. High-titer homotypic serum neutralizing antibody was induced in all rabbits, and low-level heterotypic neutralizing antibody was induced in a subset of rabbits. The rabbits immunized with the G1 or G3/G1 VLPs in QS-21 were challenged orally with live G3 ALA rotavirus. Protection levels were similar in rabbits immunized with homotypic G3 2/4/6/7-VLPs, heterotypic G1 2/4/6/7-VLPs, or G3/G1 2/4/6/7-VLPs. Therefore, G1 2/4/6/7-VLPs can induce protective immunity against a live heterotypic rotavirus challenge in an adjuvant with potential use in humans. Following challenge, broad serum heterotypic neutralizing antibody responses were detected in rabbits parenterally immunized with G1, G3/G1, or G3 VLPs but not with SA11. Immunization with VLPs may provide sufficient priming of the immune system to induce protective anamnestic heterotypic neutralizing antibody responses upon subsequent rotavirus infection. Therefore, a limited number of serotypes of VLPs may be sufficient to provide a broadly protective subunit vaccine.

Animals↗
PubMed1999

Adjunctive therapy in sepsis: a critical analysis of the clinical trial programme.

Despite intensive efforts, the development of novel drugs for the treatment of sepsis has proved to be extremely difficult. A large number of clinical trials have ended in failure. A critical analysis of this record suggests that there is no single reason for these problems. Rather, the explanation lies in part with unexpected failures in the drugs themselves, and in part with the difficulties of trial design in this particular group of patients. In future, trials in this area are likely to be more highly focused, with even stricter protocol definitions to try and ensure a homogeneous patient population.

Endotoxins↗
PubMed1999

A phase I safety and immunogenicity trial with the candidate malaria vaccine RTS,S/SBAS2 in semi-immune adults in The Gambia.

RTS,S is a novel pre-erythrocytic malaria vaccine based on the circumsporozoite surface protein (CSP) of Plasmodium falciparum linked to hepatitis B surface antigen (HBs) and combined with a novel adjuvant system (SBAS2). We have conducted a Phase I trial with three doses of this vaccine given at 0, 1, and 6 months to 20 semi-immune, adult, male volunteers in The Gambia to assess its safety and immunogenicity. Eighteen of the 20 volunteers completed the study. There were no clinically significant local or systemic adverse events following each vaccination. Hematologic and biochemical indices before and two weeks after each vaccination showed no evidence of toxicity. Antibody titers to both CSP and HBs showed a significant increase after vaccination; these were the largest after the third dose. We conclude that the RTS,S/SBAS2 vaccine induces no significant toxicity in this semi-immune population and produces significant increases in antibody titers to CSP.

Adolescent↗
PubMed1999

Behaviour of DRG sensory neurites at the intact and injured adult rat dorsal root entry zone: postnatal neurites become paralysed, whilst injury improves the growth of embryonic neurites.

The dorsal root entry zone is a PNS-CNS junction between Schwann cells and astrocytes, defining the site where dorsal root ganglia (DRG) axons enter the adult mammalian spinal cord. Following dorsal root injury (rhizotomy), DRG axons regenerate within the PNS environment of the root but stop at the DREZ and fail to re-enter the spinal cord. We have used an in vitro model to compare how neurites growing from embryonic (E13) and postnatal (P0 and adult) DRG neurons behave at the uninjured and rhizotomized adult rat DREZ. We find that both freshly dissected and conditioned-lesioned postnatal DRG neurons seldom grow neurites across cryosections of the uninjured or rhizotomized DREZ. However, embryonic DRG neurons more readily grow neurites across cryosections of the uninjured and 7-day post-lesion (dpl) DREZ and are dramatically better able to cross the 21 dpl DREZ. This enhanced growth was abolished by co-incubation with a function-blocking antiserum to beta1-integrin receptors, whilst immunoreactivity for some beta1-integrin ligands (tenascin-C and fibronectin) increased at the DREZ by 21 dpl, suggesting that beta1-integrin ligands may stimulate the growth of embryonic neurites across the 21 dpl DREZ. Fluorescence time-lapse video-microscopy was used to record the behaviour of dye-labelled postnatal DRG neurites as they encounter the uninjured adult DREZ in vitro. Neurites rarely turned around at the DREZ, but instead became paralysed. Of a variety of chemical modifications to uninjured DREZ cryosections, only treatment with methanol, chloroform, or the protease inhibitor D-phe-pro-arg chloromethylketone hydrochloride (PPACK, 100 microM) caused any increase in the proportion of postnatal neurites which crossed the DREZ.

Animals↗
PubMed1999

Preventive care of the elderly.

BACKGROUND: As the population ages, there is an increasing proportion of the population which will be reflected in the nature of general practice. OBJECTIVE: To supply a framework for family physicians to intervene, prevent or minimise the many adverse factors affecting the function of our elderly patients. DISCUSSION: Whilst organic disease is important in itself, loss of function is more important to our patients and general practitioners should be in the forefront of efforts to improve their quality of life.

Aged↗
PubMed1999

Why homebirth?

Explore the source record for details and available documents.

Choice Behavior↗
PubMed1999

Trapidil inhibits monocyte chemoattractant protein-1 and macrophage accumulation after balloon arterial injury in rabbits.

Trapidil (triazolopyrimidine) is an antiplatelet agent that acts in part as a phosphodiesterase inhibitor and as a competitive inhibitor of the platelet-derived growth factor (PDGF) receptor. Trapidil has been shown to attenuate intimal hyperplasia in rat and hamster models of balloon arterial injury and to inhibit restenosis after percutaneous transluminal coronary angioplasty in several small clinical trials. Monocyte chemoattractant protein-1 (MCP-1) is a PDGF-inducible monocyte chemoattractant that is thought to play a particularly important role in recruiting monocyte/macrophages to sites of atherosclerosis and vessel injury. We hypothesized that, because of its ability to antagonize PDGF-mediated events, trapidil would inhibit the synthesis of MCP-1 and decrease macrophage accumulation in the injured arterial wall. Hypercholesterolemic rabbits were treated with trapidil (60 mg/kg/day subcutaneously) the day before and then daily for 6 days after balloon injury of the femoral artery; control rabbits received vehicle only. Trapidil resulted in a 75% reduction in MCP-1 expression and macrophage accumulation in the arterial wall 7 days after injury. This study suggests that trapidil has potent anti-inflammatory properties and that its activity in attenuating intimal hyperplasia may be in part attributed to its effects on macrophage accumulation.

Animals↗