Immunocryosurgery for basal cell carcinoma: results of a pilot, prospective, open-label study of cryosurgery during continued imiquimod application

Background/aim  Theoretical considerations support the combination of cryosurgery and topical imiquimod to treat basal cell carcinomas (BCC). The aim of the present study was to test the feasibility and efficacy of 'cryosurgery during continued imiquimod application' ('immunocryosurgery') to treat 'high-risk-for-recurrence' BCCs.
Methods  Thirteen patients with 21 biopsy-proven tumours (4 of 21 relapses after prior surgery) were included. After 2–5 weeks (median, 3) of daily 5% imiquimod cream application, the tumours were treated by liquid N₂ cryosurgery (spray, two cycles, 10–20 s) and imiquimod was continued for additional 2–12 weeks (median, 4). The outcome after at least 18 months of follow-up (18–24 months) is currently reported.
Results  Nineteen of 21 tumours responded promptly to immunocryosurgery; two tumours required additional treatment cycles to clear. Thus, the clinical clearance rate was 100%. Only 1 of 21(5%) tumour relapsed after at least 18 months of follow-up (cumulative efficacy: 95%).
Conclusions  'Immunocryosurgery' is a promising non-surgical combination modality to treat 'high-risk-for-recurrence BCCs'. Initial evidence is suggestive of an at least additive effect of the two combined modalities. Further studies comparing immunocryosurgery directly with cryosurgery and imiquimod monotherapies will confirm the reported results.     

Low plasma growth hormone binding protein in IDDM.

Poorly controlled insulin-dependent diabetes mellitus (IDDM) is associated with elevated basal plasma growth hormone (GH), disproportionally low insulin-like growth factor I (IGF-I) levels, and impaired somatic growth. These derangements in the GH-IGF axis imply a state of GH resistance. The mechanism of GH resistance is unknown; it may involve a defect at the level of the GH receptor, unresponsiveness due to a postreceptor defect in GH action, or both. To investigate a potential receptor involvement, we measured plasma high-affinity GH-binding protein (GHBP), which represents a truncated GH receptor and may reflect GH receptor levels in tissues, in patients with IDDM, patients with non-insulin-dependent diabetes (NIDDM), and nondiabetic control subjects. Patients with IDDM had significantly lower plasma GHBP levels than either patients with NIDDM or nondiabetic control subjects (mean value 18.2 vs. 24.6 and 23.8% GH bound/ml plasma, respectively, P less than 0.001). This difference persisted when only lean patients (less than 115% ideal body wt) were included in the analysis. Basal plasma GH levels were significantly elevated in IDDM compared with either patients with NIDDM or nondiabetic control subjects (mean 6.9 vs. 2.1 and 2.0 micrograms/L, respectively, P less than 0.001), whereas IFG-I levels were not significantly different in IDDM and NIDDM. No correlations were found between levels of GHBP and HbA1, duration of diabetes, or plasma GH. GHBP and IGF-I levels were significantly correlated in NIDDM but not in IDDM. We conclude that IDDM is associated with low GHBP levels and that GH resistance found in this disorder may be mediated, at least in part, by a decrease in GH receptor levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Uroscopy in the 21st century: high-field NMR spectroscopy

From the experiments described, it can be seen that there are different research approaches that can be taken and these are summarized in Table 1. Whereas much scientific research is principally hypothesis led, there remains, nevertheless, an important place for exploratory research. High resolution NMR can measure, directly and simultaneously, a wide range of endogenous metabolites in biological fluids and has the unique capability of providing structural information on the metabolites detected. It has proved to be a powerful research tool with which to study inherited metabolic diseases, renal disease, drug metabolism, and toxicity, and can be used to monitor the effects of drug therapy. For instance, by using a library of experimental toxins one can map the metabolic profile of site-specific nephron injury. With this approach in man one could eventually take an unknown disease such as Balkan nephropathy and predict the initial site of tubular injury, the mode of injury and therefore the kind of toxin capable of producing that injury. NMR spectroscopic techniques are still advancing rapidly, with ever increasing sensitivity and sophistication of NMR pulse sequences to enhance structural elucidation in complex mixtures. Given the advances in directly coupled HPLC-NMR and even HPLC-NMR-mass spectroscopy it is likely that these technologies in conjunction with pattern recognition will make major contribution to our understanding of renal processes and provide new diagnostic insights in the 21st century.      

Adenoid cystic carcinoma of the breast diagnosed by fine-needle aspiration

Fine-needle aspiration cytology remains a useful tool for preoperative diagnosis of breast lesions. We describe a case of adenoid cystic carcinoma (ACC) of the breast detected by ultrasound-guided fine-needle aspiration (FNA). Subsequent histopathology corroborated the diagnosis. ACC is a rare but distinctive neoplasm of the breast that can be accurately diagnosed by FNA. Its infrequent presentation, favorable prognosis, and relatively conservative management in the breast prompt us to reinforce its features.     

Increased serum levels of growth hormone and insulin-like growth factor-I associated with simultaneous decrease of circulating insulin in postmenopausal women receiving hormone replacement therapy

OBJECTIVE: Decreases in circulating growth hormone (GH) and its main biological messenger insulin-like growth factor-I (IGF-I) have been interpreted as part of the aging process. Because estrogens participate in modulating GH synthesis and secretion, hypoestrogenism in menopausal women may lead to GH deficiency. The aim of the present study was to determine the effect of hormone replacement therapy (HRT) on both GH and IGF-I levels as well as insulin concentrations in 50 menopausal women. DESIGN: Patients were assigned randomly into two treatment groups of 25 each; one group received three cycles of conjugated equine estrogen (CEE) 0.625 mg/day for 21 days, and the other, 1.25 mg/day during 21 days. Each also received chlormadinone acetate for 5 days. There was a control group consisting of regularly menstruating women. RESULTS: In the menopausal women, HRT increased significantly (p < 0.001) the low levels of GH and IGF-I; on the contrary the baseline insulin levels declined (p < 0.001) with HRT. A significant linear correlation (r = 0.90) was found between GH and IGF-I as well as with estradiol levels (r = 0.74) in the group of menopausal women receiving CEE 0.625 mg/day. This group of patients had a significant correlation (r = -0.63) between insulin and estradiol levels. No correlation was observed in the group receiving CEE 1.25 mg/day. CONCLUSIONS: HRT restored GH, IGF-I, and insulin levels to normal values in all women. Further research needs to be done to establish the beneficial effect of HRT regarding the prevention of the metabolic effects presumably caused by derangement in the somatotropic axis associated with aging.     

Detection of infectious bursal disease viruses by using cloned cDNA probes.

A molecular clone representing 445 base pairs at the 3' end of infectious bursal disease virus (IBDV) genome segment B was used in a dot blot hybridization assay to detect viral RNA from cell culture and from chicken bursa and spleen tissue specimens. The cloned nucleotide sequence represents approximately 14% of the virus-encoded polymerase (VP-1) gene. The lower detection limit of radiolabeled probes prepared from this clone was 0.1 ng of IBDV double-stranded RNA. The probe had broad specificity and was used to detect four serotype 1 IBDV strains and one serotype 2 IBDV strain. This probe, however, did not cross-react with nucleic acid extracted from nine unrelated poultry viruses. A rapid procedure for isolation of IBDV genomic RNA from bursa and spleen tissue specimens was developed and used with the dot blot hybridization assay to detect IBDV strains in tissue samples from experimentally infected and commercially reared chickens.     

Mesh repair for lateral inguinal hernias: a non-evidence-based practice

Introduction

The EHS clinical guidelines recommend the use of mesh to repair symptomatic primary inguinal hernias (PIH) in adult males but, in spite of this, it begs the question as to why there is still place for tissue techniques. Lack of stratification of patients according to risk of recurrence in RCTs might be a cause of results disparity, since medial and mixed are hernias with higher risk of recurrence (HRRH), whereas lateral hernias present a lower risk (LRRH).

Objective

To determine whether the lack of stratification may lead to questionable conclusions regarding the protective effect of mesh techniques and to identify other methodological flaws.

Methods

In the RCTs included in the clinical guidelines that addressed recurrences of PIH after mesh and non-mesh techniques, we assessed the type of hernias classification used, the number needed to treat in LRRH and HRRH and the statistical power.

Results

Most of trials were underpowered; five studies classified the hernia types; in the three studies that compared the recurrence rates of LRRH and HRRH the effect of mesh techniques was small; only two trials record data needed to calculate the NNT in LRRH (46 y 84 patients, respectively).

Conclusion

The idea that mesh techniques reduce the recurrence rate in all PIHs is not supported by high level of evidence. The NNT for pure lateral hernias was very high and should be interpreted taking into account chronic pain rates and costs.

     

Giant cell reparative granuloma of the orbit

PURPOSE: To report a case of giant cell reparative granuloma occurring in the orbit and to discuss its clinical, radiologic, and histopathologic characteristics in contrast with other similar lesions. METHODS: A 38-year-old man developed pain and mild proptosis of the left eye. Computed tomography and magnetic resonance imaging demonstrated an intraosseous cystic orbital mass. Excisional biopsy disclosed giant cell reparative granuloma of the orbit. RESULT: At 11 months' follow-up, the patient had normal vision, with no tumor recurrence. CONCLUSION: Giant cell reparative granuloma of the orbit is a rare benign fibro-osseous proliferation that is generally seen in young adulthood. It should be considered in the differential diagnosis of orbital fibro-osseous proliferation. Surgical excision and curettage is the therapeutic method of choice.     

Hypothalamic dopaminergic tone and prolactin bioactivity in women with polycystic ovary syndrome

BACKGROUND: The present study was carried out to investigate the functional significance of the reduced dopaminergic tone in subjects affected with polycystic ovary syndrome (PCOS). METHODS: Our group evaluated the response of pituitary PRL, LH, FSH, and TSH to the administration of a single 10-mg oral dose of the dopamine (DA) receptor antagonist metoclopramide in lean (n = 7) and obese (n = 8) PCOS women and in 11 regularly cycling age- and weight-matched controls (six lean and five obese). In addition, circulating PRL bioactivity was evaluated by its mitogenic activity on a lymphoma cell bioassay. RESULTS: Oral administration of metoclopramide resulted in a significant increase in serum PRL in all subjects; however, the highest increments, regardless of body mass index (BMI), were observed in control women (p <0.005). Measurements of PRL mitogenic activity on the Nb2 lymphoma cell bioassay revealed a significant increase in the bioactive/immunoreactive (B/I) ratio of PRL under basal and stimulated conditions in obese PCOS subjects (p <0.05). Mean fasting glucose/insulin and glucose/insulin-AUC ratios were significantly lower (p <0.001) in obese PCOS when compared with all other groups. CONCLUSIONS: These data support the existence of low DA hypothalamic tone in PCOS women that is likely involved in the inappropriate LH and PRL secretion frequently seen in this syndrome. In addition, our results suggest changes in PRL bioactivity in obese PCOS that may play a role in the development of hyperinsulinemia; however, whether PRL has a functional significance in the development of the metabolic disturbances frequently seen in PCOS remains to be elucidated.