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Biomedical subjects

C A Holden

Publications and source records attributed to C A Holden.

At least 19 recordsLinked to original sources
PubMed1997

Frozen-thawed epididymal spermatozoa for intracytoplasmic sperm injection.

OBJECTIVE: To report the fertilization rate and pregnancy results for intracytoplasmic sperm injection (ICSI) cycles using frozen-thawed epididymal spermatozoa. DESIGN: Retrospective analysis of consecutive ICSI cycles. SETTING: Tertiary referral center for infertility. PATIENT(S): Infertile couples in whom 39 patients (59 ICSI cycles) required the use of frozen-thawed epididymal spermatozoa. As no cycles were performed using fresh epididymal spermatozoa, outcomes were compared with those of 130 couples (170 ICSI cycles) using fresh ejaculated spermatozoa for severe oligoasthenozoospermia-teratozoospermia, in which < 200,000 motile spermatozoa were retrieved after Percoll density gradient centrifugation. INTERVENTION(S): Epididymal sperm aspiration during microsurgery, followed by ICSI. MAIN OUTCOME MEASURE(S): Fertilization, embryo cleavage, ET, and clinical pregnancy rates (PRs). RESULT(S): A total of 484 metaphase II oocytes were injected with frozen-thawed epididymal spermatozoa, resulting in a two-pronuclear fertilization rate per injected metaphase II oocyte of 47%, significantly lower than in cycles using fresh ejaculated spermatozoa (73%). Embryo implantation rates (12.0% versus 13.3%) and clinical PRs per transfer (18.4% versus 27.0%) were not different. When the prefreeze vitality was > 20%, compared with lower vitality, both the fertilization (56% versus 22%) and embryo cleavage (91% versus 57%) rates were significantly greater. CONCLUSION(S): The routine collection and cryopreservation of epididymal spermatozoa at microsurgery allows multiple ICSI treatment cycles with success rates similar to those of ejaculated spermatozoa. However, when the vitality of aspirated spermatozoa is < 20%, the poor fertilization rates indicate the need to consider an alternative source of viable spermatozoa.

Adult↗
PubMed1995

Clinical results from intracytoplasmic sperm injection at monash IVF.

The impact of a modification of the intracytoplasmic sperm injection (ICSI) technique on fertilization and pregnancy rates was examined in a retrospective analysis of 171 consecutive ICSI treatment cycles (156 patients). Patients were selected for ICSI on the basis of severe oligoasthenozoospermia (65 patients) or following conventional in vitro fertilization (IVF) with failed or poor fertilization (70 patients). Seven patients in which epididymal or testicular sperm was used, 10 patients with sperm antibodies and 4 patients with retrograde ejaculation or who required electro-ejaculation were also treated with ICSI. In the first 105 cycles (102 patients), single sperm, rendered immotile, were injected into the ooplasm of 979 metaphase II (M II) oocytes using an established technique (Method 1). In the following 66 cycles (513 M II oocytes injected), the ICSI procedure was modified by increased aspiration of the oolemma to ensure the intracytoplasmic deposition of sperm (Method 2). The patient groups did not differ between the two injection procedures. The normal (two pronuclear) fertilization rate increased significantly (P < 0.001) from 34.3% with Method 1 to 73.1% with Method 2, with no difference in the oocyte degeneration rate (4.3% v. 4.5% respectively). The incidence of failed fertilization was significantly (P < 0.01) reduced from 17.1% (18 cycles) to 1.6% (1 cycle) with the change in technique. As a consequence of the increased fertilization rates with Method 2, more embryos were available for assessment and transfer, and a pregnancy rate per oocyte retrieval of 21.2% was obtained for Method 2. Fertilization, embryo transfer and pregnancies were obtained in all patient groups treated with ICSI.(ABSTRACT TRUNCATED AT 250 WORDS)

Australia↗
PubMed1995

Pentoxifylline-supplemented cryoprotectant improves human sperm motility after cryopreservation.

In this study, human spermatozoa obtained from donors (n = 15) with normal semen characteristics were cryopreserved in human sperm preservation medium, supplemented with the phosphodiesterase inhibitor pentoxifylline at concentrations of 0, 1, 3 and 10 mM. The effect of pentoxifylline on cryopreserved spermatozoa was determined by monitoring changes in sperm motility and acrosome morphology by labelling the spermatozoa with fluorescein-conjugated concanavalin A lectin. Cryoprotectant supplemented with 1 mM pentoxifylline was found to improve post-thaw progressive motility from 15.3 +/- 2.4 (control) to 23.1 +/- 3.8% (P < 0.01), and total motility from 27.4 +/- 3.3 (control) to 38.2 +/- 3.9% (P < 0.05) without reducing the percentage of spermatozoa with normal acrosomal regions, and so appears useful for cryopreservation purposes. The beneficial effects of 1 mM pentoxifylline on sperm motility were shown to be maintained post-thaw over a 6 h time course. Cryoprotectant supplemented with 3 mM pentoxifylline was found to improve only post-thaw progressive motility, from 15.3 +/- 2.4 (control) to 20.7 +/- 3.0% (P < 0.05). However, cryopreservation in the presence of 10 mM pentoxifylline was found to have a significantly (P < 0.01) detrimental effect on acrosome morphology post-thaw, reducing it from 29.0 +/- 2.0 (control) to 21.0 +/- 2.4% without affecting sperm motility. This suggests that assessment of the acrosomal region may indicate subtle deleterious effects of cryoprotectant supplements that cannot be determined from post-thaw motility assessments alone. These findings differ from previous studies in that a lower concentration of pentoxifylline (1 mM) was found to be optimal for cryopreservation purposes.

Acrosome↗
PubMed1995

gamma-interferon production in atopic dermatitis shows differential modification by phosphodiesterase and prostaglandin inhibition.

Interferon-gamma (IFN-gamma) production by peripheral blood mononuclear leucocytes (MNL) is reduced in atopic dermatitis (AD) patients. This may be related to abnormalities in second messenger systems, and increased prostaglandin E2 (PGE2) release from monocytes. We compared the effects of manipulating the second messenger activity using the phosphodiesterase (PDE) inhibitor Ro 20-1724, dibutyryl cyclic adenosine monophosphate (cAMP), and cyclooxygenase inhibition of PGE2, on IFN-gamma production by cultured MNL from AD patients (n = 9) and normal controls (n = 10). Ficoll-Hypaque-separated MNL were cultured for 48 h with OKT3 stimulation, and cAMP, Ro 20-1724, or indomethacin. Supernatants were analysed for IFN-gamma by ELISA. Basal IFN-gamma was lower in AD patients, and the increase in IFN-gamma production with OKT3 was 6.5-fold greater in control subjects than patients with AD. Culture with indomethacin significantly enhanced OKT3-stimulated IFN-gamma production in both groups, whereas OKT3-stimulated IFN-gamma production was abolished with dibutyryl cAMP. IFN-gamma production was significantly lower with Ro 20-1742 in AD than in normal controls. We have shown reduced IFN-gamma release from unstimulated and stimulated MNL in AD patients compared with normal controls. The addition of indomethacin increased IFN-gamma production in both groups, although the increase was less in AD patients, suggesting an intrinsic cellular defect. IFN-gamma release from AD MNL was more sensitive to the inhibitory effects of PDE, and this may be due to increased PDE activity, or the hyperdynamic cAMP system present in atopics.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1995

Cutaneous infiltration in T-cell prolymphocytic leukaemia.

T-cell prolymphocytic leukaemia (T-PLL) is an aggressive leukaemia accounting for over 30% of all mature T-cell malignancies. We describe the clinical manifestations and histology of cutaneous involvement in a series of 92 patients with T-PLL. Of the 92 patients, 26 (28%) had cutaneous involvement, and in 23 this was present at the time of the diagnosis of the leukaemia. Skin manifestations included a diffuse infiltrated erythema, infiltration localized to the face and ears, nodules and erythroderma. Histology showed a perivascular and periappendageal dermal infiltrate of lymphoid cells with the morphology of prolymphocytes. An early skin biopsy in these patients should help to reveal the underlying diagnosis.

Adult↗
PubMed1994

Dowling-Degos disease associated with Kitamura's reticulate acropigmentation.

A family with features of Dowling-Degos disease associated with Kitamura's reticulate acropigmentation is reported. There have been three previous reports describing the association of these two conditions. Our family extends four generations, and the proband shows some unusual features not typical of Dowling-Degos disease or Kitamura's reticulate acropigmentation.

Female↗
PubMed1993

Are pigmented lesion clinics worthwhile?

To assess the effect of a pigmented lesion clinic on referral patterns and thickness of melanoma at presentation, we have compared data from the centralized pathology services of the adjacent health authorities of Wandsworth, and Merton and Sutton. Both districts were the subject of a CRC public awareness campaign in 1987, but only Wandsworth is served by a pigmented lesion clinic. All patients presenting with malignant melanoma were included; from 1981 to 1990 for Wandsworth, and from 1984 to 1990 for Merton and Sutton. The Breslow thickness and clinic source of all melanomas was documented. Approximately equal numbers of melanomas were seen in the two districts, with no obvious difference in the numbers of thin (< 1.5 mm thick) 'good prognosis' tumours. Both districts saw an increase in the total number of tumours, and the number of thin tumours, after the CRC publicity campaign. However, there was considerable cross-boundary referral to the pigmented lesion clinic in Wandsworth, with 60% of all melanomas coming from outside the district. The presence of a pigmented lesion clinic within a given district confers no obvious benefit with regard to the number of thin, 'good prognosis' melanomas being seen as a whole, but the cross-boundary referral pattern suggests that it fulfils a demand from both general practitioners (GPs) and patients, and it does provide a centralized source for the collection of much-needed data.

Health Education↗
PubMed1993

Atopic dermatitis--messengers, second messengers and cytokines.

Atopic dermatitis (AD) shows many complex and interacting abnormalities of pharmacology, immunology and cellular control. Recent research in atopy has concentrated on abnormalities of cytokine production by T-helper cells. It is possible that cytokine imbalance causes many of the pharmacological and immunological changes seen in the disease. However, studies of second messenger control of cytokine release show that different second messenger signals may relate to the release and activation of particular cytokines. This review summarizes these findings and discusses how the second messenger defects reported in AD may relate to the abnormal cytokine profiles and the pharmacological abnormalities seen in the condition.

Cyclic AMP↗
PubMed1992

Influence of a capacitation period on human sperm acrosome loss.

The present study investigates whether a 5 hour capacitation period modifies the ability of human spermatozoa to undergo induced acrosomal loss. Human sperm acrosomal loss was induced by treatment with either the calcium ionophore A23187, low concentrations of the phospholipid dilauroylphosphatidylcholine (PC12), or 2 hours incubation in conditioned medium prepared from human cumulus cells (CM/CC). The use of a dual staining method (FITC-ConA and Hoechst 33258) for simultaneous assessment of acrosomal status and viability demonstrated that induction of acrosomal loss with calcium ionophore was not dependent on a capacitation period. A short (5 hour) incubation period was not sufficient to induce acrosomal loss with CM/CC above spontaneous acrosome reaction rates in medium alone. A significant capacitation-dependent increase (P < 0.05) in acrosomal loss was observed when human spermatozoa were incubated with PC12. Induction of acrosomal loss of capacitated human spermatozoa with PC12 therefore provides a simple assay for the simultaneous assessment of human sperm capacitation and the acrosome reaction in vitro.

Acrosome↗
PubMed1992

Comparative study of calcipotriol (MC 903) ointment and betamethasone 17-valerate ointment in patients with psoriasis vulgaris.

BACKGROUND: Topical vitamin D analogues have been reported to be an effective treatment in patients with psoriasis. Comparative studies with existing treatments are required. OBJECTIVE: Our purpose was to compare the effectiveness of calcipotriol (50 micrograms/gm) and betamethasone 17-valerate (1 mg/gm) ointments twice daily in the treatment of stable plaque psoriasis. METHODS: This study was a randomized, double-blind comparison over 6 weeks in 409 patients. Efficacy, as measured by the Psoriasis Area and Severity Index (PASI), and safety were assessed at 2, 4, and 6 weeks. RESULTS: Reduction of PASI was statistically significant at all time points for both treatments but there were no significant between-treatment differences. At the completion of 6 weeks of treatment, the mean PASI reduction was 5.50 for calcipotriol and 5.32 for betamethasone (95% confidence interval [CI] -0.40 to 0.78). Analysis of patient assessment at 6 weeks showed clearance or marked improvement in 61.2% of the calcipotriol patients and 50.5% with betamethasone (95% CI 1.4 to 20.8). Calcipotriol produced significantly more local side effects (19.5% compared with 3.9%, p less than 0.001); however, these were minimal leading to withdrawal in only 3 of 205 patients. CONCLUSION: Calcipotriol ointment was as effective as betamethasone 17-valerate ointment as measured by the PASI and superior as measured by self-assessment in patients with stable plaque psoriasis. Both treatments were well tolerated.

Betamethasone Valerate↗
PubMed1992

Acral persistent papular mucinosis.

The case is reported of a 56-year-old man with an unusual papular eruption on the forearms with deposition of mucin in the dermis. The clinical and histopathological features were consistent with acral persistent papular mucinosis, a recently described focal type of cutaneous mucinosis.

Forearm↗
PubMed1992

Measurement of phosphoinositide-specific phospholipase C activity in mononuclear leucocytes from atopic and normal subjects.

The intracellular inositol pathway is an important route for cell activation and relies on the stimulation of membrane-bound phosphoinositide-specific phospholipase C (PLC). Previously we have shown abnormalities of inositol metabolism in mononuclear cells (MNL) in atopic dermatitis (AD) using an indirect method. We now describe a direct method of measuring PLC activity in membrane and cytosol preparations of MNL in AD. We compare PLC activity in AD with that in normal controls and examine the effect of substrate concentration and nucleotide stimulation on the system. Our findings show increased membrane-bound PLC activity in AD compared with normal controls. Non-specific stimulation of AD PLC activity by nucleotides suggests that the enzyme of atopics is more sensitive to substrate-driven activity than that of non-atopics.

Adenosine Triphosphate↗
PubMed1992

Increased urine neopterin levels in psoriasis.

The production of neopterin closely reflects activation of T-lymphocyte-mediated immunity. Oxidized and reduced forms of urine neopterin were measured by reversed-phase ion-pair high-performance liquid chromatography in patients with moderate to severe chronic plaque psoriasis (n = 40), and in a heterogeneous group of patients (n = 14) with cutaneous T-cell malignancies (CTCM). Results were compared with healthy non-psoriatic control subjects (n = 30). Neopterin levels were repeated after a course of ultraviolet B therapy (UVB) plus topical tar or dithranol, or photochemotherapy (PUVA), in 12 psoriatic patients. Fully oxidized urine neopterin levels and neopterin/creatinine ratios were significantly elevated in the psoriatic group compared with controls (P < 0.002, P < 0.05) but not in the CTCM group. Both neopterin and its creatinine ratio were significantly reduced by treatment (P < 0.05, P < 0.01). Psoriasis area and severity index scores (PASI) correlated strongly with urine neopterin levels (P < 0.001). These findings indicate that urine neopterin concentrations may be a marker of psoriatic disease activity, and further support the importance of activated T lymphocytes in the pathogenesis of psoriasis.

Adolescent↗
PubMed1992

Coexistent cutaneous T-cell lymphoma and B-cell chronic lymphocytic leukaemia.

Three patients with cutaneous T-cell lymphoma (CTCL) are reported who had concurrent B-cell chronic lymphocytic leukaemia (B-CLL). The separate lineage and clonal nature of the individual lymphoid malignancies were confirmed by gene-rearrangement analysis. The chronology of the illnesses did not support the hypothesis that CTCL predisposes to the development of B-cell proliferative disorders. There was no clear association with immunosuppressive therapy, and HTLV-1 studies were negative in all patients. Consequently, we speculate that a lymphoid stem cell defect, which may lead to the development of either aberrant B- or T-cell clones, may be responsible for such cases of dual lymphoid neoplasia.

Aged↗
PubMed1992

Acquired eruptive haemangiomata with primary biliary cirrhosis and prostatic carcinoma.

We report a male patient with acquired eruptive haemangiomata occurring in association with primary biliary cirrhosis and a carcinoma of the prostate. The possible explanations include an abnormality of sex sterol metabolism associated with his liver disease, secretion of an angiogenic factor by his carcinoma or a combination of the two mechanisms.

Aged↗